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The article discusses the results of a study on the preparation and properties of a covalently functionalized organoclay and its polypropylene (PP) nanocomposite. A condensation reaction between sodium hydroxyl groups and acryloyl chloride was used to prepare organoclay which was then modified through ion exchange with hexadecyltrimethylammonium bromide. PP nanocomposites loaded with organoclay were produced by melt mixing. The composites showed improved higher storage modulus and viscosity.

Abstract: Thin films of Al2O3 grown using atomic layer deposition (ALD) techniques can protect polymers from erosion by oxygen atoms. To quantify this protection, polyimide substrates with the same chemical repeat unit as Kapton® were applied to quartz crystal microbalance (QCM) sensors. Al2O3 ALD films with varying thicknesses were grown on the polyimide substrates. The ALD-coated polyimide materials were then exposed to a hyperthermal atomic-oxygen beam. The mass loss versus oxygen-atom exposure time was measured in situ by the QCM. Al2O3 ALD film thicknesses of ∼35 Å were found to protect the polymer from erosion. [Copyright &y& Elsevier]

This study aims to develop an effective bivalent subunit vaccine that is promising to prevent both porcine deltacoronavirus (PDCoV) and porcine epidemic diarrhea virus (PEDV). The receptor-binding domains (RBDs) of PDCoV and PEDV were fused and cloned into the eukaryotic expression vector pCDNA3.1(+). The fusion protein PDCoV-RBD-PEDV-RBD (pdRBD-peRBD) was expressed by the ExpiCHO TM expression system and purified. Mice were immunized with the fusion protein at three different doses (10, 20, and 30 μg). The humoral immune response and cellular immune response induced by the fusion protein were evaluated by ELISA and flow cytometry. The neutralization titers of the serum of immunized mice against PDCoV and PEDV were determined by the microneutralization test. The results showed that high levels of IgG antibodies were induced in the three different dose groups after booster immunization, and there was no significant difference in the antibody level between different dose groups, indicating that the immunization dose of 10 μg could achieve the fine immune effect. The results of flow cytometry showed that the immunization groups demonstrated increased proportion of CD 3 + CD 4 + T cells and decreased proportion of CD 3 + CD 8 + T cells, which was consistent with the expectation about the humoral immune response induced by the subunit vaccine. At the same time, the levels of interleukin (IL)-2, IL-4, and interferon (IFN)-γ in the serum were determined. The results showed that the fusion protein induced both humoral immune effect and cellular immune response. The results of the neutralization test showed that the antibody induced by 10 μg fusion protein neutralized both PDCoV and PEDV in vitro , with the titers of 1:179.25 and 1:141.21, respectively. The above results suggested that the pdRBD-peRBD could induce a high level of humoral immune response at a dose of 10 μg, and the induced antibody could neutralize both PDCoV and PEDV. Therefore, the fusion protein pdRBD-peRBD is expected to be an effective subunit vaccine that can simultaneously prevent PDCoV and PEDV.

Background: Undifferentiated small round-cell sarcomas (uSRCSs) are a subgroup of sarcomas that are difficult to diagnose. Some uSRCSs have specific gene re-arrangements, but others do not. Currently, there is no specific treatments for advanced uSRCSs, and its treatment is largely based on general experience with sarcomas, which includes chemotherapy, targeted therapy, and immunotherapy. In this article, we report a patient with uSRCS who responded to treatment with anti-VEGF inhibitor surufatinib and anti-PD-1 inhibitor camrelizumab after progression on first-line chemotherapy, second-line anlotinib combined with immunotherapy, and third-line chemotherapy., Case Description: In July 2020, a 37-year-old female patient was diagnosed with advanced uSRCS. Results for the Ewing sarcoma RNA binding protein 1 and Wilms tumor suppressor (EWSR1/WT1) fusion gene were negative. The patient was also negative with BCOR (BCL6 co-repressor) and CIC (capicua transcriptional repressor) fusion gene. The next-generation sequencing results revealed point mutations on Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta (PIK3CB), Transcription Factor Binding To IGHM Enhancer 3 (TFE3), Mucin 16 (MUC16), and AXL (Axl, also called UFO, ARK, and Tyro7, is part of a family of receptor tyrosine kinases). The patient received 4 cycles of the Ifosfamide and epirubicin hydrochloride regimen, and her best objective response was stable disease. On November 3, 2020, a computed tomography (CT) scan revealed progressive disease (PD). Two cycles of camrelizumab (a programmed death-1 inhibitor) plus anlotinib (an anti- vascular endothelial growth factor drug) were administered, but PD was again observed. Thus, a regimen of gemcitabine plus docetaxel was adopted. Unfortunately, the disease progressed once again after two cycles of the treatment. On February 4, 2021, the patient began to receive targeted therapy with surufatinib combined with camrelizumab. A CT scan showed that the tumor achieved a partial response. As of April 2023, the patient had a progression-free survival time of 26 months., Conclusions: Surufatinib in combination with camrelizumab could be effective in the treatment of advanced uSRCSs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Huang, Chen, Ye, Du, Voutsadakis, Seetharam, Zhang and Lu.)

Background: Sepsis is initiated by the dysfunctional response of the host immune system to infection. Septic shock and acute lung injury (ALI) are the main etiology of death caused by sepsis. Glucocorticoids, which are commonly used in clinic to antagonize the inflammatory response of sepsis, may cause serious side effects. Isoforskolin (ISOF) from the plant Coleus forskohlii stimulates adenylyl cyclase, increases the cAMP level and inhibits inflammatory response. The aim of this study was to investigate the synergistic effect of ISOF with dexamethasone (DEX) to prevent and ameliorate septic inflammation., Methods: Lipopolysaccharide (LPS) of 30 and 5 mg/kg (iv.) was used to induce sepsis and ALI mice model respectively in vivo. BEAS-2B cells stimulated by LPS were applied as cell model in vitro. The cumulative survival of mice with LPS-induced sepsis and the histopathological changes of lungs in mice with acute lung injury were observed, and the secretion of pro-inflammatory cytokines was analyzed by ELISA. The expression of RGS2 in BEAS-2B cells was detected by immunoblotting assay and PCR., Results: In the sepsis mice model, ISOF (10 mg/kg) combined with DEX (10 mg/kg.) (ip.) pretreatment significantly increased mice survival rate from 33.3% to 58.3%, which was significantly higher than that of ISOF or DEX treated alone. In the ALI mice model, ISOF, DEX pretreatment alone and combined application attenuated pulmonary pathological changes in ALI mice. Furthermore, ISOF, DEX alone or combined administration decreased MPO, MDA, IL-6, and IL-8 levels, while significantly synergistic effects were observed in the combined treatment group compared with ISOF or DEX alone. In BEAS-2B cells, combined pretreatment with ISOF and DEX significantly decreased the expression of IL-8 and increased the expression of RGS2., Conclusion: The results indicated that ISOF in combination with DEX synergistically improves survival rate and attenuates ALI in mice model through anti-inflammatory and antioxidant effects., Competing Interests: The authors declare no competing interests in this work., (© 2023 Fang et al.)

The mammalian Sterile 20-like kinase 1/2 (MST1/2) belongs to the serine/threonine (GC) protein kinase superfamily. Collective studies confirm the vital role MST1/2 in inflammation and immunity. MST1/2 is closely related to the progress of inflammation. Generally, MST1/2 aggravates the inflammatory injury through MST1-JNK, MST1-mROS, MST1-Foxo3, and NF-κB pathways, as well as several regulatory factors such as tumor necrosis factor-α (TNF-α), mitochondrial extension factor 1 (MIEF1), and lipopolysaccharide (LPS). Moreover, MST1/2 is also involved in the regulation of immunity to balance immune activation and tolerance by regulating MST1/2-Rac, MST1-Akt1/c-myc, MST1-Foxos, MST1-STAT, Btk pathways, and lymphocyte function-related antigen 1 (LFA-1), which subsequently prevents immunodeficiency syndrome and autoimmune diseases. This article reviews the effects of MST1/2 on inflammation and immunity.

Background: Machine learning algorithms used to classify cystic renal masses (CRMs) nave not been applied to unenhanced CT images, and their diagnostic accuracy had not been compared against radiologists., Method: This retrospective study aimed to develop radiomics models that discriminate between benign and malignant CRMs in a triple phase computed tomography (CT) protocol and compare the diagnostic accuracy of the radiomics approach with experienced radiologists. Predictive models were established using a training set and validation set of unenhanced and enhanced (arterial phase [AP] and venous phase [VP]) CT images of benign and malignant CRMs. The diagnostic capabilities of the models and experienced radiologists were compared using Receiver Operating Characteristic (ROC) curves., Results: On unenhanced, AP and VP CT images in the validation set, the AUC, specificity, sensitivity and accuracy for discriminating between benign and malignant CRMs were 90.0 (95%CI: 81-98%), 90.0%, 90.5% and 90.2%; 93.0% (95%CI: 86-99%), 86.7%, 95.2% and 88.3%; and 95.0% (95%CI: 90%-100%), 93.3%, 90.5% and 92.1%, respectively, for the radiomics models. Diagnostic accuracy of the radiomics models differed significantly on unenhanced images in the training set vs. each radiologist (p = 0.001 and 0.003) but not in the validation set (p = 0.230 and 0.590); differed significantly on AP images in the validation set vs. each radiologist (p = 0.007 and 0.007) but not in the training set (p = 0.663 and 0.663); and there were no differences on VP images in the training or validation sets vs. each radiologist (training set: p = 0.453 and 0.051, validation set: p = 0.236 and 0.786)., Conclusions: Radiomics models may have clinical utility for discriminating between benign and malignant CRMs on unenhanced and enhanced CT images. The performance of the radiomics model on unenhanced CT images was similar to experienced radiologists, implying it has potential as a screening and diagnostic tool for CRMs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Beauveria bassiana is a well-known insecticidal biocontrol agent. Despite its broad field applications, its survival, colonization, and stability under field conditions remained unclear, mainly due to the lack of a quick and reliable detection method. In this study, we developed a quantitative real-time PCR technology to monitor the stability and population dynamics of B. bassiana in different substrates (water, soil, and on the cotton leaves surface), different spores of B. bassiana applied on Chinese cabbage leaves surface, and the lethality of Pieris rapae spraying with different spores of B. bassiana . Our results showed a decreased concentration of B. bassiana DNA in all three substrates from the 1 st day till 9 th day of post inoculation (dpi) period, possibly due to the death of B. bassiana . After this decrease, a quick and significant rebound of B. bassiana DNA concentration was observed, starting from the 11 th dpi in all three substrates. The B. bassiana DNA concentration reached the plateau at about 13 th dpi in water and 17 th dpi in the soil. On cotton leaves surface, the B. bassiana DNA concentration reached the highest level at the 17 th dpi followed by a small decline and then stabilized. This increase of DNA concentration suggested recovery of B. bassiana growth in all three substrates. We found that the most suitable killing effectiveness of P. rapae was the 1.0 × 10 7  spores/mL of B. bassiana. In summary, we have established a detection technology that allows a fast and reliable monitoring for the concentration and stability of B. bassiana under different conditions. This technology can benefit and help us in the development of proper management strategies for the application of this biocontrol agent in the field., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Zepei Gu et al.)

Imidacloprid (IMI) is the first-generation neonicotinoid insecticide. But, the long-term use of IMI as a pesticide has caused severe water pollution. Recently, the toxicity of IMI to aquatic organisms has received increasing attention. This study aimed to investigate the absorption and distribution of IMI in various tissues (gills, intestine, liver, muscle, brain and gonads) of goldfish through short-term and continuous exposure tests over 28 days. The results of short-term exposure indicated that the concentration of IMI and its metabolites in tissues at the transfer stage decreased steadily after 1 day of 40 mg/L IMI water treatment and was below the detection limit after 3 days. Continuous exposure for 28 days at various treatment concentrations showed that the concentrations of IMI and its metabolites differed significantly among the different tissues of the goldfish. In the 20 mg/L treatment group (S1), the highest concentration of IMI was found in the liver (12.04 μg/g tissue ), followed by the intestine (9.91 μg/g tissue ), muscle (6.20 μg/g tissue ), gill (6.11 μg/g tissue ), gonads (5.22 μg/g tissue ) and brain (2.87 μg/g tissue ). In the 40 mg/L treatment group (S2), the order of the tissue concentrations was similar to that of the S1 group, with the highest concentration observed in the liver (12.04 μg/g tissue ), followed by the intestine (9.91 μg/g tissue ), muscle (6.20 μg/g tissue ), gill (6.11 μg/g tissue ), gonads (5.22 μg/g tissue ) and brain (2.87 μg/g tissue ). Furthermore, the study detected 5-hydroxy-IMI, IMI urea and 6-chloronicotinic acid in IMI metabolites in all tissues, while IMI was detected only in the intestine and liver. Overall, the results of this study contribute to a better understanding of the metabolic behavior of IMI in organisms and provide new data to support the assessment of IMI toxicity in fish.

Objectives: To evaluate amide proton transfer-weighted (APTw)-derived whole-tumor histogram analysis parameters in predicting pathological extramural venous invasion (pEMVI) positive status of rectal adenocarcinoma (RA)., Methods: Preoperative MR including APTw imaging of 125 patients with RA (mean 61.4 ± 11.6 years) were retrospectively analyzed. Two radiologists reviewed each case's EMVI status based on the MR-based modified 5-point scale system with conventional MR images. The APTw histogram parameters of primary tumors were obtained automatically using whole-tumor volume histogram analysis. The independent risk factors markedly correlated with pEMVI-positive status were assessed using univariate and multivariate logistic regression analyses. Diagnosis performance was assessed by receiver operating characteristic curve (ROC) analysis. The AUCs were compared using the Delong method., Results: Univariate analysis demonstrated that MR-tumor (T) stage, MR-lymph node (N) stage, APTw-10%, APTw-90%, interquartile range, APTw-minimum, APTw-maximum, APTw-mean, APTw-median, entropy, kurtosis, mean absolute deviation (MAD), and robust MAD were significantly related to pEMVI-positive status (all p < 0.05). Multivariate analysis demonstrated that MR-T stage (OR = 4.864, p = 0.018), MR-N stage (OR = 4.967, p = 0.029), interquartile range (OR = 0.892, p = 0.037), APT-minimum (OR = 1.046, p = 0.031), entropy (OR = 11.604, p = 0.006), and kurtosis (OR = 1.505, p = 0.007) were the independent risk factors enabling prediction of pEMVI-positive status. The AUCs for diagnostic ability of conventional MRI assessment, the APTw histogram model, and the combined model (including APTw histogram and clinical variables) were 0.785, 0.853, and 0.918, respectively. The combined model outperformed the APTw histogram model (p = 0.013) and the conventional MRI assessment (p = 0.006)., Conclusions: Whole-tumor histogram analysis of APTw images combined with clinical factors showed better diagnosis efficiency in predicting EMVI involvement in RA., Key Points: • Rectal adenocarcinomas with pEMVI-positive status are typically associated with higher APTw-SI values. • APTw-minimum, interquartile range, entropy, kurtosis, MR-T stage, and MR-N stage are the independent risk factors for EMVI involvement. • The best prediction for EMVI involvement was obtained with a combined model of APTw histogram and clinical variables (area under the curve, 0.918)., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

The increase in the insecticide resistance of pests, such as Mythimna separata , Aphis craccivora Koch , and Tetranychus cinnabarinus , necessitates the development of new heterocyclic compounds with high insecticidal activity. A series of novel 2-phenylpyridine derivatives containing N -phenylbenzamide moieties were designed and synthesised with Suzuki-Miyaura cross-coupling, nucleophilic substitution, and amidation reactions. The reaction conditions in each step are mild, and the product is easy to separate (yield is about 85%). The structures of the compounds were characterised using 1 H and 13 C NMR spectroscopy and HRMS. Moreover, the insecticidal activity of the compounds was analysed using the leaf dipping method. The compounds 5a , 5d , 5g , 5h , and 5k at 500 mg/L exhibited 100% inhibition against Mythimna separata . Therefore, the 2-phenylpyridine moieties have the potential to lead to the discovery of novel and effective insecticides.

Inflammation and metabolic reprogramming are hallmarks of cancer. How inflammation regulates cancer metabolism remains poorly understood. In this study, we found that 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL), the enzyme that catalyzes the catabolism of leucine and promotes the synthesis of ketone bodies, was downregulated in lung cancer. Downregulation of HMGCL was associated with a larger tumor size and a shorter overall survival time. In a functional study, overexpression of HMGCL increased the content of β-hydroxybutyrate (β-HB) and inhibited the tumorigenicity of lung cancer cells, and deletion of HMGCL promoted de novo tumorigenesis in KP (Kras G12D ;P53 f/f ) mice. Mechanistically, tumor necrosis factor α (TNFα) treatment decreased the HMGCL protein level, and IKKβ interacted with HMGCL and phosphorylated it at Ser258, which destabilized HMGCL. Moreover, NEDD4 was identified as the E3 ligase for HMGCL and promoted its degradation. In addition, mutation of Ser258 to alanine inhibited the ubiquitination of HMGCL by NEDD4 and thus inhibited the anchorage-independent growth of lung cancer cells more efficiently than did wild-type HMGCL. In summary, this study demonstrated a link between TNFα-mediated inflammation and cancer metabolism., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Chronic obstructive pulmonary disease (COPD) as a common, preventable and treatable chronic respiratory disease in clinic, gets continuous deterioration and we can't take effective intervention at present. Lung macrophages (LMs) are closely related to the occurrence and development of COPD, but the specific mechanism is not completely clear. In this review we will focus on the role of LMs and potential avenues for therapeutic targeting for LMs in COPD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To assess the utility of Dual-layer spectral-detector CT (DLCT) in predicting the pT stage and histologic grade for colorectal adenocarcinoma (CRAC)., Methods: A total of 131 patients (mean 62.7 ± 12.9 years; 72 female, 59 male) with pathologically confirmed CRAC (35 pT1-2, 61 pT3, and 35 pT4; 32 high grade and 99 low grade), who received dual-phase DLCT were enrolled in this retrospective study. Normalized iodine concentration (NIC), slope of the spectral HU curve (λHU), and effective atomic number (Eff-Z) were measured for each lesion by two radiologists independently. Intraobserver reliability and interobserver agreement were assessed. The above values were compared between three pT-stage and two histologic-grade groups. The correlation between the pT stages and above values were assessed. Receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic efficacy., Results: Intra-class correlation coefficients were ranged from 0.856 to 0.983 for all measurements. Eff-Z [7.21(0.09) vs 7.31 (0.10) vs 7.35 (0.19)], NIC AP [0.11 (0.05) vs 0.15 (0.08) vs 0.15 (0.08)], NIC VP [0.27 (0.06) vs 0.34 (0.11) vs 0.35 (0.12)], λHU AP [1.20 (0.45) vs 1.93 (1.18) vs 2.37 (0.91)], and λHU VP [2.07 (0.68) vs 2.35 (0.62) vs 3.09 (1.07)] were significantly different among pT stage groups (all  P <0.001) and exhibited a positive correlation with pT stages ( r = 0.503, 0.455, 0.394, 0.512, 0.376, respectively, all  P <0.001). Eff-Z [7.37 (0.10) vs 7.28 (0.08)], NIC AP [0.20 (0.10) vs 0.13 (0.08)], NIC VP [0.35 (0.07) vs 0.31 (0.11)], and λHU AP [2.59 (1.11) vs 1.63 (0.75)] in the high-grade group were markedly higher than those in the low-grade group (all  P <0.05). For discriminating the advanced- from early-stage CARC, the AUCs of Eff-Z, NIC AP , NIC VP , λHU AP , and λHU VP were 0.83, 0.80, 0.79, 0.86, and 0.68, respectively (all  P <0.001). For discriminating the high- from low-grade CARC, the AUCs of Eff-Z, NIC AP , NIC VP , and λHU AP were 0.81, 0.81, 0.64, and 0.81, respectively (all  P <0.05)., Conclusions: The quantitative parameters derived from DLCT may provide new markers for assessing pT stages and histologic differentiation in patients with CRAC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Ye, Zhang, Mao, Guo, Zhang, Du, Deng, Liu and Liu.)

To discover new compounds with favorable herbicidal activity, a range of phenylpyridine moiety-containing pyrazole derivatives were designed, synthesized, and identified via NMR and HRMS. Their herbicidal activities against six species of weeds were evaluated in a greenhouse via both pre- and post-emergence treatments at 150 g a.i./hm 2 . The bioassay revealed that a few compounds exhibited moderate herbicidal activities against Digitaria sanguinalis , Abutilon theophrasti , and Setaria viridis in post-emergence treatment. For instance, compounds 6a and 6c demonstrated 50% inhibition activity against Setaria viridis , which was slightly superior to pyroxasulfone. Thus, compounds 6a and 6c may serve as the new possible leading compounds for the discovery of post-emergence herbicides.

To find novel herbicidal compounds with high activity and broad spectrum, a series of phenylpyridine moiety-containing α-trifluoroanisole derivatives were designed, synthesized, and identified via nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). Greenhouse-based herbicidal activity assays revealed that compound 7a exhibited > 80% inhibitory activity against Abutilon theophrasti, Amaranthus retroflexus, Eclipta prostrate, Digitaria sanguinalis, and Setaria viridis at a dose of 37.5 g a.i./hm2, which was better than fomesafen. Compound 7a further exhibited excellent herbicidal activity against Abutilon theophrasti and Amaranthus retroflexus in this greenhouse setting, with respective median effective dose (ED50) values of 13.32 and 5.48 g a.i./hm2, both of which were slightly superior to fomesafen (ED50 = 36.39, 10.09 g a.i./hm2). The respective half-maximal inhibitory concentration (IC50) for compound 7a and fomesafen when used to inhibit the Nicotiana tabacum protoporphyrinogen oxidase (NtPPO) enzyme, were 9.4 and 110.5 nM. The docking result of compound 7a indicated that the introduction of 3-chloro-5-trifluoromethylpyridine and the trifluoromethoxy group was beneficial to the formation of stable interactions between these compounds and NtPPO. This work demonstrated that compound 7a could be further optimized as a PPO herbicide candidate to control various weeds.

Background: Cucumber downy mildew (CDM) is a severe plant disease and affects the yield of cucumber production worldwide. As the resistance toward conventional fungicides is emerging as a ubiquitous issue, it is urgent to discover efficient fungicides with unique structures., Results: In this study, a series of novel phenylpyridine derivatives were designed and synthesized. Bioassays revealed that most of these compounds possessed excellent fungicidal activities against CDM. Among the phenylpyridine compounds, 2-(4-(4-(tert-butyl)benzyl)piperazin-1-yl)-6-phenylnicotinonitrile (C8) [half-maximal effective concentration (EC 50 ) = 4.40 mg L -1 ] displayed the highest activity, which was better than those of the commercial fungicides, such as azoxystrobin (EC 50  = 42.77 mg L -1 ) and flumorph (EC 50  = 41.94 mg L -1 ). Furthermore, the molecular electrostatic potential of high-activity compound C8 indicated that nitrogen atom of the cyano group on the pyridine ring was in the negative region and may easily form hydrogen bonds and allow for electrostatic interactions with potential receptors., Conclusions: This study demonstrated that the novel N-substituted piperazine-containing phenylpyridine derivatives could be further developed as a candidate compound to control CDM., (© 2022 Society of Chemical Industry.)

An air-fluid level within a gastrointestinal stromal tumor (GIST) is unusual and indicates the presence of a fistula within the lumen of the GI tract. Until recently, the optimal management of such patients was not clear-cut. This retrospective study investigated the clinicopathological characteristics, surgical procedures, pre-and post-operative management, and prognosis of patients with GIST containing an air-fluid level. Data of GIST patients, spanning 5 years, including 17 GIST patients with air-fluid levels in the experimental group and 34 GIST patients without air-fluid levels in the control group, were retrieved from two hospitals in China. The clinicopathological characteristics, types of surgery, management, and clinical outcomes of GIST patients were compared between the two groups. GISTs containing air-fluid levels were significantly different from GISTs without air-fluid levels regarding tumor morphology, NIH risk category, invasion of adjacent organs, and necrosis or ulceration. Most GIST patients with air-fluid levels (14/17, 82.4%) received open surgery, significantly higher than the 20.6% in the control group. Targeted therapy with Imatinib mesylate (IM) was implemented in all GIST patients in the experimental group (17/17, 100%); markedly higher than those (3/34, 8.8%) in the control group. During follow-up, recurrence and death rates (5.9% and 5.9%) in the experimental group were higher than those (2.9% and 0%) in the control group. Open surgery is commonly performed in GIST patients with air-fluid levels who also require targeted therapy with IM. The Torricelli-Bernoulli sign could be a risk factor, adversely affecting the patient's prognosis., Competing Interests: The authors have declared that no competing interests exist.

Lipin-1 is known to play a regulatory role in tissues that function in lipid metabolism. In dairy cows, the lipin-1 gene ( LPIN1 ) is highly expressed in the mammary gland, but its function in milk production is less understood. In this study, we used PCR-single strand conformation polymorphism analysis to investigate sequence variation in three regions of bovine LPIN1 in New Zealand Holstein-Friesian × Jersey (HF × J)-cross dairy cows, including part of the 5' non-coding region, the region containing the LPIN1β -spliced exon, and the sixth coding exon that encodes the putative transcriptional activating domain of the protein. No variation was found in the LPIN1β -spliced exon, but two sequence variants containing one single nucleotide polymorphism (SNP) were identified in the 5' non-coding region and four sequence variants containing four non-synonymous SNPs were identified in the sixth coding exon. Among the three common variants of the sixth coding exon, variant C was found to be associated with an increase in milk fat percentage (presence 4.96 ± 0.034% vs. absence 4.81 ± 0.050%; p = 0.006) and milk protein percentage (presence 4.09 ± 0.017% vs. absence 3.99 ± 0.025%; p = 0.001), but no associations ( p > 0.01) were detected for milk yield. These results suggest that variation in LPIN1 affect the synthesis of fat and proteins in milk and has potential as a gene-marker to improve milk production traits.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by limited airflow due to pulmonary and alveolar abnormalities from exposure to cigarette smoke (CS). Current therapeutic drugs are limited and the development of novel treatments to prevent disease progression is challenging. Isoforskolin (ISOF) from the plant Coleus forskohlii is an effective activator of adenylyl cyclase (AC) isoforms. Previously we found ISOF could attenuate acute lung injury in animal models, while the effect of ISOF on COPD has not been elucidated., Purpose: In this study, we aimed to evaluate the efficacy of ISOF on COPD and reveal its potential mechanisms., Methods: A rat model of COPD was established by long-term exposure to CS, then the rats were orally administered with ISOF (0.5, 1 and 2 mg/kg). The pulmonary function, lung morphology, inflammatory cells and cytokines in serum or bronchoalveolar lavage fluid (BALF) were evaluated. Transcriptomics, proteomics and network pharmacology analysis were utilized to identify potential mechanisms of ISOF. Droplet digital PCR was used to detect the mRNA expression of AC1-10 in donor lung tissues. AC activation was determined in recombinant human embryonic kidney 293 (HEK293) cells stably expressing human AC isoforms. In addition, ISOF caused trachea relaxation ex vivo were assessed in isolated trachea rings from guinea pigs., Results: ISOF significantly ameliorated pathological damage of lung tissue and improved pulmonary function in COPD rats. ISOF treatment decreased the number of inflammatory cells in peripheral blood, and also the levels of pro-inflammatory cytokines in serum and BALF. Consistent with omics-based analyses, ISOF markedly downregulated the mTOR level in lung tissue. Flow cytometry analysis revealed that ISOF treatment reduced the ratio of Th17/Treg cells in peripheral blood. Furthermore, the expression levels of AC1 and AC2 are relatively higher than other AC isoforms in normal lung tissues, and ISOF could potently activate AC1 and AC2 in vitro and significantly relax isolated guinea pig trachea., Conclusion: Collectively, our studies suggest that ISOF exerts its anti-COPD effect by improving lung function, anti-inflammation and trachea relaxation, which may be related to AC activation, mTOR signaling and Th17/Treg balance., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

The telencephalon is also known as the cerebrum, and it consists of the largest part of the brain. It makes up about 85% of the total weight of the brain. Neuroglobin (Ngb) is a protein found in neurons of both the peripheral and central nervous system that appears to convey some resilience to hypoxia, while the hypoxia-inducible factor (Hif-1α) is a dimeric protein complex that plays an integral role in the body's response to low oxygen concentrations, or hypoxia. The study examines the expression of Ngb and Hif-1α in the telencephalon of adult yak in the telencephalon. The immunohistochemistry (IHC), quantitative real-time PCR and Western blot (WB) were employed to investigate Ngb and Hif-1α expression in the telencephalon. Ngb and Hif-1α are significantly expressed in all tissues of the telencephalon except the hypothalamus. The cerebellar cortex, hippocampus, amygdala, cerebellum and corpus callosum recorded the highest expression but not significant. The overall expression revealed that Ngb expression was higher as compared to Hif-1α. The IHC results also showed that the expression of Ngb and Hif-1α were higher in the cerebellar cortex, hippocampus, amygdala, cerebellum and corpus callosum as compared to other regions. The results suggested that Ngb and Hif-1α expression influence the adaptive mechanism of yak to the high altitude environment. Both Ngb and Hif-1α participate in oxygen transports throughout the telencephalon and have functions in neuroprotection. Further studies are needed to confirm the mechanism of adaptation., (© 2021 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

The standard third-line treatment of metastatic colorectal cancer (mCRC) includes the small-molecule anti-vascular drugs (Regofenib and Fruquintinib) and the chemotherapy drug trifluridine and tipiracil hydrochloride (TAS-102). There is no standard treatment for mCRC if the third-line treatment failed. Therefore, it is a pressing need to develop new therapeutic approaches to improve the survival of patients who developed drug resistance to the third-line treatment. In this study, we report a case of mCRC with RAS/BRAF wild-type, who was successfully treated using cetuximab in combination with fruquintinib after resistance to chemotherapy, bevacizumab, cetuximab and regorafenib. This patient responded to this combination regimen. Then, we discuss the mechanisms of action of this combination. Furthermore, we introduce the clinical trials on the combination regimens of anti-EGFR with anti-vascular monoclonal antibodies. Finally, we discuss the clinical explorations of using combination of anti-EGFR with small-molecule anti-VEGF drugs and their potential benefits. The clinical effects of small-molecule anti-vascular drugs in combination with anti-EGFR in the treatment of CRC warrant further explored., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Chen, Li, Ye, Du, Sun, Liu and Zhang.)

RecurIndex, a multigene profiling assay, can predict the risk of local recurrence and distant metastasis in female breast cancer (FBC), but its role in male breast cancer (MBC) remains unclear. In this study, the clinicopathological data of 43 consecutive MBC patients undergoing surgeries between 2009 and 2018 were retrospectively analysed. Their paraffin-embedded tissue sections were examined by RecurIndex test which comprised 2 models: recurrence index for local recurrence (RI-LR) and recurrence index for distant recurrence (RI-DR). Of 43 patients, there were 26 low-risk and 17 high-risk patients assessed by RI-LR, while 17 low-risk and 26 high-risk patients by RI-DR. For RI-LR, tumor N stage showed statistically significant (P < 0.001) between low- and high-risk patients; for RI-DR, differences were pronounced in tumor grade (P = 0.033), T stage (P = 0.043) and N stage (P = 0.003). In terms of clinical outcomes, the overall survival (OS) of low- and high-risk patients stratified by RI-LR showed no statistically significant differences (P = 0.460), while high-risk patients identified by RI-DR had a significantly worse distant recurrence-free survival (DRFS) (P = 0.035), progression-free survival (PFS) (P = 0.019) and OS (P = 0.044) than low-risk patients. Overall, RI-DR can effectively predict the DRFS, PFS and OS of MBC patients and identify those at low risk of recurrence, which may serve as a potential prognostic tool for MBC.

G-negative bacteria produce myriad N -acyl-homoserine lactones (AHLs) that can function as quorum sensing (QS) signaling molecules. AHLs are also known to regulate various plant biological activities. p -Coumaroyl-homoserine lactone ( p C-HSL) is the only QS molecule produced by a photosynthetic bacterium, Rhodopseudomonas palustris . The role of p C-HSL in the interaction between R. palustris and plant has not been investigated. In this study, we investigated the effect of p C-HSL on plant immunity and found that this QS molecule can induce a systemic resistance to Tobacco mosaic virus (TMV) infection in Nicotiana benthamiana . The results show that p C-HSL treatment can prolong the activation of two mitogen-associated protein kinase genes (i.e., NbSIPK and NbWIPK ) and increase the expression of transcription factor WRKY8 as well as immune response marker genes NbPR1 and NbPR10 , leading to an increased accumulation of reactive oxygen species (ROS) in the TMV-infected plants. Our results also show that p C-HSL treatment can increase activities of two ROS-scavenging enzymes, peroxidase and superoxide dismutase. Knockdown of NbSIPK or NbWIPK expression in N. benthamiana plants through virus-induced gene silencing nullified or attenuated p C-HSL-induced systemic resistance, indicating that the functioning of p C-HSL relies on the activity of those two kinases. Meanwhile, p C-HSL-pretreated plants also showed a strong induction of kinase activities of NbSIPK and NbWIPK after TMV inoculation. Taken together, our results demonstrate that p C-HSL treatment increases plant resistance to TMV infection, which is helpful to uncover the outcome of interaction between R. palustris and its host plants.

Development of a genetic tool for visualization of photosynthetic bacteria (PSB) is essential for understanding microbial function during their interaction with plant and microflora. In this study, Rhodopseudomonas palustris GJ-22-gfp harboring the vector pBBR1-pckA PT -gfp was constructed using an electroporation transformation method and was used for dynamic tracing of bacteria in plants. The results showed that strain GJ-22-gfp was stable and did not affect the biocontrol function, and the Confocal Laser Scanning Microscopy (CLSM) results indicated it could successfully colonised on the surface of leaf and root of tobacco and rice. In tobacco leaves, cells formed aggregates on the mesophyll epidermal cells. While in rice, no aggregate was found. Instead, the fluorescent cells colonise the longitudinal intercellular spaces between epidermal cells. In addition, the results of strain GJ-22 on the growth promotion and disease resistance of tobacco and rice indicated that the different colonization patterns might be related to the bacteria could induce systemic resistance in tobacco.

Background: Asthma is a chronic disease that seriously harms the health of patients. Oxidative stress is involved in asthma. As an oxidative stress-inducible protein, sestrin2 is elevated in oxidative stress-related diseases. We aimed to explore whether sestrin2 was involved in asthma., Methods: Seventy-six subjects (44 in the asthma group, 32 in the control group) were recruited in this study. Plasma sestrin2 levels, peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV 1 ) % predicted, forced vital capacity (FVC) % predicted and FEV 1 /FVC ratio were measured in controls and in asthmatics both during an exacerbation and when controlled after the exacerbation., Results: The asthma group had a significant higher sestrin2 level than the control group (asthmatics during exacerbation, 1.75 ± 0.53 ng/mL vs. 1.32 ± 0.48 ng/mL, p < 0.001; asthmatics when controlled after the exacerbation, 1.56 ± 0.46 ng/mL vs. 1.32 ± 0.48 ng/mL, p = 0.021, respectively). In addition, sestrin2 was negatively correlated with FEV 1 % predicted and FEV 1 /FVC ratio in asthmatics during exacerbation (r = - 0.393, p = 0.008; r = - 0.379, p = 0.011; respectively). Moreover, negative correlations between sestrin2 and FEV 1 % predicted and FEV 1 /FVC ratio also existed in asthmatics when controlled after the exacerbation (r = - 0.543, p < 0.001; r = - 0.433, p = 0.003 respectively). More importantly, multiple linear regression analysis demonstrated that FEV 1 % predicted was independently associated with sestrin2 in asthmatics both during exacerbation and when controlled after the exacerbation., Conclusions: Sestrin2 is involved in asthma. Sestrin2 levels increase in asthmatics both during exacerbation and when controlled after the exacerbation. In addition, sestrin2 is independently associated with FEV 1 % predicted., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Objective: Accidental or intentional cyanide ingestion is an-ever present danger. Rapidly acting, safe, inexpensive oral cyanide antidotes are needed that can neutralize large gastrointestinal cyanide reservoirs. Since humans cannot be exposed to cyanide experimentally, we studied oral cyanide poisoning in rabbits, testing oral sodium thiosulfate with and without gastric alkalization., Setting: University research laboratory., Subjects: New Zealand white rabbits., Interventions: Seven animal groups studied; Groups 1-5 received high dose oral NaCN (50 mg, >LD100) and were treated immediately with oral ( via nasogastric tube): 1) saline, 2) glycine, 3) sodium thiosulfate or 4) sodium thiosulfate and glycine, or 5) after 2 min with intramuscular injection of sodium nitrite and sodium thiosulfate plus oral sodium thiosulfate and glycine. Groups 6-7 received moderate dose oral NaCN (25 mg, LD70) and delayed intramuscular 6) saline or 7) sodium nitrite-sodium thiosulfate., Measurements and Main Results: All animals in the high dose NaCN group receiving oral saline or glycine died very rapidly, with a trend towards delayed death in glycine-treated animals; saline versus glycine-treated animals died at 10.3+3.9 and 14.6+5.9 min, respectively (p=0.13). In contrast, all sodium thiosulfate-treated high dose cyanide animals survived (p<0.01), with more rapid recovery in animals receiving both thiosulfate and glycine, compared to thiosulfate alone (p<0.03). Delayed intramuscular treatment alone in the moderate cyanide dose animals increased survival over control animals from 30% to 71%. Delayed treatment in high dose cyanide animals was not as effective as immediate treatment, but did increase survival time and rescued 29% of animals (p<0.01 versus cyanide alone)., Conclusions: Oral sodium thiosulfate with gastric alkalization rescued animals from lethal doses of ingested cyanide. The combination of oral glycine and sodium thiosulfate may have potential for treating high dose acute cyanide ingestion and merits further investigation. The combination of systemic and oral therapy may provide further options.

A novel arylalkoxycarbonylation of N-aryl acrylamides with carbazates leading to alkoxycarbonylated oxindoles has been developed. The reported reactions employ economical and environmentally benign FeCl2·4H2O as a catalyst and easily accessible and safe carbazates as alkoxycarbonyl radical precursors.

Subarachnoid hemorrhage (SAH) is a medical emergency which can lead to death or severe disability. Misinterpretation of computed tomography (CT) in patients with SAH is a common problem. How to improve the accuracy of diagnosis is a great challenge to both the clinical physicians and medical researchers. In this paper we proposed a method for the automatic detection of SAH on clinical non-contrast head CT scans. The novelty includes approximation of the subarachnoid space in head CT using an atlas based registration, and exploration of support vector machine to the detection of SAH. The study included 60 patients with SAH and 69 normal controls from clinical hospitals. Thirty patients with SAH and 30 normal controls were used for training, while the rest were used for testing to achieve a testing sensitivity of 100% and specificity of 89.7%. The proposed algorithm might be a potential tool to screen the existence of SAH.

Very thin films deposited using atomic layer deposition (ALD) on aluminum mirrors showed extraordinary resistance toward concentrated alkali solutions, various chemical etchants, and solvents. Aluminum mirrors with no surface protection dissolved immediately in 24% aqueous KOH. Mirrors protected with 30 nm electron-beam deposited silica film were fully removed in 30 min. Mirrors with 10, 30, and 120 nm films grown by ALD required, respectively, 10, 15, and 60 h of exposure to the alkali for the mirror to be fully removed. Likewise, large-scale hydrogen bubbling was observed immediately upon immersing mirrors coated with electron-beam deposited silica in aqueous KOH, whereas no visible hydrogen bubbling was detected for the mirror protected by ALD silica. For mirrors protected by 120 nm ALD silica, a 2 h soak in various acid and solvent media produced no discernible change.

In the title compound, C(10)H(11)NO(5), the six-membered 1,3-dioxane ring displays a chair conformation, with the hydr-oxy and 2-nitro-phenyl groups in equatorial positions, which minimizes steric hindrance. In the crystal, mol-ecules are linked into chains along the b axis by inter-molecular O-H⋯O hydrogen bonds.

Yak is a unique domestic animal of Qinghai-Tibetan Plateau. Its unique adaptability to the high altitude environment has been hypothesized due to special pulmonary microvasculature. However, the anatomical evidence is still less. The present study characterized the subpleural pulmonary microvascular architecture of newborn yak by vascular corrosion cast and the scanning electron microscopy. The results showed the dense vascular network occurred in subpleural area in newborn yak. Subpleural vascular network was found in most of observed areas, while the sparse vascular network crept onto the subpleural network in some fields of view. The subpleural microvessels and their branches made up of the subpleural microvascular network. According to the branching sequence of vessels, the subpleural arterioles could be divided into four grades: the arteriole, terminal arteriole, precapillary arteriole and capillary. The subpleural capillary network in the local area could be classified into three different forms, including sheetlike vascular network, wrinkled vascular network and weblike vascular network. It was the specific characteristics on the cast surface of the microvessels that was the adaptable peculiarities. Anastomoses were found between the pleural microvessels and the interlobular capillaries, or between the pleural microvessels and the subpleural capillaries, or between the interlobular capillaries and the subpleural capillaries. Therefore, there was significant difference on the subpleural pulmonary microvasculature between newborn yak and other adult mammals.

Despite the significant recent increase in quantum-based optoelectronics device research, few deposition techniques can reliably create the required functional nanoscale systems. Atomic layer deposition (ALD) was used here to study the quantum effects attainable through the use of this ångström-level controlled growth process. Size-dependent quantum confinement has been demonstrated using TiO(2) layers of nanoscale thickness applied to the surfaces of silicon wafers. TiO(2) films were deposited at 100 °C using TiCl(4) and H(2)O(2) in a viscous flow ALD reactor, at a rate of 0.61 Å/cycle. The low-temperature process was utilized to guarantee the amorphous deposition of TiO(2) layers and post-deposition thermal annealing was employed to promote crystallite-size modification. Hydrogen peroxide significantly reduced the residual chlorine that remained from a typical TiCl(4)-H(2)O ALD process at this temperature, down to 1.6%. Spectroscopic ellipsometry was used to quantify the optical properties both below and above the bandgap energy. A central composite design was employed to map the surface response of the film thickness-dependent bandgap shift for the as-deposited case and up to a thermal annealing temperature of 550 °C. The Brus model was used to develop a correlation between the amorphous TiO(2) film thickness and the quantum length to promote equivalent bandgap shifts.