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Abstract Background In daily life, people often follow others’ gaze direction to infer their attention and mental state. This phenomenon is known as gaze following. Objective This study aimed to explore whether gaze following in different age groups is influenced by celebrity identity. Methods We recruited 70 participants, including 35 older adults and 35 young adults. The experimental materials consisted of three faces with different identity information (a political leader, a movie star, and an ordinary person). Each face had left and right gaze conditions. Targets and cues were presented with both longer and shorter stimulus onset asynchrony (SOA) conditions. Results Both older adults and young adults exhibited similar gaze following behaviors. Importantly, the celebrity effect on gaze following was observed in both groups, with stronger effects induced by the leader’s and star’s gazes compared to the ordinary person’s gaze. Older adults showed a larger facilitation effect under the longer SOA condition compared to the shorter SOA, while no such SOA-related facilitation effect was found for young adults. Conclusion These findings suggest that older adults can integrate social information from others’ faces (celebrity identity) into the process of gaze following as effectively as young adults.

Abstract Solanaceous plants produce tropane alkaloids (TAs) via esterification of 3α- and 3β-tropanol. Although littorine synthase is revealed to be responsible for 3α-tropanol esterification that leads to hyoscyamine biosynthesis, the genes associated with 3β-tropanol esterification are unknown. Here, we report that a BAHD acyltransferase from Atropa belladonna, 3β-tigloyloxytropane synthase (TS), catalyzes 3β-tropanol and tigloyl-CoA to form 3β-tigloyloxytropane, the key intermediate in calystegine biosynthesis and a potential drug for treating neurodegenerative disease. Unlike other cytosolic-localized BAHD acyltransferases, TS is localized to mitochondria. The catalytic mechanism of TS is revealed through molecular docking and site-directed mutagenesis. Subsequently, 3β-tigloyloxytropane is synthesized in tobacco. A bacterial CoA ligase (PcICS) is found to synthesize tigloyl-CoA, an acyl donor for 3β-tigloyloxytropane biosynthesis. By expressing TS mutant and PcICS, engineered Escherichia coli synthesizes 3β-tigloyloxytropane from tiglic acid and 3β-tropanol. This study helps to characterize the enzymology and chemodiversity of TAs and provides an approach for producing 3β-tigloyloxytropane.

ABSTRACTBackground The prognosis for advanced intrahepatic cholangiocarcinoma (iCCA) is poor, and there remains an urgent need to develop efficient systemic therapy. The efficacy of Pembrolizumab immunotherapy combined with lenvatinibin in iCCA is still unclear. The role of Epstein–Barr-virus (EBV) as a biomarker in iCCA for response to immunotherapy needs further exploration.Case presentation We report a case of a 60-year-old female with EBV-associated advanced iCCA (EBVaiCCA) who progressed after first-line therapy. She accomplished an available response to the combination therapy of pembrolizumab with lenvatinib, with overall survival of 20 months.Conclusions As far as we know, this is the first case report about the application of Pembrolizumab with lenvatinib for EBVaiCCA patients. This case indicates that the combination of immunotherapy and antiangiogenic therapy provides a glimmer of hope for advanced EBVaiCCA patients.

Photocatalysis, recognized as an eco-friendly and efficient energy conversion and utilization technology, has garnered widespread attention owing to its potential to address environmental and energy-related challenges. Its capacity to harness sunlight as an energy source makes it particularly promising. Photocatalytic materials are central to the advancement of photocatalytic technology, and the emergence of new visible-light-responsive photocatalysts represents a noteworthy trend in this field. WO3 is a semiconductor material composed of transition-metal oxides. It exhibits excellent responsiveness to visible light and is considered to be an ideal photocatalytic material. However, the persistent issue of low photogenerated charge separation efficiency has hindered their development. In contrast to pure WO3, its hydrated form, WO3·nH2O, has garnered considerable interest from researchers because of its enhanced charge transfer and separation efficiency. This study comprehensively reviews recent applications and research progress in photocatalysis using WO3·nH2O. This study introduces the crystal structure of WO3·nH2O photocatalysts and analyzes the impact of crystal water on WO3. This analysis covered the crystal structure, charge transfer, separation, and band structure. The study then extensively discusses the preparation methods for WO3·nH2O and modified photocatalysis based on WO3·nH2O, with particular emphasis on elucidating these methods. Finally, this study summarizes the diverse applications of WO3·nH2O and its composite materials in water desorption for hydrogen production, CO2 reduction, and dye pollutant degradation. In addition, it delves into the prospects for future development of these materials. The overarching goal of this study was to serve as a valuable reference for advancing WO3·nH2O photocatalytic systems.

BackgroundObservational studies have found associations between blood cell traits and inflammatory bowel diseases (IBDs), whereas the causality and dose-effect relationships are still undetermined.MethodsTwo-sample Mendelian randomization (MR) analyses using linear regression approaches, as well as Bayesian model averaging (MR-BMA), were conducted to identify and prioritize the causal blood cell traits for Crohn’s disease (CD) and ulcerative colitis (UC). An observational study was also performed using restricted cubic spline (RCS) to explore the relationship between important blood cell traits and IBDs.ResultsOur uvMR analysis using the random effects inverse variance weighted (IVW) method identified eosinophil (EOS) as a causal factor for UC (OR = 1.36; 95% CI: 1.13, 1.63). Our MR-BMA analysis further prioritized that high level of lymphocyte (LYM) decreased CD risk (MIP = 0.307; θ^MACE = −0.059; PP = 0.189; θ^λ = −0.173), whereas high level of EOS increased UC risk (MIP = 0.824; θ^MACE = 0.198; PP = 0.627; θ^λ = 0.239). Furthermore, the observational study clearly depicts the nonlinear relationship between important blood cell traits and the risk of IBDs.ConclusionUsing MR approaches, several blood cell traits were identified as risk factors of CD and UC, which could be used as potential targets for the management of IBDs. Stratified genome-wide association studies (GWASs) based on the concentration of traits would be helpful owing to the nonlinear relationships between blood cell traits and IBDs, as demonstrated in our clinical observational study. Together, these findings could shed light on the clinical strategies applied to the management of CD and UC.

Building an ecological security pattern (ESP) can safeguard and improve the structure, functions and services of regional ecosystems. Furthermore, it is also one of the significant spatial methods to mitigate the conflict between ecological conservation and economic growth. Most previous researches on the construction of ESP have directly utilized extensive regions of forestland, grassland, water area or nature reserves as ecological sources (ESs) without weighing the habitat quality (HQ) and ecological protection red line (EPRL). The ES of the Dawen River basin (DRB) was identified through morphological spatial pattern analysis (MSPA) and landscape connectivity index. By employing the minimum cumulative resistance model (MCR), the potential ecological corridor (EC) was identified, and its importance was evaluated by gravity model. Simultaneously, the spatial properties of HQ and ecological resistance (ER) were analyzed. Finally, this paper proposed an optimization strategy for ESP in accordance with the EPRL. The results indicate that: (1) The DRB contained 15 important ESs, mainly concentrated in water and mountain forest areas. (2) 105 ECs were extracted by MCR and gravity model, including 35 level 1 corridors and 70 level 2 corridors, which were primarily concentrated in the eastern region of the basin. (3) Based on the spatial characteristics of HQ and ER, as well as the EPRL in the research, the ESP of “one axis, two belts and five zones” in the DRB was constructed and control strategies were proposed. This research offers some reference for ecological environment protection and restoration and regional sustainable development in the Yellow River basin.

Salmonella enterica Typhimurium DT104 (S. Typhimurium DT104) is an important foodborne pathogen that is associated with poultry and poultry products. Currently, there is very little information on the underlying molecular mechanisms that allow DT104 to survive and propagate in poultry meat and the poultry processing environment. The current study assessed the global gene expression of DT104 in ground chicken extract (GCE) compared to brain heart infusion (BHI) medium using RNA-Seq technology. DT104 was grown to the early stationary phase (ESP), inoculated into GCE or BHI, and then re-grown to the log phase before RNA was extracted and transcripts were quantified by RNA-Seq. Gene expression for DT104 grown in GCE was then compared to that of DT104 grown in BHI for samples grown to the ESP. Growth in GCE resulted in the up-regulated expression of genes related to translation, carnitine metabolism (23–283-fold change), and cobalamin (vitamin B12) biosynthesis (14-fold change). In particular, the presence of carnitine in chicken meat, and thus, in GCE, which lacks carbohydrates, may allow Salmonella to utilize this compound as a carbon and nitrogen source. This study demonstrates that RNA-Seq data can provide a comprehensive analysis of DT104 gene expression in a food model for poultry products. This study also provides additional evidence for the importance of metabolic adaptation in the ability of S. enterica to successfully adapt to and occupy niches outside of its host and provides potential targets that could be used to develop intervention strategies to control Salmonella in poultry.

Abstract Background Coronary Artery Disease (CAD) is primarily caused by inflammation which is closely linked to the gut microbiota. Si-Miao-Yong-An (SMYA) decoction is a traditional Chinese herbal formula with anti-inflammatory properties that found to be effective against CAD. However, it is still unclear whether SMYA can modulate gut microbiota and whether it contributes to the improvement of CAD by reducing inflammation and regulating the gut microbiota. Methods The identification of components in the SMYA extract was conducted using the HPLC method. A total of four groups of SD rats were orally administered with SMYA for 28 days. The levels of inflammatory biomarkers and myocardial damage biomarkers were measured through ELISA, while echocardiography was used to assess heart function. Histological alterations in the myocardial and colonic tissues were examined following H&E staining. Western blotting was performed to evaluate protein expression, whereas alterations in gut microbiota were determined by 16 s rDNA sequencing. Results SMYA was found to enhance cardiac function and decrease the expression of serum CK-MB and LDH. SMYA was also observed to inhibit the TLR4/NF-κB signaling pathway by downregulating the protein expression of myocardial TLR4, MyD88, and p-P65, leading to a reduction in serum pro-inflammatory factors. SMYA modified the composition of gut microbiota by decreasing the Firmicutes/Bacteroidetes ratio, modulating Prevotellaceae_Ga6A1 and Prevotellaceae_NK3B3 linked to the LPS/TLR4/NF-κB pathway, and increasing beneficial microbiota such as Bacteroidetes, Alloprevotella, and other bacterial species. Moreover, SMYA was found to safeguard the intestinal mucosal and villi structures, elevate the expression of tight junction protein (ZO-1, occludin), and reduce intestinal permeability and inflammation. Conclusions The results indicate that SMYA has the potential to modulate the gut microbiota and protect the intestinal barrier, thereby reducing the translocation of LPS into circulation. SMYA was also found to inhibit the LPS-induced TLR4/NF-κB signaling pathway, leading to a decrease in the release of inflammatory factors, which ultimately mitigated myocardial injury. Hence, SMYA holds promise as a therapeutic agent for the management of CAD.

AbstractBackground Si-Miao-Yong-An decoction (SMYAD) is a conventional therapeutic formula for treat thromboangiitis obliterans (TAO), consisting of four Chinese herbs: Lonicerae japonicae Thunb. (Jinyinhua), Scrophularia ningpoensis Hemsl. (Xuanshen), Angelica sinensis (Oliv.) Diels (Danggui) and Glycyrrhiza uralensis Fisch. (Gancao). However, the mechanism of SMYAD in TAO treatment remains unclear.Methods Components, as well as potential targets of SMYAD in TAO therapy, were downloaded from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Subsequently, with the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signalling pathways of the targets enrichment were performed. Next, based on STRING online database, the protein interaction network of vital targets was built and analysed. Molecular docking and calculation of the binding affinity were performed using AutoDock. The PyMOL software was employed to observe docking outcomes of active compounds and protein targets. Based on the predicted outcomes of network pharmacology, in vivo and in vitro tests were performed for validation. In vivo experiment, the TAO rats model was established using sodium laurate injection into the femoral artery. The symptoms as well as pathological changes of the femoral artery were observed. Besides, the predicted targets were verified by the RT-qPCR, in vitro experiment. The cell viability in LPS-induced human umbilical vein endothelial cells (HUVECs) was detected using CCK-8 kit, and the predicted targets were also verified by the RT-qPCR.Results In the network pharmacology analysis, we obtained 105 chemical components in SMYAD and 24 therapeutic targets. We found that the mechanism SMYAD in TAO therapy was primarily associated with inflammation and angiogenesis by constructing multiple networks. Quercetin, vestitol and beta-sitosterol were important compounds, and interleukin-6 (IL6), MMP9, and VEGFA were key targets. According to molecular docking, active compounds (quercetin, vestitol and beta-sitosterol) and targets (IL6, MMP9 and VEGFA) showed good binding interactions. In in vivo experiment, SMYAD ameliorated the physical signs and pathological changes, inhibited the expression of IL6 and MMP9, and enhanced the expression of VEGFA. In an in vitro experiment, SMYAD increased the cell viability of LPS-induced HUVECs and the expression of VEGFA, and reduced the expression of IL6 and MMP9.Conclusions This study showed that SMYAD improves TAO symptoms and inhibits the development of TAO. The mechanism could be associated with anti-inflammatory and therapeutic angiogenesis.

Abstract In the production process, the manufacturing behavior and all the essential factors are affected by several disturbance factors, showing a complex dynamic fluctuation law. It makes the stability control process a difficult problem in environmental constraints. In this paper, the workshop production process is considered, and an improved coupled map lattice workshop production network state model is proposed. On this basis, the controller with the function of resource load protection is designed, and the network state model of the workshop based on the pinning control is developed. Three kinds of stability control strategies, SAC (Self-adaption Control) , SC (Self-acting Control) and PC (Pinning Control) , are designed based on disturbance triggering behavior and node state transition rules. In addition, two control effect evaluation indexes, RTS (Recovery Time Steps) and NFT (Node Failure Times) are designed. Considering the actual production data of diesel fuel injection system parts production workshop as example, the model is simulated and verified. The results show that under different disturbance intensities, compared with the SAC strategy, the RTS-Average value of the PC strategy is reduced by 29.83% on average, and the NFT-Average values are reduced by 46.9% on average. This proves that the pinning control strategy has certain advantages in controlling time length and propagation scale of disturbance propagation.

Tropane alkaloids (TAs) are synthesized by some species in Solanaceae. Here, the authors assemble the genomes of two representative TAs producing species, show that gene loss shapes uneven distribution of TAs in Solanaceae, and identify a cytochrome P450 gene catalyzing N-demethylation of hyoscyamine to generate norhyoscyamine.

Anthocyanins are water-soluble flavonoid pigments that play a crucial role in plant growth and metabolism. They serve as attractants for animals by providing plants with red, blue, and purple pigments, facilitating pollination and seed dispersal. The fruits of solanaceous plants, tomato (Solanum lycopersicum) and eggplant (Solanum melongena), primarily accumulate anthocyanins in the fruit peels, while the ripe fruits of Atropa belladonna (Ab) have a dark purple flesh due to anthocyanin accumulation. In this study, an R2R3-MYB transcription factor (TF), AbMYB1, was identified through association analysis of gene expression and anthocyanin accumulation in different tissues of A. belladonna. Its role in regulating anthocyanin biosynthesis was investigated through gene overexpression and RNA interference (RNAi). Overexpression of AbMYB1 significantly enhanced the expression of anthocyanin biosynthesis genes, such as AbF3H, AbF3′5′H, AbDFR, AbANS, and Ab3GT, leading to increased anthocyanin production. Conversely, RNAi-mediated suppression of AbMYB1 resulted in decreased expression of most anthocyanin biosynthesis genes, as well as reduced anthocyanin contents in A. belladonna. Overall, AbMYB1 was identified as a fruit-expressed R2R3-MYB TF that positively regulated anthocyanin biosynthesis in A. belladonna. This study provides valuable insights into the regulation of anthocyanin biosynthesis in Solanaceae plants, laying the foundation for understanding anthocyanin accumulation especially in the whole fruits of solanaceous plants.

BackgroundImmune-checkpoint inhibitors (ICIs) combined with chemotherapy have been successfully used in clinical trials to treat advanced gastric cancer. However, the efficacy and safety of first-line immunotherapy combined with chemotherapy in Chinese patients are unknown.MethodsThis multicenter retrospective study included patients with human epidermal growth factor receptor-2 (HER-2) negative advanced gastric cancer treated with first-line chemotherapy or chemotherapy with an ICI between January 2019 and December 2022. Propensity score matching was used to compare progression-free survival (PFS), overall survival, objective response rates, and adverse reactions between cohorts.ResultsAfter propensity score matching, 138 patients, who had balanced baseline characteristics, were included in the chemotherapy and combination treatment groups. The median follow-up duration was 16.90 months, and the median PFS was 8.53 months (95% confidence interval [CI] 7.77-9.28) in the combination treatment group and 5.97 months (95% CI 4.56-7.37) in the chemotherapy group. The median survival duration was 17.05 months (95% CI 14.18-19.92) in the combination treatment group and 16.46 months (95% CI 12.99-19.93) in the chemotherapy group. The PFS subgroup analysis revealed that age ≥65 years, women, Eastern Cooperative Oncology Group performance status of 1, non-signet ring cell carcinoma, esophagogastric junction, liver metastasis, peritoneal metastasis, no massive ascites, only one metastatic organ, and combined platinum-based chemotherapy correlated with treatment benefit. The incidences of adverse events above grade 3 were comparable between groups.ConclusionsOur study confirmed the ATTRACTION-4 trial results. Compared with chemotherapy, first-line ICIs combined with chemotherapy prolonged PFS but did not improve overall survival in patients with HER-2-negative advanced gastric cancer.

IntroductionAs the third largest food crop in the world, maize has wide varieties with similar appearances, which makes identification difficult. To solve the problem of identification of hybrid maize varieties, a method based on hyperspectral image technology combined with a convolutional neural network (CNN) is proposed to identify maize varieties.MethodsIn this study, 735 maize seeds from seven half-parent hybrid maize varieties were regarded as the research object. The maize seed images in the range of 900 ~ 1700nm were obtained by hyperspectral image acquisition system. The region of interest (ROI) of the embryo surface was selected, and the spectral reflectance of maize seeds was extracted. After Savitzky-Golay (SG) Smoothing pretreatment, Maximum Normalization (MN) pretreatment was performed. The 56 feature wavelengths were selected by Competitive Adaptive Reweighting Algorithm (CARS) and Successive Projection Algorithm (SPA). And the 56 wavelengths were mapped to high-dimensional space by high-dimensional feature mapping and then reconstructed into three-dimensional image features. A five-layer convolution neural network was used to identify three-dimensional image features, and nine (SG+MN)-(CARS+SPA)-CNN maize variety identification models were established by changing the input feature dimension and the depth factor size of the model layer.Results and DiscussionThe results show that the maize variety classification model works best, when the input feature dimension is 768 and the layer depth factor d is 1.0. At this point, the model accuracy of the test set is 96.65% and the detection frame rate is1000 Fps/s in GPU environment, which can realize the rapid and effective non-destructive detection of maize varieties. This study provides a new idea for the rapid and accurate identification of maize seeds and seeds of other crops.

Artemisinin is a potent anti-malarial sesquiterpene lactone that is naturally biosynthesized in glandular trichomes of a Chinese herbal plant, Artemisia annua. Although semi-synthesis of artemisinin in yeast has been feasible, at present the A. annua plant is still the main commercial source of artemisinin. The content of artemisinin however is low in A. annua, limiting its supply to malarial victims. So it's crucial to elevate artemisinin production in A. annua. Up to date artemisinin biosynthetic pathway has been completely elucidated. And many regulatory factors, mediating diverse plant hormone or environmental signaling routes, have been identified to get involved in the regulation of artemisinin biosynthesis and glandular trichome formation. Understanding the regulatory mechanisms of artemisinin biosynthesis and glandular trichome formation will be conducive to our practice for improving artemisinin production by metabolic engineering. In this review, the metabolic regulatory network with regard to artemisinin biosynthesis and glandular trichome formation is summarized, and the advance on metabolic engineering to increase artemisinin content in A. annua is also discussed.

ObjectiveTo compare the efficacy and safety of different-course corticosteroids plus mycophenolate mofetil (MMF) as maintenance therapy in autoimmune encephalitis (AE) with neuronal surface antibodies (NSAbs) without tumor and explore the optimal course of corticosteroids.MethodsFifty-five patients with definite AE without tumor were enrolled consecutively between June 2015 and November 2020 and retrospectively divided three groups according to the course of treatment with corticosteroid, i.e., a group of patients with a course of 3-6 months (Group 3-6mo), 6-12 months (Group 6-12mo), and >12 months (Group >12mo). Demographic data, clinical manifestation and ancillary tests results were recorded. The dosage and courses of corticosteroid treatment, the recovery of neurological function, the occurrence of adverse effects, and relapses were followed up.ResultsA total of 55 patients were included in the final analysis. The numbers of patients in Group 3-6 mo, Group 6-12 mo, and Group >12 mo was 14, 17, and 24, respectively. A significantly higher proportion of patients in Group >12 mo showed a decreased level of consciousness at the onset (12, 50%) than in Group 3-6 mo and Group 6-12 mo (2,14.3%; 3, 17.6%) (p = 0.033). The incidence of MRI abnormalities was significantly higher in Group 6-12 mo and Group >12 mo (10, 58.8%; 16, 66.7%) than in Group 3-6 mo (3, 21.4%) (P=0.023). Ordinal regression analysis indicated that decreased level of consciousness was associated with the course of corticosteroid (OR=3.838, 95% CI: 1.103-13.323, P=0.035). No significant difference was observed between the three groups regarding the cumulative dose of corticosteroids administered during the first three months of long-term treatment (P>0.05). Additionally, no significant difference in the cumulative dosage of corticosteroids was found between patients in Group 6-12 months and Group >12 months during the first 6 months after beginning long-term treatment. The mRS scores of the three groups were not statistically significant before and after first-line treatment or at the last follow-up. Bonferroni multiple comparison test indicated that the mRS scores of patients in Group 6-12 months and Group >12 months were not statistically significant at 3 months and 12 months after the start of long-term treatment. During the follow-up, 50 (90.9%) patients achieved satisfactory neurological function (mRS score ≤2). Five patients (9.1%) experienced a first relapse and 2 of them were overlapped with both anti-NMDA receptor and glial antibodies. The incidence of adverse effects was significantly higher in Group >12 mo (17, 70.8%) than in Group 3-6 mo (3, 21.4%) and Group 6-12 mo (5, 29.4%) (P=0.003).ConclusionsThe beneficial effects of oral corticosteroid treatment may do not persist beyond 12 months and may even contribute to an increased incidence of adverse effects. In order to optimize the effectiveness and safety of treatment, we recommend a corticosteroid course of 3-12 months. Patients with reduced levels of consciousness may be more inclined to choose longer courses of corticosteroids for long-term treatment. Patients with an “overlapping syndrome” may require more intense immunotherapy to prevent relapse.

Objective: This article aims to longitudinally compare nasopharyngeal carcinoma (NPC) patients' quality of life (QoL) during radiotherapy (RT) and identify QoL correlates. Methods: This study included 98 patients, with 85 completing full follow-up. Data were collected at baseline (T1), midpoint of RT (T2), and RT completion (T3), between October 2021 and November 2022. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). RIOM severity was evaluated by the toxicity criteria of Radiation Therapy Oncology Group (RTOG). The nutritional status was evaluated using the Nutritional Risk Screening 2002 (NRS 2002), body mass index (BMI), and the Patient-Generated Subjective Global Assessment (PG-SGA). The generalized estimating equation described the QoL evolution and correlated it with RIOM, nutritional status, and other influential factors. Results: Significant deterioration was observed in various subscales of EORTC QLQ-C30 during RT, including global health status (GHS), physical function, role function, emotional function, fatigue, nausea/vomiting, pain, insomnia, appetite loss, and constipation (all P ​

Alzheimer’s disease (AD), a neurodegenerative disorder, is characterized by its ability to cause memory loss and damage other cognitive functions. Aggregation of amyloid beta (Aβ) plaques and neurofibrillary tangles in the brain are responsible for the development of Alzheimer’s disease (AD). While attempts targeting Aβ and tau proteins have been extensively conducted in the past decades, only two FDA-approved drugs (i.e., monoclonal antibodies) tackle the underlying biology of Alzheimer’s disease. In this study, an integrated computational framework was developed to identify new drug targets for Alzheimer’s disease and identify small molecules as potential therapeutical options. A systematic investigation of the gene networks firstly revealed that the Apolipoprotein E4 (ApoE4) gene plays a central role among genes associated with Alzheimer’s disease. The ApoE4 protein was then chosen as the protein target based on its role in the main pathological hallmarks of AD, which has been shown to increase Aβ accumulation by directly binding to Aβ as well as interfering with Aβ clearance that is associated with other receptors. A library of roughly 1.5 million compounds was then virtually screened via a ligand-protein docking program to identify small-molecule compounds with potential binding capacity to the ApoE4 N-terminal domain. On the basis of compound properties, 312 compounds were selected, analyzed and clustered to further identify common structures and essential functional groups that play an important role in binding ApoE4. The in silico prediction suggested that compounds with four common structures of sulfon-amine-benzene, 1,2-benzisothiazol-3-amine 1,1-dioxide, N-phenylbenzamide, and furan-amino-benzene presented strong hydrogen bonds with residues E27, W34, R38, D53, D153, or Q156 in the N terminal of ApoE4. These structures might also form strong hydrophobic interactions with residues W26, E27, L28, L30, G31, L149, and A152. While the 312 compounds can serve as drug candidates for further experiment assays, the four common structures, along with the residues for hydrogen bond or hydrophobic interaction, pave the foundation to further optimize the compounds as better binders of ApoE4.

Livestock dung, discarded crop straws, and residual plastic film are the primary agricultural non-point sources of pollution. For livestock dung and discarded crop straw, the general treatment focuses on compost, animal fodder, industrial raw material, and new energy. The development of degradable mulch film is the main way to solve pollution from residual plastic film. However, an effective way to solve the above three types of pollution simultaneously and use them for ecological circular agriculture has been less studied. In this study, using cow dung and flax straw wastes as raw materials, we prepared natural, fibre-based paper mulch using the rapid-Kothen method and analysed the film-forming mechanism. Based on the Van Soest method, the cow dung and flax straw waste contain abundant cellulose fibres: 36.75% and 54.69%, respectively. The tensile strength and tear strength of fibre paper mulch are 1.87 kN/m and 19.91 N/mm, respectively. To enhance the adaptability of the fibre paper mulch in humid environments, the surface of the mulch was treated with alkyl ketene dimer (AKD). The AKD-coated fibre paper mulch displays hydrophobic properties, indicated by a contact angle of 128° ± 2°. It has a wet tensile strength of 0.64 kN/m and a wet tear strength of 8.23 N/mm. Additionally, it exhibits a dry tensile strength and a tear strength of 2.13 kN/m and 16.43 N/mm, respectively. Notably, the dry tensile strength is increased by 16.31%. In this way, the livestock dung and discarded crop straw can be reused, reducing dung pollution and straw burning in livestock farms, and the final products can alleviate the residual film pollution simultaneously.

miRNAs moderately inhibit the translation and enhance the degradation of their target mRNAs via cognate binding sites located predominantly in the 3′-untranslated regions (UTR). Paradoxically, miRNA targets are also polysome-associated. We studied the polysome association by the comparative translationally less-active light- and more-active heavy-polysome profiling of a wild type (WT) human cell line and its isogenic mutant (MT) with a disrupted DICER1 gene and, thus, mature miRNA production. As expected, the open reading frame (ORF) length is a major determinant of light- to heavy-polysome mRNA abundance ratios, but is rendered less powerful in WT than in MT cells by miRNA-regulatory activities. We also observed that miRNAs tend to target mRNAs with longer ORFs, and that adjusting the mRNA abundance ratio with the ORF length improves its correlation with the 3′-UTR miRNA-binding-site count. In WT cells, miRNA-targeted mRNAs exhibit higher abundance in light relative to heavy polysomes, i.e., light-polysome enrichment. In MT cells, the DICER1 disruption not only significantly abrogated the light-polysome enrichment, but also narrowed the mRNA abundance ratio value range. Additionally, the abrogation of the enrichment due to the DICER1 gene disruption, i.e., the decreases of the ORF-length-adjusted mRNA abundance ratio from WT to MT cells, exhibits a nearly perfect linear correlation with the 3′-UTR binding-site count. Transcription factors and protein kinases are the top two most enriched mRNA groups. Taken together, the results provide evidence for the light-polysome enrichment of miRNA-targeted mRNAs to reconcile polysome association and moderate translation inhibition, and that ORF length is an important, though currently under-appreciated, transcriptome regulation parameter.

Abstract Background Primary gastric lymphoma (PGL) is the most common extranodal non-Hodgkin lymphoma (NHL). Due to the rarity of the disease, it is important to create a predictive model that provides treatment and prognosis for patients with PGL and physicians. Methods A total of 8898 and 127 patients diagnosed with PGL were obtained from the SEER database and from our Cancer Center as training and validation cohorts, respectively. Univariate and multivariate Cox proportional hazards models were used to investigate independent risk factors for the construction of predictive survival nomograms, and a web nomogram was developed for the dynamic prediction of survival of patients with PGL. The concordance index (C-index), calibration plot, and receiver operating characteristics (ROC) curve were used to evaluate and validate the nomogram models. Results There were 8898 PGL patients in the SEER cohort, most of whom were married men over the age of 60, 16.1% of the primary tumors were localized in the antrum and pylori of the stomach, which was similar to the composition of 127 patients in the Chinese cohort, making both groups comparable. The Nomogram of overall survival (OS) was compiled based on eight variables, including age at diagnosis, sex, race, marital status, histology, stage, radiotherapy and chemotherapy. Cancer-specific survival (CSS) nomogram was developed with eight variables, including age at diagnosis, sex, marital status, primary tumor site, histology, stage, radiotherapy and chemotherapy. The C-index of OS prediction nomogram was 0.948 (95% CI: 0.901–0.995) in the validation cohort, the calibration plots showed an optimal match and a high area below the ROC curve (AUC) was observed in both training and validation sets. Also, we established the first web-based PGL survival rate calculator ( https://yangjinru.shinyapps.io/DynNomapp/ ). Conclusion The web dynamic nomogram provided an insightful and applicable tool for evaluating PGL prognosis in OS and CSS, and can effectively guide individual treatment and monitoring.

ObjectiveThe study aimed to compare the clinical characteristics and short-term outcomes of pediatric and adult Japanese encephalitis (JE) patients in order to find out the differences.MethodsFrom August 2006 to October 2019, 107 patients (62 pediatric patients and 45 adult patients) with JE were enrolled. Clinical characteristics and short-term outcomes were analyzed. The short-term outcome of each patient was defined as a good outcome or poor outcome according to their Glasgow Coma Scale (GCS) scores (GCS > 8 vs. GCS ≤ 8) at discharge.ResultsAs for acute complications, the incidence of pulmonary infection was higher in 25 adults (25/45, 55.6%) than in 19 children (19/62, 30.6%; P = 0.01). Upper gastrointestinal bleeding was more common in patients with pulmonary infection, with 10 of these patients experiencing the symptom (10/44, 22.7%) compared to only one patient without pulmonary infection (1/63, 1.6%; P = 0.001). The proportion of mechanical ventilation and admission to the intensive care unit (ICU) for supportive care was higher in patients with pulmonary infection than in patients without infection (P < 0.001, P = 0.008, respectively). The GCS scores at discharge in patients with pulmonary infection (7, 4–12.75) were lower than in patients without pulmonary infection (14, 10-14; P < 0.001). Although the GCS scores at the admission of children (9.5, 7–13) were similar to that of adults (7, 6–13), the GCS scores at the discharge of adults (7, 3.5–13) were lower than that of children (13, 10.75–14; P < 0.001).ConclusionThe short-term outcome of JE was worse in adults. Pulmonary infection was correlated with a high incidence of upper gastrointestinal bleeding, mechanical ventilation, and ICU hospitalization in JE. Pulmonary infection is a prognostic predictor of short-term outcomes in patients with JE. Vaccination for adults should be initiated.

IntroductionDepression is a serious psychiatric disorder characterized by prolonged sadness, loss of interest or pleasure. The dominant alpha peak activity in resting-state EEG is suggested to be an intrinsic neural marker for diagnosis of mental disorders.MethodsTo investigate an association between alpha peak activity and depression severity, the present study recorded resting-state EEG (EGI 128 channels, off-line average reference, source reconstruction by a distributed inverse method with the sLORETA normalization, parcellation of 68 Desikan–Killiany regions) from 155 patients with depression (42 males, mean age 35 years) and acquired patients’ scores of Self-Rating Depression Scales. We measured both the alpha peak amplitude that is more related to synchronous neural discharging and the alpha peak frequency that is more associated with brain metabolism.ResultsThe results showed that over widely distributed brain regions, individual patients’ alpha peak amplitudes were negatively correlated with their depressive scores, and individual patients’ alpha peak frequencies were positively correlated with their depressive scores.DiscussionThese results reveal that alpha peak amplitude and frequency are associated with self-rating depressive score in different manners, and the finding suggests the potential of alpha peak activity in resting-state EEG acting as an important neural factor in evaluation of depression severity in supplement to diagnosis.

Artemisia annua is the main natural source of artemisinin production. In A. annua, extended drought stress severely reduces its biomass and artemisinin production while short-term water-withholding or abscisic acid (ABA) treatment can increase artemisinin biosynthesis. ABA-responsive transcription factor AabZIP1 and JA signaling AaMYC2 have been shown in separate studies to promote artemisinin production by targeting several artemisinin biosynthesis genes. Here, we found AabZIP1 promote the expression of multiple artemisinin biosynthesis genes including AaDBR2 and AaALDH1, which AabZIP1 does not directly activate. Subsequently, it was found that AabZIP1 up-regulates AaMYC2 expression through direct binding to its promoter, and that AaMYC2 binds to the promoter of AaALDH1 to activate its transcription. In addition, AabZIP1 directly transactivates wax biosynthesis genes AaCER1 and AaCYP86A1. The biosynthesis of artemisinin and cuticular wax and the tolerance of drought stress were significantly increased by AabZIP1 overexpression, whereas they were significantly decreased in RNAi-AabZIP1 plants. Collectively, we have uncovered the AabZIP1-AaMYC2 transcriptional module as a point of cross-talk between ABA and JA signaling in artemisinin biosynthesis, which may have general implications. We have also identified AabZIP1 as a promising candidate gene for the development of A. annua plants with high artemisinin content and drought tolerance in metabolic engineering breeding.

Paper mulch has the advantages of simple process, low production cost and strong degradability, but it is still a great challenge to prepare paper mulch with excellent water resistance and light transmittance. In this paper, through a simple physical brushing method, Zinc oxide (ZnO) solution and silica (SiO2) solution were brushed on the surface of paper mulch film respectively, and ZnO/SiO2 composite superhydrophobic paper mulch film (CSPMF) with micro-nano rough structure was constructed. The microstructure of original paper mulch film (OPMF) and ZnO/SiO2 CSPMF was studied by scanning electron microscope (SEM), and the superhydrophobic surface elements were analyzed by energy dispersive spectrometer (EDS). The contact angle (CA) and rolling angle (RA) of two kinds of sample surfaces are measured by contact angle meter. The static CA and RA of ZnO/SiO2 CSPMF were 160 ± 0.4° and 3 ± 0.3°, respectively. The self-cleaning behavior of soil simulated dust environment was tested on the surface of OPMF and ZnO/SiO2 CSPMF respectively. The horizontal bounce performance and tilt bounce performance of the superhydrophobic surface were tested by high-speed camera. In addition, frost experiments and delayed icing experiments were carried out. The results show that ZnO/SiO2 CSPMF has good self-cleaning performance, bouncing performance and delayed icing performance.

HJ11 is a novel traditional Chinese medicine developed from the appropriate addition and reduction of Si-Miao-Yong-An decoction, which has been commonly used to treat ischemia-reperfusion (I/R) injury in the clinical setting. However, the mechanism of action of HJ11 components remains unclear. Ferroptosis is a critical factor that promotes myocardial I/R injury, and the pathophysiological ferroptosis-mediated lipid peroxidation causes I/R injury. Therefore, this study explored whether HJ11 decoction ameliorates myocardial I/R injury by attenuating ACSL4-mediated ferroptosis. This study also explored the effect of ACSL4 expression on iron-dependent programmed cell death by preparing a rat model of myocardial I/R injury and oxygen glucose deprivation/reperfusion (OGD/R)–induced H9c2 cells. The results showed that HJ11 decoction improved cardiac function; attenuated I/R injury, apoptosis, oxidative stress, mitochondrial damage, and iron accumulation; and reduced infarct size in the myocardial I/R injury rat model. Additionally, HJ11 decoction suppressed the expression of ferroptosis-promoting proteins [Acyl-CoA synthetase long-chain family member 4 (ACSL4) and cyclooxygenase-2 (COX2)] but promoted the expression of ferroptosis-inhibiting proteins [ferritin heavy chain 1 (FTH1) and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4)] in the myocardial tissues of the I/R injury rat model. Similar results were found with the OGD/R-induced H9c2 cells. Interestingly, ACSL4 knockdown attenuated iron accumulation, oxidative stress, and ferroptosis in the OGD/R-treated H9c2 cells. However, ACSL4 overexpression counteracted the inhibitory effect of the HJ11 decoction on OGD/R-triggered oxidative stress and ferroptosis in H9c2 cells. These findings suggest that HJ11 decoction restrained the development of myocardial I/R injury by regulating ACSL4-mediated ferroptosis. Thus, HJ11 decoction may be an effective medication to treat myocardial I/R injury.

Background: Transient tumor marker elevations caused by chemotherapy were defined as ‘Flare’ and have been demonstrated in some solid tumors. In clinical practice, we observed that some patients were accompanied by elevated tumor markers during treatment, but subsequent imaging proved that the treatment they received was effective. Objectives: We aimed to study the Flare and the prognosis in advanced gastric cancer. Design: This is an observational retrospective study. A total of 167 patients were enrolled in this study. Carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 and CA125 values were obtained before the first, second, third, fourth, fifth and sixth cycles of treatment, respectively. Methods: Imaging for the first efficacy assessment was reviewed according to the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) criteria. Kaplan–Meier analyses and log-rank tests were performed for overall survival (OS) analyses. Univariate and multivariate Cox analyses were used to determine the prognostic factor for OS and progression-free survival (PFS). Results: 37.1% of patients were accompanied with at least one tumor marker Flare during the course of treatment. The median time to tumor marker peak was 24–30 days and the Flare duration lasted 49–53 days. Patients with tumor markers Flare had a worse OS. Flare may be associated with the use of 5-fluorouracil. Baseline CEA and CA125 levels were the independent prognostic factors for OS and baseline CA125 level was the independent prognostic factor for PFS. Conclusion: Initial elevation of tumor markers during treatment is not an indication of tumor progression. Patients with tumor markers ‘Flare’ may had a worse OS.

Objective This study aimed to investigate the risk factors of venous thromboembolism (VTE) in admitted patients with lung carcinoma before surgery. Methods We conducted a retrospective case-control study of 94 preoperative lung cancer patients with VTE between January 2017 to December 2020. Each VTE patients was randomly matched with 2 control patients according to residence and gender. The clinical characteristics and related laboratory test results between the groups were compared by univariate analysis, while the risk factors of VTE in preoperative patients with lung cancer were analyzed using multivariate logistic regression analysis. Results Patients aged ≥60 years, a history of arrhythmia, homocysteine>15ummol/L, Fibrinogen (FIB) >4 g/L and D-dimer>500 ng/mL were found to be associated with an increased risk of VTE by univariate analysis. The multivariate logistic regression analysis revealed that age ≥60 years (OR=10.985), FIB >4 g/L (OR=8.861) and D-Dimer >500 ng/mL (OR=6.613) were independent risk factors for VTE in patients with lung carcinoma before surgery (P4 g/L and D-Dimer >500 ng/mL. As for these patients, prophylactic anticoagulant therapy should be considered before surgery.

The pathological processes of cancer are complex. Current methods used for chemotherapy have various limitations, such as cytotoxicity, multi-drug resistance, stem-like cells growth, and lack of specificity. Several types of nanomaterials are used for cancer treatment. Nanomaterials 1–100 nm in size have special optical, magnetic, and electrical characteristics. Nanomaterials have been fabricated for cancer treatments to overcome cytotoxicity and low specificity, and improve drug capacity and bioavailability. Despite the increasing number of related studies, few nanodrugs have been approved for clinical use. To improve translation of these materials, studies of targeted drug delivery using nanocarriers are needed. Cytotoxicity, enhanced permeability and retention effects, and the protective role of the protein corona remain to be addressed. This mini-review summarizes new nanomaterials manufactured in studies and in clinical use, analyses current barriers preventing their translation to clinical use, and describes the effective application of nanomaterials in cancer treatment.

Silica (SiO2) powder and physical deposition technique were performed to fabricate superhydrophobic silicone rubber (SR) surfaces, and the contact angle and the rolling angle were 160.3 ± 1.0° and 2.8 ± 0.3°, respectively (the contact angle and the rolling angle of the original surface of the SR were 130 ± 1.8° and 36.7 ± 0.8°, respectively). The surface roughness of the sample was measured by interferometric three-dimensional topography profiler, and the results showed that the surface roughness increased after being treated by SiO2. A self-cleaning test was designed to verify the self-cleaning effect of the sample surface. Besides, a scanning electron microscope (SEM) was employed to observe the microstructure of the sample surface and the dispersion of SiO2, and energy dispersive spectroscopy (EDS) was utilized to determine the element composition and content of the sample surface. In order to further demonstrate the superhydrophobic property of the surface of the sample, the horizontal bouncing test at room temperature (25 °C) and the tilted bouncing test at an angle of 10° with the horizontal plane were carried out, and it was found that the sample had remarkable bouncing performance. Moreover, high temperature bounce tests were performed to investigate the stability of the surface superhydrophobic property of the sample, indicating that the sample had significant high temperature resistance.

Listeria monocytogenes is a deadly and costly foodborne pathogen that has a high fatality rate in the elderly, pregnant women, and people with weakened immunity. It can survive under various stress conditions and is a significant concern for the food industry. In this work, a data analysis approach was developed with existing tools and databases and used to create individual and combined protein interaction networks to study stress response, virulence, and antimicrobial resistance and their interaction with L. monocytogenes. The networks were analyzed, and 28 key proteins were identified that may serve as potential targets for new strategies to combat L. monocytogenes. Five of the twenty-eight proteins (i.e., sigB, flaA, cheA, cheY, and lmo0693) represent the most promising targets because they are highly interconnected within the combined network. The results of this study provide a new set of targets for future work to identify new strategies to improve food preservation methods and treatments for L. monocytogenes.

Superoxide dismutases (SODs) play an important role in protecting plants against ROS toxicity induced by biotic and abiotic stress. Recent studies have shown that the SOD gene family is involved in plant growth and development; however, knowledge of the SOD gene family in tobacco is still limited. In the present study, the SOD gene family was systematically characterized in the tobacco genome. Based on the conserved motif and phylogenetic tree, 15 NtSOD genes were identified and classified into three subgroups, including 5 NtCSDs, 7 NtFSDs and 3 NtMSDs. The predicted results of the transport peptide or signal peptide were consistent with their subcellular localization. Most NtSOD genes showed relatively well-maintained exon-intron and motif structures in the same subgroup. An analysis of cis-acting elements in SOD gene promoters showed that NtSOD expression was regulated by plant hormones, defense and stress responses, and light. In addition, multiple transcription factors and miRNAs are predicted to be involved in the regulation of NtSOD gene expression. The qPCR results indicated specific spatial and temporal expression patterns of the NtSOD gene family in different tissues and developmental stages, and this gene family played an important role in protecting against heavy metal stress. The results of functional complementation tests in the yeast mutant suggested that NtCSD1a, NtFSD1e and NtMSD1b scavenge ROS produced by heavy metal stress. This study represents the first genome-wide analysis of the NtSOD gene family, which lays a foundation for a better understanding of the function of the NtSOD gene family and improving the tolerance of plants to heavy metal toxicity.

Epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. Genomic imprinting is an epigenetically regulated process by which imprinted genes are expressed in a parent-of-origin-specific manner. It can be confounded with a phenomenon, allelic expression imbalance (AEI), which, in this paper, refers to asymmetric expression of the two alleles of a heterozygous subject at a single nucleotide polymorphism not caused by imprinting (non-imprinting AEI). Since existing methods in the literature are not amenable to distinguishing imprinting from non-imprinting AEI for data without replicates, we propose AIJ, a joint test for simultaneous detection of imprinting and non-imprinting AEI that accounts for potential confounding using RNA-seq data based on a reciprocal cross design. Through a simulation study, we show that AIJ is more powerful compared to two frequently used methods that do not account for confounding. To illustrate the practical utility of AIJ, we applied the method to a mouse dataset and identified genes with the imprinting effect and/or non-imprinting AEI phenomenon, with some already confirmed in an existing database. The results are also largely consistent with a study on human data for a set of orthologous genes, affirming earlier conclusion in the literature that non-imprinting AEI events are evolutionarily conserved.

Alzheimer’s disease (AD) is one of the most common age-associated pathologies, which inevitably leads to dementia and death. The aggregation of β-amyloid (Aβ) peptides on plaques in brain tissue is strongly associated with AD. The possible link between aluminum and AD still remains controversial. In this work, the aggregation of Aβ40 induced by Al(III) was investigated with the use of the fluorescence quenching method, UV–visible and circular dichroism spectroscopies as well as the atomic force microscopy technique. The results demonstrated that Al(III) induced the transformation of the initial random coil structure to the β-sheet configuration in the Aβ40 peptides. These structural changes facilitated the aggregation of Aβ40. Also, the binding constant was calculated with the use of the multivariate curve resolution-alternating least squares (MCR-ALS) chemometrics method. Keywords: Alzheimer’s disease, β-Amyloid peptides, Spectroscopy, Chemometrics

BackgroundIt was widely accepted that programmed death-ligand 1 (PD-L1) positive, tumor mutational burden-high (TMB-H) or microsatellite instability-high (MSI-H) tumor are prone to have better treatment response to immune checkpoint blockade. The value of immune checkpoint blockade in PD-L1 negative gastric cancer patients has been questioned due to lower objective response rate (ORR).Case PresentationWe report an unusual case of a PD-L1 negative, proficient mismatch repair (pMMR)/microsatellite stability (MSS), tumor mutational burden-low (TMB-L) gastric cancer patient who achieved good response to immune checkpoint blockade after failure of systematic treatment. Multiple lymph nodes and bone metastases are the main characteristics of this patient. The patient survived for more than 30 months after diagnosis.ConclusionsThis case suggested that PD-L1 negative gastric cancer patient may also benefit from immune checkpoint blockade. In gastric cancer, patients with lymph node metastasis may be potential beneficiaries.

Abstract Background Skin rash remains one of the most prevalent and troublesome clinical problems experienced by patients on chemotherapy and targeted therapy. To ensure high-quality care, guidelines are seen as the best guidance. Considering the quality of guidelines varies greatly, a systematical appraisal of the methodological quality of guidelines for the management of skin rash in patients on chemotherapeutic drugs and targeted anticancer therapies was undertaken, in order to identify appropriate ones for healthcare professionals. Methods A systematic search of databases and Internet was conducted to obtain pertinent guidelines. Two reviewers independently assessed the eligibility of guidelines according to the inclusion criteria. Then the guidelines included were appraised by three researchers with the methodological quality of eligible guideline using Appraisal of Guidelines for Research and Evaluation II (AGREEII). Results Totally nineteen guidelines met the inclusion criteria. The quality ranged from good to acceptable in scope and purpose (mean: 78.80%, range: 66.67–94.44%) and clarity of presentation domains (mean: 85.38%, 75.00–91.67%), but not in stakeholder involvement (mean: 50.15%, range: 36.11–75.00%), rigor of development (mean: 23.65%, range: 6.25–70.83%), applicability (mean: 23.96%, range: 4.17–52.08%), and editorial independence domains (mean: 45.18%, range: 0.00–87.50%). Overall, two guidelines were classified as “recommended”. Conclusions Only two guidelines were recommended to manage skin rash in patients on chemotherapy and targeted therapies, most guidelines issued were of low to moderate quality. Thus, more attention should be paid to the methodological quality of guideline development in this field.

Sigmoid metastasis of renal cell carcinoma (RCC) is very rare. Herein we report a case of pathologically proven asynchronous abdominal wall and sigmoid metastases after a right nephrectomy. An 84-year-old man underwent right radical nephrectomy for clear cell renal cell carcinoma (ccRCC) 13 years ago. Solitary contralateral abdominal wall metastasis was found for left abdominal mass 9 years after nephrectomy. The man experienced melena underwent resection of sigmoid colon tumor in February, 2016. The postoperative pathological examinations revealed that the tumors were metastases of ccRCC. Recurrence more than 5 years after nephrectomy has been accepted as late recurrence by the majority of urologists now. Late recurrence is one of the specific biological behaviors of RCC. Asynchronous late recurrence of abdominal wall and sigmoid metastases in ccRCC has not been reported before. When patients have sigmoid mass after nephrectomy for RCC, doctors may consider the possibility of late recurrence. Keywords: Sigmoid metastasis, Late recurrence, Renal cell carcinoma, Asynchronous metastases, Abdominal wall metastasis

Hyperforin is a major active constituent of Hypericum perforatum L. extract, which is widely used for the treatment of depressive disorders. Recent studies have reported that hyperforin reduced inflammation in stroke and suppressed proliferation and differentiation in keratinocytes. Psoriasis is a chronic immune-mediated inflammatory skin disease in which the IL-23/IL-17 axis plays an important role. To investigate the underlying inflammatory mechanisms and response of hyperforin in psoriasis, we use imiquimod (IMQ)-induced mice model, in vitro cultured murine splenic γδ T cells, and HaCaT cells in this study. Data showed that hyperforin reduced epidermal thickness and decreased IMQ-induced pathological scores of cutaneous skin lesions in mice. Meanwhile we proved that hyperforin suppressed infiltration of CD3+ T cells and downregulated expression of Il1, Il6, Il23, Il17a, Il22, antimicrobial peptides (AMPs) in the skin lesion. Hyperforin significantly inhibited imiquimod-induced splenomegaly, reduced serum levels of TNF-α and IL-6, and IL-17A in splenocytes and draining lymph nodes. Our study also suggested that hyperforin lessened the infiltration of γδ T cell and CCR6+ γδ T cells in spleen and lymph nodes. Hyperforin also suppressed the typical psoriasis-like inflammatory responses and the infiltration of IL-17A+ cells in dermal γδ T cells of IMQ treated Tcrd−/− mice transferred with γδ T cells. In vitro studies, hyperforin reduced the expression and secretion of IL-17A in γδ T cells, and suppressed the activation of MAPK/STAT3 pathways in human keratinocyte HaCaT cells and γδ T cells. In conclusion, hyperforin alleviates IMQ-induced inflammation in psoriasis through suppressing the immune responses exerted by IL-17 A-producing γδ T cells and related cytokines by modulating MAPK/STAT3 pathways. Our study provided a novel therapeutic tragedy for psoriasis by which hyperforin attenuates psoriasis-related inflammatory responses.

The newly evolved SARS-CoV-2 has caused the COVID-19 pandemic, and the SARS-CoV-2 main protease 3CLpro is essential for the rapid replication of the virus. Inhibiting this protease may open an alternative avenue toward therapeutic intervention. In this work, a computational docking approach was developed to identify potential small-molecule inhibitors for SARS-CoV-2 3CLpro. Totally 288 potential hits were identified from a half-million bioactive chemicals via a protein-ligand docking protocol. To further evaluate the docking results, a quantitative structure activity relationship (QSAR) model of 3CLpro inhibitors was developed based on existing small molecule inhibitors of the 3CLproSARS– CoV– 1 and their corresponding IC50 data. The QSAR model assesses the physicochemical properties of identified compounds and estimates their inhibitory effects on 3CLproSARS– CoV– 2. Seventy-one potential inhibitors of 3CLpro were selected through these computational approaches and further evaluated via an enzyme activity assay. The results show that two chemicals, i.e., 5-((1-([1,1′-biphenyl]-4-yl)-2,5-dimethyl-1H-pyrrol-3-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-trione and N-(4-((3-(4-chlorophenylsulfonamido)quinoxalin-2-yl)amino)phenyl)acetamide, effectively inhibited 3CLpro SARS-CoV-2 with IC50’s of 19 ± 3 μM and 38 ± 3 μM, respectively. The compounds contain two basic structures, pyrimidinetrione and quinoxaline, which were newly found in 3CLpro inhibitor structures and are of high interest for lead optimization. The findings from this work, such as 3CLpro inhibitor candidates and the QSAR model, will be helpful to accelerate the discovery of inhibitors for related coronaviruses that may carry proteases with similar structures to SARS-CoV-2 3CLpro.

Terpenes constitute the largest class of secondary metabolites in plants. Some terpenes are essential for plant growth and development, membrane components, and photosynthesis. Terpenes are also economically useful for industry, agriculture, and pharmaceuticals. However, there is very low content of most terpenes in microbes and plants. Chemical or microbial synthesis of terpenes are often costly. Plants have the elaborate and economic biosynthetic way of producing high-value terpenes through photosynthesis. Here we engineered the heterogenous sesquiterpenoid patchoulol production in A. annua. When using a strong promoter such as 35S to over express the avian farnesyl diphosphate synthase gene and patchoulol synthase gene, the highest content of patchoulol was 52.58 μg/g DW in transgenic plants. When altering the subcellular location of the introduced sesquiterpene synthetase via a signal peptide, the accumulation of patchoulol was observably increased to 273 μg/g DW. This case demonstrates that A. annua plant with glandular trichomes is a useful platform for synthetic biology studies.

Ileal neobladder construction is a common treatment for patients with bladder cancer after radical cystectomy. However, metabolic disorders caused by transposed bowel segments occur frequently. Bladder tissue engineering is a promising alternative approach. Although numerous studies have reported bladder reconstruction using acellular and cellular scaffolds, there are also disadvantages associated with these methods, such as immunogenicity of synthetic grafts and incompatible mechanical properties of the biomaterials. Here, we engineered an autologous peritoneal graft consisting of a peritoneal sheet and the seromuscular layer from the ileum. Three months after the surgery, compared with the neobladder made from the ileum, the reconstructed neobladder using our new method showed normal function and better gross morphological characteristics. Moreover, histopathological and transcriptomic analysis revealed urothelium-like cells expressing urothelial biomarkers appeared in the neobladder, while no such changes were observed in the control group. Overall, our study provides a new strategy for bladder tissue engineering and informs a variety of future research prospects.

Lack of precipitation and groundwater for irrigation limits crop production in semi-arid regions, such as the Southern High Plains (SHP). Advanced technologies, such as variable rate irrigation (VRI), can conserve water and improve water use efficiency for sustainable agriculture. However, the adoption of VRI is hindered by the lack of on-farm research focusing on the feasibility of VRI. The objective of this study was to assess the effect of irrigation rates on cotton yield as affected by soil physical properties and topography in the Southern High Plains. This study was conducted in two fields within a 194-ha commercially managed farm in Hale County, Texas, in 2017. An irrigation treatment with three rates was implemented in a randomized complete block design with two replications as separate blocks in each field. A total of 230 composite soil samples were collected from the farm in spring 2017 and analyzed for texture. Information on apparent soil electrical conductivity (ECa), elevation, and final yield were collected from the fields. A statistical model showed that the effect of irrigation rates on cotton yield depended on its interaction with soil physical properties and topography. For example, areas with slope >2% and sand content >50% had no significant response to higher irrigation rates. This model suggests that applying irrigation amounts based on the yield response can be a basis for VRI. This study provides valuable information for site-specific irrigation to optimize crop production in fields with significant variability in soil physical properties and topography.

The bacterial cell wall is essential for protecting bacteria from the surrounding environment and maintaining the integrity of bacteria cells. The MurA enzyme, which is an essential enzyme involved in bacterial cell wall synthesis, could be a good drug target for antibiotics. Although fosfomycin is used clinically as a MurA inhibitor, resistance to this antibiotic is a concern. Here we used molecular docking-based virtual screening approaches to identify potential MurA inhibitors from 1.412 million compounds from three databases. Thirty-three top compounds from virtual screening were experimentally tested in Listeria innocua (Gram-positive bacterium) and Escherichia coli (Gram-negative bacterium). Compound 2-Amino-5-bromobenzimidazole (S17) showed growth inhibition effect in both L. innocua and E. coli, with the same Minimum Inhibitory Concentration (MIC) value of 0.5 mg/mL. Compound 2-[4-(dimethylamino)benzylidene]-n-nitrohydrazinecarboximidamide (C1) had growth inhibition effect only in L. innocua, with a MIC value of 0.5 mg/mL. Two FDA-approved drugs, albendazole (S4) and diflunisal (S8), had a growth inhibition effect only in E. coli, with a MIC value of 0.0625 mg/mL. The identified MurA inhibitors could be potential novel antibiotics. Furthermore, they could be potential fosfomycin substitutes for the fosfomycin-resistant strains.

Abstract Background Cancer-related anorexia remains one of the most prevalent and troublesome clinical problems experienced by patients with cancer during and after therapy. To ensure high-quality care, systematic reviews (SRs) are seen as the best guide. Considering the methodology quality of SRs varies, we undertook a comprehensive overview, and critical appraisal of pertinent SRs. Methods Eight databases (between the inception of each database and September 1, 2017) were searched for SRs on the management of cancer-related anorexia. Two researchers evaluated the methodological quality of each SR by using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) checklist. Characteristics of the “high quality” SRs were abstracted, included information on relevant studies numbers, study design, population, intervention, control, outcome and result. Results Eighteen SRs met the inclusion criteria. The R-AMSTAR scores of methodological quality ranged from 18 to 41 out of 44, with an average score of 30. Totally eight SRs scored ≥31 points, which showed high methodological quality, and would be used for data extraction to make summaries. Anamorelin had some positive effects to relieve cancer anorexia-cachexia syndrome (CACS) and improve the quality of life (QoL). Megestrol Acetate (MA) could improve appetite, and was associated with slight weight gain for CACS. Oral nutritional interventions were effective in increasing nutritional intake and improving some aspects of QoL in patients with cancer who were malnourished or at nutritional risk. The use of thalidomide, Eicosapentaenoic Acid, and minerals, vitamins, proteins, or other supplements for the treatment of cachexia in cancer were uncertain, and there was inadequate evidence to recommend it to clinical practices, the same situation in Chinese Herb Medicine and acupuncture (acupuncture and related therapies were effective in improving QoL) for treating anorexia in cancer patients, warranting further RCTs in these areas. Conclusions Anamorelin, MA, oral nutrition interventions, and acupuncture could be considered to be applied in patients with cancer-related anorexia. Future RCTs and SRs with high quality on the pharmaceutical or non-pharmaceutical interventions of anorexia in cancer patients are warranted.

A novel method called tip-viscid electrohydrodynamic jet printing (TVEJ), which produces a viscous needle tip jet, was presented to fabricate a 3D composite osteochondral scaffold with controllability of fiber size and space to promote cartilage regeneration. The tip-viscid process, by harnessing the combined effects of thermal, flow, and electric fields, was first systematically investigated by simulation analysis. The influences of process parameters on printing modes and resolutions were investigated to quantitatively guide the fabrication of various structures. 3D architectures with high aspect ratio and good interlaminar bonding were printed, thanks to the stable fine jet and its predictable viscosity. 3D composite osteochondral scaffolds with controllability of architectural features were fabricated, facilitating ingrowth of cells, and eventually inducing homogeneous cell proliferation. The scaffold’s properties, which included chemical composition, wettability, and durability, were also investigated. Feasibility of the 3D scaffold for cartilage tissue regeneration was also proven by in vitro cellular activities.