Diagnosis and Treatment of Metastatic Colon Cancer in Pregnancy First Presenting as Multiple Liver Masses: A Case Report.

Colorectal cancer (CRC) is the second most common cancer in women in Japan. However, it is uncommon during pregnancy. CRC diagnosis during pregnancy is often complicated and delayed due to the overlapping of symptoms, such as abdominal pain and nausea, with those of pregnancy and the limitations placed on potential diagnostic imaging and testing because of concerns for the fetus. A 39-year-old woman was referred from a local hospital at 32 weeks gestation after persistent right abdominal pain, which prompted an ultrasound that showed multiple liver lesions suggestive of malignancy. A combination of non-contrast computed tomography, non-contrast magnetic resonance imaging, contrast-enhanced ultrasound, and colonoscopy was utilized to make a definitive diagnosis; ultimately, colonoscopy confirmed the diagnosis of colon cancer with liver metastasis. A discussion within a multidisciplinary team led to the decision to deliver at 34 weeks by cesarean section and a left hemicolectomy was performed after delivery. The neonate was admitted to the neonatal intensive care unit due to prematurity but had no other complications. Chemotherapy was promptly initiated, and treatment was continued on an outpatient basis. Diagnostic algorithms for CRC during pregnancy are not yet well-established; however, the prognosis of CRC during pregnancy is poor, and clinicians should not hesitate to perform the necessary testing and consult experts in fields such as neonatology, medical oncology, internal medicine, and gastrointestinal surgery. Early diagnosis and intervention are essential for optimizing outcomes for both the mother and the fetus.

One-Step Electrocatalytic Approach Applied to the Synthesis of ß-Propiolactones from CO2 and Dienes.

ß-Lactones are common substructures in a variety of natural products and drugs, and they serve as versatile synthetic intermediates in the production of valuable chemical derivatives. Traditional ß-lactone synthesis relies on laborious multi-step synthetic methods that use toxic compounds, sophisticated catalysts, expensive, and/or reactive chemicals. Based on the in situ electrochemical formation of metal-based nanoclusters, this paper describes the development of a one-step, room temperature electrocatalytic method for the formation of stable ß-lactone from CO2 and dienes. This one-step "electrosynthesis" method results in the formation of a new class of ß-lactone with high selectivity (up to 100%) and activity (up to 80% yields with respect to the reacted diene) by regulating the applied potential and current density. This work paves the way for more sustainable and environmentally friendly reaction pathways based on the in situ formation of nanoclusters as organic electrosynthesis catalysts.

COVID-19 knowledge deconstruction and retrieval: an intelligent bibliometric solution.

COVID-19 has been an unprecedented challenge that disruptively reshaped societies and brought a massive amount of novel knowledge to the scientific community. However, as this knowledge flood continues surging, researchers have been disadvantaged by not having access to a platform that can quickly synthesize emerging information and link the new knowledge to the latent knowledge foundation. Aiming to fill this gap, we propose a research framework and develop a dashboard that can assist scientists in identifying, retrieving, and understanding COVID-19 knowledge from the ocean of scholarly articles. Incorporating principal component decomposition (PCD), a knowledge mode-based search approach, and hierarchical topic tree (HTT) analysis, the proposed framework profiles the COVID-19 research landscape, retrieves topic-specific latent knowledge foundation, and visualizes knowledge structures. The regularly updated dashboard presents our research results. Addressing 127,971 COVID-19 research papers from PubMed, the PCD topic analysis identifies 35 research hotspots, along with their inner correlations and fluctuating trends. The HTT result segments the global knowledge landscape of COVID-19 into clinical and public health branches and reveals the deeper exploration of those studies. To supplement this analysis, we additionally built a knowledge model from research papers on the topic of vaccination and fetched 92,286 pre-Covid publications as the latent knowledge foundation for reference. The HTT analysis results on the retrieved papers show multiple relevant biomedical disciplines and four future research topics: monoclonal antibody treatments, vaccinations in diabetic patients, vaccine immunity effectiveness and durability, and vaccination-related allergic sensitization.

Improved production of adipic acid from a high loading of corn stover via an efficient and mild combination pretreatment.

Adipic acid is one kind of important organic dibasic acid, which has crucial role in manufacturing plastics, lubricants, resins, fibers, etc. Using lignocellulose as feedstock for producing adipic acid can reduce production cost and improve bioresource utilization. After pretreated in the mixture of 7 wt% NaOH and 8 wt% ChCl-PEG10000 at 25 °C for 10 min, the surface of corn stover became loose and rough. The specific surface area was increased after the removal of lignin. A high loading of pretreated corn stover was enzymatically hydrolyzed by cellulase (20 FPU/g substrate) and xylanase (15 U/g substrate), and the yield of reducing sugars was as high as 75%. Biomass-hydrolysates obtained by enzymatic hydrolysis were efficiently fermented to produce adipic acid, and the yield was 0.48 g adipic acid per g reducing sugar. A sustainable approach for manufacturing adipic acid from lignocellulose via a room temperature pretreatment has great potential in future.

Single von Willebrand factor C-domain protein confers host defense against white spot syndrome virus by functioning as a pattern recognition receptor in Macrobrachium nipponense.

The single von Willebrand factor C-domain proteins (SVWCs), also known as Vago, are primarily found in arthropods. Their expression was induced by nutritional status, bacterial and viral infections. Despite the prominence of SVWCs in antiviral immunity, the detailed molecular mechanisms remain poorly explained. SVWC has been proposed to elicit antiviral activities through its function as an interferon analog. In contrast, herein, we illustrate that an SVWC homolog from Macrobrachium nipponense (MnSVWC) confers host defense against white spot syndrome virus (WSSV) and covert mortality nodavirus (CMNV) as a pattern recognition receptor (PRR). qRT-PCR analyses demonstrated that the expression of MnSVWC was enhanced upon WSSV infection in all detected tissues, including gills, nerve cords, and hemocytes. Coating WSSV with recombinant MnSVWC (rMnSVWC) promoted the phagocytic activity of hemocytes and subsequent clearance of invasive WSSV from the prawn. On the other hand, the knockdown of MnSVWC with RNAi improved the proliferation ability of WSSV and CMNV in the prawn. Analysis of ELISA and Co-immunoprecipitation (Co-IP) showed that rMnSVWC could bind WSSV by interacting with the vesicle proteins VP26 and VP28. Co-IP analysis verified the interaction between MnSVWC and calmodulin, which implies a vesicle protein-SVWC-calmodulin-clathrin-dependent mechanism underlying the hemocyte-mediated phagocytosis against WSSV. Subsequently, MnSVWC was recognized to activate the expression of transcription factor STAT and an interferon-stimulating gene Viperin, illustrating its involvement in modulating humoral immunity via activation of the JAK/STAT pathway after WSSV infection. These findings indicate that MnSVWC could bind to WSSV as a PRR and participate in the promotion of hemocyte-mediated phagocytosis and the activation of the JAK/STAT pathway in prawns.

A survival model for prognostic prediction based on ferroptosis-associated genes and the association with immune infiltration in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is the primary pathological type of lung cancer with a less favorable prognosis. This study attempts to construct a ferroptosis-associated signature associated with overall survival (OS) that can predict the prognosis of LUSC and explore its relationship with immune infiltration. A 5 ferroptosis-associated gene model was constructed by LASSO-penalized regression analysis to predict the prognosis of patients with LUSC in the TCGA database and validated in the GEO and TCGA databases. Patients were stratified into high-risk and low-risk groups by the median value of the risk scores, and the former prognosis was significantly worse (P<0.001). Additionally, we found a certain association between the two risk groups and immune infiltration through CIBERSORT. Meanwhile, the differentially expressed genes (DEGs) between normal and tumor tissue were used to perform functional analysis, which showed a significant association with leukocyte transendothelial migration pathways in the TCGA cohort. In addition, immune cell infiltration analysis confirmed that M2 macrophages were significantly highly expressed in the high-risk group. Overall, the model successfully established by ferroptosis-associated genes suggests that ferroptosis may be related to immune infiltration in LUSC.

Low-acidity ALUMINUM-DEPENDENT MALATE TRANSPORTER4 genotype determines malate content in cultivated jujube.

Jujube (Ziziphus jujuba Mill.), the most economically important fruit tree in Rhamnaceae, was domesticated from sour jujube (Z. jujuba Mill. var. spinosa (Bunge) Hu ex H.F.Chow.). During domestication, fruit sweetness increased and acidity decreased. Reduction in organic acid content is crucial for the increase in sweetness of jujube fruit. In this study, the determination of malate content among 46 sour jujube and 35 cultivated jujube accessions revealed that malate content varied widely in sour jujube (0.90-13.31 mg g-1) but to a lesser extent in cultivated jujube (0.33-2.81 mg g-1). Transcriptome sequencing analysis showed that the expression level of Aluminum-Dependent Malate Transporter 4 (ZjALMT4) was substantially higher in sour jujube than in jujube. Correlation analysis of mRNA abundance and fruit malate content and transient gene overexpression showed that ZjALMT4 participates in malate accumulation. Further sequencing analyses revealed that three genotypes of the W-box in the promoter of ZjALMT4 in sour jujube associated with malate content were detected, and the genotype associated with low malate content was fixed in jujube. Yeast one-hybrid screening showed that ZjWRKY7 binds to the W-box region of the high-acidity genotype in sour jujube, whereas the binding ability was weakened in jujube. Transient dual-luciferase and overexpression analyses showed that ZjWRKY7 directly binds to the promoter of ZjALMT4, activating its transcription, and thereby promoting malate accumulation. These findings provide insights into the mechanism by which ZjALMT4 modulates malate accumulation in sour jujube and jujube. The results are of theoretical and practical importance for the exploitation and domestication of germplasm resources.

Positive response to trastuzumab deruxtecan in a patient with HER2-mutant NSCLC after multiple lines therapy, including T-DM1: a case report.

Human epidermal growth factor 2 (HER2) mutations are uncommon in non-small cell lung cancer (NSCLC), and the lack of established, effective, targeted drugs has resulted in a persistently poor prognosis. Herein, we report the case of a non-smoking, 58-year-old man diagnosed with lung adenocarcinoma (cT3N0M1c, stage IVB) harboring a HER2 mutation (Y772_A775dupYVMA) and PD-L1 (-). The patient's Eastern Cooperative Oncology Group performance status (PS) score was assessed as 1. He commenced first-line treatment with chemotherapy, followed by immuno-chemotherapy, and with disease progression, he received HER2-targeted therapy and chemotherapy with an anti-angiogenic agent. However, HER2-targeted therapy, including pan-HER tyrosine kinase inhibitors (afatinib, pyrotinib, and pozitinib) and antibody-drug conjugate (T-DM1), produced only stable disease (SD) as the best response. After the previously described treatment, primary tumor recurrence and multiple brain metastases were observed. Despite the patient's compromised overall physical condition with a PS score of 3-4, he was administered T-DXd in addition to whole-brain radiotherapy (WBRT). Remarkably, both intracranial metastases and primary lesions were significantly reduced, he achieved a partial response (PR), and his PS score increased from 3-4 to 1. He was then treated with T-DXd for almost 9 months until the disease again progressed, and he did not discontinue the drug despite the occurrence of myelosuppression during this period. This is a critical case as it exerted an effective response to T-DXd despite multiple lines therapy, including T-DM1. Simultaneously, despite the occurrence of myelosuppression in the patient during T-DXd, it was controlled after aggressive treatment.

Effect of preoperative radiotherapy on overall survival in N2 non-small-cell lung cancer: a propensity score-matched analysis of Surveillance, Epidemiology, and End Results database.

OBJECTIVES: The aim of this study was to investigate the effect of preoperative radiotherapy (PrORT) on the overall survival (OS) of patients with stage ipsilateral mediastinal lymph node metastasis (N2) non-small-cell lung cancer. METHODS: A total of 1390 patients with stage N2 non-small-cell lung cancer between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. The efficacy of PrORT combined with surgery was compared with that of surgery alone on OS. Propensity score matching (PSM) was performed to balance the baseline characteristics of patients who received (n = 239) and did not receive (n = 1151) PrORT. We compared the OS of the 2 groups using the Kaplan-Meier method and log-rank were used to compare the OS between the 2 groups test before and after PSM and to analyse subgroups of patients with squamous cell carcinoma (SCC) and adenocarcinoma. RESULTS: In whole group analysis before PSM, the median OS was superior in the PrORT group than in the surgery alone group (44.0 [34.4-56.6] vs 39.0 [34.5-43.5] months). There was a significant difference in OS [hazard ratio (HR): 0.819; 95% confidence interval (CI): 0.677-0.991; P = 0.029]. Nevertheless, no statistically significant difference was found in OS between the 2 groups after PSM (HR: 0.856; 95% CI: 0.654-1.122; P = 0.260). Among subgroup analysis of the SCC group before PSM revealed that patients who received PrORT had significantly higher median OS than those who did not receive PrORT (52.0 [40.0-NA] vs 27.0 [22.0-32.0] months; HR: 0.591, 95% CI: 0.442-0.792, P = 0.000) and the differences in OS existed after PSM (P = 0.043). However, no significant difference was found in OS before and after matching in the adenocarcinoma group (P = 0.827 and P = 0.801, respectively). CONCLUSIONS: PrORT demonstrated an OS benefit for patients with stage N2 lung SCC; however, further prospective randomized clinical trials are warranted to confirm this finding.

Determination of Factors Driving the Genome Editing Field in the CRISPR Era Using Bibliometrics.

Over the past two decades, the discovery of CRISPR-Cas immune systems and the repurposing of their effector nucleases as biotechnological tools have revolutionized genome editing. The corresponding work has been captured by 90,000 authors representing 7,600 affiliations in 126 countries, who have published more than 19,000 papers spanning medicine, agriculture, and biotechnology. Here, we use tech mining and an integrated bibliometric and networks framework to investigate the CRISPR literature over three time periods. The analysis identified seminal papers, leading authors, influential journals, and rising applications and topics interconnected through collaborative networks. A core set of foundational topics gave rise to diverging avenues of research and applications, reflecting a bona fide disruptive emerging technology. This analysis illustrates how bibliometrics can identify key factors, decipher rising trends, and untangle emerging applications and technologies that dynamically shape a morphing field, and provides insights into the trajectory of genome editing.

Exploring Topics in Bibliometric Research Through Citation Networks and Semantic Analysis.

This article surveys topic distributions of the academic literature that employs the terms bibliometrics, scientometrics, and informetrics. This exploration allows informing on the adoption of those terms and publication patterns of the authors acknowledging their work to be part of bibliometric research. We retrieved 20,268 articles related to bibliometrics and applied methodologies that exploit various features of the dataset to surface different topic representations. Across them, we observe major trends including discussions on theory, regional publication patterns, databases, and tools. There is a great increase in the application of bibliometrics as science mapping and decision-making tools in management, public health, sustainability, and medical fields. It is also observed that the term bibliometrics has reached an overall generality, while the terms scientometrics and informetrics may be more accurate in representing the core of bibliometric research as understood by the information and library science field. This article contributes by providing multiple snapshots of a field that has grown too quickly beyond the confines of library science.

Enhanced enzymatic saccharification of sorghum straw by effective delignification via combined pretreatment with alkali extraction and deep eutectic solvent soaking.

Hydrogen bond donor (HBD) in ChCl-based deep eutectic solvent (DESs) had significant influence on the Sorghum straw (SS) pretreatment. Lactic acid (LAC) was chosen as the appropriate HBD for preparing ChCl-based DES to pretreat Sorghum straw (SS). Furthermore, sequential pretreatment with dilute sodium hydroxide (0.75 wt%) for 1 h at 121 °C and ChCl:LAC soaking at 140 °C for 40 min was applied to pretreat SS for removing lignin (78.4%) and xylan (67.6%). Hydrolysis for 72 h, the reducing sugar yield reached 94.9%. Moreover, relationships of delignification and xylan removal with saccharification were explored after pretreatment. Finally, the fermentability of SS-hydrolysates was verified by bioethanol fermentation by S. cerevissiae with the yield of 0.45 g ethanol/g glucose. No significant inhibition was observed on ethanol fermentation. Obviously, establishment of high-efficient combination pretreatment with alkali extraction and ChCl:LAC soaking was successfully demonstrated for enhancing enzymatic saccharification of SS.

Radiation Toxicity in Patients With Collagen Vascular Disease: A Meta-Analysis of Case-Control Studies.

PURPOSE: Several retrospective series have reported that patients with collagen vascular disease (CVD) are at increased risk of radiation (RT) toxicity. However, the evidence is mixed, and many series lack control groups. We performed a meta-analysis including only case-cohort or randomized studies that examined the risk of RT toxicity for patients with CVD compared with controls. METHODS AND MATERIALS: Meta-analysis of Observational Studies in Epidemiology guidelines were used to perform a comprehensive search identifying case-control or randomized studies reporting RT toxicity outcomes for patients with CVD versus controls. Data were synthesized from studies reporting grade 2 to 3 or more (G2/3 +) acute and late RT toxicities. Results were analyzed with fixed effects meta-analysis on the random-effects model for between-study heterogeneity; otherwise, the fixed-effects model was used. Hazard ratio or odds ratio (OR) were the effect-size estimators, as appropriate. RESULTS: Ten studies were included, with 4028 patients (CVD: 406, control: 3622). Patients with CVD had higher rates of acute G2/3 + toxicity (26.2% vs 16.5%, OR [odds ratio] 2.01; P < .001) and late G2/3 + toxicity (18.4% vs 10.1%, OR 2.37; P < .001). Higher rates of late G2/3 + toxicity were observed for CVD patients with systemic lupus erythematous (21% vs 9.7%; OR 2.55, P = .03), systemic scleroderma (31.8% vs 9.7%, OR 3.85; P = .03), rheumatoid arthritis (11.7% vs 8.4%, OR = 2.56; P = .008), and those irradiated to the pelvis/abdomen (32.2% vs 11.9%, OR 3.29; P = .001), breast (14.7% vs 4.4%, OR 3.51; P = .003), thorax (12.5% vs 8.7%, OR 3.46; P < .001), and skin (14.6% vs 5.2%, OR 2.59; P = .02). Late grade 5 toxicities were significantly higher for patients with CVD, although absolute rates were low (3.9% vs 0.6%, OR = 7.81; P = .01). CONCLUSIONS: Moderate and severe toxicities are more likely in patients with CVD, with variable risk depending on toxicity grade, CVD subtype, treatment site, and dose. Severe toxicities are uncommon. These factors should be considered when informing patients of treatment-related risks and monitoring for morbid treatment sequelae.

Profiling COVID-19 Genetic Research: A Data-Driven Study Utilizing Intelligent Bibliometrics.

The COVID-19 pandemic constitutes an ongoing worldwide threat to human society and has caused massive impacts on global public health, the economy and the political landscape. The key to gaining control of the disease lies in understanding the genetics of SARS-CoV-2 and the disease spectrum that follows infection. This study leverages traditional and intelligent bibliometric methods to conduct a multi-dimensional analysis on 5,632 COVID-19 genetic research papers, revealing that 1) the key players include research institutions from the United States, China, Britain and Canada; 2) research topics predominantly focus on virus infection mechanisms, virus testing, gene expression related to the immune reactions and patient clinical manifestation; 3) studies originated from the comparison of SARS-CoV-2 to previous human coronaviruses, following which research directions diverge into the analysis of virus molecular structure and genetics, the human immune response, vaccine development and gene expression related to immune responses; and 4) genes that are frequently highlighted include ACE2, IL6, TMPRSS2, and TNF. Emerging genes to the COVID-19 consist of FURIN, CXCL10, OAS1, OAS2, OAS3, and ISG15. This study demonstrates that our suite of novel bibliometric tools could help biomedical researchers follow this rapidly growing field and provide substantial evidence for policymakers' decision-making on science policy and public health administration.

[Cathepsin-B involved in effect of electroacupuncture by inhibiting the activation of NLRP3 inflammasome in rats with acute gouty arthritis].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on Cathepsin-B in the synovium of the knee joint of acute gouty arthritis(AGA) rats, so as to explore the mechanism of EA in the treatment of AGA. METHODS: A total of 60 male Wistar rats were randomly divided into normal control,model, medication and EA groups, with 15 rats in each group. Rat model of AGA was established by injection of 0.2 mL sodium urate crystal suspension into the left knee joint cavity. The rats in the medication group were treated with colchicine by gavage(0.3 mg·kg-1·d-1), and the rats in the EA group were treated with EA at the left "Sanyinjiao" (SP6) and "Zusanli"(ST36) for 10 min each time, once a day for a week. The Coderre gait grading standard was used to score the gait of rats. The pathological morphology of synovial tissue of the left knee joint was observed by H.E. staining. The expression levels of Cathepsin-B protein and Nod-like receptor pyrin domain 3(NLRP3), apoptosis-associated speck-like protein containing CARD (ASC),Caspase-1, interleukin-1ß(IL-1ß) and IL-18 mRNAs were detected by Western blot and real-time fluorescence quantitative PCR, respectively. RESULTS: Compared with the normal control group, the degree of synovitis infiltration in the model group was more serious. And the gait score，the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3,ASC,Caspase-1, IL-1ß,IL-18 were significantly increased (P<0.01).After the interventions, the degree of inflammatory infiltration was mild, The gait score, the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3 and ASC,Caspase-1，IL-1ß,IL-18 were significantly decreased in both medication and EA groups in contrast to the model group (P<0.01, P<0.05). Compared with medication group, the mRNA expression levels of Caspase-1 and IL-18 in the EA group were increased (P<0.05). CONCLUSION: EA may inhibit the activation of NLRP3 inflammasome by reducing the activity of Cathepsin-B in the synovium of the knee joint, so as to treat AGA.

Topic evolution, disruption and resilience in early COVID-19 research.

The COVID-19 pandemic presented a challenge to the global research community as scientists rushed to find solutions to the devastating crisis. Drawing expectations from resilience theory, this paper explores how the trajectory of and research community around the coronavirus research was affected by the COVID-19 pandemic. Characterizing epistemic clusters and pathways of knowledge through extracting terms featured in articles in early COVID-19 research, combined with evolutionary pathways and statistical analysis, the results reveal that the pandemic disrupted existing lines of coronavirus research to a large degree. While some communities of coronavirus research are similar pre- and during COVID-19, topics themselves change significantly and there is less cohesion amongst early COVID-19 research compared to that before the pandemic. We find that some lines of research revert to basic research pursued almost a decade earlier, whilst others pursue brand new trajectories. The epidemiology topic is the most resilient among the many subjects related to COVID-19 research. Chinese researchers in particular appear to be driving more novel research approaches in the early months of the pandemic. The findings raise questions about whether shifts are advantageous for global scientific progress, and whether the research community will return to the original equilibrium or reorganize into a different knowledge configuration.

Sugar Transporter ZjSWEET2.2 Mediates Sugar Loading in Leaves of Ziziphus jujuba Mill.

In plants, sugar transporters play an important role in the allocation of sugars from cells in source organs to cells in sink organs. Hence, an understanding of the molecular basis and regulation of assimilate partitioning by sugar transporters is essential. Leaves are the main source of photosynthetic products. In jujube (Ziziphus jujuba Mill.), the mechanisms regulating initial sugar unloading in leaves are still unclear. In this study, an expression profiling analysis showed that ZjSWEET2.2, encoding a sugar transporter in the SWEET family, is highly expressed in leaves. Over-expression of ZjSWEET2.2 increased carbon fixation in photosynthetic organs. Our analyses showed that ZjSWEET2.2 encodes a plasma membrane-localized sugar transporter protein. Its expression levels were found to be suppressed under drought stress and by high concentrations of exogenous sugars, but increased by low concentrations of exogenous sugars. Finally, DNA sequence analyses revealed several cis-elements related to sugar signaling in the promoter of ZjSWEET2.2. Together, these results suggest that ZjSWEET2.2 functions to mediate photosynthesis by exporting sugars from photosynthetic cells in the leaves, and its gene expression is regulated by sugar signals.

[Effect of electroacupuncture combined with Donepezil on learning-memory ability and expression of hippocampal ß-amyloid clearance-related genes in SAMP8 mice].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) combined with Donepezil on learning-memory ability and gene expression of ß-amyloid (Aß) clearance-related factors in the hippocampus in senescence-accelerated mouse prone 8 (SAMP8) mice, so as to explore their synthetic effect in improving dementia of Alzheimer's disease (AD)．. METHODS: Male SAMP8 mice (30-week-old) were randomly divided into model, medication and EA＋medication groups (n＝6 mice in each group), and other 6 senescence-resistant 1 (SAMR1) mice were used as the control group. Mice of the medication and EA＋medication group received gavage of Donepezil (1.3 mg•kg－1•d－1) once daily for 4 weeks. EA (2 Hz, 1 mA) was applied to "Baihui"(GV20) and "Yintang" (EX-HN3) for 15 min, once daily, 6 days a week for 4 weeks for rats in the EA＋medication group. The Morris water maze (MWM) task (including place navigation tests and space exploration trials) was used to assess the mouse's learning-memory ability. Histopathological changes of hippocampus tissue were observed by H．E. staining. The expression levels of matrix metalloprotein 9 (MMP-9), low density lipoprotein receptor-related protein-1 (LRP-1), P-glycoprotein (Pgp, an important drug transporter responsible for multidrug resistance), Claudin-5 (a component of tight junction strands that serves as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets of blood-brain barrier, BBB) and Aß mRNAs of the hippocampus tissue were detected by quantitative real-time PCR. RESULTS: Compared with the control group, the average escape latency of place navigation tests, and the expression levels of MMP-9 and Aß mRNAs were significantly increased (P<0.01), and the number of platform quadrant-crossing times of space exploration trials, and the expression levels of LRP-1, Pgp and Claudin-5 mRNAs considerably decreased in the model group (P<0.01). After the intervention, the learning-memory ability was significantly improved in the medication and EA＋medication groups (P<0.01，P<0.05), the expression levels of Aß mRNAs in the medication and EA＋medication groups and MMP-9 mRNA in the EA＋medication group were obviously down-regulated (P<0.01), and those of LRP-1 and Pgp mRNAs in the medication and EA＋medication groups and Claudin-5 mRNA in the EA＋medication group were remarkably up-regulated (P<0.05, P<0.01). The therapeutic effect of EA＋medication was apparently superior to that of simple medication in shortening the escape latency (P<0.05，P<0.01) and in down-regulating the expression of MMP-9 and Aß mRNAs(P<0.01), and in increasing the number of platform quadrant-crossing times(P<0.01), and expression levels of LRP-1, Pgp and Claudin-5 mRNAs (P<0.01). H．E. staining showed scatted and loose arrangement of neurons in the hippocampus, with reduction of number of cell layers and unclear nucleoli, which was relatively milder in the medication and EA＋medication groups. CONCLUSION: EA can enhance the effect of Donepezil in improving learning-memory ability in AD mice possibly by regulating expression of MMP-9, LRP-1, Pgp and Claudin-5 mRNAs and strengthening the effect of Donepezil in transporting Aß via BBB.

A fibrinogen-related protein (Mnfico3) acts as a novel pattern recognition receptor in Macrobrachium nipponense.

Fibrinogen-related proteins (FREPs) are widely found in both vertebrates as well as invertebrates, and they play a crucial role in host immunity. In this study, we isolated a novel ficolin gene (Mnfico3) from the oriental river prawn Macrobrachium nipponense. The complete cDNA sequence of Mnfico3 was 1133 bp long, containing an open reading frame of 765 bp coding for Mnfico3, a protein consisting of 254 amino acids. The Mnfico3 protein contained a putative N-terminal signal peptide and a fibrinogen-related protein domain present at the C-terminal. Phylogenetic analysis indicated that Mnfico3 had a closer evolutionary relationship with vertebrate ficolins than with its invertebrate homologues. Tissue distribution analysis indicated that Mnfico3 was predominantly expressed in muscle, in which its transcription was increased following bacterial challenge by Aeromonas veronii. Function analysis using recombinant protein revealed that rMnFico3 had broad-spectrum binding capacity to a variety of microorganisms and pathogen-associated molecular pattern (PAMP) ligands. Furthermore, rMnFico3 exhibited Ca2+-dependent agglutinating activity against microbes in vitro, and ability to attach to the hemocyte surface which promoted phagocytosis and subsequent clearance of invasive bacteria in vivo. Silencing rMnFico3 in prawn through RNAi did not alter the expression of antimicrobial peptide genes (ALF and Crustin). These results manifested that MnFico3 functioned as a potential pattern recognition receptor (PPR) to mediate cellular immune response by recognizing PAMPs, agglutinating invasive microbes, and promoting phagocytosis of hemocytes.

Tracking and Mining the COVID-19 Research Literature.

The unprecedented, explosive growth of the COVID-19 domain presents challenges to researchers to keep up with research knowledge within the domain. This article profiles this research to help make that knowledge more accessible via overviews and novel categorizations. We provide websites offering means for researchers to probe more deeply to address specific questions. We further probe and reassemble COVID-19 topical content to address research issues concerning topical evolution and emphases on tactical vs. strategic approaches to mitigate this pandemic and reduce future viral threats. Data suggest that heightened attention to strategic, immunological factors is warranted. Connecting with and transferring in research knowledge from outside the COVID-19 domain demand a viable COVID-19 knowledge model. This study provides complementary topical categorizations to facilitate such modeling to inform future Literature-Based Discovery endeavors.