Effect of Loblolly Pine (Pinus taeda L.) Hemicellulose Structure on the Properties of Hemicellulose-Polyvinyl Alcohol Composite Film.

Hemicellulose is the second most abundant natural polysaccharide and a promising feedstock for biomaterial synthesis. In the present study, the hemicellulose of loblolly pine was obtained by the alkali extraction-graded ethanol precipitation technique, and the hemicellulose-polyvinyl alcohol (hemicellulose-PVA) composite film was prepared by film casting from water. Results showed that hemicellulose with a low degree of substitution is prone to self-aggregation during film formation, while hemicellulose with high branching has better compatibility with PVA and is easier to form a homogeneous composite film. In addition, the higher molecular weight of hemicellulose facilitates the preparation of hemicellulose-PVA composite film with better mechanical properties. More residual lignin in hemicellulose results in the better UV shielding ability of the composite film. This study provides essential support for the efficient and rational utilization of hemicellulose.

Virtual Network Embedding for Multi-Domain Heterogeneous Converged Optical Networks: Issues and Challenges.

The emerging 5G applications and the connectivity of billions of devices have driven the investigation of multi-domain heterogeneous converged optical networks. To support emerging applications with their diverse quality of service requirements, network slicing has been proposed as a promising technology. Network virtualization is an enabler for network slicing, where the physical network can be partitioned into different configurable slices in the multi-domain heterogeneous converged optical networks. An efficient resource allocation mechanism for multiple virtual networks in network virtualization is one of the main challenges referred as virtual network embedding (VNE). This paper is a survey on the state-of-the-art works for the VNE problem towards multi-domain heterogeneous converged optical networks, providing the discussion on future research issues and challenges. In this paper, we describe VNE in multi-domain heterogeneous converged optical networks with enabling network orchestration technologies and analyze the literature about VNE algorithms with various network considerations for each network domain. The basic VNE problem with various motivations and performance metrics for general scenarios is discussed. A VNE algorithm taxonomy is presented and discussed by classifying the major VNE algorithms into three categories according to existing literature. We analyze and compare the attributes of algorithms such as node and link embedding methods, objectives, and network architecture, which can give a selection or baseline for future work of VNE. Finally, we explore some broader perspectives in future research issues and challenges on 5G scenario, field trail deployment, and machine learning-based algorithms.

Azalomycin F5a Eradicates Staphylococcus aureus Biofilm by Rapidly Penetrating and Subsequently Inducing Cell Lysis.

Antimicrobial resistance has emerged as a serious threat to public health. Bacterial biofilm, as a natural lifestyle, is a major contributor to resistance to antimicrobials. Azalomycin F5a, a natural guanidine-containing polyhydroxy macrolide, has remarkable activities against Gram-positive bacteria, including Staphylococcus aureus, a major causative agent of hospital-acquired infections. To further evaluate its potential to be developed as a new antimicrobial agent, its influence on S. aureus biofilm formation was evaluated using the crystal violet method, and then its eradication effect against mature biofilms was determined by confocal laser scanning microscopy, the drop plate method, and regrowth experiments. The results showed that azalomycin F5a could significantly inhibit S. aureus biofilm formation, and such effects were concentration dependent. In addition, it can also eradicate S. aureus mature biofilms with the minimum biofilm eradication concentration of 32.0 µg/mL. As extracellular deoxyribonucleic acid (eDNA) plays important roles in the structural integrity of bacterial biofilm, its influence on the eDNA release in S. aureus biofilm was further analyzed using gel electrophoresis. Combined with our previous works, these results indicate that azalomycin F5a could rapidly penetrate biofilm and causes damages to the cell membrane, leading to an increase in DNase release and eventually eradicating S. aureus biofilm.

Novel Anthraquinone Compounds Inhibit Colon Cancer Cell Proliferation via the Reactive Oxygen Species/JNK Pathway.

A series of amide anthraquinone derivatives, an important component of some traditional Chinese medicines, were structurally modified and the resulting antitumor activities were evaluated. The compounds showed potent anti-proliferative activities against eight human cancer cell lines, with no noticeable cytotoxicity towards normal cells. Among the candidate compounds, 1-nitro-2-acyl anthraquinone-leucine (8a) showed the greatest inhibition of HCT116 cell activity with an IC50 of 17.80 µg/mL. In addition, a correlation model was established in a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Field Analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Moreover, compound 8a effectively killed tumor cells by reactive oxygen species (ROS)-JNK activation, causing an increase in ROS levels, JNK phosphorylation, and mitochondrial stress. Cytochrome c was then released into cytoplasm, which, in turn activated the cysteine protease pathway and ultimately induced tumor cell apoptosis, suggesting a potential use of this compound for colon cancer treatment.

Q482H mutation of procaspase-8 in acute myeloid leukemia abolishes caspase-8-mediated apoptosis by impairing procaspase-8 dimerization.

INTRODUCTION: Certain procaspase-8 mutations are reported to be associated with the progression and prognosis of multiple tumors. However, it remains unclear whether the poor chemotherapy response and frequent relapse after complete remission of patients with acute myeloid leukemia (AML) is also related to procaspase-8 abnormalities. METHODS: Polymerase chain reaction (PCR) amplification and Sanger sequencing of the procaspase-8 gene (CASP8) were performed. Apoptotic rates were analyzed with Annexin V-FITC staining in cells expressing wild-type (WT) procaspase-8, the Q482H or C360S mutant, or control vector after treatment with or without tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Western blot analysis was performed to detect activation of procaspase-8 and downstream apoptotic signaling pathway components in those cells. The Co-immunoprecipitation (Co-IP) assays were performed to detect interaction between WT and mutant procaspase-8 proteins. RESULTS: AML patients carrying the Q482H mutation were likely to develop chemotherapy resistance. Similar to C360S, The Q482H mutation abolished caspase-8-mediated apoptotic signaling and inhibited TRAIL-induced apoptosis. The Q482H mutation impaired procaspase-8 dimerization, thus preventing the self-activation of procaspase-8. CONCLUSION: The procaspase-8 Q482H mutation in AML patients abolishes caspase-8-mediated apoptosis by impairing procaspase-8 dimerization.

Effects of superovulation, in vitro fertilization, and oocyte in vitro maturation on imprinted gene Grb10 in mouse blastocysts.

PURPOSE: Grb10 is a key imprinted gene that is suspected to have a role in the adverse outcomes of assisted reproductive technology (ART), but little is known about the effects of ART on it. Primary ART techniques, including superovulation, in vitro fertilization (IVF), and oocyte in vitro maturation (IVM), were analyzed in this study of the effects of ART on embryo quality and Grb10. METHODS: Embryo development rates were determined. Blastocyst cell number and global methylation were analyzed at the single-embryo level, together with Grb10 methylation and mRNA expression of the imprinted genes. RESULTS: Lower blastocyst cell number, higher genome and Grb10 CGI1 methylation, and variable mRNA expression were observed in the ART groups compared with the control group. Whether fertilization was in vivo or in vitro, the changes in the genome and Grb10 CGI1 methylation level and Grb10 and H19 expression were similar in the groups with superovulation and more significant than the IVM group. CONCLUSIONS: These results suggest that superovulation had a greater impact than IVF or IVM on the genome and Grb10 DNA methylation level, and Grb10 and H19 expression.

Agromyces binzhouensis sp. nov., an actinobacterium isolated from a coastal wetland of the Yellow River Delta.

A Gram-stain-positive, heterotrophic, non-spore-forming, rod-shaped strain, designated OAct353T, belonging to the genus Agromyces was isolated from a soil sample collected from a coastal wetland of the Yellow River delta, PR China. The strain was identified using a polyphasic taxonomic approach. The strain grew in the presence of 0-10 % (w/v) NaCl (optimum 2-3 %), at pH 5.0-8.0 (optimum pH 7.0) and 12-36 °C (optimum 28 °C). The isolate contained 2,4-diaminobutyric acid, glutamic acid and glycine in its peptidoglycan. The acyl type of the cell-wall muramic acid was N-acetyl. The whole-cell sugars of this novel strain were glucose, xylose and rhamnose. The predominant menaquinones were MK-12 (74 %) and MK-11 (21 %). The major phospholipids were phosphatidylglycerol, one unknown phospholipid, three unknown glycolipids and three unknown polar lipids. The major fatty acids were iso-C16:0, anteiso-C15:0 and anteiso-C17:0. The DNA G+C content was 69.6 mol %. DNA-DNA relatedness clearly separated strain OAct353T from its closest relatives. On the basis of phenotypic, phylogenetic and chemotaxonomic data, a novel species, Agromyces binzhouensis sp. nov., is proposed. The type strain is OAct353T (=CGMCC4.7180T=DSM 28305T=NRRL B-59115T).

Microbacterium nanhaiense sp. nov., an actinobacterium isolated from sea sediment.

A Gram-staining-positive, heterotrophic, anaerobic, non-spore-forming, non-motile, rod-shaped strain, OAct400T, belonging to the genus Microbacterium was isolated from a sediment collected from a depth of 2093 m in the South China Sea, China. The strain was identified using a polyphasic taxonomic approach. The strain grew well on yeast extract/malt extract agar (ISP 2) and nutrient agar media, and formed no aerial mycelium and no diffusible pigments on any media tested. The strain grew in the presence of 0-8 % (w/v) NaCl (optimum, 2-4 %), at pH 5.0-10.0 (optimum, pH 7.0) and at 4-37 °C (optimum, 28 °C). Strain OAct400T contained ornithine as the diagnostic diamino acid. The whole-cell sugars were dominated by glucose and galactose. The predominant menaquinones were MK-11 (51 %) and MK-10 (24 %). The major phospholipids were phosphatidylglycerol and diphosphatidylglycerol. The major fatty acids were anteiso-C15 : 0 (59.35 %), iso-C16 : 0 (17.89 %) and anteiso-C17 : 0 (16.09 %). DNA-DNA relatedness with Microbacterium amylolyticum DSM 24221T and Microbacterium gubbeenense CIP 107184T, the nearest phylogenetic relatives (97.73 and 97.44 % 16S rRNA gene sequence similarity, respectively) was 31.3 ± 2.1 and 28.7 ± 1.2 %, respectively. On the basis of phenotypic, phylogenetic and genotypic data, a novel species, Microbacterium nanhaiense sp. nov., is proposed. The type strain is OAct400T ( = CGMCC 4.7181T = DSM 26811T = KCTC 29185T).

Turn-on detection of a cancer marker based on near-infrared luminescence energy transfer from NaYF4:Yb,Tm/NaGdF4 core-shell upconverting nanoparticles to gold nanorods.

A homogeneous immunoassay for the sensitive and selective determination of trace amounts of α-fetoprotein (AFP, a cancer marker) by detection in the near-infrared (NIR) region based on luminescence energy transfer (LET) from NaYF4:Yb,Tm/NaGdF4 core-shell upconverting nanoparticles to gold nanorods (GNRs) is presented. The carboxyl-functionalized NaYF4:Yb,Tm/NaGdF4 core-shell upconverting nanoparticles (UCNPs) were excited by a 980 nm continuous wavelength laser, and its emission peak appeared at a near-infrared wavelength (∼804 nm). The carboxyl-functionalized upconverting nanoparticles were conjugated with the anti-AFP (Ab1) and acted as donor. GNRs with a high absorption band around 790 nm, which was overlapped the UCNPs emission, were synthesized and acted as the acceptor. The donor (negatively charged) interacted with the acceptor (positively charged) via electrostatic interactions to bring them into close proximity. LET could occur, producing a quenching phenomenon. When the AFP antigens were added into the system, the binding affinity between AFP and Ab1 was stronger than the electrostatic interactions, which released the energy acceptors from the energy donors, interrupting luminescence energy transfer, and therefore, the luminescence was recovered. On the basis of the restored luminescence, a turn-on optical immunosening system was developed. Under the optimal conditions, the linear range of detection was from 0.18 to 11.44 ng/mL for AFP (R = 0.99), with a detection limit as low as 0.16 ng/mL. The proposed method has also been used to monitor AFP in human serum samples. Therefore, further study based on the NaYF4:Yb,Tm/NaGdF4 core-shell nanoparticles-GNRs construction may open the way for a new class of NIR-LET biosensors with wide applications.

Determination of chromium(III) in aqueous solution using CePO4 :Tb(3+) nanocrystals in a fluorescence resonance energy transfer system.

Trivalent chromium is an essential element required for normal carbohydrate, lipid and protein metabolism in humans and animals. This article describes an efficient fluorescence resonance energy transfer (FRET) system between CePO4 :Tb(3+) nanocrystals as the donor and chromium(III) as the acceptor. CePO4 :Tb(3+) nanocrystals were synthesized in aqueous solution, and characterized by transmission electron microscopy. Under optimum conditions, a linear calibration graph was obtained (R(2) = 0.996). The linear range and detection limit of chromium(III) were 0.01-2.2 µM, and 9.1 nM, respectively. The proposed method had a wide linear range and proved to be very sensitive, rapid and simple. Moreover, the method was applied successfully to the determination of chromium(III) in synthetic samples and tap water.

Diagnostic Value of Three-Dimensional Speckle Tracking Imaging Strain Parameters for Detection of Cancer Chemotherapy-Related Cardiac Dysfunction: A Meta-Analysis. / Valor Diagnóstico de Parâmetros Tridimensionais de Strain de Imagem de Speckle Tracking para Detecção de Disfunção Cardíaca Relacionada à Quimioterapia do Câncer: Uma Metanálise.

BACKGROUND: Chemotherapeutic agents (e.g., anthracyclines, trastuzumab) commonly used for treating malignant tumors have been demonstrated to have cardiotoxic effects, which is associated with poor prognosis. Three-dimensional echocardiography has been used to predict cancer chemotherapy-induced cardiac dysfunction. OBJECTIVES: Evaluation of the diagnostic performance of strain parameters, global area strain (GAS), longitudinal strain (GLS), circumferential strain (GCS), and radial strain (GRS) by meta-analysis. METHODS: Relevant studies were searched from the Embase, PubMed, and Web of Science databases. Statistical analysis was performed using Stata 12. The summary receiver operating characteristic curve, sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and corresponding 95% confidence interval for the four strain parameters were pooled. P<0.05 was considered statistically significant. RESULTS: Nine studies involving 650 participants were included. GAS and GLS showed significant diagnostic advantages over GCS and GRS. For GAS, the sensitivity was 0.85 (0.70, 0.93) and specificity was 0.82(0.78, 0.86) with PLR of 4.76 (3.55, 6.39) and NLR of 0.18 (0.09, 0.39) and an area under the curve (AUC) of 0.85 (0.82, 0.88). For GLS, the sensitivity was 0.81 (0.74, 0.86) and specificity was 0.81(0.68, 0.90) with PLR of 4.35(2.42, 7.80) and NLR of 0.23 (0.17, 0.33) and an AUC of 0.85 (0.82, 0.88). The GCS showed a sensitivity of 0.63 and a specificity of 0.79 with an AUC of 0.77. The GRS showed a sensitivity of 0.74 and a specificity of 0.66 with an AUC of 0.73. CONCLUSION: 3D-STI strain parameters GAS and GLS showed good performance in detecting early cardiac dysfunction in patients with tumors receiving chemotherapy.

FUNDAMENTO: Agentes quimioterápicos (por exemplo, antraciclinas, trastuzumabe) comumente usados para o tratamento de tumores malignos demonstraram ter efeitos cardiotóxicos, que estão associados a um prognóstico ruim. A ecocardiografia tridimensional tem sido usada para prever a disfunção cardíaca induzida pela quimioterapia do câncer. OBJETIVOS: Avaliação do desempenho diagnóstico de parâmetros de strain, área global de strain (AGS), strain longitudinal (SLG), strain circunferencial (SCG) e strain radial (SRG) por metanálise. MÉTODOS: Estudos relevantes foram pesquisados nas bases de dados Embase, PubMed e Web of Science. A análise estatística foi realizada usando Stata 12. O resumo da curva característica operacional do receptor, sensibilidade, especificidade, razão de verossimilhança positiva (RVP), razão de verossimilhança negativa (RVN), e o correspondente intervalo de confiança de 95% para os quatro parâmetros de strain foram combinados. P<0,05 foi considerado estatisticamente significativo. RESULTADOS: Nove estudos envolvendo 650 participantes foram incluídos. AGS e SLG mostraram vantagens diagnósticas significativas sobre SCG e SRG. Para AGS, a sensibilidade foi de 0,85 (0,70, 0,93) e a especificidade foi de 0,82 (0,78, 0,86) com RVP de 4,76 (3,55, 6,39) e RVN de 0,18 (0,09, 0,39) e uma área sob a curva (AUC) de 0,85 (0,82, 0,88). Para SLG, a sensibilidade foi de 0,81 (0,74, 0,86) e a especificidade foi de 0,81 (0,68, 0,90) com RVP de 4,35 (2,42, 7,80) e RVN de 0,23 (0,17, 0,33) e uma AUC de 0,85 (0,82, 0,88).OGCS mostrou uma sensibilidade de 0,63 e uma especificidade de 0,79 com uma AUC de 0,77.O SRG mostrou uma sensibilidade de 0,74e uma especificidade de 0,66 com umAUC de 0,73. CONCLUSÃO: Parâmetros 3D-STI de strain AGS e SLG mostraram bom desempenho na detecção precoce de disfunção cardíaca em pacientes com tumores recebendo quimioterapia.

TBK1 promotes thyroid cancer progress by activating the PI3K/Akt/mTOR signaling pathway.

INTRODUCTION: Thyroid cancer has received increasing attention; however, its detailed pathogenesis and pathological processes remain unclear. We investigated the role of TANK-binding kinase 1 (TBK1) in the progression of thyroid cancer. METHODS: The expression of TBK1 in thyroid cancer and normal control tissues was analyzed using real-time quantitative polymerase chain reaction. The function of TBK1 on thyroid cancer cells was detected using MTT, colony formation, wound healing, and Transwell assays. The xenograft assay was carried out to check on the role of TBK1 in thyroid cancer. RESULTS: TBK1 was highly expressed in thyroid tumors. High expression of TBK1 raised viability, proliferation, migration, and invasion of thyroid cancer cells. Gene set enrichment analysis revealed that TBK1 activated the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway. In addition, Myc-associated zinc finger protein (MAZ) was overexpressed in thyroid cancer and transcriptionally activated BK1. MAZ silence reversed the effects of TBK1 overexpression on thyroid cancer progression. Cotransfection with MAZ small-interfering RNA(siRNA) and TBK1 siRNA did not strengthen the inhibitory effect of TBK1 silencing on the thyroid cancer cells. The xenograft tumor assay showed that TBK1 short hairpinRNA inhibited tumor growth. CONCLUSION: MAZ silencing inhibited tumor progress of thyroid cancer cells, whereas this inhibitory effect was reversed by TBK1 overexpression.

Comprehensive Evaluation and Analysis of Human Settlements' Suitability in the Yangtze River Delta Based on Multi-Source Data.

The suitability of human settlements is critical for quality of life and regional development. As comprehensive evaluations and research on the suitability of human settlements are lacking, a comprehensive evaluation of human settlements in the Yangtze River Delta (YRD) was carried out in 2020 by combining natural and human environmental elements based on multi-source data such as digital elevation models, Landsat remote sensing images, meteorological station data, and points of interest, other multi-source data, and constructions of the human settlements' suitability indexes. The results showed the following: (1) The spatial suitability of the natural environment in the YRD is significantly affected by the topographic conditions and distance from the sea, showing an increasing spatial differentiation from southwest to northeast, with Shanghai and Yancheng having the best natural environment suitability. (2) The suitability of the human environment in urban areas is better than that in non-urban areas and shows a decreasing trend from the south to the north circle. Shanghai, Zhoushan, and Huaibei have the best human environment suitability. (3) The comprehensive suitability of human settlements includes both the spatial differentiation characteristics of the suitability of natural and human environments. Shanghai and Zhoushan have the mosy comprehensive suitability for human settlements, while Huaibei and Xuzhou have the worst. (4) Land with a comprehensive suitability for human settlements of greater than 0.580 accounts for 23.60% of the total and contains 30.08% of the population and 32.31% of the economy, indicating that areas with a high suitability index have been fully utilized, and the populations and economies with human settlements suitability have a high degree of matching.

Accuracy and reproducibility of the O-RADS MRI risk stratification system based on enhanced non-DCE MRI in the assessment of adnexal masses.

OBJECTIVE: Evaluation of the diagnostic performance and reproducibility of the Ovarian-Adnexal Reporting and Data System (O-RADS) Magnetic Resonance Imaging (MRI) risk stratification system based on enhanced non-dynamic contrast-enhanced (non-DCE) MRI in the diagnosis of adnexal masses. METHODS: Patients who underwent conventional pelvic enhanced non-DCE MRI examination within one month prior to surgery formed the study population. Two experienced radiologists independently evaluated the images and assigned a score according to the O-RADS MRI risk stratification system. One of the radiologists reviewed the images and reassigned the scores after three months. Intra- and inter-observer agreement was evaluated with the k coefficient value. The adnexal masses that attained scores between 1 and 3 were considered benign, while those with scores of 4 or 5 were considered malignant. Analyses were conducted to determine the sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic (ROC) curve, which were then used for evaluating the diagnostic efficacy of the developed system based on enhanced non-DCE MRI scan. The reference standard was histology. RESULTS: A total of 308 patients (mean age: 42.09 ± 12.42 years, age range: 20-84 years) were enrolled in the study. Among the 362 adnexal masses from the included patients, there were 320 benign masses and 42 malignant masses. In the case of three readers, there were no malignant tumors scored 1-2. The O-RADS MRI score ≥ 4 was associated with malignancy resulted in a good diagnostic efficacy with the areas under the curve (AUC) values of 0.918 (95 % CI, 0.864-0.972), 0.905 (95 % CI, 0.842-0.968), and 0.882 (95 % CI, 0.815-0.950), the sensitivity values of 90.5 % (95 % CI, 87.5-93.5 %), 85.7 % (95 % CI, 82.1-89.3 %), and 83.3 % (95 % CI, 79.5-87.2 %), and the specificity values of 93.1 % (95 % CI, 90.5-95.7 %), 95.3 % (95 % CI, 93.1-97.5 %), and 93.1 % (95 % CI, 90.5-95.7 %) obtained for the three readers, respectively. Excellent intra-observer agreement and inter-observer agreement were observed with the k values of 0.883 (95 % CI, 0.814-0.952) and 0.848 (95 % CI, 0.770-0.926), respectively. CONCLUSIONS: The O-RADS MRI risk stratification system based on enhanced non-DCE MRI scans exhibited high accuracy and reproducibility in the prediction of adnexal masses malignancy. Enhanced non-DCE MRI scan may offer an alternative diagnostic tool when DCE is not possible.

Prognostic significance of CDK6 amplification in esophageal squamous cell carcinoma.

Dysregulation of CDK6 plays crucial roles in the carcinogenesis of many kinds of human malignancies. However, the role of CDK6 in esophageal squamous cell carcinoma (ESCC) is not well known. We investigated the frequency and prognostic value of CDK6 amplification to improve the risk stratification in patients with ESCC. Pan-cancer analysis of CDK6 was conducted on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases. CDK6 amplification was detected in 502 ESCC samples by Fluorescence in situ hybridization (FISH) through tissue microarrays (TMA). Pan-cancer analysis revealed that CDK6 mRNA level was much higher in multiple kinds of cancers and higher CDK6 mRNA level indicated a better prognosis in ESCC. In this study, CDK6 amplification was detected in 27.5% (138/502) of patients with ESCC. CDK6 amplification was significantly correlated with tumor size (p = 0.044). Patients with CDK6 amplification tended to have a longer disease-free survival (DFS) (p = 0.228) and overall survival (OS) (p = 0.200) compared with patients without CDK6 amplification but of no significance. When further divided into I-II and III-IV stage, CDK6 amplification was significantly associated with longer DFS and OS in III-IV stage group (DFS, p = 0.036; OS, p = 0.022) rather than in I-II stage group (DFS, p = 0.776; OS, p = 0.611). On univariate and multivariate analysis of Cox hazard model, differentiation, vessel invasion, nerve invasion, invasive depth, lymph node metastasis and clinical stage were significantly associated with DFS and OS. Moreover, invasion depth was an independent factor for ESCC prognosis. Taken together, for ESCC patients in III-IV stage, CDK6 amplification indicated a better prognosis.

Kikuchi-Fujimoto disease following vaccination against COVID-19.

The purpose of this study is to explore the clinicopathological features of Kikuchi-Fujimoto disease (KFD) following vaccination against coronavirus disease 2019 (COVID-19). One case of KFD following vaccination against COVID-19 was examined clinically, histologically, and immunohistochemically. The patient was a 36-year-old Chinese man who suffered from fever and cervical lymph node swelling following simultaneous administration of the COVID-19 vaccine. The patient was diagnosed with KFD based on the histopathological findings of a lymph node core needle biopsy, and his fever and swelling resolved 2 months later without therapy. Although the exact pathogenesis of the development of KFD following immunization remains unknown, this information should be added to the list of potential triggers or factors associated with the development of KFD.

Effect of Urban fringes green space fragmentation on ecosystem service value.

In this study, an urban fringe green space classification system was established to explore the spatiotemporal variation of green space landscape and ecosystem service value (ESV) based on multi-source land-use data of Ganjingzi district from 2000 to 2018. (1) Results show that the total green space area declined from 359.57 to 213.46 km2 over the study period. Green space large plaque index (LPI) and class area both gradually declined, whereas the number of plaques (NP) and plaque density (PD) gradually increased, indicating green space landscape fragmentation. (2) Additionally, the value of green space ecosystem services reduced from 397.42 to 124.93 million yuan. The dynamic degree of ESV change in green space increased or decreased moderately, always being < 0 and showing a decreasing trend of ESV. From a spatial variation perspective, dynamic degrees of ESV variation in the western and northern regions with relatively intensive green space were higher than those in the east. Regarding ESV of various green space types, forest land had the highest functional values of ecological regulation and support, whereas arable land provided the highest functional values of production supply. (3) The ecological service function value of green space system is negatively correlated with PD, NP, edge density, landscape shape index, and Shannon's diversity index, and positively correlated with aggregation index, contagion metrics, and LPI. The correlation coefficient between the climate regulation function of forest and the change of number of plaques is -0.874. The correlation coefficient of the recreation and culture of the wetland to the plaque density change is no less than -0.214.

Antimicrobial Quantitative Relationship and Mechanism of Plant Flavonoids to Gram-Positive Bacteria.

Antimicrobial resistance (AMR) poses a serious threat to human health, and new antimicrobial agents are desperately needed. Plant flavonoids are increasingly being paid attention to for their antibacterial activities, for the enhancing of the antibacterial activity of antimicrobials, and for the reversing of AMR. To obtain more scientific and reliable equations, another two regression equations, between the minimum inhibitory concentration (MIC) (y) and the lipophilicity parameter ACD/LogP or LogD7.40 (x), were established once again, based on the reported data. Using statistical methods, the best one of the four regression equations, including the two previously reported, with regard to the antimicrobial quantitative relationship of plant flavonoids to Gram-positive bacteria, is y = -0.1285 x6 + 0.7944 x5 + 51.785 x4 - 947.64 x3 + 6638.7 x2 - 21,273 x + 26,087; here, x is the LogP value. From this equation, the MICs of most plant flavonoids to Gram-positive bacteria can be calculated, and the minimum MIC was predicted as approximately 0.9644 µM and was probably from 0.24 to 0.96 µM. This more reliable equation further proved that the lipophilicity is a key factor of plant flavonoids against Gram-positive bacteria; this was further confirmed by the more intuitive evidence subsequently provided. Based on the antibacterial mechanism proposed in our previous work, these also confirmed the antibacterial mechanism: the cell membrane is the major site of plant flavonoids acting on the Gram-positive bacteria, and this involves the damage of the phospholipid bilayers. The above will greatly accelerate the discovery and application of plant flavonoids with remarkable antibacterial activity and the thorough research on their antimicrobial mechanism.

Drug Combinations to Prevent Antimicrobial Resistance: Various Correlations and Laws, and Their Verifications, Thus Proposing Some Principles and a Preliminary Scheme.

Antimicrobial resistance (AMR) has been a serious threat to human health, and combination therapy is proved to be an economic and effective strategy for fighting the resistance. However, the abuse of drug combinations conversely accelerates the spread of AMR. In our previous work, we concluded that the mutant selection indexes (SIs) of one agent against a specific bacterial strain are closely related to the proportions of two agents in a drug combination. To discover probable correlations, predictors and laws for further proposing feasible principles and schemes guiding the AMR-preventing practice, here, three aspects were further explored. First, the power function (y = axb, a > 0) correlation between the SI (y) of one agent and the ratio (x) of two agents in a drug combination was further established based on the mathematical and statistical analyses for those experimental data, and two rules a1 × MIC1 = a2 × MIC2 and b1 + b2 = −1 were discovered from both equations of y = a1xb1 and y = a2xb2 respectively for two agents in drug combinations. Simultaneously, it was found that one agent with larger MPC alone for drug combinations showed greater potency for narrowing itself MSW and preventing the resistance. Second, a new concept, mutation-preventing selection index (MPSI) was proposed and used for evaluating the mutation-preventing potency difference of two agents in drug combination; a positive correlation between the MPSI and the mutant prevention concentration (MPC) or minimal inhibitory concentration (MIC) was subsequently established. Inspired by this, the significantly positive correlation, contrary to previous reports, between the MIC and the corresponding MPC of antimicrobial agents against pathogenic bacteria was established using 181 data pairs reported. These results together for the above three aspects indicate that the MPCs in alone and combination are very important indexes for drug combinations to predict the mutation-preventing effects and the trajectories of collateral sensitivity, and while the MPC of an agent can be roughly calculated from its corresponding MIC. Subsequently, the former conclusion was further verified and improved via antibiotic exposure to 43 groups designed as different drug concentrations and various proportions. The results further proposed that the C/MPC for the agent with larger proportion in drug combinations can be considered as a predictor and is the key to judge whether the resistance and the collateral sensitivity occur to two agents. Based on these above correlations, laws, and their verification experiments, some principles were proposed, and a diagram of the mutation-preventing effects and the resistant trajectories for drug combinations with different concentrations and ratios of two agents was presented. Simultaneously, the reciprocal of MPC alone (1/MPC), proposed as the stress factors of two agents in drug combinations, together with their SI in combination, is the key to predict the mutation-preventing potency and control the trajectories of collateral sensitivity. Finally, a preliminary scheme for antimicrobial combinations preventing AMR was further proposed for subsequent improvement research and clinic popularization, based on the above analyses and discussion. Moreover, some similar conclusions were speculated for triple or multiple drug combinations.

Codelivery of HBx-siRNA and Plasmid Encoding IL-12 for Inhibition of Hepatitis B Virus and Reactivation of Antiviral Immunity.

Chronic hepatitis B is a critical cause of many serious liver diseases such as hepatocellular carcinoma (HCC). The main challenges in hepatitis B treatment include the rebound of hepatitis B virus (HBV)-related antigen levels after drug withdrawal and the immunosuppression caused by the virus. Herein, we demonstrate that the HBV-related antigen can be effectively inhibited and antiviral immunity can be successfully reactivated through codelivery of the small interfering RNA (siRNA) targeting HBV X protein (HBx) and the plasmid encoding interleukin 12 (pIL-12) to hepatocytes and immune cells. After being treated by the siRNA/pIL-12 codelivery system, HBx mRNA and hepatitis B surface antigen (HBsAg) are dramatically reduced in HepG2.215 cells. More importantly, the downregulated CD47 and programmed death ligand 1 (PD-L1) and the upregulated interferon-ß promoter stimulator-1 (IPS-1), retinoic acid-inducible gene-1 (RIG-1), CD80, and human leukocyte antigen-1 (HLA-1) in treated HepG2.215 cells indicate that the immunosuppression is reversed by the codelivery system. Furthermore, the codelivery system results in inhibition of extracellular regulated protein kinases (ERK) and phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) pathways, as well as downregulation of B-cell lymphoma-2 (Bcl-2) and upregulation of p53, implying its potential in preventing the progression of HBV-induced HCC. In addition, J774A.1 macrophages treated by the codelivery system were successfully differentiated into the M1 phenotype and expressed enhanced cytokines with anti-hepatitis B effects such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α). Therefore, we believe that codelivery of siRNA and pIL-12 can effectively inhibit hepatitis B virus, reverse virus-induced immunosuppression, reactivate antiviral immunity, and hinder the progression of HBV-induced hepatocellular carcinoma. This investigation provides a promising approach for the synergistic treatment of HBV infection.