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Eighteen linear triquinane sesquiterpenoids (LTSs), including seventeen previously undescribed ones (hirsutuminoids A-Q), were isolated from the fermentation of the fungus Stereum hirsutum (Willd.) Pers. The structures and absolute configurations of the isolates were characterized by extensive spectroscopic analysis (1D, 2D NMR, and HRMS data), together with comparing the experimental and calculated data of both electronic circular dichroism and NMR data, as well as X-ray crystallography. Based on the literature survey and efforts on constructing the absolute configurations of these LTSs in this study, one empirical rule about the orientations of substitutions at C-2/C-3/C-7/C-9 was summarized. Anti-inflammatory and cytotoxic bioassays showed that only hirsutuminoid B inhibited the nitric oxide (NO) production in RAW 264.7 macrophages with an IC 50 value, 18.9 μM., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The present study analyzed the effect of Citri Reticulatae Pericarpium on endogenous metabolites in spleen deficiency and phlegm dampness syndrome by metabolomics, and explored the underlying mechanism of Citri Reticulatae Pericarpium in the treatment of spleen deficiency and phlegm dampness syndrome.The model of spleen deficiency and phlegm dampness syndrome was induced in rats by the multi-factor modeling method.The intervention effects of Citri Reticulatae Pericarpium on rats with spleen deficiency and phlegm dampness syndrome were preliminarily evaluated by observing the pathological changes of rat liver tissues and measuring the plasma content of pathological and biochemical indexes such as triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C).Immunohistochemistry was used to detect the expression of AQP2 in the kidney, AQP3 in the colon, and AQP5 in the submandibular gland, and the effect of Citri Reticulatae Pericarpium on aquaporin expression in rats with spleen deficiency and phlegm dampness syndrome was evaluated.Furthermore, UHPLC-ESI-MS/MS was used to analyze the metabolic profiles of rat plasma samples.Multiple methods, such as principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were used for pattern recognition.Differential metabolites were screened out by t-test and variable importance in projection(VIP), followed by pathway analysis based on MetaboAnalyst 5.0.As revealed by experimental results, Citri Reticulatae Pericarpium could improve the pathological changes of liver tissues, increase the levels of HDL-C in the plasma, reduce the levels of TC, TG, and LDL-C, and enhance the expression of AQP2 in the kidney, AQP3 in the colon, and AQP5 in the submandibular gland of rats with spleen deficiency and phlegm dampness syndrome.In addition, 87 differential metabolites of spleen deficiency and phlegm dampness syndrome were screened out by UHPLC-ESI-MS/MS(the levels of 39 metabolites increased significantly and the levels of 48 metabolites decreased significantly), with the representatives of glycine, L-isoleucine, N-acetyl-L-tyrosine, xanthine, hypoxanthine, and trigonelline.The differential metabolites were mainly enriched in the pathways of steroid hormone biosynthesis, linoleic acid metabolism, and purine metabolism.This study distinguished and revealed the characteristic metabolic pattern of spleen deficiency and phlegm dampness syndrome by metabolomics.The preliminary construction of the OPLS-DA model provides an objective basis for the differentiation of spleen deficiency and phlegm dampness syndrome in traditional Chinese medi-cine(TCM), as well as ideas and methods for exploring the biological basis of TCM syndrome from the molecular level and the overall level.

Indole is an inter-species and inter-kingdom signaling molecule widespread in the natural world. A large amount of indole in livestock wastes makes it difficult to be degraded, which causes serious malodor. Identifying efficient and eco-friendly ways to eliminate it is an urgent task for the sustainable development of husbandry. While bioconversion is a widely accepted means, the mechanism of indole microbial degradation is little understood, especially under anaerobic conditions. Herein, a new Enterococcus hirae isolate GDIAS-5, effectively degraded 100 mg/L indole within 28 h aerobically or 5 days anaerobically. Three intermediates (oxindole, isatin, and catechol) were identified in indole degradation, and catechol was further degraded by a meta-cleavage catabolic pathway. Two important processes for GDIAS-5 indole utilization were discovered. One is Fe(III) uptake and reduction, which may be a critical process that is coupled with indole oxidation, and the other is the entire pathway directly involved in indole oxidation and metabolism. Furthermore, monooxygenase ycnE responsible for indole oxidation via the indole-oxindole-isatin pathway was identified for the first time. Bioinformatic analyses showed that ycnE from E. hirae formed a phylogenetically separate branch from monooxygenases of other species. These findings provide new targets and strategies for synthetic biological reconstruction of indole-degrading bacteria., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Human cytomegalovirus (CMV) is associated with aspergillosis, but the simultaneous presence of CMV viral interleukin-10 (cmvIL-10) and aspergillosis has never been investigated. CmvIL-10 is produced by CMV-infected cells and acts as an immune modulator during CMV infection. The aim of this study was to evaluate cmvIL-10 levels in peripheral blood and its influence on the clinical outcomes of Aspergillus infection., Methods: Patients who visited or were admitted to the hospital with suspected Aspergillus infection, including invasive aspergillosis (IA) and chronic pulmonary aspergillosis (CPA), were prospectively enrolled. The cmvIL-10, human IL-10 (hIL-10), IL-1B, IL-6, IL-8, IFN-γ, and TNF-α levels in peripheral blood were measured., Results: Patients with Aspergillus infection had a higher level of cmvIL-10 than the control group (158 ± 305 vs 27.9 ± 30.4 pg/ml, p < .05). The level of cmvIL-10 was not correlated with CMV viremia or end-organ disease. The cmvIL-10 but not hIL-10 level was positively correlated with the IFN-γ level (p < .05) and marginally negatively correlated with IL-1B and IL-8 levels (p < .1). In patients with CPA, a high level of cmvIL-10 (≥100 pg/ml) was a poor prognostic factor for long-term survival (p < .05). In contrast, CMV viremia or end-organ disease was associated with poor survival in patients with IA (p = .05)., Conclusions: Aspergillus infection was associated with CMV coinfection with cmvIL-10 in blood. A cmvIL-10 concentration ≥100 pg/ml was a predictor for unfavourable outcome in CPA patients., (© 2022 Wiley-VCH GmbH.)

Coronavirus disease 2019 (COVID-19) continues to ravage world economies, and with its recent mutations, countries worldwide are finding ways of ramping up their vaccination programmes. This cross-sectional design study, therefore, examined the predictors of COVID-19 stress and COVID-19 vaccination acceptance among adolescents in Ghana. A total of 817 participants were conveniently selected to respond to measures on fear of COVID-19, perceived stigma from COVID-19, self-stigma from COVID-19, believing COVID-19 information, COVID-19 infection prevention behaviours, COVID-19 stress, and COVID-19 vaccination acceptance. It was found that females believed COVID-19 information and accepted COVID-19 vaccination more than males did. Moreover, there were significant relationships between the majority of the COVID-19-related variables. Furthermore, fear of COVID-19, self-stigma from COVID-19, and COVID-19 infection prevention behaviours were found to be significant predictors of COVID-19 stress. Additionally, believing COVID-19 information, danger and contamination fears (a subscale of COVID-19 stress), and traumatic stress (a subscale of COVID-19 stress) were significant predictors of COVID-19 vaccination acceptance. These findings imply that different factors influence different COVID-19 variable. Therefore, careful considerations and research should be employed by health authorities and policymakers in preparing COVID-19 information to target different age groups and for different COVID-19 purposes.

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder. The functions of lncRNA RMRP have been characterized mainly in various human cancers. However, the functional network of RMRP in AD progression remains unknown., Methods: Human serum samples, AD transgenic (Tg) mice as well as SH-SY5Y cells were used in this study. The RNA expression patterns of RMRP, miR-3142 and TRIB3 were assessed by quantitative real-time PCR (qRT-PCR). Levels of apoptosis- or autophagy-associated biomarkers and TRIB3 level were evaluated using immunohistochemistry (IHC), western blotting or immunofluorescence assays, respectively. Bioinformatics methods and luciferase assays were used to predict and validate the interactions among RMRP, miR-3142, and TRIB3. Flow cytometry, TUNEL staining and EdU assays were used to examine the apoptosis and proliferation of neurons, respectively., Results: The elevated RMRP and TRIB3 expressions and activation of autophagy were observed in AD. Knockdown of RMRP restrained neuronal apoptosis and autophagy activation in vitro and in vivo. Interestingly, TRIB3 overexpression reversed the biological effects of RMRP silencing on Aβ 1-42 -induced cell apoptosis and autophagy. Further mechanistic analysis showed RMRP acted as a sponge of miR-3142 to elevate TRIB3 level., Conclusion: These data illustrated that knockdown of RMRP inhibited autophagy and apoptosis via regulating miR-3142/TRIB3 axis in AD, suggesting that inhibition of RMRP maybe a therapeutic strategy for AD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In patients with multiparameter magnetic resonance imaging (mpMRI) low-possibility but highly clinical suspicion of prostate cancer, the biopsy core is unclear. Our study aims to introduce the biopsy density (BD; the ratio of biopsy cores to prostate volume) and investigates the BD-predictive value of prostate cancer and clinically significant prostate cancer (csPCa) in PI-RADS<3 patients., Methods: Patients underwent transperineal template-guided prostate biopsy from 2012 to 2022. The inclusion criteria were PI-RADS<3 with a positive digital rectal examination or persistent PSA abnormalities. BD was defined as the ratio of the biopsy core to the prostate volume. Clinical data were collected, and we grouped the patients according to pathology results. Kruskal-Wallis test and chi-square test were used in measurement and enumeration data, respectively. Logistics regression was used to choose the factor associated with positive biospy and csPCa. The receiver operating characteristic (ROC) curve was used to evaluate the ability to predict csPCa., Results: A total of 115 patients were included in our study. Biopsy was positive in 14 of 115 and the International Society of Urological Pathology grade groups 2-5 were in 7 of all the PCa patients. The BD was 0.38 (0.24-0.63) needles per milliliter. Binary logistics analysis suggested that PSAD and BD were correlated with positive biopsy. Meanwhile, BD and PSAD were associated with csPCa. The ROC curve illustrated that BD was a good parameter to predict csPCa (AUC=0.80, 95% CI: 0.69-0.91, p<0.05). The biopsy density combined with PSAD increased the prediction of csPCa (AUC=0.90, 95% CI: 0.85-0.97, p<0.05). The cut-off value of the BD was 0.42 according to the Youden index., Conclusion: In PI-RADS<3 patients, BD and PSAD are related to csPCa. A biopsy density of more than 0.42 needles per millimeter can increase the csPCa detection rate, which should be considered as an alternative biopsy method when we perform prostate biopsy in patients with PI-RADS<3., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Ding, Lu, Ding, Pi, Liu, Xiao, Zhu, Luan, Han, Chen and Liu.)

Diffraction gratings are becoming increasingly widespread in optical applications, notably in lasers. This study presents the work on the characterization and evaluation of Multilayer Dielectric Diffraction Gratings (MDG) based on the finite element method using Comsol MultiPhysics software. The optimal multilayer dielectric diffraction grating structure using a rectangular three-layer structure consisting of an aluminum oxide Al 2 O 3 layer sandwiched between two silicon dioxide SiO 2 layers on a multilayer dielectric mirror is simulated. Results show that this MDG for non-polarized lasers at 1064 nm with a significantly enhanced -1st diffraction efficiency of 97.4%, reaching 98.3% for transverse-electric (TE) polarization and 96.3% for transverse-magnetic (TM) polarization. This design is also preferable in terms of the laser damage threshold (LDT) because most of the maximum electric field is spread across the high LDT material SiO 2 for TE polarization and scattered outside the grating for TM polarization. This function allows the system to perform better and be more stable than normal diffraction grating under a high-intensity laser.

Background & Aims: Checkpoint immunotherapy is largely ineffective in pancreatic ductal adenocarcinoma (PDAC). The innate immune nuclear factor (NF)-κB pathway promotes PDAC cell survival and stromal fibrosis, and is driven by Interleukin-1 Receptor Associated Kinase-4 (IRAK4), but its impact on tumor immunity has not been directly investigated., Methods: We interrogated The Cancer Genome Atlas data to identify the correlation between NF-κB and T cell signature, and a PDAC tissue microarray (TMA) to correlate IRAK4 activity with CD8 + T cell abundance. We performed RNA sequencing (RNA-seq) on IRAK4-deleted PDAC cells, and single-cell RNA-seq on autochthonous KPC (p48-Cre/TP53 f/f /LSL-KRAS G12D ) mice treated with an IRAK4 inhibitor. We generated conditional IRAK4-deleted KPC mice and complementarily used IRAK4 inhibitors to determine the impact of IRAK4 on T cell immunity., Results: We found positive correlation between NF-κB activity, IRAK4 and T cell exhaustion from The Cancer Genome Atlas. We observed inverse correlation between phosphorylated IRAK4 and CD8 + T cell abundance in a PDAC tissue microarray. Loss of IRAK4 abrogates NF-κB activity, several immunosuppressive factors, checkpoint ligands, and hyaluronan synthase 2, all of which drive T cell dysfunction. Accordingly, conditional deletion or pharmacologic inhibition of IRAK4 markedly decreased tumor desmoplasia and increased the abundance and activity of infiltrative CD4 + and CD8 + T cells in KPC tumors. Single-cell RNA-seq showed myeloid and fibroblast reprogramming toward acute inflammatory responses following IRAK4 inhibition. These changes set the stage for successful combination of IRAK4 inhibitors with checkpoint immunotherapy, resulting in excellent tumor control and markedly prolonged survival of KPC mice., Conclusion: IRAK4 drives T cell dysfunction in PDAC and is a novel, promising immunotherapeutic target., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: There are no randomized control trials comparing the efficacy of trifluridine/tipiracil and regorafenib in patients with metastatic colorectal cancer (mCRC). Herein, we conducted an observational study to compare the oncologic outcomes of trifluridine/tipiracil-containing regimen (TAS-102) and regorafenib-containing regimen (REG) in patients with mCRC., Material and Method: Patients who were diagnosed to have mCRC in 2015 to 2021 and treated with TAS-102-containing regimen or REG-containing regimen were recruited. Monotherapy or combination therapy were all allowed in this study. Oncologic outcomes were presented with progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR)., Results: A total of 125 patients were enrolled into our study, accounting for 50 patients with TAS-102 and 75 patients with REG. Of these patients, 64% were treated with TAS-102 or REG monotherapy, while the remaining were treated with TAS-102 combination or REG combination. In general, the median PFS and OS were 3.7 versus 2.0 months ( P = 0.006) and 9.2 versus 6.8 months ( P = 0.048) in TAS-102 and REG, respectively. The ORR and DCR were 44% versus 20% ( P < 0.001) and 72% versus 43% ( P < 0.001) in TAS-102 and REG, respectively. As for treatment strategies, the survival were significantly longer in combination than in monotherapy, no matter in TAS-102 or REG group. Multivariate analysis showed TAS-102 and combination therapy were independent predictor associated with better survival., Conclusions: Our results suggested that TAS-102 had better oncologic outcomes than REG in patients with mCRC, especially in combination. Further prospective trials are warranted to confirm our results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hsieh, Rau, Lin, Liu, Chiu, Chen, Song and Chen.)

Resibufogenin (RBG) is a natural medicinal ingredient with promising cardiac protection and antitumor activity. However, poor solubility and severe gastric mucosa irritation restrict its application in the pharmaceutical field. In this study, the inclusion complex of RBG with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared using the co-evaporation method, and the molar ratio of RBG to CD was determined to be approximately 1:2 by continuous variation plot for both CDs. The formation of inclusion complexes between RBG and each CD (RBG/β-CD and RBG/HP-β-CD) was evaluated by phase solubility study, Fourier transform infrared spectroscopy, and thin-layer chromatography. Powder X-ray diffraction and differential scanning calorimetry confirmed drug amorphization and encapsulation in the molecular cage for both CDs. Moreover, the inclusion complexes' morphologies were observed using scanning electron microscopy. The dissolution rate of the inclusion complexes was markedly improved compared to that of RBG, and the complexes retained their antitumor activity, as shown in the in vitro cytotoxicity assay on a human lung adenocarcinoma cancer (A549) cell line. Moreover, less gastric mucosal irritation was observed for the inclusion complex. Thus, the inclusion complex should be considered a promising strategy for the delivery of poorly water-soluble anticancer agents, such as RBG.

Twelve new lanostane triterpenoids ( 1 - 5 , 7 - 13 ) were isolated from the fruiting bodies of the fungus Ganoderma australe . The structures of the new compounds were elucidated by extensive 1D and 2D NMR, and HRESIMS spectroscopic analysis. All the triterpenes are featured by 20(22) E configurations which are uncommon in the Ganoderma triterpene family. The absolute configuration of the C-25 of compounds 1 , 2 , and 6 were determined by the phenylglycine methyl ester (PGME) method. A postulated biosynthetic pathway for compound 1 was discussed. This study opens new insights into the secondary metabolites of the chemically underinvestigated fungus G. australe .

A small fenbufen library comprising 18 compounds was prepared via Suzuki Miyara coupling. The five-step preparations deliver 9-17% biphenyl compounds in total yield. These fenbufen analogs exert insignificant activity against the IL-1 release as well as inhibiting cyclooxygenase 2 considerably. Both the para -amino and para -hydroxy mono substituents display the most substantial COX-2 inhibition, particularly the latter one showing a comparable activity as celecoxib. The most COX-2 selective and bioactive disubstituted compound encompasses one electron-withdrawing methyl and one electron-donating fluoro groups in one arene. COX-2 is selective but not COX-2 to bioactive compounds that contain both two electron-withdrawing groups; disubstituted analogs with both resonance-formable electron-donating dihydroxy groups display high COX-2 activity but inferior COX-2 selectivity. In silico simulation and modeling for three COX-2 active- p -fluoro, p -hydroxy and p -amino-fenbufens show a preferable docking to COX-2 than COX-1. The most stabilization by the p -hydroxy fenbufen with COX-2 predicted by theoretical simulation is consistent with its prominent COX-2 inhibition resulting from experiments.

Background: To investigate the value of intraoperative frozen section examination (IFSE) in multiparametric magnetic resonance imaging/transrectal ultrasound (mpMRI/TRUS) fusion prostate biopsy in a major pandemic., Methods: A total of 35 patients were prospectively enrolled in our hospital from March 2020 to January 2021. The mpMRI/TRUS fusion system was used to perform a targeted biopsy, and the collected specimens were examined by IFSE (Observation Group 1). Then, a targeted biopsy was performed again for routine pathological examination (Observation Group 2). Finally, a systemic biopsy was performed, and the obtained specimens were routinely examined (Control Group). The positive rate, single core positive rate, Gleason score, and time to obtain pathological reports were compared between the groups., Results: The positive rate was 48.6% (17/35) in the control group, 48.6% (17/35) in Observation Group 1, and 51.4% (18/35) in Observation Group 2, showing no significant difference (P>0.05). The single core positive rates were 17.8%, 44.6%, and 47.1% in the Control Group, Observation Group 1, and Observation Group 2, respectively. Observation Group 1 and Observation Group 2 were significantly different from the Control Group (P<0.001). No participants in Observation Group 1 had increased or decreased Gleason scores compared with those in Observation Group 2. The time to obtain the pathological report was 0.025±0.014 days and 4.216±1.073 days for Observation Group 1 and Observation Group 2, respectively, showing a significant difference (P<0.001)., Conclusions: This study showed that IFSE can not only rapidly obtain the pathological report of an mpMRI/TRUS biopsy, but can also ensure the accuracy of the pathological diagnosis., Trial Registration: CHICTR, Identifier: ChiCTR2000040789. Registered 10 December 2020 - Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=63252&htm=4., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-21-473/coif). The authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

CD4-a transmembrane glycoprotein molecule expressed on the surface of helper T (Th) cells-plays a central role in adaptive immune protection. In the current study, we developed a monoclonal antibody (mAb) against the grouper CD4-1. Western blotting and immunohistochemistry results revealed that the CD4-1 mAb could recognize the recombinant and natural protein of grouper CD4-1 as well as the CD4-1 + cells in the various tissues from grouper. Tissue distribution analyses revealed that the grouper CD4-1 + cells were expressed in all tissues tested in the healthy grouper, with greater localization in the thymus, head kidney, and spleen tissues. In addition, we tested the changes in the proportion of CD4-1 + cells in the thymus, head kidney, and the gills of grouper post the infection by C. irritans. Our data suggest that the CD4-1 mAb produced against grouper in the current study can be used as a tool to characterize CD4-1 + cells and to investigate the functions of the grouper CD4-1 + cells in the host response against pathogens infection., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Sialylation of glycoproteins is modified by distinct sialyltransferases such as ST3Gal, ST6Gal, ST6GalNAc, or ST8SIA with α2,3-, α2,6-, or α2,8-linkages. Alteration of these sialyltransferases causing aberrant sialylation is associated with the progression of colon cancer. However, among the ST8- sialyltransferases, the role of ST8SIA6 in colon cancer remains poorly understood. In this study, we explored the involvement of ST8SIA6 in colon cancer using multiple gene databases. The relationship between ST8SIA6 expression and tumor stages/grades was investigated by UALCAN analysis, and Kaplan-Meier Plotter analysis was used to analyze the expression of ST8SIA6 on the survival outcome of colon cancer patients. Moreover, the biological functions of ST8SIA6 in colon cancer were explored using LinkedOmics and cancer cell metabolism gene DB. Finally, TIMER and TISMO analyses were used to delineate ST8SIA6 levels in tumor immunity and immunotherapy responses, respectively. ST8SIA6 downregulation was associated with an advanced stage and poorly differentiated grade; however, ST8SIA6 expression did not affect the survival outcomes in patients with colon cancer. Gene ontology analysis suggested that ST8SIA6 participates in cell surface adhesion, angiogenesis, and membrane vesicle trafficking. In addition, ST8SIA6 levels affected immunocyte infiltration and immunotherapy responses in colon cancer. Collectively, these results suggest that ST8SIA6 may serve as a novel therapeutic target towards personalized medicine for colon cancer.

The enteric viruses, including adenovirus (AdVs) and norovirus (NoVs), in shellfish is a significant food safety risk. This study investigated the prevalence, seasonal occurrence, genetic diversity, and quantification of AdVs and NoVs in the water and cultured shellfish samples at the four major coastal oyster breeding farms (COBF), five major fishing ports (FP), and their markets in Taiwan. The AdVs/NoVs in the water and shellfish samples were isolated by the membrane filtration and direct elution methods. The RNA of NoVs was reverse-transcribed into complementary DNA through reverse transcription reaction. Further NoVs and AdVs were detected using nested PCR. A higher detection rate was recorded in the low-temperature period than high-temperature. Detection difference was noted between nested PCR and qPCR outcomes for AdVs. The total detection rate of AdVs was higher in the water samples (COBF-40.6%, FP 20%) than the shellfish samples (COBF-11.7% and FP 6.3%). The AdVs load in the water and shellfish samples ranged from 1.23 × 10 3 to 1.00 × 10 6 copies/L and 3.57 × 10 3 to 4.27 × 10 4 copies/100g, respectively. The total detection of NoVs was highest in the water samples of the FP and their market shellfish samples (11.1% and 3.2%, respectively). Genotyping and phylogenetic analysis were identified as the prevalent AdVs and NoVs genotypes in the water and shellfish samples: A species HAdVs serotype 12; F species HAdVs serotype 41; and C species PAdVs serotype 5 (NoVs GI.2, GI.3 and GII.2). No significant differences were observed between the presence of AdVs, and all of the water quality parameters evaluated (heterotrophic plate count, water temperature, turbidity, pH, salinity, and dissolved oxygen). The virus contamination occurs mainly due to the direct discharge of domestic sewage, livestock farm, and fishing market wastewater into the coastal environment. Thus, this study suggested framing better estuarine management to prevent AdVs/NoVs transmission in water and cultured/distributed shellfish.

Chronic inflammation plays an important role in obesity-related complications, including insulin resistance, type 2 diabetes, and cardiovascular disease. The imbalances between T helper (Th)1/Th2 cells and Th17/regulatory T (Treg) cells participate in the pathogenesis of inflammation. Previously it was demonstrated that Toll-like receptor (TLR) 4 knockout (KO) prevents high-fat diet (HFD)-induced obesity of young mice (6 months of age), however the effect of TLR4 KO on spontaneous obesity in aged mice (18 month of age) is still unknown. To further study this, TLR4 KO and WT mice were fed with a standard chow diet from weaning to the endpoint of the experiment. We found that TLR4 -/- mice were thinner compared with WT mice at 6 months (M) old. However, TLR4 -/- mice spontaneously developed obesity with increased weight and adiposity in both subcutaneous and visceral fat depots by 18 M old. Our results also indicated that TLR4 KO activated TRIF/IRF3 signalling, induced inflammation, and repolarised alternatively-activated (M2) macrophages to classically-activated (M1) macrophages. In addition, TLR4 KO resulted in an increased spleen index and induced imbalances of Th1/Th2 and Th17/Treg cells which indicated the occurrence of chronic low-grade inflammation. In conclusion, chronic low-grade inflammation induced by TLR4 KO was involved in spontaneous obesity in aged mice. An emerging link was established among the TRIF/IRF3 pathway, chronic low-grade inflammation, and obesity. We hope that these novel findings will provide a potential preventive strategy for obesity and build a spontaneous obesity mouse model., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Epigenetic modifiers are proved to be effective specialized products-mining tools by rationally regulating the gene expression of fungal biosynthetic pathways. Chemical investigation on the histone deacetylase inhibitor (HDI) vorinostat (also known as SAHA)-modified cultures of the basidiomycete Cyathus stercoreus (Schwein.) De Toni (Nidulariaceae) led to the isolation of nine previously undescribed sesquiterpenes, and four previously described ones. The structures of the nine undescribed compounds were determined by extensive NMR spectroscopic analysis, HRESIMS analysis, as well as ECD and NMR calculations. Notably, the isolated sesquiterpenes are exclusive or overproduced from the epigenetic modified cultures compared to the negative control cultures. Additionally, the skeleton types of the isolated sesquiterpenes include protoilludalane, illudalane, 1,11-seco-protoilludalane, 10,11-seco-illudalane, and 14(11→10)abeo-illudalane. It is noteworthy that the 14(11→10)abeo-illudalane skeleton is reported for the first time. Cystercorodiol A, 4-O-acetylcybrodol, cystercorotone, and cybrodol showed weak inhibitory activity against the bacterium Escherichia coli ATCC25922 with the inhibitory rates 34.7%, 33.0%, 32.3%, and 29.6% at the concentration 200 μM, respectively. This study suggested that epigenetic modifiers are also an effective tool for specialized metabolite-mining in basidiomycetes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Breast cancer is the most common cancer among women and a leading cause of death worldwide. Triple negative breast cancer (TNBC) is a highly aggressive subtype which is the most challenging to treat. Due to heterogeneity and a lack of specific molecular targets, small molecule-based chemotherapy is the preferred course of treatment. However, these drugs have high toxicity due to off-target effects on healthy tissues, and tumors may develop resistance. Here, we present a polyethylene glycol-modified nanoscale liposomal formulation (LipoRV) of a new anthraquinone derivative which has potent effects on multiple TNBC cell lines. LipoRV readily inhibited the cell cycle, induced cell apoptosis, and reduced long-term proliferative potential of TNBC cells. In a xenograft animal model, LipoRV successfully cleared tumors and demonstrated a good safety profile, without detrimental effects on biochemical markers. Finally, RNA sequencing of LipoRV-treated TNBC cells was carried out, indicating that LipoRV may have immunomodulatory properties. These findings demonstrate that a liposomal anthraquinone-based molecule has excellent promise for TNBC therapy in the future., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Vaccination is the most effective way to control the COVID-19 pandemic, but vaccination hesitancy threatens this effort worldwide. Consequently, there is a need to understand what influences individuals' intention to get a COVID-19 vaccine. Restriction of information gathering on societal developments to social media may influence attitudes towards COVID-19 vaccination through exposure to disinformation and imbalanced arguments. The present study examined the association between problematic social media use and intention to get the COVID-19 vaccine, taking into account the mediating roles of cyberchondria, fear of COVID-19, and COVID-19 risk perception. In a cross-sectional survey study, a total of 10,843 residents of Qazvin City, Iran completed measures on problematic social media use, fear of COVID-19, cyberchondria, COVID-19 risk perception, and intention to get a COVID-19 vaccine. The data were analyzed using structural equation modeling (SEM). The results showed that there was no direct association between problematic social media use and intention to get a COVID-19 vaccine. Nonetheless, cyberchondria, fear of COVID-19, and COVID-19 risk perception (each or serially) mediated associations between problematic social media use and intention to get a COVID-19 vaccine. These results add to the understanding of the role of problematic social media use in COVID-19 vaccine hesitancy, i.e., it is not the quantity of social media use per se that matters. This knowledge of the mediating roles of cyberchondria, fear of COVID-19, and COVID-19 risk perception can be used by public health experts and policymakers when planning educational interventions and other initiatives in COVID-19 vaccination programs.

Background: Frankincense is a resin secreted by the Boswellia tree. It is used in perfumery, aromatherapy, skincare, and traditional Chinese medicine. However, all Boswellia species are under threat owing to habitat loss and overexploitation. As a result, the market is getting flooded with counterfeit frankincense products., Objective: This study aims to establish a high-throughput method to screen and identify the authenticity of commercial frankincense products. We report, for the first time, a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based method for rapid and high-throughput screening of frankincense samples., Methods: MALDI-TOF MS, HPLC, thin-layer chromatography (TLC), and in vitro antiinflammatory activity assay were used to examine the frankincense samples., Results: Well-resolved peaks of frankincense triterpenoids in the spectra were observed in the crude extract of commercial samples, including α-boswellic acids (αBAs), β-boswellic acids (βBAs), 11-keto-β-boswellic acids (KBAs), acetyl-11-keto-β-boswellic acids (AKBAs), and their esters. These compounds can be used as indicators for determining the authenticity of frankincense., Conclusion: Unlike LC-MS, which is a time-consuming and expensive method, and TLC, which requires a reference sample, our inexpensive, rapid high-throughput identification method based on MALDI-TOF MS is ideal for large-scale screening of frankincense samples sold in the market., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The aim of this study was to evaluate the clinical value of 16 G biopsy needle in transperineal template-guided prostate biopsy (TTPB), compared with 18 G biopsy needle., Methods: The patients who underwent TTPB from August 2020 to February 2021 were randomized into 2 groups using a random number table. The control group (n = 65) and the observation group (n = 58) performed biopsy with 18 G (Bard MC l820) and 16 G (Bard MC l616) biopsy needles, respectively. Positive rate of biopsy, Gleason score, complications, and pain score were statistically analyzed., Results: The age, prostate volume, PSA, and the number of cores were comparable between the 2 groups. The positive rate of biopsy in the observation group was 68.9% (40/58), meanwhile the control group was 46.2% (30/65). There was statistical difference between the 2 groups (p = 0.011). Gleason score of the observation group (8 [7-9]) was higher than that of the control group (8 [6-9]) (p = 0.038). There was no significant difference in pain score and complications including hematuria, hematospermia, perineal hematoma, infection, and urinary retention between the 2 groups (p > 0.05)., Conclusions: 16 G biopsy needle significantly improved the positive rates and accurately evaluate the nature of lesions, meanwhile did not increase the incidence of complications compared with 18 G biopsy needle., (© 2021 S. Karger AG, Basel.)

Objectives: Recently, molecular medicine targeting Folate Receptor Alpha (FOLR1), which mediates intracellular folate uptake and tumor cell proliferation, has been identified in several malignancies. However, the association between FOLR1 expression and rectal cancer remains unclear. Methods: Immunostaining of FOLR1 was performed on biopsy specimens from 172 rectal cancer patients undergoing preoperative chemoradiotherapy (CRT). FOLR1 expression was measured and divided into low (0+-2+) or high (3+-4+) level. Correlations between FOLR1 status and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival, and metastasis-free survival (MeFS) were analyzed, retrospectively. Results: High FOLR1 expression was significantly associated with advanced post-treatment tumor and nodal status (T3-4; N1-2, P  = .001), vascular invasion ( P  = .042), perineural invasion ( P  = .012), and poor regression change after CRT ( P  = .001). In uni- and multi-variable survival analysis, FOLR1 overexpression remained a significant predictor of lower DSS (hazard ratio [HR], 2.328; 95% confidence interval [CI], 1.014-5.344; P  = .046) and MeFS (HR, 2.177; 95% CI, 1.000-1.1286; P  = .050). Conclusion: These results indicate that high FOLR1 status is associated with aggressive tumor behavior, poor response to CRT, and worse survival. Therefore, FOLR1 expression at initial biopsy may be useful in predicting outcomes and also be a target for the exploration of FOLR1-based therapeutic agents.

Objective: Long non-coding RNA (lncRNA ) HOXC-AS3 has been characterized as a cancer-related lncRNA in many types of cancer, while its role in colorectal cancer (CRC) is unknown., Methods: The expression of HOXC-AS3 and TGF-β2 were detected by RT-qPCR. Overexpression assays were performed to explore the interaction between HOXC-AS3 and TGF-β2. A follow-up study was performed to explore the prognostic value of HOXC-AS3 for CRC. The direct interaction between HOXC-AS3 and miR-1269 was assessed with RNA-RNA pulldown assay. Transwell assays were performed to determine the role of HOXC-AS3 and TGF-β2 in regulating CRC cell invasion and migration., Results: HOXC-AS3 was significantly downregulated in CRC tissues, while TGF-β2 was significantly upregulated in CRC tissues compared to that in adjacent non-cancer tissues of CRC patients. The follow-up study showed that low expression levels of HOXC-AS3 in CRC tissues were closely correlated with poor survival. Correlation analysis showed that HOXC-AS3 and TGF-β2 were inversely correlated across CRC tissues but not non-cancer tissues. Overexpression of HOXC-AS3 in the two cell lines resulted in downregulation of TGF-β2, while the expression of HOXC-AS3 was not affected by TGF-β2. Transwell migration and invasion assay showed that overexpression of TGF-β2 increased cell invasion and migration, while overexpression of HOXC-AS3 decreased cell migration and invasion. In addition, overexpression of HOXC-AS3 attenuated the effects of overexpression of TGF-β2. MiR-1269 increased the expression of TGF-β2. HOXC-AS3 directly interacted with miR-1269 in CRC cells., Conclusions: Upregulation of HOXC-AS3 inhibited TGF-β2-induced colorectal cancer (CRC) cell migration and invasion possibly by sponging miR-1269.

Rectal cancer is a heterogeneous malignancy with different clinical responses to preoperative concurrent chemoradiotherapy (CCRT). To discover the significant genes associated with CCRT response, we performed data mining of a transcriptomic dataset (GSE35452), including 46 rectal cancer patients who received preoperative CCRT and underwent standardized curative resection. We identified ARHGEF28 as the most significantly upregulated gene correlated with resistance to CCRT among the genes related to Rho guanyl-nucleotide exchange factor activity (GO:0005085). We enrolled 172 patients with rectal cancer receiving CCRT with radical surgery. The expression of ARHGEF28 encoded protein, Rho guanine nucleotide exchange factor (RGNEF), was assessed using immunohistochemistry. The results showed that upregulated RGNEF immunoexpression was considerably correlated with poor response to CCRT ( p = 0.018), pre-CCRT positive nodal status ( p = 0.004), and vascular invasion ( p < 0.001). Furthermore, high RGNEF expression was significantly associated with worse local recurrence-free survival ( p < 0.0001), metastasis-free survival (MeFS) ( p = 0.0029), and disease-specific survival (DSS) ( p < 0.0001). The multivariate analysis demonstrated that RGNEF immunoexpression status was an independent predictor of DSS ( p < 0.001) and MeFS ( p < 0.001). Using Gene Ontology enrichment analysis, we discovered that ARHGEF28 overexpression might be linked to Wnt/β-catenin signaling in rectal cancer progression. In conclusion, high RGNEF expression was related to unfavorable pathological characteristics and independently predicted worse clinical prognosis in patients with rectal cancer undergoing CCRT, suggesting its role in risk stratification and clinical decision making.

Psidium guajava leaves (PGL) have been long used as an adjuvant therapy for diabetics. The present study evaluated the in vivo hypoglycemic and hepatoprotective effects of dried and the rice-fried PGL decoctions (PGLD and RPGLD). Our results indicated that both PGLD and RPGLD could significantly decrease the contents of fasting blood glucose (FBG) and haemoglobin A1c (HbA1c) in diabetic rats. Compared with the HFD/STZ (high-fat diet with streptozotocin) group, the PGLD and RPGLD-treated diabetic rats showed different degrees of recovery against the liver pathological changes. The upregulated expressions of glucokinase (GK), glucose transporter 2 (GLUT2), insulin growth factor-1 (IGF-1), insulin receptor substrate-1 (IRS-1), and insulin receptor substrate-2 (IRS-2) in PGLD and RPGLD-treated groups were observed. In general, RPGLD exhibited a much better antidiabetic effect than PGLD, which was further verified by the comprehensive evaluation with the TOPSIS method. Besides, HPLC (high-performance liquid chromatography) and UPLC-MS/MS (ultra-performance liquid chromatography-tandem mass spectrometry) analyses revealed that the contents of the primary constituents (ellagic acid, hyperoside, isoquercitroside, reynoutrin, guaijaverin, auicularin, and quercetin) in RPGLD increased obviously compared with PGLD. These results shed new light on the antidiabetic potential and mechanism of PGL, as well as the "higher efficacy" of the rice-fried processing method in traditional Chinese medicine., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Dan Li et al.)

Hybridization is an artificial breeding strategy for generating potentially desirable offspring. Recently, a novel Hulong grouper hybrid (Epinephelus fuscogutatus × Epinephelus lanceolatus) yielded significant growth superiority over its parent. Improved innate immunity is considered as another desirable feature during hybridization. However, whether this Hulong grouper achieved disease resistance has not yet been revealed. In this study, we first examine the infection intensity of C. irritans in the Hulong grouper, and found that the Hulong grouper is less susceptible to C. irritans primary infection. A higher immobilization titer was found in the infected Hulong grouper at Day 2 when compared with the control grouper. Furthermore, severe hyperplasia was observed in the orange-spotted grouper, but not in the Hulong grouper's skin epidermis. To further understand the innate immune mechanism against C. irritans, we conducted a comparative transcriptome analysis of the Hulong grouper during the infection. There are 6464 differentially expressed genes (DEGs) identified in the skin between the control and infected Hulong grouper. This indicates that the innate immune components, such as the complement system, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, Interleukin 17 (IL-17) signaling pathway, and Toll-like receptor (TLR) signaling pathway were up-regulated during the infection. These results show that the C. irritans infection can induce a remarkable inflammatory response in the Hulong grouper. Moreover, a total of 75 pairs of orthologs with the ratio of nonsynonymous (Ka) to synonymous (Ks) substitutions ＞1, considered rapidly evolving genes (REGs), was identified between the Hulong and orange-spotted grouper. More critically, most REGs were enriched in the immune system, suggesting that rapid evolution of the immune system might occur in the Hulong grouper. These results provide a more comprehensive understanding of the innate immunity mechanism of the hybrid Hulong grouper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Data mining of a public transcriptomic rectal cancer dataset (GSE35452) from the Gene Expression Omnibus, National Center for Biotechnology Information identified the melanophilin ( MLPH ) gene as the most significant intracellular protein transport-related gene (GO:0006886) associated with a poor response to preoperative chemoradiation. An MLPH immunostain was performed on biopsy specimens from 172 rectal cancer patients receiving preoperative chemoradiation; samples were divided into high- and low-expression groups by H-scores. Subsequently, the correlations between MLPH expression and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS) were analyzed. MLPH expression was significantly associated with CEA level ( p = 0.001), pre-treatment tumor status ( p = 0.022), post-treatment tumor status ( p < 0.001), post-treatment nodal status ( p < 0.001), vascular invasion ( p = 0.028), and tumor regression grade ( p < 0.001). After uni- and multi-variable analysis of five-year survival, MLPH expression was still associated with lower DSS (hazard ratio (HR), 10.110; 95% confidence interval (CI), 2.178-46.920; p = 0.003) and MeFS (HR, 5.621; 95% CI, 1.762-17.931; p = 0.004). In conclusion, identifying MLPH expression could help to predict the response to chemoradiation and survival, and aid in personal therapeutic modification.

Savin juniper is an excellent species for desertification control in arid and semi-arid areas, where it typically establishes under the protection of nurse plants. Ultimately, established plants emerge into full light as they grow, and this transition is accompanied by an increase in the preponderance of scale-like versus needle-like leaf forms. To test how age and variable light environments affect shade tolerance in savin juniper, we established a pot study under field conditions, with two age cohorts (1- and 4-year-old rooted scions) and three light regimes (10%, 50% and 100% light transmittance). We measured growth, leaf parameters, photosynthesis, chlorophyll fluorescence and foliar pigments on a monthly basis (seven growing months per year, from 2015 to 2017). Overall, there was little interaction among all variables, and both cohort and light regime had significant effects. Leaf form and spacing varied continuously, tending towards shorter, more closely spaced and more appressed scale leaves with higher dry leaf mass per area in older plants or under higher light. There were no clear age-related patterns in carotenoids but both cohort and light had significant effects on gas exchange and chlorophyll fluorescence variables. We conclude that savin juniper shows an intermediate tolerance to shade that changes with growth in that younger plants were less tolerant of full sun than older plants, consistent with its reliance on nurse plants for ultimate establishment in the open., (© 2021 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.)

"San Huang Powder," a nonsterile milled herb powder, is frequently used to treat burn wounds in traditional Chinese herbal medicine. However, treating a wound with a nonsterile dressing or reagent is not compatible with the current guidelines in modern medicine. Therefore, we investigated the bactericidal and anti-inflammatory activities of four herb extracts used in "San Huang Powder" in vitro . Meanwhile, an in vivo porcine model with superficial second-degree burns was used for the experiments since the size and skin composition of pigs are the closest to that of the human body. The minimal bactericidal concentration (MBC) of the herb extracts was determined. The in vitro assay indicated that Rhubarb and Phellodendron bark extracts decreased the levels of inflammatory cytokines, IL-8, and GM-CSF on LPS-induced HMEC-1 cells. In accordance with this result, the histopathological evaluation results showed that the efficacy of "San Huang Powder" containing both herb materials was much better than the group without Rhubarb. Our results not only provide a basis to understand why "San Huang Powder" has been used to clinically treat wounds without sterilization directly since ancient times but also show the advantages of using multiple herb materials simultaneously on wound sites to prevent infection during treatment. Rhubarb is the recommended ingredient involved in the preparation of "San Huang Powder" to ensure the healing efficacy of burn wounds., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Jia-Ru Wu et al.)

Background: Respiratory viruses (RVs) are among the most common pathogens for both upper and lower respiratory tract infections (RTIs). However, the viral epidemiology of RV-associated RTIs in adults has long been under-recognized. Through a sensitive molecular assay, it would be possible to have a better understanding of the epidemiology of RV-associated RTIs., Material and Methods: Respiratory tract (RT) specimens from adults hospitalized due to RTIs were tested for RVs, using the multiplex PCR-based Luminex xTAG® Respiratory Viral Panel assay. A total of nineteen RVs, including influenza viruses and non-influenza respiratory viruses (NIRVs) were detected. Positive rates were compared using a chi-square test., Results: A total of 2292 samples from adult patients hospitalized with RTIs were screened for RVs. The overall positive rate was 22%, with 17.8% samples positive for at least one NIRV. NIRVs had a higher positive rate in non-winter seasons. As many as 12.7% (46/363) of the samples collected through broncho-alveolar lavage and 20.5% (176/859) of the samples collected in ICUs were positive for RVs. Distribution of corona virus (CoV), human metapneumovirus (hMPV) and parainfluenza virus (PIV) demonstrated seasonal variation. Also, temperature was associated with the positive rates of specific viruses, including CoV, respiratory syncytial virus (RSV), hMPV and PIV., Conclusion: Respiratory viruses, notably NIRVs, were frequently detected in adults hospitalized with RTIs. Several RVs were detected with distinctive seasonal variations. A substantial number of RVs were identified in lower RT specimens or from patients admitted to ICU, highlighting their important role in causing severe respiratory infection., (Copyright © 2020. Published by Elsevier B.V.)

Background: Coronavirus disease 2019 (COVID-19) manifests symptoms as common etiologies of respiratory tract infections (RTIs). During the pandemic of COVID-19, identifying the etiologies correctly from patients with RTI symptoms was crucial in not only disease control but preventing healthcare system from collapsing. By applying sensitive PCR-based molecular assays, we detected the etiologic agents and delineated the epidemiologic picture of RTIs in the early phase of COVID-19 pandemic., Methods: From December 2019 to February 2020, we screened patients presented with RTIs using multiplex PCR-based diagnostic assays. Data from pediatric and adult patients were compared with different months and units in the hospital., Results: Of all 1631 patients including 1445 adult and 186 pediatric patients screened, 8 viruses and 4 bacteria were identified. Positive rates were 25% in December, 37% in January, and 20% in February, with pediatric patients having higher positive rates than adults (Ps < 0.001). In pediatric patients, RhV/EnV was the most commonly detected, followed by parainfluenza viruses. Most Mycoplasma pneumoniae infection occurred in pediatric patients. RhV/EnV was the most commonly detected agent in pediatric patients admitted to intensive care units (ICUs), while influenza accounted for the majority of adult cases with critical illness. Noticeably, seasonal coronavirus ranked second in both adult and pediatric patients with ICU admission., Conclusion: While we focused on the pandemic of COVID-19, common etiologies still accounted for the majority of RTIs and lead to severe diseases, including other seasonal coronaviruses., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Background: Endometrial cancer is generally one of the most evident malignant tumours of the female reproductive system, and the mechanisms underlying its cell proliferation and apoptosis are key to research in gynaecological oncology. In the paper, the in-depth molecular mechanism by which DJ-1 protein regulates the proliferation and apoptosis of Ishikawa cells was investigated., Methods and Results: DJ-1 knockdown and overexpressing Ishikawa stable cell lines were established by lentiviral transduction. The levels of DJ-1 and noncanonical NF-κB signaling key proteins were evaluated by Western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were applied to analyze the cell viability and apoptosis. Co-immunoprecipitation experiment was utilized to assess the DJ-1-Cezanne interaction. The results showed that DJ-1 overexpression conferred apoptosis resistance and high proliferation on Ishikawa cells, while DJ-1 knockdown in Ishikawa cells produced the opposite results. These findings again suggested that DJ-1 inhibits the apoptosis and promotes the proliferation of Ishikawa cells. More crucially, further data showed that the noncanonical NF-κB activation was required for the regulation of Ishikawa cell proliferation and apoptosis by DJ-1. Meanwhile, it was found that noncanonical NF-κB pathway may be activated by DJ-1 interacting with and negatively regulating Cezanne in Ishikawa cells., Conclusions: Overall, this work revealed that DJ-1 associates with and negatively regulates Cezanne and consequently triggers the noncanonical NF-κB activation, thereby regulating Ishikawa cell proliferation and apoptosis., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Dracorhodin can be isolated from the exudates of the fruit of Daemonorops draco . Previous studies suggested that dracorhodin perchlorate can promote fibroblast proliferation and enhance angiogenesis during wound healing. In the present study, the potential bioactivity of dracorhodin perchlorate in human HaCaT keratinocytes, were investigated in vitro , with specific focus on HaCaT wound healing. The results of in vitro scratch assay demonstrated the progressive closure of the wound after treatment with dracorhodin perchlorate in a time-dependent manner. An MTT assay and propidium iodide exclusion detected using flow cytometry were used to detect cell viability of HaCaT cells. Potential signaling pathways underlying the effects mediated by dracorhodin perchlorate in HaCaT cells were clarified by western blot analysis and kinase activity assays. Dracorhodin perchlorate significantly increased the protein expression levels of β-catenin and activation of AKT, ERK and p38 in HaCaT cells. In addition, dracorhodin perchlorate did not induce HaCaT cell proliferation but promoted cell migration. Other mechanisms may yet be involved in the dracorhodin perchlorate-induced wound healing process of human keratinocytes. In summary, dracorhodin perchlorate may serve to be a potential molecularly-targeted phytochemical that can improve skin wound healing., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Lu et al.)

Background: Physical distancing and facemask use are worldwide recognized as effective non-pharmaceutical interventions (NPIs) against the coronavirus disease-2019 (COVID-19). Since January 2020, Taiwan has introduced both NPIs but their effectiveness on non-COVID-19 respiratory viruses (NCRVs) remain underexplored., Methods: This retrospective observational study examined electronic records at a tertiary hospital in northern Taiwan from pre-COVID (January-December 2019) to post-COVID period (January-May 2020). Patients with respiratory syndromes were tested for both enveloped (eg, influenza virus and seasonal coronavirus) and non-enveloped RVs (eg, enterovirus and rhinovirus) using multiplex reverse transcription polymerase chain reaction assays. Monthly positivity rates of NCRVs among adult and pediatric patients were analyzed with comparison between pre- and post-COVID periods., Results: A total of 9693 patients underwent 12 127 multiplex RT-PCR tests. The average positivity rate of NCRVs reduced by 11.2% (25.6% to 14.4%) after nationwide PHIs. Despite the COVID-19 pandemic, the most commonly identified enveloped and non-enveloped viruses were influenza virus and enterovirus/rhinovirus, respectively. Observed reduction in NCRV incidence was predominantly contributed by enveloped NCRVs including influenza viruses. We did not observe epidemiological impacts of NPIs on non-enveloped viruses but an increasing trend in enterovirus/rhinovirus test positivity rate among pediatric patients. Our data were validated using Taiwan's national notification database., Conclusions: Our frontline investigation suggests that the current NPIs in Taiwan might not effectively control the transmission of non-enveloped respiratory viruses, despite their protective effects against influenza and seasonal coronavirus. Health authorities may consider using hydrogen peroxide or chloride-based disinfectants as additional preventative strategies against non-enveloped respiratory viruses in the post-COVID-19 era., (© 2021 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

The natural-product-based low-molecular-weight supramolecular hydrogels (LMWSHs) induced by heating are rarely reported. In this work, a simple salt of oleanolic acid (OA) and choline ([choline][OA]) was used as the natural product hydrogelator (NPHG) to form LMWSHs. Unlike common sol-gel transitions, the OA-based LMWSH displayed a unique property with which the system could undergo a phase transition from the sol state to the gel state upon heating. Moreover, the phase separation was observed in sol and gel states when the temperature was elevated with nonreversible transparent-turbid transitions. LMWSHs showed good stability and injectability and the potential to be a drug delivery vehicle for sustained release of drugs. In this regard, this work provided a facile approach to designing an OA-based NPHG for preparing heat-induced LMWSHs.

Life cycle assessment (LCA) is a widely applied approach used to evaluate the environmental impacts of a product or service across its life cycle stages; however, the impacts of land use on ecosystem services are less addressed in most LCA studies. This study, therefore, aims to improve the LCA model by incorporating a new impact category of land use on ecosystem services at both midpoint and endpoint levels in the existing ReCiPe2016 impact assessment method. The impacts of land use in the LCA model included land occupation and land transformation. The soil quality-based indicator, soil organic carbon (SOC), was adopted to quantify the soil quality change in ecosystem services caused by land use. A site with contaminated soils was adopted to validate the proposed impact assessment approach and to compare the results of various remediation practices. Our results revealed that the characterization factors (CFs) varied with the type of land use intervention, with land occupation of settlements presenting the highest CFs and land occupation of forest presenting the most negative CFs and thus benefitting ecosystem services. These results were well reflected in the case study, while the type of land intervention was the key factor determining the impact level. The results suggested that long-term occupation, high contamination levels, and high material or energy use contributed to relatively higher impacts of land use on ecosystem services. The proposed approach enables the quantification of land use impacts on ecosystem services as expressed in monetary loss or benefit at the endpoint resource level. The impact assessment results indicated that the in situ bioremediation scenario contributed relatively higher impacts ($12,667 USD) than the excavation and thermal treatment scenario ($-37 USD). These monetary assessment results are informative and are expected to be used in the decision-making process towards achieving beneficial environmental outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To investigate the immunogenicity and safety of a boost dose of measles, mumps, and rubella combined vaccine (MMR) for children 4 to 6 years old. Methods: Children, aged 4 to 6 years old, had vaccinated with 1 dose of measles and rubella combined vaccine(MR) at the age of 8 months and 1 dose of MMR vaccine at 18-months, were recruited in Shanxi, Inner Mongolia, and Beijing, respectively. All children were assigned into 4, 5 and 6-year-old group. The children who met inclusion and exclusion criteria were vaccinated with 1 dose MMR vaccine, and were collected blood samples before vaccination and 35 to 42 d after the vaccination. During the study period, adverse events were collected at 30 min, 1 d, 2 d, 3 d, 4-12 d, and 13 to 42 days after vaccination. Serum was tested for IgG antibodies against measles, mumps and rubella. Geometric mean concentrations (GMC) of measles, mumps, and rubella antibodies were compared among groups by analysis of variance or non-parametric test. Seropositive rates and adverse event rates were compared among groups by Chi-square test or Fisher exact test. Results: A total of 500 children were included in immunogenicity analysis and 535 children were included in safety analysis. The overall adverse event rate was 20.37%, the most of severity for adverse events was mild. The rates of local and systemic adverse events were 0.37% and 20.00%, respectively. Symptoms of local adverse events were redness. The main systemic adverse events were fever, followed by cough, rash and runny nose. Received a dose of MMR vaccine for booster immunization, the seropositive rates of measles antibody, mumps antibody and rubella antibody were above 99% for all 3 age groups, and there was no significant difference between groups. There were significant differences in mumps antibody GMC among groups ( P =0.042), but no significant differences in measles and rubella antibodies GMC. Conclusion: The immunogenicity and safety of a boosted MMR vaccintion in children aged 4, 5 and 6 years were all similar good.

Ochracines F-L (1-7), seven previously undescribed chamigrane and cadinane sesquiterpenoids, together with four known chamigranes were isolated from cultures of the wood-decaying fungus Steccherinum ochraceum HFG119. Ochracines F-L were structurally characterized by extensive analysis of HRMS and NMR spectroscopic data. The relative configurations were assigned through a combination of NOE correlations and J -based configuration analysis (JBCA), while the absolute configurations were determined by X-ray single-crystal diffraction, and calculated methods (ECD, [α], 13 C NMR). All the new isolates were evaluated for their cytotoxicity against five human cancer cell lines HL-60, SMMC-7721, A549, MCF-7, and SW-480, and inhibitory activity on NO production in RAW 264.7 macrophages., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The characters that define the subgenus Parabates of the genus Netelia are investigated. The shape of the basal apodeme of the aedeagus is considered to be a synapomorphy of this subgenus, suggesting the monophyly of Parabates. A new species, Netelia (Parabates) fusciapicalis n. sp. belonging to the ishiharai group is described from Taiwan, Vietnam and Laos. This is the sixth extant species of the subgenus, the first record of the genus Netelia from Vietnam and Laos, and the first record of the subgenus Parabates from Taiwan.

An antibody conjugated boronic acid modified silver chip (ABAS ship) is fabricated as a simple, rapid, accurate, sensitive and cost-effective sample preparation method for abused drug quantification in human urine. Ketamine, one common abused drug, was applied as proof of concept for ABAS chip with high resolution matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF MS) analysis. The overall testing process required 10 min at part per billion (ppb) sensitivity level, where current drug testing method necessitated several hours with similar sensitivity. The ABAS chip manufacture process started with slide glass by way of silver mirror reaction to form silver conductive glass for further chemical conjugation. Boronic acid functional group was decorated on silver conductive glass through the formation of silver-thiol (Ag-S) bond. Anti-ketamine antibody was covalently conjugated to boronic acid modified silver conductive glass through the formation of cyclic boronate ester between the boronic acid and the cis-diol groups on the glycans of antibody, which maintain the correct orientation to maximally capture its antigen. The resulting ABAS chip were designed to specifically capture ketamine in human urine samples, that could be directly analyzed by addition of MALDI α-Cyano-4-hydroxycinnamic acid (CHCA) matrix solution. The linear dynamic range of concentration in this method was 10-500 ng/mL with coefficient of determination 0.996. The limit of detection (LOD) and limit of quantification (LOQ) were 2.0 and 7.0 ng/mL, respectively. Importantly, the proposed method allows rapid and accurate quantification of ketamine from suspects' urine samples in 10 min and small sample volume of 1 μL was required. The resulting data were consistent with traditional gas chromatography-mass spectrometry (GC-MS) analysis. Our homemade ABAS chip could thus provide a powerful tool not only for forensic science but also for most clinical diagnosis of disease as many expression antibodies for the occurrence of diverse diseases could be simply produced and purchased., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in the manufacture of polyvinylchloride plastics and has been associated with concerns regarding male reproductive toxicity. In this study, we hypothesized that maternal exposure to DEHP induces transgenerational inheritance of adult-onset adverse reproductive outcomes through the male germline in the F1, F2, and F3 generations of male offspring. Pregnant rats were treated with 5 or 500 mg of DEHP/kg/day through gavage from gestation day 0 to birth. The offspring body weight, anogenital distance (AGD), anogenital index (AGI), sperm count, motility, and DNA fragmentation index (DFI) were measured for all generations. Methyl-CpG binding domain sequencing was performed to analyze sperm DNA methylation status in the F3. DEHP exposure at 500 mg/kg affected AGD, AGI, sperm count, mean DFI, and %DFI in the F1; AGD, sperm count, and mean DFI in the F2; and AGD, AGI, mean DFI, and %DFI in the F3. DEHP exposure at 5 mg/kg affected AGD, AGI, sperm count, and %DFI in the F1; sperm count in the F2; and AGD and AGI in F3. Compared with the control group, 15 and 45 differentially hypermethylated genes were identified in the groups administered 5 mg/kg and 500 mg/kg DEHP, respectively. Moreover, 130 and 6 differentially hypomethylated genes were observed in the groups administered 5 mg/kg and 500 mg/kg DEHP. Overall, these results demonstrated that prenatal exposure to DEHP caused transgenerational epigenetic effects, which may explain the observed phenotypic changes in the male reproductive system.

Background: Numerous studies have attempted to apply artificial intelligence (AI) in the dermatological field, mainly on the classification and segmentation of various dermatoses. However, researches under real clinical settings are scarce. Objectives: This study was aimed to construct a novel framework based on deep learning trained by a dataset that represented the real clinical environment in a tertiary class hospital in China, for better adaptation of the AI application in clinical practice among Asian patients. Methods: Our dataset was composed of 13,603 dermatologist-labeled dermoscopic images, containing 14 categories of diseases, namely lichen planus (LP), rosacea (Rosa), viral warts (VW), acne vulgaris (AV), keloid and hypertrophic scar (KAHS), eczema and dermatitis (EAD), dermatofibroma (DF), seborrheic dermatitis (SD), seborrheic keratosis (SK), melanocytic nevus (MN), hemangioma (Hem), psoriasis (Pso), port wine stain (PWS), and basal cell carcinoma (BCC). In this study, we applied Google's EfficientNet-b4 with pre-trained weights on ImageNet as the backbone of our CNN architecture. The final fully-connected classification layer was replaced with 14 output neurons. We added seven auxiliary classifiers to each of the intermediate layer groups. The modified model was retrained with our dataset and implemented using Pytorch. We constructed saliency maps to visualize our network's attention area of input images for its prediction. To explore the visual characteristics of different clinical classes, we also examined the internal image features learned by the proposed framework using t-SNE (t-distributed Stochastic Neighbor Embedding). Results: Test results showed that the proposed framework achieved a high level of classification performance with an overall accuracy of 0.948, a sensitivity of 0.934 and a specificity of 0.950. We also compared the performance of our algorithm with three most widely used CNN models which showed our model outperformed existing models with the highest area under curve (AUC) of 0.985. We further compared this model with 280 board-certificated dermatologists, and results showed a comparable performance level in an 8-class diagnostic task. Conclusions: The proposed framework retrained by the dataset that represented the real clinical environment in our department could accurately classify most common dermatoses that we encountered during outpatient practice including infectious and inflammatory dermatoses, benign and malignant cutaneous tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Wang, Chen, Gao, Shu, Wang, Yan, Yang, Xie and Liu.)

Objectives: Patients with hematologic diseases were at high risk for cytomegalovirus (CMV) diseases. In the present study, we compare various prognostic factors during CMV viremia, with specific emphasis on the relationship between viremia eradication and the long-term prognosis of patients after each episode., Methods: Adult patients with hematologic diseases who had a detectable CMV viral load (VL) (equal to or above 150 copies/mL) were included in the study. Medical records were reviewed for demographic data including age, sex, hematologic and other underlying diseases, status of stem cell transplantation, antiviral medication, serum CMV viral load before and after antiviral treatment., Results: A total of 101 episodes of CMV viremia occurred in patients with hematologic diseases. Comparison of various prognostic factors revealed non-survivors more frequently suffered from pneumonia and concomitant bacterial or fungal infections, had less frequently undergone hematopoietic stem cell transplantation (HSCT), and had higher peak VLs during viremic episodes. After antiviral therapy, eradication of viremia was much less frequently achieved in non-survivors. The Kaplan-Meier curves revealed that patients with detectable end-treatment VL had lower survival rates even if the antivirals were administered for more than 21 days. In a multivariate Cox proportional-hazard model, a detectable VL at the end of antiviral therapy independently predicted mortality within 180 days., Conclusions: In patients with hematologic diseases suffering CMV viremia, failure to eradicate viremia after antiviral therapy indicates a higher chance of mortality and can be regarded as a useful indicator in evaluating the patient's long-term prognosis., (Copyright © 2019. Published by Elsevier B.V.)

Cigarette smoke (CS)-induced macrophage activation and airway epithelial injury are both critical for the development of chronic obstructive pulmonary disease (COPD), while the eventual functions of autophagy in these processes remain controversial. We have recently developed a novel COPD mouse model which is based on the autoimmune response sensitized by CS and facilitated by elastin. In the current study, we therefore utilized this model to investigate the roles of autophagy in different stages of the development of bronchitis-like airway inflammation. Autophagic markers were increased in airway epithelium and lung tissues, and Becn +/- or Lc3b -/ - mice exhibited reduced neutrophilic airway inflammation and mucus hyperproduction in this COPD mouse model. Moreover, treatment of an autophagic inhibitor 3-methyladenine (3-MA) either during CS-initiated sensitization or during elastin provocation significantly inhibited the bronchitis-like phenotypes in mice. Short CS exposure rapidly induced expression of matrix metallopeptidase 12 (MMP12) in alveolar macrophages, and treatment of doxycycline, a pan metalloproteinase inhibitor, during CS exposure effectively attenuated the ensuing elastin-induced airway inflammation in mice. CS extract triggered MMP12 expression in cultured macrophages, which was attenuated by autophagy impairment ( Becn +/- or Lc3b -/ - ) or inhibition (3-MA or Spautin-1). These data, taken together, demonstrate that autophagy mediates both the CS-initiated MMP12 activation in macrophages and subsequent airway epithelial injury, eventually contributing to development COPD-like airway inflammation. This study reemphasizes that inhibition of autophagy as a novel therapeutic strategy for CS-induced COPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Li, Li, Jing, Liu, Xu, Chen, Dong, Zhang, Ying, Li, Shen, Li and Chen.)

Prenyltransferase (PTase) enzymes play crucial roles in natural product biosynthesis by transferring isoprene unit(s) to target substrates, thereby generating prenylated compounds. The prenylation step leads to a diverse group of natural products with improved membrane affinity and enhanced bioactivity, as compared to the non-prenylated forms. The last two decades have witnessed increasing studies on the identification, characterization, enzyme engineering, and synthetic biology of microbial PTase family enzymes. We herein summarize several examples of microbial soluble aromatic PTases for chemoenzymatic syntheses of unnatural novel prenylated compounds., Competing Interests: We declare we have no conflict of interest., (© 2021 The Authors.)

Rationale: Patients with chronic obstructive pulmonary disease (COPD) and anxiety or depression experience more symptoms and exacerbations than patients without these comorbidities. Failure to provide beneficial COPD therapies to appropriate patients (underuse) and provision of potentially harmful therapies to patients without an appropriate indication (overuse) could contribute to respiratory symptoms and exacerbations. Anxiety and depression are known to affect the provision of health services for other comorbid conditions; therefore, underuse or overuse of therapies may explain the increased risk of severe symptoms among these patients. Objectives: To determine whether diagnosed anxiety and depression, as well as significant anxiety and depression symptoms, are associated with underuse and overuse of appropriate COPD therapies. Methods: We analyzed data from a multicenter prospective cohort study of 2,376 participants (smokers and control subjects) enrolled between 2010 and 2015. We identified two subgroups of participants, one at risk for inhaled corticosteroid (ICS) overuse and one at risk for long-acting bronchodilator (LABD) underuse based on the 2011 Global Initiative for Chronic Obstructive Lung Disease statement. Our primary outcomes were self-reported overuse and underuse. Our primary exposures of interest were self-reported anxiety and depression and significant anxiety and depression symptoms. We adopted a propensity-score method with inverse probability of treatment weighting adjusting for differences in prevalence of confounders and performed inverse probability of treatment weighting logistic regression to evaluate all associations between the exposures and outcomes. Results: Among the 1,783 study participants with COPD confirmed by spirometry, 667 (37.4%) did not have an indication for ICS use, whereas 985 (55.2%) had an indication for LABD use. Twenty-five percent ( n  = 167) of patients reported ICS use, and 72% ( n  = 709) denied LABD use in each subgroup, respectively. Neither self-reported anxiety and depression nor significant anxiety and depression symptoms were associated with overuse or underuse. At least 50% of patients in both subgroups with significant symptoms of anxiety or depression did not report a preexisting mental health diagnosis. Conclusions: Underuse of LABDs and overuse of ICSs are common but are not associated with comorbid anxiety or depression diagnosis or symptoms. Approximately one-third of individuals with COPD experience anxiety or depression, and most are undiagnosed. There are significant opportunities to improve disease-specific and patient-centered treatment for individuals with COPD.

Rice grains produced on cadmium (Cd) contaminated paddy soils often exceed the maximum permissible limit. A number of mitigation methods have been proposed to decrease Cd accumulation in rice grain in contaminated acidic soils, including altering water management regimes, liming, and genetic engineering. In the present study, we conducted a pot experiment to compare these methods for their effectiveness at decreasing grain Cd concentrations in both acidic (pH 5.1-5.2) and alkaline (pH 7.5-7.9) paddy soils that varied in the degree of Cd contamination. In moderately Cd-contaminated acidic soils (with Cd concentrations lower than the intervention value of Chinese soil standard, GB15618-2018), any of the three methods was effective, reducing grain Cd concentration by 80-90% to levels below the Chinese maximum permissible limit (0.2 mg/kg). However, in the highly Cd-contaminated soils (with soil Cd concentrations exceeding the intervention value) with elevated concentrations of extractable Cd, although both liming and alternation of the water management regime (continuous flooding) was effective at decreasing grain Cd accumulation, grain Cd concentrations still exceeded the Chinese limit. Genetic engineering of rice, such as knockout of OsNramp5 (encoding the plasma membrane transporter responsible for Cd uptake into root cells) or overexpression of OsHMA3 (encoding a tonoplast Cd transporter sequestering Cd into the vacuoles), produced dramatic decreases (≥90%) in grain Cd concentration. Even in seriously contaminated soils, overexpression of OsHMA3 alone produced grain with Cd concentrations below the Chinese limit, offering a highly effective approach to produce Cd-safe rice especially in seriously Cd-contaminated paddy soils without affecting grain biomass or the concentrations of essential micronutrients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)