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Sheng-Yu Li,1 Lei Liu,1 Ding-Kun Wang,1 Xiao-Song Ding,1 Wei-Ping Li,1,2 Hong-Wei Li1,2 1Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease, Beijing, People’s Republic of ChinaCorrespondence: Wei-Ping Li; Hong-Wei Li, Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +86-13810267817 ; +86-13801396679, Email xueer09@163.com; lhw19656@sina.comPurpose: So far, ST-segment elevation myocardial infarction (STEMI) is still the main cause of morbidity and mortality of cardiovascular diseases worldwide. Recent studies showed that pentraxin-3 (PTX3) was related to the early diagnosis and prognosis of coronary heart disease. This study aimed to investigate the dynamical change of PTX3 after primary percutaneous coronary intervention (pPCI) in STEMI patients and its prognostic value.Patients and methods: In this prospective cohort study, a total of 350 patients were enrolled. The plasma level of PTX3 was measured at admission, 24-hour and 5-day after pPCI. The primary endpoint was the incidence of major adverse cardiac cerebral events (MACCEs) during 1-year follow-up.Results: Compared with the admission, PTX3 levels were significantly increased at 24 hours, and decreased at 5 days after pPCI in the whole cohort. PTX3 levels at these three time points were not significantly different between the patients with and without MACCEs. Notably, the change in PTX3 from admission to post-pPCI 24-hour (ΔPTX3) was higher in patients with MACCEs (112.83 vs 17.94 ng/dl, P = 0.001). The ROC curves showed that the cut-off value was 29.22 ng/dl and the area under curves was 0.622 (95% CI: 0.554– 0.690, p = 0.001). Multivariable cox regression models revealed that the high ΔPTX3 group was an independent predictor of MACCEs (adjusted HR = 2.010, 95% CI = 1.280– 3.186, p = 0.003). The higher ΔPTX3 group had significantly higher incidences of revascularization (HR = 2.094, 95% CI: 1.056– 4.150, p = 0.034) and composite MACCEs (HR = 2.219, 95% CI: 1.425– 3.454, p < 0.001). However, the change of PTX3 level from admission to post-pPCI 5-day had no independently predictive value.Conclusion: The higher increase of PTX3 level 24-hour after pPCI appeared to have a potential value in independently predicting the incidence of 1-year MACCEs in STEMI patients, especially for coronary revascularization.Keywords: pentraxin-3, primary percutaneous coronary intervention, ST-segment elevation myocardial infarction, prognosis

Background: Bacillus Calmette-Guérin (BCG) is capable of enhancing the infiltration of immune cells into the tumour. However the temporal dynamics of immune cell patterns in patients receiving BCG instillation remains unclear., Methods: Ninety-six patients who underwent intravesical BCG therapy, comprising 46 responders and 50 non-responders, were retrospectively enroled to explore the evolving immune landscape. This study involved a detailed examination of sequential samples collected before, during, and after BCG treatment to assess BCG's influence on the immune microenvironment, employing techniques such as immunohistochemistry, fluorescent multiplex immunohistochemistry, and mass spectrometry techniques., Results: Our study found that initial BCG instillation leads to enhanced immune cell infiltration, correlating with treatment efficacy, with responders exhibiting more pronounced increases. Non-responders experience a rise in immune cell infiltration and PD-L1 expression during the first instillation, which returns to baseline after treatment. In non-responders, BCG re-challenge fail to further increase immune cell infiltration into the tumour or improve patient outcomes. Strikingly, proteomics data revealed that GBP1 expression was induced by BCG treatment in non-responders., Conclusions: Our findings demonstrated the induction of tumour PD-L1 expression by BCG in non-responders, and therefore provide insights for the combination of BCG and anti-PD1/anti-PD-L1 therapy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Low-dimension metal halide perovskites are attractive for bandgap tunable optoelectronic materials. Among them, 1-D CsPbBr 3 quantum wires (QWs) are emerging as promising deep-blue luminescent material. However, the growth dynamics of 1-D perovskite QWs are intricate, making the study and control of 1-D QWs highly challenging. In this study, a strategy for controlling both the length and width of the CsPbBr 3 QWs was realized. The temperature-dependent isotropic growth mechanism was revealed and employed as the main tool for the oriented growth of 1-D CsPbBr 3 QWs for various aspect ratios. Our results pave the way for the controlled synthesis of ultrasmall perovskite nanocrystals.

Objectives: Gender equity studies have shown that women are underrepresented in journal editor in chief positions, which confer major professional opportunities and influence. We sought to systematically investigate editor in chief gender and journal attributes within pathology., Methods: We constructed a journal data set using the Scimago Journal & Country Rank and Clarivate Journal Citation Reports databases. We also included official journals of the major medical societies for the 12 pathology subspecialties recognized by the Association of American Medical Colleges. The final data set included 126 journals. We obtained editor in chief gender, impact factor, publication model (ie, hybrid access vs open access), year of founding, and geographic location for all included pathology journals., Results: Women made up only 18% of the 141 total editor in chief positions. This inequity was present irrespective of all pathology journal variables studied. Among 10 journals with 2 editor in chief positions, 5 had only men and 5 had 1 man and 1 woman. All 3 journals with 3 editor in chief positions had 2 men and 1 woman., Conclusions: Women are significantly underrepresented among editor in chiefs across pathology journals. Journals and affiliated members should advocate for diversity among these influential positions, given their impact on research, science, and medicine., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This study aims to investigate the effect of Xixin Decoction on the T helper 17 cell(Th17)/regulatory T cell(Treg) ba-lance of intestinal mucosa and the expression of related transcription factors in the senescence-accelerated mouse-prone 8(SAMP8) model. Fifty 14-week male mice of SAMP8 were randomized by the random number table method into model group, probiotics group, and high-, medium-, and low-dose Xixin Decoction groups, with 10 mice in each group. Ten 14-week male mice of senescence-acce-lerated mouse-resistant 1(SAMR1) served as control group. After 10 weeks of feeding, the mice were administrated with correspon-ding drugs for 10 weeks. Morris water maze test was carried out to examine the learning and memory abilities of mice. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of secretory immunoglobulin A(SIgA) in the intestinal mucosa, and flow cytometry to detect the percentage content of Th17 and Treg in the intestinal mucosa. Western blot was performed to determine the protein levels of retinoid-related orphan receptor gamma t(RORγt) and forkhead box p3(Foxp3) in the mouse colon tissue. Compared with control group, the escape latency of mice in model group was significantly prolonged(P&lt;0.01), and the number of times of crossing the platform and the residence time in the target quadrant were significantly reduced within 60 s(P&lt;0.01), intestinal mucosal SIgA content was significantly decreased(P&lt;0.01), Th17 content was increased(P&lt;0.05), Treg content was decreased(P&lt;0.01), the expression of RORγt protein was increased and Foxp3 protein was decreased in colon(P&lt;0.01). Compared with the model group, high-dose Xixin Decoction group improved the learning and memory ability(P&lt;0.05 or P&lt;0.01). Probiotics group and high-and medium-dose Xixin Decoction group increased the content of SIgA in intestinal mucosa(P&lt;0.05 or P&lt;0.01), decreased percentage content of Th17 and increased the percentage content of Treg in intestinal mucosa(P&lt;0.05 or P&lt;0.01). Furthermore, they down-regulated the protein level of RORγt and up-regulated the protein level of Foxp3 in the intestinal mucosa(P&lt;0.01). In conclusion, Xixin Decoction may act on intestinal mucosal immune barrier, affect gut-brain information exchange, and improve the learning and memory ability of SAMP8 by promoting SIgA secretion and regulating the Th17/Treg balance and the expression of RORγt and Foxp3.

Background: Observational studies have suggested that depression is associated with sarcopenia. However, the causal relationship between depression and sarcopenia remains unclear., Aim: To investigate the causal relationship between depression and sarcopenia., Methods: We performed a Mendelian randomization (MR) analysis to identify the bidirectional relationship between depression and sarcopenia-related traits. Summary-level data and independent variants used as instrumental variables came from large genome-wide association studies of depression (414055 cases and 892299 controls), of appendicular lean mass (ALM, 450243 participants), and of hand grip strength (exposure: 360000 participants; outcome: 334925 participants)., Results: We identified a negative association of depression with lower ALM [odds ratio (OR): 0.932, 95% confidence interval (95%CI): 0.889-0.979, P = 0.005]. In the reverse MR analysis, we also observed an inverse association of hand grip strength with depression (OR: 0.200, 95%CI: 0.108-0.370, P < 0.001). Similar results were obtained in sensitivity analyses., Conclusion: Depression was causally related to decreased muscle mass, and declined muscle strength might lead to a higher risk of depression., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose. They confirm that they have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Owing to the advantages of organic field-effect transistors (OFETs) in the versatility of organic synthesis, multiparameter measurement, and signal amplification, sensors based on OFETs have received increasing attention for detecting volatile organic compounds (VOCs). However, false device operation and gas-sensing measurements often occur to vitiate the advantages of OFETs and even output error gas-sensing signals. In this work, by experimentally and theoretically studying the effects of VOC adsorption on the operational characteristics of the OFET, the proper operations of OFETs in gas-sensing measurements were clarified. The multiparameter measurements of OFETs showed that the source-drain current was the optimized parameter for achieving high responsivity, and other OFET parameters could be used for fingerprint analysis. By operating OFETs in the near-threshold region, the amplification effect was switched to enhance the responsivity by orders of magnitude to VOCs, while in the overthreshold region, the OFETs had a low signal-to-noise ratio. Besides, a counteraction effect and an uncertainty effect were discovered, leading to error gas-sensing signals. A theoretical study was carried out to reveal the dependency of the gas-sensing properties of OFETs on VOC adsorption. A series of rules were proposed for guiding the measurements of OFET sensors by taking full advantage of transistors in gas-sensing applications.

Objectives: In this study we aimed to evaluate the nocebo response rate in patients with functional dyspepsia (FD) and to explore its influencing factors., Methods: A literature search of the EMBASE, PubMed, and Cochrane Library databases was conducted for all articles published up to March 2021. Randomized, parallel-designed, placebo-controlled trials on pharmacological interventions for patients with FD were included. A meta-analysis that utilized random effects to analyze the incidence of adverse events (AEs) among participants who were given placebo was conducted, and the correlation between trial characteristics and the magnitude of the nocebo response rate was analyzed., Results: Altogether, 27 studies including 1866 paitents were deemed eligible and included in the analysis. The total nocebo response rate was 26% (95% confidence interval [CI] 18%-33%). The most frequently reported AEs included nasopharyngitis (9%), constipation (6%), headache (5%), and diarrhea (3%). There were significant differences in nocebo response rates among studies conducted in different country or region, treatment duration, types of medication, sponsorship and different versions of the Rome criteria used for FD diagnosis. While number of centers engaged in the study, types of FD diagnosis and dosing frequency were not significantly associated with the nocebo response rate., Conclusions: Patients with FD exhibit notable nocebo response strength in clinical trials. The researchers should adopt a more careful approach when analyzing the relationships between AEs and interventions in such trials., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

The catalytic asymmetric cyclopropanation reaction of alkenes with diazo compounds is a direct and powerful method to construct chiral cyclopropanes that are essential to drug discovery. However, diazo compounds are potentially explosive and often require hazardous reagents for their preparation. Here, we report on the use of 1,2-dicarbonyl compounds as safe and readily available surrogates for diazo compounds in the direct catalytic asymmetric deoxygenative cyclopropanation reaction. Enabled by a class of simple and readily accessible chiral salen-Mo catalysts, the reaction proceeded with generally good enantioselectivities and yields toward a wide range of substrates (80 examples). Preliminary mechanistic studies suggested that the proposed μ-oxo bridged dinuclear Mo(III)-species was the catalytically active species. This strategy not only provides a promising route for the synthesis of chiral cyclopropanes but also opens a new window for the potential applications of chiral salen-Mo complexes in asymmetric catalysis.

The source-drain electrode with a MoO 3 interfacial modification layer (IML) is considered the most promising method to solve electrical contact issues impeding organic thin-film transistors (OTFTs) from commercialization. However, this method raises many concerns because MoO 3 might diffuse into organic materials, which causes device instability. In this work, we observed a significant device stability degradation by damaging on/off switching performance caused by MoO 3 diffusion. To prevent the MoO 3 diffusion, a source-drain electrode with a multilayered interface contact (MIC) consisting of a top-down stack of metal, MoO 3 IML, and organic buffer layer (OBL) is proposed. In the MIC device, the MoO 3 IML serves well for its intended functions of reducing contact resistance and suppressing minority carrier injection to the OTFT channel. The inclusion of OBL to the MIC helps block MoO 3 diffusion and thereby leads to better device stability and an increased on/off ratio. Through combinations with several organic compounds as a buffer layer, the MoO 3 diffusion related electrical behaviors of OTFTs are systematically studied. Key parameters related to MoO 3 diffusion such as the Fick coefficient and bias-stress stability such as carrier trapping time are extracted from numerical device analysis. Finally, we summarize a general rule of material selection for making robust source-drain contact.

Forkhead box R2 (FOXR2) is a forkhead transcription factor located on the X chromosome whose expression is normally restricted to the testis. In this study, we performed a pan-cancer analysis of FOXR2 activation across more than 10,000 adult and pediatric cancer samples and found FOXR2 to be aberrantly upregulated in 70% of all cancer types and 8% of all individual tumors. The majority of tumors (78%) aberrantly expressed FOXR2 through a previously undescribed epigenetic mechanism that involves hypomethylation of a novel promoter, which was functionally validated as necessary for FOXR2 expression and proliferation in FOXR2-expressing cancer cells. FOXR2 promoted tumor growth across multiple cancer lineages and co-opted ETS family transcription circuits across cancers. Taken together, this study identifies FOXR2 as a potent and ubiquitous oncogene that is epigenetically activated across the majority of human cancers. The identification of hijacking of ETS transcription circuits by FOXR2 extends the mechanisms known to active ETS transcription factors and highlights how transcription factor families cooperate to enhance tumorigenesis., Significance: This work identifies a novel promoter that drives aberrant FOXR2 expression and delineates FOXR2 as a pan-cancer oncogene that specifically activates ETS transcriptional circuits across human cancers. See related commentary by Liu and Northcott, p. 2977., (©2022 The Authors; Published by the American Association for Cancer Research.)

Intervertebral disc degeneration (IVDD) is the most common contributor to low back pain (LBP). Recent studies have found that oxidative stress and reactive oxygen species (ROS) play an important role in IVDD. As a by-product of aerobic respiration, ROS is mainly produced in the mitochondria by the electron transport chain and other mitochondrial located proteins. With the excessive accumulation of ROS, mitochondria are also the primary target of ROS attack in disc cells. A disrupted balance between intracellular ROS production and antioxidant capacity will lead to oxidative stress, which is the key contributor to cell apoptosis, cell senescence, excessive autophagy, and mitochondrial dysfunction. As the pivotal ingredient of oxidative stress, mitochondrial dysfunction manifests as imbalanced mitochondrial dynamics and dysregulated mitophagy. Mitochondria can alter their own dynamics through the process of fusion and fission, so that disabled mitochondria can be separated from the mitochondrial pool. Moreover, mitophagy participates by clearing these dysfunctional mitochondria. Abnormality in any of these processes either increases the production or decreases the clearance of ROS, leading to a vicious cycle that results in the death of intervertebral disc cells in large quantities, combined with degradation of the extracellular matrix and overproduction of matrix metalloproteinase. In this review, we explain the changes in mitochondrial morphology and function during oxidative stress-mediated IVDD and highlight the important role of mitochondria in this process. Eventually, we summarize the IVDD therapeutic strategies targeting mitochondrial dysfunction based on current understanding of the role of oxidative stress in IVDD., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Objective: This study aimed to investigate whether perceived stress mediated the relationship between hope and anxiety/depression symptoms among patients with COVID-19 during the epidemic. In addition, the potential moderating effect of coping styles was examined., Methods: From February 26 to March 10, 2020, patients with COVID-19 were asked to complete a questionnaire online, which included demographic characteristics, as well as the SCL-90-Anxiety, SCL-90-Depression, Chinese Perceived Stress Scale (CPSS), Herth Hope Index (HHI), and Trait Coping Style Questionnaire (TCSQ). Hierarchical linear regression was performed to explore independent factors of anxiety/depression. A multi-group structural equation modeling with the collected data from patients in the Negative Coping style (NC) group and Positive Coping style (PC) group was used to test the hypothesized mechanism., Results: In total, 382 valid questionnaires of patients were obtained, including 96 from NC patients and 286 from PC patients. In the hierarchical linear regression, hope and perceived stress were independent risk factors for both anxiety and depression in the total sample and PC group. However, hope was not independently related to anxiety/depression in the NC group. As hypothesized, the hope of patients had significant and negative indirect effects on both anxiety and depression that were mediated by perceived stress, However, the direct effect from stress on anxiety and depression was stronger for NC patients than for PC patients. Besides, hope had significant direct effects on anxiety/depression in PC patients, but not in NC patients., Conclusion: During the COVID-19 epidemic, perceived stress could mediate the relationship between hope and anxiety/depression symptoms among COVID-19 patients, with coping style moderating this cultivation process., (© 2022. Huazhong University of Science and Technology.)

We analyzed the contributions of structural variants (SVs) to gliomagenesis across 179 pediatric high-grade gliomas (pHGGs). The most recurrent SVs targeted MYC isoforms and receptor tyrosine kinases (RTKs), including an SV amplifying a MYC enhancer in 12% of diffuse midline gliomas (DMG), indicating an underappreciated role for MYC in pHGG. SV signature analysis revealed that tumors with simple signatures were TP53 wild type (TP53 WT ) but showed alterations in TP53 pathway members PPM1D and MDM4. Complex signatures were associated with direct aberrations in TP53, CDKN2A and RB1 early in tumor evolution and with later-occurring extrachromosomal amplicons. All pHGGs exhibited at least one simple-SV signature, but complex-SV signatures were primarily restricted to subsets of H3.3 K27M DMGs and hemispheric pHGGs. Importantly, DMGs with complex-SV signatures were associated with shorter overall survival independent of histone mutation and TP53 status. These data provide insight into the impact of SVs on gliomagenesis and the mechanisms that shape them., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The construction of all-carbon quaternary centers, especially those containing an alkyne-substituted framework, represents an important challenge in organic synthesis. Here we present a novel Fe-catalyzed selective formal insertion of diazo compounds into C(sp)-C(sp 3 ) bonds of propargyl alcohols under mild conditions that enables the streamlined construction of alkyne-substituted all-carbon quaternary centers. This unique strategy starts with in situ generation of an ester group in the presence of carboxylic acids, followed by insertion of metal-carbene into C(sp)-C(sp 3 ) bonds, which may open up a new reaction mode for exploring metal-carbene insertion into acyclic C-C bonds., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The radical cascade reaction is considered as one of the most powerful methods to build molecular complexity. However, highly stereoselective intermolecular radical cascade reactions that can produce complex cyclic compounds bearing multiple stereocenters via visible-light-induced photocatalysis have been challenging yet desirable. Herein we report a facile and efficient synthesis of multi-substituted trans-fused hexahydrocarbazoles via a stereoselective intermolecular radical cascade reaction of readily available tryptophans and acrylamides enabled by visible-light-induced photoredox catalysis. The trans-fused hexahydrocarbazoles with up to five stereocenters including two quaternary ones can be accessed in up to 82% yield, >20/1 diastereoselectivity, and 96% ee. Interestingly, the tetrahydrocarbazoles are favorably formed when the reaction is performed under air. Moreover, by simply switching the starting material from tryptophans to ɤ-alkenyl substituted α-amino acids, this protocol can be further applied to the stereoselective syntheses of 1,3,5-trisubstituted cyclohexanes which are otherwise challenging to access. Preliminary mechanistic studies suggest that the reaction goes through radical addition cascade and radical-polar crossover processes., (© 2022. The Author(s).)

This study aims to identify the active components and the mechanism of Jingqi Yukui Capsules(JQYK) in the treatment of gastric ulcer based on network pharmacology, and verify some key targets and signaling pathways through animal experiment. To be specific, first, the active components and targets of JQYK were retrieved from a Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of gastric ulcer from GeneCards and Online Mendelian Inheritance in Man(OMIM) with the search term &quot;gastric ulcer&quot;. The common targets of the two were the potential targets of the prescription for the treatment of the di-sease. Then, protein-protein interaction(PPI) network of key targets were constructed based on STRING and Cytoscape 3.7.2, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by matescape database and pathway visualization by Omicshare. For the animal experiment, the improved method of Okabe was used to induce gastric ulcer in rats, and the model rats were classified into the model group, JQYK high-dose(JQYK-H), medium-dose(JQYK-M), and low-dose(JQYK-L) groups, Anweiyang Capsules(WYA) group, and Rabeprazole Sodium Enteric Capsules(RBPZ) group. Normal rats were included in the blank group. Rats in the blank group and model group were given distilled water and those in the administration groups received corresponding drugs. Then gastric ulcer healing in rats was observed. The changes of the gastric histomorphology in rats were evaluated based on hematoxylin-eosin(HE) staining, and the content of inducible nitric oxide synthase(iNOS) in rat gastric tissue was detected with Coomassie brilliant blue method. The mRNA and protein levels of some proteins in rat gastric tissue were determined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot(WB) to further validate some key targets and signaling pathways. A total of 206 active components and 535 targets of JQYK, 1 305 targets of gastric ulcer, and 166 common targets of the disease and the drug were yielded. According to PPI analysis and KEGG pathway enrichment analysis, multiple key targets, such as interleukin-6(IL-6), tumor necrosis factor(TNF), mitogen-activated protein kinase 1(MAPK1), MAPK3, and MAPK14, as well as nuclear factor kappa-B(NF-κB) signaling pathway, IL-17 signaling pathway, and leukocyte transendothelial migration in the top 20 key signaling pathways were closely related to inflammation. The key protein p38 MAPK and NF-κB signaling pathway were selected for further verification by animal experiment. The gastric ulcer in the JQYK-H group recovered nearly to the level in the blank group, with significant decrease in the content of iNOS in rat gastric tissue and significant reduction in the mRNA and phosphorylation levels of p38 MAPK and the mRNA and protein levels of NF-κB p65 in rat gastric tissue. The results indicated that JQYK can inhibit the phosphorylation of the key protein p38 MAPK and the expression of NF-κB p65 in the NF-κB signaling pathway, thereby exerting the anti-inflammatory effect and effectively improving the quality of gastric ulcer healing in rats. Thus, the animal experiment result verifies some predictions of network pharmacology.

Forward osmosis membrane bioreactors (FOMBRs) are currently gaining attention from the wastewater treatment industry, for their potential to produce high effluent quality and a relatively better flux stability against fouling. However, only using physical cleaning methods is not sufficient to recover the water flux performance satisfactorily under a long-term operation. This study comprehensively investigated the efficiency of a hybrid, environmentally-friendly cleaning strategy involving a combination of physical and free nitrous acid (FNA) cleanings under a long-term FOMBR operation. During 92 days of FOMBR operation, physical cleaning recovered the water flux by 85%, whilst FNA cleaning contributed to an additional 5% of the recovery. In addition, FNA cleaning also offered a retardation of fouling deposition by maintaining the water flux 18-30% more than that obtained by only the physical cleaning. A possible mechanism for FNA's role as the cleaning reagent was proposed for the first time in this study based on the water flux performance and membrane autopsy analysis. The results showed FNA cleaning broke down the residual fouling layer, preferencing protein-based substances. A lower ratio of protein to polysaccharides of the residual fouling layer contributed to a more negatively charged membrane surface (- 42.34 ± 0.30 mV) compared to the virgin one (- 17.54 ± 0.81 mV). This resulted in a stronger electrostatic repulsion between the foulants and the membrane surface, and thus slowed down the biofouling deposition process. This study suggested FNA solution has the great potential not only to recover the membrane performance, also as a strategy to slow down fouling deposition., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Colorectal cancer (CRC) is one of the most common malignancies worldwide, and effective therapy remains a challenge. In this study, we take advantage of a drug repurposing strategy to screen small molecules with novel anticancer activities in a small-molecule library consisting of 1056 FDA-approved drugs. We show, for the first time, that lomitapide, a lipid-lowering agent, exhibits antitumor properties in vitro and in vivo. Activated autophagy is characterized as a key biological process in lomitapide-induced CRC repression. Mechanistically, lomitapide stimulated mitochondrial dysfunction-mediated AMPK activation, resulting in increased AMPK phosphorylation and enhanced Beclin1/Atg14/Vps34 interactions, provoking autophagy induction. Autophagy inhibition or AMPK silencing significantly abrogated lomitapide-induced cell death, indicating the significance of AMPK-regulated autophagy in the antitumor activities of lomitapide. More importantly, PP2A was identified as a direct target of lomitapide by limited proteolysis-mass spectrometry (LiP-SMap), and the bioactivity of lomitapide was attenuated in PP2A-deficient cells, suggesting that the anticancer effect of lomitapide occurs in a PP2A-dependent manner. Taken together, the results of the study reveal that lomitapide can be repositioned as a potential therapeutic drug for CRC treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A novel sulfonyl radical triggered selective iodosulfonylation and bicyclization of 1,6-dienes has been described for the first time. High selectivity and efficiency, mild reaction conditions, excellent functional group compatibility, and broad substrate scope are the attractive features of this synthetic protocol, which provides a unique platform for precise radical cyclization.

A series of Zr(SO 4 ) 2 /SiO 2 solid acid catalysts with different Zr(SO 4 ) 2 loadings were prepared by water-soluble-impregnation method at room temperature. Then, the prepared catalysts were characterized by Fourier transform infrared spectroscopy, transmission electron microscopy and energy-dispersive X-ray spectrum, X-ray diffraction, adsorption/desorption of N 2 , and temperature-programmed desorption of NH 3 . The results showed that the active component Zr(SO 4 ) 2 was successfully adhered to the mesoporous SiO 2 , and the acid amount of Zr(SO 4 ) 2 /SiO 2 increased with the increasing of the Zr(SO 4 ) 2 loadings. Finally, the wheat stalk was used as raw material and depolymerized over Zr(SO 4 ) 2 /SiO 2 to produce ethyl levulinate (EL). The reaction mixture was separated and purified by filtration and vacuum distillation. The kinetic characteristics and the reaction pathway were also studied. A comparative study showed that 20 wt.% Zr(SO 4 ) 2 /SiO 2 exhibited higher catalytic activity. When reaction temperature, time, catalyst dosage and Zr(SO 4 ) 2 loadings were 190 °C, 50 min, 20 wt.% and 30 wt.%, the EL yield reached a maximum of 17.14%. The relative content of EL exceeded 90% after three steps of distillation., Competing Interests: CONFLICT OF INTEREST: none declared, (Copyright © 2021 The Author(s).)

Gastrointestinal cancer is a leading cause of cancer-related mortality and remains a major challenge for cancer treatment. Despite the combined administration of modern surgical techniques and chemoradiotherapy (CRT), the overall 5-year survival rate of gastrointestinal cancer patients in advanced stage disease is less than 15%, due to rapid disease progression, metastasis, and CRT resistance. A better understanding of the mechanisms underlying cancer progression and optimized treatment strategies for gastrointestinal cancer are urgently needed. With increasing evidence highlighting the protective role of immune responses in cancer initiation and progression, immunotherapy has become a hot research topic in the integrative management of gastrointestinal cancer. Here, an overview of the molecular understanding of colorectal cancer, esophageal cancer and gastric cancer is provided. Subsequently, recently developed immunotherapy strategies, including immune checkpoint inhibitors, chimeric antigen receptor T cell therapies, tumor vaccines and therapies targeting other immune cells, have been described. Finally, the underlying mechanisms, fundamental research and clinical trials of each agent are discussed. Overall, this review summarizes recent advances and future directions for immunotherapy for patients with gastrointestinal malignancies., 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 Wang, Zuo, He and Li.)

The transition-metal-catalyzed cyclopropanation of alkenes by the decomposition of diazo compounds is a powerful and straightforward strategy to produce cyclopropanes, but is tempered by the potentially explosive nature of diazo substrates. Herein we report the Mo-catalyzed regiospecific deoxygenative cyclopropanation of readily available and bench-stable 1,2-dicarbonyl compounds, in which one of the two carbonyl groups acts as a carbene equivalent upon deoxygenation and engages in the subsequent cyclopropanation process. The use of a commercially available Mo catalyst afforded an array of valuable cyclopropanes with exclusive regioselectivity in up to 90 % yield. The synthetic utility of this method was further demonstrated by gram-scale syntheses, late-stage functionalization, and the cyclopropanation of a simple monocarbonyl compound. Preliminary mechanistic studies suggest that phosphine (or silane) acts as both a mild reductant and a good oxygen acceptor that efficiently regenerates the catalytically active Mo catalyst through reduction of the Mo-oxo complexes., (© 2021 Wiley-VCH GmbH.)

A large majority of cardiovascular nanomedicine research has focused on fabricating designer nanoparticles for improved targeting as a means to overcome biological barriers. For cardiac related disorders, such as atherosclerosis, hypertension, and myocardial infarction, designer micro or nanoparticles are often administered into the vasculature or targeted vessel with the hope to circumvent problems associated with conventional drug delivery, including negative systemic side effects. Additionally, novel nano-drug carriers that enter circulation can be selectively uptaken by immune cells with the intended purpose that they modulate inflammatory processes and migrate locally to plaque for therapeutic payload delivery. Indeed, innovative design in nanoparticle composition, formulation, and functionalization has advanced the field as a means to achieve therapeutic efficacy for a variety of cardiac disease indications. This perspective aims to discuss these advances and provide new interpretations of how nanotechnology can be best applied to aid in cardiovascular disease treatment. In an effort to spark discussions on where the field of research should go, we share our outlook in new areas of nanotechnological inclusion and integration, such as in vascular, implantable, or wearable device technologies as well as nanocomposites and nanocoatings. Further, as cardiovascular diseases (CVD) increasingly claim a number of lives globally, we propose more attention should be placed by researchers on nanotechnological approaches for risk factor treatment to aid in early prevention and treatment of CVD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Low free triiodothyronine (FT3) levels are related to a poor prognosis deterioration in patients with COVID-19 presenting with non-thyroidal illness syndrome (NTI). This study was designed to explore whether free thyroxin (FT4) or thyroid stimulating hormone (TSH) levels affected the mortality of patients with COVID-19 presenting with NTI., Methods: Patients with COVID-19 complicated with NTI who were treated at our hospital were included in this retrospective study. Patients were divided into low TSH and normal TSH groups, as well as low and normal-high FT4 group, according to the reference range of TSH or FT4 levels. The 90-day mortality and critical illness rates were compared among patients with low and normal TSH levels, as well as among patients with low FT4 levels and normal-high FT4 levels; in addition, differences in demographic and laboratory data were compared. A Kaplan-Meier analysis and Cox proportional hazards models were used to assess the associations of TSH and FT4 levels with mortality., Results: One hundred fifty patients with low FT3 levels and without a history of thyroid disease were included, 68% of whom had normal FT4 and TSH levels. Critical illness rates (74.07% VS 37.40%, P = 0.001) and mortality rates (51.85% VS 22.76%, P = 0.002) were significantly higher in the low TSH group than in the normal TSH group. Although no significant difference in the critical illness rate was found (P = 0.296), the mortality rate was significantly higher in the low FT4 group (P = 0.038). Low TSH levels were independently related to 90-day mortality (hazard ratio = 2.78, 95% CI:1.42-5.552, P = 0.003)., Conclusions: Low FT4 and TSH concentrations were associated with mortality in patients with COVID-19 presenting with NTI; moreover, low TSH levels were an independent risk factor for mortality in these patients.

Positive nucleic acid (NA) results have been found in recovered and discharged COVID-19 patients, but the proportion is unclear. This study was designed to analyze the recurrent positive rate of NA results after consecutively negative results, and the relationship between the specific antibody production and positive NA rate. According to Strengthening the Reporting of Observational Studies in Epidemiology guidelines, data of inpatients in Sino-French New City Branch of Tongji Hospital between Jan. 28 and Mar. 6, 2020 were collected. A total of 564 COVID-19 patients over 14 years old who received the examinations of NA and antibodies against SARS-CoV-2 were included. Days of viral shedding and specific antibodies were recorded and assessed. Among NA tests in respiratory samples (throat swabs, nasopharyngeal swabs, sputum and flushing fluid in alveoli), the patients with all-negative NA results accounted for 17.20%, those with single-positive results for 46.63%, and those with multiple-positive results for 36.17% respectively. Besides, the recurrent positive NA results after consecutively negative results appeared in 66 patients (11.70%). For multiple-positive patients, median viral shedding duration was 20 days (range: 1 to 57 days). Of the 205 patients who received 2 or more antibody tests, 141 (68.78%) had decreased IgG and IgM concentrations. IgM decreased to normal range in 24 patients, with a median of 44 days from symptom onset. Viral shedding duration was not significantly correlated with gender, age, disease severity, changes in pulmonary imaging, and antibody concentration. It is concluded that antibody level and antibody change had no significant correlation with the positive rate of NA tests and the conversion rate after continuous negative NA tests. In order to reduce the recurrent positive proportion after discharge, 3 or more consecutive negative NA test results with test interval more than 24 h every time are suggested for the discharge or release from quarantine.

Glioblastoma (GBM) is one of the most lethal tumor of all human cancers. Due to its poor response to chemotherapy and radiotherapy as well as its high rate of recurrence after treatment, the treatment is still undesired. The identification of potential related genes and bio-markers in the development of GBM could provide some new targets for the treatment of GBM. Our purpose in this study was to evaluate the mission of COL8A2 in GBM. Combined with TCGA, Oncomine databases, CGGA, GEPIA website and qRT-PCR analyses, we found that COL8A2 was up-regulated both in GBM tissues and cells compared to the controls. Moreover, the high COL8A2 expression was associated with the shorter overall survival of patients with GBM. The expression of COL8A2 was also positively correlated with metastasis-associated genes including vimentin, snail, slug, MMP2 and MMP7 according to GEPIA website. Knockdown of COL8A2 could suppress the cell proliferation, cell migration and invasion, whereas the overexpression of COL8A2 significantly expedited these processes. What's more, the outcome of western blot analysis manifested that COL8A2 could induced the expression of vimentin, snail, slug, MMP2 and MMP7. Taken together, COL8A2 activated cell proliferation, cell migration and invasion via raising the relative expression of EMT-related proteins in GBM. Therefore, our investigation suggests the oncogenic role of COL8A2 in GBM and provides a potential application of COL8A2 for GBM therapy.

Background: COVID-19 is highly contagious, and the crude mortality rate could reach 49% in critical patients. Inflammation concerns on disease progression. This study analyzed blood inflammation indicators among mild, severe and critical patients, helping to identify severe or critical patients early., Methods: In this cross-sectional study, 100 patients were included and divided into mild, severe or critical groups according to disease condition. Correlation of peripheral blood inflammation-related indicators with disease criticality was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve., Results: Significantly, disease severity was associated with age (R = -0.564, P < 0.001), interleukin-2 receptor (IL2R) (R = -0.534, P < 0.001), interleukin-6 (IL-6) (R = -0.535, P < 0.001), interleukin-8 (IL-8) (R = -0.308, P < 0.001), interleukin-10 (IL-10) (R = -0.422, P < 0.001), tumor necrosis factor α (TNFα) (R = -0.322, P < 0.001), C-reactive protein (CRP) (R = -0.604, P < 0.001), ferroprotein (R = -0.508, P < 0.001), procalcitonin (R = -0.650, P < 0.001), white cell counts (WBC) (R = -0.54, P < 0.001), lymphocyte counts (LC) (R = 0.56, P < 0.001), neutrophil count (NC) (R = -0.585, P < 0.001) and eosinophil counts (EC) (R = 0.299, P < 0.001). With IL2R > 793.5 U/mL or CRP > 30.7 ng/mL, the progress of COVID-19 to critical stage should be closely observed and possibly prevented., Conclusions: Inflammation is closely related to severity of COVID-19, and IL-6 and TNFα might be promising therapeutic targets.

Forward osmosis membrane bioreactor (FOMBR) is an integrated physical-biological treatment process that has received increased awareness in treating municipal wastewater for its potential to produce high effluent quality coupled with its low propensity for fouling formation. However, reverse salt diffusion (RSD) is a major issue and so far limited studies have reported long-term FOMBR operation under the elevated salinity conditions induced by RSD. This study investigated the performance of a FOMBR in treating municipal wastewater under a controlled saline environment (6-8 g L -1 NaCl) using two separate sodium chloride draw solution (NaCl DS) concentrations (35 and 70 g L -1 ) over 243 days. At 35 g L -1 NaCl DS, the water flux performance dropped from 6.75 L m -2 h -1 (LMH) to 2.07 LMH after 72 days of operation in the first experimental stage, when no cleaning procedure was implemented. In the subsequent stage, the DS concentration was increased to 70 g L -1 and a weekly physical cleaning regime introduced. Under stable operation, the water flux performance recovery was 67% after 21 cycles of physical cleaning. For the first time in FOMBR studies, a shortcut nitrogen removal via the nitrite pathway was also achieved under the elevated salinity conditions. At the end of operation (day 243), the ammonia-oxidising bacteria (Nitrosomonas sp.) was the only nitrifier species in the system and no nitrite oxidising bacteria was detected. The above study proves that a FOMBR system is a feasible process for treating municipal wastewater., 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.)

A simple, eco-friendly, and efficient methodology for performing radical cyclizations of enynes/dienes with alcohols in water has been established. This methodology showed ease of scale up, and it was designed to use mild reaction conditions and no catalyst. It was also designed to employ K 2 S 2 O 8 as a green oxidant and water as the solvent, conditions making this process clean and easy to operate, hence achieving the criteria of green chemistry.

Bias-stress instability has been a challenging problem and a roadblock for developing stable p-type organic field-effect transistors (OFETs). This device instability is hypothesized because of electron-correlated charge carrier trapping, neutralization, and recombination at semiconductor/dielectric interfaces and in semiconductor channels. Here, in this paper, a strategy is demonstrated to improve the bias-stress stability by constructing a multilayered drain electrode with energy-level modification layers (ELMLs). Several organic small molecules with high lowest unoccupied molecular orbital (LUMO) energy levels are experimented as ELMLs. The energy-level offset between the Fermi level of the drain electrode and the LUMOs of the ELMLs is shown to construct the interfacial barrier, which suppresses electron injection from the drain electrode into the channel, leading to significantly improved bias-stress stability of OFETs. The mechanism of the ELMLs on the bias-stress stability is studied by quantitative modeling analysis of charge carrier dynamics. Of all injection models evaluated, it is found that Fowler-Nordheim tunneling describes best the observed experimental data. Both theory and experimental data show that, by using the ELMLs with higher LUMO levels, the electron injection can be suppressed effectively, and the bias-stress stability of p-type OFETs can thereby be improved significantly.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Circular RNA circ-SMAD7 is downregulated in colorectal cancer and suppresses tumor metastasis by regulating epithelial mesenchymal transition, by D.-K. Wang, R.-F. Chong, B.-L. Song, K.-F. Fan, Y.-F. Liu, published in Eur Rev Med Pharmacol Sci 2020; 24 (4): 1736-1742-DOI: 10.26355/eurrev&#95;202002&#95;20350-PMID: 32141541" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20350.

Key Points: The roles of the Na + /HCO 3 - cotransporters NBCn1 and NBCn2 as well as their activators IRBIT and L-IRBIT in the regulation of the mTAL transport of NH 4 + , HCO 3 - , and NaCl are investigated. Dietary challenges of NH 4 Cl, NaHCO 3 or NaCl all increase the abundance of NBCn1 and NBCn2 in the outer medulla. The three challenges generally produce parallel increases in the abundance of IRBIT and L-IRBIT in the outer medulla. Both IRBIT and L-IRBIT powerfully stimulate the activities of the mTAL isoforms of NBCn1 and NBCn2 as expressed in Xenopus oocytes. Our findings support the hypothesis that NBCn1, NBCn2, IRBIT and L-IRBIT appropriately promote NH 4 + shunting but oppose HCO 3 - and NaCl reabsorption in the mTAL, and thus are at the nexus of the regulation pathways for multiple renal transport processes., Abstract: The medullary thick ascending limb (mTAL) plays a key role in urinary acid and NaCl excretion. NBCn1 and NBCn2 are present in the basolateral mTAL, where NBCn1 promotes NH 4 + shunting. IRBIT and L-IRBIT (the IRBITs) are two powerful activators of certain acid-base transporters. Here we use western blotting and immunofluorescence to examine the effects of multiple acid-base and electrolyte disturbances on expression of NBCn1, NBCn2 and the IRBITs in rat kidney. We also use electrophysiology to examine the functional effects of IRBITs on NBCn1 and NBCn2 in Xenopus oocytes. NH 4 Cl-induced metabolic acidosis (MAc) substantially increases protein expression of NBCn1 and NBCn2 in the outer medulla (OM) of rat kidney. Surprisingly, NaHCO 3 -induced metabolic alkalosis (MAlk) and high-salt diet (HSD) also increase expression of NBCn1 and NBCn2 (effect of NaHCO 3  > HSD). Moreover, all three challenges generally increase OM expression of the IRBITs. In Xenopus oocytes, the IRBITs substantially increase the activities of NBCn1 and NBCn2. We propose that upregulation of basolateral NBCn1 and NBCn2 plus the IRBITs in the mTAL: (1) promotes NH 4 + shunting by increasing basolateral HCO 3 - uptake to neutralize apical NH 4 + uptake during MAc; (2) inhibits HCO 3 - reabsorption during MAlk by opposing HCO 3 - efflux via the basolateral anion exchanger AE2; and (3) inhibits NaCl reabsorption by mediating (with AE2) net NaCl backflux into the mTAL cell during HSD. Thus, NBCn1, NBCn2 and the IRBITs are at the nexus of the regulatory pathways for multiple renal transport processes., (© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)

Connecting electrodes play a crucial role to assist charge injection into the adjacent electroluminescent units in tandem organic light-emitting diodes (OLEDs). In this study, we demonstrate that Mg:Ag alloy is an effective connecting electrode for bottom- and top-emitting tandem OLEDs. Optical cavity design and simulation are also conducted to predict the luminance of tandem OLEDs. It is found that the theoretical luminance of tandem OLEDs is close to but not higher than twofold enhancement over the luminance of a single OLED optimized to the first resonance mode, which is theoretically higher than high-order resonance modes. It is also found that the optical properties of Mg:Ag connecting electrodes, while having relatively small influence on weak microcavity bottom-emitting tandem OLEDs, have large influence on strong microcavity top-emitting tandem OLEDs.

Purpose: To examine the benefits of different numbers of 1064-nm Nd-YAG laser treatments in patients with onychomycosis., Methods: This was a pilot study of patients with onychomycosis who were divided into three groups: four treatment sessions (group A), eight sessions (group B), and 12 sessions (group C). Only infected nails of degrees II-III (Scoring Clinical Index for Onychomycosis) were included. Treatment was given once a week using a long-pulse Nd-YAG 1064-nm laser. Patients were followed at 8, 16, and 24 weeks after the first treatment. Side effects were recorded., Results: Treatments were completed for 442 nails in 102 patients. The efficacy rates at 8, 16, and 24 weeks were 35.5%, 38.7%, and 37.4% for group A; 31.4%, 41.7%, and 44.0% for group B; and 27.7%, 50.0%, and 55.4% for group C, respectively. There was a significant difference in the efficacy rate at 24 weeks ( P = 0.016) between groups A and C, but not for groups A vs. B, or for groups B vs. C. No difference in the efficacy rate at 8 or 16 weeks was observed among the three groups. In all three groups, the efficacy was better for degree II nails than for degree III nails (all P = 0.016) between groups A and C, but not for groups A vs. B, or for groups B vs. C. No difference in the efficacy rate at 8 or 16 weeks was observed among the three groups. In all three groups, the efficacy was better for degree II nails than for degree III nails (all., Conclusions: The 1064-nm Nd-YAG laser had clinical benefits against onychomycosis. Higher numbers of treatments provided better long-term (24-week) benefits, but had no impact on the short-term outcomes. The efficacy of laser treatment on degree II onychomycosis was better than for degree III., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2020 Rui-na Zhang et al.)

The pericardium, which surrounds the heart, provides a unique enclosed volume and a site for the delivery of agents to the heart and coronary arteries. While strategies for targeting the delivery of therapeutics to the heart are lacking, various technologies and nanodelivery approaches are emerging as promising methods for site specific delivery to increase therapeutic myocardial retention, efficacy, and bioactivity, while decreasing undesired systemic effects. Here, we provide a literature review of various approaches for intrapericardial delivery of agents. Emphasis is given to sustained delivery approaches (pumps and catheters) and localized release (patches, drug eluting stents, and support devices and meshes). Further, minimally invasive access techniques, pericardial access devices, pericardial washout and fluid analysis, as well as therapeutic and cell delivery vehicles are presented. Finally, several promising new therapeutic targets to treat heart diseases are highlighted., (Copyright © 2019. Published by Elsevier B.V.)

The electroneutral Na + /HCO 3 - cotransporter NBCn2 (SLC4A10) of solute carrier family 4 (SLC4) plays important physiological and pathological roles in the body. Our previous study showed that NBCn2 is expressed on the protein level in the small intestine of rat. Here, by reverse-transcription polymerase chain reaction (PCR), we identified a novel full-length NBCn2 variant, i.e., NBCn2-K, from rat small intestine. By pH i measurement with Xenopus oocytes, the activity of NBCn2-K is not significantly different from NBCn2-G. By western blotting, NBCn2 and the Na + /H + exchanger NHE3 (SLC9A3) are predominantly expressed in the jejunum of rat small intestine. By immunofluorescence, NBCn2 and NHE3 are localized at the apical domain of the jejunum. NaCl overload decreases the expression of NBCn2 by 56% and that of NHE3 by 40% in the small intestine. We propose that NBCn2 is involved in the transepithelial NaCl absorption in the small intestine, and that the down-regulation of NBCn2 by NaCl represents an adaptive response to high salt intake in rat., (Copyright © 2019 Wang, Zhao, Zhu, Wang, Ren, Wang, Liu, Boron and Chen.)

To study the expression changes of inflammatory factors heme oxygenase-1 (HO-1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in intracerebral hemorrhage (ICH), brain tissues surrounding hematoma were collected from ICH patients. The expressions of HO-1, TNF-α, IL- 1β, and other genes were examined at different time points of ICH. Changes in HO-1, TNF-α, and IL-1β positive cell numbers after ICH were detected by immunohistochemical staining. The results showed that the expressions of HO-1, TNF-α, and IL-1β had no significant changes in brain tissues surrounding hematoma within 6 hours after ICH (P > 0.05). Their expressions during 6-24 hours and 24-72 hours after ICH increased constantly. After reaching the peak, they remained steady or slightly decreased after 72 hours. The dynamic expression changes of HO-1, TNF-α, and IL-1β were observed and their development trends were interfered timely to alleviate the secondary neurological impairment after ICH, which was significant to prevent ICH., (Copyright 2019 Biolife Sas. www.biolifesas.org.)

Oropharyngeal cancer is one type of head and neck squamous cell carcinoma that is commonly associated with human papillomavirus (HPV) infection. Its incidence is increasing year by year. However, in the clinical treatment, it is found that the overall prognosis of HPV positive oropharyngeal cancer patients is better than that of HPV negative patients. But till now, the underlying mechanism that leads to this phenomenon has not been fully elucidated. This research analyzed the immune cell infiltration and function, as well as neoantigen loads between HPV positive and negative patients by bioinformatic analysis using the TCGA database, and found that the overall survival rate of HPV positive patients was significantly higher than those in the HPV negative group. Analysis of the relative abundance of immune cells in tumor tissues showed that CD8 + T cells in HPV positive patients were significantly increased compared to those in HPV negative patients, and the expression levels of effector molecules, like IFN-γ and Granzyme B, were significantly upregulated. Meanwhile, the analysis of tumor neoantigen load (TNB) showed that the TNB of HPV positive patients was lower than that of the HPV negative group. This study provides some basic theoretical support for the treating HPV-related oropharyngeal cancer.

The aldol-condensation reaction of biomass-derived furfural and cyclopentanone coupled with hydrogenation/hydrodeoxygenation is a promising route for the production of renewable high-quality diesel or jet fuel. In this paper, we focus on the heterogeneously catalyzed aldol condensation of furfural with cyclopentanone, in order to maximize the yield of 2,5-bis(2-furylmethylidene)cyclopentan-1-one (F 2 C, a C 15 fuel precursor). Experiments were conducted over a series of solid-base catalysts and it was found that potassium fluoride impregnated alumina shown the highest catalytic efficiency. We further investigated the effect of different parameters on the performance of KF/γ-Al 2 O 3 , including KF loading amount, solvent, reaction time and temperature. Over KF/γ-Al 2 O 3 with a 33% KF loading amount, the aldol reaction achieved an F 2 C molar yield up to 95.4% at 333 K within 2 h. Under the nearly optimal condition, the separated solid product is almost F 2 C with a purity of 100%, providing a high-quality biofuel precursor for the next processing step., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: Keratoconjunctivitis sicca (KCS) is a relatively common disease that results in discomfort, tear film instability, visual impairment, and ocular surface damage. Artificial tear substitutes may be suitable for the treatment of mild KCS, but no effective treatment currently exists for severe KCS. Therefore, this study evaluated the effectiveness of autologous microvascular submandibular gland transplantation in the treatment of severe KCS., Patients and Methods: A total of 61 eyes (56 patients) with severe KCS were treated with autologous submandibular gland transplantation from June 2002 to June 2017. The cephalic vein or the great saphenous vein was applied to solve the problem of unmatched veins., Results: In 53 cases (53 of 56, 94.6%), 58 glands (58 of 61, 95.1%) were transplanted successfully. The mean Schirmer I test value improved from 0.78 ± 0.84 mm preoperatively to 18.83 ± 5.72 mm in the stable period after transplantation. Epiphora (14 of 58, 24.14%) was the most common complication of this procedure. Other postoperative complications included venous thrombosis (6 of 61, 9.84%), local infection (2 of 58, 3.45%), xerostomia (2 of 53, 3.77%), duct fistula (1 of 58, 1.72%), sialolithiasis (1 of 58, 1.72%), and ranula (1 of 58, 1.72%)., Conclusions: Autologous microvascular submandibular gland transplantation is a credible and effective solution for severe KCS., (Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Submandibular gland autotransplantation is an effective approach for treating severe keratoconjunctivitis sicca. However, ischemia/reperfusion (I/R) injury, which inevitably occurs during transplantation, is involved in the hypofunction and structural damage that occur early after transplantation. Therefore, it is critical to identify effective strategies to ameliorate I/R injury in submandibular glands. In this study, we investigated the ability of immediate post-conditioning combined with ischemic preconditioning to attenuate I/R injury. We observed that after I/R injury, the level of reactive oxygen species was increased, inflammatory response was strengthened, and severe apoptosis had occurred. In addition, the salivary flow rate was greatly decreased. However, the pathogenesis of I/R injury was significantly ameliorated by ischemia post-conditioning or ischemia preconditioning treatments. In addition, the combination of ischemia preconditioning and post-conditioning achieved synergistic protective effects against I/R injury compared with ischemia preconditioning or ischemia post-conditioning alone. The secretion function was restored in the combination group. Furthermore, the combination treatment involved the same mechanisms of ischemia preconditioning or ischemia post-conditioning, including suppression of the inflammatory reaction and neutrophil accumulation, attenuation of oxidation stress, and inhibition of apoptosis. In conclusion, the combination of ischemia preconditioning and ischemia post-conditioning treatment is a simple and effective approach for treating I/R injury in submandibular glands., (© 2018 Eur J Oral Sci.)

Saliva is being attached great importance for its application in illness diagnosis and have more advantage on the diagnose in oral cavity cancer (OCC). Studies have showed that interleukin (IL) in the saliva could be used as a potential biomarker for OCC diagnosis. Moreover, they have a close connection with tumor genesis, invasion, and metastasis in OCC. Therefore, we reviewed research progress on the relationship between salivary interleukins and OCC.

Previously our lab has created a mouse ovarian xenograft model of copy number variation (CNV)-mediated G protein-coupled receptor (GPCR) MAS-driven tumorigenesis, and RNA profiling identified a putative chemokine tumor-induced factor (Tif). Sequence analysis and chemotactic study suggested that Tif was likely to be a hamster homolog of human GROγ (CXCL3) [IJC 125 (2009): 1316-1327]. In the present study, we report the molecular and functional characterization of the Tif gene. Genomic study of CHO-K1 cells indicated that Tif gene consisted of 4 exons, characterized with an antisense B1 element which is embedded in the fourth exon. Two Tif transcripts were identified which shared identical sequences except that a string of 71-nt derived from the antisense B1 element was deficient in the shorter transcript. Of interests, B1-like RNA ladder was detected in xenografts. Functional studies showed that TIF induced chemotaxis and neovessel formation. Pharmacological studies suggested that TIF activated Gi-coupled CXCR2 and induced both calcium mobilization and ERK1/2 phosphorylation, and suppressed forskolin-stimulated cAMP accumulation. In addition, secreted matured TIF functioned as an autocrine factor and promoted anchorage-independent growth. Unexpectedly, TIF delayed the onset of tumor formation, possibly via suppressing proliferation of stromal fibroblasts. However, TIF did not exert any inhibitory effect on tumor growth. Potentially, TIF could be used for preventing cancer relapse., (Copyright © 2017 Elsevier Ltd. All rights reserved.)