Publications by authors named "Li Tong"

1,362 Publications

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Cell activity modulation and its specific function maintenance by bioinspired electromechanical nanogenerator.

Sci Adv 2021 Sep 24;7(39):eabh2350. Epub 2021 Sep 24.

School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, P. R. China.

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abh2350DOI Listing
September 2021

Application of first-order feature analysis of DWI-ADC in rare malignant mesenchymal tumours of the maxillofacial region.

BMC Oral Health 2021 Sep 23;21(1):463. Epub 2021 Sep 23.

Department of Radiology, China-Japan Union Hospital of Jilin University, No. 829 of Xinmin Street, Chaoyang District, Changchun, 130021, China.

Background: To research the first-order features of apparent diffusion coefficient (ADC) values on diffusion-weighted magnetic resonance imaging (DWI) in maxillofacial malignant mesenchymal tumours.

Methods: The clinical data of 12 patients with rare malignant mesenchymal tumours of the maxillofacial region (6 cases of sarcoma and 6 cases of lymphoma) treated in the hospital from May 2018 to June 2020 and were confirmed by postoperative pathology were retrospectively analyzed. The patients were all examined by 1.5T magnetic resonance imaging. PyRadiomics were used to extract radiomics imaging first-order features. Group differences in quantitative variables were examined using independent-samples t-tests.

Results: The voxels number of ADC and ADC of sarcoma tissues were 44.9124 and 44.2064, respectively, significantly higher than those in lymphoma tissues (ADC (- 68.8379) and ADC (- 74.0045)), the difference considered statistically significant, so do the ADC and ADC.

Conclusions: The statistical difference of ADC and ADC is significant, it is consistent with the outcome of the manual measurement of the ADC mean value of the most significant cross-section of twelve cases of lymphoma. Development of tumour volume based on the ADC parameter map of DWI demonstrates that the first-order ADC radiomics features analysis can provide new imaging markers for the differentiation of maxillofacial sarcoma and lymphoma. Therefore, first-order ADC features of ADC combined ADC may improve the diagnosis level.
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http://dx.doi.org/10.1186/s12903-021-01835-2DOI Listing
September 2021

Degradation of steroid estrogens by UV/peracetic acid: Influencing factors, free radical contribution and toxicity analysis.

Chemosphere 2021 Sep 15;287(Pt 3):132261. Epub 2021 Sep 15.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, Jiangsu, PR China. Electronic address:

Steroid estrogens (SEs) are a group of refractory organic micropollutants detected in secondary effluent frequently. The advanced oxidation processes (AOPs) are usually used to deep remove the SEs from the secondary effluent. Herein, we first investigated the UV/peracetic acid (PAA), a PAA-based AOP, to degrade SEs. Using estrone (E1), 17β-estradiol (E2), estriol (E3), and 17α-ethinyl estradiol (EE2) as representatives, the results showed that UV can effectively activate PAA to enhance the degradation of the four SEs, which degradation followed the pseudo-first-order kinetics (R > 0.99), and the rate constant (k) of degradation increased with increasing the PAA dosage in the range investigated. Little pH dependence was also observed in the degradation of SEs by UV/PAA. Furthermore, the degradation of SEs was improved in the presence of coexisting substrates (Cl, HCO- 3, NO- 3, and HA) in relatively low concentrations. Quenching experiments revealed that the carbon-centered radicals (R-C•) produced from the UV/PAA process were recognized as the predominant contributors to the degradation of the four SEs. Also, we found that the estrogenic activity decreased by more than 94%, but the acute toxicity inhibition increased to 37% in the solution after 30 min UV/PAA treatment. In addition, the 130% additional total organic carbon (TOC) was generated after UV/PAA process. These findings obtained in this work will facilitate the development of the UV/PAA process as a promising strategy for the deep removal of SEs in secondary effluent.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132261DOI Listing
September 2021

Comparison of phytochemical profiles, antioxidant and antiproliferative activities in Chinese bayberry (Myrica rubra Sieb. et Zucc.) fruits.

J Food Sci 2021 Sep 21. Epub 2021 Sep 21.

Department of Food Science, Cornell University, Ithaca, New York, USA.

Here, we examined the phytochemical profiles, antioxidant activity (AA), and antiproliferative activity (APA) of four Chinese bayberry (Myrica rubra Sieb. et Zucc.) pulp extracts. They were found to be rich in total phenolics content (TPC; 186.45 ± 5.42 to 498.94 ± 8.25 mg of gallic acid equiv./100 g FW) and total flavonoids content (TFC; 126.28 ± 4.18 to 194.35 ± 12.03 mg of catechin equiv./100 g FW). For all varieties, the free flavonoid/phenolic/anthocyanin contents were higher than that the bound fractions. Wild pink bayberry (WPB) displayed the highest values of TPC and TFC, and also showed the highest total antioxidant activity (TAA) as revealed by peroxyl radical scavenging capacity (PSC) (451.47 ± 8.01 µmol Vit. C equiv./100 g FW), and free cellular antioxidant activity (CAA) (184.99 ± 6.11 µmol quercetin equiv./100 g FW, no PBS wash; 117.78 ± 2.34 µmol quercetin equiv./100 g FW, PBS wash) assays. Bayberry extracts had a marked reduction in the APA of HepG2 cells, and WPB exhibited the lowest EC (8.50 ± 0.83 mg/ml) value, which was probably associated with cell cycle arrest and apoptosis induction. PRACTICAL APPLICATION: Chinese bayberry (Myrica rubra Sieb. et Zucc.) fruit is rich in natural phenolic compounds, which might be a functional ingredient in food and nutraceutical products. Our findings would provide a logical strategy to promote the comprehensive utilization of phenolics in bayberry fruit with both health and economy benefits.
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http://dx.doi.org/10.1111/1750-3841.15899DOI Listing
September 2021

DcCCD4 catalyzes the degradation of α-carotene and β-carotene to affect carotenoid accumulation and taproot color in carrot.

Plant J 2021 Sep 21. Epub 2021 Sep 21.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Ministry of Agriculture and Rural Affairs Key Laboratory of Biology and Germplasm Enhancement of Horticultural Crops in East China, College of Horticulture, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, China.

Carotenoids are important natural pigments that give bright colors to plants. The difference in the accumulation of carotenoids is one of the key factors in the formation of various colors in carrot taproots. Carotenoid cleavage dioxygenases (CCDs), including CCD and nine-cis epoxycarotenoid dioxygenase (NCED), are the main enzymes involved in the cleavage of carotenoids in plants. Seven CCD genes have been annotated from the carrot genome. In this study, through expression analysis, we found that the expression level of DcCCD4 was significantly higher in the taproot of white carrot (low carotenoid content) than orange carrot (high carotenoid content). The overexpression of DcCCD4 in orange carrots caused the taproot color to be pale yellow, and the contents of α-carotene and β-carotene decreased sharply. Mutant carrot with loss of DcCCD4 function exhibited yellow color (the taproot of the control carrot was white). The accumulation of β-carotene was also detected in taproot. Functional analysis of the DcCCD4 enzyme in vitro showed that it was able to cleave α-carotene and β-carotene at the 9, 10 (9', 10') double bonds. In addition, the number of colored chromoplasts in the taproot cells of transgenic carrots overexpressing DcCCD4 was significantly reduced compared with that in normal orange carrots. Results demonstrated that DcCCD4 affects the accumulation of carotenoids through cleavage of α-carotene and β-carotene in carrot taproot.
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http://dx.doi.org/10.1111/tpj.15498DOI Listing
September 2021

Recombinant angiopoietin-like protein 4 attenuates intestinal barrier structure and function injury after ischemia/reperfusion.

World J Gastroenterol 2021 Aug;27(32):5404-5423

Department of General Surgery, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China.

Background: Intestinal barrier breakdown, a frequent complication of intestinal ischemia-reperfusion (I/R) including dysfunction and the structure changes of the intestine, is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality. To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration. Recombinant human angiopoietin-like protein 4 (rhANGPTL4) is reported to protect the blood-brain barrier when administered exogenously, and endogenous ANGPTL4 deficiency deteriorates radiation-induced intestinal injury.

Aim: To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R.

Methods: Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion. Intestinal epithelial (Caco-2) cells and human umbilical vein endothelial cells were challenged by hypoxia/ reoxygenation to mimic I/R .

Results: Indicators including fluorescein isothiocyanate-conjugated dextran (4 kilodaltons; FD-4) clearance, ratio of phosphorylated myosin light chain/total myosin light chain, myosin light chain kinase and loss of zonula occludens-1, claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation. rhANGPTL4 treatment significantly reversed these indicators, which were associated with inhibiting the inflammatory and oxidative cascade, excessive activation of cellular autophagy and apoptosis and improvement of survival rate. Similar results were observed when cells were challenged by hypoxia/reoxygenation, whereas rhANGPTL4 reversed the indicators close to normal level in Caco-2 cells and human umbilical vein endothelial cells significantly.

Conclusion: rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival maintenance of intestinal barrier structure and functions.
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http://dx.doi.org/10.3748/wjg.v27.i32.5404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409166PMC
August 2021

Discovery of novel 2-phenylamino-4-prolylpyrimidine derivatives as TRK/ALK dual inhibitors with promising antitumor effects.

Bioorg Med Chem 2021 Sep 8;47:116396. Epub 2021 Sep 8.

Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

In order to explore novel TRK and ALK dual inhibitors, a series of 2-phenylamino-4-prolylpyrimidine derivatives were designed, synthesized and evaluated for their in vitro cytotoxicity and enzymatic activities. Delightfully, most compounds were detected moderated to excellent activities in cellular assay. Among them, compound 21 exhibited encouraging cytotoxicity on KM12, H2228 and KARPAS299 cells with IC values of 0.86, 0.141 and 0.072 μM. Meanwhile, the performances of 21 in the enzymatic assays were in good accordance with anti-proliferative activity with IC values of 2.2, 9.3 and 38 nM towards TRKA, ALK and ALK, respectively. Compared with Entrectinib, compound 21 not only ensured the inhibitory activity on TRKA, but also improved the affinity with ALK and ALK to a certain extent. Ultimately, the binding model of 21 with TRKA and ALK were ideally established through molecular docking, which further confirmed the SARs analysis.
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http://dx.doi.org/10.1016/j.bmc.2021.116396DOI Listing
September 2021

Perfecting Targeting in CRISPR.

Annu Rev Genet 2021 Sep 16. Epub 2021 Sep 16.

Institute of Neuroscience, Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Center for Brain Science and Brain-Inspired Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; email:

CRISPR-based genome editing holds promise for genome engineering and other applications in diverse organisms. Defining and improving the genome-wide and transcriptome-wide specificities of these editing tools are essential for realizing their full potential in basic research and biomedical therapeutics. This review provides an overview of CRISPR-based DNA- and RNA-editing technologies, methods to quantify their specificities, and key solutions to reduce off-target effects for research and improve therapeutic applications. Expected final online publication date for the , Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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http://dx.doi.org/10.1146/annurev-genet-071719-030438DOI Listing
September 2021

Thioredoxin-like protein CDSP32 alleviates Cd-induced photosynthetic inhibition in tobacco leaves by regulating cyclic electron flow and excess energy dissipation.

Plant Physiol Biochem 2021 Sep 13;167:831-839. Epub 2021 Sep 13.

College of Life Sciences, Northeast Forestry University, Harbin, Heilongjiang, China; College of Resources and Environment, Northeast Agricultural University, Harbin, Heilongjiang, China; School of Forestry, State Key Laboratory of Tree Genetics and Breeding, Northeast Forestry University, Harbin, China. Electronic address:

Thioredoxin-like protein CDSP32 (Trx CDSP32), a thioredoxin-like (Trx-like) protein located in the chloroplast, can regulate photosynthesis and the redox state of plants under stress. In order to examine the role of Trx CDSP32 in the photosynthetic apparatus of plants exposed to cadmium (Cd), the effects of Trx CDSP32 on photosynthetic function and photoprotection in tobacco leaves under Cd exposure were studied using a proteomics approach with wild-type (WT) and Trx CDSP32 overexpression (OE) tobacco plants. Cd exposure reduced stomatal conductance, blocked PSII photosynthetic electron transport, and inhibited carbon assimilation. Increased water use efficiency (WUE), cyclic electron flow (CEF) of the proton gradient regulation 5 pathway (PGR5-CEF), and regulated energy dissipation [Y(NPQ)] are important mechanisms of Cd adaptation. However, CEF of the NAD(P)H dehydrogenase pathway (NDH-CEF) was inhibited by Cd exposure. Relative to control conditions, the expression levels of violaxanthin de-epoxidase (VDE) and photosystem II 22 kDa protein (PsbS) in OE leaves were significantly increased under Cd exposure, but those in WT leaves did not change significantly. Moreover, the expression of zeaxanthin epoxidase (ZE) under Cd exposure was significantly higher than that in WT leaves. Thus, Trx CDSP32 increased Y(NPQ) and alleviated PSII photoinhibition under Cd exposure. Trx CDSP32 not only increased PGR5-like protein 1A and 1B expression, but also alleviated the down-regulation of NAD(P)H-quinone oxidoreductase subunits induced by Cd exposure. Thus, Trx CDSP32 promotes CEF in Cd-exposed tobacco leaves. Thus, Trx CDSP32 alleviates the Cd-induced photoinhibition in tobacco leaves by regulating two photoprotective mechanisms: CEF and xanthophyll cycle-dependent energy dissipation.
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http://dx.doi.org/10.1016/j.plaphy.2021.09.016DOI Listing
September 2021

Circulating microRNAs as novel diagnostic biomarkers and prognostic predictors for septic patients.

Infect Genet Evol 2021 Sep 11;95:105082. Epub 2021 Sep 11.

Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. Electronic address:

This study was to find out novel miRNAs whether could be used as diagnostic or prognostic biomarkers in sepsis. We used miRNAs microarray assays and further confirmed the levels of miRNAs in 151 septic patients' plasma. 56 miRNAs were up-regulated and 74 miRNAs down-regulated in septic patients compared with the healthy volunteers. But only miR-519c-5p and miR-3622b-3p were up-regulated in both septic and septic shock patients. The levels of miR-519c-5p and miR-3622b-3p were statistically higher in 151 septic patients than healthy controls on day 1. The AUC for miR-519c-5p was 0.79 (95% CI, 0.688-0.892, p = 0.001) in the diagnosis of sepsis, and the AUC for miR-3622b-3p 0.752 (95% CI, 0.622-0.881, p = 0.003). The AUC for the combination of these two miRNAs was 0.831 (95% CI, 0.74-0.923, p < 0.001). Besides, the AUC for miR-519c-5p was 0.597 (p = 0.043) in predicting 28-day mortality. MiR-519c-5p, miR-3622b-3p were novel biomarkers for diagnosing septic patients. High miR-519c-5p levels suggest a worse short-term prognosis. CLINICAL TRIAL REGISTRATION INFORMATION: Name of the registry: Diagnostic and prognostic value of circulating miRNA in patients with sepsis; Trial registration ID: ChiCTR-DDD-17013150; registered 30 October 2017; http://www.chictr.org.cn/edit.aspx?pid=22528&htm=4.
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http://dx.doi.org/10.1016/j.meegid.2021.105082DOI Listing
September 2021

Mechanical Properties of Solution-Blended Graphene Nanoplatelets/Polyether-Ether-Ketone Nanocomposites.

J Phys Chem B 2021 Sep 13;125(37):10597-10609. Epub 2021 Sep 13.

Department of Engineering Mechanics, Dalian University of Technology, Dalian 116024, China.

A lightweight composite with outstanding damping effects and impact resistance is significant for the design of functional structures in advanced equipment, such as aircraft and space vehicles. In this paper, the mechanical properties of solution-blended graphene nanoplatelets (GNPs)/polyether-ether-ketone (PEEK) nanocomposites were characterized by both experimental and numerical methods. It can be found that the layer number and packing configuration of graphene layers are critical to the efficiency of energy dissipation in the composite, while a pack of six- layer graphene and the perpendicular arrangement to the shockwave direction provide the most outstanding energy dissipation ability. The reflection of shockwave caused by graphene reinforcements in the nanocomposite was found to be the dominating reason for the enhanced energy dissipation effect. Physical mechanisms of energy dissipation are investigated by a molecular modeling method to provide insights into the cross-scale design of graphene-reinforced nanocomposites as structural materials.
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http://dx.doi.org/10.1021/acs.jpcb.1c04609DOI Listing
September 2021

A 104-bp Structural Variation of the Gene Is Associated With Growth Traits in Chickens.

Front Genet 2021 26;12:691272. Epub 2021 Aug 26.

College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, China.

Analyzing marker-assisted breeding is an important method utilized in modern molecular breeding. Recent studies have determined that a large number of molecular markers appear to explain the impact of "lost heritability" on human height. Therefore, it is necessary to locate molecular marker sites in poultry and investigate the possible molecular mechanisms governing their effects. In this study, we found a 104-bp insertion/deletion polymorphism in the 5'UTR of the gene through resequencing. In cross-designed F resource groups, the indel was significantly associated with weight at 0, 2, 4, 6, and 10 weeks and a number of other traits [carcass weight (CW), semi-evisceration weight (SEW), evisceration weight (EW), claw weight (CLW), wings weight (DWW), gizzard weight (GW), pancreas weight (PW), chest muscle weight (CMW), leg weight (LW), leg muscle weight (LMW), shedding Weight (SW), liver rate (LR), and leg muscle rate (LMR)] ( < 0.05). In brief, the insertion-insertion (II) genotype was significantly associated with the greatest growth traits and meat quality traits, whereas the values associated with the insertion-deletion (ID) genotype were the lowest in the F reciprocal cross chickens. The mutation sites were genotyped in 4,526 individuals from 12 different chicken breeds and cross-designed F resource groups. The II genotype is the most important genotype in commercial broilers, and the I allele frequency observed in these breeds is relatively high. Deletion mutations tend to be fixed in commercial broilers. However, there is still considerable great potential for breeding in dual-purpose chickens and commercial laying hens. A luciferase reporter assay showed that the II genotype of the gene possessed 2.49-fold higher promoter activity than the DD genotype ( < 0.05). We hypothesized that this indel might affect the transcriptional activity of , thereby affecting the growth traits of chickens. These findings may help to elucidate the function of the gene and facilitate enhanced reproduction in the chicken industry.
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http://dx.doi.org/10.3389/fgene.2021.691272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427608PMC
August 2021

A One-pot-synthesized Double-layered Anticoagulant Hydrogel Tube.

Chem Res Chin Univ 2021 Sep 4:1-7. Epub 2021 Sep 4.

GBA Research Innovation Institute for Nanotechnology, Guangzhou, 510700 P. R. China.

Extracorporeal membrane oxygenation(ECMO) has emerged as a viable treatment in severe cases of acute respiratory distress syndrome, acute respiratory failure, and adult respiratory distress syndrome. However, thromboembolic events stemming from the use of ECMO devices results in significant morbidity and mortality rates; the inner surface of the ECMO tubing comes into contact with the blood and can readily initiate coagulation. In addition, the tubing needs to be continually replaced due to thromboses on the inner tube wall, which not only increases the risk of infection but also the economic burden. Despite considerable effort, a surface modification strategy that effectively addresses these challenges has not yet been realized. In this study, we developed an integrated hollow core-shell-shell hydrogel tube of gelatin/alginate/acrylamide-bacterial nanocellulose(GAA) that meets the anticoagulant requirements for the inner tubing layer as well as the highly elastic soft material needed for the outer layer. Using static blood from healthy volunteers, we confirmed that the platelets or coagulation is not stimulated by the GAA tubing. Importantly, experiments with dynamic blood also demonstrated that the inner layer of the tubing does not elicit blood clotting. The one-pot-synthesized process may provide guidance for the design of anticoagulation tubes used clinically.

Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s40242-021-1267-3.
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http://dx.doi.org/10.1007/s40242-021-1267-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418287PMC
September 2021

[Research advances in nano liquid chromatography instrumentation].

Se Pu 2021 Oct;39(10):1065-1076

Dalian Elite Analytical Instruments Co., Ltd., Dalian 116023, China.

The miniaturization of liquid chromatography equipment is among the most important focus areas in chromatographic technology. It involves the miniaturization of the physical dimensions of the instrument, size of the separation material, and inner diameter of the column. The advantages of a reduced inner diameter of the column have been investigated for several decades, and can be summarized as follows. First, the sample consumption is lower, which is particularly beneficial when a limited amount of sample is available, as is the case with natural products, and in biochemistry and biomedicine. Second, the consumption of the mobile phase is reduced, making the process environmentally friendly and facilitating green chemistry. This allows the addition of more expensive solvent additives, such as chiral additives or isotopic reagents, while maintaining a low analysis cost. Moreover, the degree of band dilution in the column is lower than that with conventional liquid chromatography under the same sample injection conditions. Thus, enhanced mass sensitivity is achieved. Other benefits of a reduced inner diameter of the column include temperature control due to effective heat transfer through the columns and easier coupling to mass detectors, which is particularly advantageous for analyzing complex samples. Typically, the term “nano liquid chromatography” is associated with liquid chromatography, which employs capillary columns of inner diameters less than 100 μm and flow rates in the range of tens to hundreds of nanoliters per minute. Because of the extremely low flow rates and small column volume, the extra-column effect becomes more prominent. Thus, the requirements for every component of liquid chromatographs are augmented toward improving their performance and optimizing the extra-column band broadening of the entire system. The solvent delivery equipment should be able to pump mobile phases accurately and steadily at nanoliter-level flow rates. A gradient mode is required to achieve this, which implies that the lowest flow rate for a single pump unit should reach a few nanoliters per minute. A certain operating pressure is also necessary to employ columns with different inner diameters and particle sizes. A precise and repeatable sample injection procedure is essential for nano liquid chromatography. The injection volume and mode should be suitable for capillary columns, without inducing a significant extra-column effect. A higher-sensitivity detector should be employed, and sample dispersion should be limited. The improved tubing and connection method in nano liquid chromatography should offer stability, reliability, and ease of operation. The extra-column volume should also be restricted to suit nanoliter-level flow rates. Considering that most nano liquid chromatographic instruments have been coupled with a mass detector, this review mainly focused on nanoliter solvent delivery modules, sample injection modules, and tubing and connection modules. By searching and summarizing research articles, technical patents, and brochures of instrument manufacturers, technical routes and research progress on these modules were described in detail. The pump designs can be classified into four types. Pneumatic amplifying pumps have been used in ultra-high-pressure applications. The flow-splitting delivery system, though easy to realize, may lead to a large amount of solvent wastage. Splitless pumps, which are classified based on two main principles, are widely used. Some pumps based on other physical phenomena have been suggested; however, they lacked stability and robustness. Two types of injection modes have been utilized in nano liquid chromatography. The direct nanoliter injection mode typically takes advantage of the groove on the rotor of a switching valve. The trapping injection mode uses trap columns to enable the introduction of large sample volumes. As for the tubing and connection, a few appropriate designs can be acquired from commercial suppliers. The robustness has been improved using some patented technologies. The optimization principles and research progress on optical absorption detection are briefly introduced. Finally, commercial nano liquid chromatographic systems are compared by considering the pumps and injectors.
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http://dx.doi.org/10.3724/SP.J.1123.2021.06017DOI Listing
October 2021

Transcriptome Profiling Reveals B-Lineage Cells Contribute to the Poor Prognosis and Metastasis of Clear Cell Renal Cell Carcinoma.

Front Oncol 2021 12;11:731896. Epub 2021 Aug 12.

Center for Systemic Inflammation Research (CSIR), School of Preclinical Medicine, Youjiang Medical University for Nationalities, Baise, China.

Although immune therapy can improve the treatment of clear cell renal cell carcinoma (ccRCC) significantly, there are still a large proportion of ccRCC patients who progress to metastasis. Targeting the pro-metastatic immune cell in the ccRCC microenvironment could provide a solution to this problem. In this study, B cells in ccRCC biopsies were identified by using scRNA-seq and flow cytometry. The findings indicated the presence of a pro-metastatic B cell type which could be further classified into 3 subpopulations, MARCH3, B2M and DTWD1, based on their large-scaled genetic profiles, rather than traditional Immature/Mature ones. Although all of the 3 subpopulations appeared to contribute to distant metastasis, B cell (B2M) was deemed to be the most essential. Moreover, STX16, CLASRP, ATIC, ACIN1 and SEMA4B, were genes found to be commonly up-regulated in the 3 subpopulations and this was correlated to a poor prognosis of ccRCC. Furthermore, the heterogeneity of plasma cells in ccRCC was also found to contribute to metastasis of the disease. This study offers potential novel therapeutic targets against distant metastasis of cancers, and can help to improve the therapeutic efficiency of ccRCC patients.
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http://dx.doi.org/10.3389/fonc.2021.731896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416254PMC
August 2021

An update on allosteric modulators as a promising strategy targeting histone methyltransferase.

Pharmacol Res 2021 Oct 31;172:105865. Epub 2021 Aug 31.

Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Histone methylation is a vital post-translational modification process in epigenetic regulation. The perturbation of histone methylation accounts for many diseases, including malignant cancers. Although achieving significant advances over past decades, orthosteric inhibitors targeting histone methyltransferases still suffer from challenges on subtype selectivity and acquired drug-resistant mutations. As an alternative, new compounds targeting the evolutionarily less conserved allosteric sites, exemplified by HKMTs and PRMTs inhibitors, offer a promising strategy to address this quandary. Herein, we highlight the allosteric sites and mechanisms in histone methyltransferases along with representative allosteric modulators, expecting to facilitate the discovery of allosteric modulators in favor of epigenetic therapy.
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http://dx.doi.org/10.1016/j.phrs.2021.105865DOI Listing
October 2021

Spontaneous Bile Leak in a Patient Without Recent Abdominal Surgery or Trauma.

Cureus 2021 Jul 28;13(7):e16702. Epub 2021 Jul 28.

Family and Community Medicine, Western Michigan University Homer Stryker School of Medicine, Kalamazoo, USA.

Bile leaks are a rare occurrence most often seen as a complication of cholecystectomy. Other less common etiologies include endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiography (PTC), liver surgery, percutaneous drainage of liver abscesses, living donor hepatectomy, and non-iatrogenic abdominal trauma. In this case study, we present a 67-year-old female with morbid obesity who presented with abdominal pain and was diagnosed with a spontaneous bile leak. She had no history of recent surgery or abdominal trauma. CT revealed that the patient's gallbladder was located in the right lower quadrant, most likely due to mass effect from a large ventral hernia, and possible fluid collection extending from the gallbladder along the surface of the anterior inferior right hepatic lobe. Hepatobiliary iminodiacetic acid (HIDA) was performed due to a concern for cholecystitis. HIDA demonstrated a bile leak in the right upper abdomen of unknown etiology. Initially, there was a concern for gallbladder obstruction. Gastroenterology recommended magnetic resonance cholangiopancreatography (MRCP), however, MRCP was not possible due to the patient's body habitus. The patient had normal liver function tests, was tolerating oral intake, and her abdominal pain resolved, therefore, we became less suspicious of gallbladder obstruction. This case suggests that bile leak should be included in the differential diagnosis for abdominal pain even in patients who have not had recent abdominal surgery or procedures. This case also highlights the unique anatomical finding of a right lower quadrant gallbladder secondary to mass effect from a large ventral hernia.
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http://dx.doi.org/10.7759/cureus.16702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397512PMC
July 2021

Efficient degradation of Rhodamine B by magnetically recoverable FeO-modified ternary CoFeCu-layered double hydroxides via activating peroxymonosulfate.

J Environ Sci (China) 2021 Oct 11;108:188-200. Epub 2021 Mar 11.

College of Environmental Science and Engineering, Taiyuan University of Technology, Shanxi 030024, China. Electronic address:

Environment-friendly nano-catalysts capable of activating peroxymonosulfate (PMS) have received increasing attention recently. Nevertheless, traditional nano-catalysts are generally well dispersed and difficult to be separated from reaction system, so it is particularly important to develop nano-catalysts with both good catalytic activity and excellent recycling efficiency. In this work, magnetically recoverable FeO-modified ternary CoFeCu-layered double hydroxides (FeO/CoFeCu-LDHs) was prepared by a simple co-precipitation method and initially applied to activate PMS for the degradation of Rhodamine B (RhB). X-ray diffraction (XRD), fourier transform infrared spectrometer (FT-IR), scanning electron microscope (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller method (BET), and vibrating sample magnetometer (VSM) were applied to characterize morphology, structure, specific surface area and magnetism. In addition, the effects of several key parameters were evaluated. The FeO/CoFeCu-LDHs exhibited high catalytic activity, and RhB degradation efficiency could reach 100% within 20 min by adding 0.2 g/L of catalyst and 1 mmol/L of PMS into 50 mg/L of RhB solution under a wide pH condition (3.0-7.0). Notably, the FeO/CoFeCu-LDHs showed good super-paramagnetism and excellent stability, which could be effectively and quickly recovered under magnetic condition, and the degradation efficiency after ten cycles could still maintain 98.95%. Both radicals quenching tests and electron spin resonance (ESR) identified both HO• and SO were involved and SO played a dominant role on the RhB degradation. Finally, the chemical states of the sample's surface elements were measured by X-ray photoelectron spectroscopy (XPS), and the possible activation mechanism in FeO/CoFeCu-LDHs/PMS system was proposed according to comprehensive analysis.
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http://dx.doi.org/10.1016/j.jes.2021.02.020DOI Listing
October 2021

Cation-π induced surface cleavage of organic pollutants with OH formation from HO for water treatment.

iScience 2021 Aug 16;24(8):102874. Epub 2021 Jul 16.

Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Institute of Environmental Research at Greater Bay, Guangzhou University, Guangzhou 510006, China.

High energy consumption is impedimental for eliminating refractory organic pollutants in water by applying advanced oxidation processes (AOPs). Herein, we develop a novel process for destructing these organics in chemical conjuncted Fe-FeC/Fe, graphited ZIF-8, and rGO air-saturated aqueous suspension without additional energy. In this process, a strong Fe-π interaction occurs on the composite surface, causing the surface potential energy ∼310.97 to 663.96 kJ/mol. The electrons for the adsorbed group of pollutants are found to delocalize to around the iron species and could be trapped by O in aqueous suspension producing OH, H, and adsorbed organic cation radicals, which are hydrolyzed or hydrogenated to intermediate. The target pollutants undergo surface cleavage and convert HO to OH, consuming chemical adsorption energy (∼2.852-9.793 kJ/mol), much lower than that of AOPs. Our findings provide a novel technology for water purification and bring new insights into pollutant oxidation chemistry.
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http://dx.doi.org/10.1016/j.isci.2021.102874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378836PMC
August 2021

Efficacy and Safety of a Novel Thrombectomy Device in Patients With Acute Ischemic Stroke: A Randomized Controlled Trial.

Front Neurol 2021 12;12:686253. Epub 2021 Aug 12.

Department of Stroke Center, Changhai Hospital, Naval Military Medical University, Shanghai, China.

The Tonbridge stent is a novel retriever with several design improvements which aim to achieve promising flow reperfusion in the treatment of acute ischemic stroke (AIS). We conducted a randomized controlled, multicenter, non-inferiority trial to compare the safety and efficacy of the Tonbridge stent with the Solitaire FR. AIS patients aged 18-85 years with large vessel occlusion in anterior circulation who could undergo puncture within 6 h of symptom onset were included. Randomization was performed on a 1:1 ratio to thrombectomy with either the Tonbridge stent or the Solitaire FR. The primary efficacy endpoint was successful reperfusion using a modified thrombolysis in cerebral infarction score (mTICI) of 2b/3. Safety outcomes were symptomatic intracranial hemorrhage (sICH) within 24 ± 6 h and all-cause mortality within 90 days. A clinically relevant non-inferiority margin of 12% was chosen as the acceptable difference between groups. Secondary endpoints included time from groin puncture to reperfusion, National Institutes of Health Stroke Scale (NIHSS) score at 24 h and at 7 days, and a modified Rankin Scale (mRS) score of 0-2 at 90 days. A total of 220 patients were enrolled; 104 patients underwent thrombectomy with the Tonbridge stent and 104 were treated with the Solitaire FR. In all test group patients, the Tonbridge was used as a single retriever without rescuing by other thrombectomy devices. Angioplasty with balloon and/or stent was performed in 26 patients in the Tonbridge group and 16 patients in the Solitaire group ( = 0.084). Before angioplasty, 86.5% of those in the Tonbridge group and 81.7% of those in the Solitaire group reached successful reperfusion ( = 0.343). Finally, more patients in the Tonbridge group achieved successful reperfusion (92.3 vs. 84.6%, 95% CI of difference value 0.9-16.7%, < 0.0001). There were no significant differences on sICH within 24 ± 6 h between the two groups. All-cause mortality within 90 days was 13.5% in the Tonbridge group and 16.3% in the Solitaire group ( = 0.559). We noted no significant differences between groups on the NIHSS at either 24 h or 7 days and the mRS of 0-2 at 90 days. The trial indicated that the Tonbridge stent was non-inferior to the Solitaire FR within 6 h of symptom onset in cases of large vessel occlusion stroke. ClinicalTrials.gov, number: NCT03210623.
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http://dx.doi.org/10.3389/fneur.2021.686253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397519PMC
August 2021

Selenoproteins Protect Against Avian Liver Necrosis by Metabolizing Peroxides and Regulating Receptor Interacting Serine Threonine Kinase 1/Receptor Interacting Serine Threonine Kinase 3/Mixed Lineage Kinase Domain-Like and Mitogen-Activated Protein Kinase Signaling.

Front Physiol 2021 12;12:696256. Epub 2021 Aug 12.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing, China.

Liver necroptosis of chicks is induced by selenium (Se)/vitamin E (VE) deficiencies and may be associated with oxidative cell damage. To reveal the underlying mechanisms of liver necrosis, a pool of the corn-soy basal diet (10 μg Se/kg; no VE added), a basal diet plus all-racα-tocopheryl acetate (50 mg/kg), Se (sodium selenite at 0.3 mg/kg), or both of these nutrients were provided to day-old broiler chicks ( = 40/group) for 6 weeks. High incidences of liver necrosis (30%) of chicks were induced by -SE-VE, starting at day 16. The Se concentration in liver and glutathione peroxidase (GPX) activity were decreased ( < 0.05) by dietary Se deficiency. Meanwhile, Se deficiency elevated malondialdehyde content and decreased superoxide dismutase (SOD) activity in the liver at weeks 2 and 4. Chicks fed with the two Se-deficient diets showed lower ( < 0.05) hepatic mRNA expression of , and than those fed with the two Se-supplemented diets. Dietary Se deficiency had elevated ( < 0.05) the expression of SELENOP, but decreased the downregulation ( < 0.05) of GPX1, GPX4, SELENON, and SELENOW in the liver of chicks at two time points. Meanwhile, dietary Se deficiency upregulated ( < 0.05) the abundance of hepatic proteins of p38 mitogen-activated protein kinase, phospho-p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, phospho-c-Jun N-terminal kinase, extracellular signal-regulated kinase, phospho-mitogen-activated protein kinase, receptor-interacting serine-threonine kinase 1 (RIPK1), receptor-interacting serine-threonine kinase 3 (RIPK3), and mixed lineage kinase domain-like (MLKL) at two time points. In conclusion, our data confirmed the differential regulation of dietary Se deficiency on several key selenoproteins, the RIPK1/RIPK3/MLKL, and mitogen-activated protein kinase signaling pathway in chicks and identified new molecular clues for understanding the etiology of nutritional liver necrosis.
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http://dx.doi.org/10.3389/fphys.2021.696256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397447PMC
August 2021

CXCL12/CXCR4 axis as a key mediator in atrial fibrillation via bioinformatics analysis and functional identification.

Cell Death Dis 2021 Aug 27;12(9):813. Epub 2021 Aug 27.

Department of Cardiology, The Second Affiliate Hospital of Xi'an Jiaotong University, Xi'an, China.

Atrial fibrillation (AF) is an increasingly prevalent arrhythmia with significant health and socioeconomic impact. The underlying mechanism of AF is still not well understood. In this study, we sought to identify hub genes involved in AF, and explored their functions and underlying mechanisms based on bioinformatics analysis. Five microarray datasets in GEO were used to identify the differentially expressed genes (DEGs) by Robust Rank Aggregation (RRA), and hub genes were screened out using protein-protein interaction (PPI) network. AF model was established using a mixture of acetylcholine and calcium chloride (Ach-CaCl) by tail vein injection. We totally got 35 robust DEGs that mainly involve in extracellular matrix formation, leukocyte transendothelial migration, and chemokine signaling pathway. Among these DEGs, we identified three hub genes involved in AF, of which CXCL12/CXCR4 axis significantly upregulated in AF patients stands out as one of the most potent targets for AF prevention, and its effect on AF pathogenesis and underlying mechanisms were investigated in vivo subsequently with the specific CXCR4 antagonist AMD3100 (6 mg/kg). Our results demonstrated an elevated transcription and translation of CXCL12/CXCR4 axis in AF patients and mice, accompanied with the anabatic atrial inflammation and fibrosis, thereby providing the substrate for AF maintenance. Blocking its signaling via AMD3100 administration in AF model mice reduced AF inducibility and duration, partly ascribed to decreased atrial inflammation and structural remodeling. Mechanistically, these effects were achieved by reducing the recruitment of CD3+ T lymphocytes and F4/80+ macrophages, and suppressing the hyperactivation of ERK1/2 and AKT/mTOR signaling in atria of AF model mice. In conclusion, this study provides new evidence that antagonizing CXCR4 prevents the development of AF, and suggests that CXCL12/CXCR4 axis may be a potential therapeutic target for AF.
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http://dx.doi.org/10.1038/s41419-021-04109-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397768PMC
August 2021

A Security-Enhanced Image Communication Scheme Using Cellular Neural Network.

Entropy (Basel) 2021 Jul 31;23(8). Epub 2021 Jul 31.

Zhongshan Institute, University of Electronic Science and Technology of China, Zhongshan 528402, China.

In the current network and big data environment, the secure transmission of digital images is facing huge challenges. The use of some methodologies in artificial intelligence to enhance its security is extremely cutting-edge and also a development trend. To this end, this paper proposes a security-enhanced image communication scheme based on cellular neural network (CNN) under cryptanalysis. First, the complex characteristics of CNN are used to create pseudorandom sequences for image encryption. Then, a plain image is sequentially confused, permuted and diffused to get the cipher image by these CNN-based sequences. Based on cryptanalysis theory, a security-enhanced algorithm structure and relevant steps are detailed. Theoretical analysis and experimental results both demonstrate its safety performance. Moreover, the structure of image cipher can effectively resist various common attacks in cryptography. Therefore, the image communication scheme based on CNN proposed in this paper is a competitive security technology method.
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http://dx.doi.org/10.3390/e23081000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392563PMC
July 2021

A Visual Encoding Model Based on Contrastive Self-Supervised Learning for Human Brain Activity along the Ventral Visual Stream.

Brain Sci 2021 Jul 29;11(8). Epub 2021 Jul 29.

Henan Key Laboratory of Imaging and Intelligent Processing, PLA Strategic Support Force Information Engineering University, Zhengzhou 450001, China.

Visual encoding models are important computational models for understanding how information is processed along the visual stream. Many improved visual encoding models have been developed from the perspective of the model architecture and the learning objective, but these are limited to the supervised learning method. From the view of unsupervised learning mechanisms, this paper utilized a pre-trained neural network to construct a visual encoding model based on contrastive self-supervised learning for the ventral visual stream measured by functional magnetic resonance imaging (fMRI). We first extracted features using the ResNet50 model pre-trained in contrastive self-supervised learning (ResNet50-CSL model), trained a linear regression model for each voxel, and finally calculated the prediction accuracy of different voxels. Compared with the ResNet50 model pre-trained in a supervised classification task, the ResNet50-CSL model achieved an equal or even relatively better encoding performance in multiple visual cortical areas. Moreover, the ResNet50-CSL model performs hierarchical representation of input visual stimuli, which is similar to the human visual cortex in its hierarchical information processing. Our experimental results suggest that the encoding model based on contrastive self-supervised learning is a strong computational model to compete with supervised models, and contrastive self-supervised learning proves an effective learning method to extract human brain-like representations.
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http://dx.doi.org/10.3390/brainsci11081004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391143PMC
July 2021

P3-MSDA: Multi-Source Domain Adaptation Network for Dynamic Visual Target Detection.

Front Hum Neurosci 2021 9;15:685173. Epub 2021 Aug 9.

Henan Key Laboratory of Imaging and Intelligent Processing, Chinese People's Liberation Army (PLA) Strategic Support Force Information Engineering University, Zhengzhou, China.

Single-trial electroencephalogram detection has been widely applied in brain-computer interface (BCI) systems. Moreover, an individual generalized model is significant for applying the dynamic visual target detection BCI system in real life because of the time jitter of the detection latency, the dynamics and complexity of visual background. Hence, we developed an unsupervised multi-source domain adaptation network (P3-MSDA) for dynamic visual target detection. In this network, a P3 map-clustering method was proposed for source domain selection. The adversarial domain adaptation was conducted for domain alignment to eliminate individual differences, and prediction probabilities were ranked and returned to guide the input of target samples for imbalanced data classification. The results showed that individuals with a strong P3 map selected by the proposed P3 map-clustering method perform best on the source domain. Compared with existing schemes, the proposed P3-MSDA network achieved the highest classification accuracy and F1 score using five labeled individuals with a strong P3 map as the source domain. These findings can have a significant meaning in building an individual generalized model for dynamic visual target detection.
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http://dx.doi.org/10.3389/fnhum.2021.685173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381600PMC
August 2021

Design, synthesis and anti-fibrosis evaluation of imidazo[1,2-a]pyridine derivatives as potent ATX inhibitors.

Bioorg Med Chem 2021 Aug 13;46:116362. Epub 2021 Aug 13.

Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address:

A series of imidazo[1,2-a]pyridine compounds bearing urea moiety (8-27) were designed, synthesized and evaluated for their ATX inhibitory activities in vitro by FS-3 based enzymatic assay. Delightfully, benzylamine derivatives (14-27) exhibited higher ATX inhibitory potency with IC value ranging from 1.72 to 497 nM superior to benzamide analogues (8-13). Remarkably, benzylamine derivative 20 bearing 4-hydroxypiperidine exerted an amazing inhibitory activity (IC = 1.72 nM) which exceeded the positive control GLPG1690 (IC = 2.90 nM). Simultaneously, the binding model of 20 with ATX was established which rationalized the well performance of 20 in enzymatic assay. Accordingly, further in vivo studies were carried out to evaluate direct anti-fibrotic effects of 20 through Masson staining. Notably, 20 effectively alleviated lung structural damage with fewer fibrotic lesions at an oral dose of 60 mg/kg, qualifying 20 as a promising ATX inhibitor for IPF treatment.
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http://dx.doi.org/10.1016/j.bmc.2021.116362DOI Listing
August 2021

Boraiminolithium: An Iminoborane-Transfer Reagent.

J Am Chem Soc 2021 Sep 24;143(34):13483-13488. Epub 2021 Aug 24.

School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, People's Republic of China.

BN/CC isosterism can give rise to attractive molecules with unique physical or chemical properties. We report here the synthesis, characterization, and reactivities of the boraiminolithium species , a room-temperature-stable crystalline solid accessible through a facile dehydrohalogenation/deprotonation reaction. This species, bearing a polarized B≡N triple bond and an anionic N center, is the first example of a BN analogue to the well-known alkynyllithium molecules (lithium acetylides). It has demonstrated a remarkable ability for iminoborane-transfer reactions, which allows for the isolation of a series of unprecedented N-functionalized iminoboranes as well as novel main-group heterocycles. Stable boraiminolithium reagents may become powerful tools in the exploration of new BN-containing building blocks for synthetic chemistry and materials science.
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http://dx.doi.org/10.1021/jacs.1c06152DOI Listing
September 2021

Dissociable Neural Representations of Adversarially Perturbed Images in Convolutional Neural Networks and the Human Brain.

Front Neuroinform 2021 5;15:677925. Epub 2021 Aug 5.

Henan Key Laboratory of Imaging and Intelligent Processing, PLA Strategic Support Force Information Engineering University, Zhengzhou, China.

Despite the remarkable similarities between convolutional neural networks (CNN) and the human brain, CNNs still fall behind humans in many visual tasks, indicating that there still exist considerable differences between the two systems. Here, we leverage adversarial noise (AN) and adversarial interference (AI) images to quantify the consistency between neural representations and perceptual outcomes in the two systems. Humans can successfully recognize AI images as the same categories as their corresponding regular images but perceive AN images as meaningless noise. In contrast, CNNs can recognize AN images similar as corresponding regular images but classify AI images into wrong categories with surprisingly high confidence. We use functional magnetic resonance imaging to measure brain activity evoked by regular and adversarial images in the human brain, and compare it to the activity of artificial neurons in a prototypical CNN-AlexNet. In the human brain, we find that the representational similarity between regular and adversarial images largely echoes their perceptual similarity in all early visual areas. In AlexNet, however, the neural representations of adversarial images are inconsistent with network outputs in all intermediate processing layers, providing no neural foundations for the similarities at the perceptual level. Furthermore, we show that voxel-encoding models trained on regular images can successfully generalize to the neural responses to AI images but not AN images. These remarkable differences between the human brain and AlexNet in representation-perception association suggest that future CNNs should emulate both behavior and the internal neural presentations of the human brain.
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http://dx.doi.org/10.3389/fninf.2021.677925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375771PMC
August 2021

Efficacy and Safety of Ciprofol Sedation in ICU Patients with Mechanical Ventilation: A Clinical Trial Study Protocol.

Adv Ther 2021 Aug 21. Epub 2021 Aug 21.

Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Rd, Guangzhou, 510080, Guangdong, China.

Introduction: From previous studies of pharmacodynamic data in mice, rats, beagle dogs and mini pigs, frequently in direct comparison to induction doses of propofol, ciprofol produced a rapid onset of anesthesia/sedation.

Methods: A phase 1 study suggested potential clinical advantages of ciprofol as a sedation/anesthetic agent, with no evidence of drug-related toxicity. However, the sedation effects and safety of ciprofol in intensive care unit (ICU) patients with mechanical ventilation should be further confirmed in a phase 3 study with a larger cohort of patients. During a phase 3, non-inferiority, multicenter, single-blind, randomized, propofol controlled trial, Chinese ICU patients undergoing mechanical ventilation and requiring endotracheal intubation will be sedated for 6-24 h after randomization. Considering a success rate for ICU sedation of 99% for ciprofol and the positive control drug propofol, a total sample size of 120 subjects with mechanical ventilation will be required to achieve 80% power to determine non-inferiority with a margin of 8%. Finally, taking into account 10% losses, 135 patients will be enrolled and randomly assigned to ciprofol (90 cases) and propofol (45 cases) groups in a 2:1 ratio. The primary outcome will be the success rate of sedation satisfied by the following conditions: the time within the range of Richmond Agitation and Sedation Score (+ 1 ~ - 2) must account for ≥ 70% of the study drug administration time and without other rescue treatments. Secondary outcomes will include the average time to reach the sedation goal, study drug usage, rescue medication given per unit weight, extubation time, recovery time to full consciousness and nursing scores. Safety endpoints will include adverse events (AEs), drug related AEs and serious AEs.

Planned Outcomes: The results of this study will provide crucial information on the use of ciprofol for sedation of patients in ICUs.

Trial Registration: ClinicalTrials.gov identifier, NCT04620031.
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http://dx.doi.org/10.1007/s12325-021-01877-6DOI Listing
August 2021

Safety of Receiving Anti-Vascular Endothelial Growth Factor Intravitreal Injection in Office-Based vs Operating Room Settings: A Meta-analysis.

JAMA Ophthalmol 2021 Aug 19. Epub 2021 Aug 19.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Importance: Compared with the operating room (OR), office-based intravitreal injection (IVI) is considered a more cost-effective and convenient approach, yet clinical outcomes of IVIs with anti-vascular endothelial growth factor (VEGF) agents in different settings (office-based vs OR) have not been systematically evaluated.

Objective: To evaluate the safety outcomes of IVI with anti-VEGF agents in the OR vs office-based setting.

Data Sources: PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from inception to July 2020.

Study Selection: Eligible studies reporting on patients who received IVIs with anti-VEGF drugs with a clearly stated injection setting of the office or OR.

Data Extraction And Synthesis: Two reviewers independently screened studies, extracted data, and assessed risk of bias. A meta-analysis was conducted to determine the rates of endophthalmitis (EO) and culture-positive EO.

Main Outcomes And Measures: Rates of EO and culture-positive EO following anti-VEGF IVIs in the OR and office-based setting.

Results: Thirty-one studies with a total of 1 275 815 injections were included. Comparative analysis suggested no difference between rates of EO after IVIs performed in the office and OR settings (odds ratio, 3.06; 95% CI, 0.07-139.75; P = .57; I2 = 80%) were identified, yet a higher rate of culture-positive EO was found in the office setting (odds ratio, 21.52; 95% CI, 2.39-193.55; P = .006; I2 = 0%). The pooled rates of EO following anti-VEGF IVIs were 0.03% (95% CI, 0.03-0.04) and 0.02% (95% CI, 0.01-0.04) in office and OR settings, respectively, and the pooled rates of culture-positive EO were 0.01% (95% CI, 0.01-0.02) and 0.01% (95% CI, 0-0.02). The pooled rates of other ocular and systemic adverse events were low.

Conclusions And Relevance: The rate of clinically suspected or culture-positive EO following anti-VEGF IVIs was low whether the procedure was performed in the office or OR setting. Bacterial spectrum could differ between the 2 settings. This meta-analysis could not determine if it is more appropriate to give treatment in the OR for safety reasons in low-income compared with higher-income regions in the world.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.3096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377608PMC
August 2021
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