Publications by authors named "Xian He"

45 Publications

Reversible Dendritic-Crystal-Reinforced Polymer Gel for Bioinspired Adaptable Adhesive.

Adv Mater 2021 Aug 21:e2103174. Epub 2021 Aug 21.

School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.

High-strength and reversible adhesion technology, which is a universal phenomenon in nature but remains challenging for artificial synthesis, is essential for the development of modern science. Existing adhesive designs without interface versatility hinder their application to arbitrary surfaces. Bioinspired by creeper suckers, a crystal-fiber reinforced polymer gel adhesive with ultrastrong adhesion strength and universal interface adaptability is creatively prepared via introducing a room-temperature crystallizable solvent into the polymer network. The gel adhesive formed by hydrogen bonding interaction between crystal fibers and polymer network can successfully realize over 9.82 MPa reversible adhesion strength for rough interface and 406.87 J m peeling toughness for skin tissue. In situ anchoring is achieved for adapting to different geometrical surfaces. The adhesion performance can be significantly improved with the further increase of the interfacial roughness and hydrophilicity, whose dissipation mechanism is simulated by finite element analysis. The melting-crystallization equilibrium of the crystal fibers is proved by synchrotron radiation scattering. Accordingly, reversible phase-transition triggered by light and heat can realize the controlled adhere-detach recycle. Later adjustments to the monomers or crystals are expected to broaden its applications to various fields such as bioelectronics, electronic processing, and machine handling.
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http://dx.doi.org/10.1002/adma.202103174DOI Listing
August 2021

Effect of root surface charge on the absorption and accumulation of Cu(II) by different japonica and indica rice varieties under acidic conditions.

Ecotoxicol Environ Saf 2021 Oct 27;223:112547. Epub 2021 Jul 27.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, P.O. Box 821, Nanjing, China; College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Excessive amounts of copper (Cu) in soils causes toxic effects on plants. In this study, 58 rice cultivars were classified into tolerant, moderately tolerant, and susceptible types for Cu(II) toxicity based on 50% germination (LC). Nine japonica rice varieties (three each from the tolerant, moderately tolerant, and susceptible groups) and six indica rice varieties (three from the moderately tolerant and susceptible groups) were selected for the hydroponics experiments. In the short-term adsorption experiment, Cu(II) adsorbed on rice roots was differentiated into exchangeable, complexed, and precipitated forms. Similarly, it was done for long-term culture. Absorption of Cu(II) by rice roots and shoots was also measured. The results indicated that adsorbed Cu(II) mainly existed as complexed and exchangeable forms on rice roots in the short-term adsorption experiment, and the exchangeable and complexed Cu(II) levels were greater for indica rice than for japonica rice due to the larger negative charge on the indica rice roots. The adsorbed Cu(II) mainly existed as a complexed form in the long-term culture experiment, and the exchangeable Cu(II) level was much lower than that in the short-term adsorption experiment due to the absorption of Cu(II) by rice plants. The indica varieties absorbed more Cu(II) than the japonica varieties. Furthermore, the absorption and accumulation of Cu(II) by the susceptible varieties were greater than by the tolerant and moderately tolerant varieties for both the japonica and indica rice. The absorption and accumulation of Cu(II) in rice roots were much greater than in the shoots. Chlorophyll content, and the lengths and dry matter weights of the rice roots and shoots decreased with increasing Cu(II) concentration. The Cu(II) showed greater toxicity toward indica varieties than japonica varieties, and the greater negative charge on indica roots was one of reasons for the greater exchangeable Cu(II) on the roots, the increase in Cu(II) toxicity, and the higher uptake of Cu(II) by indica rice varieties compared to japonica rice varieties.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112547DOI Listing
October 2021

Immune-Related lncRNA Signature for Predicting the Immune Landscape of Head and Neck Squamous Cell Carcinoma.

Front Mol Biosci 2021 13;8:689224. Epub 2021 Jul 13.

Department of Otorhinolaryngology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China.

Long non-coding RNA (lncRNA) plays a significant role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). This article aims to develop an immune-related lncRNA (irlncRNA) model, regardless of expression levels, for risk assessment and prognosis prediction in HNSCC patients. We obtained clinical data and corresponding full transcriptome expression of HNSCC patients from TCGA, downloaded GTF files to distinguish lncRNAs from Ensembl, discerned irlncRNAs based on co-expression analysis, distinguished differentially expressed irlncRNAs (DEirlncRNAs), and paired these DEirlncRNAs. Univariate Cox regression analysis, LASSO regression analysis, and stepwise multivariate Cox regression analysis were then performed to screen lncRNA pairs, calculate the risk coefficient, and establish a prognosis model. Finally, the predictive power of this model was validated through the AUC and the ROC curves, and the AIC values of each point on the five-year ROC curve were calculated to select the maximum inflection point, which was applied as a cut-off point to divide patients into low- or high-risk groups. Based on this methodology, we were able to more effectively differentiate between these groups in terms of survival, clinico-pathological characteristics, tumor immune infiltrating status, chemotherapeutics sensitivity, and immunosuppressive molecules. A 13-irlncRNA-pair signature was built, and the ROC analysis demonstrated high sensitivity and specificity of this signature for survival prediction. The Kaplan-Meier analysis indicated that the high-risk group had a significantly shorter survival rate than the low-risk group, and the chi-squared test certified that the signature was highly related to survival status, clinical stage, T stage, and N stage. Additionally, the signature was further proven to be an independent prognostic risk factor the Cox regression analyses, and immune infiltrating analyses showed that the high-risk group had significant negative relationships with various immune infiltrations. Finally, the chemotherapeutics sensitivity and the expression level of molecular markers were also significantly different between high- and low-risk groups. The signature established by paring irlncRNAs, with regard to specific expression levels, can be utilized for survival prediction and to guide clinical therapy in HNSCC.
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http://dx.doi.org/10.3389/fmolb.2021.689224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313825PMC
July 2021

Comparing ameliorative effects of biomass ash and alkaline slag on an acidic Ultisol under artificial Masson pine: A field experiment.

J Environ Manage 2021 Nov 16;297:113306. Epub 2021 Jul 16.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, P.O. Box 821, Nanjing, 210008, PR China.

Forest soil acidification caused by acid deposition is a serious threat to the forest ecosystem. To investigate the liming effects of biomass ash (BA) and alkaline slag (AS) on the acidic topsoil and subsoil, a three-year field experiment under artificial Masson pine was conducted at Langxi, Anhui province in Southern China. The surface application of BA and AS significantly increased the soil pH, and thus decreased exchangeable acidity and active Al in the topsoil. Soil exchangeable Ca and Mg in topsoil were significantly increased by the surface application of BA and AS, while an increase in soil exchangeable K was only observed in BA treatments. The soil acidity and active Al in subsoil were decreased by the surface application of AS. Compared with the control, soluble monomeric and exchangeable Al in the subsoil was decreased by 38.0% and 29.4% after 3 years of AS surface application. There was a minimal effect on soluble monomeric and exchangeable Al after the application of BA. The soil exchangeable Ca and Mg in the subsoil increased respectively by 54% and 141% after surface application of 10 t ha AS. The decrease of soil active Al and increase of base cations in subsoil were mainly attributed to the high migration capacity of base cations in AS. In conclusion, the effect of surface application of AS was superior to BA in ameliorating soil acidity and alleviating soil Al toxicity in the subsoil of this Ultisol.
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http://dx.doi.org/10.1016/j.jenvman.2021.113306DOI Listing
November 2021

Development and assessment of the efficacy and safety of human lung-targeting liposomal methylprednisolone crosslinked with nanobody.

Drug Deliv 2021 Dec;28(1):1419-1431

Department of Respiratory Medicine, School of Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.

Glucocorticoid (GC) hormone has been commonly used to treat systemic inflammation and immune disorders. However, the side effects associated with long-term use of high-dose GC hormone limit its clinical application seriously. GC hormone that can specifically target the lung might decrease the effective dosage and thus reduce GC-associated side effects. In this study, we successfully prepared human lung-targeting liposomal methylprednisolone crosslinked with nanobody (MPS-NSSLs-SPANb). Our findings indicate that MPS-NSSLs-SPANb may reduce the effective therapeutic dosage of MPS, achieve better efficacy, and reduce GC-associated side effects. In addition, MPS-NSSLs-SPANb showed higher efficacy and lower toxicity than conventional MPS.
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http://dx.doi.org/10.1080/10717544.2021.1921073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259875PMC
December 2021

NLRP3 ablation enhances tolerance in heat stroke pathology by inhibiting IL-1β-mediated neuroinflammation.

J Neuroinflammation 2021 Jun 6;18(1):128. Epub 2021 Jun 6.

Department of Lung Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Southern University of Science and Technology, No.29 Bulan Road, Longgang District, Shenzhen, 518055, China.

Background: Patients with prior illness are more vulnerable to heat stroke-induced injury, but the underlying mechanism is unknown. Recent studies suggested that NLRP3 inflammasome played an important role in the pathophysiology of heat stroke.

Methods: In this study, we used a classic animal heat stroke model. Prior infection was mimicked by using lipopolysaccharide (LPS) or lipoteichoic acid (LTA) injection before heat stroke (LPS/LTA 1 mg/kg). Mice survival analysis curve and core temperature (T) elevation curve were produced. NLRP3 inflammasome activation was measured by using real-time PCR and Western blot. Mice hypothalamus was dissected and neuroinflammation level was measured. To further demonstrate the role of NLRP3 inflammasome, Nlrp3 knockout mice were used. In addition, IL-1β neutralizing antibody was injected to test potential therapeutic effect on heat stroke.

Results: Prior infection simulated by LPS/LTA injection resulted in latent inflammation status presented by high levels of cytokines in peripheral serum. However, LPS/LTA failed to cause any change in animal survival rate or body temperature. In the absence of LPS/LTA, heat treatment induced heat stroke and animal death without significant systemic or neuroinflammation. Despite a decreased level of IL-1β in hypothalamus, Nlrp3 knockout mice demonstrated no survival advantage under mere heat exposure. In animals with prior infection, their heat tolerance was severely impaired and NLRP3 inflammasome induced neuroinflammation was detected. The use of Nlrp3 knockout mice enhanced heat tolerance and alleviated heat stroke-induced death by reducing mice hypothalamus IL-1β production with prior infection condition. Furthermore, IL-1β neutralizing antibody injection significantly extended endotoxemic mice survival under heat stroke.

Conclusions: Based on the above results, NLRP3/IL-1β induced neuroinflammation might be an important mechanistic factor in heat stroke pathology, especially with prior infection. IL-1β may serve as a biomarker for heat stroke severity and potential therapeutic method.
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http://dx.doi.org/10.1186/s12974-021-02179-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182902PMC
June 2021

[Anti-inflammatory target prediction of Gentianae Radix et Rhizoma based on network pharmacology and construction of a bioassay method for its quality control].

Zhongguo Zhong Yao Za Zhi 2021 May;46(10):2556-2564

China Military Institute of Chinese Medicine, Fifth Medical Center, Chinese PLA General Hospital Beijing 100039, China Department of Poisoning Treatment, Fifth Medical Center, Chinese PLA General Hospital Beijing 100071, China.

Based on the heat-clearing and detoxifying effects of Gentianae Radix et Rhizoma, the network pharmacology is mainly used to predict the potential targets of Gentianae Radix et Rhizoma for anti-inflammatory activity and to perform the experimental verification. A method for detecting the biological potency of Gentianae Radix et Rhizoma based on verifiable targets has been established to provide a reference for improving the quality evaluation and control standards of Gentianae Radix et Rhizoma. High performance liquid chromatography can be used to construct chemical fingerprints of different batches of Gentianae Radix et Rhizoma. Constructing a component-target-disease network of Gentianae Radix et Rhizoma for its anti-inflammatory activity was applied to screen potential anti-inflammatory components and related targets of Gentianae Radix et Rhizoma, and to verify the target of Gentianae Radix et Rhizoma by using biological evaluation methods. Detecting the biological potency of different batches of Gentianae Radix et Rhizoma extracts was used to inhibit COX-2 enzyme activity based the verifiable target cyclooxygenase-2(COX-2). The results showed that different batches of Gentianae Radix et Rhizoma accorded with the pharmacopoeia testing regulations, and the chemical fingerprints have a high similarity(similarity>0.93), suggesting that there is no significant difference in the characteristics of the chemical components. Based on network pharmacology predictions, 18 candidate targets were found to have potential direct interactions with the ingredients in Gentianae Radix et Rhizoma. Among them, the most important target is COX-2. Based on the experimental verification of recombinant human COX-2 protease activity inhibition, Gentianae Radix et Rhizoma can inhibit the COX-2 enzyme activity in a dose-dependent manner. It can function with a low concentration(0.75 mg·mL~(-1)), which preliminarily confirmed the accuracy of network pharmacology prediction. The biological potency detection method of Gentianae Radix et Rhizoma based on COX-2 inhibitory activity was optimized and established. The qualitative response parallel line method was used to calculate the biological potency of anti-inflammatory activity, which ranged from 23.04 to 46.60 U·mg~(-1). For network pharmacology prediction, it can screen and clarify the possible targets of traditional Chinese medicine rapidly, which can guide the establishment of a biological evaluation method for the quality of medicinal materials with related activities. Compared with chemical fingerprints, the biological potency testing can better detect quality fluctuations of traditional Chinese medicine.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201014.201DOI Listing
May 2021

Enhancement of Cd(II) adsorption by rice straw biochar through oxidant and acid modifications.

Environ Sci Pollut Res Int 2021 Aug 6;28(31):42787-42797. Epub 2021 Apr 6.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, P.O. Box 821, Nanjing, China.

To develop high-efficient biochar adsorbents, the effects and mechanisms of oxidant modification and acid modification on Cd(II) adsorption by rice straw biochar were investigated. Three rice straws from Langxi in Anhui Province, Yingtan in Jiangxi Province, and Lianyungang in Jiangsu Province were collected to prepare biochars by anaerobic pyrolysis in a muffle furnace. Rice straw biochars were modified by 15% HO and 1:1 HNO/HSO mixed acid, respectively, to obtain modified biochars. The untreated rice straw biochar and HCl-treated rice straw biochar with carbonate removed were used as controls. The functional groups on the surfaces of the biochars were qualitatively and quantitatively determined by Fourier transform infrared spectra and Boehm titration, respectively. The adsorption and desorption of Cd(II) onto and from the biochars and modified biochars were measured under various pH conditions. The results showed that oxidant modification with 15% HO and acid modification with 1:1 HNO/HSO significantly increased the number of carboxyl functional groups on the surfaces of the biochars, and acid modification was more effective than oxidant modification in amplifying carboxyl functional groups on the surfaces of the biochars. The increase of surface functional groups effectively enhanced the specific adsorption of Cd(II) on the modified biochars. Therefore, both oxidant modification and acid modification enhanced the adsorption of Cd(II) on the biochars through increasing functional groups on the surfaces of the biochars.
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http://dx.doi.org/10.1007/s11356-021-13742-8DOI Listing
August 2021

Application of measuring electrochemical characteristics on plant root surfaces in screening Al-tolerant wheat.

Environ Pollut 2021 Jul 23;281:116993. Epub 2021 Mar 23.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing, 210008, China; College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

To explore the relationship between Al phytotoxicity and the electrochemical characteristics of wheat root surfaces, a new chemical mechanism for tolerance of wheat to Al toxicity was initially proposed by conducting acute root elongation experiment, adsorption/desorption experiment, streaming potential determination, and infrared spectroscopy (ATR-FTIR) analysis respectively to classify the grade of Al tolerance of 92 wheat cultivars and quantitatively characterize the electrochemical properties of their root surfaces. Then a pot experiment was conducted with the screened wheat cultivars with different Al resistance grown on acid soils to verify their tolerance to Al toxicity. Results show that zeta potentials of the roots of 67 wheat cultivars at pH4.46 were significantly negatively correlated with Al(Ⅲ) adsorbed on the roots and their relative root elongation (P < 0.05), indicating that wheat roots with less negative charges is more tolerant to Al toxicity. Based on the mechanism, 14 Al-tolerant, 23 medium Al-tolerant and 30 Al-sensitive wheat cultivars were classified. The pot experiment reveals that the relative dry weight of Al-tolerant wheat cultivars was generally greater than that of medium Al-tolerant and Al-sensitive wheat cultivars and Al-tolerant wheat cultivars accumulate less Al in their shoots, which further verifies the relationship among charge characteristics, tolerance of wheat to Al toxicity, and Al uptake by wheat. The negative charges derived from organic functional groups on root surfaces could influence the exchangeable and complexed Al(Ⅲ) adsorbed on wheat roots and thereby affect Al tolerance of wheat cultivars. This finding not only provides a new perspective to screen Al-tolerant wheat cultivars and explain the mechanism of tolerance of wheat to Al toxicity, but is also useful for the prediction of differences in the uptake of Al in the shoots between Al-tolerant and Al-sensitive wheat cultivars, and finally contributes to the prevention of food security risk caused by Al in acid soils.
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http://dx.doi.org/10.1016/j.envpol.2021.116993DOI Listing
July 2021

Metabolomic Signatures of Autoimmune Hepatitis in the Development of Cirrhosis.

Front Med (Lausanne) 2021 12;8:644376. Epub 2021 Mar 12.

Department of Liver Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

Autoimmune hepatitis (AIH) can progress into severe outcomes, i.e., decompensated cirrhosis, from remarkable and persistent inflammation in the liver. Considering the energy-expending nature of inflammation, we tried to define the metabolomics signatures of AIH to uncover the underlying mechanisms of cirrhosis development and its metabolic biomarkers. Untargeted metabolomics analysis was performed on sera samples from 79 AIH patients at the stages (phenotypes) of non-cirrhosis ( = 27), compensated cirrhosis ( = 22), and decompensated cirrhosis ( = 30). Pattern recognition was used to find unique metabolite fingerprints of cirrhosis with or without decompensation. Out of the 294 annotated metabolites identified, 2 metabolic fingerprints were found associated with the development of cirrhosis (independent of the decompensated state, 42 metabolites) and the evolution of decompensated cirrhosis (out of 47 metabolites), respectively. The cirrhosis-associated fingerprints (eigenmetabolite) showed better capability to differentiate cirrhosis from non-cirrhosis patients than the aminotransferase-to-platelet ratio index. From the metabolic fingerprints, we found two pairs of metabolites (Mesobilirubinogen/6-Hydroxynicotinic acid and LysoPA(8:0/0:0)/7alpha-Hydroxycholesterol) calculated as ratio of intensities, which revealed robust abilities to identify cirrhosis or predict decompensated patients, respectively. These phenotype-related fingerprint metabolites featured fundamental energy supply disturbance along with the development of AIH cirrhosis and progression to decompensation, which was characterized as increased lipolysis, enhanced proteolysis, and increased glycolysis. Remodeling of metabolism to meet the liver inflammation-related energy supply is one of the key signatures of AIH in the development of cirrhosis and decompensation. Therefore, drug regulation metabolism has great potential in the treatment of AIH.
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http://dx.doi.org/10.3389/fmed.2021.644376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994277PMC
March 2021

The effect of flue-curing procedure on the dynamic change of microbial diversity of tobaccos.

Sci Rep 2021 Mar 8;11(1):5354. Epub 2021 Mar 8.

Yunnan Academy of Tobacco Agricultural Sciences, Kunming, 650021, Yunnan, China.

The purpose of the study is to explore the effect of flue-curing procedure on the diversity of microbial communities in tobaccos and the dynamic change of compositions of microbial communities in the flue-curing process. It expects to provide a theoretical basis for the application of microbes in tobacco leaves and a theoretical basis and idea for optimization of the flue-curing technologies. By investigating tobacco variety K326, the tests were carried out for comparing the conventional flue-curing procedure and dry-ball temperature set and wet-ball temperature degradation flue-curing procedure. Based on the culture-independent approach and high-throughput sequencing procedure, the relationship between the flue-curing procedure for tobaccos and microbial communities in tobaccos was revealed by measuring the dynamic change of microbial communities. The results indicated that:(1) Relative to surface wiping method, washing method was more suitable for the sampling of microbes on the surface of tobacco leaves; (2) Dry-ball temperature set and wet-ball temperature degradation flue-curing procedure was more favorable for maintaining the microbial diversity of tobaccos; (3) Relative to bacteria of the tobaccos, the succession rule of the fungal communities in tobaccos was relatively steady; (4)Compared with bacterial community diversity, the fungal community diversity presented an obvious negative correlation with temperature and humidity during the flue-curing process. (5) The function of bacterial communities in tobaccos matched with the material transformation law of tobaccos, having a direct correlation on the flue-curing process. In short, Dry-ball temperature set and wet-ball temperature degradation flue-curing procedure can more favorably maintain the microbial diversity of tobaccos; moreover, the function of the tobacco system involved in microbes in tobaccos was closely related to the material transformation law of tobaccos in the flue-curing process. It validated that the bacteria in tobaccos play an important role in the flue-curing process of tobaccos.
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http://dx.doi.org/10.1038/s41598-021-84875-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940495PMC
March 2021

Cold stress in the harvest period: effects on tobacco leaf quality and curing characteristics.

BMC Plant Biol 2021 Mar 8;21(1):131. Epub 2021 Mar 8.

Yunnan Academy of Tobacco Agricultural Sciences, Kunming, Yunnan, People's Republic of China.

Background: Weather change in high-altitude areas subjects mature tobacco (Nicotiana tabacum L.) to cold stress, which damages tobacco leaf yield and quality. A brupt diurnal temperature differences (the daily temperature dropping more than 20 °C) along with rainfall in tobacco-growing areas at an altitude above 2450 m, caused cold stress to field-grown tobacco.

Results: After the flue-cured tobacco suffered cold stress in the field, the surface color of tobacco leaves changed and obvious large browning areas were appeared, and the curing availability was extremely poor. Further research found the quality of fresh tobacco leaves, the content of key chemical components, and the production quality were greatly reduced by cold stress. We hypothesize that cold stress in high altitude environments destroyed the antioxidant enzyme system of mature flue-cured tobacco. Therefore, the quality of fresh tobacco leaves, the content of key chemical components, and the production quality were greatly reduced by cold stress.

Conclusion: This study confirmed that cold stress in high-altitude tobacco areas was the main reason for the browning of tobacco leaves during the tobacco curing process. This adverse environment seriously damaged the quality of tobacco leaves, but can be mitigated by pay attention to the weather forecast and pick tobacco leaves in advance.
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http://dx.doi.org/10.1186/s12870-021-02895-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941949PMC
March 2021

Fine tuning the glycolytic flux ratio of EP-bifido pathway for mevalonate production by enhancing glucose-6-phosphate dehydrogenase (Zwf) and CRISPRi suppressing 6-phosphofructose kinase (PfkA) in Escherichia coli.

Microb Cell Fact 2021 Feb 2;20(1):32. Epub 2021 Feb 2.

National Glycoengineering Research Center, State Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Dadao, Qingdao, 266237, People's Republic of China.

Background: Natural glycolysis encounters the decarboxylation of glucose partial oxidation product pyruvate into acetyl-CoA, where one-third of the carbon is lost at CO. We previously constructed a carbon saving pathway, EP-bifido pathway by combining Embden-Meyerhof-Parnas Pathway, Pentose Phosphate Pathway and "bifid shunt", to generate high yield acetyl-CoA from glucose. However, the carbon conversion rate and reducing power of this pathway was not optimal, the flux ratio of EMP pathway and pentose phosphate pathway (PPP) needs to be precisely and dynamically adjusted to improve the production of mevalonate (MVA).

Result: Here, we finely tuned the glycolytic flux ratio in two ways. First, we enhanced PPP flux for NADPH supply by replacing the promoter of zwf on the genome with a set of different strength promoters. Compared with the previous EP-bifido strains, the zwf-modified strains showed obvious differences in NADPH, NADH, and ATP synthesis levels. Among them, strain BP10BF accumulated 11.2 g/L of MVA after 72 h of fermentation and the molar conversion rate from glucose reached 62.2%. Second, pfkA was finely down-regulated by the clustered regularly interspaced short palindromic repeats interference (CRISPRi) system. The MVA yield of the regulated strain BiB1F was 8.53 g/L, and the conversion rate from glucose reached 68.7%.

Conclusion: This is the highest MVA conversion rate reported in shaken flask fermentation. The CRISPRi and promoter fine-tuning provided an effective strategy for metabolic flux redistribution in many metabolic pathways and promotes the chemicals production.
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http://dx.doi.org/10.1186/s12934-021-01526-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852082PMC
February 2021

Pan-cancer population pharmacokinetics and exposure-safety and -efficacy analyses of atezolizumab in patients with high tumor mutational burden.

Pharmacol Res Perspect 2020 12;8(6):e00685

Clinical Pharmacology, Genentech-Roche, Marseille, France.

We retrospectively investigated the pharmacokinetics and exposure-efficacy/safety relationships of single-agent atezolizumab based on tissue tumor mutational burden (tTMB) status (high vs low [≥16 vs <16 mutations/megabase]) in a pan-tumor population from seven clinical trials. Data sources included the OAK, POPLAR, BIRCH, FIR, IMvigor210, IMvigor211, and PCD4989g studies; 986 of 2894 treated patients (34%) had TMB data. Exposure metrics were obtained using a prior two-compartment intravenous-infusion population-pharmacokinetics model, merged with prognostic, biomarker, efficacy, and safety variables. Baseline demographic/clinical characteristics and prognostic factors were well balanced between patients with high (n = 175) and low (n = 811) tTMB. Exposure was similar in the high- and low-tTMB subgroups, with no difference seen in the evaluable vs total treated populations. The objective response rate (ORR) was 29.7% vs 13.4%, complete response rate was 6.9% vs 3.2%, and median duration of response (95% CI) was 29.0 (18.6-NE) months vs 15.9 (12.5-20.5) months for patients with high-tTMB vs low-tTMB tumors, respectively. A flat exposure-efficacy relationship was seen for ORR in patients with high-tTMB based on the cycle 1 minimum atezolizumab concentration and area under the serum concentration time curve (AUC). A nonsignificant exposure-safety profile was seen for grade 3/4 adverse events and adverse events of special interest based on the AUC of atezolizumab in the high-tTMB population. tTMB is an additional predictive biological factor affecting response to atezolizumab, and quantitative investigations of atezolizumab exposure and relationships of exposure with safety and efficacy support the use of a 1200-mg, every 3-week regimen in a tumor-agnostic high-tTMB population.
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http://dx.doi.org/10.1002/prp2.685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689240PMC
December 2020

Salicylic Acid Effects on Flue-Cured Tobacco Quality and Curing Characteristics During Harvesting and Curing in Cold-Stressed Fields.

Front Plant Sci 2020 30;11:580597. Epub 2020 Oct 30.

Yunnan Academy of Tobacco Agricultural Sciences, Kunming, China.

Salicylic acid (SA) can induce plants to actively enhance abiotic stress resistance. Spraying SA to prevent cold stress in flue-cured tobacco fields can provide theoretical support and practical guidance for the actual protection from cold stress in fields at high altitude in Yunnan. The experiment was performed in Jianchuan County Yunnan Province, China. Honghuadajinyuan, a flue-cured tobacco variety with cold resistance, was used as the research object. SA was tested at two concentrations (0.05 [SA-1] and 0.1 [SA-1] mol L) relative to an untreated control (Control) to compare the quality of fresh tobacco leaves, curing characteristics, enzyme activity of antioxidants, and quality of the first-cured tobacco leaves. The tissue structure thickness, SPAD, and plastid pigment content of fresh tobacco leaves were least in the control; there was no significant difference between SA-1 and SA-2. The change of moisture content during curing was SA-1 > SA-2 > Control, and the water loss rate was Control > SA-2 > SA-1, and both varied greatly at 38-48°C. In each curing stage, the carbon and nitrogen metabolites and polyphenols changed most rapidly at 38°C, and the sugar metabolites changed as follows: Control > SA-1 > SA-2. The activities of the antioxidant enzymes superoxide dismutase, peroxidase, and catalase in fresh tobacco leaves were SA-1 > SA-2 > Control. Malondialdehyde content and the inactivation rate of antioxidant enzymes during curing was Control > SA-2 > SA-1. The economic character and sensory smoking quality of flue-cured tobacco leaves were SA-1 > SA-2 > Control. In high-altitude tobacco planting areas prone to cold stress in the field, early warning weather forecast and field spraying 0.05 mol L SA are beneficial to protect and improve the quality of fresh tobacco leaves, curing characteristics, antioxidant system enzyme activities, and the quality of flue-cured tobacco leaves.
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http://dx.doi.org/10.3389/fpls.2020.580597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661750PMC
October 2020

Cereblon Promotes the Ubiquitination and Proteasomal Degradation of Interleukin Enhancer-Binding Factor 2.

Protein J 2020 10 3;39(5):411-421. Epub 2020 Oct 3.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, China.

Interleukin enhancer-binding factor 2 (ILF2) forms a heterodimer with interleukin enhancer-binding factor 3 (ILF3) via double-stranded RNA-binding motif and zinc finger associated domain and thus regulates gene expression and cancer cell growth. However, how ILF2 is degraded in cells remains elusive. In this work, using stable isotope labeling by amino acids in cell culture (SILAC) quantitative proteomics, we find that ILF2 is downregulated in cells expressing cereblon (CRBN). Using affinity purification and immunoblotting analysis, we demonstrate that CRBN interacts with ILF2 and functions as a substrate receptor of the cullin-4 RING E3 ligase complex. Biochemical experiments disclose that CRBN expression reduces ILF2 protein level and this reduction is diminished when the proteasome is inhibited. Upon protein synthesis inhibition, the degradation of ILF2 is enhanced by CRBN. Moreover, CRBN promotes the ubiquitination of ILF2 and thus results in the ubiquitin-mediated proteasomal degradation. Analyses of previously identified post-translational modification sites and the crystal structure of ILF2 discover the potential ubiquitination sites on ILF2. Through mutagenesis and biochemical experiments, we further reveal that the K45R mutation completely abolishes the effect of CRBN on ILF2, suggesting that this is the key residue responsible for its ubiquitination. Taken together, we identify an E3 ligase that regulates ILF2 and uncover a molecular pathway for its degradation. This work might be helpful to elucidate the molecular mechanism by which CRBN regulates diverse cellular functions.
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http://dx.doi.org/10.1007/s10930-020-09918-9DOI Listing
October 2020

An efficient genetic transformation system for Chinese medicine fungus Tolypocladium ophioglossoides.

J Microbiol Methods 2020 09 15;176:106032. Epub 2020 Aug 15.

Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Tolypocladium ophioglossoides is a rare and valuable fungus extensively used in Chinese medicine for relieving postmenopausal syndrome in women yet its bioactive molecules are unknown. To explore its molecular mechanisms, we have developed a reliable Agrobacterium-mediated transformation system using the selective marker: the chlorimuron ethyl-resistance gene sur. For this purpose, we firstly constructed a T-DNA binary vector system and then improved the transformation efficiency by optimizing conditional parameters including the Agrobacterium tumefaciens concentration, the conidia number of T. ophioglossoides, the co-culture time and the concentration of acetosyringone. Furthermore, we have knocked-out the ku70 gene,which is a key gene in non-homologous end joining (NHEJ) DNA repair pathway,and the effect of the length of the homologous arms (HA) on the genetic transformation efficacy was also examined, which increased by 60% when HA was about 3 kb in length. Our results suggest that the genetic transformation system is efficient and feasible for the truffle-parasite fungus T. ophioglossoides, which can further be used in large-scale experiments for characterization of genes of interest in future work.
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http://dx.doi.org/10.1016/j.mimet.2020.106032DOI Listing
September 2020

miR-96-5p Suppresses the Progression of Nasopharyngeal Carcinoma by Targeting CDK1.

Onco Targets Ther 2020 30;13:7467-7477. Epub 2020 Jul 30.

Department of Otolaryngology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646699, People's Republic of China.

Background: Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharyngeal mucosa. Clinically, radiotherapy is the preferred treatment for NPC, and cervical lymph node metastasis is easy to emerge in the early stage. Therefore, this study aimed to investigate the role and potential molecular mechanisms of miR-96-5p in NPC cells to develop new therapeutic horizons.

Methods: The expression of miR-96-5p and CDK1 was measured by RT-qPCR or Western blot. The target relationship between miR-96-5p and CDK1 was confirmed by luciferase reporter assay. CCK-8, sphere formation, flow cytometry and colony formation assay were employed to examine cell viability, stem-like property, apoptosis and cycle, respectively. Male BALB/c nude mice model (6-8 weeks, weigh 18-20 g) was used to evaluate the effect of miR-96-5p on tumor growth in vivo.

Results: miR-96-5p was lowly expressed and CDK1 was highly expressed in NPC tissues and cell lines. CDK1 was identified as a direct target of miR-96-5p, and its expression was negatively regulated by miR-96-5p. By targeting CDK1, miR-96-5p overexpression significantly inhibited tumor sphere formation, promoted apoptosis and cell cycle arrest in CNE-2Z cells. Importantly, CCK-8 and colony formation assay demonstrated that elevated miR-96-5p enhanced the radiotherapy and chemotherapy sensitivity of CNE-2Z cells. Animal experiments showed that the overexpression of miR-96-5p reduced tumor weight and size in tumor-bearing mice and inhibited the expression of stem-like marker proteins and apoptosis-related proteins.

Conclusion: These results, together, suggested that miR-96-5p induced cell cycle arrest and apoptosis, inhibited stem-like property, and enhanced the radiochemical sensitivity of NPC by targeting CDK1. In short, miR-96-5p may be a diagnostic and therapeutic target for NPC.
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http://dx.doi.org/10.2147/OTT.S248338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406360PMC
July 2020

Effects of crop straw biochars on aluminum species in soil solution as related with the growth and yield of canola (Brassica napus L.) in an acidic Ultisol under field condition.

Environ Sci Pollut Res Int 2020 Aug 25;27(24):30178-30189. Epub 2020 May 25.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, P.O. Box 821, Nanjing, China.

The toxicity of aluminum (Al) to plants in acidic soils depends on the Al species in soil solution. The effects of crop straw biochars on Al species in the soil solution, and canola growth and yield were investigated in this study. In a long-term field experiment, there were four treatments, which were a control, rice straw biochar (RSB), canola straw biochar (CSB), and peanut straw biochar (PSB). The soil solution was collected in situ, the Al species were identified, and the relationships between the concentration of phytotoxic Al and canola growth and yield were evaluated. The results showed that applying the three biochars resulted in significant decreases in the concentrations of total Al, monomeric Al, and monomeric inorganic Al (P < 0.05). The Al, Al-OH, and Al-SO proportions of the total Al also decreased. The abilities of the different biochars to reduce dissolved Al followed the order PSB > CSB > RSB, which was consistent with the alkalinity of these biochars. Application of the biochars significantly decreased the concentration of phytotoxic Al (Al + Al-OH), which improved canola growth and increased the canola seed and straw yields. Plant height, leaf number per plant, area per leaf, chlorophyll content, and canola yield were negatively correlated with the Al + Al-OH concentrations. Therefore, the results showed that crop straw biochars can be used to ameliorate soil acidity and alleviate Al toxicity in acidic soils, and that peanut straw biochar is the best amendment for acidic soils.
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http://dx.doi.org/10.1007/s11356-020-09330-xDOI Listing
August 2020

Variants in the 8q24 region associated with risk of breast cancer: Systematic research synopsis and meta-analysis.

Medicine (Baltimore) 2020 Feb;99(8):e19217

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China.

Breast cancer is a molecularly heterogeneous disorder associated with high lethal malignant tumors among women worldwide. Genetic factors play an important role in breast cancer development. Several single nucleotide polymorphisms in the 8q24 region associated with risk of breast cancer have been identified. Fifteen studies including 32,955 cases and 43,716 controls were collected to conduct a meta-analysis to evaluate the associations between variants in 8q24 region and risk of breast cancer. Our study showed that only rs13281615 is associated with breast cancer risk in this large-scale research synopsis and meta-analysis. Further studies are needed to explore the role of the 8q24 variants in the development of breast cancer.
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http://dx.doi.org/10.1097/MD.0000000000019217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034712PMC
February 2020

Dynamic changes in physiological and biochemical properties of flue-cured tobacco of different leaf ages during flue-curing and their effects on yield and quality.

BMC Plant Biol 2019 Dec 16;19(1):555. Epub 2019 Dec 16.

Yunnan Academy of Tobacco Agricultural Sciences, 33 Yuantong Street, Kunming, Yunnan, 650021, People's Republic of China.

Background: The leaf age for harvesting flue-cured tobacco leaves is closely related to the quality of tobacco leaves, so an appropriate leaf age for harvesting is important for improving yield and quality of flue-cured tobacco, however, at present, there are few studies on effects of leaf age on physiological and biochemical changes during flue-curing and there is no clear standard of proper leaf ages for harvesting in production.

Results: In the Yunnan tobacco-growing area, an experiment was carried from 2016 to 2017 and different leaf ages were set. The results demonstrate that leaf age has a significant on tissue cell gap, leaf age and flue-curing stages exert significant effects on upper epidermis, palisade and spongy tissue, and leaf thickness of tobacco leaves. The thicknesses of upper and lower epidermis as well as palisade and spongy tissues at different ages show an approximately W-shaped change trend during flue-curing. With the advance of flue-curing stages, contents of starch, chlorophyll, carotenoid, and water in tobacco leaves at different leaf ages decrease, while polyphenol and malondialdehyde (MDA) contents increase. The older the leaf, the faster the chlorophyll, carotenoid, and water contents reduce, while the faster the polyphenol and MDA content rise during flue-curing. The flue-cured tobacco leaves at 116 DAT (days after transplanting) show the highest contents of total nitrogen and nicotine, followed by 123 DAT and those at 130 DAT are the lowest; however, the contents of total sugar and reducing sugar demonstrate a contrary tendency, and the starch content at 116 DAT is much lower than those in the other two treatments. The proportion of superior tobacco, average price, yield, and output value of upper tobacco leaves at different leaf ages are the highest at 123 DAT. The highest sensory evaluation score is found at 123 DAT, while that at 130 DAT is significantly lower in comparison with the other two treatments.

Conclusions: Tobacco leaves harvested at 123 DAT are mature and exhibit a low degree of membrane lipid peroxidation, moderate chemical compositions, and high economic value. 123 DAT improves availability of tobacco leaves.
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http://dx.doi.org/10.1186/s12870-019-2143-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916008PMC
December 2019

Dual roles of hydrogen peroxide in promoting zebrafish renal repair and regeneration.

Biochem Biophys Res Commun 2019 08 24;516(3):680-685. Epub 2019 Jun 24.

Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China. Electronic address:

Acute renal injury (AKI) is a serious disorder of renal failure or renal damage that occurs within hours or days. At present, there is no approved pharmaceutical treatment for AKI. Zebrafish is an excellent model for studying the repair of AKI because of its remarkable ability to repair kidney injury. Using zebrafish AKI model inducing by gentamicin, we found that hydrogen peroxide (HO) plays dual roles during the period of AKI recovery including renal repair and kidney regeneration. In the repair stage of AKI, HO was produced in proximal and distal segments of renal tubules. By inhibiting HO generation using Duox Vivo-Morpholino or chemical inhibitor, it was observed of severe damage of renal tubules, and extensive cell apoptosis. In the stage of regeneration, we found that HO was highly generated in renal interstitium. Inhibiting production of HO could significantly down-regulate the ability of kidney regeneration, which was associated with the failure of proliferation of renal progenitor cells. Therefore, HO acts as a protective factor in renal repair and an initial signal of kidney regeneration, indicating the key roles of HO in promoting recovery of AKI in zebrafish.
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http://dx.doi.org/10.1016/j.bbrc.2019.06.052DOI Listing
August 2019

DNA damage-inducible transcript 4 is an innate guardian for human squamous cell carcinoma and an molecular vector for anti-carcinoma effect of 1,25(OH) D.

Exp Dermatol 2019 01 5;28(1):45-52. Epub 2018 Dec 5.

Department of Dermatology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Cutaneous squamous cell carcinoma (SCC) is one of the most common non-melanoma skin cancers worldwide. While its exact tumorigenesis mechanisms is far from well-established and less satisfied therapeutic strategy can be clinically used nowadays. In this study, we intended to investigate the role of DNA damage-inducible transcript 4 (DDIT4) in human SCC. Firstly, we identified DDIT4 is significantly suppressed in human SCC tissue and cultured A431 cell line, and reduced DDIT4 accelerates keratinocytes proliferation but impedes the autophagy flux through mTORC1 pathway by affecting the downstream S6 Kinase1, 4E-BP1, Beclin1 and LC3 II/I. While 1,25(OH) D enhanced DDIT4 expression and activated autophagy and inhibit mTORC1 to take the effect of anti-proliferation and activating autophagy. Further, formation of direct vitamin D receptor (VDR)-DDIT4 transcription complex was verified by ChIP-qPCR, which showed the molecular mechanism of how 1,25(OH) D promotes DDIT4 transcription. Thirdly, xenograft tumor-bearing mice model treated by gradient concentrations of 1,25(OH) D revealed the obvious anti-carcinoma effect of 1,25(OH) D in vivo and DDIT4 acted the molecular vector of 1,25(OH) D through mTORC1. Lastly, elevated DDIT4 expression was verified in human actinic keratoses tissue, and chronic long-term ultraviolet (UV) irradiation on mouse disclosed UV could promote DDIT4 expression inside epidermis. Conclusively, our research suggested a novel molecular mechanism about the human SCC tumorigenesis and the pharmacological mechanism about how 1,25(OH) D take its anti-carcinoma role on human SCC, as well as a striking paradoxes that how UV irradiation plays the tumorigenesis effect but synchronously take a protective role in the early stage of SCC carcinogenesis.
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http://dx.doi.org/10.1111/exd.13815DOI Listing
January 2019

Revelation of the Balanol Biosynthetic Pathway in Tolypocladium ophioglossoides.

Org Lett 2018 10 2;20(20):6323-6326. Epub 2018 Oct 2.

Institute of Pharmaceutical Biotechnology , Zhejiang University , Hangzhou 310058 , China.

A cryptic gene cluster, bln, was activated by genome mining in Tolypocladium ophioglossoides. This activation led to the production of balanol and eight other metabolites. Gene disruption and metabolite profile analysis showed that the biosynthesis of balanol involved the convergence of independent PKS and NRPS pathways, and a biosynthetic pathway for balanol was proposed.
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http://dx.doi.org/10.1021/acs.orglett.8b01543DOI Listing
October 2018

Treatment of verrucous carcinoma in penis with topical aminolevulinic acid photodynamic therapy: An effective and safe treatment method.

Photodiagnosis Photodyn Ther 2018 Dec 8;24:232-236. Epub 2018 Sep 8.

Department of Plastic & Cosmetic Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China. Electronic address:

Background: Verrucous carcinoma of the penis is a rare disease characterized by verrucous lesions. The traditional treatment methods for verrucous carcinoma result in loss of sexual function are not satisfactory. The purpose of this study was to evaluate the safety and effect of topical aminolevulinic acid photodynamic therapy in the treatment of verrucous carcinoma in penis.

Materials And Methods: In this study, four male patients, average age of (47 ± 7.58) years old, with penile verrucous carcinoma were treated with topical aminolevulinic acid photodynamic therapy (ALA-PDT) combined with curettage. First, the lesions were removed under local anesthesia. Then, the first session of PDT was performed right away. Ten percent 5-ALA cream was applied to surface of the lesions with occlusive dressing for a 3-h incubation period and the lesions were irradiated for 10 min by using a 635-nm laser beam of 177 mW/cm intensity. The ALA-PDT was repeated after 1 and 3 weeks and two other treatments applied if necessary.

Results: Three patients were cured by this treatment, with one case relapsed at 3 months. There was no other recurrence at 5 years off treatments. The satisfaction rate of patients was 75% at 3 months after treatments.

Conclusions: Topical PDT can be an effective and successful treatment modality for verrucous carcinoma in penis.
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http://dx.doi.org/10.1016/j.pdpdt.2018.08.015DOI Listing
December 2018

Effect of Spin Polarization on the Exclusion Zone of Water.

J Phys Chem B 2018 09 29;122(36):8493-8502. Epub 2018 Aug 29.

Department of Electronics , Peking University , Beijing 100080 , China.

The exclusion zone (EZ) of water near the hydrophilic surface can exclude colloid suspension for a certain distance, which is typically several hundreds of micrometers, and approximates the size of the cells. Previous studies have shown that the near-surface the EZ expands extensively in the presence of incident radiant energy, especially the infrared light. Developments of electromagnetic biology and quantum biology indicate that the spin magnetic moment may have a direct impact on the biological process. In this article, a spintronic device, with a nickel-manganese ferrite rotator and spiral magnetic vector potential, was utilized to exert the influence on the EZ. Spin states in the nickel-manganese ferrite were polarized by two different chiral configurations, i.e., right-handed and left-handed, of the spiral magnetic vector potential, through the Aharonov-Bohm (AB) effect. The variation of the the EZ width clearly reflects the presence of different chiralities of the polarization and shows a directionality effect of rotation and irradiation. The spintronic device with a right-handed magnetic vector potential can enlarge the the EZ for 30-40%, while the one with the left-handed magnetic vector potential showed no potentiation but sometimes a depression effect. Therefore, a chiral symmetry-breaking phenomenon was observed, which shows that the formation of the EZ water may evolve certain quantum effects related to the chiral induced spin selectivity effect.
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http://dx.doi.org/10.1021/acs.jpcb.8b04118DOI Listing
September 2018

Cereblon suppresses the lipopolysaccharide-induced inflammatory response by promoting the ubiquitination and degradation of c-Jun.

J Biol Chem 2018 06 10;293(26):10141-10157. Epub 2018 May 10.

From the Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu 215123, China

Chronic inflammation is associated with multiple human disorders, such as rheumatoid arthritis, metabolic diseases, and neurodegenerative diseases. Therefore, alleviation of inflammation induced by environmental stimuli is important for disease prevention or treatment. Cereblon (CRBN) functions as a substrate receptor of the cullin-4 RING E3 ligase to mediate protein ubiquitination and degradation. Although it has been reported that CRBN reduces the inflammatory response through its nonenzymatic function, its role as a substrate receptor of the E3 ligase is not explored in mediating this process. Here we used a quantitative proteomics approach to find that the major component of the activator protein 1 (AP-1) complex, c-Jun, is significantly down-regulated upon CRBN expression. Biochemical approaches further discover that CRBN interacts and partially colocalizes with c-Jun and promotes the formation of Lys-linked polyubiquitin chains on c-Jun, enhancing c-Jun degradation. We further reveal that CRBN attenuates the transcriptional activity of the AP-1 complex and reduces the mRNA expression and protein level of several pro-inflammatory cytokines. Moreover, flow cytometry analyses show that CRBN attenuates lipopolysaccharide-induced apoptosis in differentiated THP-1 cells. Through genetic manipulation and pharmacological inhibition, we uncover a new molecular mechanism by which CRBN regulates the inflammatory response and apoptosis induced by lipopolysaccharide. Our work and previous studies demonstrate that CRBN suppresses the inflammatory response by promoting or inhibiting the ubiquitination of two key molecules at different levels of the inflammatory cascade through its enzymatic function as a substrate receptor and its nonenzymatic function as a protein binding partner.
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http://dx.doi.org/10.1074/jbc.RA118.002246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028970PMC
June 2018

Erratum: Identification of a nanobody specific to a human pulmonary surfactant protein A.

Sci Rep 2017 09 27;7(1):12358. Epub 2017 Sep 27.

Department of Respiratory Medicine, Shanghai Pulmonary Hospital Tongji University, School of Medicine, Shanghai, China.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-017-12271-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617889PMC
September 2017

Identification of a nanobody specific to human pulmonary surfactant protein A.

Sci Rep 2017 05 3;7(1):1412. Epub 2017 May 3.

Department of Respiratory Medicine, Shanghai Pulmonary Hospital Tongji University, School of Medicine, Shanghai, China.

Nanobody (Nb) is a promising vector for targeted drug delivery. This study aims to identify an Nb that can specifically target the lung by binding human pulmonary surfactant protein A (SP-A). Human lung frozen tissue sections were used for 3 rounds of biospanning of our previously constructed Nb library for rat SP-A to establish a sub-library of Nb, which specifically bound human lung tissues. Phage-ELISA was performed to screen the sub-library to identify Nb4, which specifically bound human SP-A. The binding affinity Kd of Nb4 to recombinant human SP-A was 7.48 × 10 M. Nb4 (19 kDa) was stable at 30 °C-37 °C and pH 7.0-7.6 and specifically bound the SP-A in human lung tissue homogenates, human lung A549 cells, and human lung tissues, whereas didn't react with human liver L-02 cells, kidney 293T cells, and human tissues from organs other than the lung. Nb4 accumulated in the lung of nude mice 5 minutes after a tail vein injection of Nb4 and was excreted 3 hours. Short-term exposure (one month) to Nb4 didn't cause apparent liver and kidney toxicity in rats, whereas 3-month exposure resulted in mild liver and kidney injuries. Nb4 may be a promising vector to specifically deliver drugs to the lung.
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http://dx.doi.org/10.1038/s41598-017-01456-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431231PMC
May 2017

Treatment of Sweat gland carcinoma with Topical Aminolevulinic Acid Photodynamic therapy: An effective treatment method to improve surgical outcomes.

Photodiagnosis Photodyn Ther 2017 Mar 27;17:233-235. Epub 2016 Dec 27.

Plastic & Cosmetic Surgery Department, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China. Electronic address:

Background: Sweat gland carcinoma is an extremely rare skin cancer, which is hard to diagnose and completely resect without causing functional and cosmetic problems. Moreover, the high rate of recurrence is hard to handle in the treatment of sweat gland carcinoma. Photodynamic therapy is a novel treatment protocol which can selectively destroy tumor cells with good functional and cosmetic outcomes.

Methods: This is a case about a 53 years old patient with sweat gland carcinoma on his right foot, which received surgery and photodynamic therapy.

Results: There is no recurrence one year after treatment of surgery and photodynamic therapy.

Conclusions: Excision combined with photodynamic therapy during operation is a promising strategy towards tumors which are hard to resect thoroughly and have a high risk of recurrence.
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http://dx.doi.org/10.1016/j.pdpdt.2016.12.004DOI Listing
March 2017
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