Publications by authors named "Yi Hu"

1,227 Publications

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Associations between repeated measurements of childhood triclosan exposure and physical growth at 7 years.

Chemosphere 2022 Aug 8:135970. Epub 2022 Aug 8.

Department of Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address:

Background: Epidemiological studies suggested that triclosan (TCS) exposure was ubiquitous among children and could affect their physical growth. However, most studies relied on TCS exposure at single time point, and the impacts of multiple time points TCS exposure were unclear.

Objectives: To estimate the associations between repeated TCS measurements in childhood (at ages 1, 2, 5, and 7 years) and physical growth at 7 years.

Methods: This study included 206 children from Laizhou Wan Birth Cohort (LWBC), China. Urinary TCS concentrations were detected at age of 1, 2, 5, and 7 years, and physical growth including height, weight, waist circumference, and fat percentage was measured at 7 years. Multiple informant models were applied to examine the relationships of repeated TCS measurements in childhood with physical growth, and stratified analysis by gender was performed.

Results: The detection rates of TCS at age of 1, 2, 5, and 7 years were above 60%, with median declining from 0.89 to 0.33 μg/g creatinine. We found TCS at 5 years was positively associated with waist-to-height ratio, and TCS at 7 years was positively associated with physical growth, including weight z-score, BMI z-score, waist circumference, waist-to-height ratio, and fat percentage. Moreover, the above associations for weight z-score, BMI z-score, and fat percentage significantly varied by the period of exposure (pint ˂ 0.05). After stratified by gender, positive associations were only found among boys.

Conclusions: In our study, TCS levels decreased as children's age increased. TCS exposures at age of 5 and 7 years were positively associated with physical growth at 7 years, and these associations were only significant in boys. Given the relatively small sample size, our findings should be interpreted with caution until confirmed by further investigation.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135970DOI Listing
August 2022

Dual structure engineering of SiO-acrylic yarn derived carbon nanofiber based foldable Si anodes for low-cost lithium-ion batteries.

J Colloid Interface Sci 2022 Aug 2;628(Pt A):530-539. Epub 2022 Aug 2.

Key Laboratory of Advanced Textile Materials and Manufacturing Technology Ministry of Education, Zhejiang Sci-Tech University, Hangzhou 310018, PR China; Engineering Research Center for Eco-Dying & Finishing of Textiles Ministry of Education, Zhejiang Sci-Tech University, Hangzhou 310018, PR China; Dyeing and Finishing Institute of Zhejiang Sci-Tech University, Zhejiang Sci-Tech University, Hangzhou 310018, PR China. Electronic address:

Silicon (Si) is attracted much attention due to its outstanding theoretical capacity (4200 mAh/g) as the anode of lithium-ion batteries (LIBs). However, the large volume change and low electron/ion conductivity during the charge and discharge process limit the electrochemical performance of Si-based anodes. Here we demonstrate a foldable acrylic yarn-based composite carbon nanofiber embedded by [email protected] particles ([email protected]) as the anode material. Since the amorphous SiO and carbon (C) coating on the outside of the Si particles can provide a double buffer for volume expansion while reducing the contact between the Si core and the electrolyte to form a thin and stable solid electrolyte interface (SEI) film. Simultaneous in-situ electrochemical impedance spectroscopy (in-situ EIS) and galvanostatic intermittent titration technique (GITT) tests show that SiO and C have higher ion/electron transport rates, and in addition, using acrylic fiber yarn and Zn(Ac) as raw materials reduces the manufacturing cost and enhanced mechanical properties. Therefore, the half-cell can achieve a high initial Coulombic efficiency (ICE) of 82.3% and a reversible capacity of 1358.2 mAh/g after 180 cycles. It can return to its original shape and remain intact after four consecutive folds, and the soft-pack full battery can also light up LED lights under different bending conditions.
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http://dx.doi.org/10.1016/j.jcis.2022.07.186DOI Listing
August 2022

Adaptive injectable carboxymethyl cellulose/poly (γ-glutamic acid) hydrogels promote wound healing.

Biomater Adv 2022 May 18;136:212753. Epub 2022 Mar 18.

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Food Science and Light Industry, Nanjing Tech University, Nanjing 211816, China; Jiangsu National Synergetic Innovation Center for Advanced Materials Nanjing Tech University, Nanjing 211816, China. Electronic address:

The clinical acceleration of skin autogenous healing remains a great challenge, especially in the early stage after injury. In this work, a novel directly injectable hydrogel with high self-adaptability is designed as a provisional matrix to close the apposition of wound edges, using carboxymethyl cellulose and poly (γ-glutamic acid) through Schiff-base reaction. Benefiting from the dynamic covalent cross-linking structure, the functional biodegradable hydrogels are easy to prepare (gel time 5-180 s), demonstrating adequate mechanical strength (40-120 kPa), anti-fatigue abilities, and rapid self-healing (5-10 min at skin defect). Furthermore, the hydrogels exhibit biocompatibility and proliferation-promoting activity with murine fibroblasts. In the full-thickness dermal animal models, it significantly promoted collagen deposition, skin-function restoration, and VEGF expression. This hydrogel shows potential as a dressing available for skin regeneration during the healing of dermal injuries.
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http://dx.doi.org/10.1016/j.bioadv.2022.212753DOI Listing
May 2022

Immobilization of Interfacial Activated Lipase Onto Magnetic Chitosan Using Dialdehyde Cellulose as Cross-Linking Agent.

Front Bioeng Biotechnol 2022 18;10:946117. Epub 2022 Jul 18.

State Key Laboratory of Materials-Oriented Chemical Engineering, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China.

lipase (CRL) was activated with surfactants (sodium dodecyl sulfate [SDS]) and covalently immobilized onto a nanocomposite (FeO-CS-DAC) fabricated by combining magnetic nanoparticles FeO with chitosan (CS) using polysaccharide macromolecule dialdehyde cellulose (DAC) as the cross-linking agent. Fourier transform infrared spectroscopy, transmission electron microscope, thermogravimetric analysis, and X-ray diffraction characterizations confirmed that the organic-inorganic nanocomposite support modified by DAC was successfully prepared. Enzymology experiments confirmed that high enzyme loading (60.9 mg/g) and 1.7 times specific enzyme activity could be obtained under the optimal immobilization conditions. The stability and reusability of immobilized CRL (FeO-CS-DAC-SDS-CRL) were significantly improved simultaneously. Circular dichroism analysis revealed that the active conformation of immobilized CRL was maintained well. Results demonstrated that the inorganic-organic nanocomposite modified by carbohydrate polymer derivatives could be used as an ideal support for enzyme immobilization.
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http://dx.doi.org/10.3389/fbioe.2022.946117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340543PMC
July 2022

Analysis of the Geographic Transmission Differences of COVID-19 in China Caused by Population Movement and Population Density.

Bull Math Biol 2022 Aug 1;84(9):94. Epub 2022 Aug 1.

School of mathematics and statistics, Southwest University, Chongqing, 400715, People's Republic of China.

The coronavirus disease (COVID-19) has led to a global pandemic and caused huge healthy and economic losses. Non-pharmaceutical interventions, especially contact tracing and social distance restrictions, play a vital role in the control of COVID-19. Understanding the spatial impact is essential for designing such a control policy. Based on epidemic data of the confirmed cases after the Wuhan lockdown, we calculate the invasive reproduction numbers of COVID-19 in the different regions of China. Statistical analysis indicates a significant positive correlation between the reproduction numbers and the population input sizes from Wuhan, which indicates that the large-scale population movement contributed a lot to the geographic spread of COVID-19 in China. Moreover, there is a significant positive correlation between reproduction numbers and local population densities, which shows that the higher population density intensifies the spread of disease. Considering that in the early stage, there were sequential imported cases that affected the estimation of reproduction numbers, we classify the imported cases and local cases through the information of epidemiological data and calculate the net invasive reproduction number to quantify the local spread of the epidemic. The results are applied to the design of border control policy on the basis of vaccination coverage.
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http://dx.doi.org/10.1007/s11538-022-01050-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340757PMC
August 2022

Classification and Reconstruction of Biomedical Signals Based on Convolutional Neural Network.

Comput Intell Neurosci 2022 21;2022:6548811. Epub 2022 Jul 21.

School of Computer Science, South China Business College, Guangdong University of Foreign Studies, Guangzhou 510545, Guangdong, China.

The efficient biological signal processing method can effectively improve the efficiency of researchers to explore the work of life mechanism, so as to better reveal the relationship between physiological structure and function, thus promoting the generation of major biological discoveries; high-precision medical signal analysis strategy can, to a certain extent, share the pressure of doctors' clinical diagnosis and assist them to formulate more favorable plans for disease prevention and treatment, so as to alleviate patients' physical and mental pain and improve the overall health level of the society. This article in biomedical signal is very representative of the two types of signals: mammary gland molybdenum target X-ray image (mammography) and the EEG signal as the research object, combined with the deep learning field of CNN; the most representative model is two kinds of biomedical signal classification, and reconstruction methods conducted a series of research: (1) a new classification method of breast masses based on multi-layer CNN is proposed. The method includes a CNN feature representation network for breast masses and a feature decision mechanism that simulates the physician's diagnosis process. By comparing with the objective classification accuracy of other methods for the identification of benign and malignant breast masses, the method achieved the highest classification accuracy of 97.0% under different values of and gamma, which further verified the effectiveness of the proposed method in the identification of breast masses based on molybdenum target X-ray images. (2) An EEG signal classification method based on spatiotemporal fusion CNN is proposed. This method includes a multi-channel input classification network focusing on spatial information of EEG signals, a single-channel input classification network focusing on temporal information of EEG signals, and a spatial-temporal fusion strategy. Through comparative experiments on EEG signal classification tasks, the effectiveness of the proposed method was verified from the aspects of objective classification accuracy, number of model parameters, and subjective evaluation of CNN feature representation validity. It can be seen that the method proposed in this paper not only has high accuracy, but also can be well applied to the classification and reconstruction of biomedical signals.
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http://dx.doi.org/10.1155/2022/6548811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334110PMC
August 2022

MOF-derived [email protected] with high activity for electric field-assisted catalytic oxidation of aqueous pollutants.

J Hazard Mater 2022 Jul 22;439:129670. Epub 2022 Jul 22.

Anhui Province Key Laboratory of Industrial Wastewater and Environmental Treatment, East China Engineering Science & Technology Co., Ltd., Hefei 230088, China.

The activation of oxygen (O) under room condition is important for the utilization of air to perform oxidation. Here, we report a porous carbon-encapsulated MnO ([email protected]) derived from Mn metal-organic framework (MOF)grown in-situ on a graphite felt (GF) support. The [email protected] exhibits superior catalytic activity in an electric field-assisted catalytic oxidation system for the degradation of organic pollutants under room condition. The catalytic oxidation reaction applies a surface reaction pathway in which the surface-bound chemisorbed oxygen species are electro-oxidized and then involved in the oxidation of co-adsorbed organic pollutants. The abundant oxygen vacancies and oxygenated functional groups in [email protected] provide active sites for the chemisorption of O, and its conductive mesoporous structure allows facile electrons and mass transfer. As a result, the [email protected]/GF catalyst displays quite high turnover frequency (TOF) value as 0.038 mg-TOC mg-MnO min, which is 6.66 times higher than that of the MnO/GF catalyst prepared by impregnation method as a comparison. With the aid of + 1.0 V of positive electric field, the catalytic oxidation system exhibits extensive effectiveness in mineralizing a variety of dyes, pharmaceuticals, personal care products, and phenolic compounds under room condition with significantly enhanced biodegradability.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129670DOI Listing
July 2022

Preparation of the luciferase-labeled antibody for improving the detection sensitivity of viral antigen.

Virol J 2022 Jul 28;19(1):126. Epub 2022 Jul 28.

State Key Laboratory of Pathogen and Biosecurity, The Academy of Military Medical Science. Institute of Microbiology and Epidemiology, No. 20 Dongda Street, Fengtai District, Beijing, 100071, China.

Background: Viral antigen detection test is the most common method used to detect viruses in the field rapidly. However, due to the low sensitivity, it can only be used as an auxiliary diagnosis method for virus infection. Improving sensitivity is crucial for developing more accurate viral antigen tests. Nano luciferase (Nluc) is a sensitive reporter that has not been used in virus detection.

Results: In this study, we produced an intracellularly Nluc labeled detection antibody (Nluc-ch2C5) and evaluated its ability to improve the detection sensitivity of respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens. Compared with the traditional horse-radish peroxidase (HRP) labeled antibody (HRP-ch2C5), Nluc-ch2C5 was 41 times more sensitive for inactivated SARS-CoV-2 virus by sandwich chemiluminescence ELISA. Then we applied Nluc-ch2C5 to establish an automatic magnet chemiluminescence immune assay (AMCA) for the SARS-CoV-2 viral spike protein, the limit of detection was 68 pfu/reaction. The clinical sensitivity and specificity reached 75% (24/32) and 100% (48/48) using 32 PCR-positive and 48 PCR-negative swab samples for clinical evaluation, which is more sensitive than the commercial ELSA kit and colloid gold strip kit.

Conclusions: Here, monoclonal antibody ch2C5 served as a model antibody and the SARS-CoV-2 served as a model pathogen. The Nluc labeled detecting antibody (Nluc-ch2C5) significantly improved the detection sensitivity of SARS-CoV-2 antigen. This labeling principle applies to other viral infections, so this labeling and test format could be expected to play an important role in detecting other virus antigens.
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http://dx.doi.org/10.1186/s12985-022-01855-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332066PMC
July 2022

NICD3 regulates the expression of MUC5AC and MUC2 by recruiting SMARCA4 and is involved in the differentiation of mucinous colorectal adenocarcinoma.

Mol Oncol 2022 Jul 28. Epub 2022 Jul 28.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Adenocarcinoma is the most prevalent histological subtype of colorectal cancer (CRC), with mucinous colorectal adenocarcinoma (MCA) being a unique form. Although the mucinous subtype is known to elicit a worse response to chemotherapy and immunotherapy than the nonmucinous subtype, its pathogenesis remains poorly understood. Neurogenic locus notch homolog protein 3 (NOTCH3), a member of the NOTCH subfamilies, is highly expressed in CRC. In the past three decades, many studies have been performed evaluating the biological role of NOTCH3 in CRC. However, the precise activities of NOTCH3 in MCA, as well as the mechanisms involved in its transcriptional control, are yet to be elucidated. Our finding showed that the critical transcriptional regulatory factor transcription activator BRG1 (SMARCA4) directly binds to the intracellular domain of NOTCH3 to control transcriptional regulation. Moreover, RNA-sequencing results indicated a common targeting effect on the transcriptional activity of mucin-5AC (MUC5AC) and mucin-2 (MUC2) in CRC cells by NOTCH3 and SMARCA4. Furthermore, NOTCH3 was found to control the expressions of MUC5AC and MUC2 in a SMARCA4-dependent manner. MUC5AC and MUC2, which encode two secreted mucins, are located on chromosome 11p15.5, and are linked to the development of MCA. This finding suggests that the interaction between NOTCH3 and SMARCA4 may be involved in MCA differentiation by jointly targeting MUC5AC and MUC2. Patients with MCA are often treated in accordance with CRC guidelines. Determining the relationship between NOTCH3 and SMARCA4 by demonstrating their interactions in the pathophysiology of MCA could provide novel therapeutic targets and help identify potential prognostic markers for MCA.
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http://dx.doi.org/10.1002/1878-0261.13296DOI Listing
July 2022

Log P Determines Licorice Flavonoids Release Behaviors and Classification from CARBOMER Cross-Linked Hydrogel.

Pharmaceutics 2022 Jun 24;14(7). Epub 2022 Jun 24.

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.

The dynamic drug release mechanisms from Carbomer 940 (CP) hydrogels have not been systematically explored elsewhere. This study aimed to investigate the quantitative structure-activity relationship of licorice flavonoids (LFs) compounds on their drug release from CP hydrogels based on LFs-CP interactions and drug solubility in the release medium. Ten LFs-CP hydrogels were formulated, and their in vitro release study was conducted. The intermolecular forces of LFs-CP systems were characterized by FTIR, molecular docking and molecular dynamic simulation. Ten LFs compounds were classified into I (high-release capability) LFs and II (low-release capability) LFs according to the different negative correlations between drug release percent at 48 h and intermolecular forces of drugs-CP, respectively. Moreover, high-release LFs possessed significantly lower log P and higher drug solubility in the release medium than low-release LFs. All I LFs release behaviors best followed the first-order equation, while II LFs release characteristics best fitted the zero-order equation except for isoliquiritigenin. Log P mainly affect the hydrogel relaxation process for I drugs release and the drug diffusion process for II drugs release. Higher log P values for LFs resulted in higher intermolecular strength for I drugs-CP systems and lower drug solubility in the release medium for II drugs, which hindered drug release. Hydrophobic association forces in drug-CP hydrogel played a more and more dominant role in hindering I LFs release with increasing release time. On the other hand, lower drug solubility in the release medium restricted II LFs release, and the dominant role of drug solubility in the release medium increased in 24 h followed by a significant decline after 36 h. Collectively, log P of LFs served as a bridge to determine LFs compound release behaviors and classification from CP hydrogels, which provided guidelines for reasonable design of LFs hydrogels in pharmaceutical topical formulations.
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http://dx.doi.org/10.3390/pharmaceutics14071333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322780PMC
June 2022

Study on the Seismic Performance of Stiffened Corrugated Steel Plate Shear Walls with Atmospheric Corrosion.

Materials (Basel) 2022 Jul 14;15(14). Epub 2022 Jul 14.

School of Civil Engineering, Chang'an University, Xi'an 710061, China.

Corrugated steel plate shear walls (CSPWs) with three different stiffening methods are proposed in this paper, including unstiffened CSPWs (USWs), cross stiffened CSPWs (CSWs) and asymmetric diagonal-stiffened CSPWs (ASWs). A numerical model was established by ABAQUS 6.13 based on the validation of an existing cyclic test on a CSPW. This paper presents an investigation of the lateral performance under monotonic loading, seismic performance under cyclic loading and seismic performance under atmospheric corrosion of USW, CSW and ASW. The results show that (1) Stiffeners can improve the elastic critical buckling load, the initial stiffness and the ultimate shear resistance of CSPWs, and the effect of asymmetric diagonal stiffeners is more significant than that of cross stiffeners; (2) Stiffeners can improve the energy dissipation capacity and ductility, delay stiffness degradation and reduce the out-of-plane deformation of CSPWs, and the hysteretic performance of ASWs is obviously better than that of CSWs; and (3) Under atmospheric corrosion, stiffeners are conducive to inhibiting buckling and improving the seismic performance of CSPWs, while the seismic performance of CSWs is significantly affected by corrosion, so asymmetric diagonal stiffeners are better than cross stiffeners in improving the seismic performance of CSPWs. Meanwhile, the formula of ultimate shear resistance of corroded specimens is also fitted in this paper, which can provide design suggestions for practical engineering.
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http://dx.doi.org/10.3390/ma15144920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318355PMC
July 2022

Letter: a promising Helicobacter pylori regimen - vonoprazan-based therapy.

Authors:
Yi Hu Nong-Hua Lu

Aliment Pharmacol Ther 2022 Aug;56(4):752-753

Department Of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China.

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http://dx.doi.org/10.1111/apt.17114DOI Listing
August 2022

Dysbiosis of Gut Microbiota and Lipidomics of Content Induced by Dietary Methionine Restriction in Rice Field Eel ().

Front Microbiol 2022 7;13:917051. Epub 2022 Jul 7.

Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization, Hunan Agricultural University, Changsha, China.

An 8-week feeding trial was conducted using the rice field eel () with six isonitrogenous and isoenergetic experimental diets of basic feed supplemented with different levels of methionine (0, 2, 4, 6, 8, or 10 g/kg). This study built upon previous research findings that showed dietary methionine restriction (M0, 0 g/kg) inhibited hepatic fatty acid metabolism and intestinal fatty acid transportation, but both are improved by dietary supplementation with a suitable level of methionine (M8, 8 g/kg). Hence, M0 and M8 were selected to investigate how methionine regulates the gut microbiota and lipidomics of . Compared with M0, values for gut bacterial Sobs, Shannon, ACE, and Chao1 indices of M8 were remarkably increased ( < 0.05), with , , and the dominant phyla and , , and the main genera in the community under the M0 vs. M8 treatments. However, compared with M0, the proportion of phyla consisting of decreased in M8, as did the and at the genus level; conversely, the proportions corresponding to , , and phyla increased in M8, as did the and genera. Many edges appeared in the circus and networks, demonstrating the interspecies interactions among different operational taxonomic units (OTUs). In addition, various OTUs within the same phylum were clustered within one module. Cooperative interactions were predominant in the two networks, while competitive interactions were prevalent in their submodules. Gut microbiota mainly played roles in nutrition (lipid, amino acid, and carbohydrate) transport and metabolism under the M0 vs. M8 treatments. The PLS-DA scores indicated a significant difference in the main lipidomic components between the M0 and M8 treatment groups. Namely, the TG(26:0/16:0/17:0), TG(28:0/16:0/16:0), TG(26:0/16:0/16:0), and TG(30:0/16:0/16:0)-among others-comprising the gut content were reduced under the M8 treatment ( < 0.001). The genus was positively correlated with TG(18:1/18:1/22:5), TG(16:0/17:0/18:1), TG(18:0/18:1/20:3), and other compounds, yet negatively correlated with TG(18:0/17:0/20:0), TG(16:0/17:0/24:0), and TG(16:0/16:0/24:0), among others as well. According to the lipidomics analysis, the predicted KEGG pathways mainly included lipid and glycan biosynthesis and metabolism, and digestive, sensory, and immune systems. In conclusion, methionine restriction disturbed the microbial community balance and induced microbial dysfunctions, whereas methionine supplementation improved the homeostasis of gut microbiota and lipid metabolism of the rice eel.
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http://dx.doi.org/10.3389/fmicb.2022.917051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301281PMC
July 2022

Silenced LINC01134 Enhances Oxaliplatin Sensitivity by Facilitating Ferroptosis Through GPX4 in Hepatocarcinoma.

Front Oncol 2022 8;12:939605. Epub 2022 Jul 8.

Department of Oncology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China.

Purpose: Recently, long noncoding RNA LINC01134 has been shown to reduce cell viability and apoptosis the antioxidant stress pathway, thereby enhancing OXA resistance in hepatocellular carcinoma. However, the association of LINC01134 with ferroptosis and the underlying molecular mechanisms remain to be elucidated.

Methods: Bioinformatics analysis was employed to screen lncRNAs positively correlated with GPX4 and poor clinical prognosis. And Western blot and RT-PCR analysis in HCC cells confirmed the effect of LINC01134 on GPX4 expression. In addition, LINC01134 siRNA was transfected in HCC cells to detect the changes in cell viability, ROS, lipid peroxidation, MDA levels and GSH/GSSG levels. CCK-8, colony formation and apoptosis assays were performed to determine the effect of LINC01134 on cell death. The effect of LINC01134 and OXA on Nrf2 transcriptional binding to GPX4 was analyzed using dual luciferase reporter assay and CHIP. The expression of GPX4 and Nrf2 in HCC tissues was detected by FISH and IHC.

Results: LINC01134 is a novel lncRNA positively correlated with GPx4 and associated with poor clinical prognosis. Silenced LINC01134 conferred OXA sensitivity by enhancing total ROS, lipid ROS, MDA levels and decreasing GSH/GSSG ratio. Mechanistically, LINC01134 and OXA could promote Nrf2 recruitment to the GPX4 promoter region to exert transcriptional regulation of GPX4. Clinically, LINC01134 was positively correlated with GPX4 or Nrf2, demonstrating the clinical significance of LINC01134, Nrf2 and GPX4 in OXA resistance of HCC.

Conclusions: We identified LINC01134/Nrf2/GPX4 as a novel and critical axis to regulate HCC growth and progression. Targeting GPX4, knocking down LINC01134 or Nrf2 could be a potential therapeutic strategy for HCC.
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http://dx.doi.org/10.3389/fonc.2022.939605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304856PMC
July 2022

Network pharmacology, molecular docking and in vivo and in vitro experiments to explore the molecular mechanism of licorice green tea beverage to scavenge oxygen free radicals.

J Food Biochem 2022 Jul 19:e14315. Epub 2022 Jul 19.

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People's Republic of China.

Excessive oxygen free radicals can lead to aging, cancer, and other diseases. Therefore, searching for effective antioxidants to scavenge oxygen free radicals has become the focus of modern medicine. In this study, the molecular mechanism of Licorice Green Tea Beverage (LGTB) in scavenging oxygen free radicals was investigated by means of network pharmacology, molecular docking and experimental verification. Network pharmacology studies have shown that paeonol, eugenol, cinnamaldehyde, swertisin, rutin, glycyrrhetinic acid, oleic, pelargonidin-3-O-glucoside and quercetin, kaferempol were the main active components of LGTB, and SOD and CAT are important targets for LGTB in scavenging oxygen free radicals. The results of molecular docking showed that these representative compounds had good affinity to SOD and CAT target proteins. In vitro free radical scavenging experiments showed that LTGB had significant scavenging effects on both DPPH and ABTS radicals, and had strong total reducing power. In vitro cell experiments showed that LGTB could protect HaCaT cells from oxidative stress induced by H O . The mechanism of LGTB was related to the increase of SOD and CAT activity. Western blotting showed that LGTB could inhibit PI3K/AKT/HIF-1 signaling pathway and improve the antioxidant capacity of HaCaT cells. In vivo experiments showed that LGTB could significantly increase mouse visceral index, increase serum SOD and GSH-Px activity, decrease the content of MDA, and improve liver and kidney pathological state. This study reported the molecular mechanism of LTGB scavenging oxygen free radicals, which provided scientific basis for the treatment and clinical research of aging and other diseases caused by excessive free radicals. PRACTICAL APPLICATIONS: Free radicals are produced by the normal response of cells during aerobic respiration and perform various functions, such as signaling and providing protection against infection. However, excessive free radicals can lead to aging, cancer, and other diseases. The antioxidant can overcome the harm caused by excessive free radicals. In this study, we investigated the molecular mechanism of scavenging oxygen free radicals of Licorice Green Tea Beverage (LGTB) through network pharmacology and molecular docking, and its efficacy was verified by free radical scavenging experiment in vitro, HaCaT cell oxidative stress injury induced by H O , D-galactose to establish an aging model in mice and Western blotting experiment. It not only elucidates its mechanism at the system level, but also proves its validity at the biological level. It provides the theoretical basis and experimental evidence for the follow-up research and promotion of the product.
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http://dx.doi.org/10.1111/jfbc.14315DOI Listing
July 2022

Clinicopathological characteristics and prognostic significance of HDAC11 protein expression in non-small cell lung cancer: a retrospective study.

Transl Lung Cancer Res 2022 Jun;11(6):1119-1131

Department of Medical Oncology, Senior Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, China.

Background: Although the prognosis of non-small cell lung cancer (NSCLC) can be assessed based on pathological type, disease stage and inflammatory indicators, the prognostic scoring model of NSCLC still needs to improve. is associated with poor prognosis of partial tumors, but its prognostic relationship with NSCLC is poorly understood. In this study, the role of in NSCLC was studied to evaluate relationship with disease prognosis and potential therapeutic target.

Methods: The clinicopathological and paracancerous tissues of patients with NSCLC primarily diagnosed in Tangdu Hospital from 2009 to 2013 were collected. Follow-up of patients were made every three months and the last follow-up period was December 2018. The expression of was assessed by immunohistochemistry (IHC). Then, weighted gene co-expression network analysis (WGCNA) was used to analyze the relationship between expression and the prognosis of lung adenocarcinoma (LUAD) patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Kaplan-Meier plotter database was used to verify the connection between hub genes and tumor stage and prognosis. We accessed the relationship between expression and clinicopathological features, and impact on the prognosis.

Results: The study assessed 326 patients with NSCLC. Compared with adjacent tissues, expression was upregulated (HR =1.503, 95% CI: 1.172 to 1.927, P=0.001). Kaplan-Meier survival analyses showed that expression was closely related to OS of NSCLC patients (P=0.0011). Univariate and multivariate analyses showed that the independent risk factors of OS were clinical stage, expression, and differentiation (all P≤0.001). was significantly associated with prognosis in LUAD. A total of 1,174 differential genes and WGCNA were obtained to construct a co-expression network in LUAD. The GO and KEGG pathway enrichment analyses showed the relevance with staphylococcus aureus infection, NOD-like receptor signaling pathway, and others. The results of LUAD survival analysis showed that -related genes and were significantly associated with LUAD prognosis.

Conclusions: The high expression of is related to the poor prognosis of LUAD, and it is expected to become a therapeutic target and prognostic evaluation therapy for LUAD in the future. However, the relevant results need to be further studied and verified.
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http://dx.doi.org/10.21037/tlcr-22-403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271448PMC
June 2022

Concordant and Heterogeneity of Single-Cell Transcriptome in Cardiac Development of Human and Mouse.

Front Genet 2022 27;13:892766. Epub 2022 Jun 27.

Key Laboratory of Arrhythmias, Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Normal heart development is vital for maintaining its function, and the development process is involved in complex interactions between different cell lineages. How mammalian hearts develop differently is still not fully understood. In this study, we identified several major types of cardiac cells, including cardiomyocytes (CMs), fibroblasts (FBs), endothelial cells (ECs), ECs/FBs, epicardial cells (EPs), and immune cells (macrophage/monocyte cluster, MACs/MONOs), based on single-cell transcriptome data from embryonic hearts of both human and mouse. Then, species-shared and species-specific marker genes were determined in the same cell type between the two species, and the genes with consistent and different expression patterns were also selected by constructing the developmental trajectories. Through a comparison of the development stage similarity of CMs, FBs, and ECs/FBs between humans and mice, it is revealed that CMs at e9.5 and e10.5 of mice are most similar to those of humans at 7 W and 9 W, respectively. Mouse FBs at e10.5, e13.5, and e14.5 are correspondingly more like the same human cells at 6, 7, and 9 W. Moreover, the e9.5-ECs/FBs of mice are most similar to that of humans at 10W. These results provide a resource for understudying cardiac cell types and the crucial markers able to trace developmental trajectories among the species, which is beneficial for finding suitable mouse models to detect human cardiac physiology and related diseases.
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http://dx.doi.org/10.3389/fgene.2022.892766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271823PMC
June 2022

HS-GC-IMS identification of volatile aromatic compounds of freshly-cooked rice packaged with different disposable lunchboxes.

J Hazard Mater 2022 Jul 2;438:129516. Epub 2022 Jul 2.

Department of Food Science & Engineering, Jinan University, Huangpu West Avenue 601, Guangzou City 510632, Guangdong, China. Electronic address:

The rapid development of online-to-offline food delivery service has necessitated the replacement of plastic lunchbox using biodegradable ones. In current study, a total number of fourteen panelists were firstly recruited and trained to investigate how different commercial disposable lunchboxes affect the freshly cooked rice sensory properties during heat preservation (60 °C, 60 min). The lunchboxes were made of pure polypropylene (PP), polypropylene-starch (PP-S), pure wheat-straw and sugarcane-straw (WS & SS) and Paper. The discrepancy of volatile aromatic substances was then analyzed using headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) to study the possible mechanism beneath the variations of the influences of different lunchboxes on the aromatic properties of rice. Results showed that, compared with the textural attributes, the aroma was significantly and positively correlated with panelist's acceptability, among which, the aroma of starchy, sulfur and smoky are the most important ones. The moisture absorption plays an important role in affecting the aromatic characteristics of the packaged rice. While all lunchboxes have inhibitory effects on the production of volatile flavor substances including 2,6-Dimethylpyrazine, 2-Acetylpyrazine and γ-Octalactone, pure PP and PP-S lunchboxes generated undesirable flavor substances including 2-Ethyl-1-hexanl and Camphene, and thus reduced panelist's preferences. It was also found that the panelist liked the rice packaged by Paper lunchbox the best because of its better performance in maintaining the aroma of starchy and sulfur, the two substances that are associated with the higher concentration of ethereal and fruity volatile flavor substances. This study provides important information for manufacturers to understand how different disposable lunchboxes may impact the textural and aromatic properties of packaged foods.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129516DOI Listing
July 2022

Instructor-learner body coupling reflects instruction and learning.

NPJ Sci Learn 2022 Jun 28;7(1):15. Epub 2022 Jun 28.

Integrative Pain (iPain) Laboratory, School of Public Health, University of Haifa, Haifa, Israel.

It is widely accepted that nonverbal communication is crucial for learning, but the exact functions of interpersonal coordination between instructors and learners remain unclear. Specifically, it is unknown what role instructional approaches play in the coupling of physical motion between instructors and learners, and crucially, how such instruction-mediated Body-to-Body Coupling (BtBC) might affect learning. We used a video-based, computer-vision Motion Energy Analysis (MEA) to quantify BtBC between learners and instructors who used two different instructional approaches to teach psychological concepts. BtBC was significantly greater when the instructor employed a scaffolding approach than when an explanation approach was used. The importance of the instructional approach was further underscored by the fact that an increase in motion in the instructor was associated with boosted BtBC, but only during scaffolding; no such relationship between the instructor movements and BtBC was found during explanation interactions. Finally, leveraging machine learning approaches (i.e., support vector and logistic regression models), we demonstrated that both learning outcome and instructional approaches could be decoded based on BtBC. Collectively, these results show that the real-time interaction of teaching and learning bodies is important for learning and that the instructional approach matters, with possible implications for both in-person and online learning.
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http://dx.doi.org/10.1038/s41539-022-00131-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240028PMC
June 2022

Metabolic Engineering of to Efficiently Synthesize L-Ornithine From Inulin.

Front Bioeng Biotechnol 2022 8;10:905110. Epub 2022 Jun 8.

State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, China.

amyloliquefaciens is the dominant strain used to produce γ-polyglutamic acid from inulin, a non-grain raw material. B. amyloliquefaciens has a highly efficient tricarboxylic acid cycle metabolic flux and glutamate synthesis ability. These features confer great potential for the synthesis of glutamate derivatives. However, it is challenging to efficiently convert high levels of glutamate to a particular glutamate derivative. Here, we conducted a systematic study on the biosynthesis of L-ornithine by using inulin. First, the polyglutamate synthase gene pgsBCA of NB was knocked out to hinder polyglutamate synthesis, resulting in the accumulation of intracellular glutamate and ATP. Second, a modular engineering strategy was applied to coordinate the degradation pathway, precursor competition pathway, and L-ornithine synthesis pathway to prompt high levels of intracellular precursor glutamate for l-ornithine synthesis. In addition, the high-efficiency L-ornithine transporter was further screened and overexpressed to reduce the feedback inhibition of L-ornithine on the synthesis pathway. Combining these strategies with further fermentation optimizations, we achieved a final L-ornithine titer of 31.3 g/L from inulin. Overall, these strategies hold great potential for strengthening microbial synthesis of high value-added products derived from glutamate.
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http://dx.doi.org/10.3389/fbioe.2022.905110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214239PMC
June 2022

Mycotoxin DON Accumulation in Wheat Grains Caused by Fusarium Head Blight Are Significantly Subjected to Inoculation Methods.

Toxins (Basel) 2022 06 15;14(6). Epub 2022 Jun 15.

Key Laboratory of Plant Functional Genomics of the Ministry of Education/Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding/Collaborative Innovation of Modern Crops and Food Crops in Jiangsu/Jiangsu Key Laboratory of Crop Genetics and Physiology, College of Agriculture, Yangzhou University, Yangzhou 225009, China.

The disease severity and mycotoxin DON content in grains caused by fusarium head blight (FHB) have been two prioritized economical traits in wheat. Reliable phenotyping is a prerequisite for genetically improving wheat resistances to these two traits. In this study, three inoculation methods: upper bilateral floret injection (UBFI), basal bilateral floret injection (BBFI), and basal rachis internode injection (BRII), were applied in a panel of 22 near-isogenic lines (NILs) contrasting in alleles. The results showed that inoculation methods had significant influence on both disease severity and mycotoxin accumulation in grains, and the relationship between them. UBFI method caused chronic FHB symptom characterized as slow progress of the pathogen downward from the inoculation site, which minimized the difference in disease severity of the NILs, but, unexpectedly, maximized the difference in DON content between them. The BBFI method usually caused an acute FHB symptom in susceptible lines characterized as premature spike death (PSD), which maximized the difference in disease severity, but minimized the difference in DON content in grains between resistant and susceptible lines. The BRII method occasionally caused acute FHB symptoms for susceptible lines and had relatively balanced characteristics of disease severity and DON content in grains. Therefore, two or more inoculation methods are recommended for precise and reliable evaluation of the overall resistance to FHB, including resistances to both disease spread within a spike and DON accumulation in grains.
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http://dx.doi.org/10.3390/toxins14060409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229350PMC
June 2022

Use of Customized 3D-Printed Titanium Augment With Tantalum Trabecular Cup for Large Acetabular Bone Defects in Revision Total Hip Arthroplasty: A Midterm Follow-Up Study.

Front Bioeng Biotechnol 2022 1;10:900905. Epub 2022 Jun 1.

Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

In revision total hip arthroplasty (THA), large acetabular bone defects pose challenges for surgeons. Recently, wide application of trabecular tantalum, which has outstanding biocompatibility and mechanical properties, and the development of three-dimensional (3D) printing have led to the introduction of new schemes for acetabular reconstruction. However, few studies have focused on the treatment of bone defects with customized 3D-printed titanium augments combined with tantalum trabecular cup. Thus, we aimed to evaluate the effect of this therapy in patients who underwent revision THAs. We included 23 patients with Paprosky type III acetabular bone defects who underwent revision THA between January 2013 and June 2019. The preoperative hip rotation center and functional score were compared with those at 2-7 years (average 4.7 years) postoperatively to evaluate the midterm prognosis of our treatment choice. Postoperatively, the rotation centres of all hips were comparable with those of the contralateral hips. Hip function improved with average Harris Hip Score improved from 33.5 (22.7-40.2) to 86.1 (73.5-95.6) and average Oxford Hip Score improved from 8.3 (0-14) to 38.8 (35-48) during follow-up. One dislocation, which occurred due to extreme hip flexion within 6 weeks, was treated with closed reduction, and no recurrent dislocation occurred. No nerve injury, infection, aseptic loosening, or osteolysis were observed and no re-revision was performed in any patient. Satisfactory midterm outcomes were obtained with 3D-printed titanium augment combined with tantalum cup for the treatment of acetabular defects in revision THA. Changes in the Harris Hip Score and Oxford Hip Score suggested a significant improvement in hip function.
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http://dx.doi.org/10.3389/fbioe.2022.900905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198309PMC
June 2022

Altered Gut Microbiota and Short-Chain Fatty Acids After Vonoprazan-Amoxicillin Dual Therapy for Eradication.

Front Cell Infect Microbiol 2022 2;12:881968. Epub 2022 Jun 2.

Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

The combination of vonoprazan (VPZ) and amoxicillin (VA therapy) has been shown to achieve acceptable eradication rates for (). Herein, our aim was to explore the short-term effect of VA therapy on the gut microbiota and short-chain fatty acids (SCFAs) using human fecal samples. A total of 119 -positive patients were randomized into low- or high-dose VA therapy (i.e., amoxicillin 1 g b.i.d. or t.i.d. and VPZ 20 mg b.i.d.) for 7 or 10 days. Thirteen -negative patients served as controls. Fecal samples were collected from -positive and -negative patients. The gut microbiota and SCFAs were analyzed using 16S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively. The gut microbiota in -positive patients exhibited increased richness, diversity, and better evenness than matched patients. Fifty-three patients studied before and after eradication were divided into low (L-VA) and high (H-VA) amoxicillin dose groups. The diversity and composition of the gut microbiota among L-VA patients exhibited no differences at the three time points. However, among H-VA patients, diversity was decreased, and the microbial composition was altered immediately after H-VA eradication but was restored by the confirmation time point. The decreased abundance of , , and induced by H-VA was associated with altered SCFA levels. VA dual therapy for eradication has minimal negative effects on gut microbiota and SCFAs.
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http://dx.doi.org/10.3389/fcimb.2022.881968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201212PMC
June 2022

Interactions between intestinal morphology, digestion, inflammatory responses, and gut microbiota of juvenile channel catfish elicited by dietary enzymatic rice protein.

Fish Shellfish Immunol 2022 Jun 15;127:155-165. Epub 2022 Jun 15.

Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization, Hunan Agricultural University, Changsha, Hunan, 410128, China; College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China. Electronic address:

The reduction of fishmeal in aquafeeds has been the concern of researchers. Replacing fishmeal with plant proteins affects intestinal function and inflammation, but the interaction between the intestinal responses and gut microbiota remains unclear. In this study, juvenile channel catfish (Ictalurus punctatus) was fed with four diets in which enzymatic rice protein (RP) replaced fishmeal at levels of 0 (FM), 2.5% (RP2.5), 5.0% (RP5.0), and 7.5% (RP7.5) for 8 weeks to solve the problem mentioned above. Quantification of intestinal morphology showed that 2.5% or 5.0% RP significantly increased villus length and goblet cell number, accompanied by higher activities of intestinal trypsin, alkaline phosphatase (AKP), and Na/K-ATPase (NKA) in RP2.5 group (P < 0.05). In contrast, 7.5% RP slightly damaged the intestinal mucosa and significantly reduced the activities of amylase, AKP, and NKA, as well as decreased serum complement 4 (C4) and immunoglobulin M (IgM). Noteworthy, RT-qPCR showed that 2.5% RP significantly down-regulated intestinal mRNA expression level of il8, while up-regulated mif, tlr4, tlr7, tgfβ3, and cldn2. In contrast, 7.5% RP up-regulated the mRNA expression levels of il1β, il8, and mif, while down-regulated cldn3d. Analysis of gut microbiota showed that 2.5% RP increased the relative abundance of Bacteroidetes and significantly activated potential functions of gut microbiota involved in carbohydrate metabolism. The 7.5% RP increased the diversity of the gut microbiota, accompanied by a significant increase in the relative abundance of conditionally pathogenic bacteria such as Vibrio, Serratia, and Aeromonas (classified as Proteobacteria). Notably, Vibrio was the biomarker species with the greatest difference between the FM and RP7.5 groups (genus level). Correlation analysis indicated that Vibrio may affect immunity through the C4 pathway and further lead to gut inflammation and digestive impairment. Taken above, these results indicated that RP could affect intestinal morphology, digestion, and inflammation, and interact with the composition and potential function of gut microbiota. The low RP supplement (2.5%) improved intestinal morphology and digestion, while high supplement (7.5%) disrupted gut microbiota homeostasis, resulting in damage to intestinal mucosa and inflammatory response.
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http://dx.doi.org/10.1016/j.fsi.2022.06.018DOI Listing
June 2022

Amoxicillin-vonoprazan dual therapy for Helicobacter pylori eradication: A systematic review and meta-analysis.

J Gastroenterol Hepatol 2022 Jun 18. Epub 2022 Jun 18.

Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Background And Aim: The efficacy and safety of amoxicillin-vonoprazan (VA) dual therapy remained unclear.

Methods: This systematic review was conducted in accordance with the PRISMA 2009 guidelines. A systematic search of the Pubmed, Embase, and Cochrane database was conducted using the combination of "Helicobacter pylori or H. pylori or Hp," "amoxicillin or penicillin," and "Vonoprazan or TAK-438 or Takecab or (potassium AND competitive) or potassium-competitive." The initial and secondary outcome of this meta-analysis was to evaluate the efficacy and safety of VA dual therapy.

Results: Three studies and 668 H. pylori infected patients were included in this meta-analysis. The crude eradication rate of VA dual therapy was 87.5% and 89.6% by ITT and PP analysis, respectively. No significant differences were observed regarding the VA dual therapy and vonoprazan-amoxicillin-clarithromycin (VAC) triple therapy according to ITT (RR = 0.99, 95% CI, 0.93-1.05, P = 0.65) and PP (RR = 0.99, 95% CI, 0.94-1.05, P = 0.82) analysis. The side effect of VA dual therapy was 19.1% (95% CI, 5.9-32.4), which was lower than that of VAC triple therapy but there was no statistical significance (RR = 0.75, 95% CI, 0.59-1.06, P = 0.12).

Conclusion: VA dual therapy shows acceptable efficacy, good safety and avoid unnecessary antibiotic use in the first-line treatment for H. pylori infection. However, its application in other regions need to be further explored.
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http://dx.doi.org/10.1111/jgh.15917DOI Listing
June 2022

Construction and validation of an eight pyroptosis-related lncRNA risk model for breast cancer.

Am J Transl Res 2022 15;14(5):2779-2800. Epub 2022 May 15.

The Department of Breast Surgery, The Affiliated Zhuzhou Hospital of Xiang Ya School of Medicine Central South University Zhuzhou 412000, Hunan, P. R. China.

Objective: We developed a risk model based on pyroptosis-related long non-coding RNAs (lncRNAs) and assessed its prognostic value and clinical significance in breast cancer (BRCA).

Methods: BRCA RNA sequencing data with corresponding clinical information were retrieved from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression analysis was used to examine correlations between prognosis of BRCA patients and the expression levels of pyroptosis-related lncRNAs. A prognostic model was developed and validated by identifying the correlation of risk scores with tumor immune infiltration and immune cell function through immune response analysis. Functional analyses of focal dysfunction-related lncRNA were also carried out. Lastly, single sample gene set enrichment analysis (ssGSEA) was conducted to determine the differences in immune responses between the low- and high-risk groups.

Results: We divided the TCGA-BRCA dataset into 3 clusters by consensus clustering, and identified 11 pyroptosis-related lncRNAs that are differentially expressed between tumors and normal tissues. In addition, we determined if PD-L1 expression is associated with clustering and gene expression. The list was further narrowed down to eight pyroptosis-related lncRNAs and their regression coefficients were obtained through LASSO regression analysis. The relative proportion of 22 different immune cells in the BRCA microenvironment was determined using the CIBERSORT algorithm to explore the indicative effects of risk score on the tumor microenvironment (TME). We found that the resting mast cells, M0, and M2 macrophages were positively correlated with the risk scores.

Conclusion: The potential role of pyroptosis-related lncRNAs in BRCA prognosis may be exploited as a treatment target for patients with BRCA.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185044PMC
May 2022

Biosynthesis of Sordarin Revealing a Diels-Alderase for the Formation of the Norbornene Skeleton.

Angew Chem Int Ed Engl 2022 Aug 7;61(33):e202205577. Epub 2022 Jul 7.

State Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional Biomolecules, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University, Nanjing, 210023, China.

Sordarin (1) is a fungal diterpene glycoside that displays potent antifungal bioactivity through inhibition of elongation factor 2. The structures of sordarin and related compounds feature a highly rearranged tetracyclic diterpene core. In this study, we identified a concise pathway in the biosynthesis of sordarin. A diterpene cyclase (SdnA) generates the 5/8/5 cycloaraneosene framework, which is decorated by a set of P450s that catalyze a series of oxidation reactions, including hydroxylation, desaturation, and C-C bond oxidative cleavage, to give a carboxylate intermediate with a terminal alkene and a cyclopentadiene moiety. A novel Diels-Alderase SdnG catalyzes an intramolecular Diels-Alder (IMDA) reaction on this intermediate to forge the sordarin core structure. Subsequent methyl hydroxylation and glycosylation complete the biosynthesis of sordarin. Our work discloses a new strategy used by nature for the formation of the rearranged diterpene skeleton.
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http://dx.doi.org/10.1002/anie.202205577DOI Listing
August 2022

Phylotranscriptomic Analyses Reveal Multiple Whole-Genome Duplication Events, the History of Diversification and Adaptations in the Araceae.

Ann Bot 2022 Jun 7. Epub 2022 Jun 7.

Germplasm Bank of Wild Species, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, China.

Background And Aims: The Araceae are one of the most diverse monocot families with numerous morphological and ecological novelties. Plastid and mitochondrial genes have been used to investigate the phylogeny, and interpret shifts in the pollination biology and biogeography of the Araceae. In contrast, the role of whole-genome duplication (WGD) in the evolution of eight subfamilies remains unclear.

Methods: New transcriptomes or low-depth whole-genome sequences of 65 species were generated through Illumina sequencing. We reconstructed the phylogenetic relationships of Araceae using concatenated and species tree methods, estimated then the age of major clades using TreePL. We inferred the WGD events by Ks and gene tree methods. We investigated the diversification patterns applying time-dependent and trait-dependent models. The expansions of gene families and functional enrichments were analyzed using CAFE and InterProScan.

Key Results: Gymnostachydoideae was the earliest diverging lineage followed successively by Orontioideae, Lemnoideae and Lasioideae. In turn, they were followed by the clade of 'bisexual climbers' comprised of Pothoideae and Monsteroideae, which was resolved as the sister to the unisexual-flowered clade of Zamioculcadoideae and Aroideae. A special WGD event ψ (Psi) shared by the True-Araceae clade occurred in the Early Cretaceous. Net diversification rates first declined, increased then through time in the Araceae. The best diversification rate shift along the stem lineage of the True-Araceae clade was detected, and net diversification rates enhanced following the ψ-WGD. Functional enrichment analyses revealed that some genes, such as heat shock protein, glycosyl hydrolase and cytochrome P450, expanded within the True-Araceae clade.

Conclusions: Our results improve our understanding of aroid phylogeny using the large number of single/low-copy nuclear genes. In contrast to the Proto-Araceae group and the lemnoid clade adaption to aquatic environments, our analyses of WGD, diversification and functional enrichment indicated that WGD may play a more important role in the evolution of adaptations to tropical, terrestrial environments in the True-Araceae clade. These insights provide us with new resources to interpret the evolution of the Araceae.
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http://dx.doi.org/10.1093/aob/mcac062DOI Listing
June 2022

Convergent dysbiosis of gastric mucosa and fluid microbiome during stomach carcinogenesis.

Gastric Cancer 2022 Sep 4;25(5):837-849. Epub 2022 Jun 4.

Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.

Background: A complex microbiota in the gastric mucosa (GM) has been unveiled recently and its dysbiosis is identified to be associated with gastric cancer (GC). However, the microbial composition in gastric fluid (GF) and its correlation with GM during gastric carcinogenesis are unclear.

Methods: We obtained GM and GF samples from 180 patients, including 61 superficial gastritis (SG), 55 intestinal metaplasia (IM) and 64 GC and performed 16S rRNA gene sequencing analysis. The concentration of gastric acid and metabolite nitrite has been measured.

Results: Overall, the composition of microbiome in GM was distinct from GF with less diversity, and both were influenced by H. pylori infection. The structure of microbiota changed differentially in GM and GF across histological stages of GC, accompanied with decreased gastric acid and increased carcinogenic nitrite. The classifiers of GC based on microbial markers were identified in both GM and GF, including Lactobacillus, Veillonella, Gemella, and were further validated in an independent cohort with good performance. Interestingly, paired comparison between GM and GF showed that their compositional distinction remarkably dwindled from SG to GC, with some GF-enriched bacteria significantly increased in GM. Moreover, stronger interaction network between microbes of GM and GF was observed in GC compared to SG.

Conclusion: Our results, for the first time, revealed a comprehensive profile of both GM and GF microbiomes during the development of GC. The convergent microbial characteristics between GM and GF in GC suggest that the colonization of carcinogenic microbes in GM might derive from GF.
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http://dx.doi.org/10.1007/s10120-022-01302-zDOI Listing
September 2022
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