Publications by authors named "Li Tang"

1,042 Publications

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Photonic and Magnetic Dual-Responsive Molecularly Imprinted Sensor for Highly Specific Recognition of Enterovirus 71.

ACS Sens 2021 Oct 12. Epub 2021 Oct 12.

Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China.

The specific identification and detection of a virus are the critical factors to identify and control an epidemic situation. In this study, a novel photonic-magnetic responsive virus-molecularly imprinted photochemical sensor was constructed for recognition of enterovirus 71. As designed, the double-bond-modified magnetic metal organic framework and 4-(4'-acryloyloxyazo) benzoic acid were used as a magnetic carrier and light-responsive functional monomer, respectively. The structure of the recognition site of the virus-molecularly imprinted nanospheres can be photo-switched between two different structures to achieve rapid release and specific binding to the target virus. Additionally, the introduction of a magnetic core enables a rapid separation and recycling of imprinted particles. The device achieves a performance with high-specificity recognition (imprinting factor = 5.1) and an ultrahigh sensitivity with a detection limit of 9.5 × 10 U/mL (3.9 fM). Moreover, it has good reproducibility and can be stored for as long as 6 months. Thus, the approach used in this work opens a new avenue for the construction of multiresponsive virus sensors.
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http://dx.doi.org/10.1021/acssensors.1c01487DOI Listing
October 2021

Diversity of Macrophages in Lung Homeostasis and Diseases.

Front Immunol 2021 24;12:753940. Epub 2021 Sep 24.

College of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing, China.

Lung macrophages play important roles in the maintenance of homeostasis, pathogen clearance and immune regulation. The different types of pulmonary macrophages and their roles in lung diseases have attracted attention in recent years. Alveolar macrophages (AMs), including tissue-resident alveolar macrophages (TR-AMs) and monocyte-derived alveolar macrophages (Mo-AMs), as well as interstitial macrophages (IMs) are the major macrophage populations in the lung and have unique characteristics in both steady-state conditions and disease states. The different characteristics of these three types of macrophages determine the different roles they play in the development of disease. Therefore, it is important to fully understand the similarities and differences among these three types of macrophages for the study of lung diseases. In this review, we will discuss the physiological characteristics and unique functions of these three types of macrophages in acute and chronic lung diseases. We will also discuss possible methods to target macrophages in lung diseases.
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http://dx.doi.org/10.3389/fimmu.2021.753940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500393PMC
September 2021

Human telomerase reverse transcriptase (hTERT) synergistic with Sp1 upregulate Gli1 expression and increase gastric cancer invasion and metastasis.

J Mol Histol 2021 Oct 3. Epub 2021 Oct 3.

Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.

Abnormal expression of human telomerase reverse transcriptase (hTERT) has been widely identified in tumors, but the relevant mechanism is not well known. This study aims to investigate the role and mechanism of hTERT in gastric cancer metastasis. Gastric cancer and adjacent non-tumor tissues were collected and the expression levels of hTERT and Gli1 were detected by immunohistochemistry. The results demonstrated that hTERT and Gli1 expression levels in gastric cancer tissue were significantly higher than adjacent non-tumor tissues. Western blot and quantitative real-time PCR were used to an identified expression of the related protein in BGC-823 and SGC-7901 cells. The interactions between hTERT and Sp1 were tested by co-immunoprecipitation experiments. Chromatin immunoprecipitation was performed to confirm that Sp1 and hTERT could bind to the Gli1 promoter. Chromatin reimmunoprecipitation assay further demonstrated that both hTERT and Sp1 bind to the Sp1 site of the Gli1 promoter. Moreover, the hTERT, Sp1, and Gli1 were upregulate was verified in human gastric cancer tissues. These results showed that the expression levels of hTERT in GC tissues were strongly closed to the depth of invasion, lymph node metastasis, TNM (tumor, node, metastasis) stage, and distant metastasis. By combining Sp1 and Gli1 promoter, hTERT upregulated Gli1 expression and promoted invasion and metastasis of GC cells. Overall, these data provide a new molecular mechanism of hTERT to promotes gastric cancer progression. Targeting the hTERT/Sp1/Gli1 axis may represent a new therapeutic strategy.
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http://dx.doi.org/10.1007/s10735-021-10019-9DOI Listing
October 2021

Characterization of aroma and bacteria profiles of Sichuan industrial paocai by HS-SPME-GC-O-MS and 16S rRNA amplicon sequencing.

Food Res Int 2021 Nov 28;149:110667. Epub 2021 Aug 28.

College of Biomass Science and Engineering, Sichuan University, Chengdu 610065, China; School of Liquor-Brewing Engineering, Sichuan University of Jinjiang College, Meishan 620860, China. Electronic address:

Sichuan industrial paocai and traditional home-made paocai have different aroma profiles due to different manufacturing techniques, but detailed information about the aroma profiles and aroma-producing microorganism of Sichuan industrial paocai remain largely elusive. For this reason, we established and validated an external standard method of headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) combined with gas chromatography-olfactometry (GC-O) for identification and accurate quantitation of aroma-active compounds in Sichuan industrial paocai. This method was combined with 16S rRNA amplicon sequencing to comprehensively analyze the aroma and bacteria profiles of Sichuan industrial paocai. A total of 121 volatile compounds were identified, among which 36 odorants were identified as aroma-active compounds with aroma intensities (AIs) ranging from 0.67 to 5.00 by GC-O. The types of aroma-active compounds in Sichuan industrial paocai were variety-specific to some extent, but the aroma-active compounds shared by different varieties of Sichuan industrial paocai (i.e., skeleton aroma-active compounds) were phenylethyl alcohol, acetic acid, butanoic acid, 2-methylbutanoic acid, ethyl hexanoate, 4-ethylphenol and 4-ethylguaiacol. Moreover, 17 key aroma-active compounds of AI > 1 in radish paocai were quantitated by external standard method, and their odor activity values (OAVs) were calculated based on the odor thresholds. Further, 12 aroma-active compounds with OAV ≥ 1 in one of the radish paocai were selected to construct the recombination model, which revealed good agreement with the original sample. Furthermore, Lactobacillus, Pediococcus, Pseudomonas and Sphingomonas were the dominant bacteria in Sichuan industrial paocai. Correlation analysis between 16 dominant bacteria and 36 aroma-active compounds showed that Pediococcus, Arcobacter and Lactobacillus could be the core aroma-producing bacteria of Sichuan industrial paocai.
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http://dx.doi.org/10.1016/j.foodres.2021.110667DOI Listing
November 2021

Fish forewarning of comprehensive toxicity in water environment based on Bayesian sequential method.

J Environ Sci (China) 2021 Dec 24;110:150-159. Epub 2021 May 24.

State Key Joint Laboratory of Environment Simulation and Pollution Control, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Environmental impact of pollutants can be analyzed effectively by acquiring fish behavioral signals in water with biological behavior sensors. However, a variety of factors, such as the complexity of biological organisms themselves, the device error and the environmental noise, may compromise the accuracy and timeliness of model predictions. The current methods lack prior knowledge about the fish behavioral signals corresponding to characteristic pollutants, and in the event of a pollutant invasion, the fish behavioral signals are poorly discriminated. Therefore, we propose a novel method based on Bayesian sequential, which utilizes multi-channel prior knowledge to calculate the outlier sequence based on wavelet feature followed by calculating the anomaly probability of observed values. Furthermore, the relationship between the anomaly probability and toxicity is analyzed in order to achieve forewarning effectively. At last, our algorithm for fish toxicity detection is verified by integrating the data on laboratory acceptance of characteristic pollutants. The results show that only one false positive occurred in the six experiments, the present algorithm is effective in suppressing false positives and negatives, which increases the reliability of toxicity detections, and thereby has certain applicability and universality in engineering applications.
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http://dx.doi.org/10.1016/j.jes.2021.03.035DOI Listing
December 2021

A Journey to the West: The Ancient Dispersal of Rice Out of East Asia.

Rice (N Y) 2021 Sep 25;14(1):83. Epub 2021 Sep 25.

Department of Archaeology, Max Planck Institute for the Science of Human History, Jena, Thuringia, Germany.

Rice is one of the most culturally valued and widely grown crops in the world today, and extensive research over the past decade has clarified much of the narrative of its domestication and early spread across East and South Asia. However, the timing and routes of its dispersal into West Asia and Europe, through which rice eventually became an important ingredient in global cuisines, has remained less clear. In this article, we discuss the piecemeal, but growing, archaeobotanical data for rice in West Asia. We also integrate written sources, linguistic data, and ethnohistoric analogies, in order to better understand the adoption of rice outside its regions of origin. The human-mediated westward spread of rice proceeded gradually, while its social standing and culinary uses repeatedly changing over time and place. Rice was present in West Asia and Europe by the tail end of the first millennium BC, but did not become a significant crop in West Asia until the past few centuries. Complementary historical, linguistic, and archaeobotanical data illustrate two separate and roughly contemporaneous routes of westward dispersal, one along the South Asian coast and the other through Silk Road trade. By better understanding the adoption of this water-demanding crop in the arid regions of West Asia, we explore an important chapter in human adaptation and agricultural decision making.
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http://dx.doi.org/10.1186/s12284-021-00518-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464642PMC
September 2021

Cross-reactive Antibody Response to mRNA SARS-CoV-2 Vaccine After Recent COVID-19-Specific Monoclonal Antibody Therapy.

Open Forum Infect Dis 2021 Sep 10;8(9):ofab420. Epub 2021 Aug 10.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

The efficacy of coronavirus disease 2019 (COVID-19) vaccines administered after COVID-19-specific monoclonal antibody is unknown, and "antibody interference" might hinder immune responses leading to vaccine failure. In an institutional review board-approved prospective study, we found that an individual who received mRNA COVID-19 vaccination <40 days after COVID-19-specific monoclonal antibody therapy for symptomatic COVID-19 had similar postvaccine antibody responses to SARS-CoV-2 receptor binding domain (RBD) for 4 important SARS-CoV-2 variants (B.1, B.1.1.7, B.1.351, and P.1) as other participants who were also vaccinated following COVID-19. Vaccination against COVID-19 shortly after COVID-19-specific monoclonal antibody can boost and expand antibody protection, questioning the need to delay vaccination in this setting.

Trial Registration : The St. Jude Tracking of Viral and Host Factors Associated with COVID-19 study; NCT04362995; https://clinicaltrials.gov/ct2/show/NCT04362995.
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http://dx.doi.org/10.1093/ofid/ofab420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454518PMC
September 2021

Periphery kinetic perimetry: clinically feasible to complement central static perimetry.

BMC Ophthalmol 2021 Sep 23;21(1):343. Epub 2021 Sep 23.

Department of Ophthalmology, Chengdu First People's Hospital, Chengdu, Sichuan, China.

Background: Existing evidence suggests that visual field defect in eyes with glaucoma significantly varies between individuals. The following study compared the central visual field defects with the peripheral visual field defects in patients with suspect glaucoma and primary open-angle glaucoma (POAG) and investigated whether using the central visual field test alone could result in loss of clinically valuable information.

Methods: In this prospective observational study, 167 eyes from 89 patients with suspect glaucoma or POAG were first examined with static automated perimetry (SAP), followed by a peripheral visual field test on Octopus 900 perimeter (Haag-Streit, Koeniz, Switzerland). The peripheral visual field test was performed by "Auto Kinetic Perimetry" program, in which Goldmann III4e stimuli randomly moved along 16 vectors at a constant angular velocity of 5 deg/s.

Results: Glaucomatous peripheral visual field defects were seen in 18% of the eyes with a normal central visual field. In addition, 86% of glaucoma patients with moderate-to-severe central visual field defects had corresponding peripheral visual field defects in the form of localized or diffuse depression of the isopters. Furthermore, a moderate correlation was found between the central and peripheral visual fields. The median test duration was 71 s for the peripheral test and 803 s for the central test (p < 0.001).

Conclusions: Our study demonstrated the diversity of glaucomatous visual field defects, as well as the possibility of losing the clinically valuable information due to focusing on the central visual field test alone. The peripheral kinetic perimetry is clinically feasible to complement the central static perimetry for a comprehensive assessment of visual function in glaucoma patients.
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http://dx.doi.org/10.1186/s12886-021-02056-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459489PMC
September 2021

The mitochondria-targeting antioxidant MitoQ alleviated lipopolysaccharide/ d-galactosamine-induced acute liver injury in mice.

Immunol Lett 2021 Sep 12;240:24-30. Epub 2021 Sep 12.

Laboratory of Stem cell and Tissue Engineering, Chongqing Medical University, Chongqing, China; Department of Pathophysiology, Chongqing Medical University, Chongqing, China. Electronic address:

The mitochondria are the primary source of reactive oxygen species (ROS) under pathological condition, but the significance of mitochondrial ROS in the development of Lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute liver injury remains unclear. In the present study, the level of mitochondrial ROS in LPS/D-Gal has been determined by MitoSox staining and the potential roles of mitochondrial ROS in LPS/D-Gal-induced liver injury have been investigated by using the mitochondria-targeting antioxidant MitoQ. The results indicated that LPS/D-Gal exposure induced the generation of mitochondrial ROS while treatment with MitoQ reduced the level of mitochondrial ROS. Treatment with MitoQ ameliorated LPS/D-Gal-induced histopathologic abnormalities, suppressed the elevation of AST and ALT, and increased the survival rate of the experimental animals. Treatment with MitoQ also suppressed LPS/D-Gal-induced production of tumor necrosis factor α (TNF-α), inhibited the activities of caspase-3, caspase-8 and caspase-9, decreased the level of cleaved caspase-3 and reduced the counts of TUNEL positive cells. These results indicate that mitochondrial ROS is involved in the development of LPS-induced acute liver injury and the mitochondria-targeting antioxidant MitoQ might have potential value for the treatment of inflammation-based acute liver injury.
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http://dx.doi.org/10.1016/j.imlet.2021.09.003DOI Listing
September 2021

Baseline Gut Metagenomic Functional Gene Signature Associated with Variable Weight Loss Responses following a Healthy Lifestyle Intervention in Humans.

mSystems 2021 Sep 14:e0096421. Epub 2021 Sep 14.

Institute for Systems Biologygrid.64212.33, Seattle, Washington, USA.

Recent human feeding studies have shown how the baseline taxonomic composition of the gut microbiome can determine responses to weight loss interventions. However, the functional determinants underlying this phenomenon remain unclear. We report a weight loss response analysis on a cohort of 105 individuals selected from a larger population enrolled in a commercial wellness program, which included healthy lifestyle coaching. Each individual in the cohort had baseline blood metabolomics, blood proteomics, clinical labs, dietary questionnaires, stool 16S rRNA gene sequencing data, and follow-up data on weight change. We generated additional targeted proteomics data on obesity-associated proteins in blood before and after intervention, along with baseline stool metagenomic data, for a subset of 25 individuals who showed the most extreme weight change phenotypes. We built regression models to identify baseline blood, stool, and dietary features associated with weight loss, independent of age, sex, and baseline body mass index (BMI). Many features were independently associated with baseline BMI, but few were independently associated with weight loss. Baseline diet was not associated with weight loss, and only one blood analyte was associated with changes in weight. However, 31 baseline stool metagenomic functional features, including complex polysaccharide and protein degradation genes, stress-response genes, respiration-related genes, and cell wall synthesis genes, along with gut bacterial replication rates, were associated with weight loss responses after controlling for age, sex, and baseline BMI. Together, these results provide a set of compelling hypotheses for how commensal gut microbiota influence weight loss outcomes in humans. Recent human feeding studies have shown how the baseline taxonomic composition of the gut microbiome can determine responses to dietary interventions, but the exact functional determinants underlying this phenomenon remain unclear. In this study, we set out to better understand interactions between baseline BMI, metabolic health, diet, gut microbiome functional profiles, and subsequent weight changes in a human cohort that underwent a healthy lifestyle intervention. Overall, our results suggest that the microbiota may influence host weight loss responses through variable bacterial growth rates, dietary energy harvest efficiency, and immunomodulation.
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http://dx.doi.org/10.1128/mSystems.00964-21DOI Listing
September 2021

Switchable immune modulator for tumor-specific activation of anticancer immunity.

Sci Adv 2021 Sep 10;7(37):eabg7291. Epub 2021 Sep 10.

Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abg7291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442900PMC
September 2021

Upregulation of RIP3 promotes necroptosis via a ROS‑dependent NF‑κB pathway to induce chronic inflammation in HK‑2 cells.

Mol Med Rep 2021 11 9;24(5). Epub 2021 Sep 9.

Department of Renal Transplantation, Ningbo Urology and Nephrology Hospital, Ningbo, Zhejiang 315100, P.R. China.

Tubular atrophy/interstitial fibrosis (TA/IF) is a major cause of late allograft loss, and inflammation within areas of TA/IF is associated with adverse outcomes in kidney transplantation. However, there is currently no satisfactory method to suppress this inflammation to improve TA/IF. The present study aimed to determine the proinflammatory role of receptor‑interacting protein 3 (RIP3) in TA/IF to discover a novel therapeutic target. Reverse transcription‑quantitative PCR and western blotting were performed to detect the expression of RIP3 and inflammation‑associated factors. Lactate dehydrogenase release assay was used to determine necroptosis. Fluorescent 2,7‑dichlorodihydrofluorescein diacetate was used to detect the levels of reactive oxygen species (ROS). The results demonstrated that patients with chronic TA/IF exhibited upregulated receptor‑interacting protein 3 (RIP3) expression compared with the patients who had a favorable recovery after renal transplant. Therefore, the current study used normal renal tubular epithelial cells HK‑2 to establish a cellular model with a high expression level of RIP3 in order to investigate the effect of RIP3 on renal epithelial cells after transplantation. The western blotting results demonstrated that overexpression of RIP3 could significantly increase the phosphorylation level of the necroptosis executive molecule mixed lineage kinase domain‑like protein. Lactate dehydrogenase release, a key feature of necroptosis, was also markedly improved by RIP3 overexpression. Moreover, a higher inflammatory response was detected in HK‑2 cells with RIP3 overexpression, and this elevated inflammation could be restored by the necroptosis inhibitor necrosulfonamide. Of note, it was found that overexpression of RIP3 activated the NF‑κB signaling pathway via the excessive accumulation of ROS to induce necroptosis, which ultimately led to inflammation. Collectively, these findings indicated that overexpression of RIP3 promoted necroptosis via a ROS‑dependent NF‑κB pathway to induce chronic inflammation, suggesting that RIP3 may have the potential to be a therapeutic target against inflammation in TA/IF.
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http://dx.doi.org/10.3892/mmr.2021.12423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441977PMC
November 2021

tRNA-Derived Fragment tRF-Glu-TTC-027 Regulates the Progression of Gastric Carcinoma MAPK Signaling Pathway.

Front Oncol 2021 23;11:733763. Epub 2021 Aug 23.

Department of General Surgery, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China.

Transfer RNA-derived RNA fragments (tRFs) belong to non-coding RNAs (ncRNAs) discovered in most carcinomas. Although some articles have demonstrated the characteristics of tRFs in gastric carcinoma (GC), the underlying mechanisms still need to be elucidated. Meanwhile, it was reported that the MAPK pathway was momentous in GC progression. Thus we focused on investigating whether tRF-Glu-TTC-027 could act as a key role in the progression of GC with the regulation of the MAPK pathway. We collected the data of the tRNA-derived fragments expression profile from six paired clinical GC tissues and corresponding adjacent normal samples in this study. Then we screened tRF-Glu-TTC-027 for analysis by using RT-PCR. We transfected GC cell lines with tRF-Glu-TTC-027 mimics or mimics control. Then the proliferation, migration, and invasion assays were performed to assess the influence of tRF-Glu-TTC-027 on GC cell lines. Fluorescence hybridization assay was conducted to confirm the cell distribution of tRF-Glu-TTC-027. We confirmed the mechanism that tRF-Glu-TTC-027 influenced the MAPK signaling pathway and observed a strong downregulation of tRF-Glu-TTC-027 in clinical GC samples. Overexpression of tRF-Glu-TTC-027 suppressed the malignant activities of GC and . MAPK signaling pathway was confirmed to be a target pathway of tRF-Glu-TTC-027 in GC by western blot. This is the first study to show that tRF-Glu-TTC-027 was a new tumor-suppressor and could be a potential object for molecular targeted therapy in GC.
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http://dx.doi.org/10.3389/fonc.2021.733763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419445PMC
August 2021

Membranes for olefin-paraffin separation: An industrial perspective.

Proc Natl Acad Sci U S A 2021 Sep;118(37)

Packaging and Specialty Plastics, Catalysis and Hydrocarbon Process R&D, The Dow Chemical Company, Freeport, TX 77541;

In the next decade, separation science will be an important research topic in addressing complex challenges like reducing carbon footprint, lowering energy cost, and making industrial processes simpler. In industrial chemical processes, particularly in petrochemical operations, separation and product refining steps are responsible for up to 30% of energy use and 30% of the capital cost. Membranes and adsorption technologies are being actively studied as alternative and partial replacement opportunities for the state-of-the-art cryogenic distillation systems. This paper provides an industrial perspective on the application of membranes in industrial petrochemical cracker operations. A gas separation performance figure of merit for propylene/propane separation for different classes of materials ranging from inorganic, carbon, polymeric, and facilitated transport membranes is also reported. An in-house-developed model provided insights into the importance of operational parameters on the overall membrane design.
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http://dx.doi.org/10.1073/pnas.2022194118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449386PMC
September 2021

Coevolution of COVID-19 research and China's policies.

Health Res Policy Syst 2021 Sep 6;19(1):121. Epub 2021 Sep 6.

Department of Digital Communication, Soochow University, Room 5146, Building 1005, No.1 Wenjing Road, Dushu Lake Campus of Soochow University, Suzhou, Jiangsu, China.

Background: In the era of evidence-based policy-making (EBPM), scientific outputs and public policy should engage with each other in a more interactive and coherent way. Notably, this is becoming increasingly critical in preparing for public health emergencies.

Methods: To explore the coevolution dynamics between science and policy (SAP), this study explored the changes in, and development of, COVID-19 research in the early period of the COVID-19 outbreak in China, from 30 December 2019 to 26 June 2020. In this study, VOSviewer was adopted to calculate the link strength of items extracted from scientific publications, and machine learning clustering analysis of scientific publications was carried out to explore dynamic trends in scientific research. Trends in relevant policies that corresponded to changing trends in scientific research were then traced.

Results: The study observes a salient change in research content as follows: an earlier focus on "children and pregnant patients", "common symptoms", "nucleic acid test", and "non-Chinese medicine" was gradually replaced with a focus on "aged patients", "pregnant patients", "severe symptoms and asymptomatic infection", "antibody assay", and "Chinese medicine". "Mental health" is persistent throughout China's COVID-19 research. Further, our research reveals a correlation between the evolution of COVID-19 policies and the dynamic development of COVID-19 research. The average issuance time of relevant COVID-19 policies in China is 8.36 days after the launching of related research.

Conclusions: In the early stage of the outbreak in China, the formulation of research-driven-COVID-19 policies and related scientific research followed a similar dynamic trend, which is clearly a manifestation of a coevolution model (CEM). The results of this study apply more broadly to the formulation of policies during public health emergencies, and provide the foundation for future EBPM research.
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http://dx.doi.org/10.1186/s12961-021-00770-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419657PMC
September 2021

Case Report: Drug-Induced Immune Haemolytic Anaemia Caused by Cefoperazone-Tazobactam/ Sulbactam Combination Therapy.

Front Med (Lausanne) 2021 12;8:697192. Epub 2021 Aug 12.

Department of Blood Transfusion, Dongguan Maternal and Child Health Hospital, Dongguan, China.

There has previously been a report of a patient developing haemolytic anaemia following exposure to cefoperazone. Another case has been reported involving the detection of cefoperazone-dependent antibodies in the absence of immune haemolytic anaemia. To date, no serological evidence has been reported to suggest that cefoperazone can lead to drug-induced immune haemolytic anaemia (DIIHA). This report aims to fill these gaps in knowledge by describing a case of DIIHA caused by cefoperazone-dependent antibodies. A 59-year-old man developed fatal haemolytic anaemia while receiving cefoperazone-tazobactam or cefoperazone-sulbactam for the treatment of a lung infection that occurred after craniocerebral surgery. This eventually led to renal function impairment. Prior to the discontinuation of cefoperazone treatment, the patient showed strong positive (4+) results for both anti-IgG and anti-C3d direct antiglobulin test (DAT), while cefoperazone-dependent IgM and IgG antibodies were detected. The patient's plasma and O-type RBCs were incubated with tazobactam or sulbactam solution at 37°C for 3 h, the results of DAT for anti-IgG and anti-C3d were both positive. Forty-three days after the discontinuation of cefoperazone, the results of DAT for anti-IgG and anti-C3d were negative. Meanwhile incubation of the patient's fresh serum and his own RBCs with cefoperazone at 37°C, gave rise to mild haemolysis, and the results of DAT for both anti-IgG and anti-C3d were positive. It is suggested that cefoperazone-dependent antibodies can activate complement, and the non-immunologic protein adsorption effect of tazobactam or sulbactam can enhance IgG and complement binding to RBCs. This may promote the formation of immunocomplexes and complement activation, thereby aggravating haemolysis.
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http://dx.doi.org/10.3389/fmed.2021.697192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415779PMC
August 2021

Probiotic 10 and 16 enhance growth performance of broilers by improving the intestinal health.

Anim Nutr 2021 Sep 24;7(3):829-840. Epub 2021 Jul 24.

Key Laboratory of Molecular Animal Nutrition of the Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China) of the Ministry of Agriculture, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Institute of Animal Nutrition and Feed Sciences, College of Animal Sciences, Zhejiang University, 310058, Hangzhou, China.

With the ever-growing strict prohibitions on antibiotic growth promoters (AGP) in animal production, in-feed probiotics are becoming attractive alternatives to antibiotics in the poultry industry. To investigate the effects of 10 and 16 on the growth performance and intestinal health of broilers, 540 male Cobb 500 broilers of 1 d old were randomly divided into 3 groups with 6 replicates per group and 30 chicks per replicate. Broilers were fed with either a basal diet or basal diets supplemented with 1 × 10 colony-forming units (CFU)/kg 10 (BSC10) or 16 (Lac16) for 42 d. Results showed that Lac16 treatment improved ( < 0.05) the growth performance (body weight and feed conversion) of broilers at the starter phase, while BSC10 treatment slightly improved ( > 0.05) the growth performance of the starter phase broilers. The increased villus height ( < 0.05) at d 14, 21 and 42 and villus height to crypt depth ratio ( < 0.05) at d 14 and 21 were observed in the ileum of the 2 probiotic groups. Besides, transmission electron microscopy results showed that the 2 probiotics enhanced the intestinal epithelial barrier. Both probiotic treatments up-regulated ( < 0.05) the mRNA expression of fatty acid binding protein 1 () and sodium-dependent glucose transporters-1 () in the ileal mucosa of broilers at d 21. In addition, BSC10 and Lac16 treatments significantly ( < 0.05) increased the relative abundance of short-chain fatty acids-producing bacteria, such as , , and , and significantly ( < 0.05) decreased the relative abundance of enteric pathogens (, and ). Furthermore, the 2 probiotic treatments also increased the positive connection among the intestinal microbes and the carbohydrate metabolism-related pathways of the intestinal bacteria ( < 0.05), with decreasing ( < 0.05) nucleotides biosynthesis-related pathways of the intestinal bacteria. Overall, these results suggest that the 2 probiotics, especially Lac16, have a potential beneficial effect on the growth performance and intestinal health of starter phase broilers.
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http://dx.doi.org/10.1016/j.aninu.2021.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384779PMC
September 2021

Introduction of cation vacancies and iron doping into TiO enabling efficient uranium photoreduction.

J Hazard Mater 2021 Aug 17;423(Pt A):126935. Epub 2021 Aug 17.

State Key Laboratory of Environment-friendly Energy Materials, National Co-innovation Center for Nuclear Waste Disposal and Environmental Safety, Sichuan Co-Innovation Center for New Energetic Materials, Nuclear Waste and Environmental Safety Key Laboratory of Defense, School of National Defence Science & Technology, Southwest University of Science and Technology, Mianyang, Sichuan 621010, PR China. Electronic address:

The reduction of U(VI) to U(IV) in wastewater by semiconductor photocatalysis has become a new highly efficient and low-cost method for U(VI) removal. However, due to the weak absorption of visible light led by wide band gap and low carrier utilization rate resulted from the severe electron-holes recombination, the photoreduction performance of U(VI) is limited. Herein, the Ti vacancies and doped Fe atoms were simultaneously introduced into TiO nanosheet (labeled as 4%Fe-TiO) as a highly active and stable catalysis for U(VI) photoreduction. Without adding any hole sacrifice agent, 4%Fe-TiO nanosheets achieved 99.7% removal efficiency for U(VI) within 120 min. And the 92.1% removal efficiency of U(VI) via 4%Fe-TiO nanosheets was still maintained after 5 cycles. Moreover, 4%Fe-TiO exhibited dramatic removal rate, 81.6% U(VI) in the solution was removed in 10 min. Further study on the mechanism showed that simultaneously introducing the Ti vacancies and doped Fe atoms in 4%Fe-TiO nanosheets improved the visible light utilization and decreased the recombination of photogenerated electron-hole pairs, contributing to the highly efficiency removal of U(VI).
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http://dx.doi.org/10.1016/j.jhazmat.2021.126935DOI Listing
August 2021

Zero-valent iron coupled plant biomass for enhancing the denitrification performance of ecological floating bed.

Bioresour Technol 2021 Dec 21;341:125820. Epub 2021 Aug 21.

Shanghai Engineering Research Center of Landscape Water Environment, Shanghai 200031, PR China.

The ecological floating bed (EFB) coupled with zero-valent iron (ZVI) is proposed to treat low carbon-to-nitrogen ratio water. However, the application of ZVI is limited by low electron transfer efficiency. Coupling ZVI with carbon materials may improve the performance. In this study, the EFB with ZVI coupled plant biomass (IB-EFB) was established to enhance denitrification performance and compared to the EFB with ZVI coupled activated carbon (IC-EFB). The results showed that higher denitrification rate was observed in IB-EFB (68.8%) than that in IC-EFB (54.40%), which attributed to the synergistic effect of ZVI and plant biomass. Plant biomass also promoted the electron transfer of ZVI which enhanced the Fe(II)-mediated denitrification. High-throughput sequencing analysis revealed that IB-EFB enriched iron-related denitrifying bacteria more effectively than IC-EFB, and obtained high abundance of phototrophic Fe(II)-oxidizing bacteria Rhodopseudomonas (19.26%). Thus coupling ZVI with plant biomass has a potential for enhanced nitrogen removal in EFB.
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http://dx.doi.org/10.1016/j.biortech.2021.125820DOI Listing
December 2021

Novel Surrogate Neutralizing Assay Supports Parvovirus B19 Vaccine Development for Children with Sickle Cell Disease.

Vaccines (Basel) 2021 Aug 4;9(8). Epub 2021 Aug 4.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Children with sickle cell disease (SCD) suffer life-threatening transient aplastic crisis (TAC) when infected with parvovirus B19. In utero, infection of healthy fetuses may result in anemia, hydrops, and death. Unfortunately, although promising vaccine candidates exist, no product has yet been licensed. One barrier to vaccine development has been the lack of a cost-effective, standardized parvovirus B19 neutralization assay. To fill this void, we evaluated the unique region of VP1 (VP1u), which contains prominent targets of neutralizing antibodies. We discovered an antigenic cross-reactivity between VP1 and VP2 that, at first, thwarted the development of a surrogate neutralization assay. We overcame the cross-reactivity by designing a mutated VP1u (VP1uAT) fragment. A new VP1uAT ELISA yielded results well correlated with neutralization (Spearman's correlation coefficient = 0.581; = 0.001), superior to results from a standard clinical diagnostic ELISA or an ELISA with virus-like particles. Virus-specific antibodies from children with TAC, measured by the VP1uAT and neutralization assays, but not other assays, gradually increased from days 0 to 120 post-hospitalization. We propose that this novel and technically simple VP1uAT ELISA might now serve as a surrogate for the neutralization assay to support rapid development of a parvovirus B19 vaccine.
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http://dx.doi.org/10.3390/vaccines9080860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402426PMC
August 2021

Activation of PKM2 metabolically controls fulminant liver injury via restoration of pyruvate and reactivation of CDK1.

Pharmacol Res 2021 Oct 20;172:105838. Epub 2021 Aug 20.

Department of Pathophysiology, Chongqing Medical University, Chongqing, China; Laboratory of Stem cell and Tissue Engineering, Chongqing Medical University, Chongqing, China. Electronic address:

Accumulating evidence indicates that metabolic events profoundly modulate the progression of various diseases. Pyruvate is a central metabolic intermediate in glucose metabolism. In the present study, the metabolic status of pyruvate and its pharmacological significance has been investigated in mice with lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced fulminant liver injury. Our results indicated that LPS/D-Gal exposure decreased the activity of pyruvate kinase and the content of pyruvate, which were reversed by the PKM2 activator TEPP-46. Pretreatment with TEPP-46 or supplementation with the cell-permeable pyruvate derivate ethyl pyruvate (EP) attenuated LPS/D-Gal-induced liver damage. Interestingly, post-insult intervention of pyruvate metabolism also resulted in beneficial outcomes. The phospho-antibody microarray analysis and immunoblot analysis found that the inhibitory phosphorylation of cyclin dependent kinase 1 (CDK1) was reversed by TEPP-46, DASA-58 or EP. In addition, the therapeutic benefits of PKM2 activator or EP were blunted by the CDK1 inhibitor Ro 3306. Our data suggests that LPS/D-Gal exposure-induced decline of pyruvate might be a novel metabolic mechanism underlies the development of LPS/D-Gal-induced fulminant liver injury, PKM2 activator or pyruvate derivate might have potential value for the pharmacological intervention of fulminant liver injury.
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http://dx.doi.org/10.1016/j.phrs.2021.105838DOI Listing
October 2021

Yap Promotes Noncanonical Wnt Signals From Cardiomyocytes for Heart Regeneration.

Circ Res 2021 Oct 23;129(8):782-797. Epub 2021 Aug 23.

Cardiomyocyte Renewal Laboratory, Texas Heart Institute, Houston (S.L., T.R.H., J.F.M.).

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCRESAHA.121.318966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513110PMC
October 2021

Association of Ocular Surface Diseases With SARS-CoV-2 Infection in Six Districts of China: An Observational Cohort Study.

Front Immunol 2021 6;12:695428. Epub 2021 Aug 6.

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses is mainly transmitted through respiratory droplets. Notably, some coronavirus disease 2019 (COVID-19) patients have ocular manifestations, including conjunctival hyperaemia, chemosis, epiphora, and increased secretions. However, the association between SARS-CoV-2 and ocular surface diseases is poorly described. Between May 2020 and March 2021, a total of 2, 0157 participants from six districts of China were enrolled. Serum samples were tested for immunoglobulin G and M (IgG and IgM) antibodies against the SARS-CoV-2 spike protein and nucleoprotein using magnetic chemiluminescence enzyme immunoassays. Throat swabs were tested for SARS-CoV-2 RNA using RT-PCR assays in a designated virology laboratory. Fisher exact, χ test, and logistic regression analysis were performed. Of 2, 0157 serum samples tested, 1, 755 (8.71%) were from ocular surface diseases, 1, 2550 (62.26%) from no-ocular surface diseases (ocular diseases except ocular surface diseases), 5, 852 (29.03%) from no-ocular diseases. SARS-CoV-2 prevalence for the combined measure was 0.90% (182/2, 0157). Seroprevalence of SARS-CoV-2 was significantly (p<0.05) higher in the population with ocular surface diseases (2.28%, 40/1755) compared with no-ocular surface diseases (0.70%, 88/1, 2550), and no-ocular diseases (0.92%, 54/5, 852). Similar results were also observed with respect to sex, age, time, and districts. Logistic regression analyses revealed that ocular surface diseases [ocular surface diseases no-ocular diseases (p=0.001, OR =1.467, 95% CI=1.174-1.834); ocular surface diseases no-ocular surface diseases (p<0.001, OR =2.170, 95% CI=1.434-3.284)] were associated with increased risk of susceptible to SARS-CoV-2 infection. In a word, there was a significant association between ocular surface disease and SARS-CoV-2 infection. Therefore, increasing awareness of eye protection during the pandemic is necessary, especially for individuals with ocular surface diseases.
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http://dx.doi.org/10.3389/fimmu.2021.695428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378230PMC
September 2021

Forkhead domain inhibitory-6 attenuates subconjunctival fibrosis in rabbit model with trabeculectomy.

Exp Eye Res 2021 09 8;210:108725. Epub 2021 Aug 8.

Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Jinan University, Shenzhen, China. Electronic address:

Antiproliferative therapies are crucially important for improving the success rate of the glaucoma filtration surgeries. In this study, we investigated the potential efficacy of Forkhead Domain Inhibitory-6 (FDI-6) in inhibiting post-trabeculectomy subconjunctival fibrosis. In vitro, the effect of FDI-6 (10 μM) on fibrotic response and its underlying mechanism were investigated in rabbit tenon's fibroblasts (RTFs) treated with or without transforming growth factor-β1 (TGF-β1, 20 ng/mL). In vivo, FDI-6 (40 μM) was injected subconjunctivally to a rabbit trabeculectomy model. Intraocular pressure (IOP) changes were monitored within the 14-day period post-surgery. Bleb morphology and subepithelial fibrosis at the operating area were evaluated with slit lamp and confocal microscopic examinations and with histologic examinations. The results showed that, in cell culture studies, FDI-6 suppressed the proliferation, migration, collagen gel contraction and the expression levels of fibronectin (FN) and α-smooth muscle actin (α-SMA) in RTFs with TGF-β treatment by down-regulating the TGF-β1/Smad2/3 signaling pathway. In animal studies, the IOPs of the FDI-6-treated group were significantly lower than those of the saline-treated group after trabeculectomy. The FDI-6-treated eyes showed a better bleb appearance with fewer blood vessels compared to the saline-treated eyes. The analysis of confocal microscopy in vivo and histopathology revealed that subconjunctival fibrosis after trabeculectomy was significantly attenuated in the FDI-6-treated group compared to the controls. In conclusion, our studies indicate that FDI-6 exerts an inhibitory effect on subconjunctival fibrosis caused by trabeculectomy, holding potentials as a new antiproliferative agent used in anti-glaucoma filtration surgeries in the future.
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http://dx.doi.org/10.1016/j.exer.2021.108725DOI Listing
September 2021

Serum syndecan-4 is associated with nonalcoholic fatty liver disease.

J Dig Dis 2021 Sep 30;22(9):536-544. Epub 2021 Aug 30.

Department of Gastroenterology, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objectives: The accelerated shedding of extracellular domains of syndecan-4 (SDC4) is associated with central obesity and insulin resistance, while the association between serum SDC4 and nonalcoholic fatty liver disease (NAFLD) is unknown. We aimed to examine the association between SDC4 and NAFLD.

Methods: Adults undergoing a health examination from 1 June 2019 to 31 December 2019 were enrolled. A diagnosis of NAFLD was made with an abdominal ultrasound. Logistic regression models and the receiver operating characteristic (ROC) curves were used to evaluate the role of SDC4 in predicting NAFLD.

Results: In total, 533 eligible participants were finally enrolled, among them 157 (29.46%) had NAFLD. The proportion of patients with NAFLD increased with the increasing quartiles of serum SDC4. With the increase of serum SDC4 levels, metabolic features including waist circumference, serum triglyceride, total cholesterol, fasting blood glucose, fasting insulin and homeostasis model assessment of insulin resistance were significantly increased. SDC4 was an independent factor for NAFLD (odds ratio 1.963, 95% confidence interval [CI] 1.628-2.367, P < 0.001). The area under the ROC curve of SDC4 for predicting NAFLD was 0.934 (95% CI 0.910-0.959). The optimal cut-off value was 6.575 ng/mL at Youden's index of 0.767. SDC4 had the highest diagnostic sensitivity (84.1%), positive predictive value (82.5%), negative predictive value (93.3%) and positive likelihood ratio (11.356) among all the variables.

Conclusions: Elevated serum SDC4 level is associated with metabolic disorders and the prevalence of NAFLD among general population. Serum SDC4 may serve as a biomarker of NAFLD.
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http://dx.doi.org/10.1111/1751-2980.13037DOI Listing
September 2021

Antibiotic prophylaxis and the gastrointestinal resistome in paediatric patients with acute lymphoblastic leukaemia: a cohort study with metagenomic sequencing analysis.

Lancet Microbe 2021 Apr 15;2(4):e159-e167. Epub 2021 Feb 15.

Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA.

Background: Although antibiotic prophylaxis with levofloxacin can reduce the risk of serious infection in immunocompromised patients, the potential contribution of prophylaxis to antibiotic resistance is a major drawback. We aimed to identify the effects of levofloxacin prophylaxis, given to paediatric patients with acute lymphoblastic leukaemia to prevent infections during induction chemotherapy, on antibiotic resistance in gastrointestinal microbiota after completion of induction and consolidation therapy.

Methods: This prospective, single-centre (St Jude Children's Research Hospital, Memphis, TN, USA) cohort study included children (≤18 years) receiving therapy for newly diagnosed acute lymphoblastic leukaemia and who received either primary levofloxacin prophylaxis or no antibacterial prophylaxis (aside from prophylaxis with trimethoprim-sulfamethoxazole) and provided at least two stool samples, including one after completion of induction therapy. We used metagenomic sequencing to identify bacterial genes that confer resistance to fluoroquinolones, trimethoprim-sulfamethoxazole, or other antibiotics, and to identify point mutations in bacterial topoisomerases () that confer resistance to fluoroquinolones. We then used generalised linear mixed models to compare the prevalence and relative abundance of antibiotic resistance gene groups after completion of induction and consolidation therapy between participants who had received levofloxacin and those who received no prophylaxis.

Findings: Between Feb 1, 2012, and April 30, 2016, 118 stool samples (32 baseline, 49 after induction, and 37 after consolidation) were collected from 49 evaluable participants; of these participants, 31 (63%) received levofloxacin prophylaxis during induction therapy and 18 (37%) received no antibacterial prophylaxis. Over the course of induction therapy, there was an overall increase in the relative abundance of trimethoprim-sulfamethoxazole resistance genes (estimated mean fold change 5·9, 95% CI 3·6-9·6; p<0·0001), which was not modified by levofloxacin prophylaxis (p=0·46). By contrast, the prevalence of topoisomerase point mutations increased over the course of induction therapy in levofloxacin recipients (mean prevalence 10·4% [95% CI 3·2-25·4] after induction therapy 3·7% [0·2-22·5] at baseline) but not other participants (0% 0%; p<0·0001). There was no significant difference between prophylaxis groups with respect to changes in aminoglycoside, β-lactam, vancomycin, or multidrug resistance genes after completion of induction or consolidation therapy.

Interpretation: Analysing the gastrointestinal resistome can provide insights into the effects of antibiotics on the risk of antibiotic-resistant infections. In this study, antibiotic prophylaxis with trimethoprim-sulfamethoxazole or levofloxacin during induction therapy for acute lymphoblastic leukaemia appeared to increase the short-term and medium-term risk of colonisation with bacteria resistant to these antibiotics, but not to other drugs. More research is needed to determine the longer-term effects of antibacterial prophylaxis on colonisation with antibiotic-resistant bacteria.

Funding: Children's Infection Defense Center at St Jude Children's Research Hospital, American Lebanese Syrian Associated Charities, and National Institutes of Health.
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http://dx.doi.org/10.1016/s2666-5247(20)30202-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336918PMC
April 2021

Role of heparanase 2 (Hpa2) in gastric cancer.

Neoplasia 2021 09 31;23(9):966-978. Epub 2021 Jul 31.

Rappaport Faculty of Medicine, Technion Integrated Cancer Center, Technion, Haifa, Israel. Electronic address:

Heparanase is highly implicated in tumor metastasis due to its capacity to cleave heparan sulfate and, consequently, remodel the extracellular matrix underlying epithelial and endothelial cells. In striking contrast, only little attention was given to its close homolog, heparanase 2 (Hpa2), possibly because it lacks heparan sulfate-degrading activity typical of heparanase. We subjected sections of gastric carcinoma to immunostaining and correlated Hpa2 immunoreactivity with clinical records, including tumor grade, stage and patients' status. We over-expressed Hpa2 in gastric carcinoma cell lines and examined their tumorigenic properties in vitro and in vivo. We also evaluated the expression of Hpa2 by gastric carcinoma cells following inhibition of the proteasome, leading to proteotoxic stress, and the resulting signaling responsible for Hpa2 gene regulation. Here, we report that gastric cancer patients exhibiting high levels of Hpa2 survive longer. Similarly, mice administrated with gastric carcinoma cells engineered to over-express Hpa2 produced smaller tumors and survived longer than mice administrated with control cells. This was associated with increased phosphorylation of AMP-activated protein kinase (AMPK), a kinase that is situated at the center of a tumor suppressor network. We also found that MG132, an inhibitor of the proteasome that results in proteotoxic stress, prominently enhances Hpa2 expression. Notably, Hpa2 induction by MG132 appeared to be mediated by AMPK, and AMPK was found to induce the expression of Hpa2, thus establishing a loop that feeds itself where Hpa2 enhances AMPK phosphorylation that, in turn, induces Hpa2 expression, leading to attenuation of gastric tumorigenesis. These results indicate that high levels of Hpa2 in some tumors are due to stress conditions that tumors often experience due to their high rates of cell proliferation and high metabolic demands. This increase in Hpa2 levels by the stressed tumors appears critically important for patient outcomes.
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http://dx.doi.org/10.1016/j.neo.2021.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349917PMC
September 2021

Analysis of jejunum microbiota of HFD/STZ diabetic rats.

Biomed Pharmacother 2021 Jun 3;138:111094. Epub 2021 Apr 3.

Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China. Electronic address:

Currently, several studies propose that the dominant intestinal bacteria are core flora. Besides keeping the homeostasis of the intestinal environment, the intestinal microflora also plays a role in body metabolism, production of some vitamins, and control of barrier function. The study aimed to investigate the jejunum microbiota in diabetic rats as well as it's the relationship with Ceftriaxone sodium-mediated gut dysbiosis, diabetic parameters, and intestinal permeability. Thirty-two Wistar rats (Male) were enrolled and divided into four groups (A, B, C, and D; N = 8). Subsequently, T2DM was induced in C and D groups by HFD/STZ model and then gut dysbiosis in B and D groups via intragastric administration of Ceftriaxone sodium for two weeks. The food-water intake, body weight, fasting blood glucose, plasma insulin, HOMA-IR, intestinal permeability, and jejunum microbiota and it's histology were investigated. In this study, T2DM was associated with a significant decrease in the richness and diversity of jejunum microbiota, elevation in the intestinal permeability, and higher abundance of some opportunistic pathogens. Ceftriaxone sodium-induced gut dysbiosis declined food-water intake, damagedthe villi of jejunum tissue, increased intestinal permeability, and affected the diversity of jejunum microbiota. In diabetic rats, Ceftriaxone sodium-mediated gut dysbiosis also declined the abundance of someSCFAs bacteria and raised the abundant of some opportunistic bacteria such as Staphylococcus_sciuri. Interestingly, we found that several bacteria were negatively correlated with HOMA-IR, fasting blood glucose, body weight, and intestinal permeability. Overall, the study highlighted the jejunum microflora alterations in HFD/STZ diabetic rats and assessed the effect of Ceftriaxone sodium-induced gut dysbiosis on diabetic parameters, jejunum microbiota and histology, and intestinal permeability, which are of potential for further studies.
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http://dx.doi.org/10.1016/j.biopha.2020.111094DOI Listing
June 2021

Is Adherence to the Provisional Institute of Medicine Guidelines of Weight Gain Associated With Better Perinatal Outcomes? A Retrospective Cohort Study of Twin Pregnancies in Southwest China.

Asia Pac J Public Health 2021 Jul 26:10105395211026071. Epub 2021 Jul 26.

Department of Patient Center, West China Second University Hospital, Sichuan University, Chengdu, China.

The applicability of the Institute of Medicine (IOM) recommendations of gestational weight gain (GWG) for Chinese twin gestations is uncertain. In this article, we aimed to investigate the associations between GWG among twin gestations, as categorized according to the 2009 IOM guidelines and perinatal outcomes in Chengdu, China. A retrospective cohort study of pregnant women delivering live twins ≥28 weeks at a tertiary maternal and child hospital was conducted. The incidences of perinatal outcomes were compared across 3 groups-that is, women with low, adequate, and excessive GWG. Logistic regression analyses were next performed to confirm the associations while taking into account potential confounders. Results showed that low GWG was associated with a higher risk of preterm birth, low and very low birthweight, neonatal intensive care unit admission, and gestational diabetes, whereas preeclampsia was more frequent among excessive GWG women. In conclusion, adherence to the 2009 IOM guidelines for twin pregnancies are associated with improved perinatal outcomes. This has the potential to improve short- and long-term public health outcomes.
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http://dx.doi.org/10.1177/10105395211026071DOI Listing
July 2021

Design, synthesis and biological evaluation of 2-styryl-5-hydroxy-4-pyrone derivatives and analogues as multiple functional agents with the potential for the treatment of Alzheimer's disease.

Bioorg Med Chem 2021 Aug 9;44:116306. Epub 2021 Jul 9.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

A novel series of 2-styryl-5-hydroxy-4-pyrone derivatives and analogues were designed and synthesized as H receptor antagonism based multitarget-directed ligands (MTDLs) for AD therapy using pharmacophore-combine strategy. The 2-styryl-5-hydroxy-4-pyrone pharmacophore with metal ion chelation, antioxidation, and Aβ aggregation inhibition activities was employed as the "eastern part", and a typical phenoxyalkylamine moiety was used as "central ring + western part" of the H receptor antagonist. The biological evaluation revealed that the majority of the target compounds demonstrated desirable multiple functions. The two most promising compounds 8a and 8b exhibited nanomolar IC values on H receptor antagonism, excellent metal ion chelating capability, more potent ABTS scavenging activity than Trolox, efficient Aβ self-aggregation and Cu-induced aggregation inhibitory activities, as well as disaggregation activities against Aβ self/Cu-induced aggregation.
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http://dx.doi.org/10.1016/j.bmc.2021.116306DOI Listing
August 2021
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