Publications by authors named "Xin Hu"

971 Publications

Higher PEEP versus lower PEEP strategies for patients in ICU without acute respiratory distress syndrome: A systematic review and meta-analysis.

J Crit Care 2021 Oct 21;67:72-78. Epub 2021 Oct 21.

Department of Critical Care Medicine, The First Medical Centre, Chinese PLA General Hospital, Beijing, China. Electronic address:

Purpose: To evaluate the effects of high and low levels of PEEP on ICU patients without ARDS.

Methods: We searched public databases (including PubMed, EMBASE, Cochrane Library and Clinicaltrial.gov). The Cochrane Risk of Bias Assessment tool was used to evaluate the quality of the included studies.

Results: We included 2307 patients from 24 trials. Although no significant difference was found between high and low PEEP applications in in-hospital mortality (risk ratio[RR] 0.98, 95% confidence interval[CI] [0.81, 1.19], P = 0.87), high PEEP indeed decreased the incidence of ARDS, hypoxemia, and increased the level of PaO/FIO. In addition, although the overall results did not reveal any advantages of high PEEP in terms of secondary outcomes regarding 28-day mortality, the duration of ventilation, atelectasis, pulmonary barotrauma, hypotension, and so forth, the subgroup analysis concerning the level of low PEEP (ZEEP or not) and patient type (postoperative or medical ones) yielded different results. The TSA results suggested that more RCTs are needed.

Conclusions: Although ventilation with high PEEP in ICU patients without ARDS may not reduce in-hospital mortality, the decreased incidences of ARDS and hypoxemia and the improvement in PaO/FIO were found in the high PEEP arm.
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http://dx.doi.org/10.1016/j.jcrc.2021.09.026DOI Listing
October 2021

Responses of Ecological Stoichiometric Characteristics of Carbon, Nitrogen, and Phosphorus to Periodic Submergence in Mega-Reservoir: Growth of and .

Plants (Basel) 2021 Sep 28;10(10). Epub 2021 Sep 28.

Key Laboratory of Eco-Environments in the Three Gorges Reservoir Region (Ministry of Education), Chongqing Key Laboratory of Plant Resource Conservation and Germplasm Innovation, College of Life Sciences, Southwest University, Chongqing 400715, China.

Ecological stoichiometric studies can be useful for managing the deteriorated riparian zones of mega-reservoirs in which nutrients significantly impact the balanced vegetation cover. The present study aims to explore the effects of periodic submergence on the stoichiometric ecological characteristics of carbon (C), nitrogen (N), and phosphorus (P), as well as the growth conditions of two leading conifer species ( and ) in the hydro-fluctuation zone of the Three Gorges Reservoir (TGR) region, China. The stoichiometrical contents of C, N, and P in fine roots, leaves, and branches, and the growth conditions of and were measured in July 2019. The results showed that periodic submergence affected the stoichiometric characteristics and growth conditions of these two woody species, and the impact was restrained, but both grew well. The effects of inundation on the C, N, and P ecological stoichiometric characteristics differed in different parts of trees. In general, the C contents showed the following pattern: leaves > branches > fine roots. The N and P content showed the following pattern: leaves > fine roots > branches, while the C/N and C/P ratios showed an opposite trend to that of N and P. The N and P content in all parts of (with means of 17.18 and 1.70 g/kg for leaves, 4.80 and 0.57 g/kg for branches, and 6.88 and 1.10 g/kg for fine roots, respectively) and (with means of 14.56 and 1.87 g/kg for leaves, 5.03 and 0.63 g/kg for branches, and 8.17 and 1.66 g/kg for fine roots, respectively) were higher than the national average level (with means of 14.14 and 1.11 g/kg for leaves, 3.04 and 0.31 g/kg for branches, and 4.85 and 0.47 g/kg for fine roots, respectively). Except for N and P contents in the leaves of , there was a significant correlation between N and P elements in other parts ( < 0.05). Nevertheless, the N/P ratio (10.15, 8.52, 6.44, and 7.93, 8.12, 5.20 in leaves, branches, and fine roots of and , respectively) was lower than the critical ratio of 14. The growth conditions of and were significantly negatively correlated with their leaf C contents and significantly positively correlated with their fine root N and P contents. This study showed that and could maintain their normal growth needs by properly allocating nutrients between different organs to adapt to the long periodic submergence in the hydro-fluctuation zone of the TGR region.
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http://dx.doi.org/10.3390/plants10102040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540895PMC
September 2021

Glutamine involvement in nitrogen regulation of cellulase production in fungi.

Biotechnol Biofuels 2021 Oct 13;14(1):199. Epub 2021 Oct 13.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.

Background: Cellulase synthesized by fungi can environment-friendly and sustainably degrades cellulose to fermentable sugars for producing cellulosic biofuels, biobased medicine and fine chemicals. Great efforts have been made to study the regulation mechanism of cellulase biosynthesis in fungi with the focus on the carbon sources, while little attention has been paid to the impact and regulation mechanism of nitrogen sources on cellulase production.

Results: Glutamine displayed the strongest inhibition effect on cellulase biosynthesis in Trichoderma reesei, followed by yeast extract, urea, tryptone, ammonium sulfate and L-glutamate. Cellulase production, cell growth and sporulation in T. reesei RUT-C30 grown on cellulose were all inhibited with the addition of glutamine (a preferred nitrogen source) with no change for mycelium morphology. This inhibition effect was attributed to both L-glutamine itself and the nitrogen excess induced by its presence. In agreement with the reduced cellulase production, the mRNA levels of 44 genes related to the cellulase production were decreased severely in the presence of glutamine. The transcriptional levels of genes involved in other nitrogen transport, ribosomal biogenesis and glutamine biosynthesis were decreased notably by glutamine, while the expression of genes relevant to glutamate biosynthesis, amino acid catabolism, and glutamine catabolism were increased noticeably. Moreover, the transcriptional level of cellulose signaling related proteins ooc1 and ooc2, and the cellular receptor of rapamycin trFKBP12 was increased remarkably, whose deletion exacerbated the cellulase depression influence of glutamine.

Conclusion: Glutamine may well be the metabolite effector in nitrogen repression of cellulase synthesis, like the role of glucose plays in carbon catabolite repression. Glutamine under excess nitrogen condition repressed cellulase biosynthesis significantly as well as cell growth and sporulation in T. reesei RUT-C30. More importantly, the presence of glutamine notably impacted the transport and metabolism of nitrogen. Genes ooc1, ooc2, and trFKBP12 are associated with the cellulase repression impact of glutamine. These findings advance our understanding of nitrogen regulation of cellulase production in filamentous fungi, which would aid in the rational design of strains and fermentation strategies for cellulase production in industry.
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http://dx.doi.org/10.1186/s13068-021-02046-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513308PMC
October 2021

Application of Cloud Computing in the Prediction of Exercise Improvement of Cardiovascular and Digestive Systems in Obese Patients.

J Healthc Eng 2021 27;2021:4695722. Epub 2021 Sep 27.

Nanjing University of Posts and Telecommunications, Nanjing, Jiangsu, China.

Based on the cardiovascular and digestive problems of obese patients, this paper adopted the cloud computing method and selected 100 subjects with big data (23 normal weight subjects, 3740 overweight patients, and 40 obese patients) as the research objects, studying the heart configuration and their digestive system of obese people. Results show that BMI =  (24 ≥ BMI > 27.9) and BMI = XL (BMI > 27.9) were identified as target correlation projects in this experiment, associated with each cardiac structural parameters, respectively. Cloud computing facilitates early detection, early prevention, and early intervention in heart configuration changes in overweight and obese patients.
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http://dx.doi.org/10.1155/2021/4695722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490022PMC
September 2021

Hybrid Approach Reveals Novel Inhibitors of Multiple SARS-CoV-2 Variants.

ACS Pharmacol Transl Sci 2021 Oct 17;4(5):1675-1688. Epub 2021 Sep 17.

National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.

The National Center for Advancing Translational Sciences (NCATS) has been actively generating SARS-CoV-2 high-throughput screening data and disseminates it through the OpenData Portal (https://opendata.ncats.nih.gov/covid19/). Here, we provide a hybrid approach that utilizes NCATS screening data from the SARS-CoV-2 cytopathic effect reduction assay to build predictive models, using both machine learning and pharmacophore-based modeling. Optimized models were used to perform two iterative rounds of virtual screening to predict small molecules active against SARS-CoV-2. Experimental testing with live virus provided 100 (∼16% of predicted hits) active compounds (efficacy > 30%, IC ≤ 15 μM). Systematic clustering analysis of active compounds revealed three promising chemotypes which have not been previously identified as inhibitors of SARS-CoV-2 infection. Further investigation resulted in the identification of allosteric binders to host receptor angiotensin-converting enzyme 2; these compounds were then shown to inhibit the entry of pseudoparticles bearing spike protein of wild-type SARS-CoV-2, as well as South African B.1.351 and UK B.1.1.7 variants.
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http://dx.doi.org/10.1021/acsptsci.1c00176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482323PMC
October 2021

Rapid Disappearance of Acute Unilateral Epidural Hematoma Due to the Compression of Contralateral Subdural Hematoma.

Neurology 2021 Oct 4. Epub 2021 Oct 4.

Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

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http://dx.doi.org/10.1212/WNL.0000000000012888DOI Listing
October 2021

Frequency of basic public health services utilization by married female migrants in China: associations of social support, discrimination and sociodemographic factors.

BMC Womens Health 2021 09 28;21(1):344. Epub 2021 Sep 28.

Department of Family Health Care Nursing, School of Nursing, University of California, San Francisco, CA, USA.

Background: Utilization of basic public health services (BPHS) allows for disease prevention and management and is an essential component for protecting health. Disparities in utilization exist between rural-to-urban migrants and their local counterparts in China. This study sought to determine the frequency of BPHS utilization and whether social support, discrimination, and sociodemographic features were risk factors for low BPHS utilization by Chinese female migrants.

Methods: Data were derived from a survey of female rural-to-urban migrants at nine work sites in Changsha, China. The association between social support, discrimination, sociodemographic factors and BPHS utilization was obtained using Chi-square and logistic regression analysis.

Results: Between December 2017 and April 2018, 307 female participants completed the survey. A total of 24.7% reported having had health education, 26.1% had breast and cervical cancer screening, 27.2% had established a health care record, and 40.9% had received basic contraceptive services. Two factors were associated with the reduced likelihood of BPHS utilization: Length of migration and health record establishment (OR = 0.53; 95% CI = 0.31, 0.92) and years of education and basic contraceptive service use (OR = 0.36; 95% CI = 0.20, 0.67). The remaining six factors were associated with an increased likelihood of BPHS utilization: Living circumstances and health record establishment (OR = 2.11; 95% CI = 1.17, 3.80), health education (OR = 2.71; 95% CI = 1.51, 4.87) and cancer screening (OR = 2.38; 95% CI = 1.30, 4.36). Utilization of social support was associated with health record establishment (OR = 1.24; 95% CI = 1.06, 1.44), basic contraceptive service use (OR = 1.21; 95% CI = 1.04, 1.42) and cancer screening (OR = 1.29; 95% CI = 1.10, 1.51). Objective social support was associated with health education utilization (OR = 1.15; 95% CI = 1.04, 1.26), while subjective social support was associated with basic contraceptive service use (OR = 1.11; 95% CI = 1.05, 1.18) and cancer screening (OR = 1.10; 95% CI = 1.02, 1.17). Family location was associated with basic contraceptive service use (OR = 1.96; 95% CI = 1.12, 3.44) and migration time in Changsha was associated with basic contraceptive service use (OR = 2.24; 95% CI = 1.18, 4.27).

Conclusions: Overall, there was low utilization rate for four BPHS by Chinese female migrants, and social support appears to be an important factor in this setting. Government, community, and workplace education efforts for enhancing BPHS utilization among female rural-to-urban migrants are recommended.
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http://dx.doi.org/10.1186/s12905-021-01482-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480003PMC
September 2021

Leaf Polysaccharide in Conjugation with Ovalbumin Act as Delivery System Can Improve Immune Response.

Pharmaceutics 2021 Sep 1;13(9). Epub 2021 Sep 1.

College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China.

In this investigation, to maximize the desired immunoenhancement effects of PsEUL and stimulate an efficient humoral and cellular immune response against an antigen, PsEUL and the model antigen ovalbumin (OVA) were coupled using the N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) reaction to yield a novel delivery system (PsEUL-OVA). The physicochemical characteristics and immune regulation effects of this new system were investigated. We found the yield of this EDC method to be 46.25%. In vitro, PsEUL-OVA (200 μg mL) could enhance macrophage proliferation and increase their phagocytic efficiency. In vivo, PsEUL-OVA could significantly increase the levels of OVA-specific antibody (IgG, IgG1, IgG2a, and IgG2b) titers and cytokine (IL-2, IL-4, IL-6, IFN-γ) levels. Additionally, it could activate T lymphocytes and facilitate the maturation of dendritic cells (DCs). These findings collectively suggested that PsEUL-OVA induced humoral and cellular immune responses by promoting the phagocytic activity of macrophages and DCs. Taken together, these results revealed that PsEUL-OVA had the potential to improve immune responses and provide a promising theoretical basis for the design of a novel delivery system.
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http://dx.doi.org/10.3390/pharmaceutics13091384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471226PMC
September 2021

Oridonin Prolongs the Survival of Mouse Cardiac Allografts by Attenuating the NF-κB/NLRP3 Pathway.

Front Immunol 2021 10;12:719574. Epub 2021 Sep 10.

Henan Key Laboratory of Digestive Organ Transplantation, Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou Key Laboratory of Hepatobiliary and Pancreatic Diseases and Organ Transplantation, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Oridonin (Ori), the main bioactive ingredient of the natural anti-inflammatory herb , could be a covalent inhibitor of the NLRP3 inflammasome. Solid organ transplantation provides a life-saving optional therapy for patients with end-stage organ dysfunction. The long-term survival of solid organ transplantation remains restricted because of the possibility of rejection and the toxicity, infection, cardiovascular disease, and malignancy related to immunosuppressive (IS) drugs. However, the pathogenic mechanisms involved remain unclear. The ideal IS drugs to prevent allograft rejection have not been identified. Here, we investigated whether Ori could prolong the survival of completely mismatched cardiac allografts.

Methods: The cardiac transplantation models were conducted among three groups of mice from C57BL/6NCrSlc (B6/N) or C3H/HeNSlc (C3H) to C3H: the syngeneic and the allogeneic group, whose recipients were treated with vehicle of Ori, and the Ori treatment group, in which the recipients were transplanted hearts from MHC-I mismatched donors and treated with different dosages of Ori from post-operative day (POD) 0 to 7. Then, we investigated the effect of Ori on bone marrow-derived dendritic cell (BMDC) and allogeneic mixed lymphocyte reaction .

Results: Ori with 3, 10, and 15 mg/kg Ori could prolong the survival (MST = 22.8, 49.2, and 65.3 days, respectively). We found that infiltrating CD8 T cells and macrophages were decreased, and regulatory T cells (Tregs) were expanded in allografts on POD7. The mRNA level of IL-1β and IFN-γ of allografts was downregulated. Mechanistically, Ori-treated BMDCs suppressed T-cell proliferation and IFN-γCD4 T-cell differentiation, along with the expansion of Tregs and IL-10CD4 T cells. Ori inhibited NOD, LRR-, and pyrin domain-containing protein 3 (NLRP3) expression; attenuated NF-κB and IκBα phosphorylation in LPS-activated BMDCs; downregulated NLRP3, Caspase-1, IL-1β, IL-18, and IFN-γ; and upregulated IL-10 expression.

Conclusions: Our findings highlight the potential of Ori as a novel and natural IS agent to improve transplant tolerance. Ori could exert IS activity through decreasing IL-1β and IL-18 production and Th1 differentiation and proliferation and expanding Tregs inhibiting the NF-κB/NLRP3 signaling pathway.
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http://dx.doi.org/10.3389/fimmu.2021.719574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462485PMC
September 2021

Activation of Frizzled-7 attenuates blood-brain barrier disruption through Dvl/β-catenin/WISP1 signaling pathway after intracerebral hemorrhage in mice.

Fluids Barriers CNS 2021 Sep 26;18(1):44. Epub 2021 Sep 26.

Department of Physiology and Pharmacology, Center for Neuroscience Research, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA.

Background: Destruction of blood-brain barrier (BBB) ​​is one of the main mechanisms of secondary brain injury following intracerebral hemorrhage (ICH). Frizzled-7 is a key protein expressed on the surface of endothelial cells that controls vascular permeability through the Wnt-canonical pathway involving WNT1-inducible signaling pathway protein 1 (WISPI). This study aimed to investigate the role of Frizzled-7 signaling in BBB preservation after ICH in mice.

Methods: Adult CD1 mice were subjected to sham surgery or collagenase-induced ICH. Frizzled-7 activation or knockdown was performed by administration of Clustered Regularly Interspaced Palindromic Repeats (CRISPR) by intracerebroventricular injection at 48 h before ICH induction. WISP1 activation or WISP1 knockdown was performed to evaluate the underlying signaling pathway. Post-ICH assessments included neurobehavior, brain edema, BBB permeability, hemoglobin level, western blot and immunofluorescence.

Results: The brain expressions of Frizzled-7 and WISP1 significantly increased post-ICH. Frizzled-7 was expressed in endothelial cells, astrocytes, and neurons after ICH. Activation of Frizzled-7 significantly improved neurological function, reduced brain water content and attenuated BBB permeability to large molecular weight substances after ICH. Whereas, knockdown of Frizzled-7 worsened neurological function and brain edema after ICH. Activation of Frizzled-7 significantly increased the expressions of Dvl, β-Catenin, WISP1, VE-Cadherin, Claudin-5, ZO-1 and reduced the expression of phospho-β-Catenin. WISP1 knockdown abolished the effects of Frizzled-7 activation on the expressions of VE-Cadherin, Claudin-5 and ZO-1 at 24 h after ICH.

Conclusions: Frizzled-7 activation potentially attenuated BBB permeability and improved neurological deficits after ICH through Dvl​​/β-Catenin/WISP1 pathway. Frizzled-7 may be a potential target for the development of ICH therapeutic drugs.
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http://dx.doi.org/10.1186/s12987-021-00278-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474841PMC
September 2021

Fs-DSM: Few-Shot Diagram-Sentence Matching via Cross-Modal Attention Graph Model.

IEEE Trans Image Process 2021 27;30:8102-8115. Epub 2021 Sep 27.

Diagram-sentence matching is a valuable academic research because it can help learners effectively understand the diagrams with the assisted by sentences. However, there are many uncommon objects, i.e. few-shot contents in diagrams and sentences. The existing methods for image-sentence matching have great limitations when applied to diagrams. Because they focus on the high-frequency objects during training and ignore the uncommon objects. In addition, the specialty leads to the semantic non-intuition of the diagram itself. In this work, we propose a cross-modal attention graph model for the few-shot diagram-sentence matching task named Fs-DSM. Specifically, it is composed of three modules. The graph initialization module regards the region-level diagram features and word-level sentence features as the nodes of Fs-DSM, and edges are represented as similarity between nodes. The information propagation module is a key point of Fs-DSM, in which the few-shot contents are recognized by an uncommon object recognition strategy, and then the nodes are updated by a neighborhood aggregation procedure with cross-modal propagation between all visual and textual nodes, while the edges are recomputed based on the new node features. The global association module integrates the features of regions and words to represent the global diagrams and sentences. By conducting comprehensive experiments in terms of few-shot and conventional image-sentence matching, we demonstrate that Fs-DSM achieves superior performances over the competitors on the AI2D [Formula: see text] diagram dataset and two public benchmark datasets with nature images.
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http://dx.doi.org/10.1109/TIP.2021.3112294DOI Listing
September 2021

A scalable workflow to characterize the human exposome.

Nat Commun 2021 09 22;12(1):5575. Epub 2021 Sep 22.

Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, School of Medicine at Emory University, Atlanta, GA, USA.

Complementing the genome with an understanding of the human exposome is an important challenge for contemporary science and technology. Tens of thousands of chemicals are used in commerce, yet cost for targeted environmental chemical analysis limits surveillance to a few hundred known hazards. To overcome limitations which prevent scaling to thousands of chemicals, we develop a single-step express liquid extraction and gas chromatography high-resolution mass spectrometry analysis to operationalize the human exposome. We show that the workflow supports quantification of environmental chemicals in human plasma (200 µL) and tissue (≤100 mg) samples. The method also provides high resolution, sensitivity and selectivity for exposome epidemiology of mass spectral features without a priori knowledge of chemical identity. The simplicity of the method can facilitate harmonization of environmental biomonitoring between laboratories and enable population level human exposome research with limited sample volume.
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http://dx.doi.org/10.1038/s41467-021-25840-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458492PMC
September 2021

Type 2 diabetes mellitus promotes the proliferation, metastasis, and suppresses the apoptosis in oral squamous cell carcinoma.

J Oral Pathol Med 2021 Sep 22. Epub 2021 Sep 22.

Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya hospital of Central South University, Changsha, Hunan, China.

Background: Our previous study revealed that patients with oral squamous cell carcinoma and concomitant type 2 diabetes mellitus presented a lower 5-year survival rate. Hyperglycemia has been increasingly recognized as a risk factor for more advanced disease and poorer prognosis in patients with oral squamous cell carcinoma. However, its role remains unclear.

Methods: The expressions of BRIP1, Ki67, E-cadherin, and cleaved caspase-3 were detected by immunohistochemistry in oral squamous cell carcinoma tissues with or without type 2 diabetes mellitus. Cell counting kit-8 assay and wound healing assay were used to determine the proliferative and migratory ability of oral squamous cell carcinoma cells cultured with or without high glucose in vitro. Flow cytometry was applied to distinguish the role of high glucose on the cell cycle and apoptosis rates.

Results: The expression level of Ki67 was elevated while BRIP1, E-cadherin, and cleaved caspase-3 were downregulated in patients with oral squamous cell carcinoma coexisting with diabetes. The cell proliferation and migration in oral squamous cell carcinoma cell lines were significantly enhanced by high glucose. Flow cytometric analysis suggested that high glucose predisposed cancer cells to stay at S/G phase and to exhibit lower apoptosis rates.

Conclusion: Our results implicated that type 2 diabetes mellitus may play a crucial role in the development and progression of oral squamous cell carcinoma through hyperglycemia, affecting cancer cell proliferation, migration, and apoptosis. This finding might provide a new direction for the prevention and treatment of oral squamous cell carcinoma.
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http://dx.doi.org/10.1111/jop.13244DOI Listing
September 2021

A Mesenchymal-epithelial transition factor-Agonistic Antibody Accelerates Cirrhotic Liver Regeneration and Improves Mouse Survival Following Partial Hepatectomy.

Liver Transpl 2021 Sep 16. Epub 2021 Sep 16.

Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.

Small-for-size syndrome (SFSS) is a common complication following partial liver transplantation and extended hepatectomy. SFSS is characterized by postoperative liver dysfunction caused by insufficient regenerative capacity and portal hyperperfusion and is more frequent in patients with preexisting liver disease. We explored the effect of the Mesenchymal-epithelial transition factor (MET)-agonistic antibody 71D6 on liver regeneration and functional recovery in a mouse model of SFSS. Male C57/BL6 mice were exposed to repeated carbon tetrachloride injections for 10 weeks and then randomized into 2 arms receiving 3 mg/kg 71D6 or a control immunoglobulin G (IgG). At 2 days after the randomization, the mice were subjected to 70% hepatectomy. Mouse survival was recorded up to 28 days after hepatectomy. Satellite animals were euthanized at different time points to analyze liver regeneration, fibrosis, and inflammation. Serum 71D6 administration significantly decreased mouse mortality consequent to insufficient regeneration of the cirrhotic liver. Analysis of liver specimens in satellite animals revealed that 71D6 promoted powerful activation of the extracellular signal-regulated kinase pathway and accelerated liver regeneration, characterized by increased liver-to-body weight, augmented mitotic index, and higher serum albumin levels. Moreover, 71D6 accelerated the resolution of hepatic fibrosis as measured by picrosirius red, desmin, and α-smooth muscle actin staining, and suppressed liver infiltration by macrophages as measured by CD68 and F4/80 staining. Analysis of gene expression by reverse-transcription polymerase chain reaction confirmed that 71D6 administration suppressed the expression of key profibrotic genes, including platelet-derived growth factor, tissue inhibitor of metalloproteinase 3, and transforming growth factor-β1, and of key proinflammatory genes, including tumor necrosis factor-α, interleukin-1β, chemokine (C-C motif) ligand 3, and chemokine (C-C motif) ligand 5. These results suggest that activating the MET pathway via an hepatocyte growth factor-mimetic antibody may be beneficial in patients with SFSS and possibly other types of acute and chronic liver disorders.
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http://dx.doi.org/10.1002/lt.26301DOI Listing
September 2021

Circular RNA Circ_0000677 promotes cell proliferation by regulating microRNA-106b-5p/CCND1 in non-small cell lung cancer.

Bioengineered 2021 12;12(1):6229-6239

Department Of Emergency Medicine, Shanghai Seventh People's Hospital, Shanghai, China.

Recently, circular RNAs (circRNAs) have become an intense focus of research and large numbers of circRNAs have been identified, awaiting functional elucidation. Thus, the present study aims to examine the regulation of circRNAs and its molecular mechanism in lung cancer growth. Here, we show that circular RNA circ_0000677 was overexpressed and correlated with poor prognosis in non-small cell lung cancer (NSCLC) patients. Functionally, circ_0000677 knockdown markedly inhibited proliferation of NSCLC cells by observing of immunofluorescence staining of Ki67, clone formation assay, and xenograft experiments. In mechanism, circ_0000677 acted as a sponge of microRNA-106b and further regulated CCDND1 gene expression in NSCLC cells by dual luciferase activity assay and their expression examination. Taken together, these findings suggest a role for circ_0000677/miR-106b/CCND1 regulation axis in promoting NSCLC growth and progression.
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http://dx.doi.org/10.1080/21655979.2021.1965697DOI Listing
December 2021

Exposure to Perfluoroalkyl Substances and Glucose Homeostasis in Youth.

Environ Health Perspect 2021 Sep 1;129(9):97002. Epub 2021 Sep 1.

Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, USA.

Background: Exposure to per- and polyfluoroalkyl substances (PFAS), a prevalent class of persistent pollutants, may increase the risk of type 2 diabetes.

Objective: We examined associations between PFAS exposure and glucose metabolism in youth.

Methods: Overweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; ) participated in annual visits for an average of . Generalizability of findings were tested in young adults from the Southern California Children's Health Study (CHS; ) who participated in a clinical visit with a similar protocol. At each visit, oral glucose tolerance tests were performed to estimate glucose metabolism and function via the insulinogenic index. Four PFAS were measured at baseline using liquid chromatography-high-resolution mass spectrometry; high levels were defined as concentrations percentile.

Results: In females from the SOLAR, high perfluorohexane sulfonate (PFHxS) levels () were associated with the development of dysregulated glucose metabolism beginning in late puberty. The magnitude of these associations increased postpuberty and persisted through 18 years of age. For example, postpuberty, females with high PFHxS levels had higher 60-min glucose (95% CI: ; ), higher 2-h glucose (95% CI: ; ), and 25% lower function () compared with females with low levels. Results were largely consistent in the CHS, where females with elevated PFHxS levels had higher 60-min glucose (95% CI: ; ) and higher 2-h glucose, which did not meet statistical significance (95% CI: ; ). In males, no consistent associations between PFHxS and glucose metabolism were observed. No consistent associations were observed for other PFAS and glucose metabolism.

Discussion: Youth exposure to PFHxS was associated with dysregulated glucose metabolism in females, which may be due to changes in function. These associations appeared during puberty and were most pronounced postpuberty. https://doi.org/10.1289/EHP9200.
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http://dx.doi.org/10.1289/EHP9200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409228PMC
September 2021

Microwave-assisted catalytic hydrothermal carbonization of Laminaria japonica for hydrochars catalyzed and activated by potassium compounds.

Bioresour Technol 2021 Dec 25;341:125835. Epub 2021 Aug 25.

State Key Laboratory of Analytical Chemistry for Life Science, Centre of Materials Analysis and School of Chemistry & Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing 210023, PR China. Electronic address:

There are limited investigations describing preparation and application of alga-based hydrochars via microwave-assisted catalytic hydrothermal carbonization (MA-CHTC). Therefore, hydrochars were successfully prepared from macroalgae biomass Laminaria japonica impregnated with KHPO, KCl, KCO, and KOH as acidic, neutral salt, and alkaline catalysts, respectively, via the MA-CHTC. Comprehensive characterization of physicochemical properties of the hydrochars, including yields, elemental and phase composition, specific surface areas, functional groups, and morphology, confirmed different catalytic effects of these catalysts on hydrochar formation. Adsorption kinetics and isotherms of Pb(II) revealed significant improvement of adsorption capacities for Pb(II) due to synergetic chemical activation of the spiked catalysts. Therefore, the synergetic catalytic effects and chemical activation is benefic for tailored design of engineered hydrochars with different properties for special application through selection of catalysts during the MA-CHTC process.
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http://dx.doi.org/10.1016/j.biortech.2021.125835DOI Listing
December 2021

Metabolomic analysis of the grain pearling fractions of six bread wheat varieties.

Food Chem 2022 Feb 17;369:130881. Epub 2021 Aug 17.

National Key Laboratory of Crop Genetic Improvement and National Center of Plant Gene Research (Wuhan), Huazhong Agricultural University, Wuhan 430070, China; College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

Bread wheat is a staple food crop that is consumed worldwide. In this study, using widely targeted LC-MS/MS, we conducted a high-throughput metabolomic analysis and determined the contents and spatial distribution of metabolites in pearled fractions of the dried kernels of six representative bread wheat varieties cultivated in China. Our aim was to explore the cultivars and pearling fractions with a view toward developing functional food products. We accordingly identified notable differences in the nutrient and bioactive metabolomes, and established that the pearling fractions of each cultivar had distinct metabolic profiles. Flavonoids varied the most amongst the cultivars and were found in higher concentration in the outer layers of the grain, but only at low concentrations in the kernel. Data from this study add further evidence of benefits of whole grain wheat consumption but, specifically, medium-gluten and pigmented wheat offer other nutrient and bioactive benefits whole grain products.
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http://dx.doi.org/10.1016/j.foodchem.2021.130881DOI Listing
February 2022

The Improvement of Air Quality and Associated Mortality during the COVID-19 Lockdown in One Megacity of China: An Empirical Strategy.

Int J Environ Res Public Health 2021 08 18;18(16). Epub 2021 Aug 18.

Department of Occupational and Environmental Health Sciences, Peking University School of Public Health, 38 Xueyuan Road, Haidian District, Beijing 100191, China.

Although the lockdown policy implemented during the COVID-19 pandemic indeed improved the air quality and reduced the related health risks, the real effects of the lockdown and its resulting health risks remain unclear considering the effects of unobserved confounders and the longstanding efforts of the government regarding air pollution. We compared air pollution between the lockdown period and the period before the lockdown using a difference-in-differences (DID) model and estimated the mortality burden caused by the number of deaths related to air pollution changes. The NO and CO concentrations during the lockdown period (17 days) declined by 8.94 μg/m (relative change: 16.94%; 95% CI: 3.71, 14.16) and 0.20 mg/m (relative change: 16.95%; 95% CI: 0.04, 0.35) on an average day, respectively, and O increased by 8.41 μg/m (relative change: 32.80%; 95% CI: 4.39, 12.43); no meaningful impacts of the lockdown policy on the PM, PM, SO, or the AQI values were observed. Based on the three clearly changed air pollutants, the lockdown policy prevented 8.22 (95% CI: 3.97, 12.49) all-cause deaths. Our findings suggest that the overall excess deaths caused by air pollution during the lockdown period declined. It is beneficial for human health when strict control measures, such as upgrading industry structure and promoting green transportation, are taken to reduce emissions, especially in cities with serious air pollution in China, such as Shijiazhuang.
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http://dx.doi.org/10.3390/ijerph18168702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391611PMC
August 2021

Improved Method for Efficient Generation of Functional Neurons from Murine Neural Progenitor Cells.

Cells 2021 Jul 26;10(8). Epub 2021 Jul 26.

Nuclear Architecture in Neural Plasticity and Aging, German Center for Neurodegenerative Diseases, 01307 Dresden, Germany.

Neuronal culture was used to investigate neuronal function in physiological and pathological conditions. Despite its inevitability, primary neuronal culture remained a gold standard method that requires laborious preparation, intensive training, and animal resources. To circumvent the shortfalls of primary neuronal preparations and efficiently give rise to functional neurons, we combine a neural stem cell culture method with a direct cell type-conversion approach. The lucidity of this method enables the efficient preparation of functional neurons from mouse neural progenitor cells on demand. We demonstrate that induced neurons (NPC-iNs) by this method make synaptic connections, elicit neuronal activity-dependent cellular responses, and develop functional neuronal networks. This method will provide a concise platform for functional neuronal assessments. This indeed offers a perspective for using these characterized neuronal networks for investigating plasticity mechanisms, drug screening assays, and probing the molecular and biophysical basis of neurodevelopmental and neurodegenerative diseases.
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http://dx.doi.org/10.3390/cells10081894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392300PMC
July 2021

Arginine Methyltransferase PRMT1 Regulates p53 Activity in Breast Cancer.

Life (Basel) 2021 Aug 5;11(8). Epub 2021 Aug 5.

Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.

The protein p53 is one of the most important tumor suppressors, responding to a variety of stress signals. Mutations in p53 occur in about half of human cancer cases, and dysregulation of the p53 function by epigenetic modifiers and modifications is prevalent in a large proportion of the remainder. PRMT1 is the main enzyme responsible for the generation of asymmetric-dimethylarginine, whose upregulation or aberrant splicing has been observed in many types of malignancies. Here, we demonstrate that p53 function is regulated by PRMT1 in breast cancer cells. PRMT1 knockdown activated the p53 signal pathway and induced cell growth-arrest and senescence. PRMT1 could directly bind to p53 and inhibit the transcriptional activity of p53 in an enzymatically dependent manner, resulting in a decrease in the expression levels of several key downstream targets of the p53 pathway. We were able to detect p53 asymmetric-dimethylarginine signals in breast cancer cells and breast cancer tissues from patients, and the signals could be significantly weakened by silencing of PRMT1 with shRNA, or inhibiting PRMT1 activity with a specific inhibitor. Furthermore, PRMT1 inhibitors significantly impeded cell growth and promoted cellular senescence in breast cancer cells and primary tumor cells. These results indicate an important role of PRMT1 in the regulation of p53 function in breast tumorigenesis.
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http://dx.doi.org/10.3390/life11080789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400051PMC
August 2021

Artificial Plantation Responses to Periodic Submergence in Massive Dam and Reservoir Riparian Zones: Changes in Soil Properties and Bacterial Community Characteristics.

Biology (Basel) 2021 Aug 23;10(8). Epub 2021 Aug 23.

Key Laboratory of Eco-Environments in the Three Gorges Reservoir Region (Ministry of Education), Chongqing Key Laboratory of Plant Resource Conservation and Germplasm Innovation, College of Life Sciences, Southwest University, Chongqing 400715, China.

Plant and microbiome interactions are necessary for plant nutrient acquisition. However, relatively little is known about the responses of roots, bulk, and rhizosphere soil microbial communities in different artificial vegetation types (woody and herbaceous) in riparian areas of massive dams and reservoirs. Therefore, this study aims to assess such responses at elevations of 165-170 m a.s.l. in the riparian zones of the Three Gorges Dam Reservoir, China. The samples were collected containing the rhizosphere soil, bulk soil, and roots of herbaceous and woody vegetation at different emergence stages in 2018. Then, all the samples were analyzed to quantify the soil properties, bacterial community characteristics, and their interaction in the early and late emergence phases. In different periods, the weight of dominant soil bacteria, including , , , , and , was higher, and their composition was different in the rhizosphere, bulk soil, and endophytes. Moreover, the soil co-occurrence networks indicated that the weight of soil physical properties was higher than chemical properties in the early emergence stage. In contrast, the weight of chemical properties was relatively higher in the late emergence stage. Furthermore, the richness and diversity of the bacterial community were mainly affected by soil organic matter. This study suggests that these herbaceous and woody vegetation are suitable for planting in reservoir areas affected by hydrology and human disturbance in light of soil nutrients and soil microbial communities, respectively. Additionally, these results provide valuable information to inoculate the soil with key microbiota members by applying fertilizers, potentially improving plant health and soil production.
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http://dx.doi.org/10.3390/biology10080819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389660PMC
August 2021

Ecust004 Suppresses Breast Cancer Cell Growth, Invasion, and Migration via EMT Regulation.

Drug Des Devel Ther 2021 10;15:3451-3461. Epub 2021 Aug 10.

The Laboratory of Cancer Biology, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, Jilin, People's Republic of China.

Purpose: Erianin is a small chemical compound extracted from Dendrobium chrysotoxum and has excellent antineoplastic effects against a variety of cancers. Combretastatin A-4 (CA4) is the most effective member of natural phenolic stilbene compounds isolated from the African willow tree Combretum caffrum. Ecust004 (Chemical Formula: CHNOS) is a drug candidate optimized from structure-activity relationship studies of the sulfamate derivatives of Erianin and CA4, which has better bioavailability and pharmacokinetic profiles than Erianin and CA4.

Methods: To investigate the antitumor activity of Ecust004 in different types of breast cancer cells, MDA-MB-231 and MCF7 cells were treated with Ecust004. MTT and CCK8 were used to determine the effects of Ecust004 on cell proliferation. Wound-healing and Transwell assays were used to evaluate the migration and invasion level of cells treated with Ecust004. The expression of genes and proteins associated with epithelial-mesenchymal transition was detected by RT-PCR and Western blotting. In vivo studies further clarified the functional effects of Ecust004.

Results: Ecust004 treatment decreased the growth and proliferation of MDA-MB-231 and MCF7 cells at a lower dosage than Erianin. In addition, compared to Erianin and CA4, Ecust004 can better inhibit the invasion and migration of MDA-MB-231 and MCF7 cells. Accordingly, the expression of genes associated with epithelial-mesenchymal transition, such as E-cadherin and vinculin, was increased. Finally, compared with Erianin and CA4, Ecust004 exhibited a better anti-tumor activity in vivo.

Conclusion: Ecust004 inhibits the proliferation, invasion, and migration of breast cancer cells, and therefore represents a potential agent for development as an antitumor drug.
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http://dx.doi.org/10.2147/DDDT.S309132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364433PMC
August 2021

PDSS1-mediated activation of CAMK2A-STAT3 signaling promotes metastasis in triple-negative breast cancer.

Cancer Res 2021 Aug 18. Epub 2021 Aug 18.

Breast surgery, Fudan University Shanghai Cancer Center

Genomic alterations are crucial for the development and progression of human cancers. Copy number gains found in genes encoding metabolic enzymes may induce triple-negative breast cancer (TNBC) adaptation. However, little is known about how metabolic enzymes regulate TNBC metastasis. Using our previously constructed multiomic profiling of a TNBC cohort, we identified decaprenyl diphosphate synthase subunit 1 (PDSS1) as an essential gene for TNBC metastasis. PDSS1 expression was significantly upregulated in TNBC tissues compared to adjacent normal tissues and was positively associated with poor survival among TNBC patients. PDSS1 knockdown inhibited TNBC cell migration, invasion, and distant metastasis. Mechanistically, PDSS1, but not a catalytically inactive mutant, positively regulated the cellular level of coenzyme Q10 (CoQ10) and intracellular calcium levels, thereby inducing CAMK2A phosphorylation, which is essential for STAT3 phosphorylation in the cytoplasm. Phosphorylated STAT3 entered the nucleus, promoting oncogenic STAT3 signaling and TNBC metastasis. STAT3 phosphorylation inhibitors (e.g., Stattic) effectively blocked PDSS1-induced cell migration and invasion in vitro and tumor metastasis in vivo. Taken together, our study highlights the importance of targeting the previously uncharacterized PDSS1/CAMK2A/STAT3 oncogenic signaling axis, expanding the repertoire of precision medicine in TNBC.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0747DOI Listing
August 2021

Discovery of Small Molecule Entry Inhibitors Targeting the Fusion Peptide of SARS-CoV-2 Spike Protein.

ACS Med Chem Lett 2021 Aug 28;12(8):1267-1274. Epub 2021 Jul 28.

National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.

SARS-CoV-2 entry into host cells relies on the spike (S) protein binding to the human ACE2 receptor. In this study, we investigated the structural dynamics of the viral S protein at the fusion peptide (FP) domain and small molecule binding for therapeutics development. Following comparative modeling analysis and docking studies of our previously identified fusion inhibitor chlorcyclizine, we performed a pharmacophore-based virtual screen and identified two novel chemotypes of entry inhibitors targeting the FP. The compounds were evaluated in the pseudoparticle viral entry assay and SARS-CoV-2 cytopathic effect assay and showed single-digital micromole inhibition against SARS-CoV-2 as well as SARS-CoV-1 and MERS. The characterization of the FP binding site of SARS-CoV-2 S protein provides a promising target for the structure-based development of small molecule entry inhibitors as drug candidates for the treatment of COVID-19.
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http://dx.doi.org/10.1021/acsmedchemlett.1c00263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353886PMC
August 2021

Temperature mediates metabolism switching of Bacillus sp. ZT-1: Analysis of the properties and structure of exopolysaccharides.

Microbiol Res 2021 Oct 5;251:126839. Epub 2021 Aug 5.

Frontiers Science Center for Deep Ocean Multispheres and Earth System, and Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, Ocean University of China, Qingdao, 266100, China; College of Chemistry & Chemical Engineering, Ocean University of China, Qingdao, 266100, China.

Microorganism was very sensitive to external temperature change, which also affected its normal metabolism and secretion. Low temperature exopolysaccharides (LT-EPS) and normal temperature exopolysaccharides (NT-EPS) secreted by Bacillus sp. ZT-1 mediated by temperature were studied in this paper. The total carbohydrate in the LT-EPS and NT-EPS were found to be 82.54 ± 2.56 % and 94.23 ± 1.59 % (w/w). The High Performance Liquid Chromatography (HPLC) revealed the mannose and galacturonic acid accounted for 45.52 and 23.49 % in LT-EPS, respectively. In like manner, mannose and galacturonic acid contained 43.99 and 25.24 % in NT-EPS. One-dimensional nuclear magnetic resonance (NMR) revealed the connection mode of sugar chains. NT-EPS exhibited higher viscosity, better emulsification properties and the larger molecular weight than LT-EPS. Scanning electron microscopy (SEM) showed that LT-EPS was sheet-like with sugar chain branches while NT-EPS was showed as network structure. Furthermore, the 2812 differentially expressed genes (DEGs) were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and located 739 biological pathways. Finally, transcriptome analysis revealed differences in gene expression of the pentose phosphate pathway of carbohydrate metabolism might be the main reason for this difference.
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http://dx.doi.org/10.1016/j.micres.2021.126839DOI Listing
October 2021

Production of purple Ma bamboo (Dendrocalamus latiflorus Munro) with enhanced drought and cold stress tolerance by engineering anthocyanin biosynthesis.

Planta 2021 Aug 12;254(3):50. Epub 2021 Aug 12.

Basic Forestry and Proteomics Center, College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, China.

Main Conclusion: Overexpression of the leaf color (Lc) gene in Ma bamboo substantially increased the accumulation level of anthocyanin, and improved plant tolerance to cold and drought stresses, probably due to the increased antioxidant capacity. Most bamboos, including Ma bamboo (Dendrocalamus latiflorus Munro), are naturally evergreen and sensitive to cold and drought stresses, while it's nearly impossible to make improvements through conventual breeding due to their long and irregular flowering habit. Moreover, few studies have reported bamboo germplasm innovation through genetic engineering as bamboo genetic transformation remains difficult. In this study, we have upregulated anthocyanin biosynthesis in Ma bamboo, to generate non-green Ma bamboo with increased abiotic stress tolerance. By overexpressing the maize Lc gene, a bHLH transcription activator involved in the anthocyanin biosynthesis in Ma bamboo, we generated purple bamboos with increased anthocyanin levels including cyanidin-3-O-rutinoside, peonidin 3-O-rutinoside, and an unknown cyanidin pentaglycoside derivative. The expression levels of 9 anthocyanin biosynthesis genes were up-regulated. Overexpression of the Lc gene improved the plant tolerance to cold and drought stress, probably due to increased antioxidant capacity. The levels of the cold- and drought-related phytohormone jasmonic acid in the transgenic plants were also enhanced, which may also contribute to the plant stress-tolerant phenotypes. High anthocyanin accumulation level did not affect plant growth. Transcriptomic analysis showed higher expressions of genes involved in the flavonoid pathway in Lc transgenic bamboos compared with those in wild-type ones. The anthocyanin-rich bamboos generated here provide an example of ornamental and multiple agronomic trait improvements by genetic engineering in this important grass species.
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http://dx.doi.org/10.1007/s00425-021-03696-zDOI Listing
August 2021

Phenformin synergistically sensitizes liver cancer cells to sorafenib by downregulating CRAF/ERK and PI3K/AKT/mTOR pathways.

Am J Transl Res 2021 15;13(7):7508-7523. Epub 2021 Jul 15.

Department of Oncology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University Zhuzhou 412000, Hunan, China.

Sorafenib is a first-line drug to treat advanced hepatocellular carcinoma (HCC), which can prolong the median overall survival of patients by approximately 3 months. Phenformin is a biguanide derivative that has been shown to exhibit antitumor activity superior to that of metformin. We herein explored the ability of phenformin to enhance the anti-cancer activity of sorafenib against HCC and the mechanisms underlying such synergy. The Hep-G2 and SMMC-7721 HCC cell lines were treated with sorafenib and/or phenformin, after which the proliferation of these cells was evaluated via MTT and colony formation assays, while invasion and apoptotic cell death were evaluated via Transwell and flow cytometry assays, respectively. In addition, protein levels were assessed by Western blotting, drug synergy was assessed with the CompuSyn software, and xenograft models were established by implanting Hep-G2 cells into nude mice and then assessing drug antitumor efficacy. Sorafenib and phenformin exhibited a synergistic ability to suppress HCC cell proliferation, migration, and survival. Phenformin further bolstered the ability of sorafenib to inhibit the CRAF/ERK and PI3K/AKT/mTOR pathways. Strikingly, the combination of these two drugs achieved better efficacy in a murine model system, without causing significant weight loss or hepatorenal toxicity. Sorafenib and phenformin can synergistically suppress CRAF/ERK and PI3K/AKT/mTOR pathway activation in HCC cells, and may thus represent a promising approach to treating this deadly cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340162PMC
July 2021

Plasma Metabolic Phenotypes of HPV-Associated versus Smoking-Associated Head and Neck Cancer and Patient Survival.

Cancer Epidemiol Biomarkers Prev 2021 Oct 10;30(10):1858-1866. Epub 2021 Aug 10.

Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia.

Background: Metabolic differences between human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) and smoking-associated HNSCC may partially explain differences in prognosis. The former relies on mitochondrial oxidative phosphorylation (OXPHOS) while the latter relies on glycolysis. These differences have not been studied in blood.

Methods: We extracted metabolites using untargeted liquid chromatography high-resolution mass spectrometry from pretreatment plasma in a cohort of 55 HPV-associated and 82 smoking-associated HNSCC subjects. Metabolic pathway enrichment analysis of differentially expressed metabolites produced pathway-based signatures. Significant pathways ( < 0.05) were reduced via principal component analysis and assessed with overall survival via Cox models. We classified each subject as glycolytic or OXPHOS phenotype and assessed it with survival.

Results: Of 2,410 analyzed metabolites, 191 were differentially expressed. Relative to smoking-associated HNSCC, bile acid biosynthesis ( < 0.0001) and octadecatrienoic acid beta-oxidation ( = 0.01), were upregulated in HPV-associated HNSCC, while galactose metabolism ( = 0.001) and vitamin B6 metabolism ( = 0.01) were downregulated; the first two suggest an OXPHOS phenotype while the latter two suggest glycolytic. First principal components of bile acid biosynthesis [HR = 0.52 per SD; 95% confidence interval (CI), 0.38-0.72; < 0.001] and octadecatrienoic acid beta-oxidation (HR = 0.54 per SD; 95% CI, 0.38-0.78; < 0.001) were significantly associated with overall survival independent of HPV and smoking. The glycolytic versus OXPHOS phenotype was also independently associated with survival (HR = 3.17; 95% CI, 1.07-9.35; = 0.04).

Conclusions: Plasma metabolites related to glycolysis and mitochondrial OXPHOS may be biomarkers of HNSCC patient prognosis independent of HPV or smoking. Future investigations should determine whether they predict treatment efficacy.

Impact: Blood metabolomics may be a useful marker to aid HNSCC patient prognosis.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492502PMC
October 2021

Distribution Characteristics and Relevance of Heavy Metals in Soils and Colloids Around a Mining Area in Nanjing, China.

Bull Environ Contam Toxicol 2021 Aug 10. Epub 2021 Aug 10.

School of Environment, Nanjing Normal University, Nanjing, 210023, China.

Heavy metal pollution in agricultural soils poses a direct threat to food safety and human health. It has been shown that the colloids is the carrier of heavy metal transport in the polluted soil by heavy metals, but the sources of heavy metals in the soil and colloids and their interrelations are not transparent at present. This study aims to investigate the distribution characteristics of heavy metals in agricultural soils near mining areas, and reveal the relevance of heavy metal content in colloids with total content in soils and their chemical species in soils. Results showed that the concentrations of Mn, Zn, and Pb in agricultural soils and colloids were higher than those of other heavy metals. The content of heavy metals in colloids was positively correlated with the total content of heavy metals in soil. Heavy metals in soil could be easily combined by humus-like substances and tryptophan-like protein in the colloids. The primary source of heavy metals in soil and colloids was mining activities. This study provides theoretical support for revealing the pollution characteristics and migration of heavy metals in agricultural soils and colloids around mining areas.
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http://dx.doi.org/10.1007/s00128-021-03350-0DOI Listing
August 2021
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