Publications by authors named "Shi Yang"

913 Publications

Cell-based therapies for reinforcing the treatment efficacy of meshes in abdominal wall hernias:A systematic review and meta-analysis.

Asian J Surg 2021 Oct 8. Epub 2021 Oct 8.

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

To achieve a tension-free repair and reduce the recurrence rate of abdominal wall hernias (AWHs), various kinds of meshes have been applied in surgery. However, these meshes are reported to have problems with adhesion, infection, chronic pain and foreign body sensation. Recently, the introduction of cellular components on meshes seems to provide a new alternative to resolve these problems. This study aimed to evaluate the treatment efficacy of meshes seeded with cells (mesh-cell group) for AWHs, compared to meshes without cells (mesh group). Cochrane Library, Web of Science and PubMed were searched for studies that provided data about meshes, cells and AWHs. Twenty-six studies involving 578 animals were included. We found that the mesh-cell group could better control hernia recurrent than the mesh group (OR = 0.25, 95% CI = 0.15-0.42). Although the mesh-cell group did not reduce the incidence of adhesions (OR = 0.67, 95% CI = 0.26-1.74), it alleviated the extent of adhesions (WMD = -1.48, 95% CI = -1.86 to -1.10). In addition, the capillary density of mesh-cell group was also higher than that of mesh group (WMD = 26.27, 95% CI = 14.45-38.09). For incidence of infection, the two groups had no significant differences (OR = 0.94, 95% CI = 0.39-2.31). On the basis of our current evidence, AWHs were likely to receive a satisfied outcome in animal models when treated by meshes seeded with cells. Future studies with human trial data are needed to validate these findings.
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http://dx.doi.org/10.1016/j.asjsur.2021.09.019DOI Listing
October 2021

Patterns of leukocyte recovery predict infectious complications after CD19 CAR-T cell therapy in a real-world setting.

Stem Cell Investig 2021 6;8:18. Epub 2021 Sep 6.

Albert Einstein College of Medicine, Bronx, NY, USA.

Background: Adoptive immunotherapy using CD19-targeted Chimeric antigen receptor T cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Data is limited on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy.

Methods: We conducted a retrospective study including 19 patients who received axicabtagene ciloleucel and investigated associations between cytopenia and infectious complications after D30.

Results: Nineteen patients were included, consisting of 42% Hispanic, 32% Caucasian, 21% African-American, and 5% Asian subjects. Post-D30 of CAR-T infusion, 47% patients (n=9) developed an infection and 53% (n=10) remained infection-free. The most common infection type observed was viral (7 patients) followed by bacterial (5 patients) and fungal (3 patients). Of 25 total infectious events, 56% were grade 1 or 2 and 44% were grade 3 with 10 being viral in etiology. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median absolute lymphocyte count (ALC) (1,000/µL . 600/µL, P<0.05), a lower median absolute neutrophil count (ANC)/ALC ratio (1.6 . 3.1, P<0.05) and a lower median AMC/ALC at D30 (0.37 . 1.67, P<0.05). In addition, we observed that only 22% of patients had recovered ANC >1,500/µL in the infection group as opposed to 70% in the non-infection group at D90 (P<0.05). Fifty-eight percent of the patients (11/19) with relapsed refractory DLBCL achieved a complete response with a median follow-up of 233 days (7.7 months).

Conclusions: Although CAR-T cell therapy is highly effective, infectious complications remain an important cause of morbidity and mortality. Low ANC/ALC and AMC/ALC ratios at D30 are potential novel predictors of infection and can be considered in future prophylactic strategies.
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http://dx.doi.org/10.21037/sci-2021-008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449156PMC
September 2021

Multifunctional Magnesium Anastomosis Staples for Wound Closure and Inhibition of Tumor Recurrence and Metastasis.

ACS Biomater Sci Eng 2021 Oct 7. Epub 2021 Oct 7.

State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

Biodegradable magnesium (Mg) implants spontaneously releasing therapeutic agents against tumors are an intriguing therapeutic approach for both tissue repair and tumor treatment. Anastomotic staples are extensively used for wound closure after surgical resection in patients with colorectal tumors. However, the safety of Mg anastomosis implants for intestinal closure and the effect of tumor suppression remain elusive. Here, we used a high-purity Mg staple to study these issues. Based on the results, we found that it has the potential to heal wounds produced after colorectal tumor resection while inhibiting relapse of residual tumor cells in vitro and in vivo. After implantation of Mg staples for 7 weeks in rabbits, the intestinal wound gradually healed with no adverse effects such as leakage or inflammation. Furthermore, the implanted Mg staples inhibit the growth of colorectal tumor cells and block migration to normal organs because of the increased concentration of Mg ions and released hydrogen. Such an antitumor effect is further confirmed by the in vitro cell experiments. Mg significantly induces apoptosis of tumor cells as well as inhibits cell growth and migration. Our work presents a feasible therapeutic opinion to design Mg anastomotic staples to perform wound healing and simultaneously release tumor suppressor elements in vivo to decrease the risk of tumor recurrence and metastasis.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00683DOI Listing
October 2021

Structure-based classification of tauopathies.

Nature 2021 10 29;598(7880):359-363. Epub 2021 Sep 29.

MRC Laboratory of Molecular Biology, Cambridge, UK.

The ordered assembly of tau protein into filaments characterizes several neurodegenerative diseases, which are called tauopathies. It was previously reported that, by cryo-electron microscopy, the structures of tau filaments from Alzheimer's disease, Pick's disease, chronic traumatic encephalopathy and corticobasal degeneration are distinct. Here we show that the structures of tau filaments from progressive supranuclear palsy (PSP) define a new three-layered fold. Moreover, the structures of tau filaments from globular glial tauopathy are similar to those from PSP. The tau filament fold of argyrophilic grain disease (AGD) differs, instead resembling the four-layered fold of corticobasal degeneration. The AGD fold is also observed in ageing-related tau astrogliopathy. Tau protofilament structures from inherited cases of mutations at positions +3 or +16 in intron 10 of MAPT (the microtubule-associated protein tau gene) are also identical to those from AGD, suggesting that relative overproduction of four-repeat tau can give rise to the AGD fold. Finally, the structures of tau filaments from cases of familial British dementia and familial Danish dementia are the same as those from cases of Alzheimer's disease and primary age-related tauopathy. These findings suggest a hierarchical classification of tauopathies on the basis of their filament folds, which complements clinical diagnosis and neuropathology and also allows the identification of new entities-as we show for a case diagnosed as PSP, but with filament structures that are intermediate between those of globular glial tauopathy and PSP.
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http://dx.doi.org/10.1038/s41586-021-03911-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611841PMC
October 2021

Kineticharts: Augmenting Affective Expressiveness of Charts in Data Stories with Animation Design.

IEEE Trans Vis Comput Graph 2021 Sep 29;PP. Epub 2021 Sep 29.

Data stories often seek to elicit affective feelings from viewers. However, how to design affective data stories remains under-explored. In this work, we investigate one specific design factor, animation, and present Kineticharts, an animation design scheme for creating charts that express five positive affects: joy, amusement, surprise, tenderness, and excitement. These five affects were found to be frequently communicated through animation in data stories. Regarding each affect, we designed varied kinetic motions represented by bar charts, line charts, and pie charts, resulting in 60 animated charts for the five affects. We designed Kineticharts by first conducting a need-finding study with professional practitioners from data journalism and then analyzing a corpus of affective motion graphics to identify salient kinetic patterns. We evaluated Kineticharts through two user studies. The results suggest that Kineticharts can accurately convey affects, and improve the expressiveness of data stories, as well as enhance user engagement without hindering data comprehension compared to the animation design from DataClips, an authoring tool for data videos.
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http://dx.doi.org/10.1109/TVCG.2021.3114775DOI Listing
September 2021

A Design Space for Applying the Freytag's Pyramid Structure to Data Stories.

IEEE Trans Vis Comput Graph 2021 Sep 29;PP. Epub 2021 Sep 29.

Data stories integrate compelling visual content to communicate data insights in the form of narratives. The narrative structure of a data story serves as the backbone that determines its expressiveness, and it can largely influence how audiences perceive the insights. Freytag's Pyramid is a classic narrative structure that has been widely used in film and literature. While there are continuous recommendations and discussions about applying Freytag's Pyramid to data stories, little systematic and practical guidance is available on how to use Freytag's Pyramid for creating structured data stories. To bridge this gap, we examined how existing practices apply Freytag's Pyramid by analyzing stories extracted from 103 data videos. Based on our findings, we proposed a design space of narrative patterns, data flows, and visual communications to provide practical guidance on achieving narrative intents, organizing data facts, and selecting visual design techniques through story creation. We evaluated the proposed design space through a workshop with 25 participants. Results show that our design space provides a clear framework for rapid storyboarding of data stories with Freytag's Pyramid.
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http://dx.doi.org/10.1109/TVCG.2021.3114774DOI Listing
September 2021

Development of a long noncoding RNA -dependent gold nanoparticle molecular beacon for the detection of gastric cancer cells.

Nanomedicine (Lond) 2021 10 27;16(25):2255-2267. Epub 2021 Sep 27.

Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No. 83, Xinqiao Street, Shapingba District, Chongqing, 400037, China.

 Long noncoding RNA (lncRNA) -dependent gold nanoparticle molecular beacons (AuNP-MB) were constructed for the detection of gastric cancer cells. The AuNP-MBs were prepared according to well-established procedures based on the Au-S interaction between the gold lattice and thiol functionalized oligonucleotides. More importantly, the stability and targeting ability of AuNP-MB were verified by a series of and experiments. The lncRNA-dependent probes were successfully utilized for AuNP-MB-based intracellular imaging, with fluorescence effectively emitted in GC cells, but not in normal cells. Notably, such fluorescent emission was positively correlated with lncRNA BC032469 expression. The authors developed an effective fluorescent imaging probe for the recognition of gastric cancer cells.
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http://dx.doi.org/10.2217/nnm-2021-0249DOI Listing
October 2021

PLAN B for immunotherapy: Promoting and leveraging anti-tumor B cell immunity.

Authors:
Yang Shi

J Control Release 2021 Sep 24;339:156-163. Epub 2021 Sep 24.

Institute for Experimental Molecular Imaging, Uniklinik RWTH Aachen and Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen 52074, Germany. Electronic address:

Current immuno-oncology primarily focuses on adaptive cellular immunity mediated by T lymphocytes. The other important lymphocytes, B cells, are largely ignored in cancer immunotherapy. B cells are generally considered to be responsible for humoral immune response to viral and bacterial infections. The role of B cells in cancer immunity has long been under debate. Recently, increasing evidence from both preclinical and clinical research has shown that B cells can also induce potent anti-cancer immunity, via humoral and cellular immune responses. Yet it is unclear how to efficiently integrate B cell immunity in cancer immunotherapy. In the current perspective, anti-tumor immunity of B cells is discussed regarding antibody production, antigen presentation, cytokine release and contribution to intratumoral tertiary lymphoid structures. Afterwards, immunosuppressive regulatory phenotypes of B cells are summarized. Furthermore, strategies to activate and modulate B cells using nanomedicines and biomaterials are discussed. This article provides a unique perspective on "PLAN B" (promoting and leveraging anti-tumor B cell immunity) using nanomedicines and biomaterials for cancer immunotherapy. This is envisaged to form a new research direction with the potential to reach the next breakthrough in immunotherapy.
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http://dx.doi.org/10.1016/j.jconrel.2021.09.028DOI Listing
September 2021

Dosage-dependent antimicrobial activity of DNA-histone microwebs against .

Adv Mater Interfaces 2021 Sep 18;8(17). Epub 2021 Aug 18.

State Key Laboratory of Metal Matrix Composites, School of Material Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

Neutrophil extracellular traps (NETs) is an antimicrobial cobweb-structured material produced by immune cells for clearance of pathogens in the body, but paradoxically associated with biofilm formation and exacerbated lung infections. To provide a better materials perspective on the pleiotropic roles played by NETs at diverse compositions/concentrations, a NETs-like material (called 'microwebs', abbreviated as μwebs) is synthesized for decoding the antimicrobial activity of NETs against in infection-relevant conditions. We show that μwebs composed of low-to-intermediate concentrations of DNA-histone complexes successfully trap and inhibit growth and biofilm formation. However, with growing concentrations and histone proportions, the resulting microwebs appear gel-like structures accompanied by reduced antimicrobial activity that can even promote formation of biofilms. Our simplified model of NETs provides a materials-based evidence on NETs-relevant pathology in the development of biofilms.
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http://dx.doi.org/10.1002/admi.202100717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447838PMC
September 2021

The distribution of hepatitis C virus infection in Shanghai, China: a time-spatial study.

BMC Infect Dis 2021 Sep 18;21(1):974. Epub 2021 Sep 18.

Department of Viral Hepatitis Control and prevention, Division of TB and HIV/AIDS Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.

Background: Shanghai, as a pilot city of China to achieve the goal of eliminating hepatitis C, its strategy of allocating medical resources is a pressing problem to be solved. This study aims to infer the time-spatial clustering patterns of HCV-infected cases, and grasp the dynamic genotype distribution of HCV, thereby inform elimination strategies of HCV with efficacy and efficiency.

Methods: Reported HCV cases including their demographic information in Shanghai city from 2005 to 2018 were released from the National Infectious Disease Reporting Information System, population data at community scale, geographical layers of hospitals, communities and districts were gathered from former research. Blood samples of HCV-infected individuals were collected during 2014-2018 from 24 sentinel hospitals, HCV-antibody test, qualitative nucleic acid test and NS5B/5'UTR gene amplification were performed accordingly to determine the genotypes of the specimen. Furthermore, global and local spatial self-correlation analysis of both acute and chronic HCV infections were conducted at community scale year by year, then time-spatial clusters of acute and chronic HCV infections and HCV genotype distribution of specimen collected from sentinel hospitals by districts were mapped by using Arcmap10.1.

Results: A total of 2631 acute HCV cases and 15,063 chronic HCV cases were reported in Shanghai from 2005 to 2018, with a peak in 2010 and 2017, respectively. The mean age of chronic HCV patients was 49.70 ± 14.55 years, 3.34 ± 0.32 years older than the acute (t = 10.55, P-value < 0.01). The spatial distribution of acute HCV infection formed one primary cluster (Relative Risk = 2.71), and the chronic formed one primary cluster and three secondary clusters with Relative Risk ranged from 1.94 to 14.42, meanwhile, an overlap of 34 communities between acute and chronic HCV clusters were found with time period spans varied from 6 to 12 years. Genotype 1 (N = 257, 49.71%) was the most prevalent HCV genotype in Shanghai, genotype 3 infections have increased in recent years. Baoshan district presented cluster of acute HCV and the highest proportion of genotype 2, Pudong new area was the cluster of chronic HCV and occupied the highest proportion of genotype 3.

Conclusions: Despite the low prevalence of HCV infection, it is still needed to push forward the elimination process in Shanghai, as there is a certain amount of HCV infected people waiting to be treated. The time-spatial clustering patterns and the dynamic of HCV genotype distribution together indicated a changing constitution of different transmission routes of HCV infection, thus, a focused strategy may be needed for high-risk population related to genotype 3 infection like drug users, in addition to an enforcement of the existing measures of preventing the iatrogenic and hematogenic transmission of HCV.
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http://dx.doi.org/10.1186/s12879-021-06577-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449884PMC
September 2021

Novel Discrete-Time Recurrent Neural Network for Robot Manipulator: A Direct Discretization Technical Route.

IEEE Trans Neural Netw Learn Syst 2021 Sep 15;PP. Epub 2021 Sep 15.

Controlling and processing of time-variant problem is universal in the fields of engineering and science, and the discrete-time recurrent neural network (RNN) model has been proven as an effective method for handling a variety of discrete time-variant problems. However, such model usually originates from the discretization research of continuous time-variant problem, and there is little research on the direct discretization method. To address the aforementioned problem, this article introduces a novel discrete-time RNN model for solving the discrete time-variant problem in a pioneering manner. Specifically, a discrete time-variant nonlinear system, which originates from the mathematical modeling of serial robot manipulator, is presented as a target problem. For solving the problem, first, the technique of second-order Taylor expansion is used to deal with the discrete time-variant nonlinear system, and the novel discrete-time RNN model is proposed subsequently. Second, the theoretical analyses are investigated and developed, which shows the convergence and precision of the proposed discrete-time RNN model. Furthermore, three distinct numerical experiments verify the excellent performance of the proposed discrete-time RNN model. In addition, a robot manipulator example further verifies the effectiveness and practicability of the proposed novel discrete-time RNN model.
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http://dx.doi.org/10.1109/TNNLS.2021.3108050DOI Listing
September 2021

Intermediate between Idiopathic Hypereosinophilia and Chronic Eosinophilic Leukemia: A Report of Two Hypereosinophilic Cases with Possible Novel Molecular Mutations.

Case Rep Hematol 2021 31;2021:1142124. Epub 2021 Aug 31.

Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210 Street, Bronx 10467, NY, USA.

To distinguish a reactive eosinophilia from its malignant counterpart is challenging. Establishing clonality of the eosinophils is crucial and considered the determining factor for establishing a diagnosis. Cases of hypereosinophilia without clear reactive etiologies, no evidence of end-organ damage, normal cytogenetics, and no molecular mutations are termed as "Idiopathic Hypereosinophilia (IHE)." For cases which lie between the spectrum of chronic eosinophilic leukemia (CEL) and IHE, identification of underlying molecular abnormalities might be helpful in better understanding the disease process and prognosis. Here, we report two cases of hypereosinophilia in which five possible novel molecular mutations were identified by targeted next-generation sequencing (NGS) analysis. They were FBXW7, KM2A, TCF3, ERBB4, and MET. With multiple genetic mutations, these cases could be classified as chronic eosinophilic leukemia. Both these young patients responded well to steroid therapy. While targeted NGS is a useful tool in identifying new molecular mutation associated with hypereosinophilia, our cases raise the question of further investigating this entity and if there is a possibility of an intermediate category lying between the spectrum of CEL and IHE. Defining hypereosinophilia with clonal molecular abnormality as a malignant process may need to be revisited. Even though attempts are being made to identify mutations in IHE, it might be more significant clinically to differentiate them based on response to steroid therapy and prognosis.
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http://dx.doi.org/10.1155/2021/1142124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426067PMC
August 2021

Stochastic model predictive control framework for resilient cyber-physical systems: review and perspectives.

Philos Trans A Math Phys Eng Sci 2021 Oct 16;379(2207):20200371. Epub 2021 Aug 16.

Department of Mechanical Engineering, University of Victoria, Victoria, British Columbia, Canada V8W 3P6.

In the era of Industrial 4.0, the next-generation control system regards the cyber-physical system (CPS) as the core ingredient thanks to the comprehensive integration of physical systems, online computation, networking and control. A reliable, stable and resilient CPS should pledge robustness and safety. A significant concern in CPS development arises from security issues since the CPS is vulnerable to physical constraints, ubiquitous uncertainties and malicious cyber attacks. The integration of the stochastic model predictive control (MPC) framework and the resilient mechanism is a possible approach to guarantee robustness in the presence of stochastic uncertainties and enable resilience against cyber attacks. This review paper aims to offer a detailed overview of existing stochastic MPC algorithms and their CPS applications. More specifically, we first review existing stochastic MPC algorithms for both linear and nonlinear systems subject to probabilistic constraints. We then discuss how to extend the stochastic MPC framework to incorporate resilience mechanisms for constrained CPS under various malicious attacks. Finally, we present an architectural stochastic MPC-based framework for resilient CPS and identify future research challenges. This article is part of the theme issue 'Towards symbiotic autonomous systems'.
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http://dx.doi.org/10.1098/rsta.2020.0371DOI Listing
October 2021

High-density lipoprotein in Alzheimer's disease: From potential biomarkers to therapeutics.

J Control Release 2021 Oct 13;338:56-70. Epub 2021 Aug 13.

Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing 210009, China; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China; NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, Nanjing 210009, China. Electronic address:

The inverse correlation between high-density lipoprotein (HDL) levels in vivo and the risk of Alzheimer's disease (AD) has become an inspiration for HDL-inspired AD therapy, including plain HDL and various intelligent HDL-based drug delivery systems. In this review, we will focus on the two endogenous HDL subtypes in the central nervous system (CNS), apolipoprotein E-based HDL (apoE-HDL) and apolipoprotein A-I-based HDL (apoA-I-HDL), especially their influence on AD pathophysiology to reveal HDL's potential as biomarkers for risk prediction, and summarize the relevant therapeutic mechanisms to propose possible treatment strategies. We will emphasize the latest advances of HDL as therapeutics (plain HDL and HDL-based drug delivery systems) to discuss the potential for AD therapy and review innovative techniques in the preparation of HDL-based nanoplatforms to provide a basis for the rational design and future development of anti-AD drugs.
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http://dx.doi.org/10.1016/j.jconrel.2021.08.018DOI Listing
October 2021

Numerical Analysis of Space Deployable Structure Based on Shape Memory Polymers.

Micromachines (Basel) 2021 Jul 17;12(7). Epub 2021 Jul 17.

Beijing Institute of Technology, School of Aerospace Engineering, Beijing 100081, China.

Shape memory polymers (SMPs) have been applied in aerospace engineering as deployable space structures. In this work, the coupled finite element method (FEM) was established based on the generalized Maxwell model and the time-temperature equivalence principle (TTEP). The thermodynamic behavior and shape memory effects of a single-arm deployment structure (F-DS) and four-arm deployment structure (F-DS) based on SMPs were analyzed using the coupled FEM. Good consistency was obtained between the experimental data and simulation data for the tensile and S-DS recovery forces, verifying that the coupled FEM can accurately and reliably describe the thermodynamic behavior and shape memory effects of the SMP structure. The step-by-step driving structure is suitable for use as a large-scale deployment structure in space. This coupled FEM provides a new direction for future research on epoxy SMPs.
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http://dx.doi.org/10.3390/mi12070833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304941PMC
July 2021

Status and prospects of the application of root exudates in the restoration of polluted or desertated soil.

Ying Yong Sheng Tai Xue Bao 2021 Jul;32(7):2623-2632

College of Ecology and Environment, Chengdu University of Technology, Chengdu 610059, China.

Ecological and environmental problems including heavy metal pollution have received increasing concerns. Given the shortage of physical and chemical remediation methods in high cost and secondary pollution, using plants and microorganisms for joint remediation of environment has become one of the most important strategies. Root exudates are an important medium for information and nutrient exchange between plants and soil. The roles of plant root exudates in remediation of polluted and degradated soil have been widely studied. In this review, we described the composition, secretion mechanism and functions of root exudates and summarized the functions of root exudate in heavy metal absorption, allelopathy, interaction between roots and rhizosphere microorga-nisms, and changes in soil physical and chemical properties. The progress, challenges and prospect of applying root exdudates and rhizosphere microorganisms in the remediation of ecology and environment have also been discussed. This review could provide theoretical support for the application of plant-microorganism based environmental remediation.
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http://dx.doi.org/10.13287/j.1001-9332.202107.039DOI Listing
July 2021

Influence of the Hollowness and Size Distribution on the Magnetic Properties of FeO Nanospheres.

Langmuir 2021 08 26;37(31):9605-9612. Epub 2021 Jul 26.

School of Materials Science and Engineering, Xi'an University of Technology, Xi'an 710048, China.

In this study, FeO nanospheres with different levels of hollowness were successfully prepared by the solvent thermal method. The synthesized FeO nanospheres were characterized by transmission electron microscopy, X-ray diffraction, and vibrating sample magnetometry, and Image-Pro software was used to analyze the hollowness of the FeO nanospheres for the first time. It was found that excess reactants could lead to the disappearance of the hollow structure of the FeO nanospheres, and the reason for this phenomenon was discussed as due to entropy increase theory. Furthermore, the influence of the hollowness and size distribution on the magnetic properties of the FeO nanospheres was evaluated. The magnetic properties of a FeO nanosphere with a hollowness of 10.48% showed a relatively high saturation magnetization of 103 emu/g and a rather low coercivity (54 Oe). The as-prepared FeO nanospheres are expected to be useful in a wide range of fields such as drug-delivery and energy applications.
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http://dx.doi.org/10.1021/acs.langmuir.1c01498DOI Listing
August 2021

A malaria parasite phospholipid flippase safeguards midgut traversal of ookinetes for mosquito transmission.

Sci Adv 2021 Jul 23;7(30). Epub 2021 Jul 23.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signal Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

Mosquito midgut epithelium traversal is essential for malaria parasite transmission. Phospholipid flippases are eukaryotic type 4 P-type adenosine triphosphatases (P4-ATPases), which, in association with CDC50, translocate phospholipids across the membrane lipid bilayers. In this study, we investigated the function of a putative P4-ATPase, ATP7, from the rodent malaria parasite Disruption of ATP7 blocks the parasite infection of mosquitoes. ATP7 is localized on the ookinete plasma membrane. While ATP7-depleted ookinetes are capable of invading the midgut, they are eliminated within the epithelial cells by a process independent from the mosquito complement-like immunity. ATP7 colocalizes and interacts with the flippase cofactor CDC50C. Depletion of CDC50C phenocopies ATP7 deficiency. ATP7-depleted ookinetes fail to uptake phosphatidylcholine across the plasma membrane. Ookinete microinjection into the mosquito hemocoel reverses the ATP7 deficiency phenotype. Our study identifies flippase as a mechanism of parasite survival in the midgut epithelium that is required for mosquito transmission.
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http://dx.doi.org/10.1126/sciadv.abf6015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302136PMC
July 2021

A recombinant spike protein subunit vaccine confers protective immunity against SARS-CoV-2 infection and transmission in hamsters.

Sci Transl Med 2021 08 20;13(606). Epub 2021 Jul 20.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen 361102, P. R. China.

Multiple safe and effective vaccines that elicit immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary to respond to the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a protein subunit vaccine composed of spike ectodomain protein (StriFK) plus a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH002C). StriFK-FH002C generated substantially higher neutralizing antibody titers in mice, hamsters, and cynomolgus monkeys than those observed in plasma isolated from COVID-19 convalescent individuals. StriFK-FH002C also induced both T1- and T2-polarized helper T cell responses in mice. In hamsters, StriFK-FH002C immunization protected animals against SARS-CoV-2 challenge, as shown by the absence of virus-induced weight loss, fewer symptoms of disease, and reduced lung pathology. Vaccination of hamsters with StriFK-FH002C also reduced within-cage virus transmission to unvaccinated, cohoused hamsters. In summary, StriFK-FH002C represents an effective, protein subunit-based SARS-CoV-2 vaccine candidate.
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http://dx.doi.org/10.1126/scitranslmed.abg1143DOI Listing
August 2021

Intron-targeted mutagenesis reveals roles for Dscam1 RNA pairing architecture-driven splicing bias in neuronal wiring.

Cell Rep 2021 Jul;36(2):109373

MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang ZJ310058, China; Department of Neurosurgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang ZJ310058, China. Electronic address:

Drosophila melanogaster Down syndrome cell adhesion molecule (Dscam1) can generate 38,016 different isoforms through largely stochastic, yet highly biased, alternative splicing. These isoforms are required for nervous functions. However, the functional significance of splicing bias remains unknown. Here, we provide evidence that Dscam1 splicing bias is required for mushroom body (MB) axonal wiring. We generate mutant flies with normal overall protein levels and an identical number but global changes in exon 4 and 9 isoform bias (DscamΔ4D and DscamΔ9D), respectively. In contrast to DscamΔ4D, DscamΔ9D exhibits remarkable MB defects, suggesting a variable domain-specific requirement for isoform bias. Importantly, changes in isoform bias cause axonal defects but do not influence the self-avoidance of axonal branches. We conclude that, in contrast to the isoform number that provides the molecular basis for neurite self-avoidance, isoform bias may play a role in MB axonal wiring by influencing non-repulsive signaling.
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http://dx.doi.org/10.1016/j.celrep.2021.109373DOI Listing
July 2021

Analysis of m6A RNA methylation in Caenorhabditis elegans.

Cell Discov 2020 Jul 14;6(1):47. Epub 2020 Jul 14.

Division of Newborn Medicine and Epigenetics Program, Department of Medicine, Boston Children's Hospital, Boston, MA, 02115, USA.

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http://dx.doi.org/10.1038/s41421-020-00186-6DOI Listing
July 2020

Evaluation of a five-gene signature associated with stromal infiltration for diffuse large B-cell lymphoma.

World J Clin Cases 2021 Jun;9(18):4585-4598

Department of Hematology, Chongqing University Cancer Hospital, Chongqing 400030, China.

Background: Diffuse large B-cell lymphoma (DLBCL) is a common non-Hodgkin lymphoma. The development of immunotherapy greatly improves the patient prognosis but there are some exceptions. Thus, screening for better biomarkers for prognostic evaluation could contribute to the treatment of DLBCL patients.

Aim: To screen the novel mediators involved in the development of DLBCL.

Methods: The GSE60 dataset was applied to identify the differentially expressed genes (DEGs) in DLBCL, and the principal components analysis plot was used to determine the quality of the included samples. The protein-protein interactions were analyzed by the STRING tool. The key hub genes were entered into to the GEPIA database to determine their expressions in DLBCL. Furthermore, these hub gene alterations were analyzed in cBioportal. The UALCAN portal was employed to analyze the expression of the hub genes in different stages of DLBCL. The Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Score was conducted to evaluate the correlation between the gene expression and tumor purity. The gene-gene correlation analysis was conducted in the GEPIA. The stromal score analysis was conducted in TIMER to confirm the correlation between the gene expression and infiltrated stromal cells. The correlation between the indicated genes and infiltration level of cancer-associated fibroblasts (CAFs) was also completed in TIMER with two methods, MCP-Counter and Tumor immune dysfunction and exclusion. The correlation between fibronectin (FN1) protein level and secreted protein acidic and cysteine-rich (SPARC) messenger ribonucleic acid expression was confirmed in the cBioportal.

Results: The top 20 DEGs in DLBCL were identified, and the principal components analysis plot confirmed the quality of the significant DEGs. The pairwise correlation coefficient analysis among all samples showed that these DEGs have a certain co-expression pattern. The DEGs were subjected to STRING to identify the hub genes, alpha-2-macroglobulin (), cathepsin B (), , matrix metallopeptidase 9 (), and . The five hub genes were confirmed to be overexpressed in DLBCL. The cBioportal portal detected these five hub genes that had gene alteration, including messenger ribonucleic acid high amplification and missense mutation, and the gene alteration percentages of , , , , and were 5%, 8%, 5%, 2.7%, and 5%, respectively. Furthermore, the five hub genes had a potential positive correlation with tumor stage. The correlation analysis between the five genes and tumor purity confirmed that the five genes were overexpressed in DLBCL and had a positive correlation with the development of DLBCL. More interestingly, the five genes had a significant correlation with the stromal infiltration scores. The correlation analysis between the fives genes and CAFs also showed a significant value, among which the top two genes, and , had a remarkable co-expression pattern.

Conclusion: The top DEGs were identified, and the five hub genes were overexpressed in DLBCL. Furthermore, the gene alterations were confirmed and the positive correlation with tumor purity revealed the overexpression of the five genes and close association with the development of DLBCL. More interestingly, the five genes were positively correlated with stromal infiltration, especially in CAFs. The top two genes, and , showed a co-expression pattern, which indicates their potential as novel therapeutic targets for DLBCL.
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http://dx.doi.org/10.12998/wjcc.v9.i18.4585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223837PMC
June 2021

Genome sequencing identified novel mechanisms underlying virescent mutation in upland cotton Gossypiuma hirsutum.

BMC Genomics 2021 Jul 3;22(1):498. Epub 2021 Jul 3.

Jiangsu Coastal Area Institute of Agricultural Sciences/Observation and Experimental Station of Saline Land of Costal Area, Ministry of Agriculture, Yancheng, 224002, Jiangsu, People's Republic of China.

Background: Virescent mutation broadly exists in plants and is an ideal experimental material to investigate regulatory mechanisms underlying chlorophyll synthesis, photosynthesis and plant growth. Up to date, the molecular mechanisms in two virescent mutations have been clarified in cottons (Gossypiuma hirsutum). A virescent mutation has been found in the cotton strain Sumian 22, and the underlying molecular mechanisms have been studied.

Methods: The virescent mutant and wild type (WT) of Sumian 22 were cross-bred, and the F population were self-pollinated to calculate the segregation ratio. Green and yellow leaves from F populations were subjected to genome sequencing and bulked-segregant analysis was performed to screen mutations. Real-time quantitative PCR (RT-qPCR) were performed to identify genes in relations to chlorophyll synthesis. Intermediate products for chlorophyll synthesis were determined to validate the RT-qPCR results.

Results: The segregation ratio of green and virescent plants in F2 population complied with 3:1. Compared with WT, a 0.34 Mb highly mutated interval was identified on the chromosome D10 in mutant, which contained 31 genes. Among them, only ABCI1 displayed significantly lower levels in mutant than in WT. Meanwhile, the contents of Mg-protoporphyrin IX, protochlorophyllide, chlorophyll a and b were all significantly lower in mutant than in WT, which were consistent with the inhibited levels of ABCI1. In addition, a mutation from A to T at the -317 bp position from the start codon of ABCI1 was observed in the genome sequence of mutant.

Conclusions: Inhibited transcription of ABCI1 might be the mechanism causing virescent mutation in Sumian 22 cotton, which reduced the transportation of protoporphyrin IX to plastid, and then inhibited Mg-protoporphyrin IX, Protochlorophyllide and finally chlorophyll synthesis. These results provided novel insights into the molecular mechanisms underlying virescent mutation in cotton.
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http://dx.doi.org/10.1186/s12864-021-07810-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254239PMC
July 2021

Involvement of TIGIT in Natural Killer Cell Exhaustion and Immune Escape in Patients and Mouse Model With Liver Echinococcus multilocularis Infection.

Hepatology 2021 Jun 30. Epub 2021 Jun 30.

State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, Xinjiang Medical University, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Background And Aims: Alveolar echinococcosis (AE) is a lethal helminthic liver disease caused by persistent infection with Echinococcus multilocularis. Although more attention has been paid to the immunotolerance of T cells caused by E. multilocularis infection, the role of natural killer (NK) cell, a critical player in liver immunity, is seldom studied.

Approach And Results: Here, we observed that NK cells from the blood and closed liver tissue (CLT) of AE patients expressed a higher level of inhibitory receptor TIGIT and were functionally exhausted with a lower expression of granzyme B, perforin, interferon-gamma (IFN-γ), and TNF-α. Addition of anti-TIGIT (T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain) monoclonal antibody into AE patients' peripheral blood mononuclear cell culture significantly enhanced the synthesis of IFN-γ and TNF-α by NK cells, indicating the reversion of exhausted NK cells by TIGIT blockade. In the mouse model of E. multilocularis infection, liver and splenic TIGIT NK cells progressively increased dependent of infection dosage and timing and were less activated and less degranulated with lower cytokine secretion. Furthermore, TIGIT deficiency or blockade in vivo inhibited liver metacestode growth, reduced liver injury, and increased the level of IFN-γ produced by liver NK cells. Interestingly, NK cells from mice with persistent chronic infection expressed a higher level of TIGIT compared to self-healing mice. To look further into the mechanisms, more regulatory CD56 and murine CD49a NK cells with higher TIGIT expression existed in livers of AE patients and mice infected with E. multilocularis, respectively. They coexpressed higher surface programmed death ligand 1 and secreted more IL-10, two strong inducers to mediate the functional exhaustion of NK cells.

Conclusions: Our results indicate that inhibitory receptor TIGIT is involved in NK cell exhaustion and immune escape from E. multilocularis infection.
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http://dx.doi.org/10.1002/hep.32035DOI Listing
June 2021

New Biotransformation Mode of Zearalenone Identified in Y816 Revealing a Novel ZEN Conjugate.

J Agric Food Chem 2021 Jul 28;69(26):7409-7419. Epub 2021 Jun 28.

National Technology Innovation Center of Synthetic Biology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.

An increasing number of strains have been identified, and the removal capacity of zearalenone (ZEN) was determined; however, they failed to reveal the detoxification mechanism and transformation product. Here, Y816, which could transform 40 mg/L of ZEN within 7 h of fermentation, was identified and studied. First, the biotransformation products of ZEN and 17-β-estradiol (E2) were identified as ZEN-14-phosphate and E2-3-phosphate by HPLC-TOF-MS and NMR, respectively. An intracellular zearalenone phosphotransferase (ZPH) was found through transcriptome sequencing analysis of Y816. The phosphorylated reaction conditions of ZEN by ZPH were further revealed in this work. Furthermore, the phosphorylated conjugates showed reduced estrogenic toxicity compared with their original substances (ZEN and α/β-zearalenol) using an engineered yeast biosensor system. The first report on the phosphorylated conjugated mode of ZEN in Y816 will inspire new perspectives on the biotransformation of ZEN in strains.
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http://dx.doi.org/10.1021/acs.jafc.1c01817DOI Listing
July 2021

Characterization of a carbapenem-resistant coharbouring and genes.

J Med Microbiol 2021 Jun;70(6)

The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, PR China.

Members of the genus are facultative anaerobic Gram-negative bacilli belonging to the [Janda 1994; 32(8):1850-1854; Arens 1997;3(1):53-57]. Formerly, were occasionally reported as nosocomial pathogens with low virulence [Pepperell 2002;46(11):3555-60]. Now, they are consistently reported to cause nosocomial infections of the urinary tract, respiratory tract, bone, peritoneum, endocardium, meninges, intestines, bloodstream and central nervous system. Among species, the most common isolates are and , while has seldom been isolated [Janda 1994; 32(8):1850-1854; Marak 2017;49(7):532-9]. Further, spp. are usually susceptible to carbapenems, aminoglycosides, tetracyclines and colistin [Marak 2017;49(7):532-9]. As is rare, only one clinical isolate, coharbouring carbapenem resistance gene and quinolone resistance gene , has been reported. To characterize a carbapenem-resistant strain from PR China coharbouring and . Three hundred and forty nonrepetitive carbapenem-resistant (CRE) strains were collected during 2011-2018. A carbapenem-resistant strain was detected and confirmed using a VITEK mass spectrometry-based microbial identification system and 16S rRNA sequencing. Minimum inhibitory concentrations (MICs) for clinical antimicrobials were obtained by the broth microdilution method. Whole-genome sequencing (WGS) was performed for antibiotic resistance gene analysis, and a phylogenetic tree of strains was constructed using the Bacterial Pan Genome Analysis (BPGA) tool. The transferability of the resistance plasmid was verified by conjugal transfer. A rare carbapenem-resistant strain (CA71) was recovered from a patient with cerebral obstruction and the sequences of 16S rRNA gene shared more than 99 % similarity with CITRO86, FDAARGOS 165. CA71 is resistant to β-lactam, quinolone and aminoglycoside antibiotics, and even imipenem and meropenem (MICs of 2 and 4 mg l respectively), and is only sensitive to polymyxin B and tigecycline. Six antibiotic resistance genes were detected via WGS, including the β-lactam genes , and , the quinolone gene , and the aminoglycoside genes . Interestingly, and coexist on an IncN1-type plasmid (pCA71-IMP) and successfully transferred to J53 via conjugal transfer. Phylogenetic analysis showed that CA71 is most similar to strain CJ25 and belongs to the same evolutionary cluster along with seven other strains. To the best of our knowledge, this is the first report of a carbapenem-resistant isolate coharbouring and .
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http://dx.doi.org/10.1099/jmm.0.001364DOI Listing
June 2021

Overexpressing low-density lipoprotein receptor reduces tau-associated neurodegeneration in relation to apoE-linked mechanisms.

Neuron 2021 08 21;109(15):2413-2426.e7. Epub 2021 Jun 21.

Department of Neurology, Washington University, St. Louis, MO 63110, USA. Electronic address:

APOE is the strongest genetic risk factor for late-onset Alzheimer's disease. ApoE exacerbates tau-associated neurodegeneration by driving microglial activation. However, how apoE regulates microglial activation and whether targeting apoE is therapeutically beneficial in tauopathy is unclear. Here, we show that overexpressing an apoE metabolic receptor, LDLR (low-density lipoprotein receptor), in P301S tauopathy mice markedly reduces brain apoE and ameliorates tau pathology and neurodegeneration. LDLR overexpression (OX) in microglia cell-autonomously downregulates microglial Apoe expression and is associated with suppressed microglial activation as in apoE-deficient microglia. ApoE deficiency and LDLR OX strongly drive microglial immunometabolism toward enhanced catabolism over anabolism, whereas LDLR-overexpressing microglia also uniquely upregulate specific ion channels and neurotransmitter receptors upon activation. ApoE-deficient and LDLR-overexpressing mice harbor enlarged pools of oligodendrocyte progenitor cells (OPCs) and show greater preservation of myelin integrity under neurodegenerative conditions. They also show less reactive astrocyte activation in the setting of tauopathy.
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http://dx.doi.org/10.1016/j.neuron.2021.05.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349883PMC
August 2021

Combined epigenetic and metabolic treatments overcome differentiation blockade in acute myeloid leukemia.

iScience 2021 Jun 25;24(6):102651. Epub 2021 May 25.

Division of Newborn Medicine, Boston Children's Hospital, Boston, MA 02115, USA.

A hallmark of acute myeloid leukemia (AML) is the inability of self-renewing malignant cells to mature into a non-dividing terminally differentiated state. This differentiation block has been linked to dysregulation of multiple cellular processes, including transcriptional, chromatin, and metabolic regulation. The transcription factor HOXA9 and the histone demethylase LSD1 are examples of such regulators that promote differentiation blockade in AML. To identify metabolic targets that interact with LSD1 inhibition to promote myeloid maturation, we screened a small molecule library to identify druggable substrates. We found that differentiation caused by LSD1 inhibition is enhanced by combined perturbation of purine nucleotide salvage and lipogenesis pathways, and identified multiple lines of evidence to support the specificity of these pathways and suggest a potential basis of how perturbation of these pathways may interact synergistically to promote myeloid differentiation. In sum, these findings suggest potential drug combination strategies in the treatment of AML.
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http://dx.doi.org/10.1016/j.isci.2021.102651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192696PMC
June 2021

Thermal treatment's enhancement on high solid anaerobic digestion: effects of temperature and reaction time.

Environ Sci Pollut Res Int 2021 Jun 18. Epub 2021 Jun 18.

School of Civil and Surveying & Mapping Engineering, Jiangxi University of Science and Technology, Ganzhou, Jiangxi Province, China.

The methane production rate of high solid anaerobic digestion (HSAD) was poor although it was a promising technology with the advantages of small reactor, low energy consumption, and less digestate. In our research before, thermal treatment was proved to enhance HSAD's methane production rate via both batch experiments and continuous experiments of swine manure. However, the effect or investigation of thermal treatment's temperature-time combinations was not yet reported. In this study, swine manure was firstly thermally treated in 500-mL glass bottles with 400-mL work volume at 45-65 °C for 1-4 days. HSAD experiment of 10% solid content was then set up. The VS ratio of substrate to inoculum was 1:1. Thermal treatment at 45 °C (3 days), 55 °C (1 day), and 65 °C (3 days) could obtain the highest methane production rate, which was around 40% higher. Kinetics analysis suggested that the degradation of swine manure was quite different at different temperatures. Furthermore, energy assessment indicated that "thermal treatment + HSAD" had significant advantages in improving HSAD economic feasibility, because the improved methane production rate could compensate for the extra energy utilized for thermal treatment. Heat treatment at 45 °C (4 days) was preferred when the heating equipment was limited. Heat treatment at 55 °C (1 day) was preferred when the floor space and reactor volume were restricted. Heat treatment at 65°C (3 days) was preferred when the requirement of the digestate's sanitary condition is strict.
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http://dx.doi.org/10.1007/s11356-021-14926-yDOI Listing
June 2021

Molecular detection and quantification of in juice from symptomless sugarcane stalks using a real-time quantitative PCR assay.

Plant Dis 2021 Jun 18. Epub 2021 Jun 18.

Fujian Agriculture and Forestry University, Sugarcane Research Institute, 15 Shang Xia Dian Rd, Cangshan District, Fuzhou, Fujian, China, 350002;

Leaf scald, a bacterial disease caused by (Ashby) Dowson, is a major limiting factor for sugarcane production worldwide. Accurate identification and quantification of is a prerequisite for successful management of this disease. A very sensitive and robust qPCR assay was developed in this study for detection and quantification of using TaqMan probe and primers targeting a putative adenosine triphosphate-binding cassette (ABC) transporter gene (abc). The novel qPCR assay was highly specific to the 43 tested strains belonging to different pulsed-field gel electrophoresis (PFGE) groups. The detection thresholds were 100 copies/µL of plasmid DNA, 100 fg/µL of bacterial genomic DNA, and 100 CFU/ml of bacterial suspension prepared from pure culture. This qPCR assay was 100 times more sensitive than a conventional PCR assay. The pathogen was detected by qPCR in 75.1% (410/546) symptomless stalk samples, whereas only 28.4% (155/546) samples tested positive by conventional PCR. Based on qPCR data, population densities of in symptomless stalks of the same varieties differed between two sugarcane production areas in China, Beihai (Guangxi province) and Zhanjiang (Guangdong province), and no significant correlation between these populations was identified. Furthermore, no relationship was found between these populations of the pathogen in asymptomatic stalks and the resistance level of the sugarcane varieties to leaf scald. The newly developed qPCR assay proved to be highly sensitive and reliable for the detection and quantification of in sugarcane stalks.
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http://dx.doi.org/10.1094/PDIS-03-21-0468-REDOI Listing
June 2021
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