Publications by authors named "Peng Sha"

91 Publications

Research on Adolescents Regarding the Indirect Effect of Depression, Anxiety, and Stress between TikTok Use Disorder and Memory Loss.

Int J Environ Res Public Health 2021 08 21;18(16). Epub 2021 Aug 21.

School of Journalism and Communication, Southwest University, Chongqing 400715, China.

This research involved the participation of 3036 Chinese students in the first and second years of senior high school. The adolescents were active users of TikTok. The mediating effect of depression, anxiety, and stress between TikTok use disorder and memory loss was investigated. A forward and backward digit span test was applied to measure memory loss. Structural equation modeling (SEM) was established, and SPSS Amos was used for analysis. The results show a partial mediation effect of depression and anxiety between TikTok use disorder and forward digit span. A partial mediation effect of depression, anxiety, and stress between TikTok use disorder and backward digit span is also shown. These results also show gender differences. Attention should be given to male students, who have more depression, anxiety, and stress than female students; they also have more memory loss.
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http://dx.doi.org/10.3390/ijerph18168820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393543PMC
August 2021

Melatonin relieves heat-induced spermatocyte apoptosis in mouse testes by inhibition of ATF6 and PERK signaling pathways.

Zool Res 2021 07;42(4):514-524

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A & F University, Yangling, Shaanxi 712100, China.

Normal spermatogenic processes require the scrotal temperature to be lower than that of the body as excessive heat affects spermatogenesis in the testes, reduces sperm quality and quantity, and even causes infertility. Endoplasmic reticulum stress (ERS) is a crucial factor in many pathologies. Although several studies have linked ERS to heat stress, researchers have not yet determined which ERS signaling pathways contribute to heat-induced testicular damage. Melatonin activates antioxidant enzymes, scavenges free radicals, and protects the testes from inflammation; however, few studies have reported on the influence of melatonin on heat-induced testicular damage. Using a murine model of testicular hyperthermia, we observed that heat stress causes both ERS and apoptosis in the testes, especially in the spermatocytes. These observations were confirmed using the mouse spermatocyte cell line GC2, where the and signaling pathways were activated during heat stress. Knockout of the above genes effectively reduced spermatocyte damage caused by heat stress. Pretreatment with melatonin alleviated heat-induced apoptosis by inhibiting the and signaling pathways. This mitigation was dependent on the melatonin receptors. experiments verified that melatonin treatment relieved heat-induced testicular damage. In conclusion, our results demonstrated that ATF6 and PERK are important mediators for heat-induced apoptosis, which can be prevented by melatonin treatment. Thus, our study highlights melatonin as a potential therapeutic agent in mammals for subfertility/infertility induced by testicular hyperthermia.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2021.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317181PMC
July 2021

Responses and coping methods of different testicular cell types to heat stress: overview and perspectives.

Biosci Rep 2021 Jun;41(6)

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.

To facilitate temperature adjustments, the testicles are located outside the body cavity. In most mammals, the temperature of the testes is lower than the body temperature to ensure the normal progression of spermatogenesis. Rising temperatures affect spermatogenesis and eventually lead to a decline in male fertility or even infertility. However, the testes are composed of different cell types, including spermatogonial stem cells (SSCs), spermatocytes, spermatozoa, Leydig cells, and Sertoli cells, which have different cellular responses to heat stress. Recent studies have shown that using different drugs can relieve heat stress-induced reproductive damage by regulating different signaling pathways. Here, we review the mechanisms by which heat stress damages different cells in testes and possible treatments.
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http://dx.doi.org/10.1042/BSR20210443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209165PMC
June 2021

Single-cell RNA sequencing reveals atlas of dairy goat testis cells.

Zool Res 2021 Jul;42(4):401-405

College of Veterinary Medicine, Northwest A & F University, Shaanxi Centre of Stem Cells Engineering & Technology, Yangling, Shaanxi 712100, China.

Single-cell RNA sequencing (scRNA-seq) is useful for exploring cell heterogeneity. For large animals, however, little is known regarding spermatogonial stem cell (SSC) self-renewal regulation, especially in dairy goats. In this study, we described a high-resolution scRNA-seq atlas derived from a dairy goat. We identified six somatic cell and five spermatogenic cell subtypes. During spermatogenesis, genes with significantly changed expression were mainly enriched in the Notch, TGF-β, and Hippo signaling pathways as well as the signaling pathway involved in the regulation of stem cell pluripotency. We detected and screened specific candidate marker genes ( and ) for spermatogonia. Our study provides new insights into goat spermatogenesis and the development of testicular somatic cells.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317185PMC
July 2021

Histone demethylase complexes KDM3A and KDM3B cooperate with OCT4/SOX2 to define a pluripotency gene regulatory network.

FASEB J 2021 06;35(6):e21664

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China.

The pluripotency gene regulatory network of porcine induced pluripotent stem cells(piPSCs), especially in epigenetics, remains elusive. To determine the biological function of epigenetics, we cultured piPSCs in different culture conditions. We found that activation of pluripotent gene- and pluripotency-related pathways requires the erasure of H3K9 methylation modification which was further influenced by mouse embryonic fibroblast (MEF) served feeder. By dissecting the dynamic change of H3K9 methylation during loss of pluripotency, we demonstrated that the H3K9 demethylases KDM3A and KDM3B regulated global H3K9me2/me3 level and that their co-depletion led to the collapse of the pluripotency gene regulatory network. Immunoprecipitation-mass spectrometry (IP-MS) provided evidence that KDM3A and KDM3B formed a complex to perform H3K9 demethylation. The genome-wide regulation analysis revealed that OCT4 (O) and SOX2 (S), the core pluripotency transcriptional activators, maintained the pluripotent state of piPSCs depending on the H3K9 hypomethylation. Further investigation revealed that O/S cooperating with histone demethylase complex containing KDM3A and KDM3B promoted pluripotency genes expression to maintain the pluripotent state of piPSCs. Together, these data offer a unique insight into the epigenetic pluripotency network of piPSCs.
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http://dx.doi.org/10.1096/fj.202100230RDOI Listing
June 2021

inhibits family phosphatases and activates MAPK signaling pathway to maintain pluripotency in porcine induced pluripotent stem cells.

Zool Res 2021 May;42(3):377-388

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A & F University, Yangling, Shaanxi 712100, China.

LIN28A, an RNA-binding protein, plays an important role in porcine induced pluripotent stem cells (piPSCs). However, the molecular mechanism underlying the function of in the maintenance of pluripotency in piPSCs remains unclear. Here, we explored the function of in piPSCs based on its overexpression and knockdown. We performed total RNA sequencing (RNA-seq) of piPSCs and detected the expression levels of relevant genes by quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis, and immunofluorescence staining. Results indicated that piPSC proliferation ability decreased following knockdown. Furthermore, when expression in the LIN28A2 group was lower (by 20%) than that in the negative control knockdown group ( NC), the pluripotency of piPSCs disappeared and they differentiated into neuroectoderm cells. Results also showed that overexpression inhibited the expression of (dual-specificity phosphatases) family phosphatases and activated the mitogen-activated protein kinase (MAPK) signaling pathway. Thus, appears to activate the MAPK signaling pathway to maintain the pluripotency and proliferation ability of piPSCs. Our study provides a new resource for exploring the functions of in piPSCs.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175949PMC
May 2021

Mir-34c affects the proliferation and pluripotency of porcine induced pluripotent stem cell (piPSC)-like cells by targeting c-Myc.

Cells Dev 2021 06 23;166:203665. Epub 2021 Feb 23.

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:

MicroRNAs are important regulators in stem cells, which involve in gene regulation, including cell proliferation, differentiation and apoptosis. As an important one, miR-34c participates in various processes by targeting protein-coding genes. It is generally considered as a tumor suppressor and cell adhesion inhibitor. However, whether miR-34c has effects on pluripotent stem cells is not clear. Here, by mir-34c mimics transfection, the function of miR-34c on porcine induced pluripotent stem cell (piPSC)-like cells was investigated. Bioinformatics analyses showed that c-Myc is miR-34c's candidate target, which was confirmed by dual Luciferase assay. The knockout of miR-34c indicated that mir-34c affects the proliferation and pluripotency of piPSC-like cells by targeting c-Myc. Our study explored the regulatory mechanism of miR-34c on piPSC-like cells, providing a reference for the establishment of true porcine PSCs.
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http://dx.doi.org/10.1016/j.cdev.2021.203665DOI Listing
June 2021

Photosensitizer-free synthesis of β-keto sulfones visible-light-induced oxysulfonylation of alkenes with sulfonic acids.

Org Biomol Chem 2021 May;19(20):4537-4541

College of Chemistry and Bioengineering, Hunan University of Science and Engineering, Yongzhou 425100, China.

A practical and environment-friendly methodology for the construction of β-keto sulfones through visible-light induced direct oxysulfonylation of alkenes with sulfonic acids at ambient temperature under open-air conditions was developed. Most importantly, the reaction proceeded smoothly without the addition of any photocatalyst or strong oxidant, ultimately minimizing the production of chemical waste.
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http://dx.doi.org/10.1039/d1ob00552aDOI Listing
May 2021

Effects of BMP-2 compound with fibrin on osteoporotic vertebral fracture healing in rats.

J Musculoskelet Neuronal Interact 2021 03;21(1):149-156

Department of Orthopedic Surgery, Xuzhou Third Hospital, Affiliated Xuzhou Hospital of Jiangsu University, Xuzhou, China.

Objectives: To investigate the effects of bone morphogenetic protein-2 (BMP-2) compound with fibrin on osteoporotic vertebral fracture healing in rats.

Methods: For the present study 160 Specific-Pathogen Free 32-week-old female Sprague-Dawley rats were used. 120 rats were randomly divided in three groups (experimental, model and sham operation group- n=40 per group) and were ovariectomized to establish the osteoporosis model. 40 rats served as a control group without treatment. The expression of BMP-2 in the fracture zone at the 4th, 6th, 8th, and 12th weeks was detected by qRT-PCR. The expression of BALP and CTX-I in serum at the 12th week was detected by Elisa.

Results: At week 8, the morphology of the sham operation group was the same and the fracture healing occurred more slowly than in the other groups. At week 12, the expression of BMP-2 in the model group was significantly higher than that in the other three groups (p<0.05). At week 12, the maximum load, maximum strain, and elastic modulus of model group were significantly lower than those of the other three groups.

Conclusions: BMP-2 compound with fibrin can enhance the timing and quality of bone fracture healing in rats.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020021PMC
March 2021

The investigation of surface composition of nitrogen-doped niobium for superconducting RF cavities.

Nanotechnology 2021 Mar 3. Epub 2021 Mar 3.

Sichuan University, Chengdu, Sichuan, CHINA.

Systematic analysis of the surface morphology, crystalline phase, chemical composition and elemental distribution along depth for nitrogen-doped niobium was carried out through different ways of characterization, including SEM, AFM, GIXRD, RBS and layer-by-layer XPS analysis. The results showed that, after nitrogen doping, the surface was covered by densely distributed trigonal precipitates with average crystallite size of 32 ± 8 nm, in line with the calculation result (29.9 nm) of nitrogen-enriched β-Nb2N from GIXRD, demonstrating the phase composion of trigonal precipitates. The depth analysis through RBS and XPS indicated that β-Nb2N was dominant in the topmost 9.7 nm and extended to depth of 575 nm with gradually decreased content. In addition, the successive change of naturally oxidized states of niobium after nitrogen doping along depth was revealed along depth. It was interesting to find that oxygen diffusion depth could be moderately enhanced by nitridation process. These results established the near-surface phase composition of nitrided niobium, which was of great significance for evaluating the effect of nitrogen doping and further understanding the Q improvement of the SRF cavities.
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http://dx.doi.org/10.1088/1361-6528/abeb99DOI Listing
March 2021

Promotes the Proliferation of Spermatogonial Stem Cells by Activating ERK Signaling.

Stem Cells Int 2021 29;2021:6668658. Epub 2021 Jan 29.

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.

The future fertility of males with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Spermatogonial stem cell transplantation is believed to be a way to restore fertility in men. However, the survival efficiency of transplanted cells is still low. Eukaryotic translation initiation factor 2 subunit 3 and structural gene Y-linked () located on the Y chromosome of male animals is a coding gene of eIF2 which mainly functions in translation initiation. Recently, the emerging role of in spermatogenesis has been emphasized in several studies. However, the underlying mechanism is still unclear. In addition, how functions in large animals remains largely unknown. In this study, we obtained the CDS sequence of the gene from the testis of dairy goats and found that this gene was highly expressed in the testis and was evolutionarily conserved among different species. Interestingly, overexpression of promoted the proliferation of spermatogonial stem cells of dairy goats by activating the ERK signaling pathway. In animal experiments, overexpressing promoted transplanted goat spermatogonial stem cells and produced more colonies after microinjection into the seminiferous tubules of infertile mice. In conclusion, our study highlights an undiscovered role of in dairy goat reproduction. This finding may provide an important basis for future works regarding male spermatogenic cell restoration and represent a major advance toward surrogate sires becoming a tool for disseminating and regenerating germplasm in all mammals.
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http://dx.doi.org/10.1155/2021/6668658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869416PMC
January 2021

Immortalized canine adipose-derived mesenchymal stem cells alleviate gentamicin-induced acute kidney injury by inhibiting endoplasmic reticulum stress in mice and dogs.

Res Vet Sci 2021 May 5;136:39-50. Epub 2021 Feb 5.

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China. Electronic address:

Adipose-derived mesenchymal stem cells have been used to treat acute kidney injury (AKI). The role of endoplasmic reticulum (ER) stress in AKI treatment with canine adipose-derived mesenchymal stem cells (cADSCs) remains unknown. This study intended to investigate the therapeutic effects of cADSCs cultured in different media on AKI in mice and dogs and reveal the role of ER stress in this process. The mice were divided into two branches: a control group and a gentamicin induced group (this group treated with low-serum ADSC or high-serum ADSC or 4-phenylbutyric acid (4-PBA)). The dogs were divided into control, model, and cell-injected groups. To suppress ER stress, mice were simultaneously treated with 4-PBA. The results showed there were improvements in renal function and tissue damage and a corresponding decrease in ER stress in the kidneys of the mice that received cell injection. However, the cells cultured with 2% FBS showed a better growth state and resulted in lower ER stress levels in treated kidneys. In the 4-PBA-treated group, ER stress was suppressed, and there was corresponding kidney injury recovery. Similarly, both kidney damage and ER stress were alleviated after AKI dogs were injected with the cells. Our findings reveal that both allogeneic and xenogeneic cADSCs were effective treatments for AKI by inhibiting ER stress. These results also provide evidence for a new clinical therapy for acute renal disease in pets.
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http://dx.doi.org/10.1016/j.rvsc.2021.02.001DOI Listing
May 2021

Dmrt1 regulates the immune response by repressing the TLR4 signaling pathway in goat male germline stem cells.

Zool Res 2021 01;42(1):14-27

College of Veterinary Medicine, Northwest A & F University, Shaanxi Centre of Stem Cells Engineering & Technology, Yangling, Shaanxi 712100, China.

Double sex and mab-3-related transcription factor 1 (Dmrt1), which is expressed in goat male germline stem cells (mGSCs) and Sertoli cells, is one of the most conserved transcription factors involved in sex determination. In this study, we highlighted the role of Dmrt1 in balancing the innate immune response in goat mGSCs. Dmrt1 recruited promyelocytic leukemia zinc finger (Plzf), also known as zinc finger and BTB domain-containing protein 16 (Zbtb16), to repress the Toll-like receptor 4 (TLR4)-dependent inflammatory signaling pathway and nuclear factor (NF)-κB. Knockdown of Dmrt1 in seminiferous tubules resulted in widespread degeneration of germ and somatic cells, while the expression of proinflammatory factors were significantly enhanced. We also demonstrated that Dmrt1 stimulated proliferation of mGSCs, but repressed apoptosis caused by the immune response. Thus, Dmrt1 is sufficient to reduce inflammation in the testes, thereby establishing the stability of spermatogenesis and the testicular microenvironment.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840460PMC
January 2021

Targeting neuroinflammation: The therapeutic potential of ω-3 PUFAs in substance abuse.

Nutrition 2021 03 10;83:111058. Epub 2020 Nov 10.

Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, Hunan, China. Electronic address:

Substance abuse is a chronic relapsing disorder that results in serious health and socioeconomic issues worldwide. Addictive drugs induce long-lasting morphologic and functional changes in brain circuits and account for the formation of compulsive drug-seeking and drug-taking behaviors. Yet, there remains a lack of reliable therapy. In recent years, accumulating evidence indicated that neuroinflammation was implicated in the development of drug addiction. Findings from both our and other laboratories suggest that ω-3 polyunsaturated fatty acids (PUFAs) are effective in treating neuroinflammation-related mental diseases, and indicate that they could exert positive effects in treating drug addiction. Thus, in the present review, we summarized and evaluated recently published articles reporting the neuroinflammation mechanism in drug addiction and the immune regulatory ability of ω-3 PUFAs. We also sought to identify some of the challenges ahead in the translation of ω-3 PUFAs into addiction treatment.
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http://dx.doi.org/10.1016/j.nut.2020.111058DOI Listing
March 2021

Human torpor: translating insights from nature into manned deep space expedition.

Biol Rev Camb Philos Soc 2021 04 14;96(2):642-672. Epub 2020 Dec 14.

Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China.

During a long-duration manned spaceflight mission, such as flying to Mars and beyond, all crew members will spend a long period in an independent spacecraft with closed-loop bioregenerative life-support systems. Saving resources and reducing medical risks, particularly in mental heath, are key technology gaps hampering human expedition into deep space. In the 1960s, several scientists proposed that an induced state of suppressed metabolism in humans, which mimics 'hibernation', could be an ideal solution to cope with many issues during spaceflight. In recent years, with the introduction of specific methods, it is becoming more feasible to induce an artificial hibernation-like state (synthetic torpor) in non-hibernating species. Natural torpor is a fascinating, yet enigmatic, physiological process in which metabolic rate (MR), body core temperature (T ) and behavioural activity are reduced to save energy during harsh seasonal conditions. It employs a complex central neural network to orchestrate a homeostatic state of hypometabolism, hypothermia and hypoactivity in response to environmental challenges. The anatomical and functional connections within the central nervous system (CNS) lie at the heart of controlling synthetic torpor. Although progress has been made, the precise mechanisms underlying the active regulation of the torpor-arousal transition, and their profound influence on neural function and behaviour, which are critical concerns for safe and reversible human torpor, remain poorly understood. In this review, we place particular emphasis on elaborating the central nervous mechanism orchestrating the torpor-arousal transition in both non-flying hibernating mammals and non-hibernating species, and aim to provide translational insights into long-duration manned spaceflight. In addition, identifying difficulties and challenges ahead will underscore important concerns in engineering synthetic torpor in humans. We believe that synthetic torpor may not be the only option for manned long-duration spaceflight, but it is the most achievable solution in the foreseeable future. Translating the available knowledge from natural torpor research will not only benefit manned spaceflight, but also many clinical settings attempting to manipulate energy metabolism and neurobehavioural functions.
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http://dx.doi.org/10.1111/brv.12671DOI Listing
April 2021

Comparison of the clinical effect of DHS and PFNA on senile osteoporotic fracture and their significance of changes in BALP expression level.

J Musculoskelet Neuronal Interact 2020 12;20(4):556-562

Department of Orthopedic Surgery, Affiliated Xuzhou Hospital of Jiangsu University, Xuzhou 3rd Hospital, Xuzhou, China.

Objective: To investigate the clinical effects of dynamic hip screw (DHS) and proximal femoral nail anti-rotation (PFNA) on senile osteoporosis patients and their effects on the expression level of bone-specific alkaline phosphatase (BALP).

Methods: 116 elderly patients with osteoporotic fracture were divided into DHS group (n=67) and PFNA group (n=49). BALP values were measured by ELISA before operation and 30 days after operation.

Results: The operation time, the bleeding volume, and the weight-bearing time of PFNA group was shorter than DHS group (p<0.05); the dominant blood loss and occult blood loss in PFNA group were less than those in DHS group (p<0.05); the healing time and detumescence time, the complications of PFNA group was fewer than the DHS group (p<0.05). The ten-meter walking speed and the five sitting tests in PFNA group were shorter than that in DHS group (p<0.05); the excellent and good rate and Harris score in PFNA group were higher than those in DHS group (p<0.05). The expression of BALP in PFNA group was lower than that in DHS group (p<0.05).

Conclusion: PFNA surgery has less trauma, fewer complications, more optimistic postoperative healing and recovery degree, and is more conducive to the reduction of BALP expression level.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716689PMC
December 2020

BCL2 enhances survival of porcine pluripotent stem cells through promoting FGFR2.

Cell Prolif 2021 Jan 26;54(1):e12932. Epub 2020 Oct 26.

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, China.

Objectives: The establishment of porcine pluripotent stem cells (pPSCs) is still a critical topic. However, all pPSCs were failed to contribute to efficient chimeric pig and were extremely sensitive to changes of culture conditions. This study aimed to investigate the role of BCL2 in pPSCs and further explain the mechanism.

Materials And Methods: Porcine BCL2 gene was cloned and overexpressed in porcine induce pluripotent stem cells (piPSCs). Digital RNA-seq was performed to explain the mechanism of anti-apoptosis. Finally, the cells carrying BCL2 were injected into mouse early embryo to evaluate its chimeric ability.

Results: Here, we found that overexpression of porcine BCL2 gene significantly improved the survivability of piPSCs and the efficiency of embryonic chimerism, and did not wreck the pluripotency of piPSCs. Furthermore, the Digital RNA-seq analysis revealed that BCL2, as a downstream gene of the PI3K signal pathway, enhanced the expression of PI3K signal pathway receptors, such as FGFR2, and further promoted oxidoreductases activity and lipid metabolism, thus maintaining the survival and pluripotency of piPSCs.

Conclusion: Our data not only suggested that porcine BCL2 gene could enhance the survivability and chimeric ability of pPSCs, but also explained the positive feedback mechanism in this process, providing strong support for the chimeric experiment of pPSCs.
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http://dx.doi.org/10.1111/cpr.12932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791183PMC
January 2021

Folic acid promotes proliferation and differentiation of porcine pancreatic stem cells into insulin-secreting cells through canonical Wnt and ERK signaling pathway.

J Steroid Biochem Mol Biol 2021 01 19;205:105772. Epub 2020 Oct 19.

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, 712100, PR China. Electronic address:

Porcine pancreatic stem cells (pPSCs) can be induced to differentiate into insulin-producing cells in vitro and thus serve as a major cells source for β-cell regeneration. However, this application is limited by the weak cell proliferation ability and low insulin induction efficiency. In this study, we explored the role of folic acid in the proliferation of pPSCs and the formation of insulin-secreting cells. We found that FA-treated pPSCs cells had a high EDU positive rate, and the proliferation marker molecules PCNA, CyclinD1 and c-Myc were up-regulated, while the expression of folate receptor α (FOLRα) was up-regulated. In further research, interference FOLRα or adding canonical Wnt signaling pathway or ERK signaling pathway inhibitors could significantly inhibit the effect of FA on pPSCs proliferation. Meanwhile, during the differentiation of pPSCs into insulin-secreting cells, we found that the maturation marker genes Insulin, NKX6.1, MafA, and NeuroD1 was upregulated in insulin-secreting cell masses differentiationed from pPSCs after FA treatment, and the functional molecules Insulin and C-peptide were increased, the ability to secrete insulin in response to high glucose was also increased. With the addition of Wnt and ERK signaling pathway inhibitors, the pro-differentiation effect of FA was weakened. In conclusion, FA promotes the proliferation of pPSCs by binding to folate receptor α (FOLRα) and increase the efficiency of directed differentiation of pPSCs into insulin-producing cells by regulating canonical Wnt and ERK signaling pathway. This study lays theoretical foundation for solving the bottleneck in the treatment of diabetes with stem cell transplantation in future.
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http://dx.doi.org/10.1016/j.jsbmb.2020.105772DOI Listing
January 2021

Melatonin alleviates LPS-induced endoplasmic reticulum stress and inflammation in spermatogonial stem cells.

J Cell Physiol 2021 05 29;236(5):3536-3551. Epub 2020 Sep 29.

Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.

Orchitis is one of the leading causes of male animal infertility and is associated with inflammatory reactions caused by the bacterium. It has been reported that there is a mutual coupling effect between endoplasmic reticulum stress (ERS) and inflammatory response. Our studies showed that lipopolysaccharide (LPS) could cause testicular damages, apoptosis, ERS, and inflammatory responses in spermatogonial stem cells (SSCs); ERS-related apoptosis proteins were activated and the expression of ERS genes was significantly upregulated; meanwhile, the expression of Toll-like receptor 4 and inflammation factors was apparently increased with LPS treatment. Moreover, melatonin (MEL) could rescue testicular damage, and significantly inhibited the expression of ERS-related apoptosis genes, ERS markers, and inflammatory factors in SSCs and MEL played repairing and anti-infection roles in LPS-induced testicular damage. Therefore, MEL may be used as a drug to prevent and control bacterial infections in male reproductive systems. However, the specific molecular mechanism of MEL to resist ERS and inflammatory response remains to be further studied.
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http://dx.doi.org/10.1002/jcp.30088DOI Listing
May 2021

Particulate Alum via Pickering Emulsion for an Enhanced COVID-19 Vaccine Adjuvant.

Adv Mater 2020 Oct 30;32(40):e2004210. Epub 2020 Aug 30.

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

For rapid response against the prevailing COVID-19 (coronavirus disease 19), it is a global imperative to exploit the immunogenicity of existing formulations for safe and efficient vaccines. As the most accessible adjuvant, aluminum hydroxide (alum) is still the sole employed adjuvant in most countries. However, alum tends to attach on the membrane rather than entering the dendritic cells (DCs), leading to the absence of intracellular transfer and process of the antigens, and thus limits T-cell-mediated immunity. To address this, alum is packed on the squalene/water interphase is packed, forming an alum-stabilized Pickering emulsion (PAPE). "Inheriting" from alum and squalene, PAPE demonstrates a good biosafety profile. Intriguingly, with the dense array of alum on the oil/water interphase, PAPE not only adsorbs large quantities of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antigens, but also harbors a higher affinity for DC uptake, which provokes the uptake and cross-presentation of the delivered antigens. Compared with alum-treated groups, more than six times higher antigen-specific antibody titer and three-fold more IFN-γ-secreting T cells are induced, indicating the potent humoral and cellular immune activations. Collectively, the data suggest that PAPE may provide potential insights toward a safe and efficient adjuvant platform for the enhanced COVID-19 vaccinations.
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http://dx.doi.org/10.1002/adma.202004210DOI Listing
October 2020

[Study on efficacy markers of heat-clearing and detoxifying effect of Lonicerae Japonicae Flos based on systematic traditional Chinese medicine].

Zhongguo Zhong Yao Za Zhi 2020 Jul;45(14):3275-3281

State Administration of Traditional Chinese Medicine, Research Center of Traditional Chinese Medicine-Information Engineering,Key Technology of Traditional Chinese Medicine Pharmacy and New Drug Development Engineering Research Center of Ministry of Education, School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 102488, China.

Lonicerae Japonicae Flos has a long history of heat-clearing and detoxifying effect. The description of its efficacy in Chinese Pharmacopoeia of past dynasties is relatively stable, and it is an excellent carrier for the study of efficacy markers. Guided by the theory of systematic traditional Chinese medicine, heat-clearing and detoxifying effect efficacy system of Lonicerae Japonicae Flos was taken as an example in this study to clarify the elements(active ingredients) of Lonicerae Japonicae Flos in heat-clearing and detoxifying efficacy system, determine the boundary(signal pathway), establish the structure(system dynamics model), identify the system functions corresponding to pharmacology, efficacy and effects(heat-clearing and detoxifying effect), and explore the application of system dynamics model in the discovery of efficacy markers of traditional Chinese medicine. In this paper, the dynamic models of interleukin 1(IL-1) and interleukin 6(IL-6) in vivo were established to predict the expression of related factors in IL-1 and IL-6 signaling pathways of different components and their combinations in Lonicerae Japonicae Flos by dynamic network, so as to find the effective markers of heat-clearing and detoxification of Lonicerae Japonicae Flos. The results showed that the lower the concentration of chlorogenic acid, the higher the inhibition rate of Jun N-terminal kinase(JNK) at downstream of IL-1 by the combination of chlorogenic acid and linalool; the higher the concentration of luteolin in IL-6 pathway, the higher the inhibition rate of C-reactive protein(CRP) at downstream of IL-6 by the combination of chlorogenic acid and luteolin. It revealed that the potential efficacy markers of Lonicerae Japonicae Flos in heat-clearing and detoxifying effect based on IL-1 signaling pathway were chlorogenic acid and linalool, and the potential efficacy markers of Lonicerae Japonicae Flos in heat-clearing and detoxifying effect based on IL-6 signaling pathway were chlorogenic acid and luteolin. This study provided methodological guidance for the discovery of efficacy markers of traditional Chinese medicine.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200210.403DOI Listing
July 2020

[Exploration of potential efficacy markers of Astragali Radix for invigorating Qi based on systematic traditional Chinese medicine].

Zhongguo Zhong Yao Za Zhi 2020 Jul;45(14):3266-3274

State Administration of Traditional Chinese Medicine, Research Center of Traditional Chinese Medicine-Information Engineering,Key Technology of Traditional Chinese Medicine Pharmacy and New Drug Development Engineering Research Center of Ministry of Education, School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 102488, China.

Astragali Radix is the elixir for invigorating Qi, with the effects of invigorating Qi, promoting Yang and nourishing the body. With the deepening researches on the chemical constituents of Astragali Radix, it is used more extensively in clinical application. Based on systematic traditional Chinese medicine theory, in this paper, we characterized the effect of Astragali Radix on invigo-rating Qi from the molecular level, and explored the markers of Astragali Radix on invigorating Qi. Through TCMSP and ChEMBL databases, the active components-targets database of Astragali Radix was constructed to clarify the targets(elements) involved in Astragali Radix's Qi invigorating efficacy system. According to the relationship between the targets, the protein interaction network was constructed, and the network modules(structure) were divided according to the theoretic clustering algorithm molecular complex detection(MCODE), and the boundary of the Qi invigorating efficacy system was defined by the pharmacological function of Astragali Radix. The active components of Astragali Radix for invigorating Qi were characterized from the aspects of composition, target and efficacy. The results showed that eight key components of Astragali Radix, such as hederagenin, quercetin, calycosin, formononetin, jaranol, isorhamnetin, astragalosideⅢ, and 9,10-dimethoxypterocarpan-3-O-β-D-glucoside, could act on eight functional modules composed of 17 key targets, and participate in G-protein coupled receptor protein signaling pathway, regulation of lipid metabolic process, positive regulation of nitrogen compound metabolic process, positive regulation of programmed cell death, fatty acid metabolic process and other biological processes to produce pharmacological effects such as regulating immune function, strengthening heart, protecting myocardial cells, improving material metabolism, and antioxidation effects, thus playing the role of invigorating Qi. Based on the systematic Chinese medicine theory, this study explored the effective markers of Astragali Radix at the level of molecular network, which provided new ideas for the interpretation of the effective substance basis of systematic traditional Chinese medicine and the quality control of traditional Chinese medicine. In the future, it can focus on the compatibility research of these components, and then carry out more in-depth studies on the efficacy of Astragali Radix in invigorating Qi, and strengthen the development of the corresponding pharmacological mechanism and related preparations.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200210.405DOI Listing
July 2020

[Discovery and application of traditional Chinese medicine efficacy markers based on systematic traditional Chinese medicine].

Zhongguo Zhong Yao Za Zhi 2020 Jul;45(14):3245-3250

State Administration of Traditional Chinese Medicine, Research Center of Traditional Chinese Medicine-Information Engineering,Key Technology of Traditional Chinese Medicine Pharmacy and New Drug Development Engineering Research Center of Ministry of Education, School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 102488, China.

The quality marker(Q-marker) of traditional Chinese medicine(TCM) is a new concept of TCM quality control proposed in recent years. It is a hot issue in the research of modern Chinese medicine. The TCM efficacy is a high-level summary of the TCM therapeutic effect under the guidance of TCM theory. On this basis, it is of considerable significance to explore the TCM efficacy marker for the TCM modernization. However, the traditional research strategy based on the single herb and decoction piece in macro TCM level, or the drug research strategy based on the biological effect of the targets, is quite different from the characteristics of multiple components of TCM, as well as the weak and low-selective effect of Chinese medicine ingredients on targets. Therefore, how to select representative ingredients to characterize the TCM overall efficacy is a problematic point in establishing TCM efficacy markers. In this paper, the concept and method of Q-marker were introduced into the study of Chinese medicine efficacy. The research method for systematic TCM was used to systematically discuss the connotation of TCM efficacy markers, the principles of discovery and determination, common research ideas and techniques by taking the representative research results as an example. This study provides new ideas for the research and discovery of TCM efficacy markers.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200210.402DOI Listing
July 2020

Eif2s3y regulates the proliferation of spermatogonial stem cells via Wnt6/-catenin signaling pathway.

Biochim Biophys Acta Mol Cell Res 2020 10 1;1867(10):118790. Epub 2020 Jul 1.

College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering & Technology, Northwest A & F University, Yangling, Shaanxi, China. Electronic address:

Eukaryotic translation initiation factor 2 subunit 3 and structural gene Y-linked (Eif2s3y) gene, the gene encoding eIF2γ protein, is globally expressed in all tissues and plays important roles in regulating global and gene-specific mRNA translation initiation. It has been noticed that Eif2s3y plays crucial roles in spermatogenesis, however, the mechanism remains unclear. In the current study, transgenic Eif2s3y mice were generated to test our hypothesis that the Eif2s3y promotes the proliferation of spermatogonial stem cells (SSCs). Transgenic Eif2s3y mouse had enhanced SSCs proliferation rate when compared to WT mouse. Interesting, the testes from transgenic Eif2s3y mouse had increased Active-β-catenin protein expression and higher expression pattern of Wnt ligand Wnt6 when compared to testes from WT mouse. This study revealed novel roles of Eif2s3y in the activation Wnt6/β-catenin signal pathway in SSCs. Taken together, we identified Eif2s3y-Wnt6-β-catenin as a critical pathway in the regulation of spermatogenesis, which provides a platform for investigating the molecular mechanisms of male reproduction.
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http://dx.doi.org/10.1016/j.bbamcr.2020.118790DOI Listing
October 2020

Carbon emissions in the transportation sector of Yangtze River Economic Belt: decoupling drivers and inequality.

Environ Sci Pollut Res Int 2020 Jun 7;27(17):21098-21108. Epub 2020 Apr 7.

Center of Hubei Cooperative Innovation for Emissions Trading System, School of Low Carbon Economics, Research Center of Hubei Financial Development and Financial Security, Hubei University of Economics, Wuhan, 430205, People's Republic of China.

Carbon emissions in the transportation sector are of great concern, since they are the third leading contributor to China's carbon emissions. This research examines the decoupling relationship between economic outputs and carbon emissions of 11 provinces in 2000-2016 by focusing on Yangtze River Economic Belt (YREB), which is the densest traffic and economic corridor in China. Although many studies have focused on the decoupling state and its driving forces between economic outputs and carbon emissions, few studies further addressed the microscale analysis for decoupling drivers. This paper reveals the characteristic, inequality contribution ratio, and dynamic evolution of the drivers by integrating Dagum's Gini ratio with kernel density estimation in YREB. Results are as follows: (1) The decoupling states presented weak decoupling state at the whole belt in the majority of the latter observed sub-periods. The decoupling states at the provincial level turned more satisfactory during the four observed sub-periods, especially for Shanghai and Zhejiang. (2) The energy intensity (EI) effect is the predominant driver for promoting the decoupling state in the vast majority of provinces, whereas value added per capita effect is the major role for inhibiting the decoupling state. (3) During the four observed sub-periods, the Gini inequality and transvariation intensity of the EI effect between sub-regions are the main sources of the provincial differences in YREB. The driving force of EI effect is increasing, but the provincial differences are expanding in the upstream and downstream regions by analyzing its dynamic evolution. Understanding the temporal and spatial microscale inequality of the decoupling drivers provides governments with differentiated and forward-looking suggestions towards coordinating regional economic growth and carbon emissions reduction.
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http://dx.doi.org/10.1007/s11356-020-08479-9DOI Listing
June 2020

Rosmarinic Acid as a Candidate in a Phenotypic Profiling Cardio-/Cytotoxicity Cell Model Induced by Doxorubicin.

Molecules 2020 Feb 14;25(4). Epub 2020 Feb 14.

School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China.

Advances in cancer treatment have led to significant improvements in long-term survival in many types of cancer, but heart dysfunction and heart failure, associated with cancer treatment, have also increased. Anthracyclines are the main cause of this type of cardiotoxicity. In this study, we describe a combined experimental and cell morphology analysis approach for the high-throughput measurement and analysis of a cardiomyocyte cell profile, using partial least square linear discriminant analysis (PLS-LDA) as the pattern recognition algorithm. When screening a small-scale natural compound library, rosmarinic acid (RosA), as a candidate drug, showed the same cardioprotective effect as the positive control. We investigated the protective mechanism of RosA on a human cardiomyocyte cell line (AC16) and human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). We showed that RosA pretreatment suppressed doxorubicin (Dox)-induced cell apoptosis and decreased the activity of caspase-9. RosA promotes the expression of Heme oxygenase-1 (HO-1) and reduces the production of reactive oxygen species (Ros), which is induced by Dox. Meanwhile, it can also promote the expression of cardiac-development-related protein, including histone deacetylase 1 (HDAC1), GATA binding protein 4 (GATA4) and troponin I3, cardiac type (CTnI). Collectively, our data support the notion that RosA is a protective agent in hiPSC-CMs and has the potential for therapeutic use in the treatment of cancer therapy-related cardiac dysfunction and heart failure.
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http://dx.doi.org/10.3390/molecules25040836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070289PMC
February 2020

Effects of hip replacement combined with alendronate sodium on postoperative healing of osteoporotic femoral neck fracture and levels of CTX-1 and BALP in patients.

Exp Ther Med 2019 Dec 1;18(6):4583-4590. Epub 2019 Nov 1.

Department of Orthopedic Surgery, Affiliated Xuzhou Hospital of Jiangsu University, Xuzhou Third Hospital, Xuzhou, Jiangsu 221005, P.R. China.

This study aimed to explore the improvement of hip replacement combined with alendronate sodium on the condition of patients with osteoporotic femoral neck fracture and factors affecting the efficacy of patients. In total, 140 patients with femoral neck fracture from July 2015 to October 2017 in the Affiliated Xuzhou Hospital of Jiangsu University were collected. Of these, 61 patients were treated with hip replacement as the control group and 79 patients were treated with alendronate sodium as the observation group on the basis of the control group. ELISA was used to detect levels of carboxy-terminal opeptide of type I collagen (CTX-I) and bone alkaline phosphatase (BALP) in serum of patients before and after treatment. Harris score was used to compare the clinical efficacy of patients after treatment. Changes in the expression of CTX-I and BALP before and after treatment were compared between the two groups, and the correlation between CTX-I and BALP levels and Harris score was analyzed. According to the clinical efficacy of patients, the two groups were divided into the significant effect group and poor effect group. Risk factors affecting the efficacy of patients were analyzed, and the ROC of subjects with risk factors was drawn. After treatment, the expression of BALP in serum increased significantly compared with that before treatment, and the expression of CTX-I decreased significantly. After treatment, the expression of BALP in serum in the observation group was significantly higher than that in the control group (P<0.05). Multivariate analysis revealed that age, time of operation, CTX-I after treatment and BALP after treatment were independent risk factors affecting the efficacy of patients. In conclusion, hip replacement combined with alendronate sodium can effectively improve the clinical efficacy of patients, and age, time of operation, CTX-I after treatment and BALP after treatment are found to be independent risk factors affecting the postoperative efficacy of patients.
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http://dx.doi.org/10.3892/etm.2019.8158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880394PMC
December 2019

SerpinB1 promotes the proliferation of porcine pancreatic stem cells through the STAT3 signaling pathway.

J Steroid Biochem Mol Biol 2020 04 27;198:105537. Epub 2019 Nov 27.

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, 712100, PR China. Electronic address:

Porcine pancreatic stem cells (pPSCs) can be induced to insulin-secreting cells and therefore considered the most promising seeding cells for curing human diabetes in future. However, insufficient pPSCs number is one of the bottleneck problems before its clinical application. SerpinB1 is a serine protease inhibitor in neutrophils and can directly promote the proliferation of β cells. Whether SerpinB1 is involved in pPSC proliferation and differentiation remains unknown. The effects of SerpinB1 on pPSCs proliferation were measured by Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, qRT-PCR, western blot, and flow cytometry assays. We found that pPSCs did not efficiently reach the S phase when SerpinB1 expression was knocked down with short hairpin RNA (sh-SerpinB1), the expression of Cyclin D1, CDK-2, and PCNA also decreased. Meanwhile, cell viability and proliferation ability were both declined. Further analyses showed that the expression level of phosphorylated STAT3/STAT3was downregulated, along with an upregulation of p53 and p21. We used a two-step induction method to induce pPSCs to insulin-secreting cells and found that SerpinB1 expression in insulin-secreting cells was higher than in pPSCs. Meanwhile, the protein expression level of phosphorylated STAT3/STAT3 was increased while p53 and p21 was decreased in induced insulin-secreting cells in comparison with control cells. The insulin-secreting cells derived from the sh-SerpinB1 cells secreted less insulin and showed poor sensitivity to high glucose than control group. However, the insulin-secreting cells derived from the ov-SerpinB1 cells has a quite contrary tendency. In conclusion, this study demonstrates that SerpinB1 promotes the proliferation of pPSCs through the STAT3 signaling pathway, and SerpinB1 is a key factor for maintaining the viability of pPSCs during the transition to insulin-secreting cells.
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http://dx.doi.org/10.1016/j.jsbmb.2019.105537DOI Listing
April 2020

Therapeutic applications of adipose-derived mesenchymal stem cells on acute liver injury in canines.

Res Vet Sci 2019 Oct 12;126:233-239. Epub 2019 Sep 12.

College of Veterinary Medicine, Shaanxi Stem Cell Engineering and Technology Research Center, Northwest A&F University, Yangling 712100, China. Electronic address:

In this study, canine adipose-derived mesenchymal stem cells (cADSCs) therapeutic potential was investigated in artificially induced acute liver injury model by CCl in canines. The primary cADSCs cells were cultured and then intravenously administered into the canine animal model. Six cross-breed dogs were divided into three groups including blank control group, CCl model group, CCl induced cADSCs transplantation group. The results showed that after intraperitoneal injection of CCl solution, the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Albumin (ALB) in peripheral blood of experimental canines confirmed the correct induction of acute liver injury. Moreover, the liver structure showed clear macroscopic damage. The cADSCs were homed in the liver of the administered animals. The AST, ALT and ALB in the peripheral blood rapidly decreased. H&E and PAS histological evaluation showed that both the structure of canine liver tissue and the ability to synthesize hepatic glycogen could be restored to the control level after cADSCs transplantation. Therefore, cADSCs can play a therapeutic role in the recovery of liver injury. Overall, this study demonstrates that the primary cADSCs transplantation into the acute liver injury model induced by intravenous injection can play a certain therapeutic role in the recovery of liver in canines. These results may provide a new treatment idea for acute liver disease in pets clinically.
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http://dx.doi.org/10.1016/j.rvsc.2019.09.004DOI Listing
October 2019

Mapping the research of energy subsidies: a bibliometric analysis.

Environ Sci Pollut Res Int 2019 Oct 3;26(28):28817-28828. Epub 2019 Aug 3.

School of Low Carbon Economics, Hubei Financial Development and Financial Security Research Center, Hubei University of Economics, Wuhan, 430205, People's Republic of China.

A review of energy subsidy research from a bibliometric perspective was conducted. Based on the bibliometric method, a statistical analysis of energy subsidy-related publications from 1997 to 2016 was undertaken using the Science Citation Index (SCI) and Social Science Citation Index (SSCI) databases. A total of 1182 publications were retrieved, with a significant increase in the number of publications observed after 2006. The majority of these publications were within the disciplines of Energy & Fuels and Environmental Science & Ecology. Although the USA and China contributed the most papers, authors from 96 countries were involved in the various studies. The USA was the center of global collaborations, while other countries/territories mainly conducted bilateral or regional collaborations in their research activities. Five of the top 11 most productive institutes were from China, followed by the USA. The frequency of collaborations among institutes was relatively low. However, the institute-keyword 2-mode network showed that institutes had great potential to cooperate on a number of common topics. Five major themes were identified from the co-keywords analysis: general renewable energy research, bio-energies, sustainability, subsidies, and welfare. The findings, as a complement to previous conventional reviews, will be useful in future energy subsidy research.
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http://dx.doi.org/10.1007/s11356-019-06025-wDOI Listing
October 2019
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