Publications by authors named "Jie Ding"

985 Publications

Preparation of WPU-based super-amphiphobic coatings functionalized by modified SiO particles and their anti-biofilm mechanism.

Biomater Sci 2021 Oct 13. Epub 2021 Oct 13.

Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China.

Fabrication of anti-wetting coatings with anti-biofouling and anti-biofilm properties has become a hot spot of attention in recent years. However, the anti-biofilm mechanism of anti-bacterial adhesion coatings with different wet resistance properties has not been explored in detail. In this work, SiO micro-nano particles were prepared by the Stöber method and were modified. The SiO/waterborne polyurethane (WPU) coatings were prepared by the drop coating method, and the coatings with different hydrophobic and oleophobic properties were constructed by modifying the process conditions using SiO micro-nano particles as the roughness construction factor. Taking the dominant spoilage bacteria of aquatic products, as the object, the anti-bacterial adhesion properties and anti-biofilm mechanism of the SiO/WPU coatings were investigated. The results show that, with the unmodified SiO particles increasing from 1.2% (w/V) to 4.0% (w/V), the hydrophobicity and thermal stability of the SiO/WPU coatings are significantly enhanced, but the oil repellency becomes worse due to the mesoporous structure. After SiO micro-nano particles are modified with 1,1,2,2-perfluorooctyl trichlorosilane (PFOTS), the surface energy of the SiO/WPU coatings is decreased, the liquid repellency is improved, and the surfaces are rough with the appearance of fluorocarbon compounds, but the thermal stabilities are slightly reduced. Among them, after the secondary modification of SiO micro-nano particles, the SiO/WPU coatings showed excellent oil repellency, lower surface energies and higher fluorocarbon content on the surface. Particularly, SiO/WPU coatings exhibited super-amphiphobicity after adjusting the amount of concentrated ammonia added during the secondary modification process. Meanwhile, we found that for the hydrophobic SiO/WPU coatings, the stronger the oleophobic property, the greater the anti-bacterial adhesion ability is, while the anti-bacterial adhesion ability of hydrophobic and selectively oleophobic or superhydrophobic and oleophobic SiO/WPU coatings is poor than that of amphiphilic SiO/WPU coatings. However, because the super-amphiphobic SiO/WPU coatings can be in the Cassie state with the bacterial solution for a long time, it can "capture" enough air to inhibit the irreversible adhesion of the bacteria. More importantly, the coatings can also inhibit the metabolic activity, secretion of extracellular polysaccharides, and activities of ATPase and AKP of the adherent bacteria, so it has a better anti-biofilm property. The anti-biofilm coatings can be used as food packaging materials or coated on the inner surface of packaging boxes to prevent the microbial infection.
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http://dx.doi.org/10.1039/d1bm01285aDOI Listing
October 2021

Hif-1α/Hsf1/Hsp70 signaling pathway regulates redox homeostasis and apoptosis in large yellow croaker ( ) under environmental hypoxia.

Zool Res 2021 Nov;42(6):746-760

Key Laboratory of Applied Marine Biotechnology by the Ministry of Education, School of Marine Sciences, Ningbo University, Ningbo, Zhejiang 315211, China.

Oxygen is an essential molecule for animal respiration, growth, and survival. Unlike in terrestrial environments, contamination and climate change have led to the frequent occurrence of hypoxia in aquatic environments, thus impacting aquatic animal survival. However, the adaptative mechanisms underlying fish responses to environmental hypoxia remain largely unknown. Here, we used large yellow croaker ( ) and large yellow croaker fry (LYCF) cells to investigate the roles of the Hif-1α/Hsf1/Hsp70 signaling pathway in the regulation of cellular redox homeostasis, and apoptosis. We confirmed that hypoxia induced the expression of Hif-1α, Hsf1, and Hsp70 and . Genetic knockdown/overexpression indicated that Hsp70 was required for maintaining redox homeostasis and resisting oxidative stress in LYCF cells under hypoxic stress. Hsp70 inhibited caspase-dependent intrinsic apoptosis by maintaining normal mitochondrial membrane potential, enhancing Bcl-2 mRNA and protein expression, inhibiting and mRNA expression, and suppressing caspase-3 and caspase-9 activation. Hsp70 suppressed caspase-independent intrinsic apoptosis by inhibiting nuclear translocation of apoptosis-inducing factor (AIF) and disturbed extrinsic apoptosis by inactivating caspase-8. Genetic knockdown/overexpression of and dual-luciferase reporter assay indicated that Hif-1α activated the DNA promoter and enhanced mRNA transcription. Hsf1 enhanced mRNA transcription in a similar manner. In summary, the Hif-1α/Hsf1/Hsp70 signaling pathway plays an important role in regulating redox homeostasis and anti-apoptosis in under hypoxic stress.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2021.224DOI Listing
November 2021

Competitive Wetting: A New Approach to Prevent Liquid Penetration through Porous Materials with Superior Synergistic Effect.

Small 2021 Oct 8:e2103695. Epub 2021 Oct 8.

Institute for Superconducting and Electronic Materials, Australian Institute for Innovative Materials, University of Wollongong, Innovation Campus. Squires Way, North Wollongong, NSW, 2500, Australia.

Blocking liquid penetration in porous materials is a key function for several applications including chemical protective clothing (CPC), wound healing, and hygiene products. Enormous efforts are made to prevent liquid penetration through porous media by the modification of materials. CPC is used as an example to demonstrate the effect of the synergistic effect on liquid penetration. A common strategy to achieve liquid protection is the use of liquid-repellent surfaces with the aid of a liquid absorption liner layer. However, this strategy demonstrates limited success for low surface energy liquids. Herein, a novel approach is reported to prevent the permeation of liquid across porous materials by a synergistic effect. Both fabrics are individually susceptible to be wetted by low surface tension liquids. However, when they are assembled, they can prevent low surface tension liquids from penetrating because of the wettability gap between the two fabrics. The fabric assembly demonstrates an increase in the liquid prevention capacity by 70-1000 times compared with a commercial CPC material. This novel synergistic effect may offer a breakthrough in the development of various applications including protective clothing baby nappies, hygiene products, food preparation, soil water retention, and sporting/camping/ski equipment and clothing.
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http://dx.doi.org/10.1002/smll.202103695DOI Listing
October 2021

Albumin Binder-Conjugated Fibroblast Activation Protein Inhibitor Radiopharmaceuticals for Cancer Therapy.

J Nucl Med 2021 Sep 30. Epub 2021 Sep 30.

Peking University, China.

Fibroblast activation protein (FAP) has become an attractive target for diagnosis and therapy, and a series of FAP inhibitor (FAPI) based radiotracers have been developed and performed excellent diagnosis outcome in clinical applications. Yet, their fast clearance and insufficient tumor retention have hampered their further clinical applications for cancer treatment. In this study, we developed two albumin binder-conjugated FAPI radiotracers, TEFAPI-06 and TEFAPI-07. They are derived from FAPI-04, and optimized by conjugating two types of well-studied albumin binders, 4-(p-iodophenyl) butyric acid moiety (TEFAPI-06) and truncated Evans blue moiety (TEFAPI-07), to try to overcome the above limitations at the expense of prolonging the blood circulation. TEFAPI-06 and TEFAPI-07 were synthesized and labeled with Ga, 86Y and Lu successfully. A series of cell assays were performed to identify the binding affinity and FAP specificity in vitro. PET imaging, SPECT imaging and biodistribution study were performed to evaluate the pharmacokinetics in the pancreatic cancer patient-derived xenografts (PDX) animal models. The cancer treatment efficacy of Lu-TEFAPI-06 and Lu-TEFAPI-07 have been evaluated and the comparative study with Lu-FAPI-04 has also been performed in pancreatic cancer PDX-bearing mice. The binding affinity (Kd) to FAP of Ga-TEFAPI-06 and Ga-TEFAPI-07 is 10.16 ± 2.56 nM and 7.81 ± 2.28 nM, respectively, which were comparable with that of Ga-FAPI-04. Comparative PET imaging of HT-1080-FAP and HT-1080 tumor-bearing mice and blocking study showed the FAP targeting ability in vivo of these two tracers. Compared with Lu-FAPI-04, PET imaging, SPECT imaging and biodistribution studies of TEFAPI-06 and TEFAPI-07 have demonstrated their remarkably enhanced tumor accumulation and retention, respectively. Notable tumor growth inhibitions of Lu-TEFAPI-06 and Lu-TEFAPI-07 have been observed, while the control groups and the group treated by Lu-FAPI-04. Two albumin binder-conjugated FAPI radiopharmaceuticals have been developed and evaluated in vitro and in vivo. Notably improved tumor uptake and retention have been observed compared to the original FAPI tracer. Both Lu-TEFAPI-06 and Lu-TEFAPI-07 showed remarkable growth inhibition to PDX tumors while the side effect is negligible, showing that they are promising for further clinical translational studies.
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http://dx.doi.org/10.2967/jnumed.121.262533DOI Listing
September 2021

Immunomodulatory functions of TRPM7 and its implications in autoimmune diseases.

Immunology 2021 Sep 24. Epub 2021 Sep 24.

Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, China.

An autoimmune disease is an inappropriate response to one's tissues due to a break in immune tolerance and exposure to self-antigens. It often leads to structural and functional damage to organs and systemic disorders. To date, there are no effective interventions to prevent the progression of autoimmune diseases. Hence, there is an urgent need for new treatment targets. TRPM7 is an enzyme-coupled, transient receptor ion channel of the subfamily M that plays a vital role in pathologic and physiologic conditions. While TRPM7 is constitutively activated under certain conditions, it can regulate cell migration, polarization, proliferation and cytokine secretion. However, a growing body of evidence highlights the critical role of TRPM7 in autoimmune diseases, including rheumatoid arthritis, multiple sclerosis and diabetes. Herein, we present (a) a review of the channel kinase properties of TRPM7 and its pharmacological properties, (b) discuss the role of TRPM7 in immune cells (neutrophils, macrophages, lymphocytes and mast cells) and its upstream immunoreactive substances, and (c) highlight TRPM7 as a potential therapeutic target for autoimmune diseases.
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http://dx.doi.org/10.1111/imm.13420DOI Listing
September 2021

Study on the Mechanism of Qigu Capsule in Upregulating NF-B/HIF-1 Pathway to Improve the Quality of Bone Callus in Mice at Different Stages of Osteoporotic Fracture Healing.

Evid Based Complement Alternat Med 2021 13;2021:9943692. Epub 2021 Sep 13.

Shi's Center of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Objective: The present study intends to investigate the effects and underlying molecular mechanism of Qigu Capsule (QG) on fracture healing in mice with osteoporosis.

Methods: Ten-week-old female C57BL/6 mice were ovariectomized and three weeks later were evaluated for successful modeling. Then, all mice were prepared into models of transverse fracture in the right middle femoral shaft. Mice were treated daily using a gavage with normal saline (the NS group), Qigu Capsule (the QG group), or alendronate (the ALN group) postoperatively. Fracture callus tissues were collected and analyzed by X-ray, micro-CT, western blot (WB), and transmission electron microscope (TEM) on postoperation Day 14 (POD14), POD28, and POD42.

Results: (1) X-ray results showed that on POD14, the QG group had the fracture healing score significantly higher than the NS and ALN groups, and on POD28, it had the fracture healing score higher than the NS group, suggesting that QG could promote fracture healing. (2) Micro-CT results showed that on POD14, the QG group had tissue bone density (TMD) significantly higher than the NS and ALN groups, and on POD28 and POD42, it had bone volume fraction, trabecular number, and TMD significantly higher than the NS group. (3) WB results showed that, compared with the NS group, the QG group had significantly increased expression of nuclear factor kappa-B (NF-B), hypoxia-inducible factor-1 (HIF-1), bone alkaline phosphatase (BALP), runt-related transcription factor 2 (Runx2), bone Gla protein (BGP) and collagen I1 (COLI1) on POD14, significantly increased expression of NF-B, HIF-1, BALP and COLI1 on POD28, and significantly increased expression of NF-B, HIF-1, and Runx2 on POD42. (4) TEM scanning results showed that, compared with the NS and ALN groups, the QG group had significantly increased numbers of autophagic vacuoles (AVs) in osteocytes on POD14, POD28, and POD42.

Conclusion: QG could accelerate osteoporotic fracture healing by promoting bone formation and osteocyte autophagy, possibly through upregulating the NF-B/HIF-1 signaling pathway.
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http://dx.doi.org/10.1155/2021/9943692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455191PMC
September 2021

Unraveling the Origin of Sulfur-doped Fe-N-C Single Atom Catalyst for Enhanced Oxygen Reduction Activity: Effect of Fe-spin State Tuning.

Angew Chem Int Ed Engl 2021 Sep 22. Epub 2021 Sep 22.

Wuhan University, The Institute for Advanced Studies, Wuhan, 430072, Wuhan, CHINA.

Heteroatom doped atomically dispersed Fe 1 -NC catalysts have been found to show excellent activity toward oxygen reduction reaction (ORR). However, the origin of the enhanced activity is still controversial because the structure-function relationship governing the enhancement remains elusive. Herein, sulfur(S)-doped Fe 1 -NC catalyst was obtained as a model, which displays a superior activity for ORR towards the traditional Fe-NC materials. 57 Fe Mössbauer spectroscopy and electron paramagnetic resonance spectroscopy revealed that incorporation of S in the second coordination sphere of Fe 1 -NC can induce the transition of spin polarization configuration. Operando 57 Fe Mössbauer spectra definitively identified the low spin  single-Fe 3+ -atom of C-FeN 4 -S moiety as the active site for ORR. Moreover, DFT calculations unveiled that lower spin state of the Fe center after the S doping promotes OH* desorption process. This work elucidates the underlying mechanisms towards S doping for enhancing ORR activity, and paves a way to investigate the function of broader heteroatom doped Fe 1 -NC catalysts to offer a general guideline for spin-state-determined ORR.
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http://dx.doi.org/10.1002/anie.202110243DOI Listing
September 2021

Comment on "The relationship between thyroidectomy complications and body mass index".

Rev Assoc Med Bras (1992) 2021 Jun;67(5):771

Yankuang New Journey General Hospital, Department of Spinal Surgery - Jining China.

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http://dx.doi.org/10.1590/1806-9282.20210152DOI Listing
June 2021

Femoral neck fracture combined with anterior dislocation of the femoral head: injury mechanism and proposed novel classification.

BMC Musculoskelet Disord 2021 Sep 21;22(1):810. Epub 2021 Sep 21.

Department of Orthopedics, The Second Hospital of Jilin University, 218 Ziqiang Road, Nanguan Street, Changchun, 130041, Jilin Province, China.

Background: Femoral neck fracture combined with anterior dislocation of the femoral head is very rare. To our knowledge, there is no classification system yet for this rare form of injury, and the injury mechanism of femoral neck fracture combined with obturator head dislocation has not been described in the literature. In this study, we systematically reviewed the literature and the cases treated in our hospital, and identified and classified all injury types according to the injury mechanism of femoral neck fracture combined with anterior dislocation of the femoral head. Further, based on the experience of treating a patient with femoral neck fracture and obturator dislocation of the femoral head, a theoretical hypothesis was proposed for the injury mechanism of this rare type of injury.

Methods: A comprehensive search was conducted on PubMed, WOS, CNKI database. These fractures were classified according to the dislocation site and injury mechanism (one injury or two injuries).

Results: 1891 articles were initially identified through PubMed and other databases, and after bibliographic research, study screening, and removing duplicates, 1455 articles were selected. After applying the exclusion criteria, a total of 18 full-text articles describing femoral neck fractures combined with anterior dislocation of the femoral head. Different dislocation sites have different injury mechanisms. Our classification system, to the best of the authors' knowledge, allowed us to include all types of femoral neck fractures combined with anterior dislocation of the femoral head from the literature. According to the proposed classification system, the morphological features of femoral neck fracture combined with anterior dislocation of the femoral head can be accurately conveyed between doctors.

Conclusions: All injury patterns can likely be identified using the proposed classification system. This can help avoid confusion in the nomenclature of femoral neck fractures combined with anterior dislocation of the femoral head and help surgeons to more accurately detect lesions, thereby guiding surgical treatment.
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http://dx.doi.org/10.1186/s12891-021-04703-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456574PMC
September 2021

Correction to: Expanding the Genetic and Phenotypic Spectrum of Female Infertility Caused by TUBB8 Mutations.

Reprod Sci 2021 Sep 20. Epub 2021 Sep 20.

State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China.

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http://dx.doi.org/10.1007/s43032-021-00742-9DOI Listing
September 2021

Cost-effectiveness of a Digital Health Intervention for Acute Myocardial Infarction Recovery.

Med Care 2021 Nov;59(11):1023-1030

Johns Hopkins Bloomberg School of Public Health.

Background: Acute myocardial infarction (AMI) is a common cause of hospital admissions, readmissions, and mortality worldwide. Digital health interventions (DHIs) that promote self-management, adherence to guideline-directed therapy, and cardiovascular risk reduction may improve health outcomes in this population. The "Corrie" DHI consists of a smartphone application, smartwatch, and wireless blood pressure monitor to support medication tracking, education, vital signs monitoring, and care coordination. We aimed to assess the cost-effectiveness of this DHI plus standard of care in reducing 30-day readmissions among AMI patients in comparison to standard of care alone.

Methods: A Markov model was used to explore cost-effectiveness from the hospital perspective. The time horizon of the analysis was 1 year, with 30-day cycles, using inflation-adjusted cost data with no discount rate. Currencies were quantified in US dollars, and effectiveness was measured in quality-adjusted life-years (QALYs). The results were interpreted as an incremental cost-effectiveness ratio at a threshold of $100,000 per QALY. Univariate sensitivity and multivariate probabilistic sensitivity analyses tested model uncertainty.

Results: The DHI reduced costs and increased QALYs on average, dominating standard of care in 99.7% of simulations in the probabilistic analysis. Based on the assumption that the DHI costs $2750 per patient, use of the DHI leads to a cost-savings of $7274 per patient compared with standard of care alone.

Conclusions: Our results demonstrate that this DHI is cost-saving through the reduction of risk for all-cause readmission following AMI. DHIs that promote improved adherence with guideline-based health care can reduce hospital readmissions and associated costs.
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http://dx.doi.org/10.1097/MLR.0000000000001636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516712PMC
November 2021

Identification of short peptide sequences that activate human mast cells via Mas-related G-protein coupled receptor member X2.

Acta Biomater 2021 Sep 13. Epub 2021 Sep 13.

Department of Chemical and Materials Engineering, Donadeo Innovation Center for Engineering, University of Alberta, 9211-116 Street NW, Edmonton, AB T6G1H9, Canada. Electronic address:

Peptide based therapeutics are desirable owing to their high biological specificity. However, a number of these fail in clinical testing due to an adverse inflammatory response. Mast cells play a key role in directing the host response to drugs and related products. Although the role of FcεRI receptor is well known, Mas-related G-protein coupled receptor X2 (MRGPRX2) binding of endogenous peptides, and drugs will activate mast cells independent of FcεRI. Identifying peptides that activate mast cells through MRGPRX2, and their respective activation potency, can be used to reduce the failure rate of peptide therapeutics at clinical trial. Moreover, it will allow for peptide design where mast cell activation is actually desired. It was found that FRKKW and WNKWAL are two motifs that activate human LAD2 cells similar to PAMP-12 controls. Peptide activators of MRGPRX2 could be reduced to X-(Y)-X where: X is an aromatic residue; X is a hydrophobic residue; and Y is a minimum 3 residue long sequence, containing a minimum of one positively charged residue with the remainder being uncharged residues. Artificial peptides WKKKW and FKKKF were constructed to test this structural functionality and were similar to PAMP-12 controls. Peptides with different activation potentials were found where FRKKW = WKKKW = FKKKF > PAMP-12 = WNKWAL > YKKKY > FRKKANKWALSR = FRKKWNKAALSR > KWKWK > FRKK = WNKWA > KYKYK > NKWALSR = YKKY = WNK. These sequences should be considered when designing peptide-based therapeutics. STATEMENT OF SIGNIFICANCE: Mast cells release immune regulating molecules upon activation that direct host's immune response. MRGPRX2 receptor provides an alternate pathway for mast cell activation that is independent of FcεRI receptor. It is thought that mast cell activation through MRGPRX2 plays a critical role in high failure rates of drugs in clinical trials. Identifying peptide sequences that activate mast cells through MRGPRX2 can serve two important purposes, namely, sequences to avoid when designing peptide therapeutics, and artificial peptides with different activation potentials for mast cells. Herein, we have identified a general amino acid sequence that induces mast cell activation through MRGPRX2. Furthermore, by modulating the identified sequence, artificial peptides have been designed which activate mast cells by varying degrees for therapeutic applications.
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http://dx.doi.org/10.1016/j.actbio.2021.09.011DOI Listing
September 2021

Fluorescent light energy modulates healing in skin grafted mouse model.

Open Med (Wars) 2021 27;16(1):1240-1255. Epub 2021 Aug 27.

Divisions of Plastic and Reconstructive Surgery and Critical Care, 2D2.28 Walter C MacKenzie Health Sciences Centre & Wound Healing Research Group, 161 HMRC, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.

Skin grafting is often the only treatment for skin trauma when large areas of tissue are affected. This surgical intervention damages the deeper dermal layers of the skin with implications for wound healing and a risk of scar development. Photobiomodulation (PBM) therapy modulates biological processes in different tissues, with a positive effect on many cell types and pathways essential for wound healing. This study investigated the effect of fluorescent light energy (FLE) therapy, a novel type of PBM, on healing after skin grafting in a dermal fibrotic mouse model. Split-thickness human skin grafts were transplanted onto full-thickness excisional wounds on nude mice. Treated wounds were monitored, and excised xenografts were examined to assess healing and pathophysiological processes essential for developing chronic wounds or scarring. Results demonstrated that FLE treatment initially accelerated re-epithelialization and rete ridge formation, while later reduced neovascularization, collagen deposition, myofibroblast and mast cell accumulation, and connective tissue growth factor expression. While there was no visible difference in gross morphology, we found that FLE treatment promoted a balanced collagen remodeling. Collectively, these findings suggest that FLE has a conceivable effect at balancing healing after skin grafting, which reduces the risk of infections, chronic wound development, and fibrotic scarring.
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http://dx.doi.org/10.1515/med-2021-0329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402934PMC
August 2021

A mechanistic model for denitrifying anaerobic methane oxidation coupled to dissimilatory nitrate reduction to ammonium.

Chemosphere 2021 Sep 6;287(Pt 2):132148. Epub 2021 Sep 6.

State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150090, China. Electronic address:

Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) is an important process linking nitrogen and carbon cycle. It is recently demonstrated that n-DAMO archaea are able to couple n-DAMO to dissimilatory nitrate reduction to ammonium (DNRA). In this work, a mathematical model is developed to describe DNRA by n-DAMO archaea for the first time. The anabolic and catabolic processes of n-DAMO archaea, n-DAMO bacteria and anaerobic ammonium oxidation (Anammox) bacteria are involved. The different impacts of exogenous and endogenous nitrite on DNRA and n-DAMO microbes are considered. The developed model is calibrated and validated using experimental data collected from a sequencing batch reactor (SBR) and a counter-diffusion membrane biofilm bioreactor (MBfR). The model outputs fit well with the profiles of nitrogen (N) dynamics and biomass changes in both reactors, demonstrating its good predictive ability. The developed model is further used to simulate the counter-diffusion MBfR incorporating n-DAMO and Anammox process to treat sidestream wastewater. The simulated distribution profiles of N removal/production rates by different microbes along biofilm depth reveal that DNRA by n-DAMO archaea plays an important role in N transformation of the integrated n-DAMO and Anammox process. It is further suggested that the counter-diffusion MBfR under the investigated conditions should be operated at proper hydraulic retention times (HRTs) (i.e. 6h and 8h) with exogenous NO in the range of 0-10 mg N/L or at HRTs >3h with the absence of exogenous NO in order to achieve dischargeable effluent.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132148DOI Listing
September 2021

mRNA analysis identifies deep intronic variants causing Alport syndrome and overcomes the problem of negative results of exome sequencing.

Sci Rep 2021 Sep 10;11(1):18097. Epub 2021 Sep 10.

Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.

Mutations in COL4A3, COL4A4 and COL4A5 genes lead to Alport syndrome (AS). However, pathogenic variants in some AS patients are not detected by exome sequencing. The aim of this study was to identify the underlying genetic causes of five unrelated AS probands with negative NGS test results. Urine COL4A3-5 mRNAs were analyzed in the probands with an uncertain inherited mode of AS, and COL4A5 mRNA of skin fibroblasts was analyzed in the probands with X-linked AS. RT-PCR and direct sequencing were performed to detect mRNA abnormalities. PCR and direct sequencing were used to analyze the exons with flanking intronic sequences corresponding to mRNA abnormalities. Six novel deep intronic splicing variants in COL4A4 and COL4A5 genes that cannot be captured by exome sequencing were identified in the four AS probands. Skipping of an exon was caused by an intronic variant, and retention of an intron fragment caused by five variants. In the remaining AS proband, COL4A5 variants c.2677 + 646 C > T and r.2678_r.2767del were detected at the DNA and RNA level, respectively, whereas it is unclear whether c.2677 + 646 C > T may not lead to r.2678_r.2767del. Our results reveal that mRNA analysis for AS genes from either urine or skin fibroblasts can resolve genetic diagnosis in AS patients with negative NGS results. We recommend analyzing COL4A3-5 mRNA from urine as the first choice for these patients because it is feasible and non-invasive.
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http://dx.doi.org/10.1038/s41598-021-97414-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433132PMC
September 2021

Expanding the Genetic and Phenotypic Spectrum of Female Infertility Caused by TUBB8 Mutations.

Reprod Sci 2021 Sep 7. Epub 2021 Sep 7.

State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China.

Tubulin beta eight class VIII (TUBB8) is a subtype of β-tubulin that only exists in primates. TUBB8 mutations have been reported to cause arrest of oocyte maturation and embryonic development. We aim to further investigate the mutational spectrum of TUBB8 and its relevance with female infertility. In our study, infertile patients were recruited, and their basal and clinical characteristics were analyzed. Genomic DNA was extracted from peripheral blood donated by patients. Candidate variants were identified by whole-exome sequencing, selected by relevant criteria, and validated by Sanger sequencing. We found five heterozygous variants: c.C208A(p.P70T), c.T907C(p.C303R), c.G173A(p.R58K), c.G326T(p.G109V), and c.C916T(p.R306C) in TUBB8 among six infertile patients characterized by abnormal phenotypes in oocyte maturation, fertilization, or embryo development. Most of oocytes retrieved from affected individuals were arrested at GV (germinal vesicle) stage and early embryos were arrested at variable stages. In vitro experiments were performed, and the relationship between variant c.G173A(p.R58K), c.C208A(p.P70T), and infertility phenotype was confirmed. We also discussed the possibility about patient II-1 from family 4 is affected by germinal/germline mosaicism. These results expand the kinds of variants and phenotypic spectrum of TUBB8 variants with regard to female infertility.
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http://dx.doi.org/10.1007/s43032-021-00694-0DOI Listing
September 2021

Blood lipids and risk of colon or rectal cancer: a Mendelian randomization study.

J Cancer Res Clin Oncol 2021 Sep 6. Epub 2021 Sep 6.

Cancer Center, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 68 Gehu Road, Wujin District, Changzhou, 213164, Jiangsu, China.

Purpose: Recent Mendelian randomization (MR) studies derived inconsistent results of blood lipids' effect on colorectal cancer, and whether the blood lipids' effect on colon and rectal cancer is different is still unknown. Here, we sought to answer these questions.

Methods: Primarily, we employed univariable MR to explore the blood lipids' effect on colon and rectal cancer, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol and triglycerides. Then, multivariable MR was also employed to reassess each blood lipid's effect on the two cancers with adjustment of the other lipids. Reverse MR analysis was adopted to determine whether colon or rectal cancer could affect the levels of blood lipids. The Cochrane's Q value was used to evaluate the heterogeneity, and MR-PRESSO was used to appraise the pleiotropy.

Results: Generally, we did not find any significant result between blood lipids and the colon/rectal cancer after Bonferroni correction in the univariable MR analysis. The multivariable MR analysis also obtained the same results. However, it should be noted that higher total cholesterol level might increase the risk of colon cancer (OR = 1.15 [1.01, 1.31], IVW p value = 0.029) but not rectal cancer (OR = 1.02 [0.85, 1.21], IVW p value = 0.853). Such causal relationship turned insignificant in the multivariable MR. The reverse MR analysis suggested that either colon or rectal cancer could increase the levels of blood lipids.

Conclusion: We found no association between blood lipids and risk of colon or rectal cancer, except for a positive association between total cholesterol and colon cancer risk.
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http://dx.doi.org/10.1007/s00432-021-03790-5DOI Listing
September 2021

A cell-free ROS-responsive hydrogel/oriented poly(lactide-co-glycolide) hybrid scaffold for reducing inflammation and restoring full-thickness cartilage defects.

Biomed Mater 2021 09 14;16(6). Epub 2021 Sep 14.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China.

The modulation of inflammation in tissue microenvironment takes an important role in cartilage repair and regeneration. In this study, a novel hybrid scaffold was designed and fabricated by filling a reactive oxygen species (ROS)-scavenging hydrogel (RS Gel) into a radially oriented poly(lactide-co-glycolide) (PLGA) scaffold. The radially oriented PLGA scaffolds were fabricated through a temperature gradient-guided phase separation and freeze-drying method. The RS Gel was formed by crosslinking the mixture of ROS-responsive hyperbranched polymers and biocompatible methacrylated hyaluronic acid (HA-MA). The hybrid scaffolds exhibited a proper compressive modulus, good ROS-scavenging capability, and cell compatibility.tests showed that the hybrid scaffolds significantly regulated inflammation and promoted regeneration of hyaline cartilage after they were implanted into full-thickness cartilage defects in rabbits for 12 w. In comparison with the PLGA scaffolds, the neo-cartilage in the hybrid scaffolds group possessed more deposition of glycosaminoglycans and collagen type II, and were well integrated with the surrounding tissue.
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http://dx.doi.org/10.1088/1748-605X/ac21ddDOI Listing
September 2021

Reliability and validity of the novel self-reported spine functional scale (SSFS) in healthy participants.

J Orthop Surg Res 2021 Aug 25;16(1):529. Epub 2021 Aug 25.

Nanjing University of Posts and Telecommunications, Sports Department, Nanjing, China.

Objectives: To develop the novel self-reported spine functional scale (SSFS) and conduct reliability and validity analysis, so that the public can better understand their own spine function in a more simple and scientific way, so as to effectively prevent spinal disorders and improve the quality of life through targeted rehabilitation therapeutic measures.

Methods: This study was approved by an institutional review board, and all subjects gave informed consent to participate.

Results: (1) Using Spearman correlation analysis to evaluate the content validity, each item was significantly correlated with the total score, and the project design was reasonable. The exploratory factor analysis method is used to evaluate the structural validity of the scale, and the standing position and the lying position of the posture evaluation can be attributed to the factor 2, which is called posture evaluation: the cervical flexor strength, the flat support, the prone back, and the supine knee. The back arch of the wall and the angel on the wall is attributed to factor 1, called the overall spine function test, and the cumulative contribution rate of the two factors was 46.057%. Confirmatory factor analysis showed that the two-factor model fits well (χ/df = 2.440, RMSEA = 0.04 < 0.05, GFI = 0.945, AGFI = 0.920, CFI = 0.967, IFI = 0.967, TLI = 0.951, GFI, AGFI, CFI, IFI, and TLI are > 0.90) and the validity is ideal. (2) The test-retest reliability shows that the test-retest reliability of each entry, each dimension, and the total score is greater than 0.5, and the test-retest reliability is high. The Cronbach α coefficient was used to evaluate the overall internal consistency of the scale, α > 0.70, indicating that the scale has high reliability. After deleting each item one by one, the α coefficient is 0.692-0.717, and there is no significant increase. (3) Sex and occupation did not affect the level of spinal function (P > 0.05), and there was interaction. Different BMI levels significantly affected the score of spinal function (P < 0.05). The rate of spinal dysfunction in overweight and obese subjects was significantly higher than the normal group; the overall score of spinal function was worse than the normal group.

Discussion: The reliability and validity analyses of this study verified the reliability and scientificity of SSFS in the young healthy population. Body weight had a significant influence on SSFS score, and the performance levels were different for the two sexes.

Conclusion: The novel Self-Reported Spine Functional Scale (SSFS) has high reliability and validity and is applicable to the self-assessment and maintenance of spinal health and the prevention of related spinal disorders in the young healthy population. Body weight has a significant influence on the SSFS score in healthy young people. Overweight and obese males were found to be more likely to have spinal dysfunction, while underweight males displayed poor cervical flexor muscle strength. Underweight females were found to have better overall spinal function and stronger cervical flexor muscle strength.
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http://dx.doi.org/10.1186/s13018-021-02620-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386065PMC
August 2021

Effects of acute low temperature stress on the hormones and gene expression of glucocorticoid receptor of large yellow croaker Larimichthys crocea.

J Therm Biol 2021 Jul 4;99:103018. Epub 2021 Jun 4.

Key Laboratory of Applied Marine Biotechnology of Ministry of Education, School of Marine Sciences, Ningbo University, Ningbo, 315211, Zhejiang, China. Electronic address:

The neuroendocrine system of fish responds to low temperature via regulating hormones. To explore the adaptability of Larimichthys crocea to low temperature, the levels of the plasma cortisol, thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), total cholesterol (TC), and glucose were determined after exposure to low temperature and during subsequent rewarming. Furthermore, the mRNA expression of the glucocorticoid receptor (GR) gene was analyzed under the stress. We found that the levels of the plasma cortisol, TSH, T3, glucose, and TC increased under the low temperature stress, suggesting that elevated hormones may be conducive to promoting the mobilization of the glucose and lipid in L. crocea exposed to low temperature. During the rewarming period, the plasma cortisol level decreased, whereas the T3 level was still significantly higher than that in the control group. Notably, the plasma T4 level was unaffected by the temperature changes. Furthermore, the sequence alignment and phylogenetic tree analysis revealed that the GR protein of L. crocea had high homology and a similar protein structure with those from other teleosts. Under the low temperature stress, the GR mRNA expression increased in the brain and head kidney, whereas it basically returned to the control level following rewarming. These findings revealed the changes of the hormones and the potential function of the GR gene in L. crocea following exposure to low temperature, providing some insights into breeding low temperature-resistant varieties of L. crocea.
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http://dx.doi.org/10.1016/j.jtherbio.2021.103018DOI Listing
July 2021

Scavenging reactive oxygen species is a potential strategy to protect against environmental hypoxia by mitigating oxidative stress.

Zool Res 2021 Sep;42(5):592-605

State Key Laboratory of Large Yellow Croaker Breeding, Ningbo Academy of Oceanology and Fishery, Ningbo, Zhejiang 315012, China.

The large yellow croaker (), which is an economically important mariculture fish in China, is often exposed to environmental hypoxia. Reactive oxygen species (ROS) homeostasis is essential for the maintenance of normal physiological conditions in an organism. Direct evidence that environmental hypoxia leads to ROS overproduction is scarce in marine fish. Furthermore, the sources of ROS overproduction in marine fish under hypoxic stress are poorly known. In this study, we investigated the effects of hypoxia on redox homeostasis in . and the impact of impaired redox homeostasis on fish. We first confirmed that hypoxia drove ROS production mainly via the mitochondrial electron transport chain and NADPH oxidase complex pathways in . and its cell line (large yellow croaker fry (LYCF) cells). We subsequently detected a marked increase in the antioxidant systems of the fish. However, imbalance between the pro-oxidation and antioxidation systems ultimately led to excessive ROS and oxidative stress. Cell viability showed a remarkable decrease while oxidative indicators, such as malondialdehyde, protein carbonylation, and 8-hydroxy-2 deoxyguanosine, showed a significant increase after hypoxia, accompanied by tissue damage. N-acetylcysteine (NAC) reduced ROS levels, alleviated oxidative damage, and improved cell viability . Appropriate uptake of ROS scavengers (e.g., NAC and elamipretide Szeto-Schiller-31) and inhibitors (e.g., apocynin, diphenylene iodonium, and 5-hydroxydecanoate) may be effective at overcoming hypoxic toxicity. Our findings highlight previously unstudied strategies of hypoxic toxicity resistance in marine fish.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2021.079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455462PMC
September 2021

A Stable Cell Line Expressing Clustered AChR: A Novel Cell-Based Assay for Anti-AChR Antibody Detection in Myasthenia Gravis.

Front Immunol 2021 8;12:666046. Epub 2021 Jul 8.

Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Cell-based assays (CBAs) and radioimmunoprecipitation assay (RIPA) are the most sensitive methods for identifying anti-acetylcholine receptor (AChR) antibody in myasthenia gravis (MG). But CBAs are limited in clinical practice by transient transfection. We established a stable cell line (KL525) expressing clustered AChR by infecting HEK 293T cells with dual lentiviral vectors expressing the genes encoding the human AChR α1, β1, δ, ϵ and the clustering protein rapsyn. We verified the stable expression of human clustered AChR by immunofluorescence, immunoblotting, and real-time PCR. Fluorescence-activated cell sorting (FACS) was used to detect anti-AChR antibodies in 103 MG patients and 58 healthy individuals. The positive results of MG patients reported by the KL525 was 80.6% (83/103), 29.1% higher than the 51.4% (53/103) of RIPA. 58 healthy individuals tested by both the KL525 CBA and RIPA were all negative. In summary, the stable expression of clustered AChR in our cell line makes it highly sensitive and advantageous for broad clinical application in CBAs.
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http://dx.doi.org/10.3389/fimmu.2021.666046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297518PMC
October 2021

Functional characterization of adrenocortical masses in nononcological patients using [Ga]-pentixafor.

J Nucl Med 2021 Jul 22. Epub 2021 Jul 22.

The Medical University of Vienna.

We aimed to investigate the diagnostic and prognostic value of Ga-pentixafor positron emission tomography (PET)/computed tomography (CT) imaging in non-cancer patients with suspected adrenal masses. Sixty-four patients who had benign adrenal masses on CT were retrospectively included in our study. All patients underwent Ga-pentixafor PET/CT scans, and 56 of these patients subsequently underwent adrenalectomy. The subtypes of 81 adrenal tumors including 14 nonfunctioning adrenal nodules, 4 cortisol-producing adenomas, 41 aldosterone-producing adenomas, 5 suspected unilateral adrenal hyperplasia, 15 idiopathic aldosterone hyperplasia and 2 pheochromocytomas, were determined by histology or follow-up evaluations. The functional lateralization diagnosis efficiency was calculated by visual analysis. Semi-quantitative parameters of these lesions including maximum standardized uptake value (SUV), the ratio of lesional SUV to normal liver SUVmean (LLR), and the ratio of lesional SUV to contralateral adrenal tissue SUVmean (LCR) have also been calculated. Dynamic analysis has also been performed on fifteen patients. Besides, clinical outcomes were assessed and compared in patients who underwent adrenalectomy. The sensitivity and specificity of Ga-pentixafor PET for functional lateralization of patients with adrenocortical lesions were 97.8% (45/46) and 87.5% (14/16) respectively. The two pheochromocytoma lesions had lower pentixafor uptake compared to the normal adrenal glands. Functioning (active) adrenocortical adenomas showed an elevated SUV of 16.3±7.9 in comparison to 4.4±1.7 in nonfunctioning (inactive) adenomas and 5.5±2.7 in hyperplasia lesions (P<0.0001). To identify active adrenocortical adenomas, a cutoff value of 7.1 for SUV showed a sensitivity of 90.9% and a specificity of 85.3% (AUC=0.96, P<0.0001); a cutoff value of 2.5 for LLR showed a sensitivity of 95.5% and a specificity of 88.2% (AUC=0.97, P<0.0001); and a cutoff value of 2.4 for LCR showed a sensitivity of 88.6% and a specificity of 91.8% (AUC=0.95, P<0.0001). The graphical Ki of active adrenocortical adenomas was significantly higher than in-active adenomas. Uptake values for Ga-pentixafor were significantly higher in patients with preferable outcomes (cured/improved) (SUV=15.5±8.0, LLR=6.5±4.3, LCR=6.2±5.0) than in patients with nonpreferable outcomes (no improvement) (SUV=4.2±0.5, LLR=1.3±0.2, LCR =1.5±0.6, all P<0.0001). Ga-pentixafor PET/CT imaging exhibits great potential for noninvasive functional lateralization and characterization of patients with adrenocortical masses.
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http://dx.doi.org/10.2967/jnumed.121.261964DOI Listing
July 2021

Spectrum of Mutations in Pediatric Non-glomerular Chronic Kidney Disease Stages 2-5.

Front Genet 2021 6;12:697085. Epub 2021 Jul 6.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Renal hypodysplasia and cystic kidney diseases, the common non-glomerular causes of pediatric chronic kidney disease (CKD), are usually diagnosed by their clinical and imaging characteristics. The high degree of phenotypic heterogeneity, in both conditions, makes the correct final diagnosis dependent on genetic testing. It is not clear, however, whether the frequencies of damaged alleles vary among different ethnicities in children with non-glomerular CKD, and this will influence the strategy used for genetic testing. In this study, 69 unrelated children (40 boys, 29 girls) of predominantly Han Chinese ethnicity with stage 2-5 non-glomerular CKD caused by suspected renal hypodysplasia or cystic kidney diseases were enrolled and assessed by molecular analysis using proband-only targeted exome sequencing and array-comparative genomic hybridization. Targeted exome sequencing discovered genetic etiologies in 33 patients (47.8%) covering 10 distinct genetic disorders. The clinical diagnoses in 13/48 patients (27.1%) with suspected renal hypodysplasia were confirmed, and two patients were reclassified carrying mutations in nephronophthisis () genes. The clinical diagnoses in 16/20 patients (80%) with suspected cystic kidney diseases were confirmed, and one patient was reclassified as carrying a deletion in the hepatocyte nuclear factor-1-beta gene (). The diagnosis of one patient with unknown non-glomerular disease was elucidated. No copy number variations were identified in the 20 patients with negative targeted exome sequencing results. genes were the most common disease-causing genes in the patients with disease onsets above 6 years of age (14/45, 31.1%). The children with stage 2 and 3 CKD at onset were found to carry causative mutations in paired box gene 2 () and gene (11/24, 45.8%), whereas those with stage 4 and 5 CKD mostly carried causative mutations in genes (19/45, 42.2%). The causative genes were not suspected by the kidney imaging patterns at disease onset. Thus, our data show that in Chinese children with non-glomerular renal dysfunction caused by renal hypodysplasia and cystic kidney diseases, the common causative genes vary with age and CKD stage at disease onset. These findings have the potential to improve management and genetic counseling of these diseases in clinical practice.
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http://dx.doi.org/10.3389/fgene.2021.697085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290170PMC
July 2021

Environmentally relevant perinatal exposure to DBP disturbs testicular development and puberty onset in male mice.

Toxicology 2021 07 16;459:152860. Epub 2021 Jul 16.

Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address:

Di-n-butyl phthalate (DBP) is considered as a potential modifier of puberty. However, different results indicate that DBP plays an accelerated, delayed, or neutral role in the initiation of puberty. Furthermore, whether the effect of DBP on puberty will disrupt the function of reproductive system in the adults is still ambiguous. Therefore, we aimed to investigate the effect of maternal exposure to DBP on the onset of puberty in male offspring mice and the subsequent changes in the development of reproductive system. Here, pregnant mice were treated with 0 (control), 50, 250, or 500 mg/kg/day DBP in 1 mL/kg corn oil administered daily by oral gavage from gestation day (GD) 12.5 to parturition. Compared with the control group, the 50 mg/kg/day DBP group accelerated puberty onset and testicular development were quite remarkable in male offspring mice during early puberty. Furthermore, in 22-day male offspring mice, 50 mg/kg/day DBP induced increased levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone in serum, and promoted the expression of steroidogenesis-related genes in the testes. Testicular Leydig cells (LCs) were isolated from the testes of 3-week-old mice and treated with 0 (control), 0.1, 1 mM monobutyl phthalate (MBP, the active metabolite of DBP) for 24 h. Consistent with the in vivo results, the expression of steroidogenesis-related genes and testosterone production were increased in LCs following exposure to 0.1 mM MBP. In adulthood, testes of the male offspring mice exposed to all doses of DBP exhibited adverse morphology compared with the control group. These results demonstrated that maternal exposure to 50 mg/kg/day DBP induced earlier puberty and precocious development of the testis, and eventually damaged the reproductive system in the later life.
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http://dx.doi.org/10.1016/j.tox.2021.152860DOI Listing
July 2021

Decoration of Ru/RuO hybrid nanoparticles on MoO plane as bifunctional electrocatalyst for overall water splitting.

J Colloid Interface Sci 2021 Dec 10;604:508-516. Epub 2021 Jul 10.

Green Catalysis Center, College of Chemistry, Zhengzhou University, 100 Science Road, Zhengzhou 450001, PR China.

Hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are the two branches of artificial overall water splitting (OWS), in which the reaction efficiency usually depends on different specific catalysts. Although effective bifunctional electrocatalyst for OWS (HER and OER) are highly desired, designing and constructing such suitable materials is full of challenges to overcome several difficulties, involving slow kinetics, differences in catalytic mechanisms, large overpotential values, and low round-trip efficiencies. In this work, we reported a new bifunctional electrocatalyst Ru/RuO-MoO catalyst (RRMC) via a redox solid phase reaction (RSPR) strategy to achieve the high electrocatalytic activity of OWS. Briefly, due to the restricted transport behavior of atoms in solid state precursor, the designed redox reaction occurred between the adjacent part of RuO and MoS, forming Ru/RuO hybrid NPs and MoO plane. Therefore, the newly formed Ru/RuO hybrid NPs and MoO plane were tightly combined and used as an electrocatalyst for OWS. Benefiting from the exposed active sites and optimized electronic structure, the RRMC sample annealed at 500 °C (RRMC-500) exhibited low overpotential for HER (18 mV) and for OER (260 mV) at 10 mA cm under alkaline conditions. Especially, a low cell voltage of 1.54 V was required at 10 mA cm under alkaline condition.
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http://dx.doi.org/10.1016/j.jcis.2021.07.038DOI Listing
December 2021

The Predictive Value of Cervical Length During the Second Trimester for Non-Medically Induced Preterm Birth.

Int J Gen Med 2021 9;14:3281-3285. Epub 2021 Jul 9.

Department of Obstetrics and Gynecology, Beijing Fengtai Hospital, Beijing, 100071, People's Republic of China.

Objective: The aim of the present study was to investigate the predictive value of transvaginal ultrasonography measurement of cervical length (CL) during the second trimester for spontaneous preterm birth.

Methods: Data from 1222 women with a single fetus pregnancy, who delivered at our hospital between March 2019 and May 2020, were retrospectively analyzed. CL was measured during the second trimester, with a length of <25 mm regarded as cervical shortening. The relationship between CL, cervical shortening, and pregnancy outcome was analyzed.

Results: The incidence of spontaneous preterm birth and cervical shortening in the 1222 women was 7.3% (89/1222) and 0.33% (4/1222), respectively. The average CL during the second trimester was 37.9 ± 5.7 mm for the spontaneous preterm birth group and 39.3 ± 3.8 mm for those who gave birth at full term. Three of the four cases of cervical shortening resulted in a spontaneous preterm birth. This showed a predictive sensitivity of 3.33% and a specificity of 99.9%.

Conclusion: CL measurement during the second trimester can be used as a routine test to predict spontaneous preterm birth. During the second trimester, the distribution of CL in women with single fetus pregnancies in China is different compared with other countries. Reducing the threshold of CL may improve the predictive value for preterm birth.
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http://dx.doi.org/10.2147/IJGM.S311390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276818PMC
July 2021

Digital Health Intervention in Acute Myocardial Infarction.

Circ Cardiovasc Qual Outcomes 2021 Jul 15;14(7):e007741. Epub 2021 Jul 15.

Digital Health Innovation Laboratory, Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (F.A.M., E.M.S., J.D., J.W., H.X., L.M.S., D.W., V.V., D.N.L., R.S., P.P.H., S.W., S.S.M.).

Background: Thirty-day readmissions among patients with acute myocardial infarction (AMI) contribute to the US health care burden of preventable complications and costs. Digital health interventions (DHIs) may improve patient health care self-management and outcomes. We aimed to determine if patients with AMI using a DHI have lower 30-day unplanned all-cause readmissions than a historical control.

Methods: This nonrandomized controlled trial with a historical control, conducted at 4 US hospitals from 2015 to 2019, included 1064 patients with AMI (DHI n=200, control n=864). The DHI integrated a smartphone application, smartwatch, and blood pressure monitor to support guideline-directed care during hospitalization and through 30-days post-discharge via (1) medication reminders, (2) vital sign and activity tracking, (3) education, and (4) outpatient care coordination. The Patient Activation Measure assessed patient knowledge, skills, and confidence for health care self-management. All-cause 30-day readmissions were measured through administrative databases. Propensity score-adjusted Cox proportional hazard models estimated hazard ratios of readmission for the DHI group relative to the control group.

Results: Following propensity score adjustment, baseline characteristics were well-balanced between the DHI versus control patients (standardized differences <0.07), including a mean age of 59.3 versus 60.1 years, 30% versus 29% Women, 70% versus 70% White, 54% versus 54% with private insurance, 61% versus 60% patients with a non ST-elevation myocardial infarction, and 15% versus 15% with high comorbidity burden. DHI patients were predominantly in the highest levels of patient activation for health care self-management (mean score 71.7±16.6 at 30 days). The DHI group had fewer all-cause 30-day readmissions than the control group (6.5% versus 16.8%, respectively). Adjusting for hospital site and a propensity score inclusive of age, sex, race, AMI type, comorbidities, and 6 additional confounding factors, the DHI group had a 52% lower risk for all-cause 30-day readmissions (hazard ratio, 0.48 [95% CI, 0.26-0.88]). Similar results were obtained in a sensitivity analysis employing propensity matching.

Conclusions: Our results suggest that in patients with AMI, the DHI may be associated with high patient activation for health care self-management and lower risk of all-cause unplanned 30-day readmissions. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03760796.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.121.007741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288197PMC
July 2021

Roles of long noncoding RNAs on tumor immune escape by regulating immune cells differentiation and function.

Am J Cancer Res 2021 15;11(6):2369-2385. Epub 2021 Jun 15.

Department of Oncology, Second Affiliated Hospital, Nanjing Medical University Nanjing, Jiangsu, People's Republic of China.

A long noncoding RNA (lncRNA) transcript is generally more than 200 nucleotides in length and rarely codes for any protein. Currently, many lncRNAs have been identified among mammalian genomes, and their known functions are associated with various physiological activities or pathological processes. Some lncRNAs are dysregulated in a variety of malignant tumors, while increasing evidence indicates that abnormal expression can contribute to the regulation of immune cells in tumors and to shaping the immune response. More specifically, lncRNAs participate in regulating the differentiation of immune cells, also known as myeloid and lymphoid cells, as well as recruiting various immunosuppressive factors to influence the tumor microenvironment, thereby promoting tumor cell immune escape. However, we still know very little about the specific mechanism of lncRNAs in immune escape of cancer. Nonetheless, although unprecedented achievements have allowed the development of a new generation of anti-tumor immune therapies to be applied in clinical trials, the drug resistance caused by immune escape has become a major clinical challenge. The focus of this review is to describe the relationship among lncRNAs, immune cells, and tumor immune escape, in order to identify novel diagnostic and therapeutic targets in human cancers.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263655PMC
June 2021

Partial inhibition of activin receptor-like kinase 4 alleviates bladder fibrosis caused by bladder outlet obstruction.

Exp Cell Res 2021 09 6;406(1):112724. Epub 2021 Jul 6.

Department of Urology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China. Electronic address:

The bladder undergoes profound structural alterations after bladder outlet obstruction (BOO), characterized by hypertrophy of the bladder wall and accumulation of extracellular matrix (ECM). Transforming growth factor-β (TGF-β) has been found to promote fibrosis of the bladder induced by partial bladder outlet obstruction (pBOO). Activin receptor-like kinase 4 (ALK4) is a downstream receptor of the TGF-β superfamily. However, the role of the ALK4-Smad2/3 pathway in the pathogenesis of bladder fibrosis caused by pBOO remains unknown. This study focused on learning the role of ALK4 in the process of bladder fibrosis caused by pBOO. The pBOO mice models showed that ALK4 expression was found to upregulate in the wild-type bladder 6 weeks after pBOO compared to control group. Then, mice with heterozygous knockout of the ALK4 gene (ALK4+/-) were generated. Histological analysis and Western blot (WB) results showed significant suppression of collagen expression in the bladders of ALK4+/- mice after pBOO compared with WT mice. WB also showed that ALK4+/- mice demonstrated significant suppression of phosphorylated Smad2/3 (p-Smad2/3) expression in the bladder 6 weeks after pBOO but not of phosphorylated extracellular signal-regulated kinase, c-Jun N-terminal kinase or protein 38 (p-ERK, p-JNK, p-P38) expression. This effect might have occurred through partial inactivation of the Smad2/3 signaling pathway. In vitro, ALK4 overexpression promoted collagen production in cultured BSMCs and activated the Smad2/3 signaling pathway. Taken together, our results demonstrated that ALK4 insufficiency alleviated bladder fibrosis in a mouse model of pBOO partly by suppressing Smad2/3 activity.
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http://dx.doi.org/10.1016/j.yexcr.2021.112724DOI Listing
September 2021
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