Publications by authors named "Na Yu"

331 Publications

Magnetism-induced topological transition in EuAs.

Nat Commun 2021 Nov 30;12(1):6970. Epub 2021 Nov 30.

State Key Laboratory of Surface Physics, Department of Physics, and Laboratory of Advanced Materials, Fudan University, 200433, Shanghai, China.

The nature of the interaction between magnetism and topology in magnetic topological semimetals remains mysterious, but may be expected to lead to a variety of novel physics. We systematically studied the magnetic semimetal EuAs, demonstrating a magnetism-induced topological transition from a topological nodal-line semimetal in the paramagnetic or the spin-polarized state to a topological massive Dirac metal in the antiferromagnetic ground state at low temperature. The topological nature in the antiferromagnetic state and the spin-polarized state has been verified by electrical transport measurements. An unsaturated and extremely large magnetoresistance of ~2 × 10% at 1.8 K and 28.3 T is observed. In the paramagnetic states, the topological nodal-line structure at the Y point is proven by angle-resolved photoemission spectroscopy. Moreover, a temperature-induced Lifshitz transition accompanied by the emergence of a new band below 3 K is revealed. These results indicate that magnetic EuAs provides a rich platform to explore exotic physics arising from the interaction of magnetism with topology.
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http://dx.doi.org/10.1038/s41467-021-26482-7DOI Listing
November 2021

Effect of different tooth preparation designs on the marginal and internal fit discrepancies of cobalt-chromium crowns produced by computer-aided designing and selective laser melting processes.

J Adv Prosthodont 2021 Oct 27;13(5):333-342. Epub 2021 Oct 27.

College of Stomatology, Chongqing Medical University, Chongqing, China.

Purpose: To evaluate the impact of five different tooth preparation designs on the marginal and internal fit discrepancies of cobalt-chromium (CoCr) crowns produced by computer-aided designing (CAD) and selective laser melting (SLM) processes.

Materials And Methods: Five preparation data were constructed, after which design crowns were obtained. Actual crowns were fabricated using an SLM process. After the data of actual crowns were obtained with structural light scanning, intaglio surfaces of the design crown and actual crown were virtually superimposed on the preparation. The fit-discrepancies were displayed with colors, while the root means square was calculated and analyzed with one-way analysis of variance (ANOVA), Tukey's test or Kruskal-Wallis test (α =.05).

Results: The marginal or internal color-coded images in the five design groups were not identical. The shoulder-lip and sharp line angle groups in the CAD or SLM process had larger marginal or internal fit discrepancies compared to other groups ( < .05). In the CAD process, the mean marginal and internal fit discrepancies were 10.0 to 24.2 µm and 29.6 to 31.4 µm, respectively. After the CAD and SLM processes, the mean marginal and internal fit discrepancies were 18.4 to 40.9 µm and 39.1 to 47.1 µm, respectively. The SLM process itself resulted in a positive increase of the marginal (6.0 - 16.7 µm) and internal (9.0 - 15.7 µm) fit discrepancies.

Conclusion: The CAD and SLM processes affected the fit of CoCr crowns and varied based on the preparation designs. Typically, the shoulder-lip and sharp line angle designs had a more significant effect on crown fit. However, the differences between the design groups were relatively small, especially when compared to fit discrepancies observed clinically.
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http://dx.doi.org/10.4047/jap.2021.13.5.333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558576PMC
October 2021

Chlorination Enabling a Low-cost Benzodithiophene-based Wide-bandgap Donor Polymer with an Efficiency of over 17.

Adv Mater 2021 Nov 13:e2105483. Epub 2021 Nov 13.

College of Textiles & Clothing, Qingdao University, Qingdao, 266071, China.

Three regio-regular benzodithiophene-based donor-donor (D-D)-type polymers (PBDTT, PBDTT1Cl, and PBDTT2Cl) are designed, synthesized, and used as donor materials in organic solar cells (OSCs). Because of the weak intramolecular charge transfer effect, these polymers exhibit large optical bandgaps (>2.0 eV). Among these three polymers, PBDTT1Cl exhibits more ordered and closer molecular stacking, and its devices demonstrate higher and more balanced charge mobilities and a longer charge separated (CS) state lifetime. As a result of these comprehensive benefits, PBDTT1Cl-based OSCs give a very impressive power conversion efficiency (PCE) of 17.10% with a low nonradiative energy loss (0.19 eV). Moreover, PBDTT1Cl also possesses a low figure-of-merit (FOM) value and good universality to match with different acceptors. Our work provides a simply and efficient strategy to design low-cost high-performance polymer donor materials. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202105483DOI Listing
November 2021

Total Synthesis of Isorosthin L and Isoadenolin I.

Angew Chem Int Ed Engl 2021 Nov 12. Epub 2021 Nov 12.

ShanghaiTech University, School of Physical Science and Technology, 94 Weijin Road, Nankai District, 300071, Tianjin, CHINA.

Total syntheses of two Isodon diterpenes, isorosthin L and isoadenolin I, are reported. The synthetic strategy features a quick assembly of two simple building blocks through a diastereoselective intermolecular aldol reaction and a subsequent radical cyclization for efficient construction of a rather complex advanced intermediate bearing a quaternary stereocenter present in all Isodon diterpenes. Oxidative cleavage of the C-C bond in the cyclopentane enabled the conversion to a lactone moiety which is desired for the construction of the molecular skeleton through reductive coupling with an aldehyde carbonyl group.
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http://dx.doi.org/10.1002/anie.202114489DOI Listing
November 2021

Genomic Identification and Functional Analysis of JHAMTs in the Pond Wolf Spider, .

Int J Mol Sci 2021 Oct 29;22(21). Epub 2021 Oct 29.

Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China.

Juvenile hormone (JH) plays a critical role in many physiological activities of Arthropoda. Juvenile hormone acid methyltransferase (JHAMT) is involved in the last steps of JH biosynthesis as an important rate-limiting enzyme. In recent studies, an increasing number of JHAMTs were identified in arthropods, but no JHAMT was reported in spiders. Herein, eight JHAMTs were identified in the pond wolf spider, , all containing the well conserved S-adenosyl-L-methionine binding motif. and the other seven were located at chromosome 13 and chromosome 1, respectively. Multiple alignment and phylogenetic analysis showed that JHAMT-1 was grouped together with insect JHAMTs independently and shared high similarities with insect JHAMTs compared to the other seven JHAMTs. In addition, , , and were highly expressed in the abdomen of spiderlings and could respond to the stimulation of exogenous farnesoic acid. Meanwhile, knockdown of these three caused the overweight and accelerated molting of spiderlings. These results demonstrated the cooperation of multi-JHAMTs in spider development and provided a new evolutionary perspective of the expansion of in Arachnida.
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http://dx.doi.org/10.3390/ijms222111721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584100PMC
October 2021

Evaluation of pelvic floor muscle function (PFMF) in cervical cancer patients with Querleu-Morrow type C hysterectomy: a multicenter study.

Arch Gynecol Obstet 2021 Oct 28. Epub 2021 Oct 28.

Department of OB/Gyn, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng Dist., Beijing, 100044, China.

Introduction: To evaluate the pelvic floor muscle function (PFMF) of cervical cancer patients after type QM-C hysterectomy and to explore the relationship between decreased PFMF and related factors.

Methods: This was a multi-centered retrospective cohort study. 181 cervical cancer patients who underwent type QM-C hysterectomy were enrolled from 9 tertiary hospitals. Strength of PFMF were measured using neuromuscular apparatus (Phenix U8, French). Risk factors contributing to decreased PFMF were analyzed by univariate and multivariate ordinal polytomous logistic regression.

Results: Totally 181 patients were investigated in this study. 0-3 level of type I muscle fibre strength (MFSI) was 52.6% (95/181), 0-3 level of type IIA muscle fibre strength (MFSIIA) was 50% (91/181). Subjective stress urinary incontinence was 46% (84/181), urinary retention was 27.3% (50/181), dyschezia was 41.5% (75/181), fecal incontinence was 9% (18/181). ① MFSI: Multivariate ordinal polytomous logistic regression shows that the follow-up time (p < 0.05), chemotherapy and radiotherapy (p = 0.038) are independent risk factors of MFSI's reduction after type QM-C hysterectomy. ② MFSIIA: multivariate ordinal polytomous logistic regression shows that the follow-up time (p < 0.05) are independent risk factors of MFSIIA's reduction after type QM-C hysterectomy. The pelvic floor muscle strength (PFMS) increased after 9 months than in 9 months after operation, which showed that the PFMS could be recovered after operation.

Conclusions: We advocate for more attention and emphasis on the PFMF of Chinese female patients with cervical cancer postoperation.

Peking University People's Hospital: PFMF after QM-C hysterectomy has not been analyzed by current study. The contribution is that patients with radical hysterectomy should do pelvic floor rehabilitation exercises in 3 months after operation. Clinical Trails NCT number of this study is 02492542.
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http://dx.doi.org/10.1007/s00404-021-06290-6DOI Listing
October 2021

Letter to the Editor From Bin Zhou et al: "Association Between Body Weight and Telomere Length Is Predominantly Mediated Through C-Reactive Protein".

J Clin Endocrinol Metab 2021 Oct 23. Epub 2021 Oct 23.

Fuwai Hospital, National Centre for Cardiovascular Diseases, National Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.1210/clinem/dgab764DOI Listing
October 2021

Excited-state engineering of oligothiophenes phosphorus chemistry towards strong fluorescent materials.

Phys Chem Chem Phys 2021 Nov 3;23(42):24265-24272. Epub 2021 Nov 3.

School of Physical Science and Technology, ShanghaiTech University, 201210 Shanghai, People's Republic of China.

Due to efficient intersystem crossing (ISC), combined with efficient non-radiative processes of the triplet excited state, oligothiophenes generally exhibit very weak photoluminescence. Phosphorus (P)-bridged terthiophenes (P-terThs) and phosphorus (P)-bridged bithiophenes (P-biThs) were synthesized. The diverse and well-defined P-chemistry has been applied to fine tune the photophysical properties of these materials. The asymmetric electronic coupling between the P-center and terThs suppressed the electronic interactions of two terTh and biTh moieties in the ground state S. Particularly, P-terThs and P-biThs having a positively charged P(+)-center induce pronounced asymmetric electronic environments on the two terThs and two biThs, respectively, which allows relaxation from the initial excited state symmetry breaking charge transfer (SBCT) to give the charge separated state S. P-terThs and P-biThs having a positively charged P(+)-center exhibit stronger SBCT than others, which may result in a weaker ISC of oligothiophenes, and consequently lead to the photoluminescence quantum yields (PLQYs) being as high as 71% and 39%, respectively. The current study uncovered detailed insights on the effects of phosphorus chemistry on the SBCT of oligothiophenes and their resulting effects on the photophysical properties of P-bridged oligothiophenes, which have not been previously addressed in oligothiophenes.
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http://dx.doi.org/10.1039/d1cp03737dDOI Listing
November 2021

The betaine-dependent remethylation pathway is a homocysteine metabolism pathway associated with the carnivorous feeding habits of spiders.

Insect Sci 2021 Oct 14. Epub 2021 Oct 14.

Key laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Nanjing, 210095, China.

Homocysteine (Hcy) is a sulfur-containing amino acid derived from the essential amino acid methionine (Met). Circulating levels of Hcy in animals can be increased by feeding on Met-enriched diets, which is generally considered harmful. Spiders are one of the largest groups of obligate carnivores and feed on animals high in protein and Met. We analyzed the Hcy metabolism pathways in 18 species of three taxa (Mammalia, Insecta, and Arachnida) and found that the betaine-dependent remethylation pathway (BRP) was present in all carnivorous arachnid species and mammals but absent in insects and red spider mites. We then studied the Hcy metabolism pathway in Pardosa pseudoannulata. In P. pseudoannulata, Hcy is metabolized through the transsulfuration pathway, BRP, and S-methylmethionine-dependent remethylation pathway. Because of a prior duplication event of the betaine homocysteine S-methyltransferase (BHMT) gene in the BRP, BHMTa and BHMTb are present in tandem in the genome of P. pseudoannulata. The high expression levels of BHMTa and its high abundance in detoxification tissues indicate that it plays an important role in the BRP; the ability of BHMTa and BHMTb to remethylate Hcy using betaine as substrate was similar. Compared with other Hcy metabolic enzyme genes, BHMT responded quickly to the application of Hcy or betaine. In sum, the BRP is important in Hcy metabolism in P. pseudoannulata and in other spider species. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/1744-7917.12976DOI Listing
October 2021

Triple therapy with adalimumab, ustekinumab and methotrexate for induction of remission in moderate to severe ileocolonic Crohn's disease with upper gastrointestinal involvement in a biologic-experienced individual.

BMJ Case Rep 2021 Oct 13;14(10). Epub 2021 Oct 13.

Department of Medicine, Division of Gastroenterology, University of Kansas Medical Center, Kansas City, Kansas, USA

Induction of remission in biologic-experienced individuals with moderate to severe Crohn's disease (CD) can be a challenge. We hereby present a case of CD with secondary non-response to infliximab. Adding methotrexate and switching to ustekinumab plus methotrexate did not stop the inflammatory process. Therefore, combination therapy with two classes of biologics consisting of ustekinumab and adalimumab plus methotrexate was initiated. He achieved clinical remission in 4 weeks and remained on triple therapy for 6 months which was subsequently tailored to adalimumab/methotrexate combination therapy due to insurance restriction on ustekinumab. He remained in remission for the duration of follow-up, 14 months after initiation of triple therapy and 8 months after switching to methotrexate/adalimumab biologic monotherapy. Triple therapy with anti-TNF, IL-12/23 inhibitor and methotrexate could potentially be an option for induction of remission in biologic-experienced individuals with good initial clinical response to anti-TNF agents.
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http://dx.doi.org/10.1136/bcr-2021-243500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515434PMC
October 2021

The FGFR Family Inhibitor AZD4547 Exerts an Antitumor Effect in Ovarian Cancer Cells.

Int J Mol Sci 2021 Oct 6;22(19). Epub 2021 Oct 6.

Department of Gynecology and Obstetrics, School of Medicine, Keimyung University, Daegu 42601, Korea.

The dysregulation of fibroblast growth factor (FGF) signaling has been implicated in tumorigenesis, tumor progression, angiogenesis, and chemoresistance. The small-molecule AZD4547 is a potent inhibitor of FGF receptors. This study was performed to investigate the antitumor effects and determine the mechanistic details of AZD4547 in ovarian cancer cells. AZD4547 markedly inhibited the proliferation and increased the apoptosis of ovarian cancer cells. AZD4547 also suppressed the migration and invasion of ovarian cancer cells under nontoxic conditions. Furthermore, it attenuated the formation of spheroids and the self-renewal capacities of ovarian cancer stem cells and exerted an antiangiogenic effect. It also suppressed in vivo tumor growth in mice. Collectively, this study demonstrated the antitumor effect of AZD4547 in ovarian cancer cells and suggests that it is a promising agent for ovarian cancer therapy.
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http://dx.doi.org/10.3390/ijms221910817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509426PMC
October 2021

Modular ketal-linked prodrugs and biomaterials enabled by organocatalytic transisopropenylation of alcohols.

Nat Commun 2021 09 20;12(1):5532. Epub 2021 Sep 20.

Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology and Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, P.R. China.

Isopropenyl ethers are critical intermediates for accessing medicinally valuable ketal-based prodrugs and biomaterials, but traditional approaches for the synthesis of isopropenyl ethers suffer from poor functional group compatibility and harsh reaction conditions. Here, we develop an organocatalytic transisopropenylation approach to solve these challenges, enabling the synthesis of isopropenyl ethers from various hydroxyl-group-containing small-molecule drugs, polymers, and functional building blocks. The method provides a straightforward and versatile synthesis of isopropenyl ethers, features excellent tolerance of diverse functional groups, applies to a wide range of substrates, and allows scalable synthesis. The development of this organocatalytic transisopropenylation approach enables access to modular preparation of various acid-sensitive ketal-linked prodrugs and functionalized ketalated biomaterials. We expect our syntheses and transformations of isopropenyl ethers will find utility in several diverse fields, including medicinal chemistry, drug delivery, and biomaterials.
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http://dx.doi.org/10.1038/s41467-021-25856-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452702PMC
September 2021

The short-term efficacy of DEB-TACE loaded with epirubicin and raltitrexed in the treatment of intermediate and advanced primary hepatocellular carcinoma.

Am J Transl Res 2021 15;13(8):9562-9569. Epub 2021 Aug 15.

Department of Oncology, Ji'an Central Hospital Ji'an, Jiangxi Province, China.

Objective: To investigate the short-term efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) loaded with epirubicin and raltitrexed in the treatment of intermediate and advanced primary hepatocellular carcinoma (PHC).

Methods: One hundred patients with intermediate or advanced PHC were randomly divided into a control group (the CG, n=50) and an observation group (the OG, n=50). The CG was treated with conventional TACE (cTACE), and the OG was treated with DEB-TACE loaded with epirubicin and raltitrexed. The overall efficiency, the liver function indices, the tumor markers, the macrophage migration inhibitory factor (MIF) levels , the lesion diameters, the Child-Pugh scores, the adverse reactions, the median times to disease progression, the 1-year and 2-year recurrence rates, and the survival rates were compared between the two groups.

Results: At 6 months after the surgery, the overall response rate in the OG (82.00%) was higher than it was in the CG (62.00%) (<0.05). The serum alanine aminotransferase, total bilirubin, and aspartate aminotransferase levels were elevated in both groups after the intervention, but they were lower in the OG than they were in the CG (<0.05). The serum alpha-fetoprotein, carcinoembryonic antigen, and MIF levels, and the lesion diameters were lower in both groups at one month after the intervention, and they were lower in the OG than they were in the CG (<0.05). The incidence of abnormal blood test results in the OG was lower than it was in the CG (<0.05). The OG also exhibited a longer median time to disease progression, lower 1-year and 2-year recurrence rates, and higher 1- and 2-year survival rates than the CG (<0.05).

Conclusion: DEB-TACE loaded with epirubicin and raltitrexed improves the short-term outcomes, reduces the tumor load, decreases the incidence of adverse events, and improves the survival rate in patients with intermediate and advanced PHC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430112PMC
August 2021

Impact of Injection Frequency of Adipose-Derived Stem Cells on Allogeneic Skin Graft Survival Outcomes in Mice.

Cell Transplant 2021 Jan-Dec;30:9636897211041966

Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Previous studies indicated that mesenchymal stem cells (MSCs) exhibit immunomodulatory properties in composite tissue allotransplantation. However, due to the high immunogenicity of skin, although the single administration of MSCs improves survival of the skin allotransplant, immune rejection is still inevitable. The aim of our study was to evaluate whether multiple administrations of MSCs would improve immune tolerance in the allogeneic skin graft, compared to that with a single administration in a mouse model. After full-thickness skin allotransplantation on the backs of the mice, the recipient mice were infused with phosphate-buffered saline and isogenic 1.5 × 10/mL adipose-derived stem cells (ADSCs). ADSCs were transplanted into different mice according to the different injection frequencies such as single, once a week, and twice a week. Skin sections were taken on days 7 and 21 post-transplantation in all groups for gene expression and histological studies. ADSCs increased skin allograft survival compared to that in control mice ( < 0.05). Interleukin-6 and tumor necrosis factor-alpha messenger RNA levels were decreased, and the abundance of lymphocytes, based on immunohistochemistry, was also decreased in ADSC-infused mice ( 0.05). However, among the different ADSC injection frequency groups, multiple ADSC infusion did not improve the survival rate and decreased proinflammatory cytokines and lymphocytes, compared to those with the single administration of ADSCs ( 0.05). Conversely, the results with single administration were slightly better than those with multiple administrations. Our study demonstrated that ADSCs have the potential for immunomodulation in vivo. However, the results with multiple ADSC administration were not as good as those with single administration, which indicates the complexity of ADSCs in vivo and implying the need for adequate preclinical experimentation.
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http://dx.doi.org/10.1177/09636897211041966DOI Listing
September 2021

TLRs induce Th1/Th2 responses by affecting the secretion of CCL2 at the maternal-foetal interface.

Int Immunopharmacol 2021 Nov 25;100:108070. Epub 2021 Aug 25.

Reproductive Medical Center, Department of Gynecology and Obstetrics, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address:

Research Question: In previous studies, we demonstrated that the human decidua and decidual stromal cells express high levels of CCL2 (chemokine (C-C motif) ligand 2, also known as monocyte chemotactic protein-1) and its receptor CCR2 (chemokine receptor 2). DSC-derived CCL2 interacts with CCR2 on DICs, causing the production and secretion of Th2-type cytokines, which promotes a Th2 bias at the maternal-foetal interface. Many pathogens may be present in the genital tract during pregnancy, but whether they affect immune regulation, especially Th2 regulation remains unknown. Toll-like receptors (TLRs) are a family of pattern-recognition receptors that recognise specific components of microbes and certain host molecules and play an important role in the host innate immune response. We examined TLR expression and evaluated whether TLRs could affect CCL2 secretion and subsequently induce Th1/Th2 responses.

Design: We used quantitative real-time PCR to measure TLR expression in the decidua and DSCs (decidual stromal cells). DSCs were cultured in the presence or absence of the TLR2 agonists PAM3CSK4, PGN-Sa, and zymosan, the TLR3 agonist poly (I:C) and the TLR4 agonist LPS. Then, the supernatants were assayed for CCL2 secreted by DSCs and IL-4, IFN-γ, IL-10, and TNF-α produced by DICs.

Results: Costimulation with TLR2, TLR3 and TLR4 agonists resulted in enhancing CCL2 production compared with that in the controls. Additionally, these TLR2, 3, and 4 agonists stimulated CD80/CD86 on DSCs and regulated IL-4 and IL-10 secretion on DICs. TLR2 and TLR3 agonists may promote Th1/Th2 immune bias.

Conclusions: TLRs may induce Th1/Th2 responses by affecting the secretion of CCL2 at the maternal-foetal interface.
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http://dx.doi.org/10.1016/j.intimp.2021.108070DOI Listing
November 2021

The Role of Apoptosis Pathway in the Cytotoxicity Induced by Fresh and Aged Zinc Oxide Nanoparticles.

Nanoscale Res Lett 2021 Aug 9;16(1):129. Epub 2021 Aug 9.

Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, No. 81, Mei-Shan Road, Hefei, 230032, Anhui, People's Republic of China.

Zinc oxide nanoparticles (ZnO NPs) are used in a wide range of applications including industry, commercial products and medicine field. Numerous mechanistic studies for ZnO NPs' toxicity were performed on pristine (fresh) NPs. However, the cytotoxicity induced by the transformed (aged) ZnO NPs and the underlying mechanisms remain unclear. Here, we observed the physicochemical transformation of ZnO NPs underwent over time, followed by evaluating the cytotoxicity of fresh and aged NPs. We found that fresh ZnO NPs induced higher apoptosis level than their aged counterparts. Accordingly, RNA sequencing data from aged ZnO NP-treated human-hamster hybrid (A) cells showed that p53, PI3k-Akt, FoXO, Glutathione, ErbB, HIF-1, Oxytocin and Jak-STAT signaling pathways were enriched but no apoptosis pathway. Quantitative PCR results revealed the significantly higher mRNA level of IL1B and CD69 in fresh NP-treated groups compared to that of aged ZnO NP- and zinc chloride-treated groups. The above results indicated that the lower cytotoxicity of aged ZnO NPs is partially attributed to their reduced potency in inducing apoptosis. The transcriptional regulation of multiple signal pathways activated by aged NPs may help to build the cellular homeostasis. Taken together, our findings highlight the influence of aging (environmental transformation) process of ZnO NPs on their toxicities and biological consequences.
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http://dx.doi.org/10.1186/s11671-021-03587-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353024PMC
August 2021

Daratumumab Immunopolymersome-Enabled Safe and CD38-Targeted Chemotherapy and Depletion of Multiple Myeloma.

Adv Mater 2021 Oct 8;33(39):e2007787. Epub 2021 Aug 8.

Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and, Materials Science, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, P. R. China.

Multiple myeloma (MM) is a second ranking hematological malignancy. Despite the fast advancement of new treatments such as bortezormib and daratumumab, MM patients remain incurable and tend to eventually become relapsed and drug-resistant. Development of novel therapies capable of depleting MM cells is strongly needed. Here, daratumumab immunopolymersomes carrying vincristine sulfate (Dar-IPs-VCR) are reported for safe and high-efficacy CD38-targeted chemotherapy and depletion of orthotopic MM in vivo. Dar-IPs-VCR made by postmodification via strain-promoted click reaction holds tailored antibody density (2.2, 4.4 to 8.7 Dar per IPs), superb stability, small size (43-49 nm), efficacious VCR loading, and glutathione-responsive VCR release. Dar -IPs-VCR induces exceptional anti-MM activity with an IC of 76 × 10 m to CD38-positive LP-1 MM cells, 12- and 20-fold enhancement over nontargeted Ps-VCR and free VCR controls, respectively. Intriguingly, mice bearing orthotopic LP-1-Luc MM following four cycles of i.v. administration of Dar -IPs-VCR at 0.25 mg VCR equiv. kg reveal complete depletion of LP-1-Luc cells, superior survival rate to all controls, and no body weight loss. The bone and histological analyses indicate bare bone and organ damage. Dar-IPs-VCR appears as a safe and targeted treatment for CD38-overexpressed hematological malignancies.
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http://dx.doi.org/10.1002/adma.202007787DOI Listing
October 2021

Comparison of Different Methods for Spongin-like Collagen Extraction from Marine Sponges ( and ): Physicochemical Properties and In Vitro Biological Analysis.

Membranes (Basel) 2021 Jul 12;11(7). Epub 2021 Jul 12.

Department of Biosciences, Universidade Federal de São Paulo (UNIFESP), Santos 11015-220, SP, Brazil.

This study aimed to compare different protocols (Protocol 1: P1; Protocol 2: P2; Protocol 3: P3; Protocol 4: P4) for the extraction of spongin-like collagen (SC) from marine sponges. The SEM micrographs demonstrated a fibrillar structure for the extracts from and the nodular/particulate aggregates for . FTIR showed for all samples peaks similar to collagen for both species. For , the extracts obtained using P2, P3, and P4 protocols presented higher values of extraction yield, TPQ, and GAGs. P2 and P4 showed higher values of SC concentration and for antioxidant analysis. For , P2, P3, and P4 provided a higher extraction yield besides an increase in the antioxidant assay. For both species, no difference was observed for Col quantification and TPQ analysis; also, higher values of GAGs were found using P2 and P4. Fibroblast proliferation observed for was lower for P1 on day 1 and for P2 and P3 on day 3 (for 50%) compared to the control group. There was a significant reduction in fibroblast cell proliferation for all extracts evaluated. It can be concluded that protocols P2 and P4 were more efficient for extracting SC from .
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http://dx.doi.org/10.3390/membranes11070522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304306PMC
July 2021

Development of a Primary Care Transitions Clinic in an Academic Medical Center.

J Gen Intern Med 2021 Jul 29. Epub 2021 Jul 29.

Brigham Health Physician's Organization, 75 Francis Street, Boston, MA, 02215, USA.

Introduction: Transitions of care experiences leave patients vulnerable to adverse outcomes, including readmissions, worsening symptoms, and reductions in functional status.

Aim: To describe and evaluate a primary care transitions clinic that serves patients with medical and/or social needs that must be addressed prior to establishment of primary care.

Setting: Brigham Health, an academic medical center in Boston, MA.

Program Description: The transitions clinic opened within an existing primary care practice in January 2019. It employs one full-time nurse care coordinator and one full-time medical assistant, and is staffed by one primary care physician (PCP) or nurse practitioner each weekday afternoon. Both medical and social diagnoses that require follow-up post-discharge are addressed. Patients with any insurance are seen as many times as necessary until PCP care is established.

Program Evaluation: In the year after its establishment (January 20, 2019, to January 19, 2020), the transitions clinic received 498 referrals (73.2% from the emergency department (ED), 23.3% from inpatient), with 207 patients ultimately seen. Patients were seen 5 (median; IQR 4-6) work days post-discharge, with 2 (median; IQR 1-3) visits per patient. Patients seen in the transitions clinic had significantly fewer ED visits than a comparator cohort referred to Brigham Health Primary Care after ED or hospital discharge in the year prior (January 20, 2018, to January 20, 2019). Patients seen in the transitions clinic additionally had significantly fewer ED visits and hospitalizations in the three months post-referral than in the three months pre-referral. The most common social determinants addressed by the clinic's nurse coordinator were insurance, transportation, and housing.

Discussion: A primary care transitions clinic can provide accessible, attentive care post-discharge with positive effects on healthcare utilization. Availability of a multidisciplinary team that can see patients for repeated visits until establishment of PCP care was a key success factor for the transitions clinic.
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http://dx.doi.org/10.1007/s11606-021-07019-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321504PMC
July 2021

Protective Effect of Jiang Tang Xiao Ke Granules against Skeletal Muscle IR via Activation of the AMPK/SIRT1/PGC-1 Signaling Pathway.

Oxid Med Cell Longev 2021 3;2021:5566053. Epub 2021 Jul 3.

College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

The Jiang Tang Xiao Ke (JTXK) granule is a classic Chinese herbal formula that has been put into clinical use in the treatment of type 2 diabetes mellitus for decades. However, whether its ability to ameliorate skeletal muscle insulin resistance (IR) is through modulation of the AMPK/SIRT1/PGC-1 signaling pathway remains unknown. Therefore, we aimed to investigate the effects of JTXK granules on IR in skeletal muscle of high-fat diet-induced diabetic mice and C2C12 cells and analyze the underlying mechanisms. In the present study, we showed that JTXK granules attenuated body weight gain, reduced body fat mass, improved body lean mass, and enhanced muscle performance of diabetic mice. JTXK granules also improved glucose metabolism and skeletal muscle insulin sensitivity and partially reversed abnormal serum lipid levels, which might be related to the regulation of the AMPK/SIRT1/PGC-1 pathway, both in skeletal muscle tissue of diabetic mice and in C2C12 cells. Furthermore, drug-containing serum of JTXK granules was capable of enhancing glucose uptake and mitochondrial respiration in C2C12 cells, and AMPK was proven to be closely involved in this process. Taken together, these results suggest that the JTXK granule ameliorates skeletal muscle IR through activation of the AMPK/SIRT1/PGC-1 signaling pathway, which offers a novel perspective of this formula to combat IR-related metabolic diseases.
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http://dx.doi.org/10.1155/2021/5566053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277912PMC
July 2021

An Activity-Based Sensing Fluorogenic Probe for Monitoring Ethylene in Living Cells and Plants.

Angew Chem Int Ed Engl 2021 09 26;60(40):21934-21942. Epub 2021 Aug 26.

Key Laboratory of Plant Immunity, College of Plant Protection, Nanjing Agricultural University, Nanjing, 210095, P. R. China.

Ethylene (ET) is an important gaseous plant hormone. It is highly desirable to develop fluorescent probes for monitoring ethylene in living cells. We report an efficient Rh -catalysed coupling of N-phenoxyacetamides to ethylene in the presence of an alcohol. The newly discovered coupling reaction exhibited a wide scope of N-phenoxyacetamides and excellent regioselectivity. We successfully developed three fluorophore-tagged Rh -based fluorogenic coumarin-ethylene probes (CEPs) using this strategy for the selective and quantitative detection of ethylene. CEP-1 exhibited the highest sensitivity with a limit of detection of ethylene at 52 ppb in air. Furthermore, CEP-1 was successfully applied for imaging in living CHO-K1 cells and for monitoring endogenous-induced changes in ethylene biosynthesis in tobacco and Arabidopsis thaliana plants. These results indicate that CEP-1 has great potential to illuminate the spatiotemporal regulation of ethylene biosynthesis and ethylene signal transduction in living biological systems.
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http://dx.doi.org/10.1002/anie.202108335DOI Listing
September 2021

The importance of vitellogenin receptors in the oviposition of the pond wolf spider, Pardosa pseudoannulata.

Insect Sci 2021 Jul 8. Epub 2021 Jul 8.

Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Nanjing, 210095, China.

Vitellogenin receptor (VgR) is crucial for vitellogenin (Vg) uptake by oocytes. VgR is less known in Arachnida, especially in spiders. Different from only one VgR in an arthropod species, two VgRs, VgR-1 and VgR-2, were found in the pond wolf spider, Pardosa pseudoannulata. Both VgRs had the typical domains of the low-density lipoprotein receptor family except for the absence of the ligand-binding domain 1 in VgR-2. Spatiotemporal expression profiles showed that two VgR genes were consistently highly expressed in females and their ovaries, but VgR-1 was 48-fold that of VgR-2 in ovaries. The transcriptional level of VgR-1 was significantly downregulated by RNAi, but it did not work for VgR-2 although several trials were performed. Vg-1 and Vg-2 might be the ligands of VgR-1 because their expressions were also decreased in the dsVgR-1-treated females. Silencing VgR-1 prolonged the pre-oviposition period by 56 h. The expression of VgRs and Vgs were upregulated by juvenile hormones (JHs), which suggested that JHs were the essential factors to vitellogenesis in the spider. The present study revealed the importance of VgR-1 in the spider oviposition, which will improve the understanding on VgR physiological functions in spiders.
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http://dx.doi.org/10.1111/1744-7917.12933DOI Listing
July 2021

Multiple Magnetic Topological Phases in Bulk van der Waals Crystal MnSb_{4}Te_{7}.

Phys Rev Lett 2021 Jun;126(24):246601

School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China.

The magnetic van der Waals crystals MnBi_{2}Te_{4}/(Bi_{2}Te_{3})_{n} have drawn significant attention due to their rich topological properties and the tunability by external magnetic field. Although the MnBi_{2}Te_{4}/(Bi_{2}Te_{3})_{n} family have been intensively studied in the past few years, their close relatives, the MnSb_{2}Te_{4}/(Sb_{2}Te_{3})_{n} family, remain much less explored. In this work, combining magnetotransport measurements, angle-resolved photoemission spectroscopy, and first principles calculations, we find that MnSb_{4}Te_{7}, the n=1 member of the MnSb_{2}Te_{4}/(Sb_{2}Te_{3})_{n} family, is a magnetic topological system with versatile topological phases that can be manipulated by both carrier doping and magnetic field. Our calculations unveil that its A-type antiferromagnetic (AFM) ground state stays in a Z_{2} AFM topological insulator phase, which can be converted to an inversion-symmetry-protected axion insulator phase when in the ferromagnetic (FM) state. Moreover, when this system in the FM phase is slightly carrier doped on either the electron or hole side, it becomes a Weyl semimetal with multiple Weyl nodes in the highest valence bands and lowest conduction bands, which are manifested by the measured notable anomalous Hall effect. Our work thus introduces a new magnetic topological material with different topological phases that are highly tunable by carrier doping or magnetic field.
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http://dx.doi.org/10.1103/PhysRevLett.126.246601DOI Listing
June 2021

The clinical guiding value of a radiomics model for androgen deprivation therapy for prostate cancer.

J Int Med Res 2021 Jun;49(6):3000605211014301

Department of Imaging Diagnosis, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.

Objective: Three models were used to evaluate prostate cancer after androgen deprivation therapy (ADT) and to determine the value of detecting residual lesions after treatment.

Methods: We retrospectively analysed patients with prostate cancer who received ADT from January 2018 to June 2019. Patients were divided into ADT responder and ADT non-responder groups, and clinical risk factors were determined. Regions of interest were manually contoured on each slice on fat-saturated-T2-weighted imaging, and radiomic features were extracted. Uni- and multivariate logistic regression were used to establish radiomics, clinical and combined models.

Results: There were 23 ADT non-responders and 20 ADT responders. In the clinical model, total prostate-specific antigen concentration and T stage were independent predictors of efficacy (area under the curve (AUC) = 0.774). The characteristics, MinIntensity and Correlation_ angle135_offset4 indicated an effective clinical model (AUC = 0.807). GLCMEntropy_ AllDirection_offset1_SD was the best feature to differentiate residual lesions from the central gland (CG) (Lesion-CG model, AUC = 0.955). Correlation_angle135_offset4, GLCMEntropy_ AllDirection_offset4_SD and GLCMEntropy_AllDirection_offset7_SD differentiated residual lesions from the peripheral zone (PZ) (Lesion-PZ model, AUC = 0.855). The AUC for the combined model was 0.904.

Conclusions: Our models can guide the clinical treatment of patients with different ADT responses. Furthermore, the radiomics model can detect prostate cancer that is non-responsive to ADT.
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http://dx.doi.org/10.1177/03000605211014301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258766PMC
June 2021

Roles of IL-25 in Type 2 Inflammation and Autoimmune Pathogenesis.

Front Immunol 2021 28;12:691559. Epub 2021 May 28.

Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China.

Interleukin-17E (IL-25) is a member of the IL-17 cytokine family that includes IL-17A to IL-17F. IL-17 family cytokines play a key role in host defense responses and inflammatory diseases. Compared with other IL-17 cytokine family members, IL-25 has relatively low sequence similarity to IL-17A and exhibits a distinct function from other IL-17 cytokines. IL-25 binds to its receptor composed of IL-17 receptor A (IL-17RA) and IL-17 receptor B (IL-17RB) for signal transduction. IL-25 has been implicated as a type 2 cytokine and can induce the production of IL-4, IL-5 and IL-13, which in turn inhibits the differentiation of T helper (Th) 17. In addition to its anti-inflammatory properties, IL-25 also exhibits a pro-inflammatory effect in the pathogenesis of Th17-dominated diseases. Here, we review recent advances in the roles of IL-25 in the pathogenesis of inflammation and autoimmune diseases.
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http://dx.doi.org/10.3389/fimmu.2021.691559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194343PMC
October 2021

Effects of Salvianolic acid B on RNA expression and co-expression network of lncRNAs in brown adipose tissue of obese mice.

J Ethnopharmacol 2021 Oct 4;278:114289. Epub 2021 Jun 4.

Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, China. Electronic address:

Ethnopharmacological Relevance: Salvianolic acid B (SalB) is a polyphenolic compound in Salvia miltiorrhiza Bunge ("Danshen"), which has been largely used in Traditional Chinese Medicine for the treatment of metabolic syndrome, obesity, diabetes, among others.

Aim Of Study: This study was to investigate the effects of Salvianolic acid B (SalB) on mRNA, lncRNA and circRNA's expression profile in brown adipose tissue (BAT) of obese mice.

Materials And Methods: High-fat-diet induced obese C57BL/6J mice were treated with SalB (100 mg/kg/day) for 8 weeks. Then, BAT was harvested for RNA-Seq analysis. Differentially expressed mRNAs, lncRNAs and circRNAs were analyzed using the Illumina Hiseq 4000. Following this procedure, bioinformatic tools including Gene ontology (GO), KEGG pathway and lncRNA-mRNA co-network analysis were utilized. Finally, RT-qPCR was performed to validate the differentially expressed RNAs.

Results: Compared with control group, 2532 mRNAs, 774 lncRNAs and 25 circRNAs were differentially expressed in SalB group. Additionally, 40 upregulated and 109 downregulated gene-related pathways were identified in the SalB group. Among them, metabolic pathways showed the highest enrichment coefficient in upregulated genes. Moreover, 54 up-regulated and 626 down-regulated coding mRNAs associated with lncRNA-Hsd11b1 and lncRNA-Vmp1.

Conclusions: SalB may play an anti-obesity role by adjusting the expression of mRNAs correlated with inflammatory response and energy metabolism through regulating the expression of lncRNA-Hsd11b1. The findings of this research provide new directions to study the mechanisms of SalB, and would open therapeutic avenues for the treatment of obesity.
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http://dx.doi.org/10.1016/j.jep.2021.114289DOI Listing
October 2021

Corneal Epithelial Thickness Changes Following SMILE for Myopia With High Astigmatism.

J Refract Surg 2021 Apr 1;37(4):224-230. Epub 2021 Apr 1.

Purpose: To evaluate the corneal epithelial thickness (CET) profile changes after small incision lenticule extraction (SMILE) surgery for myopic astigmatism correction of greater than 2.00 diopters (D).

Methods: This prospective observational study included 40 eyes (23 patients) treated with SMILE for myopia with cylinders of -2.25 to -4.50 D. Along with standard ophthalmic examinations, CET maps with a diameter of 9 mm were measured by high-resolution spectral-domain optical coherence tomography preoperatively and postoperatively. Correlations between the degree of residual astigmatism and the difference in CET values between preoperative flat and steep meridians were analyzed.

Results: The CET showed significant changes in the central (2 mm), paracentral (2 to 5 mm), midperipheral (5 to 7 mm), and peripheral (7 to 9 mm) zones 6 months after SMILE ( < .001). Among the regions, the CET in the paracentral zones displayed the largest increase (9.75%) with the highest average thickness (57.29 µm). Moreover, symmetrical regional epithelial thickening at the preoperative astigmatism axis was observed in the midperipheral zones. The difference in CET between preoperative flat and steep meridians in the mid-peripheral zones continuously increased from postoperative 1 day to 6 months. This difference was positively correlated with the residual cylinder errors at 6 months postoperatively ( = -0.334, = .035).

Conclusions: The 9-mm diameter CET in eyes with high astigmatism significantly increased 6 months after SMILE. Additionally, the difference in CET between preoperative flat and steep meridians in midperipheral zones may be related to astigmatic undercorrection in SMILE. .
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http://dx.doi.org/10.3928/1081597X-20210126-01DOI Listing
April 2021

Curcumin improves adipocytes browning and mitochondrial function in 3T3-L1 cells and obese rodent model.

R Soc Open Sci 2021 Mar 17;8(3):200974. Epub 2021 Mar 17.

Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China.

Accumulating evidence suggests that mitochondrial dysfunction and adipocyte differentiation promote lipid accumulation in the development of obesity and diabetes. Curcumin is an active ingredient extracted from that has been shown to exhibit antioxidant and anti-inflammatory potency in metabolic disorders. However, the underlying mechanisms of curcumin in adipocytes remain largely unexplored. We studied the effects of curcumin on adipogenic differentiation and mitochondrial oxygen consumption and analysed the possible mechanisms. 3T3-L1 preadipocytes were used to assess the effect of curcumin on differentiation of adipocytes. The Mito Stress Test measured by Seahorse XF Analyzer was applied to investigate the effect of curcumin on mitochondrial oxygen consumption in 3T3-L1 adipocytes. The effect of curcumin on the morphology of both white and brown adipose tissue (WAT and BAT) was evaluated in a high-fat diet-induced obese mice model. We found that curcumin dose-dependently (10, 20 and 35 µM) induced adipogenic differentiation and the intracellular fat droplet accumulation. Additionally, 10 µM curcumin remarkably enhanced mature adipocyte mitochondrial respiratory function, specifically, accelerating basic mitochondrial respiration, ATP production and uncoupling capacity via the regulation of peroxisome proliferator-activated receptor γ (PPARγ) ( < 0.01). Curcumin administration also attenuated the morphological changes in adipose tissues in high-fat diet-induced obese mice. Moreover, curcumin markedly increased the mRNA and protein expressions of mitochondrial uncoupling protein 1 (UCP1), PPARγ, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and PR domain protein 16 (PRDM16) and . Collectively, the results demonstrate that curcumin promotes the adipogenic differentiation of preadipocytes and mitochondrial oxygen consumption in 3T3-L1 mature adipocytes by regulating UCP1, PRDM16, PPARγ and PGC-1α expression.
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http://dx.doi.org/10.1098/rsos.200974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074937PMC
March 2021

Neonicotinoids stimulate H-limited methane emission in Periplaneta americana through the regulation of gut bacterium community.

Environ Pollut 2021 Sep 27;285:117237. Epub 2021 Apr 27.

Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Weigang 1, Nanjing, 210095, China. Electronic address:

Methane emitted by insects is considered to be an important source of atmospheric methane. Here we report the stimulation of methane emission in the cockroach Periplaneta americana and termite Coptotermes chaohuensis, insects with abundant methanogens, by neonicotinoids, insecticides widely used to control insect pests. Cycloxaprid (CYC) and imidacloprid (IMI) caused foregut expansion in P. americana, and increased the methane emission. Antibiotics mostly eliminated the effects. In P. americana guts, hydrogen levels increased and pH values decreased, which could be significantly explained by the gut bacterium community change. The proportion of several bacterium genera increased in guts following CYC treatment, and two genera from four could generate hydrogen. Hydrogen is a central intermediate in methanogenesis. All increased methanogens in both foregut and hindgut used hydrogen as electron donor to produce methane. Besides, the up-regulation of mcrA, encoding the enzyme for the final step of methanogenesis suggested the enhanced methane production ability in present methanogens. In the termite, hydrogen levels in gut and methane emission also significantly increased after neonicotinoid treatment, which was similar to the results in P. americana. In summary, neonicotinoids changed bacterium community in P. americana gut to generate more hydrogen, which then stimulated gut methanogens to produce and emit more methane. The finding raised a new concern over neonicotinoid applications, and might be a potential environmental risk associated with atmospheric methane.
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http://dx.doi.org/10.1016/j.envpol.2021.117237DOI Listing
September 2021

New Trends in Pharmacological Treatments for Osteoarthritis.

Front Pharmacol 2021 15;12:645842. Epub 2021 Apr 15.

Department of Rheumatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.

Osteoarthritis (OA) is the leading cause of function loss and disability among the elderly, with significant burden on the individual and society. It is a severe disease for its high disability rates, morbidity, costs, and increased mortality. Multifactorial etiologies contribute to the occurrence and development of OA. The heterogeneous condition poses a challenge for the development of effective treatment for OA; however, emerging treatments are promising to bring benefits for OA management in the future. This narrative review will discuss recent developments of agents for the treatment of OA, including potential disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics for pain relief. This review will focus more on drugs that have been in clinical trials, as well as attractive drugs with potential applications in preclinical research. In the past few years, it has been realized that a complex interaction of multifactorial mechanisms is involved in the pathophysiology of OA. The authors believe there is no miracle therapeutic strategy fitting for all patients. OA phenotyping would be helpful for therapy selection. A variety of potential therapeutics targeting inflammation mechanisms, cellular senescence, cartilage metabolism, subchondral bone remodeling, and the peripheral nociceptive pathways are expected to reshape the landscape of OA treatment over the next few years. Precise randomized controlled trials (RCTs) are expected to identify the safety and efficacy of novel therapies targeting specific mechanisms in OA patients with specific phenotypes.
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http://dx.doi.org/10.3389/fphar.2021.645842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085504PMC
April 2021
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