Publications by authors named "Yao Fu"

560 Publications

Antimicrobial Action of Biocompatible Silver Microspheres and Their Role in the Potential Treatment of Fungal Keratitis.

ACS Biomater Sci Eng 2021 Oct 11. Epub 2021 Oct 11.

Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 20025, P.R. China.

Silver nanoparticles have drawn considerable attention as excellent antimicrobial agents because of their characteristics, including broad antimicrobial spectrum, durable antimicrobial property, and large specific surface area. However, the toxicity of silver nanoparticles limits the in vivo application in the antimicrobial therapy field. Here, we developed a novel silver-based biomaterial to achieve favorable biocompatibility as well as enhanced antimicrobial activity. Silver microspheres (AgMPs) were synthesized using bovine serum albumin as a template and HO as an activator. Electron microscopy results showed that AgMPs had a honeycombed inner structure with an approximate diameter of 800 nm. The minimum inhibitory concentration results exhibited that AgMPs had effective antimicrobial action against bacteria and fungi when the concentration was greater than 32 and 16 μg/mL, respectively. The cell proliferation results suggested that AgMPs have no influence on corneal epithelial cell growth when the concentration was under 25 μg/mL. The in vivo antifungal therapy experiments demonstrated that 25 μg/mL AgMPs could effectively combat wound infections. Overall, AgMPs exhibited substantial antimicrobial action on fungi in addition to biosafety on corneal epithelial cells at a concentration within 16-25 μg/mL. Our study shows that AgMPs can be used as an ocular surface drop candidate to treat fungal keratitis.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00815DOI Listing
October 2021

Secure quantum secret sharing without signal disturbance monitoring.

Opt Express 2021 Sep;29(20):32244-32255

Quantum secret sharing (QSS) is an essential primitive for the future quantum internet, which promises secure multiparty communication. However, developing a large-scale QSS network is a huge challenge due to the channel loss and the requirement of multiphoton interference or high-fidelity multipartite entanglement distribution. Here, we propose a three-user QSS protocol without monitoring signal disturbance, which is capable of ensuring the unconditional security. The final key rate of our protocol can be demonstrated to break the Pirandola-Laurenza-Ottaviani-Banchi bound of quantum channel and its simulated transmission distance can approach over 600 km using current techniques. Our results pave the way to realizing high-rate and large-scale QSS networks.
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http://dx.doi.org/10.1364/OE.440365DOI Listing
September 2021

Removing the influence of the angle of incidence in a dual rotating retarder Mueller matrix polarimeter.

Appl Opt 2021 Sep;60(27):8472-8479

Due to the sensitivity of wave plates to the angle of incidence (AOI) of light, the accuracy of a dual rotating retarder Mueller matrix polarimeter is also influenced by the AOI. Unlike other conventional systematic errors, the phase retardance error of wave plates caused by AOI is a periodic perturbation rather than a constant. We propose a new method to eliminate the influence of AOI based on a numerical calibration method. To verify the reliability of the proposed calibration method, we measured various types of samples in a transmission Mueller matrix measuring system, such as air, dichroic samples, and birefringent samples, with different AOI conditions. It is demonstrated that the new calibration method can effectively eliminate the influence of AOI. After calibration, the maximum measurement error can be reduced to less than 0.02.
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http://dx.doi.org/10.1364/AO.435283DOI Listing
September 2021

Antihyperuricemia and antigouty arthritis effects of Persicaria capitata herba in mice.

Phytomedicine 2021 Sep 23;93:153765. Epub 2021 Sep 23.

State Key Laboratory of Functions and Applications of Medicinal Plants & School of Pharmacy, Guizhou Medical University, Guian New Area, 550025, Guizhou, China; National Engineering Research Center of Miao's Medicines & Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education & Guizhou Provincial Key Laboratory of Pharmaceutics, Guiyang, 550004, Guizhou, China. Electronic address:

Background: Hyperuricemia (HUA) is an important risk factor for gout, renal dysfunction and cardiovascular diseases. The whole plant of Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross, namely Persicaria capitata herba, is a well-known ethnic herb with potent therapeutic effects on urinary tract infections and urinary calculus, yet previous reports have only focused on its effect on urinary tract infections.

Purpose: To evaluate the therapeutic potential of P. capitata herba against gout by investigating its antihyperuricemia and antigouty arthritis effects and possible mechanisms.

Methods: The ethanol extract (EP) and water extract (WP) of P. capitata herba were prepared by extracting dried and ground whole plants of P. capitata with 75% ethanol and water, respectively, followed by removal of solvents and characterization by UHPLC-Q-TOF/MS. The antihyperuricemia and antigouty arthritis effects of the two extracts were evaluated in a potassium oxonate- and hypoxanthine-induced hyperuricemia mouse model and a monosodium urate crystal (MSUC)-induced acute gouty arthritis mouse model, respectively. The mechanisms were investigated by testing their effects on the expression of correlated proteins (by Western blot) and mRNAs (by RT-PCR).

Results: UHPLC-HRMS fingerprinting and two chemical markers (i.e., quercetin and quercitrin) determination were used for the characterization of the WP and EP extracts. Both WP and EP extracts showed pronounced antihyperuricemia activities, with a remarkable decline in serum uric acid and a marked increase in urine uric acid in hyperuricemic mice. Unlike the clinical xanthine oxidase (XOD) inhibitor allopurinol, WP and EP did not show any distinct renal toxicities. The underlying antihyperuricemia mechanism involves the inhibition of the activity and expression of XOD and the downregulation of the mRNA and protein expression of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1). The extracts of P. capitata herba also demonstrated remarkable anti-inflammatory activity in MSUC-induced acute gouty arthritis mice. The mechanism might involve inhibitory effects on the expression of proinflammatory factors.

Conclusions: The extracts of P. capitata herba possessed pronounced antihyperuricemia and antigouty arthritis effects and were, therefore, promising natural medicines for hyperuricemia-related disorders and gouty arthritis. The use of P. capitata herba for the treatment of urinary calculus may be, at least to some degree, related to its potential as an antihyperuricemia and antigouty arthritis drug.
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http://dx.doi.org/10.1016/j.phymed.2021.153765DOI Listing
September 2021

Down-expression of TaPIN1s Increases the Tiller Number and Grain Yield in Wheat.

BMC Plant Biol 2021 Sep 30;21(1):443. Epub 2021 Sep 30.

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai'an, 271018, Shandong, China.

Background: Tiller number is a factor determining panicle number and grain yield in wheat (Triticum aestivum). Auxin plays an important role in the regulation of branch production. PIN-FORMED 1 (PIN1), an auxin efflux carrier, plays a role in the regulation of tiller number in rice (Oryza sativa); however, little is known on the roles of PIN1 in wheat.

Results: Nine homologs of TaPIN1 genes were identified in wheat, of which TaPIN1-6 genes showed higher expression in the stem apex and young leaf in wheat, and the TaPIN1-6a protein was localized in the plasma membrane. The down-expression of TaPIN1s increased the tiller number in TaPIN1-RNA interference (TaPIN1-RNAi) transgenic wheat plants, indicating that auxin might mediate the axillary bud production. By contrast, the spikelet number, grain number per panicle, and the 1000-grain weight were decreased in the TaPIN1-RNAi transgenic wheat plants compared with those in the wild type. In summary, a reduction of TaPIN1s expression increased the tiller number and grain yield per plant of wheat.

Conclusions: Phylogenetic analysis and protein structure of nine TaPIN1 proteins were analyzed, and subcellular localization of TaPIN1-6a was located in the plasma membrane. Knock-down expression of TaPIN1 genes increased the tiller number of transgenic wheat lines. Our study suggests that TaPIN1s is required for the regulation of grain yield in wheat.
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http://dx.doi.org/10.1186/s12870-021-03217-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482684PMC
September 2021

and Properties of an Injectable Hydrogel Derived From Acellular Ear Cartilage Extracellular Matrix.

Front Bioeng Biotechnol 2021 13;9:740635. Epub 2021 Sep 13.

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Extracellular matrix (ECM) hydrogels provide advantages such as injectability, the ability to fill an irregularly shaped space, and the adequate bioactivity of native matrix. In this study, we developed decellularized cartilage ECM (dcECM) hydrogels from porcine ears innovatively via the main method of enzymatic digestion and verified good biocompatible properties of dcECM hydrogels to deliver chondrocytes and form subcutaneous cartilage . The scanning electron microscopy and turbidimetric gelation kinetics were used to characterize the material properties and gelation kinetics of the dcECM hydrogels. Then we evaluated the biocompatibility of hydrogels via the culture of chondrocytes . To further explore the dcECM hydrogels , grafts made from the mixture of dcECM hydrogels and chondrocytes were injected subcutaneously in nude mice for the gross and histological analysis. The structural and gelation kinetics of the dcECM hydrogels altered according to the variation in the ECM concentrations. The 10 mg/ml dcECM hydrogels could support the adhesion and proliferation of chondrocytes . , at 4 weeks after transplantation, cartilage-like tissues were detected in all groups with positive staining of toluidine blue, Safranin O, and collagen II, indicating the good gelation of dcECM hydrogels. While with the increasing concentration, the tissue engineering cartilages formed by 10 mg/ml dcECM hydrogel grafts were superior in weights, volumes, collagen, and glycosaminoglycan (GAG) content compared to the dcECM hydrogels of 1 mg/ml and 5 mg/ml. At 8 weeks after grafting, dcECM hydrogel grafts at 10 mg/ml showed very similar qualities to the control, collagen I grafts. After 12 weeks of culture, the histological analysis indicated that 10 mg/ml dcECM hydrogel grafts were similar to the normal cartilage from pig ears, which was the source tissue. In conclusion, dcECM hydrogel showed the promising potential as a tissue engineering biomaterial to improve the regeneration and heal injuries of ear cartilage.
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http://dx.doi.org/10.3389/fbioe.2021.740635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474061PMC
September 2021

Malignant Gastrointestinal Neuroectodermal Tumor in the Right Heart: A Report of an Extremely Rare Case Presenting With a Cardiac Mass.

Front Cardiovasc Med 2021 1;8:702215. Epub 2021 Sep 1.

Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.

Malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare soft tissue sarcoma and has been designated as a new entity recently. At present, GNET virtually exclusively occurs in the gastrointestinal tract. Here we report a case of extra-GNET that arose in the right heart. A 62-year-old male complained of chest distress and breathing difficulty while lying down at night for over 1 month at admission. The radiological findings revealed an occupying lesion involving the right atrium and the right ventricle without any abdominal abnormalities. The patient then underwent a surgical resection. Microscopically, neoplastic cells proliferated in the pattern of nests and sheets with fibrous separation. Focal areas with cellular dyscohesion imparted a vague pseudopapillary pattern. These tumor cells were small to medium in size with fine chromatin and predominantly pale eosinophilic cytoplasm. The nuclei were typically round to oval with somewhat irregular contours and contained small nucleoli. The mitotic figures were easily found. Immunohistochemically, the neoplastic cells were positive for S100 and SOX-10 but negative for HMB-45, A103, and CD99. - rearrangement was detected by fluorescence hybridization and further confirmed by whole-transcriptome sequence analysis. The patient had pulmonary metastasis 8 months later and soon died of the disease. The overall survival of the patient was 20 months. In summary, we reported an extremely rare case of cardiac GNET, indicating that the location of GNET should not be confined to the GI tract as initially defined. Due to the lack of a specific effective treatment and the occurrence of early metastasis, cardiac GNET conferred a poor prognosis. More clinical and experimental studies are warranted to better manage this disease in the future.
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http://dx.doi.org/10.3389/fcvm.2021.702215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440875PMC
September 2021

Enhancing red luminescence by doping Yb into Er self-sensitized GdOS upconverting nanoparticles under excitation at 1530 nm.

Dalton Trans 2021 Oct 5;50(38):13468-13475. Epub 2021 Oct 5.

School of Science, Dalian Maritime University, Dalian, Liaoning 1160126, P. R. China.

Red upconversion luminescence (UCL) nanoparticles are of significant importance for applications in the fields of deep tissue imaging, photothermal therapy and security ink. In this work, a highly efficient red emission was achieved by introducing Yb ions as mediators in Er self-sensitized GdOS nanoparticles under excitation at 1530 nm. The results show that the GdOS:Yb,Er nanoparticles synthesized by a homogeneous precipitation method exhibit a uniform spherical shape and narrow size distribution with a mean particle diameter of ≈65 nm. Moreover, the integral emission intensity ratio of red to green of the GdOS:Yb,Er sample is significantly enhanced 3-fold compared with the GdOS:Er sample without Yb doping. The enhancement mechanisms are discussed in detail on the basis of steady-state luminescence spectra and decay dynamics measurements under various excitations at 380, 808, 980 and 1530 nm, respectively. It has been demonstrated that the enhanced red luminescence is induced by cross-relaxation energy transfer from Er to YbS (Er) + F (Yb) → I (Er) + F (Yb) and I (Er) + F (Yb) → I (Er) + F (Yb), and further followed by back energy transfer from Yb to Er through I (Er) + F (Yb) → F (Er) + F (Yb). The former cross-relaxation procedure effectively populates the red emission level of F by depopulating the green emission level of S. Our findings provide a feasible way to enhance the red UCL and new insights into red UCL mechanisms in the Er self-sensitized system under ≈1500 nm excitation, by combining with the nontoxic oxysulfide host, indicating their potential application as safe fluorescent nanoprobes in the bio-field.
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http://dx.doi.org/10.1039/d1dt01929eDOI Listing
October 2021

1, 8-cineole protects against ISO-induced heart failure by inhibiting oxidative stress and ER stress in vitro and in vivo.

Eur J Pharmacol 2021 Nov 2;910:174472. Epub 2021 Sep 2.

Medicinal Chemistry and Pharmacology Institute, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, PR China. Electronic address:

Sugemule-3 is widely adopted in clinical practice to manage cardio-cerebral diseases. 1, 8-cineole is the main ingredient of Sugemule-3, however, the underlying cellular mechanisms for its protective effect are poorly understood. 1, 8-cineole improved the survival of H9C2 cardiomyocytes during isoproterenol (ISO) injury and reduced ISO-induced apoptosis. Compared to the ISO group, 1, 8-cineole highly attenuated the generation of ISO-induced reactive oxygen species (ROS), the depolarization of △ψm, suppression of the Bax/Bcl-2 ratio, and p-caspase 3 expression, in vitro. Furthermore, 1, 8-cineole treatment in H9C2 cardiomyocytes lowered the expressions of 78-kDa glucose-regulated protein (GRP78), p-protein kinase-like ER kinase (PERK), activation of transcription factor (ATF) 4, and ER stress effector protein C/EBP and homologous protein (CHOP). These findings implied that 1, 8-cineole contribute to cardioprotection via the GRP78/CHOP pathways. Using animal models, 1, 8-cineole was revealed to markedly alleviate ISO-induced heart injury, and reduce cardiac hypertrophy, formation of the cytoplasmic vacuole, loss of myofiber, and fibrosis by inhibiting oxidative stress and ER stress. 1, 8-cineole reduces apoptosis by inhibiting signaling pathways related to oxidative stress and ER stress. These findings implicate 1, 8-cineole as a potential therapeutic target for cardiac hypertrophy-related heart diseases, including heart failure.
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http://dx.doi.org/10.1016/j.ejphar.2021.174472DOI Listing
November 2021

Effect of carbon nitride synthesized by different modification strategies on the performance of carbon nitride/PVDF photocatalytic composite membranes.

J Hazard Mater 2021 Aug 10;422:126877. Epub 2021 Aug 10.

Jinan Environmental Research Academy, Jinan 250102, China.

Carbon nitride (CN)/polyvinylidene fluoride (PVDF) photocatalytic composite membrane (PCM) is considered as a promising candidate to improve the anti-fouling characteristic of conventional PVDF membrane and overcome the difficulty encountered during recovery of powder catalyst simultaneously. However, the effects of differently-modified CN on PCM and its mechanism are still unclear. In this study, bulk-CN (BCN), carbon defects CN (CCN), nitrogen defect CN (DCN), mesoporous CN (MCN), and nitrogen-rich CN (NCN) were incorporated into PVDF by phase inversion method. The influence of changes in the physical and chemical properties of CN, including hydrophilic groups, photocatalytic activity, and particle size, on the permeability, anti-fouling characteristic, and photocatalytic self-cleaning activity of CN/PVDF was systematically analyzed. The mechanism of excellent performance of PCM was revealed by experimental test and theoretical calculation. The flux of PCM was significantly improved by increasing the hydrophilic group on modified CN. However, the differences in particle size and interaction between different types of modified CN and PVDF chains endowed the CN/PVDF with different porosity. DCN/PVDF showed high porosity and hydrophilicity, leading to high water flux and rejection rate of 293.6 L (m h) and 90.1%, respectively. Compared to pure PVDF, the flux recovery rate of DCN/PVDF increased by 27.6%, and the irreversible fouling decreased from 36.9% to 9.2%. The modified CN/PVDF showed excellent photocatalytic activity for the removal of cefotaxime (CFX) and E. coli. Owing to the narrow band gap of DCN, large specific surface area, and low photogenerated carrier recombination rate, the CFX removal rate reached 99% in 2 h, and E. coli inactivation achieved 3.7 log within 4 h via DCN/PVDF.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126877DOI Listing
August 2021

An Organic Hybrid Indium-Telluride Incorporating Binuclear Complexes [In(ea)] with a Bridging Oxygen Donor.

Inorg Chem 2021 Sep 23;60(17):12724-12729. Epub 2021 Aug 23.

Chongqing Key Laboratory of Inorganic Functional Materials, College of Chemistry, Chongqing Normal University, Chongqing 401331, P. R. China.

The new organic hybrid indium-telluride [In(ea)Te] (; Hea = ethanolamine) exhibits a new type of one-dimensional polymeric chain based on the linkages of dinuclear [In(ea)] and [InTe] units, which offers the first example of an indium-telluride framework incorporating binuclear complexes [In(ea)] with a bridging O donor. shows a distinctive photocurrent response and photocatalytic properties under visible-light illumination.
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http://dx.doi.org/10.1021/acs.inorgchem.1c02065DOI Listing
September 2021

Prognostic and predictive role of a metabolic rate-limiting enzyme signature in hepatocellular carcinoma.

Cell Prolif 2021 Oct 23;54(10):e13117. Epub 2021 Aug 23.

Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Objectives: Abnormal expression of metabolic rate-limiting enzymes drives the occurrence and progression of hepatocellular carcinoma (HCC). This study aimed to elucidate the comprehensive model of metabolic rate-limiting enzymes associated with the prognosis of HCC.

Materials And Methods: HCC animal model and TCGA project were used to screen out differentially expressed metabolic rate-limiting enzyme. Cox regression, least absolute shrinkage and selection operation (LASSO) and experimentally verification were performed to identify metabolic rate-limiting enzyme signature. The area under the receiver operating characteristic curve (AUC) and prognostic nomogram were used to assess the efficacy of the signature in the three HCC cohorts (TCGA training cohort, internal cohort and an independent validation cohort).

Results: A classifier based on three rate-limiting enzymes (RRM1, UCK2 and G6PD) was conducted and serves as independent prognostic factor. This effect was further confirmed in an independent cohort, which indicated that the AUC at year 5 was 0.715 (95% CI: 0.653-0.777) for clinical risk score, whereas it was significantly increased to 0.852 (95% CI: 0.798-0.906) when combination of the clinical with signature risk score. Moreover, a comprehensive nomogram including the signature and clinicopathological aspects resulted in significantly predict the individual outcomes.

Conclusions: Our results highlighted the prognostic value of rate-limiting enzymes in HCC, which may be useful for accurate risk assessment in guiding clinical management and treatment decisions.
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http://dx.doi.org/10.1111/cpr.13117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488553PMC
October 2021

1, 8-cineole attenuates cardiac hypertrophy in heart failure by inhibiting the miR-206-3p/SERP1 pathway.

Phytomedicine 2021 Oct 17;91:153672. Epub 2021 Jul 17.

Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, P.R. China., Tongliao, Inner Mongolia, PR China. Electronic address:

Background: 1,8-Cineole (1,8-CIN) is a monoterpene found in diverse dietary and medicinal herbs that has been reported to be effective against cardiovascular diseases.

Purpose: The present research was designed to elucidate the treatment effects and the underlying mechanism of 1,8-CIN on heart failure (HF).

Method: An in vitro cardiac hypertrophy model and an in vivo heart failure (HF) model induced by isoprenaline (ISO) were established and treated with or without 1,8-CIN. In vitro miR-206-3p mimic or inhibitors were created. MiR-206-3p, SERP1 and related mRNAs or proteins were detected using qPCR or western blotting. Cell viability was tested by MTT assay, and apoptosis was measured using TUNEL assay, AO/EB assay and flow cytometry. Actin was stained with FITC-phalloidin. MiR-206-3p and related mRNAs or proteins in cardiac muscle tissues were measured using qPCR or western blotting, HE staining, Masson staining.

Results: ISO subcutaneous injection increased cardiac hypertrophy, cytoplasmic vacuole formation, myofiber loss and fibrosis and decreased cardiomyocyte viability. 1,8-CIN treatment improved cardiomyocyte viability and reduced cardiac hypertrophy, cytoplasmic vacuole formation, myofibre loss and fibrosis. We found that 1,8-CIN attenuated apoptosis. We observed that expression of miR-206-3p was dramatically increased in ISO-exposed cardiomyocytes or ISO-treated rat hearts. MiR-206-3p was identified to target the 3'UTR of SERP1, resulting in the accumulation of un- or misfolded proteins, leading to endoplasmic reticulum (ER) stress.

Conclusion: These results suggest that 1,8-CIN reduces the apoptosis induced by ER stress through inhibiting miR-206-3p, which inhibits the expression of SERP1.
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http://dx.doi.org/10.1016/j.phymed.2021.153672DOI Listing
October 2021

Characteristics of fine particulate matter (PM) at Jinsha Site Museum, Chengdu, China.

Environ Sci Pollut Res Int 2021 Aug 4. Epub 2021 Aug 4.

Chengdu Institute of Cultural Relics and Archaeology, Chengdu, 610074, China.

Air pollution is a serious threat to ancient sites and cultural relicts. In this study, we collected indoor and outdoor PM samples and individual particles at the Exhibition Hall of Jinsha Site Museum in June 2020, and then the chemical components, sources, morphology, and mixing state of the fine particulate matter were analyzed. Our results show that the indoor and outdoor PM concentrations at the Exhibition Hall were 33.3±6.6 and 39.4±11.4 μg m, respectively. Although the indoor and outdoor concentrations of OC and EC were close, the proportion of secondary organic carbon in OC outdoor (33%) was higher than that indoor (27%). The PM was alkaline both indoors and outdoors, and the outdoor alkalinity was stronger than the indoor alkalinity. SNA (SO, NO, and NH) was the dominant component in the water-soluble inorganic ions; Na, Mg, and Ca were well correlated (R> 0.9), and Cl and K were also highly correlated (R> 0.8). Enrichment factor analysis showed that Cu (indoor) and Cd were the main anthropogenic elements and that Cd was heavily enriched. Principal components analysis showed that the main sources of PM at Jinsha Site Museum were motor vehicles, dust, secondary sources, and combustion sources. The individual particles were classified as organic matter, S-rich, soot, mineral, and fly ash/metal particles, and most of these particles were internally mixed with each other. At last, we proposed pollution control measures to improve the air quality of museums and the preservation of cultural relicts.
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http://dx.doi.org/10.1007/s11356-021-15743-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336903PMC
August 2021

Environmentally-induced contributes to the severity of COVID-19 through fostering expression of SARS-CoV-2 receptor NRPs and glycan metabolism.

Theranostics 2021 6;11(16):7970-7983. Epub 2021 Jul 6.

Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA.

The novel β-coronavirus, SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), has infected more than 177 million people and resulted in 3.84 million death worldwide. Recent epidemiological studies suggested that some environmental factors, such as air pollution, might be the important contributors to the mortality of COVID-19. However, how environmental exposure enhances the severity of COVID-19 remains to be fully understood. In the present report, we provided evidence showing that , a previously reported environmentally-induced oncogene that antagonizes repressive trimethylation of histone proteins, is an important regulator for SARS-CoV-2 receptors neuropilin-1 (NRP1) and NRP2, cathepsins, glycan metabolism and inflammation, key determinants for viral infection and cytokine storm of the patients. Depletion of in bronchial epithelial cells by CRISPR-Cas-9 gene editing resulted in a decreased expression of NRP1, NRP2, cathepsins, and genes involved in protein glycosylation and inflammation, largely due to a substantial enrichment of lysine 9 and/or lysine 27 trimethylation of histone H3 (H3K9me3/H3K27me3) on these genes as determined by ChIP-seq. Meanwhile, we also validated that environmental factor arsenic is able to induce , NRP1 and NRP2, and genetic disruption of lowered expression of NRP1 and NRP2. Furthermore, may coordinate with the Neanderthal variants linked to an elevated mortality of COVID-19. These data, thus, suggest that is a key mediator for the severity of COVID-19 in response to environmental exposure and targeting may be the one of the effective strategies in ameliorating the symptom and reducing the mortality of COVID-19.
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http://dx.doi.org/10.7150/thno.62138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315075PMC
August 2021

Enhanced Production of (S)-2-arylpropionic Acids by Protein Engineering and Whole-Cell Catalysis.

Front Bioeng Biotechnol 2021 7;9:697677. Epub 2021 Jul 7.

Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Urban Pollutant Conversion, Anhui Province Key Laboratory of Biomass Clean Energy, iChEM, University of Science and Technology of China, Hefei, China.

Esterases are important biocatalysts for chemical synthesis. Several bHSL family esterases have been used to prepare ()-2-arylpropionic acids with stronger anti-inflammatory effects kinetic resolution. Here, we presented the discovery of key residues that controlled the enantioselectivity of bHSL family esterases to ethyl 2-arylpropionates, through careful analysis of the structural information and molecular docking. A new bHSL family esterase, Est924, was identified as a promising catalyst for kinetic resolution of racemic ethyl 2-arylpropionates with slight ()-stereopreference. Using Est924 as the starting enzyme, protein engineering was conducted at hotspots, and the substitution of A203 was proved to enhance the enantioselectivity. The stereopreference of the mutant M1 (A203W) was inverted to ethyl ()-2-arylpropionates, and this stereopreference was further improved in variant M3 (I202F/A203W/G208F). In addition, the optimal variant, M3, was also suitable for the resolution of ibuprofen ethyl ester and ketoprofen ethyl ester, and their efficient ()-isomers were synthesized. Next, the whole-cell catalyst harboring M3 was used to prepare ()-ketoprofen. ()-ketoprofen with 86%ee was produced by whole-cell catalyst with a single freeze-thaw cycle, and the cells could be reused for at least five cycles. Our results suggested that Est924 variants could kinetically resolve economically important racemates for industrial production and further offer the opportunity for the rational design of enzyme enantioselectivity. Moreover, it is an economical process to prepare optically pure ()-ketoprofen and ()-naproxen by using an engineered strain harboring M3 as the catalyst.
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http://dx.doi.org/10.3389/fbioe.2021.697677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293918PMC
July 2021

Advances in the Functional Nucleic Acid Biosensors for Detection of Lead Ions.

Crit Rev Anal Chem 2021 Jul 25:1-17. Epub 2021 Jul 25.

College of Chemical Engineering, North China University of Science and Technology, Tangshan, China.

Lead ions (Pb) are destructive to the natural environment and public health, so the efficient detection of Pb is particularly important. Although the instrumental analysis methods have high accuracy, they require high cost and precise operation, which limits their wide application. Therefore, many strategies have been extensively studied for detecting Pb by biosensors. Functional nucleic acids have become an efficient tool in this field. This review focuses on the recent biosensors of detecting Pb based on functional nucleic acids from 2010 to 2020, in which DNAzyme, DNA G-quadruplex and aptamer will be introduced. The biosensors are divided into three categories that colorimetric, fluorometric and electrochemical biosensors according to the different reported signals. The action mechanism and detection effect of each biosensor are explained. Finally, the present situation of nucleic acid biosensor for the detection of Pb is summarized and the future research direction is prospected.
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July 2021

Insight into levofloxacin loaded biocompatible electrospun scaffolds for their potential as conjunctival substitutes.

Carbohydr Polym 2021 Oct 17;269:118341. Epub 2021 Jun 17.

Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China. Electronic address:

The rehabilitation of visual acuity with severe conjunctival fibrosis depends on ocular reconstruction with suitable conjunctival substitutes. In this study, we have developed poly(lactic acid) (PLA) electrospun nanofibrous membranes (EFMs) surface coated by cellulose nanofibrils (CNF) and/or silk peptide (SP). The CNF coating improved the hydrophilicity and the SP coating proliferated conjunctival epithelial cells (CjECs). To prevent post-operative infections, the composite scaffolds were loaded with levofloxacin (LF), constantly exerting efficient bactericidal effects. In in vivo evaluations, the PLA EFMs presented excellent therapeutic effects by promoting structural and functional restoration of conjunctiva after transplant. Even with reduced topical administration of antibiotics, the coloboma treated with LF loaded scaffolds presented no infections. It could be deduced that the potent bacterial inhibition feature could save troubles for patients by minimizing the application of antibiotics post-surgery. Hence, the developed PLA EFMs loaded with LF could be promising conjunctival substitutes.
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http://dx.doi.org/10.1016/j.carbpol.2021.118341DOI Listing
October 2021

Pollution level and risk assessment of lead, cadmium, mercury, and arsenic in edible mushrooms from Jilin Province, China.

J Food Sci 2021 Aug 19;86(8):3374-3383. Epub 2021 Jul 19.

Department of Physical and Chemical Test, Jilin Provincial Center for Disease Control and Prevention, Changchun, China.

To evaluate the pollution level of toxic elements in edible mushrooms from Jilin Province, China, the lead, cadmium, mercury, and arsenic content present in them were monitored and evaluated. A total of 610 edible mushroom samples, including fresh and dried, were collected from nine cities in the Jilin Province. The concentrations of lead, cadmium, mercury, and arsenic ranged from 0.007 to 3.31, 0.006 to 48.52, 0.003 to 0.56, and 0.008 to 57.34 mg/kg, respectively, in dried samples, and 0.007 to 0.06, 0.006 to 0.17, 0.003 to 0.06, and 0.008 to 0.12 mg/kg, respectively, in fresh samples. The concentration  of cadmium and arsenic exceeded the standard (Cd ≤ 0.2 mg/kg, Cd of Lentinus edodes ≤ 0.5 mg/kg, and As ≤ 0.5 mg/kg) in some mushroom samples. The bioconcentration levels of lead, cadmium, mercury, and arsenic depended on the edible mushroom species, environment, and the physicochemical properties of lead, cadmium, mercury, and arsenic. The results of the single factor pollution index, a method used to calculate the level of single elements in substances, showed that all edible mushrooms were at the level of unpolluted except Tricholoma matsutake and Pleurotus eryngii. The comprehensive factor (P) for T. matsutake was 1.093. The comprehensive factor pollution index, a method used to calculate the level of combined mixture in substances, was in the unpolluted level, except for T. matsutake. The pollution index results showed that cadmium and arsenic concentrations were lightly polluting in some mushroom samples. The health risk index for arsenic was the highest. Therefore, more attention should be paid to arsenic contamination in T. matsutake and P. eryngii in the Jilin Province, China. PRACTICAL APPLICATION: In this paper, we evaluated the contamination levels and associated safety issues of four toxic elements, lead, cadmium, mercury, and arsenic, in edible mushrooms. The results showed that cadmium and arsenic concentrations were lightly polluting in some mushroom samples.
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http://dx.doi.org/10.1111/1750-3841.15849DOI Listing
August 2021

Successful resuscitation from cardiac arrest due to acute pulmonary edema following tibial intramedullary nail insertion: A case report.

Asian J Surg 2021 Jul 17. Epub 2021 Jul 17.

Department of Anesthesia, Sichuan Provincial Orthopedic Hospital, Chengdu, 610041, Sichuan Province, China.

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http://dx.doi.org/10.1016/j.asjsur.2021.07.007DOI Listing
July 2021

Neurovascular protection of salvianolic acid B and ginsenoside Rg1 combination against acute ischemic stroke in rats.

Neuroreport 2021 09;32(13):1140-1146

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Ischemic stroke continues to be a major global health problem associated with considerable mortality and morbidity. Thus, it is still targeted by researchers for developing new strategies or drugs to alleviate the lesion of stroke. In the present study, both the permanent occlusion of the middle cerebral artery (MCAO) model and the restoration of cerebral blood flow after middle cerebral artery occlusion (CI/R) model were set up for evaluating the efficiency of salvianolic acid B and ginsenoside Rg1 combination (SalB-Rg1). SalB-Rg1 decreased infarct area through 3,5-triphenyltetrazolium chloride stain and improved neurological behavior through Longa Score or Left-Biased Swings on both MCAO rats and CI/R rats. Neural protection of SalB-Rg1 against ischemia or ischemic reperfusion injury was evidenced by the inhibition of nucleus pyknosis, liquefaction necrosis through H&E stain and Nissl stain. Furthermore, protection of SalB-Rg1 on blood-brain barrier (BBB) was more significant on CI/R rats, accompanying with the downregulation of matrix metalloproteinase-2 and matrix metalloproteinase-9, and recovery of zonula occludens-1 expression. These results provide compelling evidence that SalB-Rg1 holds the potential to be developed as an optimal therapeutic strategy to alleviate the injury of ischemia or ischemic reperfusion.
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http://dx.doi.org/10.1097/WNR.0000000000001706DOI Listing
September 2021

Variants on the UBE2L3-YDJC autoimmune disease risk haplotype increase UBE2L3 gene expression by modulating CTCF and YY1 binding.

Arthritis Rheumatol 2021 Jul 19. Epub 2021 Jul 19.

Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.

Objective: Genetic variants spanning the ubiquitin-conjugating enzyme E2 L3 (UBE2L3) gene are associated with increased expression of the UBE2L3-encoded E2 ubiquitin-conjugating enzyme, UbcH7, that facilitates activation of proinflammatory NF-κB signaling, and susceptibility to autoimmune diseases. This study aims to delineate how genetic variants carried on the UBE2L3-YDJC autoimmune risk haplotype function to drive hypermorphic UBE2L3 expression.

Methods: We used bioinformatic analyses, electrophoretic mobility shift assays, and luciferase reporter assays to identify and functionally characterize allele-specific effects of risk variants positioned in chromatin accessible regions of immune cells. Chromatin conformation capture (3C)-qPCR, ChIP-qPCR, and siRNA knockdown assays were performed on patient-derived EBV-transformed B cells homozygous for the UBE2L3-YDJC non-risk or risk haplotype to determine if the risk haplotype increases UBE2L3 expression by altering the regulatory chromatin architecture in the region.

Results: Five of the seven prioritized variants demonstrated allele-specific increases in nuclear protein binding affinity and regulatory activity. HiChIP and 3C-qPCR uncovered a long-range interaction between the UBE2L3 promoter (rs140490, rs140491, rs11089620) and downstream YDJC promoter (rs3747093) that was strengthened in the presence of the UBE2L3-YDJC risk haplotype, and correlated with the loss of CTCF binding and gain of YY1 binding at the risk alleles. Depleting YY1 by siRNA disrupted the long-range interaction between the two promoters and reduced UBE2L3 expression.

Conclusion: The UBE2L3-YDJC autoimmune risk haplotype increases UBE2L3 expression through strengthening a YY1-mediated interaction between the UBE2L3 and YDJC promoters.
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http://dx.doi.org/10.1002/art.41925DOI Listing
July 2021

Extremely enhanced N lasing in a filamentary plasma grating in ambient air.

Opt Lett 2021 Jul;46(14):3404-3407

Cavity-free air lasing offers a promising route towards the realization of atmospheric lasers for various applications such as remote sensing and standoff spectroscopy; however, achieving efficient generation and control of air lasing in ambient air is still a challenge. Here we show the experimental realization of a giant lasing enhancement by three to four orders of magnitude in ambient air for the self-seeded 2+ lasing at 428 nm, assigned to the +(=0) and +(=1) emission, by modulating the spatiotemporal overlap of ultrashort near-infrared control-pump pulses in a filamentary plasma grating; meanwhile, the spontaneous emission from the same transition is only enhanced by three to four times. We find that this enhancement is sensitive to the relative polarization and interference time of the two pulses, and reveal that the formation of the plasma grating induces different population variations in the +(=0) and +(=1) levels, resulting in an enormous population inversion between the two levels, thereby a higher gain for the giant enhancement of 2+ lasing in ambient air.
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http://dx.doi.org/10.1364/OL.428065DOI Listing
July 2021

Oxypeucedanin is a mechanism-based inactivator of CYP2B6 and CYP2D6.

Curr Drug Metab 2021 Jun 29. Epub 2021 Jun 29.

Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China.

Background: Herbal medicine Angelica dahurica is widely employed for the treatment of rheumatism and pain relief in China. Oxypeucedanin is a major component of the herb.

Objectives: The objectives of this study are aimed at the investigation of mechanism-based inactivation of CYP2B6 and CYP2D6 by oxypeucedanin, characterization of the reactive metabolites associated with the enzyme inactivation, and identification of the P450s participating in the bioactivation of oxypeucedanin.

Methods: Oxypeucedanin was incubated with liver microsomes or recombinant CYPs2B6 and 2D6 under designed conditions, and the enzyme activities were measured by monitoring the generation of the corresponding products. The resulting reactive intermediates were trapped with GSH and analyzed by LC-MS/MS.

Results: Microsomal incubation with oxypeucedanin induced a time-, concentration-, and NADPH-dependent inhibition of CYPs2B6 and 2D6 with kinetic values of KI/kinact 1.82 µM/0.07 min-1 (CYP2B6) and 8.47 µM/0.044 min-1 (CYP2D6), respectively. Ticlopidine and quinidine attenuated the observed time-dependent enzyme inhibitions. An epoxide and/or γ-ketoenal intermediate(s) derived from oxypeucedanin was/were trapped in microsomal incubations. CYP3A4 was the primary enzyme involved in the bioactivation of oxypeucedanin.

Conclusion: Oxypeucedanin was a mechanism-based inactivator of CYP2B6 and CYP2D6. An epoxide and/or γ-ketoenal intermediate(s) may be responsible for the inactivation of the two enzymes.
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http://dx.doi.org/10.2174/1389200222666210629114830DOI Listing
June 2021

Time series prediction of COVID-19 transmission in America using LSTM and XGBoost algorithms.

Results Phys 2021 Aug 22;27:104462. Epub 2021 Jun 22.

School of Physical and Mathematical Sciences, Nanjing Tech University, Nanjing, Jiangsu 211816, China.

In this paper, we establish daily confirmed infected cases prediction models for the time series data of America by applying both the long short-term memory (LSTM) and extreme gradient boosting (XGBoost) algorithms, and employ four performance parameters as MAE, MSE, RMSE, and MAPE to evaluate the effect of model fitting. LSTM is applied to reliably estimate accuracy due to the long-term attribute and diversity of COVID-19 epidemic data. Using XGBoost model, we conduct a sensitivity analysis to determine the robustness of predictive model to parameter features. Our results reveal that achieving a reduction in the contact rate between susceptible and infected individuals by isolated the uninfected individuals, can effectively reduce the number of daily confirmed cases. By combining the restrictive social distancing and contact tracing, the elimination of ongoing COVID-19 pandemic is possible. Our predictions are based on real time series data with reasonable assumptions, whereas the accurate course of epidemic heavily depends on how and when quarantine, isolation and precautionary measures are enforced.
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http://dx.doi.org/10.1016/j.rinp.2021.104462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216863PMC
August 2021

Natural Glycan Derived Biomaterials for Inflammation Targeted Drug Delivery.

Macromol Biosci 2021 Sep 18;21(9):e2100162. Epub 2021 Jun 18.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.

Inflammation is closely related to a variety of fatal or chronic diseases. Hence, targeting inflammation provides an alternative approach to improve the therapeutic outcome of diseases such as solid tumors, neurological diseases, and metabolic diseases. Polysaccharides are natural components with immune regulation, anti-virus, anti-cancer, anti-inflammation, and anti-oxidation activities. Herein, this review highlights recent progress in the polysaccharide-based drug delivery systems for achieving inflammation targeting and its related disease treatment. Moreover, the chemical modification and the construction of polysaccharide materials for drug delivery are discussed in detail.
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http://dx.doi.org/10.1002/mabi.202100162DOI Listing
September 2021

PGC-1 Protects against Hepatic Ischemia Reperfusion Injury by Activating PPAR and PPAR and Regulating ROS Production.

Oxid Med Cell Longev 2021 19;2021:6677955. Epub 2021 May 19.

Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.

Peroxisome proliferator-activated receptors (PPARs) and have been shown to be protective in hepatic ischemia/reperfusion (I/R) injury. However, the precise role of PPAR coactivator-1 (PGC-1), which can coactivate both of these receptors, in hepatic I/R injury, remains largely unknown. This study was designed to test our hypothesis that PGC-1 is protective during hepatic I/R injury in vitro and in vivo. Our results show that endogenous PGC-1 is basally expressed in normal livers and is moderately increased by I/R. Ectopic PGC-1 protects against hepatic I/R and hepatocyte anoxia/reoxygenation (A/R) injuries, whereas knockdown of endogenous PGC-1 aggravates such injuries, as evidenced by assessment of the levels of serum aminotransferases and inflammatory cytokines, necrosis, apoptosis, cell viability, and histological examination. The EMSA assay shows that the activation of PPAR and PPAR is increased or decreased by the overexpression or knockdown of PGC-1, respectively, during hepatic I/R and hepatocyte A/R injuries. In addition, the administration of specific antagonists of either PPAR (MK886) or PPAR (GW9662) can effectively decrease the protective effect of PGC-1 against hepatic I/R and hepatocyte A/R injuries. We also demonstrate an important regulatory role of PGC-1 in reactive oxygen species (ROS) metabolism during hepatic I/R, which is correlated with the induction of ROS-detoxifying enzymes and is also dependent on the activations of PPAR and PPAR. These data demonstrate that PGC-1 protects against hepatic I/R injury, mainly by regulating the activation of PPAR and PPAR. Thus, PGC-1 may be a promising therapeutic target for the protection of the liver against I/R injury.
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http://dx.doi.org/10.1155/2021/6677955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159639PMC
May 2021

Ophthalmic Manifestation and Pathological Features in a Cohort of Patients With Linear Nevus Sebaceous Syndrome and Encephalocraniocutaneous Lipomatosis.

Front Pediatr 2021 20;9:678296. Epub 2021 May 20.

Department of Ophthalmology, Shanghai 9th Peoples Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.

This study aimed to figure out the association between ophthalmic and pathological features in patients with Linear Nevus Sebaceous Syndrome (LNSS) and in patients with Oculoectodermal Syndrome-Encephalocraniocutaneous Lipomatosis (OES-ECCL). It is a retrospective, non-consecutive, observational case series. Twenty-seven patients (12 with LNSS and 15 with OES-ECCL, 41 eyes) referred to the Department of Ophthalmology of the Shanghai Ninth People's Hospital between 2000 and 2020 were included. The mean age of the study population for the first-time consult was 5.7 years, ranging from 3 months to 34 years. Clinical notes, pathological records, and imaging findings were reviewed in all the patients. Fourteen (51.9%) cases showed bilateral ocular involvement. Epibulbar choristomas were seen in all the patients. All the lesions involved the conjunctiva and cornea simultaneously. Multiple lesions were observed in 12 eyes. Of the 14 excised lesions, 11 were found to be complex choristomas. Further, 24 (89%) patients had eyelid coloboma. Also, 13 patients (48%) were diagnosed with strabismus, and 12 patients (44%) had abnormal fundus imaging, including optic nerve hypoplasia. LNSS and OES-ECCL shared common ophthalmic features, including epibulbar choristomas with distinctive characteristics, eyelid coloboma, strabismus, and optic nerve hypoplasia. The complex choristoma was found to be associated with the diseases. These specific patterns can be diagnostic clues to distinguish them from other syndromes, such as craniofacial defects, and to remind ophthalmologists that such patients require additional dermatological and neurological examinations and referral. Moreover, a thorough evaluation of ocular conditions is imperative for early interventions.
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http://dx.doi.org/10.3389/fped.2021.678296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177968PMC
May 2021

Nickel-catalyzed three-component olefin reductive dicarbofunctionalization to access alkylborates.

Chem Sci 2020 Jul 8;11(30):7950-7956. Epub 2020 Jul 8.

Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Urban Pollutant Conversion, Anhui Province Key Laboratory of Biomass Clean Energy, iChEM, University of Science and Technology of China Hefei 230026 China

We report a three-component olefin reductive dicarbofunctionalization for constructing alkylborates, specifically, nickel-catalyzed reductive dialkylation and alkylarylation of vinyl boronates with a variety of alkyl bromides and aryl iodides. This reaction exhibits good coupling efficiency and excellent functional group compatibility, providing convenient access to the late-stage modification of complex natural products and drug molecules. Combined with alkylborate transformations, this reaction could also find applications in the modular and convergent synthesis of complex compounds.
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http://dx.doi.org/10.1039/d0sc02054kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163243PMC
July 2020

Extended-release of therapeutic microRNA via a host-guest supramolecular hydrogel to locally alleviate renal interstitial fibrosis.

Biomaterials 2021 08 27;275:120902. Epub 2021 May 27.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China. Electronic address:

Activated fibroblasts are critical contributors to renal interstitial fibrosis thus becoming the cellular target for fibrosis treatment. Previously, microRNA 29 b (miR-29 b) is shown to be down-regulated in various animal models of renal fibrosis. Herein, we describe a facile strategy to achieve localized and sustained delivery of therapeutic microRNA to the kidney via a host-guest supramolecular hydrogel. Specifically, cationic bovine serum albumin is used to complex with miR-29 b to afford nanocomplexes (cBSA/miR-29 b), which is proven to specifically inhibit fibroblast activation in a dose-dependent manner in vitro. Following unilateral ureteral obstruction in mice, a single injection of the hydrogel loaded with cBSA/miR-29 b in vivo, significantly down-regulated proteins and genes related to fibrosis for up to 21 days without affecting the normal liver or kidney functions. Overall, the localized delivery of cBSA/miR-29 b via a host-guest supramolecular hydrogel represents a safe and effective intervention strategy to delay and reverse the progression of interstitial renal fibrosis.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120902DOI Listing
August 2021
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