Publications by authors named "Tianyu Li"

247 Publications

CO/chemosensitization/antiangiogenesis synergistic therapy with HO-responsive diselenide-containing polymer.

Biomaterials 2021 Feb 17;271:120721. Epub 2021 Feb 17.

Key Laboratory of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing, 100084, China. Electronic address:

Carbon monoxide (CO) therapy and antiangiogenesis therapy (AAT) are regarded as promising approaches for cancer treatment. However, the poor tumor targeting ability and inevitable side effects prevent their clinical application. In this study, we developed HO-responsive diselenide-containing micelles that combined CO therapy with chemosensitization therapy and AAT in a single system. Under the interaction of intratumoral HO, CO and gemcitabine (GEM) were released in situ from the micelles to reduce side effects, and CO significantly sensitized the chemotherapeutic effect of GEM by elevating the level of reactive oxygen species (ROS) in human gastric cancer AGS cells. Furthermore, diselenide bonds in the micelles were oxidized to seleninic acid in organic form, which suppressed the expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) to realize AAT. This study provides an integrated solution to combine CO therapy with chemosensitization therapy and AAT together with good biocompatibility.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120721DOI Listing
February 2021

The influence of previous arthroscopic treatment on subsequent primary total knee arthroplasty: the comparison between bilateral knees of the same patient.

BMC Musculoskelet Disord 2021 Jan 29;22(1):125. Epub 2021 Jan 29.

Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.

Background: To explore whether previous arthroscopic knee surgery affects future total knee arthroplasty (TKA) results or not.

Methods: A total of 56 patients with the previous arthroscopic treatment on one knee underwent subsequent bilateral total knee arthroplasty in our hospital from September 2012 to July 2018. Data on each patient were collected in regards to changes in postoperative clinical and functional scores, various other scores, as well as postoperative functional recovery and complications. We defined the knees with a previous arthroscopic history as group A, and the counter side as group B. The Knee Society clinical score, functional scores, range of motion (ROM), finger joint size (FJS), visual analogue scale (VAS) scores were assessed before and after surgery. Using the Kolmogorov-Smirnov Test to test the normality of continuous variables, and the chi-square test to compare the rate of reoperation and complications between two groups. For all statistical comparisons, P < 0.05 was considered significant.

Results: There were no statistically significance differences found in postoperative Knee Society clinical scores and functional scores between group A and group B, as well as in ROM, FJS, VAS scores and local complications.

Conclusion: There were no statistically significant differences found in postoperative functional recovery and complications in patients, who underwent total knee arthroplasty with previous knee arthroscopy.
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http://dx.doi.org/10.1186/s12891-021-04003-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847036PMC
January 2021

A novel oncotherapy strategy: Direct thrombin inhibitors suppress progression, dissemination and spontaneous metastasis in non-small cell lung cancer.

Br J Pharmacol 2021 Jan 22. Epub 2021 Jan 22.

Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Fudan University, Shanghai, China.

Background And Purpose: Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer. Nevertheless, thrombin expression in non-small cell lung cancer (NSCLC) primary tumour tissues and the association between prognosis of NSCLC patients remain largely unknown.

Experimental Approach: Clinical pathological analysis was performed to determine the relationship between thrombin and tumour progression. Effects of r-hirudin and direct thrombin inhibitor peptide (DTIP) on cancer progression were evaluated. Western blotting, immunohistochemistry, and immunofluorescence were used to explore the inhibition mechanism of r-hirudin and DTIP. The therapeutic effect of the combination of DTIP and chemotherapy was determined.

Key Results: Thrombin expression in NSCLC tissues was closely related to clinicopathological features and the prognosis of patients. Thrombin deficiency inhibited tumour progression. The novel thrombin inhibitors, r-hirudin and DTIP, inhibited cell invasion and metastasis in vitro. They inhibited tumour growth and metastasis in orthotopic lung cancer model, inhibited cell invasion, and prolonged survival after injection of tumour cells via the tail vein. They also inhibited angiogenesis and spontaneous metastases from subcutaneously inoculated tumours. The promotion by thrombin of invasion and metastasis was abolished in PAR-1-deficient NSCLC cells. r-hirudin and DTIP inhibited tumour progression through the thrombin-PAR-1-mediated RhoA and NF-κB signalling cascades via inhibiting MMP9 and IL6 expression. DTIP potentiated chemotherapy-induced growth and metastatic inhibition and inhibited chemotherapy-induced resistance in mice.

Conclusions And Implications: Thrombin makes a substantial contribution, together with PAR-1, to NSCLC malignancy. The anti-coagulants, r-hirudin and DTIP, could be used in anti-tumour therapy and a combination of DTIP and chemotherapy might improve therapeutic effects.
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http://dx.doi.org/10.1111/bph.15384DOI Listing
January 2021

Phenylene-Bridged Bispyridinium with High Capacity and Stability for Aqueous Flow Batteries.

Adv Mater 2021 Feb 14;33(7):e2005839. Epub 2021 Jan 14.

Key Laboratory on Fuel Cell Technology of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510641, P. R. China.

A rotating phenyl ring is introduced between the two pyridinium rings, namely, 1,1'-bis[3-(trimethylamonium)propyl]-4,4'-(1,4-phenylene)bispyridinium tetrachloride ((APBPy)Cl ), to form a switchable conjugation. In this design, the conjugation is switched "off" in the oxidized state and the two pyridinium rings behave independently during the redox process, yielding a concomitant transfer of two electrons at the same potential and, thus, simplifying the battery management. The conjugation is switched "on" in the reduced state and the charge can be effectively delocalized, lowering the Lewis basicity and improving its chemical stability. By pairing 0.50 m (APBPy)Cl with a 2,2,6,6-tetramethylpiperidin-1-yl oxyl derivative as the positive electrolyte, a flow battery delivers a high standard cell voltage of 1.730 V and a high specific capacity of 20.0 Ah L . The battery also shows an exceptionally high energy efficiency of 80.8% and a superior cycling stability at 80 mA cm . This strategy proves itself a great success in engineering viologen as a two-electron storage mediator with high capacity and stability.
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http://dx.doi.org/10.1002/adma.202005839DOI Listing
February 2021

Long-Term Outcomes of Single-Vessel Percutaneous Coronary Intervention on Culprit Vessel vs. Multivessel Percutaneous Coronary Intervention in Non-ST-Segment Elevation Acute Coronary Syndrome Patients With Multivessel Coronary Artery Disease.

Circ J 2021 Jan 9;85(2):185-193. Epub 2021 Jan 9.

Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College.

Background: The optimal percutaneous coronary intervention (PCI) strategy for multivessel lesions in the setting of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) remains controversial. This study sought to compare long-term prognosis between single-vessel PCI (SV-PCI) and multivessel PCI (MV-PCI) in patients with multivessel coronary artery disease (MV-CAD) presenting with NSTE-ACS in a real-world population.Methods and Results:NSTE-ACS patients with MV-CAD undergoing PCI in Fuwai Hospital in 2013 were consecutively enrolled. SV-PCI was defined as targeting only the culprit vessel, whereas MV-PCI was defined as treating ≥1 coronary artery(s) in addition to the culprit vessel at the index procedure. The primary endpoint was the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) at 2 years, consisting of all-cause death, cardiac death, myocardial infarction, unplanned revascularization, or stroke. A total of 3,338 patients were included. Both SV-PCI and MV-PCI were performed in 2,259 patients and 1,079 patients, respectively. During a median follow up of 2.1 years, the MACCE rates and adjusted risk were not significantly different between the SV-PCI and MV-PCI groups (13.1% vs. 14.0%, P=0.735; adjusted HR=0.967, 95% CI: 0.792-1.180). Similar results were observed in propensity-score matching and inverse probability of treatment weighting analyses. Subgroup analysis revealed a consistent effect on 2-year MACCE across different subgroups.

Conclusions: In NSTE-ACS patients with MV-CAD, MV-PCI is not superior to SV-PCI in terms of long-term MACCE.
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http://dx.doi.org/10.1253/circj.CJ-20-0369DOI Listing
January 2021

An Overview of Glycerol Electrooxidation Mechanisms on Pt, Pd and Au.

ChemSusChem 2021 Jan 11. Epub 2021 Jan 11.

Department of Chemistry, University of Victoria, Victoria, BC, Canada, V8W 3V6.

In the most recent decade, glycerol electrooxidation (GEOR) has attracted extensive research interest for valorization of glycerol: the conversion of glycerol to value-added products. These reactions at platinum, palladium, and gold electrodes have a lot of uncertainty in their reaction mechanisms, which has generated some controversies. This review gathers many reported experimental results, observations and proposed reaction mechanisms in order to draw a full picture of GEOR. A particular focus is the clarification of two propositions: Pd is inferior to Pt in cleaving the C-C bonds of glycerol during the electrooxidation and the massive production of CO at high overpotentials is due to the oxidation of the already-oxidized carboxylate products. It is concluded that the inferior C-C bond cleavability with Pd electrodes, as compared with Pt electrodes, is due to the inefficiency of deprotonation, and the massive generation of CO as well as other C1/C2 side products is partially caused by the consumption of OH at the anodes, as a lower pH reduces the amount of carboxylates and favors the C-C bond scission. A reaction mechanism is proposed in this review, in which the generation of side products are directly from glycerol ("competition" between each side product) rather than from the further oxidation of C2/C3 products. Additionally, GEOR results and associated interpretations for Ni electrodes are presented, as well as a brief review on the performances of multi-metallic electrocatalysts (most of which are nanocatalysts) as an introduction to these future research hotpots.
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http://dx.doi.org/10.1002/cssc.202002669DOI Listing
January 2021

Research on the Preparation and Anticorrosion Properties of EP/CeO-GO Nanocomposite Coating.

Polymers (Basel) 2021 Jan 6;13(2). Epub 2021 Jan 6.

College of Civil and Transportation Engineering, Hohai University, Nanjing 210000, China.

Due to its special two-dimensional lamellar structure, graphene possesses an excellent shielding effect, hydrophobic characteristics and large specific surface area, which can effectively isolate the internal structure from the external corrosive media. However, lamellar graphene is easy to stack and agglomerate, which limits its anti-corrosion performance. In this paper, cerium oxide-graphene oxide (CeO-GO) nanocomposites were prepared by a hydrothermal synthesis method. Field emission scanning electron microscope (FESEM) and transmission electron microscope (TEM) were applied for microstructure examination, showing that a large number of nanoscale granular cerium oxide grew on the lamellar graphene oxide surface, which improved the dispersion performance of graphene inside the matrix. The anti-corrosion properties of the coating were analyzed and illustrated by open circuit potential (OCP), frequency response analysis, Tafel curve and Mott-Schottky curve. The results indicated that the CeO-GO (4:1) nanocomposite not only eliminated the agglomeration of graphene to some extent, but also prepared the graphene epoxy coating with good dispersion, which further promoted its anti-corrosion performance. The paper proposed a feasible solution for GO dispersion in cement-based materials and lays a solid theoretical foundation for the engineering application of cerium oxide-graphene oxide modified anticorrosive coating.
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http://dx.doi.org/10.3390/polym13020183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825610PMC
January 2021

Structural elucidation and osteogenic activity of a novel heteropolysaccharide from Alhagi pseudalhagi.

Int J Biol Macromol 2021 Feb 5;171:185-197. Epub 2021 Jan 5.

Clinical Pharmacy of the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510006, China; School of Clinical Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address:

Alhagi pseudalhagi, commonly known as camel thorn, is used as an indigenous medicinal plant in China. The present study was designed to elucidate the structure of a novel polysaccharide, APP90-2, isolated from Alhagi pseudalhagi and evaluate its osteogenic activity. A homogeneous polysaccharide (APP90-2) was obtained from A. pseudalhagi via DEAE-52 and Sephacryl S-100 columns, with a molecular weight of 5.9 kDa. Monosaccharide, GC-MS, and NMR analyses showed that APP90-2 consisted of α-l-Rhap-(1→, →3)-α-l-Araf-(1→, →5)-α-l-Araf-(1→, →4)-β-d-Xylp-(1→, α-d-Glcp-(1→, →3,5)-α-l-Araf-(1→, →4)-β-d-GlcAp-(1→, →4)-3-OAc-α-d-Glcp-(1→, →3)-α-d-Galp-(1→, →3)-β-d-GalAp-(1→, →4)-α-d-Galp-(1→, →6)-α-d-Manp-(1→, →4,6)-β-d-Galp-(1→, and →3,6)-β-d-Glcp-(1→ with relative molar ratios of 4.1:1.8:6.1:6.7:1.7:1.0:1.5:2.7:2.4:1.1:2.3:2.6:1.4:2.0. Morphological analyses revealed that APP90-2 interacted with Congo-red and had an obvious honeycomb structure. Additionally, APP90-2 significantly promoted proliferation, differentiation, and mineralization of MC3T3-E1 cells, indicating that APP90-2 exhibited pronounced osteogenic activity. Therefore, our findings suggest that A. pseudalhagi may be used as an alternative medicine or health supplement for the prevention and treatment of osteoporosis.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.12.189DOI Listing
February 2021

Enhanced degradation of sulfamethoxazole by a novel Fenton-like system with significantly reduced consumption of HO activated by g-CN/MgO composite.

Water Res 2021 Feb 23;190:116777. Epub 2020 Dec 23.

Tongji University, College of Environmental Science & Engineering, State Key Lab Pollut Control & Resource Reuse, Shanghai 200092, Shanghai, China.

Advanced oxidation processes (AOP) based on nonradicals have attracted growing attentions because nonradical systems require much less oxidants and have low susceptibility to radical scavengers. Herein, a novel Fenton-like system that utilizes nonradicals was explored. It was derived from g-CN/MgO activated HO, and can reduce the HO stoichiometry from 0.94%-0.18% to 0.03%. Sulfamethoxazole (SMX), a widely used sulfonamide, was used as the model pollutant to evaluate the efficacy of the system. It was observed for the first time that organic pollutants can be degraded with singlet oxygen (O) through a nonradical pathway in the g-CN/MgOHO system. The reduced HO consumption was the net result of continuously-recycled HO from the reactions between HO and g-CN/MgO. Based on experimental results and theoretical calculations, the synthesis of g-CN and MgO forms a N-Mg bond with strong ability to absorb electrons and the electron transfer of HO to N-Mg bonding is accelerated, activation of HO to generate O. Experimental data showed that organic pollutants can be degraded rapidly over a wide pH range. Findings of this study point to a cyclical but stable Fenton-like system with reduced HO requirement for cost-effective remediation and treatment of organic pollutants and toxic wastes.
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http://dx.doi.org/10.1016/j.watres.2020.116777DOI Listing
February 2021

Stop Four Gaps with One Bush: Versatile Hierarchical Polybenzimidazole Nanoporous Membrane for Highly Durable Li-S Battery.

ACS Appl Mater Interfaces 2020 Dec 7;12(50):55809-55819. Epub 2020 Dec 7.

Division of Energy Storage, Dalian National Laboratory for Clean Energy (DNL), Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, P. R. China.

Lithium-sulfur (Li-S) batteries are considered as one of the most prospective candidates for electric vehicles, due to their superior theoretical energy density and low cost. However, the issues of polysulfide ion (PS) shuttling and uncontrollable Li dendrite growth hindered their further application. Herein, a multifunctional nanoporous polybenzimidazole (PBI) membrane with well-controllable morphology was successfully designed and fabricated to address the aforementioned obstacles. In this design, the PBI membrane could offer strong chemical binding interaction with PS, thus applying dynamic adsorption toward PS as well as stable sulfur electrochemistry, which is further verified by experiments and density functional theory (DFT) simulation. Moreover, PBI membranes with high porosity and high electrolyte uptake capability can provide ample lithium storage space and abundant Li supplements to facilitate Li deposition and improve Li metal batteries' cyclic stability. Besides that, the PBI membrane has excellent mechanical and thermal stability and exclusive flame resistance, which guarantees the safety of the Li-S battery as well. As a result, Li-S batteries assembled with an as-developed PBI membrane demonstrated a remarkable rate capability of 780 mAh g at 2C and an impressive reversible capacity of 523 mAh g at 0.5C after 400 cycles, which is much higher than the commercial separators. More importantly, even with a lofty sulfur loading of 3 mg cm, a high discharge capacity of 744 mAh g (capacity retention 93.96%, at 0.1C after 100 cycles) can also be achieved. Overall, the current study highlighted a robust material platform for stable, safe, and efficient multifunctional separators for high-performance Li-S batteries.
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http://dx.doi.org/10.1021/acsami.0c15549DOI Listing
December 2020

Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer.

Clin Cancer Res 2021 Feb 30;27(4):983-991. Epub 2020 Nov 30.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Purpose: We report results from a phase II study assessing the efficacy of the WEE1 inhibitor adavosertib with cisplatin in metastatic triple-negative breast cancer (mTNBC).

Patients And Methods: Patients with mTNBC treated with 0-1 prior lines of chemotherapy received cisplatin 75 mg/m i.v. followed 21 days later by cisplatin plus adavosertib 200 mg oral twice daily for five doses every 21 days. The study had 90% power to detect the difference between null (20%) and alternative (40%) objective response rates (ORR) with a one-sided type I error of 0.1: an ORR >30% was predefined as making the regimen worthy of further study. RNA sequencing and multiplex cyclic immunofluorescence on pre- and post-adavosertib tumor biopsies, as well as targeted next-generation sequencing on archival tissue, were correlated with clinical benefit, defined as stable disease ≥6 months or complete or partial response.

Results: A total of 34 patients initiated protocol therapy; median age was 56 years, 2 patients (6%) had mutations, and 14 (41%) had one prior chemotherapy. ORR was 26% [95% confidence interval (CI), 13-44], and median progression-free survival was 4.9 months (95% CI, 2.3-5.7). Treatment-related grade 3-5 adverse events occurred in 53% of patients, most commonly diarrhea in 21%. One death occurred because of sepsis, possibly related to study therapy. Tumors from patients with clinical benefit demonstrated enriched immune gene expression and T-cell infiltration.

Conclusions: Among patients with mTNBC treated with 0-1 prior lines, adavosertib combined with cisplatin missed the prespecified ORR cutoff of >30%. The finding of immune-infiltrated tumors in patients with clinical benefit warrants validation.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887044PMC
February 2021

UBC9 coordinates inflammation affecting development of bladder cancer.

Sci Rep 2020 11 26;10(1):20670. Epub 2020 Nov 26.

Department of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Dysregulation of SUMO modification is linked to carcinogenesis. UBC9 is the sole conjugating enzyme in sumoylation and plays a pivotal role in maintaining homeostasis and restraining stress reactions. However, the clinical significance and function of UBC9 in bladder cancer remain unclear. In this study, immunohistochemistry was used to determine the expression of UBC9. UBC9 knock-down and SUMO inhibition were conducted followed by proliferation, migration, and cell cycle assays. RNA sequencing and bioinformatic analysis were used to identify potential mechanisms of UBC9. Cytokine membrane antibody array was used to detect the expression of cytokine. The mass cytometry TOF (CyTOF) was used to explore the association between bladder cancer stem cell-like population and UBC9 expression. Our results showed that UBC9 played a dual role in bladder cancer. UBC9 was up-regulated in bladder cancer, but was negatively correlated with TNM stage and grade. Knocking-down of UBC9 resulted in dramatic activation of inflammatory gene expression, which might cause inhibition of cell proliferation and inducing cell apoptosis. IL6 was the hub gene in UBC9 regulatory network. Markedly up-regulated IL6 after knocking-down of UBC9 activated the expression of CD44, which was a prominent marker of cancer stem cells. Thus, our results revealed an important and previously undescribed role for UBC9 in modulation of inflammatory signaling of bladder cancer. UBC9 in bladder cancer cells is required to maintain high sumoylation levels and alleviate stress-related inflammation threats to cell survival. Lacking UBC9 contributes to inflammation activation, epithelial-mesenchymal transition and stem cell-like population formation, leading to cancer progression.
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http://dx.doi.org/10.1038/s41598-020-77623-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691338PMC
November 2020

Effect of particulate matter exposure on the prevalence of allergic rhinitis in children: A systematic review and meta-analysis.

Chemosphere 2021 Apr 2;268:128841. Epub 2020 Nov 2.

Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China. Electronic address:

Among various air pollutants, particulate matter (PM) is the most harmful and representative pollutant. At the same time, allergic rhinitis (AR) is getting more and more attention, so we explore the relationship between PM and the prevalence of AR among children. Then, PubMed, Web of Science, Google Scholar was used to search for relevant studies up to January 2020. Literature quality assessment was processed using the Newcastle-Ottawa Scale (NOS) evaluation scale. Adjusted odds ratio (OR) with corresponding 95% confidence interval (CI) was retrieved from individual studies and pooled to generate a summary effect via STATA software. Besides, we test the result stability by Egger's test and funnel plot, and using the trim-and-fill method to modify the possible asymmetric funnel graph. 21 studies were included in the meta-analysis. 9 articles reported about PM on childhood AR (1.09, 95%CI: 1.01, 1.17, per 10 μg/m increase). 15 articles reported about PM on childhood AR (1.06, 95%CI: 1.02,1.11, per 10 μg/m increase), PM exposure has a bigger effect on children AR than PM. In addition, a series of subgroup analysis was performed, and we found that PM and PM have different performances in different subgroups. In addition to this, we analyzed the sources of heterogeneity of the study. Apart from the results we got all have good stability without publication bias. Therefore, it can be concluded that exposure to PM may increase the prevalence of AR among children.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128841DOI Listing
April 2021

Biomimetic Diselenide-Bridged Mesoporous Organosilica Nanoparticles as an X-ray-Responsive Biodegradable Carrier for Chemo-Immunotherapy.

Adv Mater 2020 Dec 9;32(50):e2004385. Epub 2020 Nov 9.

CAS Key Laboratory of Bio Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China.

Chemotherapy causes off-target toxicity and is often ineffective against solid tumors. Targeted and on-demand release of chemotherapeutics remains a challenge. Here, cancer-cell-membrane-coated mesoporous organosilica nanoparticles (MONs) containing X-ray- and reactive oxygen species (ROS)-responsive diselenide bonds for controlled release of doxorubicin (DOX) at tumor sites are developed. DOX-loaded MONs coated with 4T1 breast cancer cell membranes (CM@MON@DOX) show greater accumulation at tumor sites and prolonged blood circulation time versus an uncoated control in mice bearing 4T1 orthotopic mammary tumors. Under low-dose X-ray radiation, the DOX-loaded MONs exhibit carrier degradation-controlled release via cleavage of diselenide bonds, resulting in DOX-mediated immunogenic cell death at the tumor site. Combination with a PD-L1 checkpoint blockade further enhances inhibition of tumor growth and metastasis with low systemic toxicity. Together, the findings show the promise of these biomimetic, radiation-responsive diselenide-bond-bridged MONs in chemo-immunotherapy.
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http://dx.doi.org/10.1002/adma.202004385DOI Listing
December 2020

Low-Cost Titanium-Bromine Flow Battery with Ultrahigh Cycle Stability for Grid-Scale Energy Storage.

Adv Mater 2020 Dec 1;32(49):e2005036. Epub 2020 Nov 1.

Division of Energy Storage, Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, P. R. China.

Flow batteries are one of the most promising large-scale energy-storage systems. However, the currently used flow batteries have low operation-cost-effectiveness and exhibit low energy density, which limits their commercialization. Herein, a titanium-bromine flow battery (TBFB) featuring very low operation cost and outstanding stability is reported. In this battery, a novel complexing agent, 3-chloro-2-hydroxypropyltrimethyl ammonium chloride, is employed to stabilize bromine/polybromides and suppress Br diffusion. The results reveal that the complexing agent effectively inhibits Br crossover and reduces Br-induced corrosivity, which in turn significantly improves the reliability of the TBFB system. The novel TBFB demonstrates 95% coulombic efficiency and 83% energy efficiency at 40 mA cm current density. Moreover, it can run smoothly for more than 1000 cycles without any capacity decay. Furthermore, an assembled 300 W TBFB stack can be continuously operated for more than 500 cycles, thereby confirming the practical applicability of the proposed TBFB. Because the TBFB utilizes an ultralow-cost electrolyte (41.29 $ kWh ) and porous polyolefin membranes, it serves as a reliable and low-cost energy-storage device. Therefore, considering its ultrahigh stability and low cost, the TBFB can be used as a large-scale energy-storage device.
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http://dx.doi.org/10.1002/adma.202005036DOI Listing
December 2020

Hemorrhagic Transformation After Tissue Plasminogen Activator Treatment in Acute Ischemic Stroke.

Cell Mol Neurobiol 2020 Oct 30. Epub 2020 Oct 30.

Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.

Hemorrhagic transformation (HT) is a common complication after thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) in ischemic stroke. In this article, recent research progress of HT in vivo and in vitro studies was reviewed. We have discussed new potential mechanisms and possible experimental models of HT development, as well as possible biomarkers and treatment methods. Meanwhile, we compared and analyzed rodent models, large animal models and in vitro BBB models of HT, and the limitations of these models were discussed. The molecular mechanism of HT was investigated in terms of BBB disruption, rt-PA neurotoxicity and the effect of neuroinflammation, matrix metalloproteinases, reactive oxygen species. The clinical features to predict HT were represented including blood biomarkers and clinical factors. Recent progress in neuroprotective strategies to improve HT after stroke treated with rt-PA is outlined. Further efforts need to be made to reduce the risk of HT after rt-PA therapy and improve the clinical prognosis of patients with ischemic stroke.
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http://dx.doi.org/10.1007/s10571-020-00985-1DOI Listing
October 2020

The relationship between long-term exposure to PM and hypertension in women:A meta-analysis.

Ecotoxicol Environ Saf 2021 Jan 26;208:111492. Epub 2020 Oct 26.

Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China. Electronic address:

Objective: Gender difference and PM exposure all have effects on hypertension, change of estrogen level in different women's stage bring complex influence on blood pressure. Then we conduct this meta-analysis to investigate the association between long-term exposure (at least one year) to fine particulate matter (PM) and hypertension in adult non-pregnant women.

Method: Four major databases: PubMed, Cochrane Library, Web of Science and Embase were searched with specific search terms, and 11 studies were finally selected. The meta-analysis module of software Stata 12.0 was used for data processing with the effect values hazard ratio (HR) and odds ratio (OR) respectively.

Results: After sensitivity analysis, we removed a study with highly heterogeneity and finally included 10 studies. Meta-analysis results showed that exposure to PM (per 10 μg/m increase) was associated with hypertension in non-pregnancy adult women, HR = 1.23, 95%CI: 1.08-1.40; OR = 1.07, 95%CI: 1.00-1.14. And subgroup analysis showed that menopause, non-White and diabetes are the key risk factors of hypertension when exposed to PM.

Conclusion: This is the first meta-analysis to explore the association between PM and non-pregnancy women, and calculate OR and HR respectively for the first time. Exposure to PM could increase the risk of hypertension in non-pregnancy women, and the combined 'HR' was much higher than 'OR'.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111492DOI Listing
January 2021

Repeated Nitrous Oxide Exposure Exerts Antidepressant-Like Effects Through Neuronal Nitric Oxide Synthase Activation in the Medial Prefrontal Cortex.

Front Psychiatry 2020 3;11:837. Epub 2020 Sep 3.

Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.

Clinical studies have demonstrated that exposure to the inhalational general anesthetic nitrous oxide (NO) produces antidepressant effects in depressed patients. However, the mechanisms underlying the antidepressant effects of NO remain largely unknown. Neuronal nitric oxide synthase (nNOS)-mediated nitric oxide (NO) synthesis is essential for brain function and underlies the molecular mechanisms of many neuromodulators. We hypothesized that activation of the nNOS/NO pathway in the medial prefrontal cortex (mPFC) might mediate the antidepressant effects of NO. In this study, we revealed that repeated NO exposure produced antidepressant-like responses in mice. Our mechanistic exploration showed that repeated NO exposure increased burst firing activity and that the expression levels of BDNF with nNOS activation were dependent in the mPFC. In particular, the antidepressant-like effects of NO were also antagonized by local nNOS inhibition in the mPFC. In summary, our results indicated that NO exposure enhances BDNF expression levels and burst firing rates in an nNOS activation dependent manner, which might underlie the pharmacological mechanism of the antidepressant-like effects of NO exposure. The present study appears to provide further mechanistic evidence supporting the antidepressant effects of NO.
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http://dx.doi.org/10.3389/fpsyt.2020.00837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495238PMC
September 2020

Porous Membrane with High Selectivity for Alkaline Quinone-Based Flow Batteries.

ACS Appl Mater Interfaces 2020 Oct 16;12(43):48533-48541. Epub 2020 Oct 16.

Division of Energy Storage, Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, P. R. China.

Aqueous organic-based flow batteries are increasingly receiving attention owing to their appealing traits of high safety and low cost. An economic and high-performance membrane is always regarded as the heart of the batteries. Here, we introduce a cost-effective, homemade porous membrane with high performance for alkaline quinone-based flow batteries. The membrane is constituted by highly stable poly(ether sulfone) (PES) and sulfonated poly(ether ether ketone) (SPEEK) that serves dual functions of (1) adjusting the membrane microstructure and (2) endowing the membrane with a charge trait. Benefiting from the well-tuned structure and charge property of the membrane, a high ion selectivity and transport of OH with much higher mobility serving as the primary charge-balancing ion can be realized. By employing alkaline alizarin red (ARS)/ferro-ferricyanide flow battery as the platform, a battery delivers a coulombic efficiency (CE) of 98.28% and an energy efficiency (EE) of 85.81% at 40 mA cm, which is higher than that of the battery with a Nafion 212 membrane (CE ∼ 99.19%, EE ∼ 84.60%), however, with much lower cost. The successful application of homemade porous membrane may provide a new strategy to engineer and fabricate membranes with high efficiency for alkaline quinone-based flow batteries and further decrease the batteries' cost.
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http://dx.doi.org/10.1021/acsami.0c13172DOI Listing
October 2020

Comprehensive Analysis of Immunoinhibitors Identifies LGALS9 and TGFBR1 as Potential Prognostic Biomarkers for Pancreatic Cancer.

Comput Math Methods Med 2020 30;2020:6138039. Epub 2020 Sep 30.

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Pancreatic cancer (PC) is one of the most deadly cancers worldwide. To uncover the unknown novel biomarker used to indicate early diagnosis and prognosis in the molecular therapeutic field of PC is extremely of importance. Accumulative evidences indicated that aberrant expression or activation of immunoinhibitors is a common phenomenon in malignances, and significant associations have been noted between immunoinhibitors and tumorigenesis or progression in a wide range of cancers. However, the expression patterns and exact roles of immunoinhibitors contributing to tumorigenesis and progression of pancreatic cancer (PC) have not yet been elucidated clearly. In this study, we investigated the distinct expression and prognostic value of immunoinhibitors in patients with PC by analyzing a series of databases, including TISIDB, GEPIA, cBioPortal, and Kaplan-Meier plotter database. The mRNA expression levels of IDO1, CSF1R, VTCN1, KDR, LGALS9, TGFBR1, TGFB1, IL10RB, and PVRL2 were found to be significantly upregulated in patients with PC. Aberrant expression of TGFBR1, VTCN1, and LGALS9 was found to be associated with the worse outcomes of patients with PC. Bioinformatics analysis demonstrated that LGALS9 was involved in regulating the type I interferon signaling pathway, interferon-gamma-mediated signaling pathway, RIG-I-like receptor signaling pathway, NF-kappa B signaling pathway, cytosolic DNA-sensing pathway, and TNF signaling pathway. And TGFB1 was related to mesoderm formation, cell matrix adhesion, TGF-beta signaling pathway, and Hippo signaling pathway. These results suggested that LGALS9 and TGFBR1 might serve as potential prognostic biomarkers and targets for PC.
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http://dx.doi.org/10.1155/2020/6138039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545442PMC
September 2020

The restoration of Wnt/β-catenin signalling activity by a tuna backbone-derived peptide ameliorates hypoxia-induced cardiomyocyte injury.

Am J Transl Res 2020 15;12(9):5221-5236. Epub 2020 Sep 15.

Department of Neonatology, The Affiliated Wuxi Children's Hospital of Nanjing Medical University Wuxi 214023, Jiangsu, China.

Myocardial infarction (MI) is a serious disease with high morbidity and mortality worldwide. Reducing myocardial reperfusion injury in MI patients remains a challenge. The generation of excessive reactive oxygen species (ROS) during reperfusion is known to be responsible for injury. A peptide from tuna backbone protein (APTBP) captured our attention due to its strong antioxidant activity. Here, we aimed to assess the function of APTBP in protecting against myocardial ischaemia-reperfusion (I/R) injury and to clarify the associated mechanism. Two in vitro models generated by hypoxia and cobalt chloride treatment were used to determine the effect of APTBP on cardiomyocytes under hypoxic stress. In vivo, a rat model of I/R was generated to evaluate APTBP functions. As a result, APTBP attenuated hypoxia- or cobalt chloride-induced injury to H9C2 cells and primary cardiomyocytes. Moreover, hypoxia-induced apoptosis, ROS generation and impaired mitochondrial function were also suppressed by APTBP administration. In vivo, tail vein injection of APTBP ameliorated pathological damage and mildly restored cardiac function. To clarify the mechanism, RNA-seq was performed and revealed that the Wnt signalling pathway may be associated with this mechanism. Rescue analysis showed that β-catenin knockdown diminished the protective effect of APTBP and that the expression of an ROS generator abolished the restoration of Wnt/β-catenin signalling induced by APTBP. Collectively, our findings suggest that APTBP reduces cardiomyocyte apoptosis and protects against myocardial ischaemia-reperfusion injury by scavenging ROS and subsequently restoring Wnt/β-catenin signalling.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540155PMC
September 2020

Particulate matter exposure and biomarkers associated with blood coagulation: A meta-analysis.

Ecotoxicol Environ Saf 2020 Dec 30;206:111417. Epub 2020 Sep 30.

Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China. Electronic address:

Objective: Find the correlation between particulate matter (PM) and biomarkers related to blood coagulation, offer medical evidence to sensitive indicators and carry out early diagnosis of cardiovascular diseases.

Method: A combination of computer and manual retrieval was used to search for the keywords in PubMed (584 records), Cochrane Library (28 records), Web of Science (162 records) and Embase (163 records). Finally, a total of 25 articles were included in this meta-analysis. Stata 13.0 was applied to examine the heterogeneity among the studies and to calculate the combined effect estimates, percent variation (%) and 95% CI by selecting corresponding models. Additionally, sensitivity analysis and publication bias test were also conducted.

Results: Meta-analysis indicated that there was an association between PM exposure (per 10 µg/m increase) and fibrinogen. With the increase of PM exposure (per 10 µg/m increase), the content of fibrinogen revealed a high level (2.26%; 95% CI: 1.08-3.44%); and the increase of UFPs exposure (per 5000/cm increase) was correlated with some biomarkers such as cell surface antigen and protein ligand including ICAM-1, sCD40L, P-selectin, E-selectin and PAI-1 that indirectly related to blood coagulation, yielding a percent variation of 10.83% (95% CI: 3.49%-18.17%).

Conclusion: This meta-analysis expounded that PM-related biomarkers were associated with blood coagulation, and the relationship with fibrinogen was much stronger.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111417DOI Listing
December 2020

Ambiguous clear cell carcinoma in medullary sponge kidney: A case report.

Asian J Urol 2020 Oct 13;7(4):369-372. Epub 2019 Sep 13.

Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Medullary sponge kidney (MSK) is a characteristic renal malformation, with a relatively low incidence. Radiologically, identification of MSK is sometimes ambiguous when compared to a renal mass. Here, we report a novel renal clear cell carcinoma in MSK, and discuss our approach to treatment. We recommended that a preoperative biopsy should be performed, followed by a comprehensive discussion regarding the appropriate perioperative preparations and careful surgical techniques that should be performed for this complex disease.
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http://dx.doi.org/10.1016/j.ajur.2019.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498938PMC
October 2020

The Impact of COVID-19 on Clinical Trial Execution at the Dana-Farber Cancer Institute.

J Natl Cancer Inst 2020 Sep 22. Epub 2020 Sep 22.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.

Interventions designed to limit the spread of COVID-19 are having profound effects on the delivery of healthcare, but data showing the impact on oncology clinical trial enrollment, treatment, and monitoring are limited. We prospectively tracked relevant data from oncology clinical trials at Dana-Farber Cancer Institute (DFCI) from January 1, 2018 to June 30, 2020, including the number of open trials, new patient enrollments, in-person and virtual patient visits, dispensed investigational infusions, dispensed/shipped oral investigational agents, research biopsies, and blood samples. We ascertained why patients came off trials and determined on-site clinical research staffing levels. We used two-sided Wilcoxon rank sum tests to assess the statistical significance of the reported changes. Nearly all patients on interventional treatment trials were maintained, and new enrollments continued at just under half the pre-pandemic rate. The median number of investigational prescriptions shipped to patients increased from 0-74 (range: 22-107) per week from March-June 2020. The median number of telemedicine appointments increased from 0-107 (range: 33-267) per week from March-June 2020. Research biopsies and blood collections decreased dramatically after DFCI implemented COVID-19-related policies in March 2020. The number of research nurses and clinical research coordinators on-site also decreased after March 2020. Substantial changes were required to safely continue clinical research during the pandemic; yet, we observed no increases in serious adverse events or major violations related to drug dosing. Lessons learned from adapting research practices during COVID-19 can inform industry sponsors and governmental agencies to consider altering practices to increase operational efficiency and convenience for patients.
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http://dx.doi.org/10.1093/jnci/djaa144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543498PMC
September 2020

Identifying Activating Mutations in HER2-Negative Breast Cancer: Clinical Impact of Institute-Wide Genomic Testing and Enrollment in Matched Therapy Trials.

JCO Precis Oncol 2019 15;3. Epub 2019 Nov 15.

Dana-Farber Cancer Institute, Boston, MA.

Purpose: The yield of comprehensive genomic profiling in recruiting patients to molecular-based trials designed for small subgroups has not been fully evaluated. We evaluated the likelihood of enrollment in a clinical trial that required the identification of a specific genomic change based on our institute-wide genomic tumor profiling.

Patients And Methods: Using genomic profiling from archived tissue samples derived from patients with metastatic breast cancer treated between 2011 and 2017, we assessed the impact of systematic genomic characterization on enrollment in an ongoing phase II trial (ClinicalTrials.gov identifier: NCT01670877). Our primary aim was to describe the proportion of patients with a qualifying mutation identified by our institutional genomic panel (OncoMap or OncoPanel) who enrolled in the trial. Secondary objectives included median time from testing result to trial registration, description of the spectrum of mutations, and survival. Associations were calculated using Fisher's exact test.

Results: We identified a total of 1,045 patients with metastatic breast cancer without amplification who had available genomic testing results. Of these, 42 patients were found to have mutation and 19 patients (1.8%) were eligible for the trial on the basis of the presence of an activating mutation, 18 of which were identified by OncoPanel testing. Fifty-eight percent of potentially eligible patients were approached, and 33.3% of eligible patients enrolled in the trial guided exclusively by OncoPanel testing.

Conclusion: More than one half of eligible patients were approached for trial participation and, significantly, one third of those were enrolled in NCT01670877. Our data illustrate the ability to enroll patients in trials of rare subsets in routine clinical practice and highlight the need for these broadly based approaches to effectively support the success of these studies.
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http://dx.doi.org/10.1200/PO.19.00087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446367PMC
November 2019

Effect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer: A Randomized Clinical Trial.

JAMA Oncol 2020 10;6(10):1598-1605

Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Importance: Prior studies have shown that only a small proportion of patients with hormone receptor (HR)-positive metastatic breast cancer (MBC) experience benefit from programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors given as monotherapy. There are data suggesting that activity may be greater with combination strategies.

Objective: To compare the efficacy of eribulin plus pembrolizumab vs eribulin alone in patients with HR-positive, ERBB2 (formerly HER2)-negative MBC.

Design, Setting, And Participants: Multicenter phase 2 randomized clinical trial of patients with HR-positive, ERBB2-negative MBC who had received 2 or more lines of hormonal therapy and 0 to 2 lines of chemotherapy.

Interventions: Patients were randomized 1:1 to eribulin, 1.4 mg/m2 intravenously, on days 1 and 8 plus pembrolizumab, 200 mg/m2 intravenously, on day 1 of a 21-day cycle or eribulin alone. At time of progression, patients in the eribulin monotherapy arm could cross over and receive pembrolizumab monotherapy.

Main Outcomes And Measures: The primary end point was progression-free survival (PFS). Secondary end points were objective response rate (ORR) and overall survival (OS). Exploratory analyses assessed the association between PFS and PD-L1 status, tumor-infiltrating lymphocytes (TILs), tumor mutational burden (TMB), and genomic alterations.

Results: Eighty-eight patients started protocol therapy; the median (range) age was 57 (30-76) years, median (range) number of prior lines of chemotherapy was 1 (0-2), and median (range) number of prior lines of hormonal therapy was 2 (0-5). Median follow-up was 10.5 (95% CI, 0.4-22.8) months. Median PFS and ORR were not different between the 2 groups (PFS, 4.1 vs 4.2 months; hazard ratio, 0.80; 95% CI, 0.50-1.26; P = .33; ORR, 27% vs 34%, respectively; P = .49). Fourteen patients started crossover treatment with pembrolizumab; 1 patient experienced stable disease. All-cause adverse events occurred in all patients (grade ≥3, 65%) including 2 treatment-related deaths in the combination group, both from immune-related colitis in the setting of sepsis, attributed to both drugs. The PD-L1 22C3 assay was performed on archival tumor samples in 65 patients: 24 (37%) had PD-L1-positive tumors. Analysis indicated that PD-L1 status, TILs, TMB, and genomic alterations were not associated with PFS.

Conclusions And Relevance: In this randomized clinical trial of patients with HR-positive, ERBB2-negative MBC, the addition of pembrolizumab to eribulin did not improve PFS, ORR, or OS compared with eribulin alone in either the intention-to-treat or PD-L1-positive populations. Further efforts to explore the benefits of adding checkpoint inhibition to chemotherapy among less heavily pretreated patients are needed.

Trial Registration: ClinicalTrials.gov Identifier: NCT03051659.
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http://dx.doi.org/10.1001/jamaoncol.2020.3524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489368PMC
October 2020

Molecular insights into the human CLC-7/Ostm1 transporter.

Sci Adv 2020 Aug 12;6(33):eabb4747. Epub 2020 Aug 12.

Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.

CLC family proteins translocate chloride ions across cell membranes to maintain the membrane potential, regulate the transepithelial Cl transport, and control the intravesicular pH among different organelles. CLC-7/Ostm1 is an electrogenic Cl/H antiporter that mainly resides in lysosomes and osteoclast ruffled membranes. Mutations in human CLC-7/Ostm1 lead to lysosomal storage disorders and severe osteopetrosis. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human CLC-7/Ostm1 complex and reveal that the highly glycosylated Ostm1 functions like a lid positioned above CLC-7 and interacts extensively with CLC-7 within the membrane. Our complex structure reveals a functionally crucial domain interface between the amino terminus, TMD, and CBS domains of CLC-7. Structural analyses and electrophysiology studies suggest that the domain interaction interfaces affect the slow gating kinetics of CLC-7/Ostm1. Thus, our study deepens understanding of CLC-7/Ostm1 transporter and provides insights into the molecular basis of the disease-related mutations.
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http://dx.doi.org/10.1126/sciadv.abb4747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423370PMC
August 2020

Short-term PM exposure and circulating von Willebrand factor level: a meta-analysis.

Sci Total Environ 2020 Oct 15;737:140180. Epub 2020 Jun 15.

Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China. Electronic address:

Background: Ambient fine particulate matter (PM) is a major threat to cardiovascular health. Endothelial dysfunction is the initiating event associated with the PM-induced cardiovascular disease (CVD). A sensitive marker of endothelial function-circulating von Willebrand factor (vWF), is an independent predictor of adverse clinical outcome in CVD patients. PM exposure may cause CVD, but the reports of relationship between short-term PM exposure and circulating vWF are inconsistent.

Objective: To explore the influence of short-term PM exposure on circulating vWF.

Methods: By using a combination of computer and manual retrieval, a systematic literature retrieval was conducted on PubMed, Cochrane Library, Web of Science, Embase and Scopus databases up to October 2019. The heterogeneity among studies was tested by Stata 12.0, and the pooled %-change (percentage change per 10 μg/m increase in PM) and its 95% confidence interval (95%CI) were calculated by using random effect model. Sensitivity analysis and publication bias detection were also carried out.

Results: 12 articles were included in this meta-analysis. Short-term PM exposure (per 10 μg/m increase) was associated with the increased vWF (%-change = 0.41, 95%CI: 0.11-0.71). The pooled effect estimates of subgroup with PM exposure level < 25 μg/m was higher (%-change = 8.26; 95%CI: 1.99-14.53) than that with PM exposure level ≥ 25 μg/m (%-change = 0.36; 95%CI: 0.09-0.63).

Conclusion: Short-term PM exposure is associated with the increased circulating vWF. It suggests that short-term PM exposure causes endothelial dysfunction.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140180DOI Listing
October 2020

The relationship between exposure to PM and heart rate variability in older adults: A systematic review and meta-analysis.

Chemosphere 2020 Dec 19;261:127635. Epub 2020 Jul 19.

Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China. Electronic address:

Ambient air pollution is recognized as a major threat to those with cardiovascular disease (CVD), especially among old adults within this high risk group. Heart rate variability (HRV) is a marker of cardiac autonomic system, which links air pollution and CVD. However, the relationship between PM and HRV has been inconsistently reported. To investigate the associations of PM and HRV in old adults whose average age was 55 years old or above, we conducted a meta-analysis of nineteen longitudinal studies including nine short-term and ten long-term studies. In the short-term exposure group, per 10 μg/m increase of PM was associated with decreases in the time-domain measurements, for SDNN -0.39% (95% CI: -0.72%, -0.06%) and for RMSSD -1.20% (95% CI: -2.17%, -0.23%) and in frequency-domain measurements, for LF -2.31% (95% CI: -3.85%, -0.77%) and for HF -1.87% (95% CI: -3.45%, -0.29%); In the long-term exposure group, per 10 μg/m increase of PM was associated with decreases in the time-domain measurements, for SDNN -0.92% (95% CI: -2.14%, 0.31%) and for RMSSD -1.96% (95% CI: -3.48%, -0.44%) and in frequency-domain measurements, for LF -2.78% (95% CI: -4.02%, -1.55%) and for HF -1.61% (95% CI: -4.02%, 0.80%). Exposure to PM is associated with decreased indicators of HRV in older adults suggesting an affected cardiac autonomic system upon exposure, which may explain the association between PM and risk of CVD in older adults. Long-term exposure to PM was more strongly associated with indicators of HRV than short-term exposure.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127635DOI Listing
December 2020

Pulsatilla Saponin A Induces Apoptosis and Differentiation of Myeloma Cells.

Anticancer Agents Med Chem 2020 Jul 21. Epub 2020 Jul 21.

Leukemia Research Division, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of the Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou. China.

Objectives: To investigate the performance of Pulsatilla saponin A (PsA) in multiple myeloma (MM) cells.

Methods: Proliferation, cell cycle analysis, apoptosis and TUNEL assays were conducted to detect the growth and apoptosis in MM cells. Western blotting was used to identify the change in protein.

Results: In cells assays, PsA significantly inhibited the growth and apoptosis in MM cells. Cyclin B1, caspase-3, cleavedcaspase-3, PARP, cleaved-PARP, p-ERK were increased, while Bcl-2 were decreased after PSA treated. The CD49e positive rate of U266 cells was increased after PsA treated 96h. At the same time immunoglobulin and the free light chain (FLC) ratio in the culture supernatant obviously increased after treated. Also, the differentiation induced by PsA was confirmed in the primary myeloma cells.

Conclusions: Our findings revealed PsA may exert its antitumor effect by causing G2 arrest and apoptosis in myeloma cells. And low-dose PsA can induce the differentiation of myeloma cell lines and primary myeloma cells, probably through the MEK/ERK signaling pathway in vitro.
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http://dx.doi.org/10.2174/1871520620666200721125036DOI Listing
July 2020