Publications by authors named "Gang Han"

375 Publications

Enhancing Rechargeable Persistent Luminescence via Organic Dye Sensitization.

Angew Chem Int Ed Engl 2021 Apr 15. Epub 2021 Apr 15.

University of Massachusetts-Medical School, 364 plantation street Lrb806, 01605, Worcester, UNITED STATES.

Due to their unique afterglow ability, long wavelength light activatable persistent luminescence (PersL) nanoparticles (PLNPs) have been emerging as an important category of imaging probes. In particular, long wavelength LED light has been shown to be effective in recharging these nanoparticles. However, finding a simple and effective method to amplify such renewable PersL signals under long wavelength light is still a key challenge. Herein, we discovered that a dye-sensitization strategy was able to effectively boost the renewable PersL signals of the NIR emitting ZnGa 2 O 4 :Cr 3+ (ZGC)) under long wavelength LED light. Moreover, as a proof-of-principle tumorectomy demonstration, this new class of dye sensitized ZGC enabled simultaneous intraoperative anatomic tumor navigation and effective microscopic detection of tumor cells in pathological diagnosis. Thus, this work will offer a simple way to the development of PLNPs with enhanced luminescence and provides new opportunities for a wide variety of biophotonic and photonic applications.
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http://dx.doi.org/10.1002/anie.202101492DOI Listing
April 2021

Exosome-mediated delivery of an anti-angiogenic peptide inhibits pathological retinal angiogenesis.

Theranostics 2021 5;11(11):5107-5126. Epub 2021 Mar 5.

Department of Ophthalmology, Tianjin Medical University General Hospital, 300070, Tianjin, China.

Pathological angiogenesis is the hallmark of many vision-threatening diseases. Anti-VEGF is a primary treatment with substantial beneficial effects. However, such agents require frequent intravitreal injections. Our previous work established a method for effectively modifying exosomes (EXOs) for loading therapeutic peptides. Here, we used this system to load the anti-angiogenic peptide KV11, aiming to establish an EXO-based therapy strategy to suppress neovascularization in the retina. Using an anchoring peptide, CP05, we linked KV11 to endothelial cell (EC) derived EXOs, yielding EXO. We tested the delivery efficiency of EXO via two commonly used ocular injection methods: retro-orbital injection and intravitreal injection. Deploying an oxygen-induced retinopathy (OIR) model and a VEGF injection model, we tested the effects of EXO on neovascular formation, EC proliferation, and vascular permeability. experiments were used to test the mechanism and to analyze the effects of EXO on EC proliferation, migration, and sprouting. : By using the EXO loading system, KV11 was more efficiently delivered to the blood vessels of the mouse retina via retro-orbital injection. In both OIR model and VEGF injection model, EXO was more effective than KV11 alone in inhibiting neovascularization and vessel leakage. The therapeutic effect of retro-orbital injection of EXO was comparable to the intravitreal injection of VEGF-trap. Mechanistically, KV11 alone inhibited VEGF-downstream signaling, while EXO showed a stronger effect. We used EXOs as a carrier for intraocular delivery of KV11. We showed that KV11 itself has an anti-angiogenic effect through retro-orbital injection, but that this effect was greatly enhanced when delivered with EXOs. Thus, this system has the potential to treat proliferative retinopathy via retro-orbital injection which is a less invasive manner compared with intravitreal injection.
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http://dx.doi.org/10.7150/thno.54755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039955PMC
March 2021

A new darwinopteran pterosaur reveals arborealism and an opposed thumb.

Curr Biol 2021 Apr 10. Epub 2021 Apr 10.

Key Laboratory of Stratigraphy and Palaeontology (Ministry of Natural Resources), Institute of Geology, Chinese Academy of Geological Sciences, Beijing, China.

Pterosaurs, which lived during the Mesozoic, were the first known vertebrates to evolve powered flight. Arboreal locomotion has been proposed for some taxa, and even considered to have played a role in the origin of pterosaur flight. Even so, there is still need for comprehensive quantitative ecomorphological analyses. Furthermore, skeletal adaptations correlated to specialized lifestyles are often difficult to recognize and interpret in fossils. Here we report on a new darwinopteran pterosaur that inhabited a unique forest ecosystem from the Jurassic of China. The new species exhibits the oldest record of palmar (or true) opposition of the pollex, which is unprecedented for pterosaurs and represents a sophisticated adaptation related to arboreal locomotion. Principal-coordinate analyses suggest an arboreal lifestyle for the new species but not for other closely related species from the same locality, implying a possible case of ecological niche partitioning. The discovery adds to the known array of pterosaur adaptations and the history of arborealism in vertebrates. It also adds to the impressive early bloom of arboreal communities in the Jurassic of China, shedding light on the history of forest environments.
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http://dx.doi.org/10.1016/j.cub.2021.03.030DOI Listing
April 2021

Utility of a 31-gene expression profile for predicting outcomes in patients with primary cutaneous melanoma referred for sentinel node biopsy.

Am J Surg 2021 Mar 17. Epub 2021 Mar 17.

Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, Portland, OR, USA. Electronic address:

Background: A 31-gene genetic expression profile (31-GEP; Class 1 = low risk, Class 2 = high risk) developed to predict outcome in cutaneous melanoma (CM) has been validated by retrospective, industry-sponsored, or small series.

Methods: Tumor features, sentinel node biopsy (SNB) results, and outcomes were extracted from a prospective database of 383 C M patients who underwent SNB and had a 31-GEP run on their primary tumor. Groups were compared by uni- and multi-variable analysis. Relapse-free and distant metastasis-free survival (RFS, DMFS) were estimated by Kaplan-Meier method.

Results: Breslow thickness, T stage, and SNB positivity were significantly higher in Class 2 patients. Recurrence rates were higher for Class 2 vs Class 1 patients and highest in patients who were Class 2 and SNB positive. GEP class was predictive of RFS and DMFS and independently predicted relapse in AJCC "low risk" (stages IA-IIA) patients.

Conclusions: 31-GEP adds prognostic information in CM patents undergoing SNB.
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http://dx.doi.org/10.1016/j.amjsurg.2021.03.028DOI Listing
March 2021

Enzymatic enhancing of triplet-triplet annihilation upconversion by breaking oxygen quenching for background-free biological sensing.

Nat Commun 2021 03 26;12(1):1898. Epub 2021 Mar 26.

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, United States.

Triplet-triplet annihilation upconversion nanoparticles have attracted considerable interest due to their promises in organic chemistry, solar energy harvesting and several biological applications. However, triplet-triplet annihilation upconversion in aqueous solutions is challenging due to sensitivity to oxygen, hindering its biological applications under ambient atmosphere. Herein, we report a simple enzymatic strategy to overcome oxygen-induced triplet-triplet annihilation upconversion quenching. This strategy stems from a glucose oxidase catalyzed glucose oxidation reaction, which enables rapid oxygen depletion to turn on upconversion in the aqueous solution. Furthermore, self-standing upconversion biological sensors of such nanoparticles are developed to detect glucose and measure the activity of enzymes related to glucose metabolism in a highly specific, sensitive and background-free manner. This study not only overcomes the key roadblock for applications of triplet-triplet annihilation upconversion nanoparticles in aqueous solutions, it also establishes the proof-of-concept to develop triplet-triplet annihilation upconversion nanoparticles as background free self-standing biological sensors.
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http://dx.doi.org/10.1038/s41467-021-22282-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997900PMC
March 2021

Molecularly soldered covalent organic frameworks for ultrafast precision sieving.

Sci Adv 2021 Mar 24;7(13). Epub 2021 Mar 24.

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, State Key Laboratory of Urban Water Resource and Environment, and School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China.

The weak interlamellar interaction of covalent organic framework (COF) nanocrystals inhibit the construction of highly efficient ion/molecular sieving membranes owing to the inferior contaminant selectivity induced by defects in stacked COF membranes and stability issues. Here, a facile in situ molecularly soldered strategy was developed to fabricate defect-free ultrathin COF membranes with precise sieving abilities using the typical chemical environment for COF condensation polymerization and dopamine self-polymerization. The experimental data and density functional theory simulations proved that the reactive oxygen species generated during dopamine polymerization catalyze the nucleophilic reactions of the COF, thus facilitating the counter-diffusion growth of thin COF layers. Notably, dopamine can eliminate the defects in the stacked COF by soldering the COF crystals, fortifying the mechanical properties of the ultrathin COF membranes. The COF membranes exhibited ultrafast precision sieving for molecular separation and ion removal in both aqueous and organic solvents, which surpasses that of state-of-the-art membranes.
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http://dx.doi.org/10.1126/sciadv.abe8706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990329PMC
March 2021

Effect of PRM1201 Combined With Adjuvant Chemotherapy on Preventing Recurrence and Metastasis of Stage III Colon Cancer: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Front Oncol 2021 3;11:618793. Epub 2021 Mar 3.

Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Chemotherapy is the standard adjuvant treatment for colon cancer. Chinese herbal formula PRM1201 improves the efficacy of chemotherapy when used in combination with Cetuximab or Bevacizumab in patients with metastatic colorectal cancer. This study aims to explore the benefits of treatment with chemotherapy plus PRM1201 in the postoperative adjuvant setting.

Methods: In this parallel-group study, patients who had undergone curative resection for stage III colon cancer were randomly assigned to receive adjuvant chemotherapy (FOLFOX q2w for 6 months, or CapeOx q3w for 6 months) plus PRM1201 (chemo+PRM1201 group) or adjuvant chemotherapy plus placebo (chemo+placebo group). The primary endpoint was disease-free survival (DFS), and the secondary endpoints were quality of life (QOL) and toxicity.

Results: A total of 370 patients were randomly assigned to chemotherapy plus PRM1201 group (n = 184) and chemotherapy plus placebo group (n = 186). Up to October 30, 2019, 96 events of recurrence, metastasis, or death had been reported, of which 38 events were in the group of chemotherapy plus PRM1201 and 58 events in the chemo+placebo group. The 3-year DFS rate was 77.1 and 68.6% in the chemo+PRM1201 and chemo+placebo group, respectively (hazard ratio [HR], 0.63; 95% CI, 0.42 to 0.94). The QOL of patients in the chemo+PRM1201 group were significantly improved in terms of global quality of life, physical functioning, role functioning, emotional functioning, fatigue, and appetite loss. The incidence of grade 3 or 4 treatment-related adverse event (TRAEs) were similar between the two arms.

Conclusions: Chemotherapy in combination with PRM1201 improved the adjuvant treatment of colon cancer. PRM1201 can be recommended as an effective option in clinical practice.

Clinical Trial Registration: Chinese Clinical Trials Registry, identifier ChiCTR-IOR-16007719.
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http://dx.doi.org/10.3389/fonc.2021.618793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968418PMC
March 2021

Classification of the Use of Online Health Information Channels and Variation in Motivations for Channel Selection: Cross-sectional Survey.

J Med Internet Res 2021 Mar 9;23(3):e24945. Epub 2021 Mar 9.

Greenlee School Journalism and Communication, Iowa State University, Ames, IA, United States.

Background: Existing health education and communication research routinely measures online channel use as a whole by, for example, evaluating how frequently people use the internet to search for health information. This approach fails to capture the complexity and diversity of online channel use in health information seeking. The measurement of generic online channel use may cause too much error, and it lends no support to media planning in public health promotion campaigns or scholarly research involving online channel use.

Objective: This study intends to present a thorough picture of patterns of online health information channel use and classify the use of various types of online health information channels, including WeChat, microblogs, web portals, search engines, mobile apps, and online forums. Under the framework of the risk information seeking and processing model, this study also analyzes the differences in individuals' motivations for channel selection to offer further evidence to validate the classification scheme.

Methods: This study sampled 542 Chinese internet users in Beijing. The average age of the respondents was 33 years, female respondents accounted for 52.0% (282/542) of the sample, and the average monthly income ranged from US $900 to $1200. The study surveyed the use of 13 commonly used online health information channels and various sociopsychological factors associated with online health information seeking.

Results: This study derived 3 categories of online health information channels: searching, browsing, and scanning channels. It was found that the use of online searching channels was affect driven (B=0.11; β=0.10; P=.02) and characterized by a stronger need for health knowledge (B=0.09; β=0.01; P<.001). The use of browsing channels was directly influenced by informational subjective norms (B=0.33; β=0.15; P=.004) and perceived current knowledge (B=0.007; β=0.09; P=.003). The use of scanning channels was mainly influenced by informational subjective norms (B=0.29; β=0.15; P=.007).

Conclusions: The results of this study suggest that health communication practitioners and scholars may consider measuring the use of internet, new media, or online media more precisely instead of simply asking the public about the frequency of online channel use or internet use in the acquisition of health information. Scholars and practitioners may consider measuring the use of online health information channels by using the 3-category scheme described in this study. Future research is encouraged to further explore how people process health information when using different online channels.
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http://dx.doi.org/10.2196/24945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988389PMC
March 2021

Trap Energy Upconversion-Like Near-Infrared to Near-Infrared Light Rejuvenateable Persistent Luminescence.

Adv Mater 2021 Apr 26;33(15):e2008722. Epub 2021 Feb 26.

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.

Persistent-luminescence phosphors (PLPs) have a wide variety of applications in the fields of photonics and biophotonics due to their ultralong afterglow lifetime. However, the existing PLPs are charged and recharged with short-wavelength high-energy photons or inconvenient and potentially risky X-ray beams. To date, deep tissue penetrable NIR light has mainly been used for photostimulated afterglow emission, which continues to decay and weaken after each cycle, Herein, a new paradigm of trap energy upconversion-like near-infrared (NIR) to near-infrared light rejuvenateable persistent luminescence in bismuth-doped calcium stannate phosphors and nanoparticles is reported. In contrast to the existing PLPs and persistent-luminescence nanoparticles, the materials enable the occurrence of a reversed transition of the carriers from a deep-level energy trap to a shallow-level trap upon excitation by low-energy NIR photons. Thus these new materials can be charged circularly via deep-tissue penetrable NIR photons, which is unable to be done for existing PLPs, and emit afterglow signals. This conceptual work will lay the foundation to design new categories of NIR-absorptive-NIR-emissive PLPs and nanoparticles featuring physically harmless and deep tissue penetrable NIR light renewability and sets the stage for numerous biological applications, which have been limited by current materials.
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http://dx.doi.org/10.1002/adma.202008722DOI Listing
April 2021

Aqueous One-Step Modulation for Synthesizing Monodispersed ZIF-8 Nanocrystals for Mixed-Matrix Membrane.

ACS Appl Mater Interfaces 2021 Mar 24;13(9):11296-11305. Epub 2021 Feb 24.

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, State Key Laboratory of Urban Water Resource and Environment, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, P. R. China.

Enhancing the monodispersity and surface properties of nanoporous zeolitic imidazolate frameworks (ZIFs) are crucial for maximizing their performance in advanced nanocomposites for separations. Herein, we developed an in situ method to synthesize monodispersed ZIF-8 nanocrystals with unique dopamine (DA) surface decoration layer (ZIF-8-DA) in an aqueous solution at room temperature. Interestingly, the in situ formation of the monodispersed ZIF-8-DA nanocrystals experiences a triple-stage crystallization process, resulting in a rhombic dodecahedron architecture, which is greatly different from the synthesis of conventional ZIF-8. The crystallinity and abundant microporosity of ZIF-8-DA nanocrystals is well maintained even with the DA surface decoration. Owing to the advanced surface compatibility and pore properties of ZIF-8-DA, ZIF-8-DA/Matrimid mixed-matrix membranes exhibit both higher gas permeability and selectivity than the pristine Matrimid polyimide membrane, which breaks out the traditional "trade-off" phenomena between permeability and selectivity.
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http://dx.doi.org/10.1021/acsami.0c22910DOI Listing
March 2021

Hafnium oxide layer-enhanced single-walled carbon nanotube field-effect transistor-based sensing platform.

Anal Chim Acta 2021 Feb 31;1147:99-107. Epub 2020 Dec 31.

Key Laboratory of Control of Quality and Safety for Aquatic Products, Ministry of Agriculture, Chinese Academy of Fishery Sciences, Beijing, 100141, China. Electronic address:

Single-walled carbon nanotube-based field effect transistors (SWCNT-FETs) are ideal candidates for fabricating sensors and have been widely used for chemical sensing applications. SWCNT-FETs have low selectivity because of the environmentally sensitive electronic properties of SWCNTs, and SWCNT-FETs also show a high noise signal and poor sensitivity because of charge trapping from Si-OH hydration of the SiO/Si substrate on the SWCNTs. Herein, poly (4-vinylpyridine) (P4VP) was used for noncovalent attachment to SWCNTs and selective binding to copper ions (Cu). Importantly, the introduction of a hafnium-oxide (HfO) layer through atomic layer deposition (ALD) overcame the charge trapping by SiO hydration and remarkably decreased the interference signal. The sensitivity of the P4VP/SWCNT/HfO-FET sensor for Cu was 7.9 μA μM, which was approximately 100 times higher than that of the P4VP/SWCNT/SiO-FET sensor, and its limit of detection (LOD) was as low as 33 pmol L. Thus, the P4VP/SWCNT/HfO-FET sensor is a promising candidate for the development of Cu-selective sensors and can be designed for the large-scale manufacturing of custom-made sensors in the future.
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http://dx.doi.org/10.1016/j.aca.2020.12.040DOI Listing
February 2021

A Multifunctional Nanovaccine based on L-Arginine-Loaded Black Mesoporous Titania: Ultrasound-Triggered Synergistic Cancer Sonodynamic Therapy/Gas Therapy/Immunotherapy with Remarkably Enhanced Efficacy.

Small 2021 Feb 20;17(6):e2005728. Epub 2021 Jan 20.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

In order to achieve better antitumor therapeutic efficacy and inhibit tumor metastasis, a multifunctional nanovaccine based on L-arginine (LA)-loaded black mesoporous titania (BMT) is fabricated. In this system, LA is utilized as the exogenous NO supplementation for gas therapy, and BMT is served as acoustic sensitizer for sonodynamic therapy. The ultrasound (US) as the exogenous stimulus can simultaneously trigger BMT and LA to produce singlet oxygen ( O ) and NO gas at tumor sites, respectively. Interestingly, O from US-excited BMT can promote the oxidation of LA to produce more NO. The high concentration of O and NO in cancer cell can cause intracellular strong oxidative stress level and DNA double-strand breaks to induce cancer cell apoptosis ultimately. The US-triggered BMT@LA "nanovaccine" combining with immune checkpoint inhibitor PD-L1 antibody (αPD-L1) can induce strong antitumor immune response thus effectively killing primary tumors and further inhibiting metastatic tumors. Hence, BMT@LA-based "nanovaccine" combining with αPD-L1 checkpoint blockade treatment can realize synergetic sonodynamic/gas/immunotherapy with enhanced antitumor therapeutic effects.
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http://dx.doi.org/10.1002/smll.202005728DOI Listing
February 2021

A Phase-Change Mechanism of GST-SL Based Superlattices upon Sb Flipping.

Materials (Basel) 2021 Jan 13;14(2). Epub 2021 Jan 13.

Key Laboratory of Trans-Scale Laser Manufacturing Technology, Beijing University of Technology, Ministry of Education, 100 Ping Leyuan, Chaoyang District, Beijing 100124, China.

Reversible phase-change behaviors of Ge-Sb-Te based superlattices (GST-SL) were studied by ab initio molecular dynamics (AIMD) simulations based on three models containing Ge/Sb intermixing, namely the Petrov-mix, Ferro-mix, and Kooi-mix models. The flipping behavior of Sb atoms was found in all the three GST-SL models in the melting process. Among them the Kooi-mix model exhibited the best stability, and the analyses of bond length distribution and electron localization function provided a better explanation on the phase transition of GST-SL. Finally, we proposed a fast switching model for GST-SL based on Sb flipping.
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http://dx.doi.org/10.3390/ma14020360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828381PMC
January 2021

Long wavelength single photon like driven photolysis via triplet triplet annihilation.

Nat Commun 2021 01 5;12(1):122. Epub 2021 Jan 5.

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.

Photolysis has enabled the occurrence of numerous discoveries in chemistry, drug discovery and biology. However, there is a dearth of efficient long wavelength light mediated photolysis. Here, we report general and efficient long wavelength single photon method for a wide array of photolytic molecules via triplet-triplet annihilation photolysis. This method is versatile and "LEGO"-like. The light partners (the photosensitizers and the photolytic molecules) can be energetically matched to adapt to an extensive range of electromagnetic spectrum wavelengths and the diversified chemical structures of photoremovable protecting groups, photolabile linkages, as well as a broad array of targeted molecules. Compared to the existing photolysis methods, our strategy of triplet-triplet annihilation photolysis not only exhibits superior reaction yields, but also resolves the photodamage problem, regardless of whether they are single photon or multiple photon associated. Furthermore, the biological promise of this "LEGO" system was illustrated via developing ambient air-stable nanoparticles capable of triplet-triplet annihilation photolysis.
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http://dx.doi.org/10.1038/s41467-020-20326-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785739PMC
January 2021

Diagnosis and Management of Intraabdominal Infection: Guidelines by the Chinese Society of Surgical Infection and Intensive Care and the Chinese College of Gastrointestinal Fistula Surgeons.

Clin Infect Dis 2020 Dec;71(Supplement_4):S337-S362

Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

The Chinese guidelines for IAI presented here were developed by a panel that included experts from the fields of surgery, critical care, microbiology, infection control, pharmacology, and evidence-based medicine. All questions were structured in population, intervention, comparison, and outcomes format, and evidence profiles were generated. Recommendations were generated following the principles of the Grading of Recommendations Assessment, Development, and Evaluation system or Best Practice Statement (BPS), when applicable. The final guidelines include 45 graded recommendations and 17 BPSs, including the classification of disease severity, diagnosis, source control, antimicrobial therapy, microbiologic evaluation, nutritional therapy, other supportive therapies, diagnosis and management of specific IAIs, and recognition and management of source control failure. Recommendations on fluid resuscitation and organ support therapy could not be formulated and thus were not included. Accordingly, additional high-quality clinical studies should be performed in the future to address the clinicians' concerns.
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http://dx.doi.org/10.1093/cid/ciaa1513DOI Listing
December 2020

MOTS-c promotes phosphorodiamidate morpholino oligomer uptake and efficacy in dystrophic mice.

EMBO Mol Med 2021 Feb 18;13(2):e12993. Epub 2020 Dec 18.

Tianjin Key Laboratory of Cellular Homeostasis and Human Diseases & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics &, Department of Cell Biology, Tianjin Medical University, Tianjin, China.

Antisense oligonucleotide (AO)-mediated exon-skipping therapies show promise in Duchenne muscular dystrophy (DMD), a devastating muscular disease caused by frame-disrupting mutations in the DMD gene. However, insufficient systemic delivery remains a hurdle to clinical deployment. Here, we demonstrate that MOTS-c, a mitochondria-derived bioactive peptide, with an intrinsic muscle-targeting property, augmented glycolytic flux and energy production capacity of dystrophic muscles in vitro and in vivo, resulting in enhanced phosphorodiamidate morpholino oligomer (PMO) uptake and activity in mdx mice. Long-term repeated administration of MOTS-c (500 μg) and PMO at the dose of 12.5 mg/kg/week for 3 weeks followed by 12.5 mg/kg/month for 3 months (PMO-M) induced therapeutic levels of dystrophin expression in peripheral muscles, with up to 25-fold increase in diaphragm of mdx mice over PMO alone. PMO-M improved muscle function and pathologies in mdx mice without detectable toxicity. Our results demonstrate that MOTS-c enables enhanced PMO uptake and activity in dystrophic muscles by providing energy and may have therapeutic implications for exon-skipping therapeutics in DMD and other energy-deficient disorders.
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http://dx.doi.org/10.15252/emmm.202012993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863382PMC
February 2021

Exosome-mediated improvement in membrane integrity and muscle function in dystrophic mice.

Mol Ther 2021 04 15;29(4):1459-1470. Epub 2020 Dec 15.

Tianjin Key Laboratory of Cellular Homeostasis and Human Diseases, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Cell Biology, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin 300070, China; School of Medical Laboratory, Tianjin Medical University, Guangdong Road, Tianjin 300203, China; Department of Neurology, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address:

Duchenne muscular dystrophy (DMD) is a devastating genetic disorder that leads to compromised cellular membranes, caused by the absence of membrane-bound dystrophin protein. Muscle membrane leakage results in disrupted intracellular homeostasis, protein degradation, and muscle wasting. Improving muscle membrane integrity may delay disease progression and extend the lifespan of DMD patients. Here, we demonstrate that exosomes, membranous extracellular vesicles, can elicit functional improvements in dystrophic mice by improving muscle membrane integrity. Systemic administration of exosomes from different sources induced phenotypic rescue and mitigated pathological progression in dystrophic mice without detectable toxicity. Improved membrane integrity conferred by exosomes inhibited intracellular calcium influx and calcium-dependent activation of calpain proteases, preventing the degradation of the destabilized dystrophin-associated protein complex. We show that exosomes, particularly myotube-derived exosomes, induced functional improvements and alleviated muscle deterioration by stabilizing damaged muscle membrane in dystrophic mice. Our findings suggest that exosomes may have therapeutic implications for DMD and other diseases with compromised membranes.
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http://dx.doi.org/10.1016/j.ymthe.2020.12.018DOI Listing
April 2021

Religiosity, Acculturation, and Preterm Birth in Mexican-Origin Women: A Pilot Study.

Hisp Health Care Int 2020 Dec 8:1540415320976643. Epub 2020 Dec 8.

College of Medicine, 2655Texas A&M University, Bryan, TX, USA.

Introduction: Explanations for racial disparities in preterm birth (PTB) are elusive, especially when comparing high rates in some racial groups with low rates in Mexican-immigrant women. The purpose of this study was to examine potential protective factors against PTB such as religiosity and acculturation.

Methods: This study was a prospective investigation of Mexican- and U.S.-born pregnant women. Women were recruited from a low-income-serving prenatal clinic in Texas. Survey instruments included socioeconomic variables, acculturation, and religiosity/spirituality (R/S). Logistic regression was used to examine the associations between acculturation, religiosity, and PTB. Because of the low prevalence of PTB in our sample, we were not able to adjust for confounding characteristics.

Results: Ninety-one low-income women, mostly Mexican immigrants, participated in the study. PTB in our sample was lower than the national average in the United States (5.5% vs. 9.9%) and was positively but moderately associated with high R/S. R/S scores were high, particularly for frequency of attendance, prayer, and religious coping. Women with lower acculturation had higher scores on the religiosity measures.

Conclusion: Further research is needed with a larger sample to include other ethnic and racial minorities to more fully understand the relationships between acculturation, religiosity, and PTB.
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http://dx.doi.org/10.1177/1540415320976643DOI Listing
December 2020

Leveraging Free Volume Manipulation to Improve the Membrane Separation Performance of Amine-Functionalized PIM-1.

Angew Chem Int Ed Engl 2021 Mar 12;60(12):6593-6599. Epub 2021 Feb 12.

Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA, 02139, USA.

Gas-separation polymer membranes display a characteristic permeability-selectivity trade-off that has limited their industrial use. The most comprehensive approach to improving performance is to devise strategies that simultaneously increase fractional free volume, narrow free volume distribution, and enhance sorption selectivity, but generalizable methods for such approaches are exceedingly rare. Here, we present an in situ crosslinking and solid-state deprotection method to access previously inaccessible sorption and diffusion characteristics in amine-functionalized polymers of intrinsic microporosity. Free volume element (FVE) size can be increased while preserving a narrow FVE distribution, enabling below-upper bound polymers to surpass the H /N , H /CH , and O /N upper bounds and improving CO -based selectivities by 200 %. This approach can transform polymers into chemical analogues with improved performance, thereby overcoming traditional permeability-selectivity trade-offs.
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http://dx.doi.org/10.1002/anie.202012441DOI Listing
March 2021

Malignancy in giant cell tumor of bone in the extremities.

J Bone Oncol 2021 Feb 5;26:100334. Epub 2020 Nov 5.

Deptartment of Orthopaedic Oncology Surgery, Beijing Jishuitan Hospital, Peking University, Beijing 100035, PR China.

Background: Malignancy in giant cell tumor of bone (GCTB) is a rare tumor with relevant literature being sparse. In primary malignant GCTB, distinct areas of benign GCTB are juxtaposed with high-grade sarcoma, while in secondary malignant GCTB sarcoma occurs at the site of previously managed GCTB. This study assesses the distinguishing characteristics of patients with this condition, the time interval for development of secondary malignant GCTB, the outcome of treatment, and explores factors associated with oncologic outcomes.

Methods: This is a retrospective case series of patients from a prospectively collected institutional musculoskeletal oncology database. From January 1998 to December 2016, 1365 patients were managed for extremity GCTBs. 32 (2.3%) patients had malignant GCTB, including 12 with primary malignant GCTB and 20 with secondary malignant GCTB. The study population comprised 18 males and 14 females presenting at a mean age of 33.7 years (±13.0) and followed for a mean of 9.5 years (±7.4). Data were collected on patient and treatment-related factors, and the occurrence of local recurrence, metastasis, and death. The time from the diagnosis of GCTB to the secondary malignant GCTB was defined as the latent period.

Results: Malignant GCTB most commonly presents in the distal femur and proximal tibia with pain and swelling. Radiologically, they are aggressive Campanacci Grade III tumors with prominent bony destruction and soft tissue extension. In the 20 patients with secondary malignant GCTB, the tumors were osteosarcoma in 15, undifferentiated pleomorphic sarcoma in 4 patients and fibrosarcoma in one patient. The mean latent period in patients with secondary malignant GCTB was 7.9 year (±7.3). The median recurrence-free survival (RFS) of secondary malignant GCTB (latent period) and benign GCTB were 61.5 and 19 months respectively (p < 0.001), receiver operating curve analysis found 49.5 months to be the critical threshold, with a longer interval to recurrence being seen in malignant recurrence. The 5 and 10-year overall survival rate of malignant GCTB were 45.8% and 36.1% respectively. The 5-year survival rates of primary malignant GCTB and secondary malignant GCTB were 56.2% and 40.0% respectively (p = 0.188). Adequate surgical margins decreased the local recurrence (LR) rate (P = 0.006). Pulmonary metastasis developed in 69% of patients. The median distant metastasis-free survival between malignant GCTB and benign GCTB were 9 and 21 months (p = 0.002). Chemotherapy was associated with a longer pulmonary metastasis free survival (13 months Vs 6 months, P = 0.002), but not with increased overall survival (57.0% Vs 33.3%, P = 0.167).

Conclusions: Malignant GCTB carries a poor prognosis. Accurate diagnosis is critical to avoid inadequate surgical margins when treating primary malignant GCTB. Aggressive tumors and pulmonary metastasis should raise suspicion for malignant GCTB. Secondary malignant transformation should be suspected in patients presenting with recurrence especially after 4 years. Adjuvant chemotherapy use did not benefit survival, but was associated with increased pulmonary progression-free survival.
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http://dx.doi.org/10.1016/j.jbo.2020.100334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680773PMC
February 2021

Erratum: Long-Term Morpholino Oligomers in Hexose Elicit Long-Lasting Therapeutic Improvements in Mice.

Mol Ther Nucleic Acids 2020 Dec 17;22:196-197. Epub 2020 Sep 17.

[This corrects the article DOI: 10.1016/j.omtn.2018.06.005.].
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http://dx.doi.org/10.1016/j.omtn.2020.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502408PMC
December 2020

Prediction of postoperative hematoma occurrence after ultrasound-guided vacuum-assisted breast biopsy in minimally invasive surgery for percutaneous removal of benign breast lesions.

Gland Surg 2020 Oct;9(5):1346-1353

Department of General Surgery, Beijing Chaoyang Hospital Affiliated with Capital Medical University, Beijing, China.

Background: The exact factors and mechanisms involved in the development of hematoma after breast ultrasound (US)-guided vacuum-assisted biopsy (VAB) are not clear. This study aimed to analyze the occurrence, prognosis, and risk factors of hematoma after US-guided VAB for the removal of benign breast lesions.

Methods: This was a retrospective study of consecutive female patients with breast lesions (BI-RADS 3/4a/4b and confirmed as benign by core needle biopsy) removed by percutaneous excisional biopsy by US-guided VAB at the Beijing Chaoyang Hospital from April 2016 to December 2018. Univariable analyses were conducted to identify the factors associated with hematoma (age, nodule size, laterality, nodule location, number of nodules, BI-RADS classification of ultrasound, pathology, breast shape, menstrual period, efficacy time of bandage, and hemostatic agents). Multivariable analysis was performed to identify the factors independently associated with hematoma.

Results: A total of 293 patients (343 breast lesions) were included. Lesion removal was successful in all cases. Hematomas ≥1 cm were found in 39 patients. Finally, 38 (97.4%) hematomas were absorbed completely within 6 months. The multivariable logistic regression analysis revealed that lesion size (P<0.001; OR: 5.775; 95% CI: 2.752-12.121), number of lesions (P=0.011; OR: 3.205, 95% CI: 1.311-7.834), and the efficacy time of bandage 12-24 h (P=0.003; OR: 5.257, 95% CI: 1.792-15.421) were independently associated with hematoma occurrence after US-guided VAB excision of breast lesions. A lesion size cut-off of 23.4 mm (AUC 0.764, 95% CI: 0.692-0.837; 59.0% sensitivity; 80.3% specificity; 77.5% accuracy; P<0.001) could predict hematoma occurrence.

Conclusions: US-guided excisional VAB can effectively remove benign breast lesions. The factors independently associated with postoperative hematoma are lesion size, lesion number, and effective postoperative compression time of bandage.
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http://dx.doi.org/10.21037/gs-20-344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667065PMC
October 2020

Coloring Afterglow Nanoparticles for High-Contrast Time-Gating-Free Multiplex Luminescence Imaging.

Adv Mater 2020 Dec 3;32(49):e2003881. Epub 2020 Nov 3.

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.

Afterglow nanoparticles (AGNPs) possessing inherently long lifetime with tailorable emission colors and uniform size have long been sought due to their time-gating-free high-contrast multiplexing imaging. Herein, via a straightforward template method, it is reported that such multicolor AGNPs can be accomplished. The resultant AGNPs exhibit a series of tunable afterglow emissions, including blue, yellow, green, and white. These multicolor AGNPs are found to be highly bright, enabling them to perform high-contrast multichannel afterglow imaging in vitro and in vivo without the use of any complicated time-gating algorithms or systems, which existing tools are unable to do.
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http://dx.doi.org/10.1002/adma.202003881DOI Listing
December 2020

Highly Effective Near-Infrared Activating Triplet-Triplet Annihilation Upconversion for Photoredox Catalysis.

J Am Chem Soc 2020 10 19;142(43):18460-18470. Epub 2020 Oct 19.

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.

Organic triplet-triplet annihilation upconversion (TTA-UC) materials have considerable promise in areas as broad as biology, solar energy harvesting, and photocatalysis. However, the development of highly efficient near-infrared (NIR) light activatable TTA-UC systems remains extremely challenging. In this work, we report on a method of systematically tailoring an annihilator to attain such outstanding systems. By chemical modifications of a commonly used perylene annihilator, we constructed a family of perylene derivatives that have simultaneously tailored triplet excited state energy (T) and singlet excited state energy (S), two key annihilator factors to determine TTA-UC performance. this method, we were able to tune the TTA-UC system from an endothermic type to an exothermic one, thus significantly elevating the upconversion performance of NIR light activatable TTA upconversion systems. In conjunction with the photosensitizer PdTNP (10 μM), the upconversion efficiency using the optimal annihilator (100 μM) identified in this study was measured to be 14.1% under the low-power density of NIR light (100 mW/cm, 720 nm). Furthermore, using such a low concentration of perylene derivative, we demonstrated that the optimal TTA-UC pair developed in our study can act as a highly effective light wavelength up-shifter to enable NIR light to drive a photoredox catalysis that otherwise requires visible light. We found that such an NIR driven method is highly effective and can even surpass directly visible light driven photoredox catalysis. This method is important for photoredox catalysis as NIR light can penetrate much deeper in colored photoredox catalysis reaction solutions, especially when done in a large-scale manner. Furthermore, this TTA-UC mediated photoredox catalysis reaction is found to be outdoor sunlight operable. Thus, our study provides a solution to enhance NIR activatable organic upconversion and set the stage for a wide array of applications that have previously been limited by the suboptimal efficiency of the existing TTA upconversion materials.
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http://dx.doi.org/10.1021/jacs.0c06976DOI Listing
October 2020

Wavelength-Selective Light-Controlled Stepwise Photolysis from Single Gold Nanoparticles.

Adv Healthc Mater 2021 03 7;10(5):e2000321. Epub 2020 Jul 7.

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.

Light-controlled sequential photolysis from a single nanoparticle is a challenge for controlled release. A wavelength-selective sequential photolysis from single gold nanoparticles is reported for the first time. In particular, it is also demonstrated that such nanoparticle can be used to sequentially release two payloads in living cells. In principle, this system can be extended to sequential release of multiple different types of payloads by rational design of diverse photocleavable linkers. It is expected that this work can provide a new tool for better orderly controlling cellular events that request high spatiotemporal manners.
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http://dx.doi.org/10.1002/adhm.202000321DOI Listing
March 2021

Self-standing and flexible covalent organic framework (COF) membranes for molecular separation.

Sci Adv 2020 Oct 7;6(41). Epub 2020 Oct 7.

Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore.

Almost all covalent organic framework (COF) materials conventionally fabricated by solvothermal method at high temperatures and pressures are insoluble and unprocessable powders, which severely hinder their widespread applications. This work develops an effective and facile strategy to construct flexible and free-standing pure COF membranes via the liquid-liquid interface-confined reaction at room temperature and atmospheric pressure. The aperture size and channel chemistry of COF membranes can be rationally designed by bridging various molecular building blocks via strong covalent bonds. Benefiting from the highly-ordered honeycomb lattice, high solvent permeances are successfully obtained and follow the trend of acetonitrile > acetone > methanol > ethanol > isopropanol. Interestingly, the imine-linked COF membrane shows higher nonpolar solvent permeances than b-ketoenamine-linked COF due to their difference in pore polarity. Both kinds of COF membranes exhibit high solvent permeances, precise molecular sieving, excellent shape selectivity, and sufficient flexibility for membrane-based separation science and technology.
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http://dx.doi.org/10.1126/sciadv.abb1110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541068PMC
October 2020

Solasonine inhibits gastric cancer proliferation and enhances chemosensitivity through microRNA-486-5p.

Am J Transl Res 2020 15;12(7):3522-3530. Epub 2020 Jul 15.

Department of Gastrointestinal Surgery, The Affiliated Shanghai Shuguang Hospital of Shanghai University of Traditional Chinese Medicine Shanghai 201203, China.

Previous studies have proved the anticancer effects of solasonine against a number of human cancers. Considering this, the present was study designed to explore the anticancer effects of solasonine against the human gastric cancer cells with an emphasis on elucidation of the underlying molecular mechanism. The results showed that solasonine significantly () inhibited the cancer cell proliferation and also reduced the colony forming potential of gastric cancer cells. The antiproliferative effects of solasonine were due to the induction of apoptosis in the gastric cancer cells as evident from the DAPI, AO/EB and PI staining assays. Further, the chemosensitivity of gastric cancer cells was seen to be enhanced markedly under solasonine administration. Solasonine was shown to exert its anticancer effects through miR-486-5p and its treatment increased the expression of miR-486-5p significantly. The up-regulation of miR-486-5p imitated the growth inhibitory effects of solasonine treatment on gastric cancer cells. The miR-486-5p in turn exerted its molecular role by targeting PIK3R1. The results of this study are suggestive of anticancer role of solasonine against the gastric cancer via modulation miR-486-5p/PI3KR1 axis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407716PMC
July 2020