Publications by authors named "Gang Xu"

1,354 Publications

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The probiotic L. casei Zhang slows the progression of acute and chronic kidney disease.

Cell Metab 2021 Jul 8. Epub 2021 Jul 8.

Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China. Electronic address:

The relationship between gut microbial dysbiosis and acute or chronic kidney disease (CKD) is still unclear. Here, we show that oral administration of the probiotic Lactobacillus casei Zhang (L. casei Zhang) corrected bilateral renal ischemia-reperfusion (I/R)-induced gut microbial dysbiosis, alleviated kidney injury, and delayed its progression to CKD in mice. L. casei Zhang elevated the levels of short-chain fatty acids (SCFAs) and nicotinamide in the serum and kidney, resulting in reduced renal inflammation and damage to renal tubular epithelial cells. We also performed a 1-year phase 1 placebo-controlled study of oral L. casei Zhang use (Chinese clinical trial registry, ChiCTR-INR-17013952), which was well tolerated and slowed the decline of kidney function in individuals with stage 3-5 CKD. These results show that oral administration of L. casei Zhang, by altering SCFAs and nicotinamide metabolism, is a potential therapy to mitigate kidney injury and slow the progression of renal decline.
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http://dx.doi.org/10.1016/j.cmet.2021.06.014DOI Listing
July 2021

Stanniocalcin-1 Protected Astrocytes from Hypoxic Damage Through the AMPK Pathway.

Neurochem Res 2021 Jul 15. Epub 2021 Jul 15.

Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Chongqing, China.

Our previous studies revealed that the expression of stanniocalcin-1 (STC1) in astrocytes increased under hypoxic conditions. However, the role of STC1 in hypoxic astrocytes is not well understood. In this work, we first showed the increased expression of STC1 in astrocyte cell line and astrocytes in the brain tissues of mice after exposure to hypoxia. Then, we found that knockdown of STC1 inhibited cell viability and increased apoptosis. These effects were mediated by decreasing the levels of SIRT3, UCP2, and glycolytic genes and increasing the levels of ROS. Further studies suggested that STC1 silencing promoted oxidative stress and suppressed glycolysis by downregulating AMPKα1. Moreover, HIF-1α knockdown in hypoxic astrocytes led to decreased expression of STC1 and AMPKα1, indicating that the expression of STC1 was regulated by HIF-1α. In conclusion, our study showed that HIF-1α-induced STC1 could protect astrocytes from hypoxic damage by regulating glycolysis and redox homeostasis in an AMPKα1-dependent manner.
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http://dx.doi.org/10.1007/s11064-021-03393-zDOI Listing
July 2021

Modulation of Perturbed Cardiac Metabolism in Rats Under High-Altitude Hypoxia by Combination Treatment With L-carnitine and Trimetazidine.

Front Physiol 2021 28;12:671161. Epub 2021 Jun 28.

Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China.

High-altitude hypoxia has long been recognized as a vital etiology for high-altitude illnesses. High-altitude myocardial injury (HAMI) usually occurs in people who suffered from high-altitude exposure. To date, the molecular mechanism of HAMI remains elusive, which seriously hinders the prevention and treatment of HAMI. L-carnitine and trimetazidine are classic cardiovascular protective medicines. In this study, we used the metabolomic method, based on GC/MS, to explore the changes in metabolites in rats exposed to high-altitude hypoxia and then illustrate the metabolic pathways associated with the modulatory effect of L-carnitine combined with trimetazidine on rats with high-altitude exposure. The results showed that metabolites in the myocardium in rats under high-altitude hypoxia were markedly changed, such as branched-chain amino acids (BCAA, leucine, isoleucine, and valine), taurine, succinic acid, fumaric acid, lactic acid, pyruvic acid, 3-hydroxybutyrate, and docosahexaenoic acid (DHA), while L-carnitine combined with trimetazidine modulated and improved the abnormal changes in energy substances caused by high-altitude hypoxia. L-carnitine mainly promoted the metabolism of fatty acids, while trimetazidine enhanced the glycolysis process. The combined administration of the two components not only increased the metabolism of fatty acids but also promoted aerobic glycolysis. Meanwhile, it contributed to the decrease in the elevation in some of the intermediates of the tricarboxylic acid (TCA) cycle, decrease in the production of 3-hydroxybutyric acid, and relief of the abnormal energy metabolism process in organisms and the cardiac tissue. Our analysis delineates the landscape of the metabolites in the myocardial tissue of rats that were exposed to high altitude. Moreover, L-carnitine combined with trimetazidine can relieve the HAMI through modulated and improved abnormal changes in energy substances caused by high-altitude hypoxia.
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http://dx.doi.org/10.3389/fphys.2021.671161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273437PMC
June 2021

Tumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse.

J Exp Med 2021 09 13;218(9). Epub 2021 Jul 13.

Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA.

Astrocytes, a major glial cell type in the brain, play a critical role in supporting the progression of medulloblastoma (MB), the most common malignant pediatric brain tumor. Through lineage tracing analyses and single-cell RNA sequencing, we demonstrate that astrocytes are predominantly derived from the transdifferentiation of tumor cells in relapsed MB (but not in primary MB), although MB cells are generally believed to be neuronal-lineage committed. Such transdifferentiation of MB cells relies on Sox9, a transcription factor critical for gliogenesis. Our studies further reveal that bone morphogenetic proteins (BMPs) stimulate the transdifferentiation of MB cells by inducing the phosphorylation of Sox9. Pharmacological inhibition of BMP signaling represses MB cell transdifferentiation into astrocytes and suppresses tumor relapse. Our studies establish the distinct cellular sources of astrocytes in primary and relapsed MB and provide an avenue to prevent and treat MB relapse by targeting tumor cell transdifferentiation.
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http://dx.doi.org/10.1084/jem.20202350DOI Listing
September 2021

Identification of a seven-long non-coding RNA signature associated with Jab1/CSN5 in predicting hepatocellular carcinoma.

Cell Death Discov 2021 Jul 10;7(1):178. Epub 2021 Jul 10.

Department of Systems Biology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, accounting for over 700,000 deaths each year. The lack of predictive and prognostic biomarkers for HCC, with effective therapy, remains a significant challenge for HCC management. Long non-coding RNAs (lncRNAs) play a key role in tumorigenesis and have clinical value as potential biomarkers in the early diagnosis and prediction of HCC. Jun activation domain-binding protein 1 (Jab1, also known as COP9 signalosome subunit 5, CSN5) is a potential oncogene that plays a critical role in the occurrence of HCC. Here, we performed a comprehensive analysis for Jab1/CSN5-associated lncRNAs to predict the prognosis of HCC. The differentially expressed (DE) lncRNAs between in HCC were analyzed based on the TCGA RNA-seq data. We detected 1031 upregulated lncRNAs in 371 HCC tissues and identified a seven-lncRNA signature strongly correlated with Jab1/CSN5 (SNHG6, CTD3065J16.9, LINC01604, CTD3025N20.3, KB-1460A1.5, RP13-582O9.7, and RP11-29520.2). We further evaluated the prognostic significance of these lncRNAs by GEPIA ( http://gepia.cancer-pku.cn/ ). The expression data in 364 liver tumors indicated that this seven-lncRNA signature could better predict worse survival in HCC patients. Moreover, 35 clinical HCC samples were evaluated to assess the validity and reproducibility of the bioinformatic analysis. We found that the targeted lncRNAs were upregulated, with a strong association with Jab1/CSN5 and prognostic value in HCC. Functional enrichment analysis by Gene Ontology (GO) showed that these seven prognostic lncRNAs exhibit oncogenic properties and are associated with prominent hallmarks of cancer. Overall, our findings demonstrate the clinical implication of Jab1/CSN5 with the seven-lncRNAs in predicting survival for patients with HCC.
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http://dx.doi.org/10.1038/s41420-021-00560-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272716PMC
July 2021

Renin-angiotensin system inhibitor is associated with the reduced risk of all-cause mortality in COVID-19 among patients with/without hypertension.

Front Med 2021 Jul 9. Epub 2021 Jul 9.

Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China.

Consecutively hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) in Wuhan, China were retrospectively enrolled from January 2020 to March 2020 to investigate the association between the use of renin-angiotensin system inhibitor (RAS-I) and the outcome of this disease. Associations between the use of RAS-I (angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)), ACEI, and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status. A total of 2771 patients with COVID-19 were included, with moderate and severe cases accounting for 45.0% and 36.5%, respectively. A total of 195 (7.0%) patients died. RAS-I (hazard ratio (HR)= 0.499, 95% confidence interval (CI) 0.325-0.767) and ARB (HR = 0.410, 95% CI 0.240-0.700) use was associated with a reduced risk of all-cause mortality among patients with COVID-19. For patients with hypertension, RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352 (95% CI 0.162-0.764) and 0.279 (95% CI 0.115-0.677), respectively. RAS-I exhibited protective effects on the survival outcome of COVID-19. ARB use was associated with a reduced risk of all-cause mortality among patients with COVID-19.
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http://dx.doi.org/10.1007/s11684-021-0850-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267232PMC
July 2021

Covalent Organic-Inorganic Hybrid Superlattice Covered with Organic Functional Group for Highly Sensitive and Selective Gas Sensing.

Angew Chem Int Ed Engl 2021 Jul 9. Epub 2021 Jul 9.

Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, 350002, Fuzhou, CHINA.

Organic-inorganic hybrid superlattices (OIHSLs) hold attractive physical and chemical properties, while the construction of single-crystal covalent OIHSLs has not been achieved. Herein a coordination assembly strategy was proposed to create a single-crystal covalent OIHSL PbBDT (BDT=1,4-benzenedithiolate), where layered [PbS 2 ] sublattice covalently connects with benzene sublattice. The covalent bonding offers better thermo-/chemi-stability, inter-sublattice electron transport, and unique organic-group-functionalized surface, which may enable better performances in chemical applications than non-covalent OIHSL. These features endow PbBDT with the highest sensitivity, the lowest detection limit and excellent selectivity towards NO 2 at room temperature among all chemiresistive gas-sensing materials with reported response time less than 2 min without the need of light assistance.
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http://dx.doi.org/10.1002/anie.202107185DOI Listing
July 2021

Postoperative oxaliplatin-based hyperthermic intraperitoneal chemotherapy: an effective and safe palliative treatment option for colorectal cancer with peritoneal metastasis.

World J Surg Oncol 2021 Jul 6;19(1):200. Epub 2021 Jul 6.

Department of Surgical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Yanta west street No.277, Xi'an, 710061, Shaanxi, China.

Background: The prognosis of patients with colorectal cancer and peritoneal metastasis (CRC-PM) after incomplete cytoreductive surgery (CRS) or palliative surgery is poor. Novel and effective therapies are urgently needed. This study aimed to assess the effects of palliative postoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with CRC-PM.

Methods: This retrospective study included patients with CRC-PM at the First Affiliated Hospital of Xi'an Jiaotong University in 05/2014-05/2019. Observation indicators included overall survival (OS), ascites-free survival, peritoneal cancer index (PCI), and completeness of cytoreduction (CC). Kaplan-Meier survival curves and multivariable Cox regression models were used to determine the factors associated with OS and ascites-free survival. The ascites-specific quality of life (QoL) was measured using the Functional Assessment of Chronic Illness Therapy-Ascites Index (FACIT-AI).

Results: Eighty-two patients were included, including 37 and 45 in the HIPEC and non-HIPEC groups, respectively. Mean OS was 10.3±3.7 (95% CI 9.5-11.2) months. Multivariable Cox proportional hazard regression suggested that PCI (HR=6.086, 95% CI 3.187-11.620, P < 0.0001) was independently associated with OS. The degree of ascites (HR=2.059, 95% CI 1.412-3.005, P < 0.0001), PCI (HR=6.504, 95% CI 2.844-14.875, P < 0.0001), and HIPEC (HR=0.328, 95% CI 0.191-0.562, P < 0.0001) were independently associated with ascites-free survival. In patients with survival >6 months, postoperative ascites-specific QoL was significantly improved after HIPEC compared with the non-HIPEC group (P < 0.001). Oxaliplatin-based HIPEC significantly increased the rates of neutropenia and peripheral neurotoxicity (both P < 0.05).

Conclusion: These data indicate that postoperative oxaliplatin-based HIPEC might help increase ascites-free survival in CRC-PM patients after incomplete CRS or palliative surgery, with improved QoL after 6 months of follow-up.
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http://dx.doi.org/10.1186/s12957-021-02320-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262040PMC
July 2021

Efficacy of Transcutaneous Electrical Nerve Stimulation in the Management of Neurogenic Overactive Bladder: A Randomized Controlled Trial.

Am J Phys Med Rehabil 2021 Jul 3. Epub 2021 Jul 3.

Department of Rehabilitation Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.

Objective: To investigate the therapeutic effect of transcutaneous electrical nerve stimulation (TENS) on neurogenic overactive bladder (NOAB) that is refractory to pharmacotherapy.

Methods: This randomized trial recruited 83 participants with NOAB that were non-responsive to 3 months first-line anticholinergic drug treatment. Participants were randomized into treatment and control groups. TENS current consisting of biphasic square wave with pulse durations of 150 μs and pulse frequency set at 20 Hz were applied to for 30 min once a day for 90 days. Stimulation was provided over the lateral aspect of the sacrum bilaterally of the electrodes. Patients in the TENS group stopped taking the anticholinergic drugs. The control group continued to receive anticholinergic drugs for 90 days. The participants' Overactive Bladder Symptom Score (OABSS), Medical Outcomes Study 36-Item Short Form Survey (SF-36) scores, urodynamic values, and voiding diary data were assessed before and after the therapy.

Results: The TENS treatment group had significantly decreased OABSS scores compared with the control group (P < 0.001); additionally, half of the SF-36 scores were significantly improved in the TENS group (P < 0.05). The patients treated with TENS improved significantly voiding diary parameters at P < 0.05. Similarly, urodynamic values at P < 0.05 favoured the experimental group over the control group.

Conclusion: Applying daily TENS over the sacral region for 90 days to patient with neurogenic overactive bladder improved OAB symptoms of patients whose response to anticholinergic drugs is far inferior.
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http://dx.doi.org/10.1097/PHM.0000000000001836DOI Listing
July 2021

Efficacy of perioperative chemotherapy for synovial sarcoma: a retrospective analysis of a Nationwide database in Japan.

BMC Cancer 2021 Jul 3;21(1):773. Epub 2021 Jul 3.

Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Background: Synovial sarcoma is an aggressive but chemosensitive soft-tissue tumor. We retrospectively analyzed the efficacy of perioperative chemotherapy for synovial sarcoma with data from the nationwide database, Bone and Soft Tissue Tumor Registry in Japan.

Methods: This study included 316 patients diagnosed with synovial sarcoma between 2006 and 2012. Oncologic outcomes were analyzed using a Cox-hazard regression model. Moreover, the effects of perioperative chemotherapy on outcomes were evaluated using a matched-pair analysis. The oncologic outcomes of patients who did or did not receive chemotherapy were compared (cx + and cx-).

Results: Multivariate analysis revealed significant correlations of age (over 40, hazard ratio [HR] = 0.61, p = 0.043), margin status (marginal resection, HR = 0.18, p < 0.001 and intralesional resection, HR = 0.30, p = 0.013 versus wide resection) with overall survival; surgical margin type (marginal resection, HR = 0.14, p = 0.001 and intralesional resection, HR = 0.09, p = 0.035 versus wide resection) with local recurrence; and postoperative local recurrence (HR = 0.30, p = 0.027) and surgical margin (marginal resection, HR = 0.31, p = 0.023 versus wide resection) with distant relapse-free survival. Before propensity score matching, perioperative chemotherapy was mainly administered for young patients and patients with deeper tumor locations, larger tumors, more advanced-stage disease, and trunk location. The 3-year overall survival, local control, and distant relapse-free survival rates were 79.8%/89.3% (HR = 0.64, p = 0.114), 89.6%/93.0% (HR = 0.37, p = 0.171) and 71.4%/84.5% (HR = 0.60, p = 0.089) in the cx+/cx- groups, respectively. After propensity score matching, 152 patients were selected such that the patient demographics were nearly identical in both groups. The 3-year overall survival, local control, and distant relapse-free survival rates were 71.5%/86.0% (HR = 0.48, p = 0.055), 92.5%/93.3% (HR = 0.51, p = 0.436) and 68.4%/83.9% (HR = 0.47, p = 0.046) in the cx+/cx- groups, respectively.

Conclusion: This large-sample study indicated that the margin status and postoperative disease control were associated directly or indirectly with improved oncologic outcomes. However, the efficacy of perioperative chemotherapy for survival outcomes in synovial sarcoma patients was not proven in this Japanese database analysis.
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http://dx.doi.org/10.1186/s12885-021-08485-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255009PMC
July 2021

Spontaneous symmetry breaking of dissipative optical solitons in a two-component Kerr resonator.

Nat Commun 2021 Jun 29;12(1):4023. Epub 2021 Jun 29.

Department of Physics, University of Auckland, Auckland, New Zealand.

Dissipative solitons are self-localized structures that can persist indefinitely in open systems driven out of equilibrium. They play a key role in photonics, underpinning technologies from mode-locked lasers to microresonator optical frequency combs. Here we report on experimental observations of spontaneous symmetry breaking of dissipative optical solitons. Our experiments are performed in a nonlinear optical ring resonator, where dissipative solitons arise in the form of persisting pulses of light known as Kerr cavity solitons. We engineer symmetry between two orthogonal polarization modes of the resonator and show that the solitons of the system can spontaneously break this symmetry, giving rise to two distinct but co-existing vectorial solitons with mirror-like, asymmetric polarization states. We also show that judiciously applied perturbations allow for deterministic switching between the two symmetry-broken dissipative soliton states. Our work delivers fundamental insights at the intersection of multi-mode nonlinear optical resonators, dissipative structures, and spontaneous symmetry breaking, and expands upon our understanding of dissipative solitons in coherently driven Kerr resonators.
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http://dx.doi.org/10.1038/s41467-021-24251-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242005PMC
June 2021

Polycyclic polyprenylated acylphloroglucinol congeners from Garcinia yunnanensis Hu with inhibitory effect on α-hemolysin production in Staphylococcus aureus.

Bioorg Chem 2021 Jun 9;114:105074. Epub 2021 Jun 9.

Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

α-Hemolysin (Hla) is an extracellular protein secreted by methicillin-resistant Staphylococcus aureus (MRSA) strains that plays a critical role in the pathogenesis of pulmonary, intraperitoneal, intramammary, and corneal infections, rendering Hla a potential therapeutic target. In this study, 10 unreported polycyclic polyprenylated acylphloroglucinol (PPAP) derivatives, garciyunnanins C-L (1-10), with diverse skeletons, were isolated from Garcinia yunnanensis Hu. The structures of these new compounds were determined by HRMS, NMR, electronic circular dichroism (ECD) calculations, single-crystal X-ray diffraction, and biomimetic transformation. Garciyunnanins C and D (1 and 2) were found to be potent Hla inhibitors in the anti-virulence efficacy evaluation against MRSA strain.
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http://dx.doi.org/10.1016/j.bioorg.2021.105074DOI Listing
June 2021

Role of IL-6-IL-27 Complex in Host Antiviral Immune Response.

J Immunol 2021 Jun 18. Epub 2021 Jun 18.

State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China; and

The IL family of cytokines participates in immune response and regulation. We previously found that soluble IL-6 receptor plays an important role in the host antiviral response. In this study, we detected the IL-6-IL-27 complex in serum and throat swab samples from patients infected with influenza A virus. A plasmid expressing the IL-6-IL-27 complex was constructed to explore its biological function. The results indicated that the IL-6-IL-27 complex has a stronger antiviral effect than the individual subunits of IL-6, IL-27A, and EBV-induced gene 3. Furthermore, the activity of the IL-6-IL-27 complex is mainly mediated by the IL-27A subunit and the IL-27 receptor α. The IL-6-IL-27 complex can positively regulate virus-triggered expression of IFN and IFN-stimulated genes by interacting with adaptor protein mitochondrial antiviral signaling protein, potentiating the ubiquitination of TNF receptor-associated factors 3 and 6 and NF-κB nuclear translocation. The secreted IL-6-IL-27 complex can induce the phosphorylation of STAT1 and STAT3 and shows antiviral activity. Our results demonstrate a previously unrecognized mechanism by which IL-6, IL-27A, and EBV-induced gene 3 form a large complex both intracellularly and extracellularly, and this complex acts in the host antiviral response.
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http://dx.doi.org/10.4049/jimmunol.2100179DOI Listing
June 2021

Unconventional chiral charge order in kagome superconductor KVSb.

Nat Mater 2021 Jun 10. Epub 2021 Jun 10.

Laboratory for Topological Quantum Matter and Advanced Spectroscopy (B7), Department of Physics, Princeton University, Princeton, NJ, USA.

Intertwining quantum order and non-trivial topology is at the frontier of condensed matter physics. A charge-density-wave-like order with orbital currents has been proposed for achieving the quantum anomalous Hall effect in topological materials and for the hidden phase in cuprate high-temperature superconductors. However, the experimental realization of such an order is challenging. Here we use high-resolution scanning tunnelling microscopy to discover an unconventional chiral charge order in a kagome material, KVSb, with both a topological band structure and a superconducting ground state. Through both topography and spectroscopic imaging, we observe a robust 2 × 2 superlattice. Spectroscopically, an energy gap opens at the Fermi level, across which the 2 × 2 charge modulation exhibits an intensity reversal in real space, signalling charge ordering. At the impurity-pinning-free region, the strength of intrinsic charge modulations further exhibits chiral anisotropy with unusual magnetic field response. Theoretical analysis of our experiments suggests a tantalizing unconventional chiral charge density wave in the frustrated kagome lattice, which can not only lead to a large anomalous Hall effect with orbital magnetism, but also be a precursor of unconventional superconductivity.
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http://dx.doi.org/10.1038/s41563-021-01034-yDOI Listing
June 2021

Separated parabiont reveals the fate and lifespan of peripheral-derived immune cells in normal and ischaemia-induced injured kidneys.

Open Biol 2021 Jun 9;11(6):200340. Epub 2021 Jun 9.

Division of Nephrology, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei 430030, People's Republic of China.

Immune cell infiltration plays a key role in acute kidney injury (AKI) to chronic kidney disease (CKD) progression. T lymphocytes, neutrophils, monocytes/macrophages and other immune cells regulate inflammation, tissue remodelling and repair. To determine the kinetics of accumulation of various immune cell populations, we established an animal model combining parabiosis and separation surgery to explore the fate and lifespan of peripheral leucocytes that migrate to the kidney. We found that peripheral T lymphocytes could survive for a long time (more than 14 days), whereas peripheral neutrophils survived for a short time in both healthy and ischaemia-induced damaged kidneys. Nearly half of the peripheral-derived macrophages disappeared after 14 days in normal kidneys, while their existing time in the inflammatory kidneys was prolonged. A fraction of F4/80 macrophages were renewed from the circulating monocyte pool. In addition, we found that after renal ischaemia reperfusion, neutrophils increased significantly in the early phase, and T lymphocytes mainly accumulated in the late stage, whereas macrophages infiltrated throughout AKI-CKD progression and were sustained longer in injured as opposed to normal kidneys. In conclusion, peripheral-derived macrophages, T lymphocytes and neutrophils exhibit different lifespans in the kidney, which may play different roles during AKI-CKD progression.
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http://dx.doi.org/10.1098/rsob.200340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187026PMC
June 2021

Porcupine inhibitor LGK‑974 inhibits Wnt/β‑catenin signaling and modifies tumor‑associated macrophages resulting in inhibition of the malignant behaviors of non‑small cell lung cancer cells.

Mol Med Rep 2021 Aug 3;24(2). Epub 2021 Jun 3.

Department of Thoracic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China.

Tumor‑associated macrophages (TAMs) are critical components of the tumor microenvironment that are tightly associated with malignancies in human cancers, including lung cancer. LGK‑974, a small molecular inhibitor of Wnt secretion, was reported to block Wnt/β‑catenin signaling and exert anti‑inflammatory effects by suppressing pro‑inflammatory gene expression in cancer cells. Although it was reported that Wnt/β‑catenin was critical in regulating TAMs, it is still largely unknown whether LGK‑974 regulates tumor malignancies by regulating TAMs. The present study firstly verified that the polarization of TAMs was regulated by LGK‑974. LGK‑974 increased M1 macrophage functional markers and decreased M2 macrophage functional markers. The addition of Wnt3a and Wnt5a, two canonical Wnt signaling inducers, reversed the decrease in M1 macrophage functional markers, including mannose receptor, IL‑10 and Arg1, by activating Wnt/β‑catenin signaling. Conditioned medium from LGK‑974‑modified TAMs inhibited the malignant behaviors in A549 and H1299 cells, including proliferation, colony formation and invasion, by blocking Wnt/β‑catenin signaling. LGK‑974‑modified TAMs blocked the cell cycle at the G/G phase, which was reversed by the addition of Wnt3a/5a, indicating that LGK‑974 regulates the microenvironment by blocking Wnt/β‑catenin signaling. Taken together, the results indicate that LGK‑974 indirectly inhibited the malignant behaviors of A549 and H1299 cells by regulating the inflammatory microenvironment by inhibiting Wnt/β‑catenin signaling in TAMs.
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http://dx.doi.org/10.3892/mmr.2021.12189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185506PMC
August 2021

Optomechanical Design and Application of Solar-Skylight Spectroradiometer.

Sensors (Basel) 2021 May 28;21(11). Epub 2021 May 28.

Key Laboratory of Atmospheric Optics, Anhui Institute of Optics and Fine Mechanics, HFIPS, Chinese Academy of Sciences, Hefei 230031, China.

Using a solar radiometer is an effective approach for improving the remote sensing of solar irradiance distribution and atmospheric composition. Long-term development of a solar scanning radiometer enables frequent and reliable measurement of atmospheric parameters such as the water vapor column and aerosol optical properties. However, the discrete wavelength radiometer has encountered a bottleneck with respect to its insufficient spectral resolution and limited observation waveband, and it has been unable to satisfy the needs of refined and intelligent on-site experiments. This study proposes a solar-skylight spectroradiometer for obtaining visible and near-IR fine spectrum with two types of measurement: direct-sun irradiance and diffuse-sky radiance. The instrument adopts distributed control architecture composed of the ARM-Linux embedded platform and sensor networks. The detailed design of the measuring light-path, two-axis turntable, and master control system will be addressed in this study. To determine all coefficients needed to convert instrument outputs to physical quantities, integrating sphere and Langley extrapolation methods are introduced for diffuse-sky and direct-sun calibration, respectively. Finally, the agreement of experimental results between spectroradiometers and measuring benchmarks (DTF sun-photometer, microwave radiometer, and Combined Atmospheric Radiative Transfer simulation) verifies the feasibility of the spectroradiometer system, and the radiation information of feature wavelengths can be used to retrieve the characteristics of atmospheric optics.
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http://dx.doi.org/10.3390/s21113751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198637PMC
May 2021

Nujiangexanthone A Inhibits Cervical Cancer Cell Proliferation by Promoting Mitophagy.

Molecules 2021 May 12;26(10). Epub 2021 May 12.

Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528, Zhangheng Road, Shanghai 201203, China.

Nujiangexanthone A (NJXA), a bioactive component isolated from the leaves of , has been reported to exhibit anti-inflammatory, antioxidant, and antitumor effects. Our previous work has shown that NJXA induced G arrest and apoptosis, thus suppressing cervical cancer cell growth. The present study provides new evidence that NJXA can induce cell death in HeLa cells by promoting mitophagy. We first identified that NJXA triggered GFP-LC3 and YFP-Parkin puncta accumulation, which are biomarkers of mitophagy. Moreover, NJXA degraded the mitochondrial membrane proteins Tom20 and Tim23 and mitochondrial fusion proteins MFN1 and MFN2, downregulated Parkin, and stabilized PINK1. Additionally, we revealed that NJXA induced lysosome degradation and colocalization of mitochondria and autophagosomes, which was attenuated by knocking down ATG7, the key regulator of mitophagy. Furthermore, since mitophagy is induced under starvation conditions, we detected the cytotoxic effect of NJXA in nutrient-deprived HeLa cells and observed better cytotoxicity. Taken together, our work contributes to the further clarification of the mechanism by which NJXA inhibits cervical cancer cell proliferation and provides evidence that NJXA has the potential to develop anticancer drugs.
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http://dx.doi.org/10.3390/molecules26102858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150697PMC
May 2021

Evaluation of clinical value and potential mechanism of MTFR2 in lung adenocarcinoma via bioinformatics.

BMC Cancer 2021 May 26;21(1):619. Epub 2021 May 26.

Department of Thoracic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China.

Background: Mitochondrial fission regulator 2 (MTFR2) was involved in the progression and development of various cancers. However, the relationship between MTFR2 with lung adenocarcinoma (LUAD) had not been reported. Herein, this study analyzed the clinical significance and potential mechanisms of MTFR2 in LUAD via bioinformatics tools.

Results: We found that the level of MTFR2 was increased, and correlated with sex, age, smoking history, neoplasm staging, histological subtype and TP53 mutation status in LUAD patients. Kaplan-Meier survival analysis showed LUAD patients with increased MTFR2 had a poor prognosis. In addition, univariate COX regression analysis showed neoplasm staging, T stage, distant metastasis and MTFR2 level were risk factors for the prognosis of LUAD. A total of 1127 genes were coexpressed with MTFR2, including 840 positive and 208 negative related genes. KEGG and GSEA found that MTFR2 participated in the progression of LUAD by affecting cell cycle, DNA replication, homologous recombination, p53 signaling pathway and other mechanisms. The top 10 coexpressed genes, namely CDK1, CDC20, CCNB1, PLK1, CCNA2, AURKB, CCNB2, BUB1B, MAD2L1 and BUB1 were highly expressed, and were associated with poor prognosis in LUAD.

Conclusions: Consequently, we elucidated MTFR2 was a biomarker for diagnosis and poor prognosis in LUAD, and might participate in the progression of LUAD via affecting cell cycle, DNA replication, homologous recombination and p53 signaling pathway.
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http://dx.doi.org/10.1186/s12885-021-08378-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157440PMC
May 2021

Stereodivergent Strategy in Structural Determination: Asymmetric Total Synthesis of Garcinol, Cambogin, and Related Analogues.

Org Lett 2021 Jun 24;23(11):4203-4208. Epub 2021 May 24.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

The asymmetric total synthesis of five biologically significant polycyclic polyprenylated acylphloroglucinols (PPAPs), including garcinol and cambogin, was achieved through a highly diastereoselective and stereodivergent strategy. Along the way, an efficient cascade Dieckmann cyclization was employed to construct the bicyclo[3.3.1]nonane core in one step. The synthesis provided a general approach toward the chiral -type B PPAPs and their C-30 diastereomers in a single sequence, which resolved the challenges of the absolute configuration determination/structural revision of PPAPs bearing exocyclic stereocenters.
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http://dx.doi.org/10.1021/acs.orglett.1c01139DOI Listing
June 2021

Inducible ATP1B1 Upregulates Antiviral Innate Immune Responses by the Ubiquitination of TRAF3 and TRAF6.

J Immunol 2021 Jun 19;206(11):2668-2681. Epub 2021 May 19.

State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China

The antiviral innate immune responses are crucial steps during host defense and must be strictly regulated, but the molecular mechanisms of control remain unclear. In this study, we report increased expression of human ATPase Na/K transporting subunit β 1(ATP1B1) after DNA and RNA virus infections. We found that the expression of ATP1B1 can inhibit viral replication and increase the levels of IFNs, IFN-stimulated genes, and inflammatory cytokines. Knockdown of ATP1B1 by specific short hairpin RNA had the opposite effects. Upon viral infection, ATP1B1 was induced, interacted with TRAF3 and TRAF6, and potentiated the ubiquitination of these proteins, leading to increased phosphorylation of downstream molecules, including TGF-β-activated kinase 1 (TAK1) and TANK-binding kinase 1 (TBK1). These results reveal a previously unrecognized role of ATP1B1 in antiviral innate immunity and suggest a novel mechanism for the induction of IFNs and proinflammatory cytokines during viral infection.
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http://dx.doi.org/10.4049/jimmunol.2001262DOI Listing
June 2021

[Development of handshape -cupping instrument based on pulsating airflow technology].

Zhongguo Zhen Jiu 2021 May;41(5):553-6

Teaching and Research Office of TCM Engineering, College of Acupuncture-Moxibustion and Tuina, Shanghai University of TCM, Shanghai 201203, China.

A new type of handshape -cupping instrument is developed to overcome the shortcomings of traditional cupping therapy, such as indentation and pain, and simulates the manipulation, so as to realize the combination of cupping therapy and manipulation. The handshape -cupping instrument has a trumpet-shaped, silica gel edge. At the same time, the finger-belly shape is added at the cupping edge to simulate the shape of fingers during . Under the action of air suction and deflation of pulsating airflow, the purpose of simulating manipulation is achieved, and the indentation and pain caused by the handshape -cupping instrument is significantly less than that of the traditional cupping instrument.
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http://dx.doi.org/10.13703/j.0255-2930.20200421-0006DOI Listing
May 2021

Alternative splicing perturbation landscape identifies RNA binding proteins as potential therapeutic targets in cancer.

Mol Ther Nucleic Acids 2021 Jun 9;24:792-806. Epub 2021 Apr 9.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.

Alternative splicing (AS) plays an important role in gene regulation, and AS perturbations are frequently observed in cancer. RNA binding protein (RBP) is one of the molecular determinants of AS, and perturbations in RBP-gene network activity are causally associated with cancer development. Here, we performed a systematic analysis to characterize the perturbations in AS events across 18 cancer types. We showed that AS alterations were prevalent in cancer and involved in cancer-related pathways. Given that the extent of AS perturbation was associated with disease severity, we proposed a computational pipeline to identify RBP regulators. Pan-cancer analysis identified a number of conserved RBP regulators, which play important roles in regulating AS of genes involved in cancer hallmark pathways. Our application analysis revealed that the expression of 68 RBP regulators helped in cancer subtyping. Specifically, we identified four subtypes of kidney cancer with differences in cancer hallmark pathway activities and prognosis. Finally, we identified the small molecules that can potentially target the RBP genes and suggested potential candidates for cancer therapy. In summary, our comprehensive AS perturbation landscape analysis identified RBPs as potential therapeutic targets in cancer and provided novel insights into the regulatory functions of RBPs in cancer.
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http://dx.doi.org/10.1016/j.omtn.2021.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099609PMC
June 2021

Evolutions of the Management of Colorectal Cancer Liver Metastasis: A Bibliometric Analysis.

J Cancer 2021 30;12(12):3660-3670. Epub 2021 Apr 30.

Department of Liver Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College (PUMC) and Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, China.

Tremendous progress has been made in the treatment of colorectal cancer liver metastasis (CRCLM) in recent decades, and thousands of papers have been published. Therefore, we conducted a bibliometric analysis of articles related to CRCLM treatment to explore its evolution. The Clarivate Analytics Web of Science (WOS) Core Collection database was searched through June 2020 using terms related to CRCLM treatment. We analyzed the bibliographic information of the literature related to CRCLM treatment and explored the research topics to understand its evolution over time. We identified 3436 records related to CRCLM treatment in the WOS database. The total number of times these documents were cited ranged 0-2352, and the years of publication spanned 1976-2020. The greatest numbers of articles were published in the United States, Japan, and France. Among institutions, Memorial Sloan-Kettering Cancer Center, MD Anderson Cancer Center, and Oslo University Hospital published the most articles. Regarding authors, Jarnagin WR, Adam R, Vauthey JN published the most articles. The research topics of these articles included systemic chemotherapy, molecular targeted therapy, the outcome of liver resection, prognosis prediction, hepatic artery infusion, radiofrequency ablation, and two-stage hepatectomy. Bibliometric analysis of studies related to CRCLM treatment can help doctors and researchers quickly understand the development trend in this field. These data emphasize the current management of patients with CRCLM, and they can potentially guide the direction of future research.
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http://dx.doi.org/10.7150/jca.52842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120180PMC
April 2021

Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2.

Cell Chem Biol 2021 06 27;28(6):855-865.e9. Epub 2021 Apr 27.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China. Electronic address:

The COVID-19 pandemic has been disastrous to society and effective drugs are urgently needed. The papain-like protease domain (PLpro) of SARS-CoV-2 (SCoV2) is indispensable for viral replication and represents a putative target for pharmacological intervention. In this work, we describe the development of a potent and selective SCoV2 PLpro inhibitor, 19. The inhibitor not only effectively blocks substrate cleavage and immunosuppressive function imparted by PLpro, but also markedly mitigates SCoV2 replication in human cells, with a submicromolar IC. We further present a convenient and sensitive activity probe, 7, and complementary assays to readily evaluate SCoV2 PLpro inhibitors in vitro or in cells. In addition, we disclose the co-crystal structure of SCoV2 PLpro in complex with a prototype inhibitor, which illuminates their detailed binding mode. Overall, these findings provide promising leads and important tools for drug discovery aiming to target SCoV2 PLpro.
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http://dx.doi.org/10.1016/j.chembiol.2021.04.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075810PMC
June 2021

Correction to: Isoprenylated Flavonoids as Ca3.1 Low Voltage-Gated Ca Channel Inhibitors from Salvia digitaloides.

Nat Prod Bioprospect 2021 May 12. Epub 2021 May 12.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, 650201, People's Republic of China.

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http://dx.doi.org/10.1007/s13659-021-00308-xDOI Listing
May 2021

Evolutions in the Management of Hepatocellular Carcinoma over Last 4 Decades: An Analysis from the 100 Most Influential Articles in the Field.

Liver Cancer 2021 Apr 2;10(2):137-150. Epub 2021 Feb 2.

Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China.

Introduction: Over the past 4 decades, the management of hepatocellular carcinoma (HCC) has changed dramatically. The publications that have had the most significant impact on HCC management have not been quantitatively analyzed. In this article, we analyzed the 100 most influential articles over the past 4 decades using bibliometric citation analysis to characterize the evolution in HCC treatment.

Methods: The top-cited publications were identified and analyzed from the Clarivate Analytics Web of Science Core Collection database.

Results: The 100 most cited articles were identified with an average of 738 citations (range: 349-6,799). There was an increase in the number of influential articles in the late 1990s, which was paralleled by an increase in reports focused on locoregional treatment of HCC. Most top 100 articles came from the USA ( = 35), followed by Italy ( = 28), mainland China ( = 26), and Japan ( = 24). The surgical management was the most studied topic ( = 33). The published the highest number of papers ( = 26) with 13,978 citations. While other 3 topics (surgical management, locoregional treatment, and outcome prediction) declined among publications beginning in the 2000s, there was an emergence of highly cited papers on targeted drugs and immune checkpoint inhibitors with a concomitant increase in the number of publications on systemic therapy.

Conclusions: Based on bibliometric analysis of the literature over the last 40 years, a comprehensive analysis of the most historically significant HCC management articles highlighted the key contributions made to the evolution and advancement of this specialist field. The data should provide clinicians and researchers insight into future directions relative to the advancement of HCC management.
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http://dx.doi.org/10.1159/000513412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077437PMC
April 2021

Esophageal metastases from primary lung cancer: a case report.

J Med Case Rep 2021 May 12;15(1):265. Epub 2021 May 12.

Department of Cardiothoracic Surgery, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210000, Jiangsu, China.

Background: Primary lung cancer is one of the most frequently diagnosed cancers. The common metastatic sites are the liver, bones, brain, adrenal glands and central nervous system. However, gastrointestinal metastases, particularly esophageal metastases, from lung cancer are rare. There are no cases of esophageal metastases from lung cancer which refer to its particular treatment.

Case Presentation: We report a case of esophageal metastases from lung cancer. The patient was a 55-year-old Han Chinese man who first attended our hospital due to dry cough and was diagnosed with late-stage lung cancer. Three months later, the patient complained of dysphagia. Endoscopic ultrasonography (EUS) and pathological examination of the biopsy specimen was performed to confirm the lesion was metastases from lung cancer. Thyroid transcription factor 1 (TTF-1), cytokeratin 7 (CK-7) and napsin A were positive by immunohistochemistry examination. These results reconfirmed the diagnosis of esophageal metastases from lung cancer.

Conclusions: Esophageal metastasis from lung cancer is very rare. It may be alleviated with personalized chemotherapy. In addition, molecular targeted therapy for patients with epidermal growth factor receptor (EGFR) mutations may be reasonable.
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http://dx.doi.org/10.1186/s13256-021-02765-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114513PMC
May 2021

Understanding the hierarchical behavior of BiWO with enhanced photocatalytic nitrogen fixation activity.

Dalton Trans 2021 Jun;50(21):7427-7432

State Key Laboratory of Silicon Materials and Department of Materials Science and Engineering, Zhejiang University, Hangzhou 310027, China.

Hierarchical Bi2WO6 nanostructures self-assembled with planar arranged nanosheets and dispersed Bi2WO6 nanosheets were synthesized with different dosages of EG via a simple hydrothermal route. The Bi2WO6 photocatalysts were analyzed by X-ray diffraction (XRD), transmission electron microscopy (TEM), UV-vis diffuse reflectance spectroscopy (DRS) and X-ray photoelectron spectroscopy (XPS). A control experiment was conducted to test the effect of EG dosage on the growth mechanism and behavior of the highly (010) exposed hierarchical lamellar nanostructures and dispersed nanosheets. The photocatalytic nitrogen fixation rate of the hierarchical Bi2WO6 nanostructures was estimated to be 948 μmol g-1 h-1 across the full spectrum, which was 23% higher than that of the dispersed nanosheets (770 μmol g-1 h-1) due to chemisorption on the hierarchical structures and enhanced surface oxygen vacancies (OVs).
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http://dx.doi.org/10.1039/d1dt00762aDOI Listing
June 2021