Publications by authors named "Xu Liu"

1,468 Publications

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Homocysteine and Folic Acid: Risk Factors for Alzheimer's Disease-An Updated Meta-Analysis.

Front Aging Neurosci 2021 26;13:665114. Epub 2021 May 26.

Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Recent studies have reported that homocysteine (Hcy) may play a vital role in the pathogenesis of vascular dementia (VaD) and Alzheimer's disease (AD). Our study explored the relationship between the plasma Hcy and folate levels and the risk of dementia. We searched Embase, PubMed, and Web of Science for published literature, including case-control studies and prospective cohort studies, and performed a systematic analysis. The results of our meta-analysis, consisting of case-control studies, showed higher levels of Hcy and lower levels of folate in dementia, AD, and VaD patients than those in non-demented controls (for dementia: SMD = 0.812, 95% CI [0.689, 0.936], = 0.000 for Hcy; SMD = -0.677, 95% CI [-0.828, -0.525], = 0.000 for folate). AD patients showed significantly lower plasma Hcy levels compared to VaD patients (SMD = -0.278, 95% CI [-0.466, -0.09], = 0.000). Subgroup analysis revealed that ethnicity, average age, and dementia type had no significant effect on this association. Furthermore, from the analysis of prospective cohort studies, we identified that elevated plasma Hcy levels were associated with an increased risk of dementia, AD, and VaD (RR = 1.22, 95% CI [1.08, 1.36]; RR = 1.07, 95% CI [1.04, 1.11]; RR = 1.13, 95% CI [1.04, 1.23]). In addition, every 5 μmol/L increase in the plasma Hcy level was associated with a 9% increased risk of dementia and a 12% increased risk of AD. Hcy and folic acid are potential predictors of the occurrence and development of AD. A better understanding of their function in dementia could provide evidence for clinicians to rationalize clinical intervention strategies.
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http://dx.doi.org/10.3389/fnagi.2021.665114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188894PMC
May 2021

Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

Lancet 2021 Jun 4. Epub 2021 Jun 4.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.

Background: Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options.

Methods: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111.

Findings: Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group.

Interpretation: The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma.

Funding: The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S0140-6736(21)01123-5DOI Listing
June 2021

The precise editing of surface sites on a molecular-like gold catalyst for modulating regioselectivity.

Chem Sci 2020 Jul 21;11(30):8000-8004. Epub 2020 Jul 21.

School of Chemistry and Chemical Engineering, Nanjing University Nanjing 210093 China

It is extremely difficult to precisely edit a surface site on a typical nanoparticle catalyst without changing other parts of the catalyst. This precludes a full understanding of which site primarily determines the catalytic properties. Here, we couple experimental data collection with theoretical analysis to correlate rich structural information relating to atomically precise gold clusters with the catalytic performance for the click reaction of phenylacetylene and benzyl azide. We also identify a specific surface site that is capable of achieving high regioselectivity. We further conduct site-specific editing on a thiolate-protected gold cluster by peeling off two monomeric RS-Au-SR motifs and replacing them with two PhP-CH-PPh staples. We demonstrate that the surface Au-PhP-CH-PPh-Au motifs enable extraordinary regioselectivity for the click reaction of alkyne and azide. The editing strategy for the surface motifs allows us to exploit previously inaccessible individual active sites and elucidate which site can explicitly govern the reaction outcome.
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http://dx.doi.org/10.1039/d0sc02207aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163066PMC
July 2020

Multifunctional nanorods based on self-assembly of biomimetic apolipoprotein E peptide for the treatment of Alzheimer's disease.

J Control Release 2021 Jun 1;335:637-649. Epub 2021 Jun 1.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address:

Targeting a single molecule or a single pathway and poor drug delivery to the brain hamper the therapy of Alzheimer's disease (AD) based on abnormal metabolism of amyloid-β (Aβ). To solve these problems, we designed and synthesized a multi - strategy peptide (MOP), an ingenious apolipoprotein E mimetic peptide, which could reduce Aβ deposition via inhibiting Aβ aggregation and at the same time accelerate Aβ clearance. Meanwhile, MOP could be self-assembled into different nanostructure, thus we constructed a multifunctional delivery system (APND-3) based on MOP self-assembled nanorods (aspect ratios of 3) that was a favorable morphology to enhance the permeation across the blood brain barrier (BBB) to address the poor delivery to brain issues. Besides, the drug delivery system introduces polydopamine (PDA) and COG1410 ligand as a shell to keep the favorable morphology of core and enhance the BBB targeting efficiency. As a result, the delivery system significantly enhances the delivery of MOP to the brain, thus reducing Aβ deposition, mitigating the memory deficits, and ameliorating neurologic damage in AD model mice. Our findings suggest that our drug and carrier integrated multifunctional delivery system has the potential for AD treatment.
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http://dx.doi.org/10.1016/j.jconrel.2021.05.044DOI Listing
June 2021

Structural Design Strategy and Active Site Regulation of High-Efficient Bifunctional Oxygen Reaction Electrocatalysts for Zn-Air Battery.

Small 2021 Jun 4:e2006766. Epub 2021 Jun 4.

Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education of the People's Republic of China, Heilongjiang University, Harbin, 150080, China.

Zinc-air batteries (ZABs) exhibit high energy density as well as flexibility, safety, and portability, thereby fulfilling the requirements of power batteries and consumer batteries. However, the limited efficiency and stability are still the significant challenge. Oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are two crucial cathode reactions in ZABs. Development of bifunctional ORR/OER catalysts with high efficiency and well stability is critical to improve the performance of ZABs. In this review, the ORR and OER mechanisms are first explained. Further, the design principles of ORR/OER electrocatalysts are discussed in terms of atomic adjustment mechanism and structural design in conjunction with the latest reported in situ characterization techniques, which provide useful insights on the ORR/OER mechanisms of the catalyst. The improvement in the energy efficiency, stability, and environmental adaptability of the new hybrid ZAB by the inclusion of additional reaction, including the introduction of transition-metal redox couples in the cathode and the addition of modifiers in the electrolyte to change the OER pathway, is also summarized. Finally, current challenges and future research directions are presented.
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http://dx.doi.org/10.1002/smll.202006766DOI Listing
June 2021

hnRNPA1 enhances FOXP3 stability to promote the differentiation and functions of regulatory T cells.

FEBS Lett 2021 Jun 3. Epub 2021 Jun 3.

Shanghai Institute of Immunology & Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Regulatory T cells (Tregs) are indispensable for the maintenance of immunological self-tolerance and homeostasis. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is required for optimal Treg induction. Here, we reveal that human induced Tregs (iTregs) lacking hnRNPA1 show reduced expression of the transcription factor FOXP3, increased ubiquitination level of FOXP3, and impaired suppressive abilities. Human naïve CD4 T cells with hnRNPA1 knockdown show a decreased Treg differentiation ratio. hnRNPA1 could interact with FOXP3 as well as with the E3 ligase Stub1. The phosphorylation at hnRNPA1-S199 could increase both interactions. The overexpression of FOXP3 in Tregs containing shhnRNPA1 could not recover the phenotype caused by hnRNPA1 knockdown. Therefore, there might be multiple essential pathways regulated by hnRNPA1 in Tregs. In conclusion, we present a new role of hnRNPA1 in promoting Treg function, indicating it as a promising target for tumor therapies.
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http://dx.doi.org/10.1002/1873-3468.14142DOI Listing
June 2021

Highly Resolved and Robust Dynamic X-Ray Imaging Using Perovskite Glass-Ceramic Scintillator with Reduced Light Scattering.

Adv Sci (Weinh) 2021 Jun 2:e2003728. Epub 2021 Jun 2.

State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Key Laboratory of Excited State Materials of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, 310027, China.

All-inorganic perovskite quantum dots (QDs) CsPbX (X = Cl, Br, and I) have recently emerged as a new promising class of X-ray scintillators. However, the instability of perovskite QDs and the strong optical scattering of the thick opaque QD scintillator film imped it to realize high-quality and robust X-ray image. Herein, the europium (Eu) doped CsPbBr QDs are in situ grown inside transparent amorphous matrix to form glass-ceramic (GC) scintillator with glass phase serving as both matrix and encapsulation for the perovskite QD scintillators. The small amount of Eu dopant optimizes the crystallization of CsPbBr QDs and makes their distribution more uniform in the glass matrix, which can significantly reduce the light scattering and also enhance the photoluminescence emission of CsPbBr QDs. As a result, a remarkably high spatial resolution of 15.0 lp mm is realized thanks to the reduced light scattering, which is so far a record resolution for perovskite scintillator based X-ray imaging, and the scintillation stability is also significantly improved compared to the bare perovskite QD scintillators. Those results provide an effective platform particularly for the emerging perovskite nanocrystal scintillators to reduce light scattering and improve radiation hardness.
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http://dx.doi.org/10.1002/advs.202003728DOI Listing
June 2021

Early Rehabilitation and Periprosthetic Bone Environment after Primary Total Hip Arthroplasty: A Randomized Controlled Trial.

Orthop Surg 2021 Jun 2. Epub 2021 Jun 2.

Department of Orthopaedic Surgery, The First Hospital of Jilin University, Jilin, China.

Objective: To investigate whether the periprosthetic bone environment could be affected by activity during the early rehabilitation period after primary total hip arthroplasty (THA) and to evaluate the safety and efficacy of activity during the early rehabilitation period.

Methods: This random clinical trial was conducted from January 2017 to July 2017. A total of 22 selected patients with advanced osteonecrosis of the femoral head (ONFH) who underwent primary unilateral THA were randomized (1:1) to a high activity level group (HA group) or a low activity level group (LA group). The HA group included nine men and two women, aged 53.18 ± 13.29 years. The LA group included five men and six women, aged 55.73 ± 11.73 years. The intervention was different postoperative daily walking distances guided by researchers: 1727.27 ± 564.08 m 0-2 months and 4272.73 ± 904.53 m 3-6 months postoperation for the HA group and 909.09 ± 583.87 m 0-2 months and 2409.09 ± 1068.13 m 3-6 months postoperation for LA group. The primary outcomes were radiographic evaluation (prosthetic stability and stress shielding based on the Engh scale) and bone mineral density (BMD) with a femoral prosthesis (individual and intergroup comparison using seven Gruen zones) at 6 months postoperatively. Secondary outcomes were set to confirm the safety and efficacy of activity during early rehabilitation, including day 1 erythrocyte sedimentation rate (ESR), day 1 hypersensitive C-reactive protein (CRP), length of hospital stay (LOS), and the Harris hip score (HHS) at discharge, 2 months postoperatively, and 6 months postoperatively.

Results: Patients were followed up for 6 months after surgery. Regarding primary outcomes, all prostheses were assessed as stable, with bone in-growth. There were no adverse events in any cases. The HA group had a higher incidence of stress shielding than the LA group, but there was no statistical significance (63.64% vs 18.18%; P > 0.05). The degree of stress shielding had a different distribution for the two groups (P < 0.05). In the HA group and the LA group, the median percentage difference of the BMD on the operated side was -25% and was -13% in Zone 1, -8% and - 1% in Zone 2, +1% and 3% in Zone 3, +6% and + 6% in Zone 4, -2% and +2% in Zone 5, -3% and -1% in Zone 6, and -24% and -12% in Zone 7 compared with the unoperated side. The BMD was significantly reduced in the medial proximal femur (Zone 1) and the lateral proximal femur (Zone 7) in both groups (P < 0.05). Furthermore, it was increased in the distal femur (Zone 4) in the HA group (P < 0.05). No difference was found in the BMD when comparing between groups. Regarding secondary outcomes, there was no statistical difference in day 1 ESR and day 1 CPR. The average LOS was similar in the HA and LA groups (7.00 days vs 7.18 days, P > 0.05). The HHS on day of discharge was higher in the HA group than in the LA group (60.73 ± 5.37 points vs 51.18 ± 8.05 points, P < 0.05); however, no statistically significant difference was found in postoperative the HHS at 2 months (81.73 ± 6.92 points vs 78.36 ± 9.18 points, P > 0.05) and 6 months (90.45 ± 5.24 points vs 91.55 ± 4.03 points, P > 0.05).

Conclusion: High activity levels during early rehabilitation after primary THA accelerate the process of bone remodeling and aggravate stress shielding, with no significant benefits for functional recovery.
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http://dx.doi.org/10.1111/os.12984DOI Listing
June 2021

Combination of Plasma Electrolytic Processing and Mechanical Polishing for Single-Crystal 4H-SiC.

Micromachines (Basel) 2021 May 23;12(6). Epub 2021 May 23.

School of Mechanical and Precision Instrument Engineering, Xi'an University of Technology, Xi'an 710048, China.

Single-crystal 4H-SiC is a typical third-generation semiconductor power-device material because of its excellent electronic and thermal properties. A novel polishing technique that combines plasma electrolytic processing and mechanical polishing (PEP-MP) was proposed in order to polish single-crystal 4H-SiC surfaces effectively. In the PEP-MP process, the single-crystal 4H-SiC surface is modified into a soft oxide layer, which is mainly made of SiO and a small amount of silicon oxycarbide by plasma electrolytic processing. Then, the modified oxide layer is easily removed by soft abrasives such as CeO, whose hardness is much lower than that of single-crystal 4H-SiC. Finally a scratch-free and damage-free surface can be obtained. The hardness of the single-crystal 4H-SiC surface is greatly decreased from 2891.03 to 72.61 HV after plasma electrolytic processing. By scanning electron microscopy (SEM) and X-ray Photoelectron Spectroscopy (XPS) observation, the plasma electrolytic processing behaviors of single-crystal 4H-SiC are investigated. The scanning white light interferometer (SWLI) images of 4H-SiC surface processed by PEP-MP for 30 s shows that an ultra-smooth surface is obtained and the surface roughness decreased from Sz 607 nm, Ra 64.5 nm to Sz 60.1 nm, Ra 8.1 nm and the material removal rate (MRR) of PEP-MP is about 21.8 μm/h.
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http://dx.doi.org/10.3390/mi12060606DOI Listing
May 2021

Synthesis, Characterization, and Specific Localization of Mitochondrial-Targeted Antioxidant Peptide SS31 Probe.

Biomed Res Int 2021 19;2021:9915699. Epub 2021 May 19.

Department of Ophthalmology, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, China.

The aim of this study is to investigate the targeting efficiency of FITC-SS31 to mitochondria in both normal and HO-induced oxidative damaged 661W cells, characterizing the properties of FITC-SS31 in the biological assays. The purity and molecular weight of FITC-SS31 were identified using HPLC and MS. MTT and LDH assays were used to evaluate the cytotoxicity and cell permeability. The binding ability of FITC-SS31 to cells was demonstrated by flow cytometry. The colocalization of FITC-SS31 and MitoTracker both in normal and oxidative cells was analyzed by a laser confocal microscope. We detected the DEGs between SS31+HO and HO-alone-treated cells by RNA seq. GO and KEGG analyses were performed to predict the functional gene of SS31. The molecular weight of FITC-SS31 was 1142.2 with the 97.76% purity. The flow cytometry results showed that the MFI (mean fluorescence intensity) of FITC-SS31 in normal cells in the 4 h probe treatment group was higher than that in the 2 h and the 0 h group. The MFI in the 2 h probe treatment group was much higher than that in the 4 h and 0 h groups in damaged cells. The positive rate of 10 M FITC-SS31 was higher than that of 1 M and 5 M. Fluorescein imaging analysis confirmed that FITC-SS31 was overlapped with MitoTracker. Through the analysis, DEGs were highly expressed in "localization, organelle, antioxidant activity, binding" functions and enriched in "AMPK signaling pathway, MAPK targets/nuclear events mediated by MAP kinase pathway and PI3K-Akt signaling pathway." It is speculated that SS31 exerts an antioxidant effect through one of these pathways. We hypothesized that SS31 could play a more efficient role in the pathological cells in the half-life period to avoid cell death due to oxidative damage. The functions of the DEGs in SS31+HO and HO-alone samples are related to the localization and antioxidant activity of SS31. DEGs are mostly enriched in the AMPK signaling pathway, which needs further studies.
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http://dx.doi.org/10.1155/2021/9915699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142804PMC
May 2021

Astragalus saponins improves stroke by promoting the proliferation of neural stem cells through phosphorylation of Akt.

J Ethnopharmacol 2021 Sep 24;277:114224. Epub 2021 May 24.

Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China. Electronic address:

Ethnopharmacological Relevance: As one of major components of Buyang Huanwu decoction, Astragali Radix is broadly used for stroke treatment. Astragalus saponins (AST), the main active compound from Astragali Radix has the potentials for neuroprotection and improving spatial memory without clear pharmacological mechanism.

Aim Of The Study: The aim of this study was to investigate that pretreatment of AST is beneficial to protect against focal ischemic stroke in mouse model and its related underlying mechanism.

Materials And Methods: The neurological and motor function of MCAO mice were assessed by TTC staining and CatWalk gait analysis. The effect of AST on proliferation of NSCs was showed by the expression of Ki67 of MCAO mice and the number and size of primary neurospheres cultured from adult SVZ. The intersection of stroke-related targets, neurogenesis targets and drug-related targets were identified by the online website (https://www.omicstudio.cn/index). Then GO functional annotation and KEGG pathway enrichment analysis were performed. Candidate target Akt was confirmed to increase proliferation of cultured NSCs from adult SVZ by CCK8 assay and Western blot.

Results: We found that with the prolongation of administration time, AST improved neurological and motor function of MCAO mice, by promoting the proliferation of NSCs both in vivo and in vitro. Then, the primary network among drug, genes and biological pathway was established by using compound-target-disease & function-pathway analysis of astragalus membranaceus. PI3K/Akt which plays a key role in cell proliferation was among the top 10 most significant GO terms from above three aspects. Further analysis using cultured NSCs from adult SVZ confirmed that AST, astragaloside I (A1) and astragaloside III (A3) increased the proliferation of NSCs through targeting Akt.

Conclusion: The present study elucidated that Astragalus saponins pretreatment could provide a protective effect on experimental stroke mainly by enhancing proliferation of NSCs through targeting Akt. The findings provided a basis for the development of novel strategies for the treatment of stroke.
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http://dx.doi.org/10.1016/j.jep.2021.114224DOI Listing
September 2021

Deeply learned broadband encoding stochastic hyperspectral imaging.

Light Sci Appl 2021 May 25;10(1):108. Epub 2021 May 25.

State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Technology, Zhejiang University, Hangzhou, 310027, China.

Many applications requiring both spectral and spatial information at high resolution benefit from spectral imaging. Although different technical methods have been developed and commercially available, computational spectral cameras represent a compact, lightweight, and inexpensive solution. However, the tradeoff between spatial and spectral resolutions, dominated by the limited data volume and environmental noise, limits the potential of these cameras. In this study, we developed a deeply learned broadband encoding stochastic hyperspectral camera. In particular, using advanced artificial intelligence in filter design and spectrum reconstruction, we achieved 7000-11,000 times faster signal processing and ~10 times improvement regarding noise tolerance. These improvements enabled us to precisely and dynamically reconstruct the spectra of the entire field of view, previously unreachable with compact computational spectral cameras.
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http://dx.doi.org/10.1038/s41377-021-00545-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149860PMC
May 2021

Evaluation of Oncology Trial Results Reporting Over a 10-Year Period.

JAMA Netw Open 2021 May 3;4(5):e2110438. Epub 2021 May 3.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, China.

Importance: Unreported clinical trial results represent a violation of human rights. Oncology trials account for nearly 30% of interventional biopharmaceutical clinical studies registered on ClinicalTrials.gov and are the most numerous among all disciplines.

Objective: To analyze the reporting of results among all interventional oncology trials registered on ClinicalTrials.gov from 2007 through 2017.

Design, Setting, And Participants: This cohort study analyzed all clinical studies registered between June 1, 2007, and May 8, 2017, on ClinicalTrials.gov, the largest public clinical trial registry in the world. Trials with a recruitment status of completed or terminated and a primary completion date of on or before September 30, 2017, were selected. Data were analyzed between February 20, 2021, and February 26, 2021.

Main Outcomes And Measures: The main outcome was the percentage of trials that reported results either on ClinicalTrials.gov or in journal publications within 24 months of the primary completion date. Journal publication was ascertained by searching ClinicalTrials.gov for a link to the publication, PubMed using national clinical trial number, and Embase using national clinical trial number and filters.

Results: Of the 12 240 clinical trials registered in ClinicalTrials.gov, 7425 trials (60.7%; 95% CI, 60.0%-61.5%) reported results, with a 34.0% (95% CI, 30.3%-37.7%) increase in 24-month reporting rate from 2007 to 2017. Multivariable analyses confirmed that more recent trials (adjusted hazard ratio [HR], 1.11 per year increase; 95% CI, 1.10-1.13) and trials with larger sample sizes (51-100 patients: adjusted HR, 1.17 [95% CI, 1.09-1.24]; >100 patients: adjusted HR, 1.43 [95% CI, 1.33-1.54]) were more likely to report results. Terminated trials were less likely to report results compared with completed trials (adjusted HR, 0.88; 95% CI, 0.83-0.93). Compared with trials funded by industry, those funded by the National Institutes of Health were more likely to report results (adjusted HR, 1.39; 95% CI, 1.29-1.49), whereas those funded by other academic or nonprofit organizations were less likely to report results (adjusted HR, 0.66; 95% CI, 0.62-0.70). Among all 7425 trials, the results of 2807 trials (37.8%; 95% CI, 36.7%-38.9%) were posted only on ClinicalTrials.gov. These trials tended to be terminated early and to have small sample sizes (≤50 patients) compared with trials that published results in journals.

Conclusions And Relevance: This study found a gradual improvement in results reporting among oncology trials over a 10-year period. Trial registries could serve as a results reporting platform for unpublished trials and as a data source of trial outcomes for future studies.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.10438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144925PMC
May 2021

Discovery of indoline derivatives as anticancer agents via inhibition of tubulin polymerization.

Bioorg Med Chem Lett 2021 Aug 20;45:128131. Epub 2021 May 20.

School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address:

Human esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in human digestive system. It is necessary to discover novel antitumor agents for the treatment of esophageal cancers because of its poor prognosis. Indoline has been reported as an efficient anticancer fragment to design novel anticancer agents. In this work, indoline derivatives were designed, synthesized and explored their anticancer activity. Compound 9d, which exhibited potent antiproliferative activity with IC values of 1.84 μM (MGC-803 cells), 6.82 μM (A549 cells), 1.61 μM (Kyse30 cells), 1.49 μM (Kyse450 cells), 2.08 μM (Kyse510 cells) and 2.24 μM (EC-109 cells), respectively. The most active compound 9d was identified as a tubulin inhibitor targeting colchicine binding site with an IC value of 3.4 µM. Compound 9d could strongly suppress the tubulin polymerization in Kyse450 cells. The results of molecular docking also suggested compound 9d could tightly bind into the colchicine binding site of β-tubulin. Besides, compound 9d inhibited the growth of KYSE450 cells in time and dose-dependent manners. All the results suggest that the indoline derivatives might be a class of novel tubulin inhibitors with potential anticancer activity and is worthy of further study.
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http://dx.doi.org/10.1016/j.bmcl.2021.128131DOI Listing
August 2021

An injectable peptide hydrogel with excellent self-healing ability to continuously release salvianolic acid B for myocardial infarction.

Biomaterials 2021 Jul 29;274:120855. Epub 2021 Apr 29.

College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address:

Drug-loaded hydrogels can improve blood supply and inhibit extracellular matrix degradation after myocardial infarction. However, due to the continual dynamic motion of cardiac tissue, the hydrogel structure cannot be reconstructed in time, causing accelerated degradation and drug burst release. Here, a novel, superior, self-healing elastin-mimic peptide hydrogel (EMH) was fabricated for the local delivery of salvianolic acid B (SaB). The self-healing ability of EMH is enhanced by SaB-loaded polydopamine nanoparticles (SaB-PDA). In vitro, the pre-hydrogel (SaB-PDA/pre-EMH) is endowed with excellent biocompatibility and a low viscosity, making it suitable for intramyocardial injection. Once injected into the myocardial infarction (MI) region, SaB-PDA/pre-EMH can form SaB-PDA/EMH with great mechanical strength under the action of upregulated transglutaminase (TGase) in heart tissue post-MI. The superior self-healing ability of SaB-PDA/EMH allows for an increase in retention time in the beating ventricular wall. Therefore, with long-term release of SaB, SaB-PDA/EMH can inhibit ventricular remodeling and promote angiogenesis for MI treatment.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120855DOI Listing
July 2021

Field synopsis and systematic meta-analyses of genetic association studies in neuromyelitis optica.

Autoimmun Rev 2021 Jul 7;20(7):102843. Epub 2021 May 7.

Department of Cell Biology, China Medical University, Shenyang, China. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2021.102843DOI Listing
July 2021

Review: The Role of Intestinal Dysbiosis in Parkinson's Disease.

Front Cell Infect Microbiol 2021 22;11:615075. Epub 2021 Apr 22.

Department of Neurology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

Several studies have highlighted the roles played by the gut microbiome in central nervous system diseases. Clinical symptoms and neuropathology have suggested that Parkinson's disease may originate in the gut, which is home to approximately 100 trillion microbes. Alterations in the gastrointestinal microbiota populations may promote the development and progression of Parkinson's disease. Here, we reviewed existing studies that have explored the role of intestinal dysbiosis in Parkinson's disease, focusing on the roles of microbiota, their metabolites, and components in inflammation, barrier failure, microglial activation, and α-synuclein pathology. We conclude that there are intestinal dysbiosis in Parkinson's disease. Intestinal dysbiosis is likely involved in the pathogenesis of Parkinson's disease through mechanisms that include barrier destruction, inflammation and oxidative stress, decreased dopamine production, and molecular mimicry. Additional studies remain necessary to explore and verify the mechanisms through which dysbiosis may cause or promote Parkinson's disease. Preclinical studies have shown that gastrointestinal microbial therapy may represent an effective and novel treatment for Parkinson's disease; however, more studies, especially clinical studies, are necessary to explore the curative effects of microbial therapy in Parkinson's disease.
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http://dx.doi.org/10.3389/fcimb.2021.615075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100321PMC
April 2021

Upregulation of LINC00511 expression by DNA hypomethylation promotes the progression of breast cancer.

Gland Surg 2021 Apr;10(4):1418-1430

Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.

Background: LINC00511 is a newly discovered long intergenic nonprotein-coding RNA (Ribonucleic acid) with unknown.

Method: Differential gene expression analysis was performed on breast cancer microarray data, and the upregulated expression of LINC00511 in breast cancer tissues and breast cancer cell lines was verified by qRT-PCR (quantitative Reverse Transcription-Polymerase Chain Reaction). A cohort study revealed a correlation between the expression of LINC00511 and the clinicopathological features in breast cancer patients. The effects of LINC00511 on breast cancer migration and invasion were studied . Then, an experiment using the Illumina Infinium Human Methylation450 Beadchip data was conducted to study the role of DNA (Deoxyribonucleic acid) methylation in LINC00511 expression, and DAVID (Database for Annotation, Visualization and Integrated Discovery) Functional Annotation Bioinformatics Microarray Analysis was used to determine the biological functions and potential pathways of LINC00511 in breast cancer. Then, LINC00511 and key genes associated with breast cancer disease progression were further studied in TCGA (The Cancer Genome Atlas), and western blotting was used to verify the results at the protein level. Finally, we further studied the effect of LINC00511 on Panobinostat drug sensitivity in breast cancer and its effect on the prognosis of breast cancer patients.

Results: LINC00511 was upregulated in breast cancer patients. The expression of LINC00511 was closely related to lymph node metastasis, tumor size and molecular subtypes of breast cancer. The studies revealed that LINC00511 could promote the migration and invasion in MDA-MB-231 and MCF-7 cells. In terms of mechanism, DNA hypomethylation promoted the expression of LINC00511, furthermore LINC00511 promoted the expression of Wnt10A, E2F2, TGFA, and MET, which participate in the progression of breast cancer. In addition, LINC00511 reduced the sensitivity of breast cancer cells to Panobinostat. Moreover, breast cancer patients with a high expression of LINC00511 had a poor prognosis.

Conclusions: DNA hypomethylation promotes the expression of LINC00511 in breast cancer, and LINC00511 promotes the progression of breast cancer by upregulating Wnt10A, E2F2, TGFA and MET. High expression of LINC00511 is associated with poor prognosis. Our study identified the mechanism of LINC00511 upregulation and provides novel information on the progression of breast cancer.
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http://dx.doi.org/10.21037/gs-21-84DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102237PMC
April 2021

Discovery of indoline derivatives as anticancer agents via inhibition of tubulin polymerization.

Bioorg Med Chem Lett 2021 Jul 11;43:128095. Epub 2021 May 11.

School of Basic Medical Sciences, Zhengzhou University Zhengzhou 450001, China. Electronic address:

Human esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in human digestive system. It is necessary to discover novel antitumor agents for the treatment of esophageal cancers because of its poor prognosis. Indoline has been reported as an efficient anticancer fragment to design novel anticancer agents. In this work, indoline derivatives were designed, synthesized and explored their anticancer activity. Compound 9d, which exhibited potent antiproliferative activity with IC values of 1.84 μM (MGC-803 cells), 6.82 μM (A549 cells), 1.61 μM (Kyse30 cells), 1.49 μM (Kyse450 cells), 2.08 μM (Kyse510 cells) and 2.24 μM (EC-109 cells), respectively. The most active compound 9d was identified as a tubulin inhibitor targeting colchicine binding site with an IC value of 3.4 µM. Compound 9d could strongly suppress the tubulin polymerization in Kyse450 cells. The results of molecular docking also suggested compound 9d could tightly bind into the colchicine binding site of tubulin. Besides, compound 9d inhibited the growth of KYSE450 cells in a time and dose-dependent manner. All the results suggest that the indoline derivatives may be a class of novel tubulin inhibitors with potential anticancer activity, and which is worthy of further study.
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http://dx.doi.org/10.1016/j.bmcl.2021.128095DOI Listing
July 2021

Application of cadmium prediction models for rice and maize in the safe utilization of farmland associated with tin mining in Hezhou, Guangxi, China.

Environ Pollut 2021 Apr 30;285:117202. Epub 2021 Apr 30.

Guangxi Bureau of Geology & Mineral Prospecting & Exploitation, Nanning, 530023, PR China.

Cadmium (Cd) contamination in soil and crops caused by mining activities has become a prevalent concern in the world. Given that different crops have varying Cd bioaccumulation factors, crops with low Cd bioaccumulation abilities can be selected for the safe usage of Cd -contaminated lands. This study aimed to investigate Cd contamination in soil and crops and the influencing factors of soil Cd activity in a tin mining area (TMA) and control area (CA) and to put forward suggestions for the safe usage of farmlands by developing prediction models of Cd content in different crop grains. We collected 72 and 40 pairs of rice and maize grain samples, respectively, along with their rhizosphere soil samples and 6176 topsoil samples. The results showed that compared with the CA, the Cd pollution was more severe in the cultivated soil and crop grains around TMA. Furthermore, rice has a strong ability to transport Cd from soil to grains, whereas maize has a poor Cd uptake ability. The total organic carbon, CaO, pH, and Mn in soil play key roles in the transfer of Cd from soil to crop grains. Using these parameters and Cd concentration in soil, two sets of accurate Cd prediction models were developed for maize and rice. Based on the Cd concentration in the topsoil and predicted Cd concentration in crop grains, the safe utilization scheme of farmland was proposed. The proportions of priority protection, safe exploitation, planting adjustment, and strict control were 72.59%, 22.77%, 3.16%, and 1.48% in the TMA, respectively. The values reached 80.51% (priority protection), 19.12% (safe exploitation), 0.37% (planting adjustment), and 0% (strict control) in the CA. Thus, given the difference between Cd accumulation in rice and maize, adjustment of planting crops in contaminated farmlands can be applied to maximize the use of farmland resources.
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http://dx.doi.org/10.1016/j.envpol.2021.117202DOI Listing
April 2021

Association of intracranial vessel wall enhancement and cerebral hemorrhage in moyamoya disease: a high-resolution magnetic resonance imaging study.

J Neurol 2021 May 6. Epub 2021 May 6.

Department of Radiology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, 100853, China.

Background And Purpose: This study aimed to investigate the enhancement characteristics of vessel wall in patients with moyamoya disease (MMD) using 3D high-resolution magnetic resonance (MR) imaging and their relationship with initial and recurrent intracranial hemorrhage.

Methods: Consecutive patients with MMD were retrospectively analyzed and classified as intracranial hemorrhagic and non-hemorrhagic groups according to the CT or MR images. The clinical features and vessel wall characteristics were compared between the two groups. Logistic regression was performed to relate the vessel wall characteristics to the initial hemorrhage in MMD patients. Patients in hemorrhagic group were followed up after surgery to evaluate the relationship between vessel wall characteristics and recurrent hemorrhage.

Results: A total of 507 MMD patients including 79 hemorrhagic and 428 non-hemorrhagic MMD patients were recruited in the study. We found that hemorrhagic group had more patients with vessel wall enhancements (40.5% vs. 25.7%, p = 0.009) and more eccentric enhanced lesions (17.7% vs. 6.5%, p = 0.001) compared to those in non-hemorrhage group and vessel wall enhancements were independently associated with ipsilateral initial hemorrhage after adjusted for clinical factors (OR = 1.99, CI 1.20-3.28, p = 0.007). Furthermore, three recurrent intracranial hemorrhagic episodes in the present study were all observed in MMD patients with vessel wall enhancement during the long-term follow-up after surgery.

Conclusions: Wall enhancement of intracranial vessels was significantly associated with intracranial hemorrhage in MMD patients. Our findings suggest that vessel wall enhancement may serve as a marker of intracranial hemorrhage.
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http://dx.doi.org/10.1007/s00415-021-10587-6DOI Listing
May 2021

Scientometric Analysis of Dental Implant Research over the Past 10 Years and Future Research Trends.

Biomed Res Int 2021 13;2021:6634055. Epub 2021 Apr 13.

Department of Periodontics, Stomatological Hospital of Tianjin Medical University, Tianjin, China.

Background: We conducted a bibliometrics analysis to explore the recent trends in dental implant research which could help researchers have a clear grasp of the relevant research hotspots and prospects. . Altogether, 15,770 articles on dental implants, from January 1, 2010, to October 31, 2019, were selected from the Web of Science Core Collection. We used BICOMB software to extract the high-frequency MeSH terms and construct binary and coword matrices. gCLUTO software was used for biclustering and visual analysis, Ucinet 6 software for social network analysis, SCIMAT software for strategic diagram building, Citespace 5.5 software to form timeline visualization, and VOSviewer software, eventually, for bibliometrics cocitation network.

Results: Altogether, 72 high-frequency keywords were extracted from the selected articles and 4 clusters and 7 subcategories were identified through biclustering analysis in the dental implant research field. The use of the strategic diagram also enabled us to find the research hotspot and development trends.

Conclusions: The survival rate of dental implants and subsequent restoration have always been the core focus of research. Sinus floor elevation and guided bone regeneration are worthy of constant exploration owing to their reliability. With continuous improvement in technology, immediate loading could become a future research hot spot.
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http://dx.doi.org/10.1155/2021/6634055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057884PMC
May 2021

Forensic nanopore sequencing of STRs and SNPs using Verogen's ForenSeq DNA Signature Prep Kit and MinION.

Int J Legal Med 2021 May 5. Epub 2021 May 5.

School of Forensic Medicine, Shanxi Medical University, Taiyuan, 030001, People's Republic of China.

The MinION nanopore sequencing device (Oxford Nanopore Technologies, Oxford, UK) is the smallest commercially available sequencer and can be used outside of conventional laboratories. The use of the MinION for forensic applications, however, is hindered by the high error rate of nanopore sequencing. One approach to solving this problem is to identify forensic genetic markers that can consistently be typed correctly based on nanopore sequencing. In this pilot study, we explored the use of nanopore sequencing for single nucleotide polymorphism (SNP) and short tandem repeat (STR) profiling using Verogen's (San Diego, CA, USA) ForenSeq DNA Signature Prep Kit. Thirty single-contributor samples and DNA standard material 2800 M were genotyped using the Illumina (San Diego, CA, USA) MiSeq FGx and MinION (with R9.4.1 flow cells) devices. With an optimized cutoff for allelic imbalance, all 94 identity-informative SNP loci could be genotyped reliably using the MinION device, with an overall accuracy of 99.958% (1 error among 2926 genotypes). STR typing was notably error prone, and its accuracy was locus dependent. We developed a custom-made bioinformatics workflow, and finally selected 13 autosomal STRs, 14 Y-STRs, and 4 X-STRs showing high consistency between nanopore and Illumina sequencing among the tested samples. These SNP and STR loci could be candidates for panel design for forensic analysis based on nanopore sequencing.
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http://dx.doi.org/10.1007/s00414-021-02604-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098014PMC
May 2021

NF-YCs modulate histone variant H2A.Z deposition to regulate photomorphogenic growth in Arabidopsis.

J Integr Plant Biol 2021 Jun 3;63(6):1120-1132. Epub 2021 Jun 3.

Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement & Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, The Chinese Academy of Sciences, Guangzhou, 510650, China.

In plants, light signals trigger a photomorphogenic program involving transcriptome changes, epigenetic regulation, and inhibited hypocotyl elongation. The evolutionarily conserved histone variant H2A.Z, which functions in transcriptional regulation, is deposited in chromatin by the SWI2/SNF2-RELATED 1 complex (SWR1c). However, the role of H2A.Z in photomorphogenesis and its deposition mechanism remain unclear. Here, we show that in Arabidopsis thaliana, H2A.Z deposition at its target loci is induced by light irradiation via NUCLEAR FACTOR-Y, subunit C (NF-YC) proteins, thereby inhibiting photomorphogenic growth. NF-YCs physically interact with ACTIN-RELATED PROTEIN6 (ARP6), a key component of the SWR1c that is essential for depositing H2A.Z, in a light-dependent manner. NF-YCs and ARP6 function together as negative regulators of hypocotyl growth by depositing H2A.Z at their target genes during photomorphogenesis. Our findings reveal an important role for the histone variant H2A.Z in photomorphogenic growth and provide insights into a novel transcription regulatory node that mediates H2A.Z deposition to control plant growth in response to changing light conditions.
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http://dx.doi.org/10.1111/jipb.13109DOI Listing
June 2021

Mechanisms and regulation underlying membraneless organelle plasticity control.

J Mol Cell Biol 2021 Apr 29. Epub 2021 Apr 29.

MOE Key Laboratory for Membraneless Organelles & Cellular Dynamics and CAS Center for Excellence in Molecular Cell Science, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China.

Evolution has enabled living cells to adopt their structural and functional complexity by organizing intricate cellular compartments, such as membrane-bound and membraneless organelles, for spatiotemporal catalysis of physiochemical reactions essential for cell plasticity control. Emerging evidence and view support the notion that membraneless organelles are built by multivalent interactions of biomolecules via phase separation and transition mechanisms. In healthy cells, dynamic chemical modifications regulate membraneless organelle plasticity, and reversible phase separation is essential for cell homeostasis. Emerging evidence revealed that aberrant phase separation results in numerous neurodegenerative disorders, cancer, and other diseases. In this review, we provide molecular underpinnings on (i) mechanistic understanding of phase separation, (ii) unifying structural and mechanistic principles that underlie this phenomenon, (iii) various mechanisms that are used by cells for the regulation of phase separation, and (iv) emerging therapeutic and other applications.
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http://dx.doi.org/10.1093/jmcb/mjab028DOI Listing
April 2021

Direct dynamics in a proton transfer reaction of isomer product competition. Insight into the suppressed formation of the isoformyl cation.

Phys Chem Chem Phys 2021 May 28;23(18):10814-10821. Epub 2021 Apr 28.

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering, State Key Laboratory of Advanced Welding and Joining, P. R. China.

Proton transfer between HOCO and CO produces the formyl cation HCO and isoformyl cation HOC isomers initiating multiple astrochemical reaction networks. Here, the direct chemical dynamics simulations are performed to uncover the underlying atomistic dynamics of the above reaction. The simulations reproduce the measured product energy and scattering angle distributions and reveal that the reaction proceeds predominantly through a direct stripping mechanism which results in the prominent forward scattering observed in experiments. The reaction dynamics show propensity for the HCO product even at a collision energy larger than the threshold for HOC formation. This is a consequence of the larger opacity and impact parameter range for HCO. In accordance with the revealed direct mechanistic feature, the reaction can be controlled by orienting the reactants into a reactive H-C orientation that also favors HCO formation. Considering the lack of equilibrated reactant complexes and the on the fly migration of the proton, the CO-catalyzed isomerization is assumed to have insignificant impact on the isomer ratios. This work provides insights of dynamical effects besides energetics into the interesting finding of strongly suppressed formation of the metastable isoformyl cation for related proton transfer reactions in the measurements.
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http://dx.doi.org/10.1039/d0cp06516aDOI Listing
May 2021

AB4 inhibits Notch signaling and promotes cancer cell apoptosis in liver cancer.

Oncol Rep 2021 Jun 28;45(6). Epub 2021 Apr 28.

Department of Pharmacy, Hospital 971 of The Navy of Chinese PLA, Qingdao, Shandong 266071, P.R. China.

The etiology for liver cancer has been clearly defined. Unfortunately, therapeutic approaches for liver cancer are rather limited, and liver cancer is insensitive to chemotherapy and radiotherapy. Traditional Chinese medicine (TCM) has become a promising strategy for cancer treatment as TCM elicits broad spectrum anticancer activity. In the present study, we evaluated the anticancer efficacy of AB4, an extract from the medical herb (Bunge) Regel, in liver cancer and . We found that AB4 readily dose‑ and time‑dependently inhibited liver cancer HepG2 and Huh‑7 cell proliferation and colony formation. Western blot and flow cytometry analyses suggested that AB4 treatment induced liver cancer cell apoptosis. Moreover, these findings could be readily recaptured , in which the AB4 regimen resulted in tumor suppression and cancer cell apoptosis in xenograft tumor‑bearing nude mice. Importantly, we noted that treatment with a Notch signaling inhibitor DAPT produced very similar anticancer efficacy in both HepG2 and Huh‑7 cell lines, and administration of DAPT also efficiently suppressed HepG2 xenograft outgrowth. To this end, we anticipated that AB4 and DAPT may act on the same signaling pathway, probably through inhibition of the Notch pathway. Indeed, we found decreased expression of Notch1 protein, as well as downstream targets Hes1 and Hey1, after AB4 treatment. Immunohistochemistry analysis further confirmed the suppression of Notch signaling in HepG2 xenograft‑bearing mice. Taken together, our study highlighted the anticancer efficacy of AB4 in liver cancer. We also provided preliminary data showing Notch as a therapeutic target of AB4. It would be interesting to investigate the anticancer efficacy of AB4 in other types of cancer with elevated Notch activity.
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http://dx.doi.org/10.3892/or.2021.8063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107656PMC
June 2021

Co-existing water and sediment bacteria are driven by contrasting environmental factors across glacier-fed aquatic systems.

Water Res 2021 Jun 11;198:117139. Epub 2021 Apr 11.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address:

Glacier-fed aquatic ecosystems provide habitats for diverse and active bacterial communities. However, the environmental vulnerabilities of co-existing water and sediment bacterial communities in these ecosystems remain unclear. Here, 16S rRNA gene sequencing was used to investigate co-existing bacterial communities in paired water and sediment samples from multiple rivers and lakes that are mainly fed by glaciers from the southeast Tibetan Plateau. Overall, the bacterial communities were dissimilar between the water and sediment, which indicated that there were limited interactions between them. Bacterial diversity was greatest in the sediments, where it was mainly driven by changes in nitrogen compounds and pH. Meanwhile water bacterial diversity was more susceptible to evapotranspiration, elevation, and mean annual temperature. Water samples contained higher proportions of Proteobacteria and Bacteroidetes, while sediment harbored higher proportions of Acidobacteria, Actinobacteria, Chloroflexi, Firmicutes, Planctomycetes, Cyanobacteria, and Gemmatimonadetes. Bacterial community composition was significantly correlated with mean annual precipitation in water, but with nitrogen compounds in sediment. The co-occurrence network of water included more keystone species (e.g., CL500-29 marine group, Nocardioides spp., and Bacillus spp.) than the sediment network. These keystone species showed stronger phylogenetic signals than the species in the modular structures. Further, ecological clusters within the networks suggested that there were contrasting environmental vulnerabilities and preferences between water and sediment communities. These findings demonstrated that co-existing water and sediment bacterial communities and ecological clusters were shaped by contrasting environmental factors. This work provides a basis for understanding the importance of bacterial communities in maintaining glacier-fed aquatic ecosystems. Further, the results provide new perspectives for water resource management and water conservation in changing environments.
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http://dx.doi.org/10.1016/j.watres.2021.117139DOI Listing
June 2021

Gut flora and metabolism are altered in epilepsy and partially restored after ketogenic diets.

Microb Pathog 2021 Jun 21;155:104899. Epub 2021 Apr 21.

Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China; Department of Neurology, Shangjin Nanfu Hospital, Chengdu, Sichuan, People's Republic of China. Electronic address:

Objective: The aim of this study was to investigate the composition of the intestinal microbiota and its association with fecal short chain fatty acids (SCFAs) in children with drug refractory epilepsy (DRE) before and after treatment with a ketogenic diet (KD).

Methods: Herein, we conducted a cross-sectional study of 12 children with DRE and 12 matched healthy controls to compare the changes in fecal microbiomes and SCFAs. Disease cohort also underwent analysis before and after 6 months of KD treatment.

Results: A higher microbial alpha diversity and a significant increase in Actinobacteria at the phylum level and Enterococcus, Anaerostipes, Bifidobacterium, Bacteroides, and Blautia at the genus level were observed in the children with DRE. The abundance of the eight epileptic-associated genera was reversed after six months of KD treatment with decreases in Bifidobacterium, Akkermansia, Enterococcaceae and Actinomyces and increases in Subdoligranulum, Dialister, Alloprevotella (p < 0.05). In particular, we identified some taxa that were more prevalent in patients with an inadequate response to KD than in those with an adequate response. Further, a significant correlation was observed between the change in the microbiome genera after KD treatment. The SCFA content in the fecal after 6 months of KD treatment increased and was highly correlated with the gut bacteria.

Significances: Dysbiosis of the microbiome could be involved in the pathogenesis of DRE in children, which can be relieved by a KD to a large extent. Gut microbiota and microbial metabolism could contribute to the antiseizure effect of KD.
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http://dx.doi.org/10.1016/j.micpath.2021.104899DOI Listing
June 2021

A high level of lncFGD5-AS1 inhibits epithelial-to-Mesenchymal transition by regulating the miR-196a-5p/SMAD6/BMP axis in gastric Cancer.

BMC Cancer 2021 Apr 23;21(1):453. Epub 2021 Apr 23.

The Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Background: Long non-coding RNA (lncRNA) was a vital factor in the progression and initiation of human cancers. This study found a new lncRNA, FGD5-AS1, which can inhibit EMT process, proliferation, and metastasis in vitro and in vivo.

Methods: qRT-PCR was employed to test the expression of lncFGD5-AS1 in 30 gastric cancer patients' cancer tissue and para-cancer tissue. Overexpressed lncFGD5-AS1 cells shown sharply decrease of proliferation, migration, and epithelial-mesenchymal transition (EMT). miR-196a-5p/SMAD6 was confirmed as downstream molecular mechanism of lncFGD5-AS1 by expression correlation analysis and mechanism experiments. In vivo study illustrated overexpression of lncFGD5-AS1 suppression tumor growth.

Results: LncFGD5-AS1 served as a ceRNA of miR-196a-5p to release its inhibition on SMAD6, a conventional inhibitor on the BMP pathway. Comparing with normal gastric cancer cells, FGD5-AS1 overexpressed group had fewer migration cells, lower cell viability, and lower EMT transformation rate. Meanwhile, xenografts nude mice injecting with overexpressed-FGD5-AS1 cells also shown smaller tumor weight and volume.

Conclusion: In conclusion, this research supported the first evidence that FGD5-AS1 suppressed proliferation and metastasis in gastric cancer by regulating miR-196a-5p/SMAD6/BMP axis and suggested a potential therapeutic candidate for gastric cancer.
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http://dx.doi.org/10.1186/s12885-021-08192-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066889PMC
April 2021