Publications by authors named "Xiao Zhang"

3,150 Publications

  • Page 1 of 1

Unveiling the Synthetic Potential of 1,3,5-Tri(10-phenothiazin-10-yl)benzene-Based Optoelectronic Material: A Metal-Free and Recyclable Photocatalyst for Sequential Functionalization of C(sp)-H Bonds.

ACS Appl Mater Interfaces 2022 Jun 27. Epub 2022 Jun 27.

Fujian Key Laboratory of Polymer Materials, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, College of Chemistry and Materials Science, Fujian Normal University, 8 Shangsan Lu, Fuzhou 350007, China.

1,3,5-Tri(10-phenothiazin-10-yl)benzene (3PTZ) is endowed with unique redox and photoresponsive characteristics and has been utilized as a p-type redox center for organic battery cathode material and a room-temperature phosphorescence (RTP) material, respectively. Conversely, its exploration in other research fields, particularly organic synthesis, remains unknown. Here, we demonstrate that 3PTZ-POP synthesized via cross-linking of 3PTZ is capable of harvesting visible-light photons and selectively converting solar energy to chemical energy. Specifically, 3PTZ-POP functions as a metal-free and recyclable photocatalyst to promote the sequential C(sp)-H functionalizations of -arylacrylamides with readily available trifluoromethylsulfonyl chloride as the radical precursor. An array of 3,3-disubstituted 2-oxindoles bearing a pharmaceutically important CF moiety are delivered in moderate to excellent yields under mild and sustainable conditions.
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http://dx.doi.org/10.1021/acsami.2c08766DOI Listing
June 2022

Three Exposure Metrics for Fine Particulate Matter Associated With Outpatient Visits for Acute Lower Respiratory Infection Among Children in Guangzhou, China.

Front Public Health 2022 9;10:876496. Epub 2022 Jun 9.

Department of Pediatrics, Guangdong Second Provincial General Hospital, Guangzhou, China.

Ambient fine particulate matter (PM) is associated with an elevated risk of acute lower respiratory infections (ALRI). However, this association has not been examined using alternative exposure metrics. We collected outpatient data of patients with ALRI aged <14 years from the administrative database of a large tertiary hospital in Guangzhou, China, from 2013 to 2019. Ambient PM was measured using three metrics: (a) daily mean, (b) daily excessive concentration hours (DECH), and (c) hourly peak. Generalized additive models were fitted to estimate the excess risk (ER) associated with PM. A total of 105,639 ALRI (35,310 pneumonia and 68,218 bronchiolitis) outpatient visits were identified during the study period. An interquartile range increment in PM DECH was consistently associated with the highest ER of ALRI-related outpatient visits: 12.30% (95% confidence interval [CI]: 9.49-15.18%), compared with 11.20% (95% CI: 8.34-14.13%) for daily mean and 9.73% (95% CI: 6.97-12.55%) for hourly peak. The associations between the three metrics of PM and ALRI-related outpatient visits were stronger in the cold season than in the warm season. Future studies should consider PM DECH as an alternative method of exposure measurement, in addition to daily mean and hourly peak concentrations of PM.
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http://dx.doi.org/10.3389/fpubh.2022.876496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218103PMC
June 2022

Distinguishable Prognostic Signatures and Tumor Immunogenicity Between Pancreatic Head Cancer and Pancreatic Body/Tail Cancer.

Front Oncol 2022 8;12:890715. Epub 2022 Jun 8.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Pancreatic head cancer and pancreatic body/tail cancer are considered to have different clinical presentations and to have altered outcomes.

Methods: Ninety cases of pancreatic adenocarcinoma (PDAC) from our institution were used as a discovery set and 166 cases of PDAC from the TCGA cohort were used as a validation set. According to the anatomical location, the cases of PDAC were divided into the pancreatic head cancer group and the pancreatic body/tail cancer group. Firstly, the different biological functions of the two groups were assessed by ssGSEA. Meanwhile, ESTIMATE and CIBERSORT were conducted to estimate immune infiltration. Then, a novel anatomical site-related risk score (SRS) model was constructed by LASSO and Cox regression. Survival and time-dependent ROC analysis was used to prove the predictive ability of our model in two cohorts. Subsequently, an integrated survival decision tree and a scoring nomogram were constructed to improve prognostic stratification and predictive accuracy for individual patients. In addition, gseaGO and gseaKEGG pathway analyses were performed on genes in the key module by the R package.

Results: Overall survival and the objective response rate (ORR) of patients with pancreatic body/tail cancer were markedly superior to those with pancreatic head cancer. In addition, distinct immune characteristics and gene patterns were observed between the two groups. Then, we screened 5 biomarkers related to the prognosis of pancreatic cancer and constructed a more powerful novel SRS model to predict prognosis.

Conclusions: Our research shed some light on the revelation of gene patterns, immune and mutational landscape characterizations, and their relationships in different PDAC locations.
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http://dx.doi.org/10.3389/fonc.2022.890715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213676PMC
June 2022

Transcription factor p8 regulates autophagy in response to disulfiram via PI3K/mTOR/p70S6K signaling pathway in pancreatic cancer cells.

Hum Cell 2022 Jun 24. Epub 2022 Jun 24.

Key Laboratory of Antibody Technology, National Health Commission, Nanjing Medical University, 101 Longmian Road, Nanjing, 211166, Jiangsu, China.

Disulfiram (DSF), which is an inhibitor of aldehyde dehydrogenase (ALDH) and approved by the FDA for the treatment of alcoholism previously, has been repurposed for use as a cancer treatment because of its potent effect in preclinical studies. In this study, we found that disulfiram forms potent complexes with copper (DSF/Cu) inhibited cell proliferation, induced apoptosis in human pancreatic cancer cells, which was detected by flow cytometry and western blotting. Meanwhile, autophagy and autophagic flux also clearly observed by transmission electron microscopy, confocal microscopy and flow cytometry. Our results also showed that DSF/Cu induced transcription factor p8 upregulation and PI3K/mTOR signaling pathway activation detected by real-time PCR and western blotting. Additionally, suppression of p8 inactivated the mTOR signaling pathway and autophagic flux maintained. Furthermore, mechanism study indicated that autophagy induced by DSF/Cu was regulated by p8 and was related to PI3K/mTOR/p70S6K signaling pathway in pancreatic cancer cells. Our findings provide insights into the role of p8 in regulating autophagy induced by DSF/Cu effects in pancreatic cancer cells.
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http://dx.doi.org/10.1007/s13577-022-00731-3DOI Listing
June 2022

Cultivated hawthorn (Crataegus pinnatifida var. major) genome sheds light on the evolution of Maleae (apple tribe).

J Integr Plant Biol 2022 Jun 24. Epub 2022 Jun 24.

College of Horticulture, Shenyang Agricultural University, Shenyang, 110866, China.

Cultivated hawthorn (Crataegus pinnatifida var. major) is an important medicinal and edible plant with a long history of use for health protection in China. Herein, we provide a de novo chromosome-level genome sequence of the hawthorn cultivar 'Qiu Jinxing'. We assembled an 823.41 Mb genome encoding 40,571 genes and further anchored the 779.24 Mb sequence into 17 pseudo-chromosomes, which account for 94.64% of the assembled genome. Phylogenomic analyses revealed that cultivated hawthorn diverged within the Maleae (apple tribe) from the combined clades of Malus and Pyrus at approximately 11.8 Mya. Notably, genes involved in the flavonoid and triterpenoid biosynthetic pathways have been significantly amplified in the hawthorn genome. In addition, our results indicated that the Maleae share a unique ancient tetraploidization event; however, no recent independent whole-genome duplication event was specifically detected in hawthorn. The amplification of long terminal repeat retrotransposons (e.g., Ty3/gypsy) contributed the most to the expansion of the hawthorn genome. Furthermore, we identified two paleo-sub-genomes in extant species of Maleae and found that these two sub-genomes showed different rearrangement mechanisms. We also reconstructed the ancestral chromosomes of Rosaceae and discussed two possible paleo-polyploid origin patterns (autopolyploidization or allopolyploidization) of Maleae. Overall, our study provides an improved context for understanding the evolution of Maleae species, and this new high-quality reference genome provides a useful resource for the horticultural improvement of hawthorn. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jipb.13318DOI Listing
June 2022

Levels of lncRNA GAS5 in Plasma of Patients with Severe Traumatic Brain Injury: Correlation with Systemic Inflammation and Early Outcome.

J Clin Med 2022 Jun 9;11(12). Epub 2022 Jun 9.

Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Scientific efforts continue to concentrate on elucidating the complex molecular mechanisms underlying traumatic brain injury (TBI), and recent reports suggest that epigenetic regulation including long non-coding RNA (lncRNA) is involved. The present study aimed to investigate the plasma concentration of a long non-coding RNA, named growth arrest-specific 5 (GAS5), in a group of 45 patients with severe TBI (sTBI), and to analyze the correlations of GAS5 with TBI onset, injury severity, systemic inflammation, and early outcome of the patients. It was found that plasma GAS5 levels were substantially increased in sTBI patients compared with the relative controls ( < 0.001). Further, significantly higher expression of plasma GAS5 was observed in patients with a Glasgow Coma Scale (GCS) score of less than five ( = 0.002) or unfavorable outcome at discharge ( < 0.001). Circulating GAS5 expression had a negative correlation with GCS score (r = -0.406, = 0.006), and positive correlations with white blood cell count (r = 0.473, = 0.001), neutrophil count (r = 0.502, < 0.001), and neutrophil/lymphocyte ratio (NLR) (r = 0.398, = 0.007). Univariate and multivariate logistic regression analyses revealed that GCS score (OR = 0.318, 95% CI 0.132-0.767, = 0.011) and GAS5 (OR = 2.771, 95% CI 1.025-7.494, = 0.045) were the two independent predictors for early outcome of patients. The receiver operating characteristic (ROC) curves showed good prognostic values of GCS score (AUC = 0.856, 95% CI: 0.719-0.943) and GAS5 expression (AUC = 0.798, 95% CI: 0.651-0.903). Importantly, the combined use of them can improve the prognostic ability of TBI with an AUC of 0.895 (95% CI: 0.767-0.966). Collectively, our study indicated that the levels of lncRNA GAS5 in circulation were elevated following severe TBI and correlated well with injury severity and inflammatory parameters. In addition, GAS5 as well as GCS scores may have the potential to predict the early outcome of TBI patients.
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http://dx.doi.org/10.3390/jcm11123319DOI Listing
June 2022

ApoM regulates PFKL through the transcription factor SREBF1 to inhibit the proliferation, migration and metastasis of liver cancer cells.

Oncol Lett 2022 Jul 16;24(1):210. Epub 2022 May 16.

Anhui Province Key Laboratory of Biological Macro-Molecules Research, Wannan Medical College, Wuhu, Anhui 241001, P.R. China.

Apolipoprotein M (ApoM) is considered a protective factor that inhibits the occurrence and development of liver cancer, but the specific underlying mechanisms require further investigation. Previous studies have demonstrated that ApoM gene knockout promotes the expression of the transcription factor sterol regulatory element-binding protein 1 (SREBP1; also known as SREBF1) in the livers of mice. SREBF1 is closely associated with factors involved in fatty acid synthesis and has a role in the promotion of tumor progression. The present study initially confirmed that the expression levels of ApoM in cancer tissues were significantly decreased compared with those in normal tissue, while the expression levels of SREBF1 were significantly increased. In addition, ApoM gene knockout significantly increased the expression levels of SREBF1 and the key glycolytic enzyme ATP-dependent 6-phosphofructokinase, liver type (PFKL). Binding site prediction and a dual-luciferase reporter gene assay indicated that SREBF1 regulates the promoter region of PFKL. To the best of our knowledge, the present study was the first to propose the regulation of glycolytic enzyme transcription levels by SREBF1. Furthermore, cell proliferation and Transwell assays demonstrated that ApoM gene knockout increased the expression levels of SREBF1 and further enhanced the activity of the promoter region of PFKL, ultimately promoting the proliferation, migration and invasion of liver cancer cells.
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http://dx.doi.org/10.3892/ol.2022.13331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178675PMC
July 2022

Investigation of the internalization and transport mechanism of Codonopsis Radix polysaccharide both in mice and Caco-2 cells.

Int J Biol Macromol 2022 Jun 17;215:23-35. Epub 2022 Jun 17.

School of Pharmaceutical, Shanxi Medical University, Shanxi 030000, China. Electronic address:

For Codonopsis Radix polysaccharides (CRPs), oral administration is generally considered the most convenient route for patients. However, the details of its absorption and transport mechanisms remain unclear. In this study, we aimed to evaluate the oral absorption of CPA (an inulin-type fructan extracted from CRPs) in mice and Caco-2 cells. It was labeled with fluorescein isothiocyanate, and the fluorescence derivative (FCPA) was used to trace the behavior of CPA. The results showed that FCPA could be absorbed after oral administration and has a wide tissue distribution, including in the stomach, intestine, kidneys, and liver. FCPA was poorly absorbed, and its internalization was time- and energy-dependent, as well as dependent on cholesterol- and dynamin-mediated endocytosis. Confocal laser scanning microscopy showed successful cellular internalization of FCPA from the cytoplasm to the nucleus. In addition, we found that FCPA was trafficked to endosomes and lysosomes, and that tubulin was required for its intracellular transport. These findings add new details to our knowledge of the internalization and transport mechanisms of CPA, which may prove useful to the development and application of oral formulations of CRPs.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.06.104DOI Listing
June 2022

JAK-STAT signaling mediates the senescence of cartilage-derived stem/progenitor cells.

J Mol Histol 2022 Jun 18. Epub 2022 Jun 18.

Department of Orthopaedics, Affiliated Hospital of Nantong University, 226001, Nantong, Jiangsu, People's Republic of China.

Aging is a major risk factor for degenerative joint diseases, such as osteoarthritis (OA). Previous studies have confirmed the link between senescent mesenchymal stem cells (MSCs) and OA. Cartilage-derived stem/progenitor cells (CSPCs) with MSCs properties have been extracted from a variety of species. We inferred that the senescence of CSPCs may promote the development of osteoarthritis. However, the cellular and molecular mechanisms of CSPCs senescence remains unknown. In this study, we investigated the role of JAK-STAT signaling pathway in a replicative senescence model of CSPCs. We showed that the late CSPCs (> 15th passage) exhibited distinct senescent phenotypes, including increased proportion of β-gal positive senescent cells and F-actin content, as well as cell cycle arrest. In late CSPCs, the activity of JAK-STAT signaling pathway was significantly increased. Activation of JAK-STAT signaling pathway promoted cell senescence in early CSPCs (< 6th passage). Conversely, pharmacological inhibition or genetic knockdown of JAK-STAT signaling pathway attenuated cell senescence in late CSPCs. In conclusion, our results demonstrated the critical role of JAK-STAT signaling pathway in CSPCs senescence.
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http://dx.doi.org/10.1007/s10735-022-10086-6DOI Listing
June 2022

Sex-specific cannabinoid 1 receptors on GABAergic neurons in the ventrolateral periaqueductal gray mediate analgesia in mice.

J Comp Neurol 2022 Jun 18. Epub 2022 Jun 18.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xian, Shaanxi Province, China.

Sex differences in analgesic effects have gradually attracted public attention in preclinical and clinical studies. Both human and animal females are more sensitive to cannabinoid antinociception than males. Expression of the cannabinoid 1 receptor (CB R) and the function of the endocannabinoid system have been explored in both male and female mice and CB Rs in the ventrolateral periaqueductal gray (vlPAG) participate in antinociception. However, whether there are cell-type- and sex-specific patterns of vlPAG CB R expression that affect analgesia is unknown. In the current study, we either activated or inhibited CB Rs in the vlPAG and found that female mice produced stronger analgesia or developed more robust mechanical allodynia than males did. Specific deletion of GABAergic CB Rs in the vlPAG promoted stronger mechanical allodynia in female mice than that in male mice. However, no sex differences in cannabinoid antinociception were found following chemogenetic inhibition of GABAergic neurons. Using fluorescence in situ hybridization, we found that the sex difference in cannabinoid antinociception was due to females having higher expression of GABAergic CB Rs in the vlPAG than males. Furthermore, activation of CB Rs in the vlPAG significantly reduced the frequency of GABA-mediated spontaneous inhibitory postsynaptic currents recorded in vGlut2-tdTomato positive neurons in both sexes. This effect was greater in females than males and this reduction was closely related to CB R expression difference between sexes. Our work indicates that vlPAG GABAergic CB Rs modulate cannabinoid-mediated analgesia in a sex-specific manner, which may provide a potential explanation of sex difference found in the analgesic effect of cannabinoids.
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http://dx.doi.org/10.1002/cne.25334DOI Listing
June 2022

Erratum: TGF-β1-Induced Upregulation of MALAT1 Promotes Kazakh's Esophageal Squamous Cell Carcinoma Invasion by EMT: Erratum.

J Cancer 2022 25;13(8):2414. Epub 2022 Apr 25.

Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, PR China.

[This corrects the article DOI: 10.7150/jca.48426.].
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http://dx.doi.org/10.7150/jca.73596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174860PMC
April 2022

Glycoprotein B Antibodies Completely Neutralize EBV Infection of B Cells.

Front Immunol 2022 27;13:920467. Epub 2022 May 27.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China.

The Epstein-Barr virus (EBV) is the first reported oncogenic herpesvirus that establishes persistent infection in B lymphocytes in 95% of adults worldwide. Glycoprotein B (gB) plays a predominant role in the fusion of the viral envelope with the host cell membrane. Hence, it is of great significance to isolate gB-specific fusion-inhibiting neutralizing antibodies (NAbs). AMMO5 is the only gB NAb but fails to antagonize B-cell infection. It is essential to isolate potent NAbs that can completely block EBV infection of B cells. Using hybridoma technology and neutralization assay, we isolate two gB NAbs 8A9 and 8C12 that are capable of completely neutralizing B-cell infection . In addition, 8A9 shows cross-reactivity with rhesus lymphocryptovirus (rhLCV) gB. Competitive binding experiments demonstrate that 8A9 and 8C12 recognize novel epitopes that are different from the AMMO5 epitope. The epitopes of 8A9 and 8C12 are mapped to gB D-II, and the AMMO5 epitope is located precisely at gB aa 410-419. We find that 8A9 and 8C12 significantly inhibit gB-derived membrane fusion using a virus-free fusion assay. In summary, this study identifies two gB-specific NAbs that potently block EBV infection of B cells. Our work highlights the importance of gB D-II as a predominant neutralizing epitope, and aids in the rational design of therapeutics or vaccines based on gB.
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http://dx.doi.org/10.3389/fimmu.2022.920467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197244PMC
June 2022

Evidence for Dopamine Abnormalities Following Acute Methamphetamine Exposure Assessed by Neuromelanin-Sensitive Magnetic Resonance Imaging.

Front Aging Neurosci 2022 30;14:865825. Epub 2022 May 30.

Department of Radiology, Second Xiangya Hospital of Central South University, Changsha, China.

Background: Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) is a newly developed MRI technique that provides a non-invasive way to indirectly measure of dopamine (DA) function. This study aimed to determine NM concentrations in brain regions following acute methamphetamine (MA) administration using NM-MRI and to explore whether NM-MRI can be used as a biomarker of DA function in non-neurodegenerative diseases.

Methods: Baseline NM-MRI, T1-weighted and T2-weighted images were acquired from 27 rats before drug/placebo injection. The control group ( = 11) received acute placebo (Normal saline), while the experimental group ( = 16) received acute MA. NM-MRI scans were performed 5, 30, 60 and 90 min after injection. Regions of interest (ROIs), including the caudate putamen (CP), nucleus accumbens (NAc), hippocampus (HIP), substantia nigra (SN) and crus cerebri (CC), were manually drawn by an experienced radiologist. NM-MRI signal intensity in five brain regions at different time points (baseline and 5, 30, 60, and 90 min) were analyzed.

Results: In both the control and experimental groups, at each time point (baseline and 5, 30, 60, and 90 min), the SN exhibited significantly higher NM-MRI signal intensity than the other brain regions ( < 0.05). In addition, acute MA administration resulted in a continuous upward trend in NM-MRI signal intensity in each brain region over time. However, there was no such trend over time in the control group. The NM-MRI signal intensity of SN in the experimental group was significantly higher at the 60 and 90 min compared with that in the control group ( values were 0.042 and 0.042 respectively). Within experimental group, the NM-MRI signal intensity of SN was significantly higher at the 60 and 90 min compared with that before MA administration ( values were 0.023 and 0.011 respectively). Increased amplitudes and rates of NM-MRI signal intensity were higher in the SN than in other brain regions after MA administration.

Conclusion: Our results indicated that NM was mainly deposited in the SN, and the conversion of DA to NM was most significant in the SN after acute MA exposure. Increased DA release induced by acute MA exposure may lead to increased accumulation of NM in multiple brain regions that can be revealed by NM-MRI. NM-MRI may serve as a powerful imaging tool that could have diverse research and clinical applications for detecting pathological changes in drug addiction and related non-neurodegenerative diseases.
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http://dx.doi.org/10.3389/fnagi.2022.865825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190254PMC
May 2022

Rationale and design of a prospective, multicenter, cohort study on the evaluation of postoperative Venous ThromboEmbolism incidence in patients with ColoRectal Cancer (CRC-VTE trial).

Transl Cancer Res 2022 May;11(5):1406-1412

Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Background: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common complication after abdominal surgery. The incidence of VTE after colorectal malignancy is higher than that after general surgery. Although more attention has been paid to the prevention of VTE, there is still a large gap between clinical practice and guideline recommendation.

Methods: The Venous ThromboEmbolism incidence in patients with ColoRectal Cancer (CRC-VTE trial) will be a prospective, multicenter, cohort study to determine the current status of the incidence, diagnosis, treatment, and prevention of VTE after colorectal cancer surgery in China, as well as to further improve the level of prevention and treatment of VTE events in these fragile patients. In this study, 1,217 patients will be enrolled at 40 centers in China and evaluated on VTE events and adverse events related to VTE prevention at 5-9 and 21-28 days after surgery. The primary outcome is the incidence of VTE events during the follow-up, and secondary outcome is the incidence of adverse events associated with VTE prevention.

Discussion: This study will comprehensively evaluate the incidence and prevention of VTE after colorectal cancer surgery in China, balance the relationship between VTE prevention and bleeding adverse events, and the formulate a guideline for the prevention of VTE after colorectal surgery that might suitable for national conditions.

Trial Registration: Clinical trial registration number NCT04588805 (The CRC-VTE trial).
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http://dx.doi.org/10.21037/tcr-21-1860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189204PMC
May 2022

Human midbrain dopaminergic neuronal differentiation markers predict cell therapy outcome in a Parkinson's disease model.

J Clin Invest 2022 Jun 14. Epub 2022 Jun 14.

CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.

Human pluripotent stem cell (hPSC)-based replacement therapy holds great promise in treating Parkinson's disease (PD). However, the heterogeneity of hPSC-derived donor cells and the low yield of midbrain dopaminergic (mDA) neurons after transplantation hinder its broad clinical application. Here, we depicted the single-cell molecular landscape during mDA neuron differentiation. We found that this process recapitulated the development of multiple but adjacent fetal brain regions including ventral midbrain, isthmus, and ventral hindbrain, resulting in heterogenous donor cell population. We reconstructed the differentiation trajectory of mDA lineage and identified CLSTN2 and PTPRO as specific surface markers of mDA progenitors, which were predictive of mDA neuron differentiation and could facilitate highly enriched mDA neurons (up to 80%) following progenitor sorting and transplantation. Marker sorted progenitors exhibited higher therapeutic potency in correcting motor deficits of PD mice. Different marker sorted grafts had a strikingly consistent cellular composition, in which mDA neurons were enriched, while off-target neuron types were mostly depleted, suggesting stable graft outcomes. Our study provides a better understanding of cellular heterogeneity during mDA neuron differentiation, and establishes a strategy to generate highly purified donor cells to achieve stable and predictable therapeutic outcomes, raising the prospect of hPSC-based PD cell replacement therapies.
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http://dx.doi.org/10.1172/JCI156768DOI Listing
June 2022

Regulatory Role and Potential Importance of GDF-8 in Ovarian Reproductive Activity.

Front Endocrinol (Lausanne) 2022 26;13:878069. Epub 2022 May 26.

Department of Pharmacy, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Growth differentiation factor-8 (GDF-8) is a member of the transforming growth factor-beta superfamily. Studies and have shown GDF-8 to be involved in the physiology and pathology of ovarian reproductive functions. experiments using a granulosa-cell model have demonstrated steroidogenesis, gonadotrophin responsiveness, glucose metabolism, cell proliferation as well as expression of lysyl oxidase and pentraxin 3 to be regulated by GDF-8 the mothers against decapentaplegic homolog signaling pathway. Clinical data have shown that GDF-8 is expressed widely in the human ovary and has high expression in serum of obese women with polycystic ovary syndrome. GDF-8 expression in serum changes dynamically in patients undergoing controlled ovarian hyperstimulation. GDF-8 expression in serum and follicular fluid is correlated with the ovarian response and pregnancy outcome during fertilization. Blocking the GDF-8 signaling pathway is a potential therapeutic for ovarian hyperstimulation syndrome and ovulation disorders in polycystic ovary syndrome. GDF-8 has a regulatory role and potential importance in ovarian reproductive activity and may be involved in folliculogenesis, ovulation, and early embryo implantation.
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http://dx.doi.org/10.3389/fendo.2022.878069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178251PMC
June 2022

Ginsenoside Rc Promotes Bone Formation in Ovariectomy-Induced Osteoporosis In Vivo and Osteogenic Differentiation In Vitro.

Int J Mol Sci 2022 May 31;23(11). Epub 2022 May 31.

Department of Stomatology, Jilin University, Changchun 130000, China.

Ginsenoside Rc is one of the active components used in traditional Chinese medicine. We aim to explore how ginsenoside Rc can be used in the treatment of osteoporosis. Micro-CT demonstrated that the treatment of ovariectomized (OVX) mice with ginsenoside Rc significantly inhibited the decrease in bone mineral density, bone volumetric fraction, and trabecular number, and the increase in trabecular separation. Histological staining, qRT-PCR, and Western blot demonstrated that ginsenoside Rc enhances the microstructure of trabecular bone, and promotes the expression of bone formation-related genes. Alkaline phosphatase (ALP) staining, Alizarin Red staining, qRT-PCR, and Western blotting demonstrated that ginsenoside Rc dose-dependently promoted the osteogenic differentiation of MC3T3-E1 cells. A ginsenoside Rc-induced increase in the expression of β-catenin, p-GSK-3β, collagen-1, ALP, and RUNX-2 family transcription factor-2 was significantly attenuated upon 10 μM XAV-939 treatment, while the decrease in the expression of GSK-3β and p-β-catenin was significantly enhanced. Ginsenoside Rc promotes bone formation in ovariectomy-induced osteoporosis in vivo and promotes osteogenic differentiation in vitro via the Wnt/β-catenin signaling pathway.
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http://dx.doi.org/10.3390/ijms23116187DOI Listing
May 2022

Cytokinin Confers Brown Planthopper Resistance by Elevating Jasmonic Acid Pathway in Rice.

Int J Mol Sci 2022 May 25;23(11). Epub 2022 May 25.

State Key Laboratory for Crop Genetics & Germplasm Enhancement, Jiangsu Provincial Research Center of Plant Gene Editing Engineering, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.

Plants have evolved a sophisticated defense system that employs various hormone pathways to defend against attacks by insect pests. Cytokinin (CK) plays an important role in plant growth and stress tolerance, but the role of CKs in plant-insect interaction remains largely unclear. Here, we report that CKs act as a positive regulator in rice resistance against brown planthopper (BPH), a devastating insect pest of rice. We found that BPH feeding promotes CK biosynthesis and signaling in rice. Exogenous application of CKs significantly increased the rice resistance to BPH. Increasing endogenous CKs by knocking out / () led to enhanced resistance to BPH. Moreover, the levels of the plant hormone jasmonic acid (JA) and the expression of JA-responsive genes were elevated by CK treatment and in knockout plants. Furthermore, JA-deficient mutant was more susceptible to BPH, and CK-induced BPH resistance was suppressed in . These results indicate that CK-mediated BPH resistance is JA-dependent. Our findings provide the direct evidence for the novel role of CK in promoting insect resistance, and demonstrate that CK-induced insect resistance is JA-dependent. These results provide important guidance for effective pest management strategies in the future.
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http://dx.doi.org/10.3390/ijms23115946DOI Listing
May 2022

Functional Interactions Between the Parafascicular Thalamic Nucleus and Motor Cortex Are Altered in Hemiparkinsonian Rat.

Front Aging Neurosci 2022 23;14:800159. Epub 2022 May 23.

Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Science, Shandong Normal University, Jinan, China.

Parkinson's disease (PD) is characterized by aberrant discharge patterns and exaggerated oscillatory activity within basal ganglia-thalamocortical circuits. We have previously observed substantial alterations in spike and local field potential (LFP) activities recorded in the thalamic parafascicular nucleus (PF) and motor cortex (M1), respectively, of hemiparkinsonian rats during rest or catching movements. This study explored whether the mutual effects of the PF and M1 depended on the amplitude and phase relationship in their identified neuron spikes or group rhythmic activities. Microwire electrode arrays were paired and implanted in the PF and M1 of rats with unilateral dopaminergic cell lesions. The results showed that the identified PF neurons exhibited aberrant cell type-selective firing rates and preferential and excessive phase-locked firing to cortical LFP oscillations mainly at 12-35 Hz (beta frequencies), consistent with the observation of identified M1 neurons with ongoing PF LFP oscillations. Experimental evidence also showed a decrease in phase-locking at 0.7-12 Hz and 35-70 Hz in the PF and M1 circuits in the hemiparkinsonian rats. Furthermore, anatomical evidence was provided for the existence of afferent and efferent bidirectional reciprocal connectivity pathways between the PF and M1 using an anterograde and retrograde neuroanatomical tracing virus. Collectively, our results suggested that multiple alterations may be present in regional anatomical and functional modes with which the PF and M1 interact, and that parkinsonism-associated changes in PF integrate M1 activity in a manner that varies with frequency, behavioral state, and integrity of the dopaminergic system.
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http://dx.doi.org/10.3389/fnagi.2022.800159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168077PMC
May 2022

Acute kidney injury in peripheral blood haploidentical hematopoietic stem cell transplantation: should attract enough attention.

Bone Marrow Transplant 2022 Jun 7. Epub 2022 Jun 7.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China.

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http://dx.doi.org/10.1038/s41409-022-01731-5DOI Listing
June 2022

High nerve density in breast cancer is associated with poor patient outcome.

FASEB Bioadv 2022 Jun 3;4(6):391-401. Epub 2022 Mar 3.

General Surgery Department Third Hospital of Shanxi Medical University and Shanxi Bethune Hospital Shanxi Academy of Medical Science Taiyuan China.

Active crosstalk between the nervous system and breast cancer cells has been experimentally demonstrated in vitro and in animal models. However, low frequencies of peripheral nerve presence in human breast cancers reported in previous studies (~30% of cases) potentially negate a major role of the nervous system in breast cancer development and progression. This study aimed to clarify the incidence of nerves within human breast cancers and to delineate associations with clinicopathological features. Immunohistochemical staining was conducted in formalin-fixed paraffin-embedded breast cancer tissue sections using antibodies against the pan-neuronal markers protein gene product 9.5 and growth-associated protein 43, and the sympathetic nerve-specific marker tyrosine hydroxylase. Nerve trunks and isolated nerve fibers were quantitated. The chi-squared test was used to determine the associations between nerve counts and clinicopathological parameters. The log-rank test was used to compare differences in patient progression-free survival (PFS) and overall survival (OS). The overall frequency of peripheral nerves in breast cancers was 85%, a markedly higher proportion than reported previously. Of note, most nerves present in breast cancers were of the sympathetic origin. While high density of nerve trunks or isolated nerve fibers was associated with poor PFS and OS of patients, high nerve trunk density appeared also to predict poor patient PFS independently of lymph node metastasis. Innervation of breast cancers is a common event correlated with poor patient outcomes. These findings support the notion that the nervous system plays an active role in breast cancer pathogenesis.
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http://dx.doi.org/10.1096/fba.2021-00147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164247PMC
June 2022

FOXF2 oppositely regulates stemness in luminal and basal-like breast cancer cells through the Wnt/beta-catenin pathway.

J Biol Chem 2022 May 31:102082. Epub 2022 May 31.

Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Therapy of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China. Electronic address:

The stemness of cancer cells contributes to tumorigenesis, the heterogeneity of malignancies, cancer metastasis, and therapeutic resistance. However, the role and regulatory mechanisms maintaining stemness among breast cancer subtypes remain elusive. Our previous studies have demonstrated that ectopic expression and dynamic alteration of the mesenchymal transcription factor forkhead box F2 (FOXF2) differentially regulates breast cancer progression and metastasis organotropism in a cell subtype-specific manner. Here, we reveal the underlying mechanism by which FOXF2 enhances stemness in luminal breast cancer cells but suppresses that in basal-like breast cancer (BLBC) cells. We show that luminal breast cancer and BLBC cells with FOXF2-regulated stemness exhibit partial mesenchymal stem cell properties that toward osteogenic differentiation and myogenic differentiation, respectively. Furthermore, we show that FOXF2 activates the Wnt signaling pathway in luminal breast cancer cells but represses this pathway in BLBC cells by recruiting nuclear receptor coactivator 3 (NCoA3) and nuclear receptor corepressor 1 (NCoR1) to the promoters of Wnt family member 2B (WNT2B) and frizzled class receptor 1 (FZD1) genes to activate and repress their transcription, respectively. We propose that targeting the Wnt signaling pathway is a promising strategy for the treatment of breast cancers with dysregulated expression of FOXF2.
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http://dx.doi.org/10.1016/j.jbc.2022.102082DOI Listing
May 2022

Conditional knockout of Cdc20 attenuates osteogenesis in craniofacial bones.

Tissue Cell 2022 May 20;77:101829. Epub 2022 May 20.

Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Beijing, China. Electronic address:

Craniofacial bone defects cause significant problems to patients with harmful consequences. Mesenchymal stem cells (MSCs) can self-renew and exhibit multilineage differentiation, which could be applied to bone regeneration. However, craniofacial bone tissue MSCs have unique properties, differing in their characteristics to MSCs derived from long bones. CDC20 promotes osteogenic differentiation in long bones; however, its role in craniofacial bone tissues remains unknown. In this study, we found that Cdc20 conditional knockout in mice triggered distinctive cranial and mandibular bone loss. Moreover, the osteogenic differentiation potential of cranial suture-derived MSCs and mandibular bone marrow-derived MSCs was impaired in Cdc20 conditional knockout mice. The conditional knockout of Cdc20 impaired osteogenesis in craniofacial bones. Our findings provide new insights into craniofacial bone regeneration and the treatments of craniofacial bone-related diseases.
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http://dx.doi.org/10.1016/j.tice.2022.101829DOI Listing
May 2022

The burden of pneumoconiosis in China: an analysis from the Global Burden of Disease Study 2019.

BMC Public Health 2022 Jun 3;22(1):1114. Epub 2022 Jun 3.

National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 27 Nanwei Road, Xicheng District, Beijing, 100050, China.

Background: Pneumoconiosis refers to a class of serious diseases threatening the health of workers exposed to coal or silicosis dust. However, the burden of pneumoconiosis is unavailable in China.

Methods: Incident cases, deaths, and disability-adjusted life years (DALYs) from pneumoconiosis and its subtypes in China were estimated from the Global Burden of Disease Study 2019 using a Bayesian meta-regression method. The trend of the burden from pneumoconiosis was analyzed using percentage change and annualized rate of change (ARC) during the period 1990-2019. The relationship between subnational socio-demographic index (SDI) and the ARC of age-standardised death rate was measured using Spearman's Rank-Order Correlation.

Results: In 2019, there were 136.8 (95% uncertainty interval [UI] 113.7-162.5) thousand new cases, 10.2 (8.1-13.6) thousand deaths, and 608.7 (473.6-779.4) thousand DALYs from pneumoconiosis in China. Of the global burdens from pneumoconiosis, more than 60% were in China. Both the total number of new cases and DALYs from pneumoconiosis was keeping increasing from 1990 to 2019. In contrast, the age-standardised incidence, death, and DALY rates from pneumoconiosis and its subtypes, except for the age-standardised incidence rate of silicosis, and age-standardised death rate of asbestosis, experienced a significant decline during the same period. The subnational age-standardised death rates were higher in western China than in eastern China. Meanwhile, the subnational ARC of age-standardised death rates due to pneumoconiosis and its subtypes were significantly negatively correlated with SDI in 2019.

Conclusion: China suffers the largest health loss from pneumoconiosis in the world. Reducing the burden of pneumoconiosis is still an urgent task in China.
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http://dx.doi.org/10.1186/s12889-022-13541-xDOI Listing
June 2022

Metabolic characterization of hemolymph in Bombyx mori varieties after Bombyx mori nucleopolyhedrovirus infection by GC-MS-based metabolite profiling.

Arch Virol 2022 Aug 2;167(8):1637-1648. Epub 2022 Jun 2.

The Sericultural Research Institute, Jiangsu University of Science and Technology, Zhenjiang, 212003, China.

The "Huakang 2" silkworm variety, bred by the Sericulture Research Institute of the Chinese Academy of Agricultural Sciences, is highly resistant to Bombyx mori nucleopolyhedrovirus (BmNPV) and effectively solves the issue of frequent Bombyx mori nuclear polyhedrosis in sericultural production. The molecular mechanism of its resistance to BmNPV, however, is still unknown. The purpose of the present study was therefore to identify these anti-BmNPV mechanisms by using metabolomics in combination with transcriptomics after subcutaneous injection of budded virus (BV) with high concentrations of BmNPV from specimens of the Baiyu N variety (which is highly resistant to BmNPV) and the Baiyu variety (which is sensitive to BmNPV). A total of 375 differential metabolites were identified, which mainly included sugars, acids, amines, alcohols, glycosides, and other small molecules. KEGG enrichment analysis and functional clustering of differential metabolites identified possible metabolic pathways, including tyrosine metabolism, oxidative phosphorylation, and alanine, aspartate, and glutamate metabolism. The differentially expressed genes (DEGs) identified by transcriptome analysis were annotated in KEGG. Association analysis showed that the metabolic pathways of different silkworm varieties are affected differently by BmNPV infection, triggering a series of complex physiological and biochemical changes in the organism. In particular, oxidative phosphorylation might be an essential pathway involved in regulation of disease resistance.
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http://dx.doi.org/10.1007/s00705-022-05463-1DOI Listing
August 2022

Low HDL-C is a non-fasting marker of insulin resistance in children.

J Pediatr Endocrinol Metab 2022 Jun 2. Epub 2022 Jun 2.

Division of Pediatric Endocrinology and Diabetes, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.

Background: Childhood obesity and associated comorbidities, including insulin resistance, are increasing in the United States. Our objectives were to (1) determine the prevalence of insulin resistance in children seen in dyslipidemia clinic and (2) evaluate which aspects of the lipid profile correlate with insulin resistance.

Methods: Children and adolescents seen in a specialized pediatric dyslipidemia clinic without secondary diagnoses known to alter the lipid panel were included. Simultaneous fasting lipid panel, insulin, and glucose levels were available in 572 children (50.5% male).

Results: Mean patient age was 15.0±3.6 years with the majority being over 10 years of age (92.5%). Mean BMI was 29.8±8.1 kg/m and BMI standard deviation score was 1.80±0.9. Mean HOMA-IR was 6.2±5.7 with a range of 0.4-49.3, and interquartile range of 2.7-7.6. Triglyceride level had a positive correlation with HOMA-IR (p<0.001). HDL-C negatively correlated with HOMA-IR even controlling for triglyceride level by multivariate analysis (p=0.001) and HDL-C <30 mg/dL predicted IR with 41.5% PPV.

Conclusions: In children and adolescents with dyslipidemia, insulin resistance is common and significantly correlates with reduced HDL-C levels. Non-fasting samples are easier to obtain in children and low HDL-C, which is minimally affected on non-fasting samples, could be an easily obtained indicator of IR. Increasing detection of insulin resistance in children with dyslipidemia may provide greater opportunities for lifestyle interventions and possible pharmacotherapy to modify cardiovascular risk.
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http://dx.doi.org/10.1515/jpem-2021-0751DOI Listing
June 2022

Protective effects of Cordyceps sinensis exopolysaccharide‑selenium nanoparticles on HO-induced oxidative stress in HepG2 cells.

Int J Biol Macromol 2022 Jul 29;213:339-351. Epub 2022 May 29.

College of Food Science and Technology and MOE Key Laboratory of Environment Correlative Dietology, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

This work investigated the protective effects of Cordyceps sinensis exopolysaccharide‑selenium nanoparticles (EPS-SeNPs) at different Se/EPS ratios (1/20, 1/3, 1/1, and 4/3) against 0.4 mM HO-induced oxidative stress in human hepatoma (HepG2) cells. Results revealed that EPS-SeNPs (0.1-4.0 μg/mL) promoted the proliferation of HepG2 cells with a cell viability of over 90% during HO stress. Different Se/EPS ratios of EPS-SeNPs provided protective effects against HO-induced oxidative stress in HepG2 cells by increasing cell viability, restoring cell and nucleus morphology, as well as reducing lactate dehydrogenase (LDH) levels. Particularly, EPS-SeNPs (Se/EPS = 1/1) with the smallest particle size showed the highest cell viability and the greatest inhibitory effect on LDH level. Besides, EPS-SeNPs also inhibited nitric oxide and reactive oxygen species (ROS) production, and increased mitochondrial membrane potential, superoxide dismutase (SOD), and catalase levels while reducing glutathione (GSH) content. Specially, EPS-SeNPs at Se/EPS ratio of 1/3 with smaller size showed the lowest ROS level and the highest antioxidant activities (SOD and GSH), implying that the ROS generation was inhibited by increasing enzymatic and non-enzymatic antioxidants. The enhanced protective effect of EPS-SeNPs (Se/EPS = 1/1 and 1/3) might be attributed to its smaller particle size.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.05.173DOI Listing
July 2022

Gradient Design for High-Energy and High-Power Batteries.

Adv Mater 2022 May 29:e2202780. Epub 2022 May 29.

Materials Science and Engineering Program and Walker Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA.

Charge transport is a key process that dominates battery performance, and the microstructures of the cathode, anode, and electrolyte play a central role in guiding ion and/or electron transport inside the battery. Rational design of key battery components with varying microstructure along the charge-transport direction to realize optimal local charge-transport dynamics can compensate for reaction polarization, which accelerates electrochemical reaction kinetics. Here, the principles of charge-transport mechanisms and their decisive role in battery performance are presented, followed by a discussion of the correlation between charge-transport regulation and battery microstructure design. The design strategies of the gradient cathodes, lithium-metal anodes, and solid-state electrolytes are summarized. Future directions and perspectives of gradient design are provided at the end to enable practically accessible high-energy and high-power-density batteries.
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http://dx.doi.org/10.1002/adma.202202780DOI Listing
May 2022

Highly stable and tunable peptoid/hemin enzymatic mimetics with natural peroxidase-like activities.

Nat Commun 2022 May 31;13(1):3025. Epub 2022 May 31.

Physical Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99352, USA.

Developing tunable and stable peroxidase mimetics with high catalytic efficiency provides a promising opportunity to improve and expand enzymatic catalysis in lignin depolymerization. A class of peptoid-based peroxidase mimetics with tunable catalytic activity and high stability is developed by constructing peptoids and hemins into self-assembled crystalline nanomaterials. By varying peptoid side chain chemistry to tailor the microenvironment of active sites, these self-assembled peptoid/hemin nanomaterials (Pep/hemin) exhibit highly modulable catalytic activities toward two lignin model substrates 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 3,3',5,5'-tetramethylbenzidine. Among them, a Pep/hemin complex containing the pyridyl side chain showed the best catalytic efficiency (V/K = 5.81 × 10 s). These Pep/hemin catalysts are highly stable; kinetics studies suggest that they follow a peroxidase-like mechanism. Moreover, they exhibit a high efficacy on depolymerization of a biorefinery lignin. Because Pep/hemin catalysts are highly robust and tunable, we expect that they offer tremendous opportunities for lignin valorization to high value products.
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http://dx.doi.org/10.1038/s41467-022-30285-9DOI Listing
May 2022
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