Publications by authors named "Chang Liu"

4,507 Publications

  • Page 1 of 1

Catellatolactams A-C, Plant Growth-Promoting Ansamacrolactams from a Rare Actinomycete of the Genus .

J Nat Prod 2022 Aug 10. Epub 2022 Aug 10.

Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.

Catellatolactams A-C (-), three novel ansamacrolactams, were isolated from the culture extract of an underexplored rare actinomycete of the genus . Spectroscopic and spectrometric analyses by NMR and MS elucidated the structure of to be a lactamized pentaketide presumably extended on a 3-amino-5-hydroxybenzoic acid starter unit. Compounds and further received epoxidation and intramolecular cross-linking to incorporate a 2-indolinone unit, with a 3-amino-5-hydroxybenzoic acid pendant on . The absolute configurations of and were unequivocally established to both be 2,6,7 by comparison of the experimental NMR chemical shifts and ECD spectra with those predicted by DFT-based quantum chemical calculation. While - showed no appreciable antimicrobial activity or cytotoxicity, root elongation of germinated lettuce seeds was promoted by and at 1-10 μM.
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http://dx.doi.org/10.1021/acs.jnatprod.2c00331DOI Listing
August 2022

Comparative analysis of the chloroplast and mitochondrial genomes of Saposhnikovia divaricata revealed the possible transfer of plastome repeat regions into the mitogenome.

BMC Genomics 2022 Aug 10;23(1):570. Epub 2022 Aug 10.

Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine from Ministry of Education, Engineering Research Center of Chinese Medicine Resources from Ministry of Education, Center for Bioinformatics, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, 100193, Beijing, P. R. China.

Background: Saposhnikovia divaricata (Turcz.) Schischk. is a perennial herb whose dried roots are commonly used as a source of traditional medicines. To elucidate the organelle-genome-based phylogeny of Saposhnikovia species and the transfer of DNA between organelle genomes, we sequenced and characterised the mitochondrial genome (mitogenome) of S. divaricata.

Results: The mitogenome of S. divaricata is a circular molecule of 293,897 bp. The nucleotide composition of the mitogenome is as follows: A, 27.73%; T, 27.03%; C, 22.39%; and G, 22.85. The entire gene content is 45.24%. A total of 31 protein-coding genes, 20 tRNAs and 4 rRNAs, including one pseudogene (rpl16), were annotated in the mitogenome. Phylogenetic analysis of the organelle genomes from S. divaricata and 10 related species produced congruent phylogenetic trees. Selection pressure analysis revealed that most of the mitochondrial genes of related species are highly conserved. Moreover, 2 and 46 RNA-editing sites were found in the chloroplast genome (cpgenome) and mitogenome protein-coding regions, respectively. Finally, a comparison of the cpgenome and the mitogenome assembled from the same dataset revealed 10 mitochondrial DNA fragments with sequences similar to those in the repeat regions of the cpgenome, suggesting that the repeat regions might be transferred into the mitogenome.

Conclusions: In this study, we assembled and annotated the mitogenome of S. divaricata. This study provides valuable information on the taxonomic classification and molecular evolution of members of the family Apiaceae.
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http://dx.doi.org/10.1186/s12864-022-08821-0DOI Listing
August 2022

Contrast-enhanced ultrasound in the assessment of Crohn's disease activity: comparison with computed tomography enterography.

Radiol Med 2022 Aug 9. Epub 2022 Aug 9.

Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Background And Objective: Continuous assessment of disease activity remains a huge challenge during the follow-ups of patients with Crohn's disease (CD). In this paper, we aimed to evaluate the performance of contrast-enhanced ultrasound (CEUS) by comparing with computed tomography enterography (CTE) in the assessment of disease activity in CD.

Materials And Methods: Fifty-two patients diagnosed with CD were included in this study, using the CEUS and CTE as imaging methods for comparison. The selected parameters included the location and thickness of the thickest part of the intestinal wall, mesenteric fat proliferation, mesenteric vessels change, enhancement pattern and the presence of complications. Patients were clinically assessed using the Crohn's disease activity index (CDAI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Simple endoscopic score for Crohn's disease (SES-CD) was regarded as the reference standard.

Results: The location of the thickest part of the intestinal wall (κ = 0.653), bowel wall thickness (ICC = 0.795), mesenteric vessels change (κ = 0.692) and complications (κ = 0.796) displayed substantial agreement (0.61-0.80) between CEUS and CTE, while the detection of mesenteric fat proliferation (κ = 0.395) and enhancement pattern (κ = 0.288) showed fair consistency (0.21-0.40) for comparison. In CEUS, bowel wall thickness, mesenteric fat proliferation, enhancement pattern and mesenteric vessels change were statistically significant in assessing CD activity, while bowel wall thickness, mesenteric fat proliferation and mesenteric vessels change in CTE. Bowel wall thickness showed the best diagnostic performance in the assessment of CD activity at CEUS and CTE.

Conclusion: CEUS provides a radiation-free and effective way to assess the CD activity in comparison with CTE, which also avoids frequent colonoscopy examinations, improves tolerance of patients, and reduces the cost of medical care, thereby serving as a useful tool for CD follow-up.
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http://dx.doi.org/10.1007/s11547-022-01535-zDOI Listing
August 2022

Association of Elevated Thyroid Stimulating Hormone with Atherosclerotic Cardiovascular Disease and Its Mortality in Elderly Community-Dwelling Chinese.

Clin Interv Aging 2022 2;17:1139-1150. Epub 2022 Aug 2.

Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.

Purpose: With increase of population aging, the prevalence of atherosclerotic cardiovascular disease (ASCVD) and elevated serum thyroid stimulating hormone (TSH) in elderly is increasing. High TSH level was reported to be associated with ASCVD and CVD mortality; however, few are studied in Chinese population, especially in the elderly. This study aimed to investigate the prevalence of elevated serum TSH and ASCVD in an elderly population of Chinese community and to explore the association between high serum TSH and ASCVD or CVD mortality.

Patients And Methods: We conducted a study involving 3814 adults who were at least 60 years of age. Questionnaires, physical examinations, and laboratory blood samples were collected in 2014, and a 78-months follow-up for cardiovascular and all-cause mortality was performed till December of 2020. Logistics regression was used to analyze the association between TSH and ASCVD. We used Cox models to assess the hazard ratios (HRs) for all-cause and CVD mortality across changes in serum TSH.

Results: In this study, the prevalence of the elevated serum TSH was 19.8%, and significantly higher in women than in men (24.5% vs 13.9%, p < 0.001). The prevalence of ASCVD was 21.7%. In logistics regression models, elevated TSH was associated with ASCVD after adjusting for the risk factors of ASCVD in people over the age of 70 years (adjusted OR 1.054, P = 0.014). After a follow-up of 6.5 years, total 441 (11.6%) all-cause death and 174 (4.6%) death of CVD were observed. In Cox regression model, no significant correlation was found between TSH and all-cause mortality or CVD mortality in the elderly population.

Conclusion: In the elderly population, there is high prevalence of elevated serum TSH and ASCVD. Elevated TSH seemed to be not associated with risk of all-cause or CVD mortality.
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http://dx.doi.org/10.2147/CIA.S368219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356737PMC
August 2022

Next-generation sequencing facilitates genetic diagnosis and improves the management of patients with hearing loss in clinical practice.

Int J Pediatr Otorhinolaryngol 2022 Jul 31;161:111258. Epub 2022 Jul 31.

Medical Genetic Center, Guangdong Women and Children Hospital, Guangzhou, Guangdong, 510010, China; Maternal and Children Metabolic-Genetic Key Laboratory, Guangdong Women and Children Hospital, Guangzhou, Guangdong, 510010, China. Electronic address:

Background: Hearing loss (HL) is a prevalent sensorineural disorder, and is among the most etiologically heterogeneous disorders. With the advent of next-generation sequencing (NGS) technologies, hundreds of candidate genes can be analyzed simultaneously in a cost-effective manner.

Methods: Ninety-four patients from 87 families diagnosed with non-syndromic or syndromic HL were enrolled. A custom-designed HL panel and clinical exome sequencing (CES) were applied to explore molecular etiology in the cohort, and the efficacy of the two panels was examined.

Results: The etiologic diagnosis for HL has been identified for 36 out of 87 probands (41.4%), 28 with an autosomal recessive (AR) inheritance pattern and 8 with an autosomal dominant (AD) pattern. Candidate variants in 18 different genes were identified in the study cohort, 10 with AR inheritance pattern and 8 with AD pattern. Fourteen of the variants identified in the study were novel.

Conclusions: The custom-designed HL panel covers almost all known HL-associated genes, and can be used as an effective clinical diagnostic platform; CES evaluates all exons related to clinical symptoms, and is also suitable for clinical diagnosis of HL. Next-generation sequencing facilitates genetic diagnosis and improves the management of patients with HL in the clinical practice.
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http://dx.doi.org/10.1016/j.ijporl.2022.111258DOI Listing
July 2022

A "Plug-and-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-binding Domain.

J Vis Exp 2022 Jul 25(185). Epub 2022 Jul 25.

National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University;

Biomimetic nanoparticles obtained from bacteria or viruses have attracted substantial interest in vaccine research and development. Outer membrane vesicles (OMVs) are mainly secreted by gram-negative bacteria during average growth, with a nano-sized diameter and self-adjuvant activity, which may be ideal for vaccine delivery. OMVs have functioned as a multifaceted delivery system for proteins, nucleic acids, and small molecules. To take full advantage of the biological characteristics of OMVs, bioengineered Escherichia coli-derived OMVs were utilized as a carrier and SARS-CoV-2 receptor-binding domain (RBD) as an antigen to construct a "Plug-and-Display" vaccine platform. The SpyCatcher (SC) and SpyTag (ST) domains in Streptococcus pyogenes were applied to conjugate OMVs and RBD. The Cytolysin A (ClyA) gene was translated with the SC gene as a fusion protein after plasmid transfection, leaving a reactive site on the surface of the OMVs. After mixing RBD-ST in a conventional buffer system overnight, covalent binding was formed between the OMVs and RBD. Thus, a multivalent-displaying OMV vaccine was achieved. By replacing with diverse antigens, the OMVs vaccine platform can efficiently display a variety of heterogeneous antigens, thereby potentially rapidly preventing infectious disease epidemics. This protocol describes a precise method for constructing the OMV vaccine platform, including production, purification, bioconjugation, and characterization.
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http://dx.doi.org/10.3791/64213DOI Listing
July 2022

Active components and molecular mechanism of Lindl. in the treatment of endometritis based on pharmacology network prediction.

Front Vet Sci 2022 22;9:885952. Epub 2022 Jul 22.

Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Antibiotic treatment of endometritis was limited by the inevitable antibiotic residues and risk of bacterial resistance. Therefore, the development of safe and effective strategies for endometritis treatment is urgently needed. Lindl. (SOL) showed great pharmacological potential against endometritis. However, the active components and underlying mechanism of SOL for endometritis treatment remain indeterminate. In our study, the active components and possible molecular mechanism of SOL against endometritis were predicted through computer data mining and biological networks construction. It was predicted that the main active components of SOL were luteolin, kaempferol, oleanolic acid, and rutin, and their anti-endometritis effect was mainly attributed to the TLRs/NF-κB signaling pathway. Furthermore, a green and efficient deep eutectic solvent combined with ultrasound-assisted extraction (DES-UAE) was performed and optimized to obtain high contents of total flavonoid, rutin, and luteolin. The four predicted active components in the SOL extracts were qualitatively and quantitatively analyzed by LC/MS and HPLC. Finally, the pharmacological effects of SOL and active components have been verified by -endometritis models in mice. H&E staining and bacterial load in uterus tissues assays initially validated the pharmacodynamic effects of SOL, and quantitative real-time PCR (RT-qPCR) and ELISA results confirmed that SOL and four active components could ameliorate the uterus injury caused by , the mechanism of action is related to the TLRs/NF-κB signaling pathway.
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http://dx.doi.org/10.3389/fvets.2022.885952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355479PMC
July 2022

Lesional Intractable Epileptic Spasms in Children: Electroclinical Localization and Postoperative Outcomes.

Front Neurol 2022 22;13:922778. Epub 2022 Jul 22.

Pediatric Epilepsy Center, Peking University First Hospital, Beijing, China.

To analyze the influence of seizure semiology, electroencephalography (EEG) features and magnetic resonance imaging (MRI) change on epileptogenic zone localization and surgical prognosis in children with epileptic spasm (ES) were assessed. Data from 127 patients with medically intractable epilepsy with ES who underwent surgical treatment were retrospectively analyzed. ES semiology was classified as non-lateralized, bilateral asymmetric, and focal. Interictal epileptiform discharges were divided into diffusive or multifocal, unilateral, and focal. MRI results showed visible local lesions for all patients, while the anatomo-electrical-clinical value of localization of the epileptogenic zone was dependent on the surgical outcome. During preoperative video EEG monitoring, among all 127 cases, 53 cases (41.7%) had ES only, 46 (36.2%) had ES and focal seizures, 17 (13.4%) had ES and generalized seizures, and 11 (8.7%) had ES with focal and generalized seizures. Notably, 35 (27.6%) and 92 cases (72.4%) showed simple and complex ES, respectively. Interictal EEG showed that 22 cases (17.3%) had bilateral multifocal discharges or hypsarrhythmia, 25 (19.7%) had unilateral dominant discharges, and 80 (63.0%) had definite focal or regional discharges. Ictal discharges were generalized/bilateral in 71 cases (55.9%) and definite/lateralized in 56 cases (44.1%). Surgically resected lesions were in the hemisphere (28.3%), frontal lobe (24.4%), temporal lobe (16.5%), temporo-parieto-occipital region (14.2%), and posterior cortex region (8.7%). Seizure-free rates at 1 and 4 years postoperatively were 81.8 and 72.7%, respectively. There was no significant difference between electroclinical characteristics of ES and seizure-free rate. Surgical treatment showed good outcomes in most patients in this cohort. Semiology and ictal EEG change of ES had no effect on localization, while focal or lateralized epileptiform discharges of interictal EEG may affect lateralization and localization. Complete resection of epileptogenic lesions identified MRI was the only factor associated with a positive surgical outcome.
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http://dx.doi.org/10.3389/fneur.2022.922778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353030PMC
July 2022

A novel HLA-DQA1*01 allele, HLA-DQA1*01:99, identified by next-generation sequencing.

HLA 2022 Aug 6. Epub 2022 Aug 6.

Department of pathology and Immunology, Washington University in St. Louis, St. Louis, Missouri, USA.

DQA1*01:99 differs from DQA1*01:01 by a missense nucleotide substitution in Exon 4. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/tan.14758DOI Listing
August 2022

Potential of Antibody Pair Targeting Conserved Antigenic Sites in Diagnosis of SARS-CoV-2 Variants Infection.

J Virol Methods 2022 Aug 3:114597. Epub 2022 Aug 3.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, 361102 Xiamen, Fujian, PR China. Electronic address:

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has become disaster for human society. As the pandemic becomes more regular, we should develop more rapid and accurate detection methods to achieve early diagnosis and treatment. Antigen detection methods based on spike protein has great potential, however, it has not been effectively developed, probably due to the torturing conformational complexity. By utilizing cross-blocking data, we clustered SARS-CoV-2 receptor binding domain (RBD)-specific monoclonal antibodies (mAbs) into 6 clusters. Subsequently, the antigenic sites for representative mAbs were identified by RBDs with designed residue substitutions. The sensitivity and specificity of selected antibody pairs was demonstrated using serial diluted samples of SARS-CoV-2 S protein and SARS-CoV S protein. Furthermore, pseudovirus system was constructed to determine the detection capability against SARS-CoV-2 and SARS-CoV. 6 RBD-specific mAbs, recognizing different antigenic sites, were identified as potential candidates for optimal antibody pairs for detection of SARS-CoV-2 S protein. By considering relative spatial position, accessibility and conservation of corresponding antigenic sites, affinity and the presence of competitive antibodies in clinical samples, 6H7-6G3 was rationally identified as optimal antibody pair for detection of both SARS-CoV-2 and SARS-CoV. Furthermore, our results showed that 6H7 and 6G3 effectively bind to SARS-CoV-2 variants of concern (VOCs). Taken together, we identified 6H7-6G3 antibody pair as a promising rapid antigen diagnostic tool in containing COVID-19 pandemic caused by multiple VOCs. Moreover, our results also provide an important reference in screening of antibody pairs detecting antigens with complex conformation.
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http://dx.doi.org/10.1016/j.jviromet.2022.114597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347178PMC
August 2022

Mettl3-mediated mRNA mA modification controls postnatal liver development by modulating the transcription factor Hnf4a.

Nat Commun 2022 Aug 5;13(1):4555. Epub 2022 Aug 5.

Biotherapy Centre, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Hepatic specification and functional maturation are tightly controlled throughout development. N6-methyladenosine (mA) is the most abundant RNA modification of eukaryotic mRNAs and is involved in various physiological and pathological processes. However, the function of mA in liver development remains elusive. Here we dissect the role of Mettl3-mediated mA modification in postnatal liver development and homeostasis. Knocking out Mettl3 perinatally with Alb-Cre (Mettl3 cKO) induces apoptosis and steatosis of hepatocytes, results in severe liver injury, and finally leads to postnatal lethality within 7 weeks. mA-RIP sequencing and RNA-sequencing reveal that mRNAs of a series of crucial liver-enriched transcription factors are modified by mA, including Hnf4a, a master regulator for hepatic parenchymal formation. Deleting Mettl3 reduces mA modification on Hnf4a, decreases its transcript stability in an Igf2bp1-dependent manner, and down-regulates Hnf4a expression, while overexpressing Hnf4a with AAV8 alleviates the liver injury and prolongs the lifespan of Mettl3 cKO mice. However, knocking out Mettl3 in adults using Alb-Cre does not affect liver homeostasis. Our study identifies a dynamic role of Mettl3-mediated RNA mA modification in liver development.
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http://dx.doi.org/10.1038/s41467-022-32169-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355946PMC
August 2022

Anatomic measurement of osseous parameters of the glenoid.

Sci Rep 2022 Aug 4;12(1):13424. Epub 2022 Aug 4.

Guangdong Provincial Key Laboratory of Medical Biomechanics and Guangdong Engineering Research Center for Translation of Medical 3D Printing Application and National Virtual and Reality Experimental Education Center for Medical Morphology (Southern Medical University) and National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, 1023 Shatai South Road, Baiyun District, Guangzhou, 510515, Guangdong, China.

The angle and position of the scapular glenoid are important in shoulder mechanics, the interpretation of diseases, and planning shoulder replacement surgery. In total shoulder replacement, understanding the bony parameters of the glenoid is also of considerable guiding significance for designing implant size and improving material adaptability. To compare glenoid parameters measured from skeletal scapula specimens with those measured by 3D modeling of CT scanning images, analyze correlations between these data, and draw conclusions to guide clinical treatment of shoulder joint injury and total shoulder joint replacement. The data of manual and CT measurements from the same Chinese dry glenoid was compared. Three-dimensional measurement data were collected from the Japanese population and compared with the Chinese population data generated in this study. There were no significant differences between manual measurement and CT measurement in the inclination angle, glenopolar angle, anteroposterior transverse diameter, upper to lower vertical diameter, and depth of the glenoid (P = 0.288, 0.524, 0.111, 0.194, and 0.055, respectively). Further, there were no significant differences between Japanese and Chinese glenoid bones in the upper and lower vertical diameters or anteroposterior transverse diameters (P > 0.05). There were no significant differences between CT and manual measurements, suggesting that the CT method may provide measurements very close to the actual specimen size. This result, however, indicated that the measurer should be careful when measuring the depth of the glenoid.
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http://dx.doi.org/10.1038/s41598-022-17783-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352768PMC
August 2022

Quantitative CT evaluation after two cycles of induction chemotherapy to predict prognosis of patients with locally advanced oesophageal squamous cell carcinoma before undergoing definitive chemoradiotherapy/radiotherapy.

Eur Radiol 2022 Aug 4. Epub 2022 Aug 4.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/ Beijing), Department of Radiology, Peking University Cancer Hospital & Institute, No. 52, Fucheng Road, Hai Dian District, Beijing, 100142, China.

Objective: To investigate the performance of quantitative CT analysis in predicting the prognosis of patients with locally advanced oesophageal squamous cell carcinoma (ESCC) after two cycles of induction chemotherapy before definitive chemoradiotherapy/radiotherapy.

Methods: A total of 110 patients with locally advanced ESCC were retrospectively analysed. Baseline chest CT and CT after two cycles of induction chemotherapy were analysed. A multivariate Cox proportional-hazard regression model was used to identify independent prognostic markers for survival analysis. Then, a CT scoring system was established. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan-Meier method were employed for analysing the prognostic value of the CT scoring system.

Results: Body mass index, treatment strategy, change ratios of thickness (ΔTH), CT value of the primary tumour (ΔCTV) and the short diameter (ΔSD-LN), and the presence of an enlarged small lymph node (ESLN) after two cycles of chemotherapy were noted as independent factors for predicting overall survival (OS). The specificity of the presence of ESLN for death after 12 months was up to 100%. Areas under the curve value of the CT scoring system for predicting OS and progression-free survival (PFS) were higher than that of the RECIST (p < 0.05). Responders had significantly longer OS and PFS than non-responders.

Conclusion: Quantitative CT analysis after two cycles of induction chemotherapy could predict the outcome of locally advanced ESCC patients treated with definitive chemoradiotherapy/radiotherapy. The CT scoring system could contribute to the development of an appropriate strategy for patients with locally advanced ESCC.

Key Points: • Quantitative CT evaluation after two cycles of induction chemotherapy can predict the long-term outcome of locally advanced oesophageal cancer treated with definitive chemoradiotherapy/radiotherapy. • A CT scoring system provides valuable imaging support for indicating the prognosis at the early stage of therapy. • Quantitative CT evaluation can assist clinicians in personalising treatment plans.
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http://dx.doi.org/10.1007/s00330-022-08994-yDOI Listing
August 2022

Botulinum Toxin A Alleviates Persistent Erythema and Flushing in Patients with Erythema Telangiectasia Rosacea.

Dermatol Ther (Heidelb) 2022 Aug 4. Epub 2022 Aug 4.

Department of Dermatology, First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.

Introduction: The persistent erythema and flushing seen in some cases of rosacea do not respond effectively to, or may easily relapse after, oral medication or light-based therapies (laser or intense pulsed light). Intradermal botulinum toxin A (BTX-A) injection can be used to treat intractable erythema and flushing, but studies with large samples and long-term observation have not been conducted to determine its effectiveness and safety. The aim of this study is thus to investigate the effective duration and safety of intradermal BTX-A injection for intractable erythema and flushing.

Methods: Sixteen patients with rosacea with erythema telangiectasia were injected with BTX-A at 1-cm intervals between each point. Clinician Erythema Assessment (CEA) scores were obtained at baseline and 1 month after injection. Flushing assessment and survey using the Dermatological Quality of Life Index (DLQI) questionnaire were conducted at baseline and at 1, 3, and 6 months after injection.

Results: At 1 month after injection, CEA scores revealed significant improvements in erythema and flushing; the results of the questionnaire on flushing and DLQI indicated that the improvement of flushing usually lasted for 3-6 months, but the effect decreased significantly at 6 months, and individual patients needed another treatment.

Conclusions: BTX-A significantly improves the symptoms and quality of life of patients with refractory rosacea with few adverse effects.
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http://dx.doi.org/10.1007/s13555-022-00784-0DOI Listing
August 2022

The mA methyltransferase Mettl3 deficiency attenuates hepatic stellate cell activation and liver fibrosis.

Mol Ther 2022 Aug 2. Epub 2022 Aug 2.

Biotherapy Centre, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Cell-gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address:

Activation of hepatic stellate cells (HSCs) is a central driver of liver fibrosis. Previous investigations have identified various altered epigenetic landscapes during the cellular progression of HSC activation. N6-methyladenosine (mA) is the most abundant internal RNA modification in eukaryotic cells and is dynamically regulated under various physiological and pathophysiological conditions. However, the functional role of Mettl3-mediated mA in liver fibrosis remains elusive. Here, we found that the HSC-specific knockout of mA methyltransferase Mettl3 suppressed HSC activation and significantly alleviated liver fibrosis. Multi-omics analysis of HSCs showed that Mettl3 depletion reduced mA deposition on mRNA transcripts of Lats2 (a central player of the Hippo/YAP signaling pathway) and slowed down their degradation. Elevated Lats2 increased phosphorylation of downstream transcription factor YAP, suppressed YAP nuclear translocation, and decreased pro-fibrotic gene expression. Overexpressing YAP mutant resistant to phosphorylation by Lats2 partially rescued the activation and pro-fibrotic gene expression of Mettl3-deficient HSCs. Our study revealed that disruption of Mettl3 in HSCs mitigated liver fibrosis by controlling the Hippo/YAP signaling pathway, providing potential therapeutic strategies to alleviate liver fibrosis by targeting epitranscriptomic machinery.
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http://dx.doi.org/10.1016/j.ymthe.2022.07.020DOI Listing
August 2022

Facile fabrication of [email protected]@C8 nanoparticles as a SERS substrate and their environmental applications.

Analyst 2022 Aug 3. Epub 2022 Aug 3.

Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, People's Republic of China.

After preparing carbon-coated silver ([email protected]) nanoparticles by a one-step hydrothermal synthesis method, the surface of the nanoparticles was modified with chlorodimethyloctylsilane (C8) to generate C8 functionalized [email protected]@C8 nanoparticles. The [email protected]@C8 nanoparticles were then employed as a substrate for surface enhancement Raman scattering (SERS). The high sensitivity, good uniformity, and long stability Raman signals for both probe dyes (rhodamine 6G and crystal violet) and a real sample (malachite green) in water demonstrated good performance of the as-synthesised [email protected]@C8 nanoparticles. SEM images and TEM images indicate the successful preparation of [email protected] nanoparticles. The results of energy disperse spectroscopy, X-ray photoelectron spectroscopy and contact angle measurements all demonstrate that C8 is successfully functionalized on the surface of [email protected] nanoparticles. The combination of an agglomeration effect and the core-shell structure improves the sensitivity and stability of the substrate. The Raman performance of both [email protected] and [email protected]@C8 nanoparticles was evaluated using representative probe molecules such as rhodamine 6G, crystal violet and malachite green. The sensitivity and enhancement factor of [email protected]@C8 were evaluated using folic acid, a non-dye molecule. Additionally, malachite green in several actual water samples was also measured to evaluate the [email protected]@C8 nanoparticles. Then, using crystal violet as a probe molecule, the long-term stability of the [email protected]@C8 nanoparticles was investigated. The results indicate that for four weeks, the intensity deviations of different characteristic peaks were less than 17.5%, and there was no further downward trend. Our strategy partially overcomes the problem of easy oxidation of Ag nanoparticles by coating them with a thin carbon layer, and subsequent functionalization with C8 can increase the SERS sensitivity for certain pollutants due to a condensation effect.
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http://dx.doi.org/10.1039/d2an01073aDOI Listing
August 2022

Enhanced biocrude production from hydrothermal conversion of municipal sewage sludge co-liquefaction with various model feedstocks.

RSC Adv 2022 Jul 13;12(31):20379-20386. Epub 2022 Jul 13.

Shenergy Environmental Technologies Co., Ltd Buiding 7. Vanka Canter, 988 Shenchang Rd Shanghai 201100 China

Hydrothermal co-liquefaction has the potential to improve biocrude yield. To investigate the influence of various types of biomass on co-liquefaction with municipal sewage sludge (MSS), experiments on MSS with three kinds of model feedstocks (soy oil, soy protein, and starch) were carried out. Reaction temperatures of 300, 320, and 340 °C proved to be the appropriate reaction temperatures for the highest biocrude yield for soy oil, soy protein, and starch, respectively. A synergistic effect on the biocrude yield of co-liquefaction was proved, and starch showed the highest synergistic effect with a 57.25% increase in biocrude yield, while soy oil only presented a slight synergistic effect. Thermal gravimetric analysis (TGA) results suggested that co-liquefaction with soy oil increased the light oil fractions in biocrude by 20.81%, but protein and starch led to more heavy oil fractions. Gas chromatography-mass spectrometry (GC-MS) indicated that co-liquefaction with protein or starch produced more cyclic compounds in the biocrude, while almost no new components appeared from co-liquefaction with soy oil.
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http://dx.doi.org/10.1039/d2ra02325cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277621PMC
July 2022

Mass Budget of Mercury (Hg) in the Seawater of Eastern China Marginal Seas: Importance of the Sediment-Water Transport Processes.

Environ Sci Technol 2022 Aug 2. Epub 2022 Aug 2.

Department of Chemistry and Biochemistry, Florida International University, Miami, Florida 33199, United States.

The Eastern China Marginal Seas (ECMS) have been facing a variety of environmental problems, including mercury (Hg) pollution. Although several previous studies have been focused on mass balance of Hg in the ECMS, the contribution of Hg transport at the sediment-water interface remains unclear. This study was aimed to access and quantify the importance of sediment-water transport processes in Hg cycling. Significantly positive correlations were observed between Hg concentrations in the overlying and bottom water and the diffusion rates of Hg from sediment to the water. Approximately 2-3 times higher of THg concentrations in the entire water column were observed in a winter cruise with strong waves which was supposed to strengthen the resuspension process. The mass budget of Hg in the ECMS further showed that diffusion and resuspension processes accounted for approximate 46%, 60%, and 16% of total input Hg in the BS, YS, and ECS, respectively. These results suggest that the sediment-water transport processes play an important role in Hg cycling in the ECMS. As an important "pool" of Hg in the ECMS, the transport of Hg at the sediment-water interface may affect the long-term risk assessment of Hg in these systems.
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http://dx.doi.org/10.1021/acs.est.2c03261DOI Listing
August 2022

Characterization of Codonopsis pilosula subsp. tangshen plastome and comparative analysis of Codonopsis species.

PLoS One 2022 1;17(8):e0271813. Epub 2022 Aug 1.

Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine from Ministry of Education, Engineering Research Center of Chinese Medicine Resources from Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, P. R. China.

Codonopsis pilosula subsp. tangshen is one of the most important medicinal herbs used in traditional Chinese medicine. Correct identification of materials from C. pilosula subsp. tangshen is critical to ensure the efficacy and safety of the associated medicines. Traditional DNA molecular markers could distinguish Codonopsis species well, so we need to develop super or specific molecular markers. In this study, we reported the plastome of Codonopsis pilosula subsp. tangshen (Oliv.) D.Y. Hong conducted phylogenomic and comparative analyses in the Codonopsis genus for the first time. The entire length of the Codonopsis pilosula subsp. tangshen plastome was 170,672 bp. There were 108 genes in the plastome, including 76 protein-coding genes, 28 transfer RNA (tRNA), and four ribosomal RNA (rRNA) genes. Comparative analysis indicated that Codonopsis pilosula subsp. tangshen had an unusual large inversion in the large single-copy (LSC) region compared with the other three Codonopsis species. And there were two dispersed repeat sequences at both ends of the inverted regions, which might mediate the generation of this inversion. We found five hypervariable regions among the four Codonopsis species. PCR amplification and Sanger sequencing experiments demonstrated that two hypervariable regions could distinguish three medicinal Codonopsis species. Results obtained from this study will support taxonomic classification, discrimination, and molecular evolutionary studies of Codonopsis species.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271813PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342729PMC
August 2022

A New Method for Early Screening of Gastric Cancer (G17 and CA724 Dual-Labeled Time-Resolved Fluorescence Immunoassay).

Comput Math Methods Med 2022 20;2022:1704948. Epub 2022 Jul 20.

Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China.

Gastric carcinoma (GC) is one of the most common malignancies in the world with the great early screening challenges. The study is aimed at establishing a new detection method for early screening GC using time-resolved fluorescence immunoassay (TRFIA) via quantitative detection of gastrin-17 (G-17) and carbohydrate antigen 724 (CA724) in serum. Time-resolved analyzer measured the fluorescence intensity. The standards of G-17/CA724 were used for drawing the standard curve, which is used to calculate the concentration of G-17 and CA724 in serum sample. The sensitivity for G-17 was 0.54 pg/mL and for CA724 was 0.28 U/mL with a wide-range analyze concentration (0.1-1000) pg/mL or U/mL. The average recoveries ranged from 100.52% to 110.30% for G-17 and 103.02% to 116.00% for CA724. All CVs of the intra- and interassay were below 10% with high specificity. There was a high coefficient between this TRFIA method and the commercially available kits (Pearson 0.9117 for G-17 and 0.9449 for CA724). Additionally, the cutoff value was 88.41 pg/mL and 5.47 U/mL for CA724 in health subjects. This study established a TRFIA method for simultaneous detection of the concentrations of G-17 and CA724 in serum, which provide a new method for sensitive, accurate, and specific early screening of gastric cancer.
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http://dx.doi.org/10.1155/2022/1704948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328981PMC
August 2022

Five-Year Outcomes After Endovascular Treatment for Large Vessel Occlusion Stroke.

Front Neurosci 2022 13;16:920731. Epub 2022 Jul 13.

Department of Neurology, The Third People's Hospital of Zigong, Zigong, China.

Background: The long-term outcomes of acute large vessel occlusion (LVO) in anterior circulation treated by endovascular treatment (EVT) remains to be determined. The aim of this study was to assess the 5-year outcomes of patients with LVO who underwent EVT.

Methods: This study was an observational, nationwide registry of consecutive patients with acute LVO who received EVT in 28 comprehensive stroke centers in China. The primary outcome was the proportion of favorable outcome [modified Rankin Scale score (mRS) 0-2] at 5 years. Secondary outcomes included proportions of patients with excellent outcome (mRS 0-1), all-cause mortality and risk of stroke recurrence at 5 years.

Results: A total of 807 patients were included into the study and had 90-day follow-up data, 657 patients had 5-year follow-up data. At 90 days, 218 patients (27.0%) had an excellent outcome, 349 patients (43.2%) had a favorable functional outcome. 199 patients (24.7%) died. At 5 years, 190 patients (28.9%) had an excellent outcome, 261 patients (39.7%) had a favorable functional outcome, 317 patients (48.2%) died and 129 (28.2%) had stroke recurrence. Because of missing 5-year follow-up data, among available 269 patients who achieved functional independence at 90 days, 208 (77.3%) maintained favorable outcome, 19 (7.1%) had disability (mRS 3-5) and 42 (15.6%) died at 5 years. Furthermore, among available 189 patients with mRS 3-5 at 90 days, 53 (28.0%) patients achieved favorable functional outcome, 60 (31.7%) patients maintained unfavorable functional outcome and 76 (40.2%) patients died within 5 years. Multivariate analyses identified that younger age [odds ratio (OR): 0.96; 95% CI, 0.93-0.99; = 0.009], lower mRS at 90 days (OR: 0.15; 95% CI, 0.10-0.23; < 0.001) and absence of stroke recurrence (OR: 0.001; 95% CI, 0.000-0.006; < 0.001) were significantly associated with favorable outcome at 5 years. Advanced age (OR: 1.06, 95% CI, 1.04-1.08; < 0.001), higher mRS at 90 days (OR: 0.84; 95% CI, 0.73-0.98; = 0.021) and atrial fibrillation (OR: 1.63; 95% CI, 1.02-2.60; = 0.04) were independent factors for stroke recurrence.

Conclusion: Our results indicated that the beneficial effect of EVT in patients with acute LVO can be sustained during the course of at least 5 years. Reducing the risk of stroke recurrence by anticoagulation for atrial fibrillation may be a crucial strategy to improve long-term outcome.
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http://dx.doi.org/10.3389/fnins.2022.920731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326078PMC
July 2022

Case Report: First Case of Endophthalmitis Caused by an Emerging Pathogen: .

Front Public Health 2022 14;10:933851. Epub 2022 Jul 14.

The Department of Ophthalmology, Beijing Children's Hospital Affiliated With Capital Medical University, Beijing, China.

endophthalmitis is a relatively uncommon form of endophthalmitis seen in clinical patients. In general, endophthalmitis tends to carry a poor prognosis. Here, we report a 3-year-old child who was admitted to the hospital due to a rupture of the left eye. The suturing and anterior chamber formation were performed immediately. Approximately, 16 days after the operation, massive whitish plump and tufted exudates gathered in the pupil area and at the bottom of the anterior chamber, and the child was diagnosed with endophthalmitis. The infection was initially considered to be caused by fungal pathogens for that the hyphae and spores were observed in the smear. However, the isolate obtained after 4 days of culturation was identified as actinomycetes using MALDI-TOF. We further classified it as by next-generation sequencing (NGS) based on the MinION platform. Amikacin and sulfamethoxazole tablets were used to control the infection and the ocular inflammation subsided gradually. Intraocular lens (IOL) implantation is planned to be performed at an appropriate future time to improve his vision. endophthalmitis is rare and usually caused by ocular trauma or surgery. In conclusion, should be considered as an emerging pathogen and deserves more attention.
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http://dx.doi.org/10.3389/fpubh.2022.933851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330429PMC
August 2022

A Novel Serum Biomarker Model to Discriminate Aortic Dissection from Coronary Artery Disease.

Dis Markers 2022 20;2022:9716424. Epub 2022 Jul 20.

Division of Cardiothoracic and Vascular Surgery, Sino-Swiss Heart-Lung Transplantation Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Background: The misdiagnosis of aortic dissection (AD) can lead to a catastrophic prognosis. There is currently a lack of stable serological indicators with excellent efficacy for the differential diagnosis of AD and coronary artery disease (CAD). A recent study has shown an association between AD and iron metabolism. Thus, we investigated whether iron metabolism could discriminate AD from CAD.

Methods: This retrospective and multicenter cross-sectional study investigated the efficacy of biomarkers of iron metabolism for the differential diagnosis of AD. We collected biomarkers of iron metabolism, liver function, kidney function, and other biochemistry test, and further, logistic regression analysis was applied.

Results: Between Oct. 8, 2020, and Mar. 1, 2021, we recruited 521 patients diagnosed with AD, CAD, and other cardiovascular diseases (OCDs) with the main symptoms of chest and back pain and assigned them to discovery set ( = 330) or validation set ( = 191). We found that six serum biomarkers, including serum iron, low-density lipoprotein, uric acid, transferrin, high-density lipoprotein, and estimated glomerular filtration rate, can serve as a novel comprehensive indicator (named FLUTHE) for the differential diagnosis of AD and CAD with a sensitivity of 0.954 and specificity of 0.905 to differentially diagnose AD and CAD more than 72 h past symptom onset.

Conclusion: Our findings provide insight into the role of iron metabolism in diagnosing and distinguishing AD, which might in the future be a key component in AD diagnosis. Furthermore, we establish a novel model named "FLUTHE" with higher efficiency, safety, and economy, especially for patients with chest pain for more than 72 h.
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http://dx.doi.org/10.1155/2022/9716424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329023PMC
August 2022

Turning lignin into treasure: An innovative filler comparable to commercial carbon black for the green development of the rubber industry.

Int J Biol Macromol 2022 Jul 27;218:891-899. Epub 2022 Jul 27.

State Key Laboratory of Inorganic Synthesis & Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012, PR China. Electronic address:

Driven by the global carbon neutrality action, biomass-derived functional materials have been applied in many fields to alleviate the pressure brought by the depletion of fossil energy. However, due to the complex structure, lignin faces many difficulties in its high-value utilization. The second largest biomass in the world has become the largest "natural waste". In this paper, the lignin-based biochar-silica (LB-S) hybrid nanoparticles were prepared via a combination of two-step acid precipitation and carbonization using lignin black liquor extracted from xylose residue and sodium silicate as raw materials. The effects of carbonization temperature and lignin-based biochar (LB) content on the reinforcing properties of LB-S were studied. The results show that the particle size, specific surface area, pore characteristics, and surface polarity of LB-S all affect the mechanical properties of the final vulcanizates. The reinforcement performance of the best sample (LB-S) with "high structure" characteristics can be comparable to that of commercial carbon black (CB) N550. This study shows that LB-S hybrid nanoparticles with economic benefits possess the potential to completely replace commercial CB, which can turn lignin waste into treasure and promote the green development of traditional rubber industry in the context of carbon neutrality.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.07.190DOI Listing
July 2022

Examining Research Domain Criteria (RDoC) constructs for anger expression and regulation in toddlers.

J Psychopathol Clin Sci 2022 Aug;131(6):588-597

Department of Psychology, The Pennsylvania State University.

The present study is focused on anger expression and regulation within the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) construct of Frustrative Nonreward. Although previous studies have examined associations between child anger regulation and expression, these studies do not directly address the dynamic processes involved in Frustrative Nonreward using microlongitudinal methods. The current study used data from 561 adopted children, their adoptive parents, and birth parents and aimed to address gaps in the literature by examining: (a) temporal associations between anger expression during a frustrating situation, and behaviors thought to regulate emotions (e.g., attempt-to-escape, support-seeking, distraction, and focus-on-restraint) on a microlongitudinal scale during an arm restraint task assessed at 27 months; (b) birth parent externalizing problems and overreactive parenting by adoptive parents as predictors of child anger expression and moderators of the moment-to-moment associations estimated in Step 1; and (c) longitudinal associations (linear vs. quadratic) between anger expressions and externalizing behaviors at 4.5 years. Findings indicated that children's attempt-to-escape and support-seeking predicted an increase in anger expression in the following 3-s interval, whereas distraction and focus-on-restraint were not associated with changes in anger expression. Furthermore, we found that birth parents' externalizing problems were significantly associated with child anger expression, suggesting heritable influences. Anger expression showed a U-shaped longitudinal association with paternal report of externalizing behaviors at 4.5 years. Taken together, the findings emphasize the significance of integrating microlongitudinal analysis approaches into the RDoC framework, helping to advance our understanding of dynamic processes underlying reactions to Frustrative Nonreward. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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http://dx.doi.org/10.1037/abn0000658DOI Listing
August 2022

Understanding the Association Between Intolerance of Uncertainty and Problematic Smartphone Use: A Network Analysis.

Front Psychiatry 2022 11;13:917833. Epub 2022 Jul 11.

BrainPark, Turner Institute for Brain and Mental Health and School of Psychological Sciences, Monash University, Clayton, VIC, Australia.

Background: Existing research has demonstrated that intolerance of uncertainty (IU) is associated with problematic smartphone use (PSU). However, little is known about how different IU components such as uncertainty-related beliefs, emotions, and behaviors may impact on different PSU symptoms.

Methods: Extending previous research, the current study examined the specific associations between IU components and PSU symptoms via a symptom-level network approach. A regularized partial correlation network consisting of different IU components and PSU symptoms was estimated among 1,849 Chinese university students. We examined pathways and influential nodes (i.e. central components/symptoms and bridge components/symptoms) within the IU-PSU network.

Results: The strongest pathway linking IU and PSU was between emotional reactions to uncertainty and coping-motivated smartphone use. Importantly, emotional reactions toward not having enough information (a reflection of emotional reactions to uncertainty) may act as both a central and a bridge component in maintaining the whole IU-PSU network.

Conclusions: The results are in line with the I-PACE model and highlight that PSU may be a coping response for negative emotions derived from uncertainty. Finally, the current findings highlight the potential of interventions targeting intolerance of uncertainty for reducing PSU.
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http://dx.doi.org/10.3389/fpsyt.2022.917833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309646PMC
July 2022

Time-Frequency Mask-Aware Bidirectional LSTM: A Deep Learning Approach for Underwater Acoustic Signal Separation.

Sensors (Basel) 2022 Jul 26;22(15). Epub 2022 Jul 26.

National Key Laboratory of Science and Technology on Communication, University of Electronic Science and Technology of China, Chengdu 610000, China.

Underwater acoustic signal separation is a key technique for underwater communications. The existing methods are mostly model-based, and cannot accurately characterize the practical underwater acoustic communication environment. They are only suitable for binary signal separation and cannot handle multivariate signal separation. However, recurrent neural networks (RNNs) show a powerful ability to extract the features of temporal sequences. Inspired by this, in this paper, we present a data-driven approach for underwater acoustic signal separation using deep learning technology. We use a bidirectional long short-term memory (Bi-LSTM) approach to explore the features of a time-frequency (T-F) mask, and propose a T-F-mask-aware Bi-LSTM for signal separation. Taking advantage of the sparseness of the T-F image, the designed Bi-LSTM network is able to extract the discriminative features for separation, which further improves the separation performance. In particular, this method breaks through the limitations of the existing methods and not only achieves good results in multivariate separation but also effectively separates signals when they are mixed with 40 dB Gaussian noise signals. The experimental results show that this method can achieve a 97% guarantee ratio (PSR), and the average similarity coefficient of the multivariate signal separation is stable above 0.8 under high noise conditions. It should be noted that our model can only handle known signals such as test signals for calibration.
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http://dx.doi.org/10.3390/s22155598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332702PMC
July 2022

Phenotypic, metabolic, and biogenesis properties of human stem cell-derived cerebellar spheroids.

Sci Rep 2022 Jul 27;12(1):12880. Epub 2022 Jul 27.

Department of Chemistry and Biochemistry, Florida State University, 102 Varsity Way, Tallahassee, FL, 32306, USA.

Human cerebellum consists of high density and complexity of neurons. Thus, it is challenging to differentiate cerebellar-like organoids with similar cellular markers and function to the human brain. Our previous study showed that the combination of retinoic acid (RA), Wingless/integrated (Wnt) activator, and Sonic Hedgehog (SHH) activator promotes cerebellar differentiation from human induced pluripotent stem cells (hiPSCs). This study examined phenotypic, metabolic, and biogenesis in early cerebellar development. Cerebellum spheroids were differentiated from human iPSK3 cells. During day 7-14, RA and Wnt activator CHIR99021 were used and SHH activator purmorphamine (PMR) was added later to promote ventralization. Gene expression for early cerebellar layer markers, metabolism, and extracellular vesicle (EV) biogenesis were characterized. Zinc-induced neurotoxicity was investigated as a proof-of-concept of neurotoxicity study. Flow cytometry results showed that there was no significant difference in NEPH3, PTF1A, OLIG2, and MATH1 protein expression between RCP (RA-CHIR-PMR) versus the control condition. However, the expression of cerebellar genes for the molecular layer (BHLE22), the granule cell layer (GABRB2, PAX6, TMEM266, KCNIP4), the Bergmann glial cells (QK1, DAO), and the Purkinje cell layer (ARHGEF33, KIT, MX1, MYH10, PPP1R17, SCGN) was significantly higher in the RCP condition than the control. The shift in metabolic pathways toward glycolysis was observed for RCP condition. The EV biogenesis marker expression was retained. Mild zinc-induced neurotoxicity may exist when zinc exposure exceeds 1.0 µM. RCP treatment can promote specific cerebellar-like differentiation from hiPSCs indicated by gene expression of early cerebellar markers and regionally enriched genes. The higher cerebellar marker expression is accompanied by the elevated glycolysis with the retained EV biogenesis. This study should advance the understanding of biomarkers during early cerebellar development for cerebellum organoid engineering and neurotoxicity study.
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http://dx.doi.org/10.1038/s41598-022-16970-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329474PMC
July 2022

Rationally designed Ru(II) metallacycles with tunable imidazole ligands for synergistical chemo-phototherapy of cancer.

Chem Commun (Camb) 2022 Aug 11;58(65):9068-9071. Epub 2022 Aug 11.

Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.

Herein, we construct a series of Ru(II) metallacycles with multimodal chemo-phototherapeutic properties, which exhibited much higher anticancer activity and better cancer-cell selectivity than cisplatin. The antitumor mechanism could be ascribed to the activation of caspase 3/7 and the resulting apoptosis. These results open new possibilities for Ru(II) metallacycles in biomedicine.
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http://dx.doi.org/10.1039/d2cc03118cDOI Listing
August 2022

Mechanistic Insights into the Mechanism of Inhibitor Selectivity toward the Dark Kinase STK17B against Its High Homology STK17A.

Molecules 2022 Jul 21;27(14). Epub 2022 Jul 21.

Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China.

As a member of the death-associated protein kinase (DAPK) family, STK17B plays an important role in the regulation of cellular apoptosis and has been considered as a promising drug target for hepatocellular carcinoma. However, the highly conserved ATP-binding site of protein kinases represents a challenge to design selective inhibitors for a specific DAPK isoform. In this study, molecular docking, multiple large-scale molecular dynamics (MD) simulations, and binding free energy calculations were performed to decipher the molecular mechanism of the binding selectivity of PKIS43 toward STK17B against its high homology STK17A. MD simulations revealed that STK17A underwent a significant conformational arrangement of the activation loop compared to STK17B. The binding free energy predictions suggested that the driving force to control the binding selectivity of PKIS43 was derived from the difference in the protein-ligand electrostatic interactions. Furthermore, the per-residue free energy decomposition unveiled that the energy contribution from Arg41 at the phosphate-binding loop of STK17B was the determinant factor responsible for the binding specificity of PKIS43. This study may provide useful information for the rational design of novel and potent selective inhibitors toward STK17B.
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http://dx.doi.org/10.3390/molecules27144655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317881PMC
July 2022
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