Publications by authors named "Yali Liu"

357 Publications

Identification of neurohypophysial hormones and the role of VT in the parturition of pregnant seahorses ().

Front Endocrinol (Lausanne) 2022 29;13:923234. Epub 2022 Jul 29.

Chinese Academy of Science (CAS) Key Laboratory of Tropical Marine Bio-resources and Ecology (LMB), Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.

Neurohypophysial hormones regulate the reproductive behavior of teleosts; however, their role in the gestation and parturition of ovoviviparous fishes with male pregnancy (syngnathids) remains to be demonstrated. In the present study, the complementary DNA (cDNA) sequences of arginine vasotocin (VT) and isotocin (IT) from the lined seahorse () were cloned and identified. We observed that the mature core peptides of seahorse VT and IT were conserved among teleosts. In the phylogenic tree, seahorse VT and IT were clustered independently with teleost VT and IT. The tissue distribution patterns of and were similar, and both were highly expressed in the brain, gills, and gonads. Interestingly, they were also expressed to some extent in the brood pouch. hybridization revealed that and messenger RNA (mRNA) signals in the brain were mainly located in the preoptic area region of the hypothalamus. Intraperitoneal administration of the VT core peptide to pregnant seahorses induced premature parturition, stimulated gonadotropin release, increased serum estrogen levels, and decreased prolactin secretion. Moreover, VT injection upregulated the mRNA expression of the membrane estrogen receptor in the brood pouch. In summary, neurohypophysial hormones promote premature parturition by regulating estrogen synthesis through the hypothalamus-pituitary-gonad axis.
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http://dx.doi.org/10.3389/fendo.2022.923234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372264PMC
August 2022

High plasma soluble thrombomodulin levels indicated poor prognosis of decompensated liver cirrhosis: a prospective cohort study.

Eur J Gastroenterol Hepatol 2022 Aug 5. Epub 2022 Aug 5.

The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University.

Objective: Hepatic sinusoidal endothelial injury is a prominent characteristic of liver cirrhosis. We determined plasma soluble thrombomodulin (sTM) levels in cirrhosis patients to evaluate the relationship between vascular injury and long-term prognosis.

Methods: A prospective single-center study was performed. The participants were followed up for every 6 months or until death or transplantation. A chemiluminescent enzyme immunoassay was used to establish a baseline sTM.

Results: Among the 219 patients with decompensated liver cirrhosis, 53.42% were caused by hepatitis B and hepatitis C. Plasma sTM levels were much higher in cirrhosis than in healthy controls and increased parallel with Child-Pugh classification (P < 0.01) and the amount of ascites (P = 0.04). After adjusting for sex, age, international normalized ratio, bilirubin, and other potential factors, multivariate Cox regression revealed that per TU/ml elevation of plasma sTM causes an increase of 8% in mortality, and per-SD elevation of thrombomodulin causes a 53% increase in mortality. As the mortality rates in low (5.90-12.60 TU/ml) and medium (12.70-18.00 TU/ml) sTM levels were similar, so we chose the cutoff of 18.00 TU/ml to divide into two groups, and K-M analysis indicated that patients with sTM >18.0 TU/ml demonstrated an additional 2.01 times death risk (95% CI, 1.13-7.93; P = 0.01) than those with sTM ≤18.0 TU/ml.

Conclusion: Plasma sTM in cirrhosis was significantly increased in parallel with the severity of liver dysfunction. sTM elevation than 18 TU/ml indicated a poor prognosis of decompensated liver cirrhosis.
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http://dx.doi.org/10.1097/MEG.0000000000002428DOI Listing
August 2022

Performance Comparison of GeneXpert MTB/RIF, Gene Chip Technology, and Modified Roche Culture Method in Detecting and Drug Susceptibility in Sputum.

Contrast Media Mol Imaging 2022 18;2022:2995464. Epub 2022 Jul 18.

Medical Laboratory, Bishan District People's Hospital of Chongqing, Chongqing, China.

Our aim of this study was to observe and analyze the performance of the real-time fluorescence quantitative nucleic acid amplification detection of /rifampicin resistance (GeneXpert MTB/RIF), gene chip technology, and modified Roche culture method in detecting MTB in sputum submitted for inspection and drug susceptibility. Patients with smear-negative suspected pulmonary TB ( = 120) in our hospital were enrolled in this study using a random number table, and sputum samples submitted for inspection were tested by the GeneXpert MTB/RIF, gene chip technology, and modified Roche culture method. With clinical diagnosis as the gold standard, the performance (mainly sensitivity and specificity) of the above three detection methods in the diagnosis of MTB was compared. Next, the drug susceptibility test (DST) was carried out on sputum samples, tested positive by the three methods. With the solid culture results as the evaluation criteria, the performance of the three detection methods in the diagnosis MTB and DST was compared. When compared with the modified Roche culture method, the GeneXpert MTB/RIF had the highest positive rate and a shorter overall test duration ( < 0.05). In contrast with the gene chip technology, the GeneXpert MTB/RIF exhibited higher sensitivity and negative predictive value (NPV) and lower specificity, accuracy, positive predictive value (PPV), and Kappa value ( < 0.05). According to analysis of the diagnostic performance of the three detection methods, GeneXpert MTB/RIF displayed the highest diagnostic sensitivity, ideal predictive values, and the highest similarity with clinical diagnosis in results ( < 0.05). The detection of susceptibility to isoniazid (INH) and RIF showed that the GeneXpert MTB/RIF and gene chip technology performed ideally in DST of MTB. In comparison with the modified Roche culture method, the GeneXpert MTB/RIF and gene chip technology have more prominent performance in detecting MTB and drug susceptibility. Besides, to further improve the accuracy of clinical diagnosis, various molecular biology detection methods can be combined to avoid delaying of the best time for the diagnosis and treatment of the disease.
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http://dx.doi.org/10.1155/2022/2995464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314178PMC
August 2022

Gut microbiome in colorectal cancer: Clinical diagnosis and treatment.

Genomics Proteomics Bioinformatics 2022 Jul 29. Epub 2022 Jul 29.

Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong Special Administrative Region 999077, China. Electronic address:

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers and the leading cause of cancer-associated deaths. Epidemiological studies have shown that both genetic and environmental risk factors contribute to the development of CRC. Several metagenomic studies of CRC have identified gut dysbiosis as a fundamental risk factor in the evolution of colorectal malignancy. Although enormous efforts and substantial progresses have been made in understanding the relationship between the human gut microbiome and CRC, the precise mechanisms involved remain elusive. Recent data have shown a direct causative role of the gut microbiome in DNA damage, inflammation, and drug resistance in CRC, suggesting that modulation of the gut microbiome can act as a powerful tool in CRC prevention and therapy. Here, we provide an overview of the relationship between the gut microbiome and CRC, and explore relevant mechanisms of colorectal tumorigenesis. We next highlight the potential of bacterial species as clinical biomarkers, as well as their roles in therapeutic response. Factors limiting the clinical translation of the gut microbiome and strategies for resolving the current challenges are further discussed.
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http://dx.doi.org/10.1016/j.gpb.2022.07.002DOI Listing
July 2022

Case Report: A Variant in Associated With CLIFAHDD Syndrome in a Chinese Infant.

Front Pediatr 2022 13;10:927392. Epub 2022 Jul 13.

Department of Cardiothoracic Surgery, Hunan Children's Hospital, Changsha, China.

Background: The encodes a sodium ion leak channel that regulates nerve-resting conductance and excitability. variants are associated with two neurodevelopmental disorders, one is CLIFAHDD (autosomal dominant congenital contractures of the limbs and face, hypotonia, and developmental delay, OMIM #616266) and another is IHPRF (infantile hypotonia with psychomotor retardation, and characteristic facies 1, OMIM #615419).

Case Presentation: In the current study, a Chinese infant that manifested abnormal facial features, adducted thumbs, and neurodevelopmental retardation was diagnosed with CLIFAHDD syndrome. A trio-based whole-exome sequencing revealed that the infant harbored a variant of the gene (c.4300A>G, p.I1434V).

Conclusions: Our findings further enriched the variant spectrum of the gene and may expand the clinical range of -related disorders.
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http://dx.doi.org/10.3389/fped.2022.927392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326163PMC
July 2022

Isolation, Molecular Characterization, and Antibiotic Resistance of Avian Pathogenic in Eastern China.

Vet Sci 2022 Jun 25;9(7). Epub 2022 Jun 25.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.

Avian pathogenic (APEC) causes colibacillosis in avians, resulting in considerable losses in the poultry industry. APEC showed zoonotic potential initially related to the fact that APEC serves as the reservoir of virulence genes and antibiotic resistance genes for other . Thus, we determine the serotypes, phylogenetic groups, virulence genes distribution, and antibiotic resistance profiles of APEC isolates in eastern China. A total of 230 APEC were isolated from diseased chicken and duck with typical colibacillosis symptoms. Serotyping identified that O78 (44.78%) was the predominant serotype. The majority of APEC isolates were classified into B2 (29.57%), A (26.96%), D (20.00%), and B1 (18.26%), respectively. Among the 15 virulence genes, a high prevalence of (99.57%), (91.74%), (91.30%), (83.04%), and (80.43%) genes was observed. Except for low resistance rates for imipenem (1.7%) and polymyxin B (0.4%), most of the APEC isolates were resistant to erythromycin (98.7%), enrofloxacin (96.1%), tetracycline (95.2%), doxycycline (93.9%), lincomycin (90.0%), and streptomycin (90.0%). Moreover, all APEC exhibit multi-drug resistance. This study indicated that APEC isolates harbor a variety of virulence genes and showed multi-antibiotic resistance profiles, providing proof for understanding the epidemiological background and zoonotic potential of APEC in poultry farms.
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http://dx.doi.org/10.3390/vetsci9070319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324180PMC
June 2022

Synchronous Surface Reconstruction and Defect Passivation for High-Performance Inorganic Perovskite Solar Cells.

Small 2022 Jul 20:e2202690. Epub 2022 Jul 20.

Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Shaanxi Key Laboratory for Advanced Energy Devices, Shaanxi Engineering Lab for Advanced Energy Technology, School of Materials Science and Engineering, Shaanxi Normal University, No. 620, West Chang'an Avenue, Xi'an, 710119, P. R. China.

The nonradiative charge recombination caused by surface defects and inferior crystalline quality are major roadblocks to further enhancing the performance of CsPbI Br perovskite solar cells (PSCs). Theoretical calculations indicate that sodium diethyldithiocarbamate (NaDDTC), a popular bacteriostatic benign material, can initiate multiple interactions with the CsPbI Br perovskite surface to effectively passivate the defects. The experimental results reveal that the NaDDTC can indeed passivate the electron trap states and lock active sites for charge traps and water adsorption. In addition, it is found that a solid-state reaction is triggered for perovskite crystal regrowth by the NaDDTC post-treatment, which not only enlarges grain size for reducing the density of grain boundary defects but also compensates some surface defects induced by the primary film growth. Consequently, the power conversion efficiency (PCE) of the CsPbI Br PSC is increased to as high as 20.40%, with significant improvement in fill factor and open-circuit voltage (V ), making it one of the highest for this type of solar cell. Furthermore, the optimized devices exhibit better environmental stability. Overall, this robust synchronous strategy provides efficient surface reconstruction and defect passivation for achieving both high PCE and stable inorganic perovskite.
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http://dx.doi.org/10.1002/smll.202202690DOI Listing
July 2022

Subxiphoid and subcostal arch versus unilateral video-assisted thoracic surgery approaches to thymectomy for myasthenia gravis.

Surg Today 2022 Jul 1. Epub 2022 Jul 1.

Department of Thoracic and Cardiovascular Surgery, Affiliated Dongguan People's Hospital, Southern Medical University (Dongguan People's Hospital), No. 3, South of Wandao Road, Wanjiang District, Dongguan, 523000, China.

Purpose: Thymectomy is an important treatment for myasthenia gravis (MG). We conducted this study to compare the clinical outcomes of the recently introduced subxiphoid and subcostal arch thymectomy (SASAT) approach with those of the standard unilateral video-assisted thoracoscopic surgery (VATS).

Methods: We analyzed, retrospectively, the perioperative, and long-term outcomes of 179 consecutive MG patients (age 18-65 years), who underwent SASAT or unilateral VATS-extended thymectomy between July, 2012 and May, 2019.

Results: All demographic and clinical characteristics were comparable in the two groups. The median surgical time, estimated blood loss, thoracotomy conversion rate, total and chest drainage, and complications did not differ significantly between the groups. The visual analog scale (VAS) score was significantly lower in the SASAT group. Complete stable remission (CSR) was achieved in a significantly larger proportion of the SASAT group patients and was significantly higher in women than in men. The Quantitative MG score was significantly lower in the SASAT group. Patients in the MG Foundation of America Clinical Classification groups I and II achieved better remission rates than those in groups III-V.

Conclusions: SASAT is a safe and feasible MG treatment, which may yield better outcomes than unilateral VATS and improve the quality of treatment.
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http://dx.doi.org/10.1007/s00595-022-02533-4DOI Listing
July 2022

Efficient adaptation of high-quality international guidelines for Chinese children with primary immune thrombocytopenia.

Authors:
Yali Liu Runhui Wu

Pediatr Investig 2022 Jun 21;6(2):149-150. Epub 2022 Mar 21.

Hematology Center Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.

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http://dx.doi.org/10.1002/ped4.12313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218985PMC
June 2022

B10 Cells Are Associated With Clinical Prognosis During Adult Symptomatic Acute HBV Infection.

Front Immunol 2022 13;13:906650. Epub 2022 Jun 13.

The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.

There are few reports about the role of B10 cells in acute hepatitis B (AHB) infection. In this study, based on 48 acute hepatitis B infected patients, we analysis the correlation of B10 cells with HBV clinical prognosis. The results showed that B10 was positively correlated with HBsAg and HBeAg and inversely correlated with anti-HBs. The level of B10 in one week before HBsAg clearance was significantly lower than 2 weeks prior to HBsAg clearance and after 1-2 weeks of HBsAg clearance. B10 cell frequency displayed no correlation with HBV DNA; however, it showed significant temporal synchronization with hepatic inflammatory markers such as ALT. B10 level also associated with hospitalization time. These results indicated that B10 is closely related to the clinical prognosis of acute HBV infection.
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http://dx.doi.org/10.3389/fimmu.2022.906650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234142PMC
June 2022

Targeting ferroptosis with miR-144-3p to attenuate pancreatic β cells dysfunction via regulating USP22/SIRT1 in type 2 diabetes.

Diabetol Metab Syndr 2022 Jun 27;14(1):89. Epub 2022 Jun 27.

School of Medicine of Pingdingshan University, Middle Section of Chongwen Road, Xincheng District, Pingdingshan, 467000, Henan, China.

Background: Recently, ferroptosis has been implicated in the pathologic process of several diseases including type 2 diabetes mellitus (T2DM). However, molecular mechanisms underlying ferroptosis in T2DM remain obscure.

Methods: Twenty four mice were included in this study. T2DM model mice were established by a high-fat diet combined with streptozotocin injection. INS-1 cells were stimulated with high glucose (HG). Cell viability was detected by CCK-8 kit. The levels of GSH, MDA, iron, and lipid ROS, and SOD activity, were detected by the corresponding kits. The interaction between miR-144-3p and USP22 was validated by dual-luciferase reporter assay. The relationship between USP22 and its substrate was verified using Co-IP and ubiquitination assays. The mRNA and protein expressions were examined by RT-qPCR and western blot, respectively. The functions of β cells in vitro and in vivo were evaluated glucose-stimulated insulin secretion test and HOMA-β, respectively.

Results: Ferroptosis occurred in the pancreas of T2DM mice and HG-induced INS-1 cells. Silencing miR-144-3p blocked the effect of HG on the cell viability and accumulation of lipid peroxides, thereby improving the insulin secretion in INS-1 cells. Mechanistically, USP22 is a direct target of miR-144-3p, which could stabilize SIRT1 expression, thereby suppressing ferroptosis. Overexpressing USP22 attenuated deleterious roles of HG in INS-1 cells; but its roles were reversed by up-regulating miR-144-3p. In vivo study demonstrated that miR-144-3p antagomir exerted an anti-hyperglycemic effect and regulated the ferroptosis-related proteins in the pancreas.

Conclusion: The up-regulation of miR-144-3p suppressed USP22/SIRT1 to induce ferroptosis, which causes pancreatic β cells dysfunction, thereby promoting T2DM development.
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http://dx.doi.org/10.1186/s13098-022-00852-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235078PMC
June 2022

Research progress and clinical application prospects of miRNAs in oral cancer.

Mol Biol Rep 2022 Jun 20. Epub 2022 Jun 20.

Northwest Minzu University, Lanzhou, China.

Oral cancer is one of the most common malignant tumors worldwide, and it is also one of the most important and difficult clinical problems to be solved. Due to the regional differences in diet culture, some areas have taken the 'hardest hit' of oral cancer cases. However, the existing clinical treatment methods (surgery as the main treatment method, radiotherapy and chemotherapy as the auxiliary ones) do not have satisfactory treatment effects; therefore, new diagnosis and treatment methods need to be developed and utilized. Micro RNAs (miRNAs), as a class of substances that play an important regulatory role in the development of tumors, have an important value in the diagnosis and treatment of various tumors. At the same time, many miRNAs have obvious expression differences in oral cancer tissues compared to normal tissues. Therefore, they may have diagnostic and therapeutic effects on oral cancer. In this review, we evaluate the miRNAs that play a regulatory role in the development of oral cancer and those that are expected to be applied in the diagnosis and treatment of oral cancer. At the same time, we summarize the important challenges that need to be addressed, aiming to provide evidence and suggestions for the application of miRNAs in the diagnosis and treatment of oral cancer.
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http://dx.doi.org/10.1007/s11033-022-07604-wDOI Listing
June 2022

Altered Mycobiota Signatures and Enriched Pathogenic Aspergillus rambellii Are Associated With Colorectal Cancer Based on Multicohort Fecal Metagenomic Analyses.

Gastroenterology 2022 Jun 18. Epub 2022 Jun 18.

Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address:

Background & Aims: The enteric mycobiota is a major component of the human gut microbiota, but its role in colorectal cancer (CRC) remains largely elusive. We conducted a meta-analysis to uncover the contribution of the fungal mycobiota to CRC.

Methods: We retrieved fecal metagenomic data sets from 7 previous publications and established an additional in-house cohort, totaling 1329 metagenomes (454 with CRC, 350 with adenoma, and 525 healthy individuals). Mycobiota composition and microbial interactions were analyzed. Candidate CRC-enriched fungal species (Aspergillus rambellii) was functionally validated in vitro and in vivo.

Results: Multicohort analysis revealed that the enteric mycobiota was altered in CRC. We identified fungi that were associated with patients with CRC or adenoma from multiple cohorts. Signature CRC-associated fungi included 6 enriched (A rambellii, Cordyceps sp. RAO-2017, Erysiphe pulchra, Moniliophthora perniciosa, Sphaerulina musiva, and Phytophthora capsici) and 1 depleted species (A kawachii). Co-occurrent interactions among CRC-enriched fungi became stronger in CRC compared with adenoma and healthy individuals. Moreover, we reported the transkingdom interactions between enteric fungi and bacteria in CRC progression, of which A rambellii was closely associated with CRC-enriched bacteria Fusobacterium nucleatum. A rambellii promoted CRC cell growth in vitro and tumor growth in xenograft mice. We further identified that combined fungal and bacterial biomarkers were more accurate than panels with pure bacterial species to discriminate patients with CRC from healthy individuals (the area under the curve relative change increased by 1.44%-10.60%).

Conclusions: This study reveals enteric mycobiota signatures and pathogenic fungi in stages of colorectal tumorigenesis. Fecal fungi can be used, in addition to bacteria, for noninvasive diagnosis of patients with CRC.
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http://dx.doi.org/10.1053/j.gastro.2022.06.038DOI Listing
June 2022

Antioxidants for Treatment of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis.

Eur Neurol 2022 Jun 13:1-12. Epub 2022 Jun 13.

Pediatric Intensive Care Unit, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Introduction: Increasing evidence has shown that oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD). Oxidative stress impairs muscle function, reduces regenerative capacity, and leads to atrophy and muscle weakness. The present study aimed to evaluate the effectiveness and safety of antioxidants in treatment of DMD patients.

Methods: Medline, Embase, EBSCOhost, and Cochrane Library databases were searched using relevant keywords regarding DMD and antioxidants. The risk of bias for all included studies was assessed using the Cochrane risk of bias tool. The effectiveness of antioxidants in improving pulmonary function and muscle strength in DMD patients and their rate of adverse events was evaluated by meta-analysis.

Results: A total of nine eligible studies were identified. Among these, two studies involving 85 patients compared idebenone with placebo. Pooled data showed a significant improvement in pulmonary function after idebenone treatment. Flavonoids- and omega 3-based compounds (FLAVOMEGA) significantly improved muscle strength. Two studies evaluated coenzyme Q10 (CoQ10) and reported clinical improvement in physical activity. The remaining four studies evaluated pentoxifylline, superoxide dismutase, vitamin E combination with penicillamine and penicillamine alone, respectively, and found no significant differences between the intervention and placebo groups, measured by pulmonary function, muscle strength, movement function, or quality of life. Most adverse events were mild, while the rates of dropout and serious adverse events were low with respect to antioxidants.

Conclusions: Idebenone appeared to be safe and effective in improving pulmonary function in DMD patients, while pentoxifylline, superoxide dismutase, penicillamine, or a combination of vitamin E with penicillamine did not show a significant therapeutic effect. CoQ10 and FLAVOMEGA might be beneficial in improving muscle strength or physical activity in DMD patients. However, additional trials with more participants are warranted in the future.
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http://dx.doi.org/10.1159/000525045DOI Listing
June 2022

Role of Posterodorsal Medial Amygdala Urocortin-3 in Pubertal Timing in Female Mice.

Front Endocrinol (Lausanne) 2022 17;13:893029. Epub 2022 May 17.

Department of Women and Children's Health, Faculty of Life Science and Medicine, King's College London, London, United Kingdom.

Post-traumatic stress disorder impedes pubertal development and disrupts pulsatile LH secretion in humans and rodents. The posterodorsal sub-nucleus of the medial amygdala (MePD) is an upstream modulator of the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator, pubertal timing, as well as emotional processing and anxiety. Psychosocial stress exposure alters neuronal activity within the MePD increasing the expression of Urocortin3 (Ucn3) and its receptor corticotropin-releasing factor type-2 receptor (CRFR2) while enhancing the inhibitory output from the MePD to key hypothalamic reproductive centres. We test the hypothesis that psychosocial stress, processed by the MePD, is relayed to the hypothalamic GnRH pulse generator to delay puberty in female mice. We exposed C57Bl6/J female mice to the predator odor, 2,4,5-Trimethylthiazole (TMT), during pubertal transition and examined the effect on pubertal timing, pre-pubertal LH pulses and anxiety-like behaviour. Subsequently, we virally infected Ucn3-cre-tdTomato female mice with stimulatory DREADDs targeting MePD Ucn3 neurons and determined the effect on pubertal timing and pre-pubertal LH pulse frequency. Exposure to TMT during pubertal development delayed puberty, suppressed pre-pubertal LH pulsatility and enhanced anxiety-like behaviour, while activation of MePD Ucn3 neurons reduced LH pulse frequency and delayed puberty. Early psychosocial stress exposure decreases GnRH pulse generator frequency delaying puberty while inducing anxiety-behaviour in female mice, an effect potentially involving Ucn3 neurons in the MePD.
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http://dx.doi.org/10.3389/fendo.2022.893029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152449PMC
May 2022

Metal organic frameworks (MOFs) as multifunctional nanoplatform for anticorrosion surfaces and coatings.

Adv Colloid Interface Sci 2022 Jul 21;305:102707. Epub 2022 May 21.

Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta T6G 1H9, Canada. Electronic address:

Corrosion of metallic materials is a long-standing problem in many engineering fields. Various organic coatings have been widely applied in anticorrosion of metallic materials over the past decades. However, the protective performance of many organic coatings is limited due to the undesirable local failure of the coatings caused by micro-pores and cracks in the coating matrix. Recently, metal organic frameworks (MOFs)-based surfaces and coatings (MOFBSCs) have exhibited great potential in constructing protective materials on metallic substrates with efficient and durable anticorrosion performance. The tailorable porous structure, flexible composition, numerous active sites, and controllable release properties of MOFs make them an ideal platform for developing various protective functionalities, such as self-healing property, superhydrophobicity, and physical barrier against corrosion media. MOFs-based anticorrosion surfaces and coatings can be divided into two categories: the composite surfaces/coatings using MOFs-based passive/active nanofillers and the surfaces/coatings using MOFs as functional substrate support. In this work, the state-of-the-art fabrication strategies of the MOFBSCs are systematically reviewed. The anticorrosion mechanisms of MOFBSCs and functions of the MOFs in the coating matrix are discussed accordingly. Additionally, we highlight both traditional and emerging electrochemical techniques for probing protective performances and mechanisms of MOFBSCs. The remaining challenging issues and perspectives are also discussed.
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http://dx.doi.org/10.1016/j.cis.2022.102707DOI Listing
July 2022

Low Level of Serum Immunoglobulin G Is Beneficial to Clinical Cure Obtained With Pegylated Interferon Therapy in Inactive Surface Antigen Carriers.

Front Immunol 2022 22;13:864354. Epub 2022 Apr 22.

The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.

Purpose: Our recent study showed a high rate of HBsAg clearance in inactive HBsAg carriers (IHCs) treated with pegylated IFN (PEG-IFN). To better understand the immune-mediated component of HBsAg clearance, this study investigated the role of serum immunoglobulin G (IgG) and its subclasses in predicting HBsAg clearance in IHCs with PEG-IFN therapy.

Methods: In this study, IHCs received PEG-IFN for 96 weeks. Subjects who achieved clearance of HBsAg were considered responders (R group), and those in whom HBsAg was not cleared were considered non-responders (NR group). The HBsAg, ALT, and serum lgG subtypes (lgG1, IgG2, IgG3, lgG4) were tested at baseline, and at 12 and 24 weeks of treatment. To evaluate the factors in predicting HBsAg clearance, univariate and multivariate logistic regression analyses were performed. The receiver operator characteristic curves and the area under the receiver operator characteristic curve (AUROC) were used to evaluate prognostic values.

Results: Our results showed that 39 cases obtained HBsAg clearance (group R), while 21 cases did not (group NR). There was no significant difference in age, ALT, and AST levels between the two groups. The serum levels of IgG1, lgG2, lgG3 and lgG4 at baseline, and at 12 and 24 weeks were significantly lower in IHC with HBsAg clearance than in the NR group. Univariate logistic regression analysis showed that serum IgG1, IgG2, IgG3, and IgG4 levels at baseline, and at 12, and 24 weeks were all strong predictors of HBsAg clearance. In all indicators, lgG2 had the highest AUROC at baseline and lgG3 the highest AUROC at week 12. A multifactor logistic analysis was performed with y=33.933-0.001*BaselinelgG1-0.002*BaselinelgG2. The area under the curve was 0.941 with 100% sensitivity and 76.19% specificity.

Conclusion: Together, our findings suggest that serum IgG has a higher predictive value compared to the convention predictors of HBsAg and ALT for HBsAg clearance and thus may be a better clinical predictor of HBsAg clearance in IHCs.
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http://dx.doi.org/10.3389/fimmu.2022.864354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9073012PMC
April 2022

Silencing of Rab23 by siRNA inhibits ultraviolet B-induced melanogenesis via downregulation of PKA/CREB/MITF.

Exp Dermatol 2022 Aug 16;31(8):1253-1263. Epub 2022 May 16.

Department of Dermatology, First Medical Center of PLA General Hospital, Beijing, China.

Recent investigations have shown that the Rab family of GTPases is associated with all aspects of melanogenesis. However, the effect of Rab23, which localizes to the plasma membrane and regulates the endocytic pathway within eukaryotic cells, in melanogenesis has not been reported. To understand the role of Rab23 in UVB-induced melanogenesis, we evaluated changes in the level of melanin, activity of tyrosinase and levels of melanogenesis-related proteins such as microphthalmia transcription factor and tyrosinase-related protein-1 (TRP-1) and the melanosome transport-related protein complex Rab27a-melanophilin-myosin Va after the downregulation of Rab23 in B16F10 and SK-MEL-2 cells with or without UVB irradiation. Our results showed that downregulating Rab23 reduced the melanin level and tyrosinase activity and inhibited the expression of proteins involved in UVB-induced melanogenesis. Rab23 colocalized with mature melanosomes marked with TRP-1. Furthermore, downregulating Rab23 induced the abnormal accumulation of melanosomes around the nucleus. We demonstrated that the downregulation of Rab23 inhibited melanin synthesis and melanosome transport by decreasing the PKA/CREB/MITF pathway, which is the key regulator of UVB-induced melanogenesis.
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http://dx.doi.org/10.1111/exd.14586DOI Listing
August 2022

Efficient recovery of Cr(vi) from electroplating wastewater by iron-modified sludge-based hollow-structured porous carbon: coexistence effects and competition for adsorption.

RSC Adv 2021 Nov 18;11(59):37233-37245. Epub 2021 Nov 18.

School of Environment Engineering, Nanjing Institute of Technology Nanjing 211167 China

In the present work, porous carbon was made from sewage sludge and hybrid liriodendron leaves, and modified with iron ions ([email protected]) carried out on Cr(vi) in aqueous solution from a single-component system and in competitive biosorption with methyl orange (MO) from a binary-component system. The iron ion-modified porous carbon ([email protected]) showed higher efficiency in the removal of Cr(vi) compared to porous carbon prepared by the co-pyrolysis of sludge and hybrid liriodendron leaves. The incorporation of the Fe element improved the ability of the material to redox Cr(vi), while imparting magnetic characteristics to the porous carbon and improving the reusability of the porous carbon. On the other hand, [email protected] exhibited a better pore volume, facilitating the contact of the material with Cr(vi) ions. The highest adsorption capacity was 0.33 mmol g, and the adsorption experimental results for the single-component and binary-component systems of Cr(vi) matched well with the Langmuir-Freundlich models. When the concentration of MO was 0.2 and 0.8 mmol L, respectively, the highest adsorption capacity of Cr(vi) was 0.35 and 0.46 mmol g in the binary system. The positively charged N-CH on the MO molecule promoted the electrostatic adsorption between HCrO , CrO , and [email protected], and increased the adsorption potential of Cr(vi).
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http://dx.doi.org/10.1039/d1ra06969aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043741PMC
November 2021

Performance and mechanism of conductive magnetite particle-enhanced excess sludge anaerobic digestion for biogas recovery.

RSC Adv 2021 Oct 4;11(56):35559-35566. Epub 2021 Nov 4.

School of Civil Engineering, Nanjing Forestry University Nanjing 210037 PR China.

The aim of this study was to evaluate the effect of magnetite particles on the anaerobic digestion of excess sludge. The results showed that methane production increased with the increase in magnetite dosage in the range of 0-5 g L, and the cumulative methane production increased by 50.1% at a magnetite dosage of 5 g L compared with the blank reactor after 20 days. Simultaneously, numerous volatile fatty acids (VFAs) were produced at high magnetite dosages, providing the required substrates for methanogenesis. The concentration of magnetite addition was positively correlated with methane production, which proved that magnetite was beneficial for the promotion of the conversion of VFAs to methane. Moreover, the degradation efficiencies of proteins and carbohydrates reached 64% and 52.6% at the magnetite dosage of 5 g L, respectively, and corresponding activities of protease and coenzyme F420 were 9.03 IU L and 1.652 μmol L. In addition, the and genus were enriched by magnetite, which often participate in direct interspecies electron transfer as electron acceptors.
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http://dx.doi.org/10.1039/d1ra06236kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043222PMC
October 2021

Assessment of evidence on reported non-genetic risk factors of congenital heart defects: the updated umbrella review.

BMC Pregnancy Childbirth 2022 Apr 29;22(1):371. Epub 2022 Apr 29.

Department of Internal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, No.251 Yaojiayuan Road, Chaoyang District, Beijing, 100026, China.

Background: Congenital heart defect (CHD) is the leading cause of birth defects globally, which results in a great disease burden. It is still imperative to detect the risk factors of CHD. This umbrella review aimed to comprehensively summarize the evidence and grade the evidence of the associations between non-genetic risk factors and CHD.

Methods: Databases including Medline, Embase, Web of Science, Cochrane Library, and four Chinese databases were searched from inception to 18 Jan 2022. The reference lists of systematic reviews (SR) and meta-analyses (MA) were screened, which aimed to explore the non-genetic risk factors of CHD. Subsequently, titles and abstracts of identified records and full texts of selected SR/MA were screened by two independent reviewers based on predefined eligibility criteria. A priori developed extraction form was used to abstract relative data following the PRISMA 2020 and MOOSE guidelines. The risk of bias was assessed with the AMSTAR2 instrument. Data were synthesized using fixed-effects and random-effects meta-analyses, respectively. Finally, the evidence on the association of non-genetic risk factors and CHD was graded using Ioannidis's five-class evidence grade.

Results: A total of 56 SRs, encompassing 369 MAs, were identified. The risk factors included relative factors on air pollution, reproductive-related factors, parental age and BMI, parental life habits, working and dwelling environment, maternal drug exposure, and maternal disease. Based on AMSTAR2 criteria, only 16% (9/56) of SRs were classified as "Moderate". One hundred and two traceable positive association MAs involving 949 component individual studies were included in further analysis and grading of evidence. Family genetic history, number of abortions, maternal obesity, especially moderate or severe obesity, decoration materials, harmful chemicals, noise during pregnancy, folic acid supplementation, SSRIs, SNRIs, any antidepressants in the first trimester, maternal DM (including both PGDM and GDM), and gestational hypertension were convincing and highly suggestive factors for CHD. After sensitivity analyses based on cohort studies, some grades of evidence changed.

Conclusion: The present umbrella review will provide evidence-based information for women of childbearing age before or during pregnancy to prevent CHD. In addition, sensitivity analysis based on cohort studies showed the changed evidence levels. Therefore, future SR/MA should concern the sensitivity analysis based on prospective birth cohort studies and case-control studies.
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http://dx.doi.org/10.1186/s12884-022-04600-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9055777PMC
April 2022

Clinical guidelines of UTIs in children: quality appraisal with AGREE II and recommendations analysis.

BMJ Open 2022 04 27;12(4):e057736. Epub 2022 Apr 27.

Department 2 of Nephrology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Objective: To explore the current Chinese and English guidelines of urinary tract infection (UTI) in children and provide a summary of the recommendations of the guidelines.

Methods: An electronic search was conducted on databases, including Pubmed, SinoMed, Wangfang Data, CHKD,VIP, NICE, WHO, GIN and Medliveto retrieve data of the clinical practice guidelines on UTI from the establishment of the database to June 2020. Four assessors assessed the quality of guidelines using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) and evaluated the specific recommendations in guidelines.

Results: (1) Nine guidelines including two from the USA (AAP and A guideline for the inpatient care of children with pyelonephritis) and the remaining from EAU/ESPU, SINEPE, KHA-CARI, CPS, ISPN, NICE and CMA-CSP were explored. (2) The AGREE II evaluation demonstrated higher scores of UTI guidelines in terms of 'scope and purpose' (72.99%±11.19%) and 'clarity of presentation' (75.62%±7.75%), whereas the average scores were lower in the aspect of 'stakeholder involvement' (35.49%±14.41%), 'rigour of development' (37.05%±10.05%), 'applicability' (37.75%±11.98%) and 'editorial independence' (43.06%±48.14%). The average scores of the guidelines were as follows: SINePe (72.57%), CMA-CSP (62.96%), EAU/ESPU (59.61%), AAP (56.86%), NICE (47.54%), CPS (40.93%), KHA-CARI (38.86%), ISPN (38.63%) and A guideline for the inpatient care of children with pyelonephritis (34.72%). (3) All the selected guidelines basically reached a consensus on urine sample retention methods in older children, the antibiotic treatment course and renal and bladder ultrasonography application but lacked a conclusion on the determination of urine culture results, the choice of voiding cystourethrography and Tc-99mdimercaptosuccinicacid, and antibiotic prophylaxis.

Conclusion: There remains a need to improve the quality of guidelinesfor UTI in clinical practice. Existing controversies on the current guidelines of UTI in some recommendations warrant further exploration to provide more evidence on formulating more unified and practical guidelines in the future.

Ethics And Dissemination: No ethical approval is required for this research, as it did not include patients or patient data.
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http://dx.doi.org/10.1136/bmjopen-2021-057736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047976PMC
April 2022

The Prognostic Value and Immune Infiltration of USP10 in Pan-Cancer: A Potential Therapeutic Target.

Front Oncol 2022 31;12:829705. Epub 2022 Mar 31.

Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.

Ubiquitin-specific peptidase 10 (USP10) can sustain cellular functions and regulate cellular processes. It plays an essential role in cancer inhibition or facilitation by reversing ubiquitin-proteasome degradation. Studies have identified USP10 to be involved in tumor progression in various cancers. However, the pan-cancer expression pattern of USP10, its prognostic value, and the association between tumor immune cell infiltration and USP10 expression remain to be discussed and thus comprised the aims of the present study. Based on clinical samples and bioinformatic analyses, high expression was observed in most cancer tissues except for ovarian cancer. High expression correlated with pathological stage and node metastasis and predicted poor patient prognosis. In addition, further analyses at the TIMER and GEPIA databases showed that USP10 is involved in the infiltration of multiple immune cells and regulated the infiltration levels of specific immune cell subpopulations, particularly in pancreatic adenocarcinoma (PAAD) and liver hepatocellular carcinoma (LIHC). Importantly, USP10 might influence survival by modulating immune infiltration in patients with PAAD and LIHC. These results identified USP10 as a potential biomarker for pan-cancer prognosis, and in certain cancers, USP10 could identify clinical prognosis linked to tumor immune infiltration.
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http://dx.doi.org/10.3389/fonc.2022.829705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009419PMC
March 2022

USF1-ATRAP-PBX3 Axis Promote Breast Cancer Glycolysis and Malignant Phenotype by Activating AKT/mTOR Signaling.

Int J Biol Sci 2022 14;18(6):2452-2471. Epub 2022 Mar 14.

Department of Breast Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin 150040, China.

Angiotensin II type 1 receptor-associated protein (ATRAP) is widely expressed in different tissues and organs, although its mechanistic role in breast cancer remains unclear. Here, we show that ATRAP is highly expressed in breast cancer tissues. Its aberrant upregulation promotes breast cancer aggressiveness and is positively correlated with poor prognosis. Functional assays revealed that ATRAP participates in promoting cell growth, metastasis, and aerobic glycolysis, while microarray analysis showed that ATRAP can activate the AKT/mTOR signaling pathway in cancer progression. In addition, ATRAP was revealed to direct Ubiquitin-specific protease 14 (USP14)-mediated deubiquitination and stabilization of Pre-B cell leukemia homeobox 3 (PBX3). Importantly, ATRAP is a direct target of Upstream stimulatory factor 1 (USF1), and that ATRAP overexpression reverses the inhibitory effects of USF1 knockdown. Our study demonstrates the broad contribution of the USF1/ATRAP/PBX3 axis to breast cancer progression and provides a strong potential therapeutic target.
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http://dx.doi.org/10.7150/ijbs.69134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990462PMC
March 2022

Smart waterborne composite coating with passive/active protective performances using nanocontainers based on metal organic frameworks derived layered double hydroxides.

J Colloid Interface Sci 2022 Aug 23;619:132-147. Epub 2022 Mar 23.

College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, PR China; Advanced Catalytic Engineering Research Center of the Ministry of Education, Hunan University, Changsha, Hunan 410082, PR China. Electronic address:

Functional surfaces and coatings with excellent anticorrosion performances are of great significance for numerous engineering applications. However, developing waterborne coatings with long-term anticorrosion properties remains challenging. In this study, we developed a multifunctional nanocontainer for a waterborne coating matrix, using zeolitic imidazolate framework (ZIF)-derived layered double hydroxides (LDHs) as the gatekeepers for benzotriazole (BTA)-encapsulated mesoporous silica nanoparticles (MSNs-BTA). The LDHs outer layer and the ZIF intermediate layer endowed the [email protected] nanocontainer with excellent compatibility, dispersion, and pH-responsive controllable release properties in the waterborne coating matrix. The waterborne epoxy composite coatings showed excellent passive and active anticorrosion performances, well-characterized by electrochemical impedance spectroscopy (EIS), permeation experiments, neutral salt spray (NSS) tests, and the scanning vibrating electrode technique (SVET). This excellent corrosion protection performance can be attributed to two factors: before corrosion, the [email protected] served as passive nanofillers against corrosive media, significantly improving the barrier properties of the composite coatings; after the occurrence of corrosion, the [email protected] acted as pH-responsive nanocontainers and released pre-loaded BTA corrosion inhibitors, preventing further damage to the exposed metal substrate. This study provides new insights into the development of multifunctional anticorrosion surfaces and coatings for various engineering applications.
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http://dx.doi.org/10.1016/j.jcis.2022.03.088DOI Listing
August 2022

Static magnetic field promotes proliferation, migration, differentiation, and AKT activation of periodontal ligament stem cells.

Cells Tissues Organs 2022 Mar 28. Epub 2022 Mar 28.

Periodontal ligament stem cells (PDLSCs) possess self-renewal and multilineage differentiation potential and exhibit great potential for the treatment of bone tissue defects caused by inflammation. Previous studies have indicated that static magnetic field (SMF) can enhance the proliferation and differentiation of mesenchymal stem cells (MSCs). SMF has been widely used to repair bone defects and for orthodontic and implantation treatment. In this study, we revealed that a 320 mT SMF upregulates the protein expression levels of cytokines such as MCM7 and PCNA in proliferating PDLSCs. Cell counting kit-8 (CCK-8) results revealed that the SMF group had higher optical density (OD) values than the control group. The ratio of cells in the S phase to those in the G2/M phase was significantly increased after exposure to a 320 mT SMF. In scratch assays, the SMF-treated PDLSCs exhibited a higher migration rate than the sham-exposed group after 24 h of culture, indicating that the SMF promoted the migratory ability of PDLSCs. The activity level of the early differentiation marker alkaline phosphatase (ALP) and the late marker matrix mineralization, as well as osteoblast-specific gene and protein expression, were enhanced in PDLSCs exposed to the SMF. Furthermore, AKT signalling pathway were activated by SMF. Our data demonstrated that the potential mechanism of action of SMF may enhance PDLSCs proliferation and osteogenic differentiation by activating the phosphorylated AKT pathways. The elucidation of this molecular mechanism may lead to a better understanding of bone repair responses and aid in improved stem cell-mediated regeneration.
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http://dx.doi.org/10.1159/000524291DOI Listing
March 2022

An Engineered Bacteria-Hybrid Microrobot with the Magnetothermal Bioswitch for Remotely Collective Perception and Imaging-Guided Cancer Treatment.

ACS Nano 2022 Mar 28. Epub 2022 Mar 28.

Shanghai East Hospital, School of Medicine, Frontiers Science Center for Intelligent Autonomous Systems, Tongji University, 1800 Yuntai Road, Shanghai 200120, China.

Microrobots driven by multiple propelling forces hold great potential for noninvasively targeted delivery in the physiologic environment. However, the remotely collective perception and precise propelling in a low Reynold's number bioenvironment remain the major challenges of microrobots to achieve desired therapeutic effects . Here, we reported a biohybrid microrobot that integrated with magnetic, thermal, and hypoxia sensitivities and an internal fluorescent protein as the dual reporter of thermal and positioning signals for targeted cancer treatment. There were three key elements in the microrobotic system, including the magnetic nanoparticle (MNP)-loaded probiotic Nissle1917 ([email protected]) for spatially magnetic and hypoxia perception, a thermal-logic circuit engineered into the bacteria to control the biosynthesis of mCherry as the temperature and positioning reporter, and NDH-2 enzyme encoded in the EcN for enhanced anticancer therapy. According to the fluorescent-protein-based imaging feedback, the microrobot showed good thermal sensitivity and active targeting ability to the tumor area in a collective manner under the magnetic field. The cancer cell apoptosis was efficiently triggered and by the hybrid microrobot coupled with the effects of magnetothermal ablation and NDH-2-induced reactive oxygen species (ROS) damage. Our study demonstrates that the biohybrid EcN microrobot is an ideal platform to integrate the physical, biological, and chemical properties for collective perception and propelling in targeted cancer treatment.
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http://dx.doi.org/10.1021/acsnano.1c11601DOI Listing
March 2022

Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer.

N Engl J Med 2022 03;386(12):1143-1154

From the International Breast Cancer Center, Quirónsalud Group, Barcelona, the Scientific Department, Medica Scientia Innovation Research, Valencia, and the Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid - all in Spain (J. Cortés); Asan Medical Center, University of Ulsan College of Medicine, Ulsan (S.-B.K.), Seoul National University Hospital, Cancer Research Institute (S.-A.I.), and Seoul National University Bundang Hospital (J.H.K.), Seoul National University College of Medicine, and Samsung Medical Center (Y.H.P.), Seoul, and Severance Hospital, Yonsei University, Yonsei (M.H.K.) - all in South Korea; the Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan (W.-P.C.), and the Department of Surgery, Taipei Veterans General Hospital, College of Medicine, National Yang-Ming Chiao Tung University (L.-M.T.), Koo Foundation Sun Yat-Sen Cancer Center (C.-F.C.), and National Taiwan University Hospital and National Taiwan University College of Medicine (C.-S.H.), Taipei - all in Taiwan; Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária (R.H.) and Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (V.P.), São Paulo, and Hospital Nossa Senhora da Conceição, Porto Alegre (J.L.P.) - all in Brazil; Aichi Cancer Center Hospital, Aichi, Japan (H.I.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (E.H.); the Department of Oncology and Hematology-Oncology, University of Milan, and the Division of Early Drug Development, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico - both in Milan (G.C.); the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (B.X.); the University of Hong Kong, Hong Kong (J.W.Y.C.); Daiichi Sankyo, Basking Ridge, NJ (C.L., Y.L., J. Cathcart, E.B.); AstraZeneca, Gaithersburg, MD (S.V.); and the David Geffen School of Medicine and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles (S.A.H.).

Background: Trastuzumab emtansine is the current standard treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer whose disease progresses after treatment with a combination of anti-HER2 antibodies and a taxane.

Methods: We conducted a phase 3, multicenter, open-label, randomized trial to compare the efficacy and safety of trastuzumab deruxtecan (a HER2 antibody-drug conjugate) with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. The primary end point was progression-free survival (as determined by blinded independent central review); secondary end points included overall survival, objective response, and safety.

Results: Among 524 randomly assigned patients, the percentage of those who were alive without disease progression at 12 months was 75.8% (95% confidence interval [CI], 69.8 to 80.7) with trastuzumab deruxtecan and 34.1% (95% CI, 27.7 to 40.5) with trastuzumab emtansine (hazard ratio for progression or death from any cause, 0.28; 95% CI, 0.22 to 0.37; P<0.001). The percentage of patients who were alive at 12 months was 94.1% (95% CI, 90.3 to 96.4) with trastuzumab deruxtecan and 85.9% (95% CI, 80.9 to 89.7) with trastuzumab emtansine (hazard ratio for death, 0.55; 95% CI, 0.36 to 0.86; prespecified significance boundary not reached). An overall response (a complete or partial response) occurred in 79.7% (95% CI, 74.3 to 84.4) of the patients who received trastuzumab deruxtecan and in 34.2% (95% CI, 28.5 to 40.3) of those who received trastuzumab emtansine. The incidence of drug-related adverse events of any grade was 98.1% with trastuzumab deruxtecan and 86.6% with trastuzumab emtansine, and the incidence of drug-related adverse events of grade 3 or 4 was 45.1% and 39.8%, respectively. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; none of these events were of grade 4 or 5.

Conclusions: Among patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane, the risk of disease progression or death was lower among those who received trastuzumab deruxtecan than among those who received trastuzumab emtansine. Treatment with trastuzumab deruxtecan was associated with interstitial lung disease and pneumonitis. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast03 ClinicalTrials.gov number, NCT03529110.).
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http://dx.doi.org/10.1056/NEJMoa2115022DOI Listing
March 2022

Effects of Coated Sodium Butyrate and Polysaccharides From on Intestinal Tissue Morphology and Ileal Microbiome of Squabs.

Front Vet Sci 2022 4;9:813800. Epub 2022 Mar 4.

College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.

This experiment was conducted to investigate the effects of dietary supplementation with different levels of coated sodium butyrate (CSB) and polysaccharides extracted from (CCP) on growth performance, intestinal tissue morphology and ileum microbiome in squabs. A total of 420 1-day-old squabs were randomly divided into seven groups with 5 replicates each and 12 squabs per replicate. The squabs were fed basal diet (control group) and basal diet supplemented with different levels of CSB (275, 550, and 1,100 mg/kg, groups CSB-275, CSB-550, CSB-1100) and CCP (27.5, 55, and 110 mg/kg, groups CCP-27.5, CCP-55, and CCP-110), respectively. The experiment was conducted for 28 days. The results revealed that the final BW and average daily gain concentration were higher ( < 0.05) in squabs of CSB-275 and CCP-110 groups than those in the CON group. Comparing with control group, the squabs in the groups CSB-275, CSB-550, and CCP-55 obtained higher villus height/crypt depth (VH/CD) of the duodenum and higher VH of the jejunum ( < 0.05). Operational taxonomic units in the groups CSB-550 and CCP-27.5 were also increased ( < 0.05). Regarding the relative abundance of flora, the abundance in the groups CSB-550, CSB-1100, and CCP-55 were higher than in control group ( < 0.05), and the abundance of CSB-275, CSB-550, CSB-1100, and CCP-110 were elevated ( < 0.05). However, the abundance in CSB-275, CSB-550, CSB-1100, and CCP-27.5 decreased ( < 0.05). In summary, results obtained in the present study indicate that CSB and CCP can improve growth performance, intestinal microbial balance and gut health of squabs.
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http://dx.doi.org/10.3389/fvets.2022.813800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931417PMC
March 2022

Squalene epoxidase drives cancer cell proliferation and promotes gut dysbiosis to accelerate colorectal carcinogenesis.

Gut 2022 Mar 1. Epub 2022 Mar 1.

Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China

Objective: Aberrant lipid metabolism is a hallmark of colorectal cancer (CRC). Squalene epoxidase (SQLE), a rate-limiting enzyme in cholesterol biosynthesis, is upregulated in CRC. Here, we aim to determine oncogenic function of SQLE and its interplay with gut microbiota in promoting colorectal tumourigenesis.

Design: Paired adjacent normal tissues and CRC from two cohorts were analysed (n=202). Colon-specific Sqle transgenic (Sqle tg) mice were generated by crossing Rosa26-lsl-Sqle mice to Cdx2-Cre mice. Stools were collected for metagenomic and metabolomic analyses.

Results: SQLE messenger RNA and protein expression was upregulated in CRC (p<0.01) and predict poor survival of patients with CRC. SQLE promoted CRC cell proliferation by inducing cell cycle progression and suppressing apoptosis. In azoxymethane-induced CRC model, Sqle tg mice showed increased tumourigenesis compared with wild-type mice (p<0.01). Integrative metagenomic and metabolomic analyses unveiled gut dysbiosis in Sqle tg mice with enriched pathogenic bacteria, which was correlated to increased secondary bile acids. Consistent with detrimental effect of secondary bile acids, gut barrier function was impaired in Sqle tg mice, with reduced tight junction proteins Jam-c and occludin. Transplantation of Sqle tg mice stool to germ-free mice impaired gut barrier function and stimulated cell proliferation compared with control mice stool. Finally, we demonstrated that terbinafine, a SQLE inhibitor, could be repurposed for CRC by synergising with oxaliplatin and 5-fluorouracil to inhibit CRC growth.

Conclusion: This study demonstrates that SQLE mediates oncogenesis via cell intrinsic effects and modulation of gut microbiota-metabolite axis. SQLE represents a therapeutic target and prognostic marker in CRC.
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http://dx.doi.org/10.1136/gutjnl-2021-325851DOI Listing
March 2022
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