Publications by authors named "Peng Zhao"

1,827 Publications

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Expanded endonasal endoscopic approach for suprasellar Rathke cleft cyst: treatment outcome and surgical nuances.

World Neurosurg 2022 Aug 7. Epub 2022 Aug 7.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, P. R. China. Electronic address:

Objective: Rathke cleft cysts (RCCs) are benign lesions originating from the remnants of Rathke pouch. RCCs has been classified into the intrasellar-based or purely suprasellar types. This research aims to study the optimal treatment nuances and evaluate the surgical outcomes of this distinct type of RCCs.

Methods: This study retrospectively reviewed 36 patients with purely suprasellar RCCs who were treated by expanded endonasal endoscopic approach (EEA) from September 2018 to January 2021. The demographic data, presenting symptoms, endocrine status, imaging findings, operative details, and surgical outcomes were analyzed.

Results: According to the relationship with pituitary stalk, the suprasellar RCCs can be divided into two different growth patterns: intra-stalk cyst (ISC, 52.8%) and extra-stalk cyst (ESC, 47.2%). Preoperative endocrine dysfunctions occurred more in patients with ISC than ESC (p=0.007), which are characterized by hypoadrenalism (p=0.004) and hypogonadism (p=0.008). Operation exerted different impacts on endocrine functions between ISC and ESC (p=0.012). When identifying by single hypothalamic-pituitary axis, 4 patients with normal endocrine function developed a new hormonal deficit, 14 patients with preoperative endocrine dysfunctions benefit from our expanded EEA surgical treatment, and 3 of them completely recovered from the endocrinopathy after surgery. And the postoperative endocrinopathy were positively associated with the numbers of preoperative abnormal endocrinal axes. 34 (94.4%) patients had achieved gross total resection. Pituitary stalk was intactly preserved in 23 of 36 patients (63.9%), partly preserved in 10 patients and not preserved in 3 patients.

Conclusion: The purely suprasellar RCCs are a distinct type of RCCs, which originate from the pituitary stalk above the diaphragmatic sellae and the treatment strategy via expanded EEA is a rational choice. The classification based on growth patterns would be beneficial to reduce endocrine disorders after surgery.
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http://dx.doi.org/10.1016/j.wneu.2022.07.114DOI Listing
August 2022

Two-dimensional speckle tracking echocardiography in assessing the subclinical myocardial dysfunction in patients with gestational diabetes mellitus.

Cardiovasc Ultrasound 2022 Aug 9;20(1):21. Epub 2022 Aug 9.

Cardiovascular Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, Hangzhou, China.

Background: Gestational diabetes mellitus (GDM) may increase the risk of cardiovascular disease and accompany asymptomatic deterioration of the myocardial function. This study aims to identify the subclinical impact of GDM on maternal left ventricular function by two-dimensional speckle tracking echocardiography (2D-STE).

Methods: We prospectively recruited 47 women with GDM and 62 healthy pregnant women who underwent transthoracic echocardiography (TTE) at 24 to 28 weeks of pregnancy. GDM diagnosis agreed with the IADPSG criteria. TTE was performed according to the criteria of the American Society of Echocardiography. Conventional echocardiographic data and 2D-STE parameters were compared between the two groups.

Results: Age, gestational weeks, heart rate, and conventional echocardiographic parameters had no difference between the two groups. The average LV global longitudinal strain (LV-GLS) of GDM patients was lower than controls (18.14 ± 2.53 vs. 22.36 ± 6.33, p < 0.001), and 31 patients (66%) in our study had an absolute LV-GLS less than 20%. The LA reservoir and conduit strain in patients with GDM were also significantly reduced (32.71 ± 6.64 vs. 38.00 ± 7.06, 20.41 ± 5.69 vs. 25.56 ± 5.73, p < 0.001). However, there was no significant difference in LA contractile function between the two groups. In multiple regression analysis, LV-GLS and LA conduit strain independently associated with GDM.

Conclusions: 2D-STE could detect the subclinical myocardial dysfunction more sensitively than conventional echocardiography, with LV-GLS and LA conduit strain as independent indicators of the GDM impact on maternal cardiac function during pregnancy.
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http://dx.doi.org/10.1186/s12947-022-00292-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9361647PMC
August 2022

Change of motifs in C. elegans reveals developmental principle of neural network.

Biochem Biophys Res Commun 2022 Aug 1;624:112-119. Epub 2022 Aug 1.

Department of Automation, Shanghai Jiao Tong University, Shanghai, 200240, China; Key Laboratory of System Control and Information Processing, Ministry of Education, Shanghai, 200240, China. Electronic address:

Revealing the organizing principles of developing neural networks is a difficult but significant task in neuroscience. As a creature with a rather compact and well-studied neural network, C. elegans is an ideal subject for neuroscience study. However, the researches on its developing neural network remain challenging. The changes in specific properties of neural network across development may uncover part of its principles. Motif is a typical structure property that can be well applied to various complex networks. Here, we study the motif changes in C. elegans neural network across development. By counting the occurrence number of all three-node subgraph motif structures in its neural network at different stages of C. elegans development, along with those in corresponding random networks, we determine which of these structures are motifs for C. elegans, finding out the regular changes of motifs during its development. Combined with the potential function of these subgraph motifs and synaptic information, we gain insight into the organizing principle of neural network during development, which may increase our understanding of neuroscience and inspire the construction of artificial neural network.
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http://dx.doi.org/10.1016/j.bbrc.2022.07.108DOI Listing
August 2022

Quantitative and Noninvasive Detection of SAH-Related MiRNA in Cerebrospinal Fluids In Vivo Using SERS Sensors Based on Acupuncture-Based Technology.

ACS Appl Mater Interfaces 2022 Aug 7. Epub 2022 Aug 7.

The Second Affiliated Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong 271000, China.

Quantitative analysis of microRNAs (miRNAs) in a noninvasive manner is of vital importance for disease diagnosis and prognosis evaluation. However, conventional strategies for realizing accurate, simple, and sensitive detection of target molecules are still a challenge, especially for miRNAs due to their low abundance and susceptibility in the complex biological environment. Here, a novel surface-enhanced Raman scattering (SERS) strategy was established for quantitative detection and monitoring of miRNA-21-5p (miR-21-5p) in living cells and in vivo cerebrospinal fluid (CSF) by applying hairpin DNA (hpDNA)-conjugated gold nanostars (GNSs) SERS probes combined with acupuncture-based technology. This strategy enabled ultrasensitive exploration toward miR-21-5p in a wide range from 1 fM to 100 pM in cell lysates. Moreover, SERS analysis facilitated the detection and long-term monitoring for in vivo miR-21-5p noninvasively. This developed strategy promises to offer a powerful method for the analysis of multiple biomolecules in single cells and living bodies.
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http://dx.doi.org/10.1021/acsami.2c03436DOI Listing
August 2022

The complete chloroplast genome sequence of (Orchidaceae).

Mitochondrial DNA B Resour 2022 24;7(6):1174-1176. Epub 2022 Jun 24.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, China.

Braem 1987 is a critically Endangered terrestrial orchid mainly occurred around the southern China and northern Vietnamese borders. Recently, the population size of this species has been sharply declined due to many threats such as climate change, habitat loss, and narrow distribution. In this study, the complete chloroplast genome sequence of was determined from Illumina pair-end sequencing data. The chloroplast genome was 155,886 bp in length, including a large single copy region (LSC) of 87,573 bp, a small single-copy region (SSC) of 2,831 bp, and a pair of inverted repeated regions (IRa and IRb) of 32,741 bp each. The chloroplast genome contained 121 genes corresponding to 76 protein-coding genes, 8 ribosomal RNA (rRNA) genes and 37 transfer RNA (tRNA) genes, respectively. The results of phylogenetic analysis indicated that was closely related to and in the genus based on sixteen whole chloroplast genome sequences. The results would provide a valuable resource for future genetic studies of .
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http://dx.doi.org/10.1080/23802359.2022.2088310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354640PMC
June 2022

Identification and analysis of smORFs in Chlamydomonas reinhardtii.

Genomics 2022 Aug 3:110444. Epub 2022 Aug 3.

School of Life Sciences and Hubei Key Laboratory of Genetic Regulation and Integrative Biology, Central China Normal University, Wuhan 430079, Hubei, China. Electronic address:

Small open reading frames (smORFs) have been acknowledged as an important partner in organism functions ranging from bacteria to higher eukaryotes. However, lack of investigation of smORFs in green algae, despite their importance in ecology and evolution. We applied bioinformatic analysis, ribosome profiling, and small peptide proteomics to provide a genome-wide and high-confident smORF database in the model green alga Chlamydomonas reinhardtii. The whole genome was screened first to mine potential coding smORFs. Then conservative analysis, ribosome profiling, and proteomics data were processed to identify conserved smORFs and generate translation evidence. The combination of procedures resulted in 2014 smORFs that might exist in the C. reinhardtii genome. The expression of smORFs in Cd treatment suggested that two smORFs might participate in redox reaction, three in inorganic phosphate transport, and one in DNA repair under stress. Our study built a genome-widely database in C. reinhardtii, providing target smORFs for further research.
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http://dx.doi.org/10.1016/j.ygeno.2022.110444DOI Listing
August 2022

Assembly of high-quality genomes of the locoweed Oxytropis ochrocephala and its endophyte Alternaria oxytropis provides new evidence for their symbiotic relationship and swainsonine biosynthesis.

Mol Ecol Resour 2022 Aug 6. Epub 2022 Aug 6.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Shaanxi, China.

Locoweeds are perennial forbs poisonous to livestock and cause extreme losses to animal husbandry. Locoweed toxicity is attributed to the symbiotic endophytes in Alternaria sect. Undifilum, which produce a mycotoxin swainsonine (SW). We performed a de novo whole genome sequencing of the most common locoweed in China, Oxytropis ochrocephala (2n = 16), and assembled a high-quality, chromosome-level reference genome. Its genome size is 958.83 Mb with 930.94 Mb (97.09 %) anchored and oriented onto 8 chromosomes, and 31,700 protein-coding genes were annotated. Phylogenetic and collinearity analysis showed it is closely related to Medicago truncatula with a pair of large interchromosomal rearrangements, and both species underwent a whole-genome duplication event. We also derived the genome of A. oxytropis at 74.48 Mb with a contig N50 of 8.87 Mb and 10,657 protein-coding genes, and refined the genes of SW biosynthesis. Multiple Alternaria species containing the swnK gene were grouped into a single clade, but in other genera, swnK's homologues are diverse. Resequencing of 41 A. oxytropis strains revealed one SNP in the SWN cluster causing changes in SW concentration. Comparing the transcriptomes of symbiotic and non-symbiotic interactions identified differentially expressed genes (DEG) linked to defense and secondary metabolism in the host. Within the endophyte DEGs were linked to cell wall degradation, fatty acids and nitrogen metabolism. Symbiosis induced the up-regulation of most of the SW biosynthetic genes. These two genomes and relevant sequencing data should provide valuable genetic resources for the study of the evolution, interaction, and SW biosynthesis in the symbiont.
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http://dx.doi.org/10.1111/1755-0998.13695DOI Listing
August 2022

Nitrogen removal intensification of aerobic granular sludge through bioaugmentation with "heterotrophic nitrification-aerobic denitrification" consortium during petroleum wastewater treatment.

Bioresour Technol 2022 Aug 2;361:127719. Epub 2022 Aug 2.

State Key Laboratory of Petroleum Pollution Control, Beijing Key Laboratory of Oil and Gas Pollution Control, China University of Petroleum-Beijing, Beijing 102249, China. Electronic address:

The bioaugmentation potential of aerobic granular sludge (AGS) was investigated using heterotrophic nitrification-aerobic denitrification (HN-AD) bacterial consortium to improve nitrogen removal during petroleum wastewater treatment. An efficient HN-AD consortium was constructed by mixing Pseudomonas mendocina K0, Brucella sp. K1, Pseudomonas putida T4 and Paracoccus sp. T9. AGS bioaugmented by immobilized HN-AD consortium enhanced nitrogen removal, which showed NH-N and TN removal efficiency of 92.4% and 79.8%, respectively. The immobilized consortium addition facilitated larger AGS formation, while granules > 2.0 mm accounted for 16.7% higher than that of control (6.7%). Further, the abundance of napA gene was 4-times higher in the bioaugmented AGS as compared to the control, which demonstrated the long-term stability of HN-AD consortium in the bioreactor. The bioaugmented AGS also showed a higher abundance of xenobiotics biodegradation and nitrogen metabolism. These results highlight that bioaugmentation of AGS technology could be effectively used for enhanced denitrification of petroleum wastewater.
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http://dx.doi.org/10.1016/j.biortech.2022.127719DOI Listing
August 2022

Discovery and engineering of an anti-TREM2 antibody to promote amyloid plaque clearance by microglia in 5XFAD mice.

MAbs 2022 Jan-Dec;14(1):2107971

Brown Foundation Institute of Molecular Medicine, Texas Therapeutics Institute, University of Texas Health Science Center at Houston, Houston, Texas, USA.

Triggering receptor expressed on myeloid cells 2 (TREM2) plays a crucial role in regulating microglial functions and removal of amyloid plaques in Alzheimer's disease (AD). However, therapeutics based on this knowledge have not been developed due to the low antibody brain penetration and weak TREM2 activation. In this study, we engineered a TREM2 bispecific antibody to potently activate TREM2 and enter the brain. To boost TREM2 activation, we increased the valency of bivalent anti-TREM2 Ab2 IgG to tetra-variable domain immunoglobulin (TVD-Ig), thus improving the EC of amyloid-β oligomer (oAβ)-lipid microglial phagocytosis by more than 100-fold. Ab2 TVD-Ig treatment also augmented both microglia migration toward oAβ and microglia survival by 100-fold over the bivalent IgG antibody. By targeting the transferrin receptor (TfR), the brain-penetrating Ab2 TVD-Ig/αTfR bispecific antibody realized broad brain parenchyma distribution with a 10-fold increase in brain antibody concentration. Ab2 TVD-Ig/αTfR treatment of 5-month-old 5XFAD mice significantly boosted microglia-plaque interactions and enhanced amyloid plaque phagocytosis by microglia. Thus, potent TREM2 activation by a multivalent agonist antibody coupled with TfR-mediated brain entry can boost microglia clearance of amyloid plaques, which suggests the antibody has potential as an AD treatment. AD: Alzheimer's disease; Ab: antibody; APOE: apolipoprotein E; Aβ: amyloid beta; BBB: blood-brain barrier; BLI: bio-layer interferometry; CNS: central nervous system; CSF: colony-stimulating factor; CytoD: cytochalasin d; DAM: microglia type associated with neurodegenerative diseases; DAP12: DNAX-activation protein 12; TVD-Ig: tetra-variable domain immunoglobulin; ECD: extracellular domain; ELISA: enzyme-linked immunoassay; ESC: embryonic stem cell; hMGLs: human embryonic stem cell-derived microglia-like lines; IBA1: ionized calcium-binding adaptor molecule 1; ITAM: immunoreceptor tyrosine-based activation motif; KiH: knob-into-hole; NFAT: nuclear factor of activated t-cells; PC: phosphatidylcholine; PK: pharmacokinetics; PS: phosphatidylserine; pSYK: phosphorylated spleen tyrosine kinase; scFv: single-chain variable fragment; SEC: size-exclusion chromatography; sTREM2: soluble triggering receptor expressed on myeloid cells 2; SYK: spleen tyrosine kinase; TfR: transferrin receptor; TREM2: triggering receptor expressed on myeloid cells 2.
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http://dx.doi.org/10.1080/19420862.2022.2107971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354770PMC
August 2022

Hemin functionalized hybrid aerogel-enabled electrochemical chip for real-time analysis of HO.

Analyst 2022 Aug 3. Epub 2022 Aug 3.

Key Laboratory for Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, PR China.

Herein, a novel hemin functionalized hybrid aerogel ([email protected]) is synthesized and applied to an electrochemical chip for real-time analysis of hydrogen peroxide (HO). The [email protected] shows a typical three-dimensional morphology and excellent peroxidase-like catalytic performance. The [email protected] electrochemical chip presents satisfactory performance for HO sensing with a low limit of detection (0.96 μM). Besides, the chip platform shows some advantages of less sample consumption and easier detection operation.
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http://dx.doi.org/10.1039/d2an00524gDOI Listing
August 2022

The TBK1/IKKε inhibitor amlexanox improves dyslipidemia and prevents atherosclerosis.

JCI Insight 2022 Aug 2. Epub 2022 Aug 2.

Department of Medicine, University of California San Diego, La Jolla, United States of America.

Cardiovascular diseases, especially atherosclerosis and its complications, are a leading cause of death. Inhibition of the non-canonical IκB kinases TBK1 and IKKε with amlexanox restores insulin sensitivity and glucose homeostasis in diabetic mice and human subjects. Here we report that amlexanox improves diet-induced hypertriglyceridemia and hypercholesterolemia in Western diet (WD)-fed Ldlr-/- mice, and protects against atherogenesis. Amlexanox ameliorates dyslipidemia, inflammation and vascular dysfunction through synergistic actions that involve upregulation of bile acid synthesis to increase cholesterol excretion. Transcriptomic profiling demonstrates an elevated expression of key bile acid synthesis genes. Furthermore, we found that amlexanox attenuates monocytosis, eosinophilia and vascular dysfunction during WD-induced atherosclerosis. These findings demonstrate the potential of amlexanox as a new therapy for hypercholesterolemia and atherosclerosis.
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http://dx.doi.org/10.1172/jci.insight.155552DOI Listing
August 2022

Personality traits influence the effectiveness of hypomania checklist-32 in screening for bipolar disorder.

Front Psychiatry 2022 15;13:919305. Epub 2022 Jul 15.

Department of Medical Psychology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Background: It is clinically challenging to distinguish bipolar disorder (BD) from major depressive disorder (MDD) in the early stages. While the hypomania checklist-32 (HCL-32) is a proper auxiliary tool that is useful to differentiate between BD and MDD, there is currently no standard cut-off value. The variations in HCL-32 cut-off values could potentially be influenced by personality traits. Therefore, the aim of this study is to explore the effect of personality traits on the screening performance of HCL-32.

Methods: In this retrospective cross-sectional study, 168 patients with BD or MDD were evaluated with the Eysenck Personality Questionnaire (EPQ) and HCL-32. The associations between demographic data, diagnosis and clinical rating scales were analyzed.

Results: Diagnosis was not associated with extraversion but was related to neuroticism. HCL-32 scores in typical extraverted patients were higher in contrast to atypical extraverted patients. The best cut-off value for BD recognition of typical and atypical extraversion groups were 15 and 12.5, respectively. In patients with MDD, HCL-32 score of typical neuroticism was higher than the atypical type, but there was no difference in patients with BD. In typical neuroticism, there was no difference in HCL-32 scores between patients with MDD and BD. But among atypical neurotic patients, HCL-32 scores of BD were higher compared to MDD, with a cut-off value of 14.5.

Limitations: This study had a small sample size.

Conclusion: HCL-32 scores were affected by personality traits, with higher scores for typical extraversion and neuroticism. Clinicians should also consider the patients' personality traits when referring to HCL-32 scores, so as to increase the recognition rate of BD and eliminate false positives.
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http://dx.doi.org/10.3389/fpsyt.2022.919305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337268PMC
July 2022

Extracellular polymeric substance profiling and biophysical analysis reveal influence factors of spontaneous flocculation in rich lipid alga Heveochlorella sp. Yu.

Sci Total Environ 2022 Jul 28:157655. Epub 2022 Jul 28.

Faculty of Life Sciences and Technology, Kunming University of Science and Technology, Kunming 650500, China. Electronic address:

Microalgae harvest and lipid accumulation were important factors influencing commercialized development of microalgae biodiesel. Spontaneous flocculation was an ideal method in microalgae harvest, but few rich lipid microalgae could be harvested by spontaneous flocculation. Rich lipid alga Heveochlorella sp. Yu has a characteristic of spontaneous flocculation to be harvested. Heveochlorella sp. Yu has high lipid productivity (105.24 mg L d) and fine spontaneous flocculation efficiency (82.93 %, 2 h) on early stationary phase (day 9). The polysaccharides consisting of glucose, mannose, galactose, rhamnose and fructose (8.67:4.90:3.27:2.16:1) in loose-bound extracellular polymeric substance (LB-EPS) might make great contribution in microalgae flocculation. Meanwhile, the zeta potential close to zero was also beneficial to microalgae flocculation. Besides, the adhesion free energy related with cells adhesion was detected by thermomechanical analysis. Afterward, Extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory was utilized to quantitatively evaluate short-range interactions involved in the spontaneous aggregation among cells. Collectively, biophysical analyses indicated that content and composition of EPS, Zeta potential, thermodynamic parameter and total interaction based on XDLVO theory were closely connected with spontaneous flocculation in microalga Yu. Our study provided a harvest-simplified process of rich microalgae, which proposes a new idea for commercial development of microalgae biodiesel.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157655DOI Listing
July 2022

Efficacy and safety of ruxolitinib for steroid-refractory graft-versus-host disease: Systematic review and meta-analysis of randomised and non-randomised studies.

PLoS One 2022 29;17(7):e0271979. Epub 2022 Jul 29.

Department of Haematology, The Affiliated Hospital of Guizhou Medical University, Guiyang, GuiZhou Province, China.

Background: Hematopoietic stem cell transplantation (HSCT) for haematological disorders. Graft-versus-host disease (GVHD), a cause of morbidity and mortality is treated with corticosteroids. However, patients with steroid-refractory GVHD after HSCT have a poor prognosis. Ruxolitinib, a selective Janus kinase inhibitor, is a novel treatment strategy for steroid-refractory GVHD.

Objectives: To assess the efficacy of ruxolitinib for the treatment of steroid-refractory GVHD and analyse its adverse effects.

Study Design: Meta-analysis.

Search Methods: Randomised controlled trials (RCTs) and non-RCTs of ruxolitinib-based therapy in patients with steroid-refractory GVHD were found in the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and Web of Science in March 2021. Outcomes included overall response rate, survival, and adverse effects. The Methodological Index for Non-randomised Studies (MINORS) and the Cochrane collaboration risk-of-bias tool were used to assess methodological quality. Funnel plots, Egger's test, and the trim and fill method were used to assess publication bias.

Results: In total, 1470 studies were identified; 19 studies (17 non-RCTs, 2 RCTs) involving 1358 patients met our inclusion criteria. Survival rates at the longest follow-up in non-RCTs, were 57.5% (95% CI 46.9-67.4) and 80.3% (95% CI 69.7-87.9) for acute GVHD (aGVHD) and chronic GVHD (cGVHD), respectively. In non-RCTs, the overall response was 74.9% (95% CI 66.6-81.8, I2 = 49%) in aGVHD and 73.1% (95% CI 62.5-81.6, I2 = 49%) in cGVHD. In aGVHD, the response rates were gastrointestinal, 61.4-90.2%; skin, 52.5-80.6%; and liver, 41.8-71.8%. In cGVHD, the response rates were gastrointestinal, 30.1-70.4%; skin, 30.1-84.4%; lung, 27.0-83.0%; and mouth 3.5-98.1%. In addition, a lower aGVHD grade and moderate cGVHD were associated with a better clinical response. Common adverse events were cytopenia and infectious complications.

Conclusions: Our systematic review and meta-analysis indicated that ruxolitinib therapy could be a potentially effective and safe treatment for patients with steroid-refractory GVHD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271979PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337651PMC
August 2022

Enlarged Pericarotid Lymph Nodes Suggest Recent Ischemic Symptoms in Patients with Carotid Atherosclerosis.

Front Immunol 2022 12;13:900642. Epub 2022 Jul 12.

Department of Neurosurgery, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, China.

Atherosclerosis is a chronic inflammatory disease closely associated with immunological activity. Lymph nodes (LNs) are essential secondary lymphoid organs, in which complex immune responses occur. Enlarged LNs are commonly observed around inflamed tissues or tumors; however, their role in atherosclerosis is not well understood. We hypothesized that enlarged pericarotid LNs would be present in symptomatic patients with carotid atherosclerosis. Therefore, we recorded the size of LNs around the carotid artery during surgery in patients undergoing carotid endarterectomy (CEA) for carotid atherosclerotic stenosis. Patients were stratified by enlarged LNs, defined as a diameter ≥ 10mm in the transverse diameters. Demographic and clinical data of participants were measured and analyzed. Hematoxylin and eosin (H&E), Sirius red, DAB-enhanced Perls' Prussian blue, alizarin red, and immunohistochemistry (IHC) staining were performed for composition identification of plaques or LNs. Symptomatic patients were defined as those presenting with an ipsilateral cerebral ischemic event. Compared with patients with non-enlarged LNs, patients with enlarged LNs were more likely to be symptomatic (22/32, 68.8% versus 9/40, 22.5%, < 0.001) and use calcium channel blocker drugs (17/32, 53.1% versus 10/40, 25%, =0.014). In addition, they showed lower body mass index (mean ± SD: 24.00 ± 2.66 versus 25.34 ± 2.56 kg/m, =0.034), lower weight (median [interquartile range]: 64 [60.00-76.00] versus 72.5 [65.00-77.50] Kg, = 0.046) and higher diastolic blood pressure (mean ± SD: 78.94 ± 9.30 versus 73.93 ± 8.84 mmHg, = 0.022). The plague from patients with enlarged LNs exhibited a lower relative percentage of fibrous tissue (29.49 ± 10.73% versus 34.62 ± 10.33%, = 0.041). The enlarged LNs remained oval-shaped by visual inspection. Compared to non-enlarged LNs, the predominant changes in enlarged LNs were atrophic lymphatic sinuses and dilated LNs parenchyma. Enlarged LNs contained more germinal centers and lymphocytes. In conclusion, symptomatic patients with carotid atherosclerosis have enlarged pericarotid LNs. The current study supports the conclusion that enlarged LNs with an activated and enhanced adaptive immune response may indicate plaque instability. Pericarotid LNs will be a promising marker of plaque stability and may be a potential therapeutic target in patients with carotid atherosclerosis.
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http://dx.doi.org/10.3389/fimmu.2022.900642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315152PMC
August 2022

A novel identified circular RNA, circSnap47, promotes heart failure progression via regulation of miR-223-3p/MAPK axis.

Mol Cell Biochem 2022 Jul 28. Epub 2022 Jul 28.

Department of Cardiac Surgery I, Yantai Yuhuangding Hospital, No.20 Yuhuangding East Road, Zhifu District, Yantai, 264000, Shandong, People's Republic of China.

The aim of this study was to investigate the effect of circSnap47 on heart failure (HF) and its potential mechanisms. Quantitative real-time PCR (qRT-PCR) was performed to detect the mRNA expression levels of circSnap47 and miR-233-3p. The viability and apoptosis of H9C2 cells were assessed using CCK-8 and TUNEL assays. The expressions of interleukin (IL)-6, IL-1β, IL-18, and tumor necrosis factor-alpha were determined using ELISA and qRT-PCR. In addition, the expression of apoptosis-related proteins and mitogen-activated protein kinase (MAPK) signaling pathway-related proteins was analyzed using western blot. Moreover, HF-related circRNAs and miRNAs were predicted via bioinformatics analysis. The relationship between circSnap47 and miR-233-3p was further confirmed using a dual-luciferase reporter gene assay. In HF tissues and H9C2 cells treated with oxygen-glucose deprivation (OGD), circSnap47 was upregulated. Silencing circSnap47 increased cell viability and inhibited apoptosis. Besides, silencing circSnap47 alleviated OGD-induced inflammation in H9C2 cells. Moreover, we found that miR-233-3p was the downstream target gene of circSnap47. Our results also revealed that silencing circSnap47 relieved OGD-induced H9C2 cell damage by inactivating the miR-223-3p/MAPK axis. We confirmed that circSnap47 silencing inhibited HF progression via regulation of miR-223/MAPK axis, which will provide for a new therapeutic direction for the treatment of HF.
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http://dx.doi.org/10.1007/s11010-022-04523-zDOI Listing
July 2022

Ciliogenesis requires sphingolipid-dependent membrane and axoneme interaction.

Proc Natl Acad Sci U S A 2022 Aug 27;119(31):e2201096119. Epub 2022 Jul 27.

Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.

Cilium formation and regeneration requires new protein synthesis, but the underlying cytosolic translational reprogramming remains largely unknown. Using ribosome footprinting, we performed global translatome profiling during cilia regeneration in and uncovered that flagellar genes undergo an early transcriptional activation but late translational repression. This pattern guided our identification of sphingolipid metabolism enzymes, including serine palmitoyltransferase (SPT), as essential regulators for ciliogenesis. Cryo-electron tomography showed that ceramide loss abnormally increased the membrane-axoneme distance and generated bulged cilia. We found that ceramides interact with intraflagellar transport (IFT) particle proteins that IFT motors transport along axoneme microtubules (MTs), suggesting that ceramide-IFT particle-IFT motor-MT interactions connect the ciliary membrane with the axoneme to form rod-shaped cilia. SPT-deficient vertebrate cells were defective in ciliogenesis, and SPT mutations from patients with hereditary sensory neuropathy disrupted cilia, which could be restored by sphingolipid supplementation. These results reveal a conserved role of sphingolipid in cilium formation and link compromised sphingolipid production with ciliopathies.
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http://dx.doi.org/10.1073/pnas.2201096119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351462PMC
August 2022

Automated and Miniaturized Pico-Liter Metabolite Extraction System for Single-Cell Mass Spectrometry.

IEEE Trans Biomed Eng 2022 Jul 27;PP. Epub 2022 Jul 27.

Objective: Mass spectrometry has become the method of choice for single cell analysis due to its high sensitivity of detection and capability in analyzing a large number of metabolites simultaneously. For a long time, an automated and miniaturized system capable of extracting cellular contents from single cells at the pico-liter level for pico-ESI analysis has been lacking.

Methods: This paper presents a first-of-its-kind automated and miniaturized pico-liter extraction system for single-cell MS. The key modules, including imaging, bus controller, and fluidic driving are customized to achieve satisfactory performance at affordable costs, resulting in a miniaturized system movable on a trolley and connectable with the MS. To enable automation, a single cell trapping device, new image-based one-pixel accuracy positioning methods for cells and micropipette, and a surface-tension-based 1-pL accuracy volume control scheme are developed.

Results: The system is able to control the solvent loading at 1.97±0.05 nL, solvent dispensing at 14-15 pL, and solvent evaporation at 689±48 pL. MS experiments demonstrate a throughput of 20 cells/h.

Conclusion: The system has achieved better performance in consistency (∼21%), sensitivity (∼28%), and success rate (up to 40%) than manual operation.

Significance: This automated and miniaturized system lays a solid basis for applying pico-ESI MS analysis in the automated and high-throughput single cell MS analysis, such as single-cell metabolomics and lipidomics.
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http://dx.doi.org/10.1109/TBME.2022.3194255DOI Listing
July 2022

Predictors and prognostic stratification for lupus low disease activity state: Results from a prospective clinical trial.

Rheumatology (Oxford) 2022 Jul 27. Epub 2022 Jul 27.

Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.

Objective: Identify predictors for lupus low disease activity state (LLDAS), early-achieved LLDAS, and long-term disease activity and refine a prognostic stratification tool for use in active systemic lupus erythematosus (SLE) patients.

Method: A total of 245 active SLE patients were enrolled, followed up quarterly from 2014 to 2016. LLDAS-50 was defined as the maintenance of LLDAS for ≥50% of the observed time. LLDAS at 3 months after cohort entry (LLDAS-3mo) was considered an early-achieved LLDAS. Multivariate analysis was performed to identify predictors for LLDAS, early-achieved LLDAS and long-term disease activity. Based on the factors associated with LLDAS, a prognostic stratification tool for LLDAS was established.

Results: The 2-year probability of achieving LLDAS was 62.9% (154/245). Multivariate analysis determined renal involvement, hematological involvement and hypocomplementemia were negative predictors for achieving LLDAS and LLDAS-50. In multivariate logistic analysis, antiphospholipid antibodies positivity, hypocomplementemia, renal involvement and hematological involvement were identified as negative predictors for achieving LLDAS-3mo. LLDAS-3mo (P < 0.0001; RR, 47.694 95% CI 13.776-165.127) was a strong predictor for LLDAS-50. The probability of achieving LLDAS, LLDAS-50 and LLDAS-3mo were 88.9% (32/36), 69.4% (25/36), and 41.7% (15/36) in the low-risk group, 65% (65/100), 51.0% (51/100), 32.0% (32/100) in intermediate-risk group, and 52.8% (57/108), 27.8% (30/108), 13.0% (14/108) in high-risk group respectively. Significant differences (P < 0.0001) were observed in the LLDAS Kaplan-Meier estimates for the 3 risk groups based on the identified risk factors.

Conclusion: Renal involvement, hematological involvement and hypocomplementemia were negative predictors of LLDAS achievement and maintenance. LLDAS-3mo was a positive predictor for the long-term sustainment of LLDAS.
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http://dx.doi.org/10.1093/rheumatology/keac419DOI Listing
July 2022

Comparative Transcriptome and Interaction Protein Analysis Reveals the Mechanism of -Overexpressing Transgenic Sweet Potato Response to Low-Temperature Stress.

Genes (Basel) 2022 Jul 14;13(7). Epub 2022 Jul 14.

Xuzhou Sweet Potato Research Center, Xuzhou Institute of Agricultural Sciences Jiangsu, China/Key Laboratory of Sweet Potato Biology and Genetic Breeding, Ministry of Agriculture/National Agricultural Experimental Station for Soil Quality, Xuzhou 221000, China.

The sweet potato is very sensitive to low temperature. Our previous study revealed that -overexpressing transgenic sweet potato (M3) plants showed stronger low-temperature stress tolerance than wild-type plants (WT). However, the mechanism of M3 plants in response to low-temperature stress is unclear. To further analyze how mediates low-temperature stress in sweet potato, WT and M3 plants were exposed to low-temperature stress for 2 h and 12 h for RNA-seq analysis, whereas normal conditions were used as a control (CK). In total, 3436 and 8718 differentially expressed genes (DEGs) were identified in WT at 2 h (vs. CK) and 12 h (vs. CK) under low-temperature stress, respectively, whereas 1450 and 9291 DEGs were detected in M3 plants, respectively. Many common and unique DEGs were analyzed in WT and M3 plants. DEGs related to low temperature were involved in Ca signaling, MAPK cascades, the reactive oxygen species (ROS) signaling pathway, hormone transduction pathway, encoding transcription factor families (, , and ), and downstream stress-related genes. Additionally, more upregulated genes were associated with the MAPK pathway in M3 plants during short-term low-temperature stress (CK vs. 2 h), and more upregulated genes were involved in secondary metabolic synthesis in M3 plants than in the WT during the long-time low-temperature stress treatment (CK vs. 12 h), such as fatty acid biosynthesis and elongation, glutathione metabolism, flavonoid biosynthesis, carotenoid biosynthesis, and zeatin biosynthesis. Moreover, the interaction proteins of IbMPK3 related to photosynthesis, or encoding CaM, NAC, and ribosomal proteins, were identified using yeast two-hybrid (Y2H). This study may provide a valuable resource for elucidating the sweet potato low-temperature stress resistance mechanism, as well as data to support molecular-assisted breeding with the gene.
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http://dx.doi.org/10.3390/genes13071247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317282PMC
July 2022

The genome of Eustoma grandiflorum reveals the whole-genome triplication event contributing to ornamental traits in cultivated lisianthus.

Plant Biotechnol J 2022 Jul 25. Epub 2022 Jul 25.

Floriculture Research Institute, Academy of Agricultural Sciences, National Engineering Research Center for Ornamental Horticulture, Key Laboratory for Flower Breeding of Yunnan Province, Yunnan, 650205, Kunming, China.

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http://dx.doi.org/10.1111/pbi.13899DOI Listing
July 2022

Soluble Receptor for Advanced Glycation End Product Is Involved in the Inflammatory Response of Human Adenovirus-Infected Patients.

Front Microbiol 2022 7;13:923215. Epub 2022 Jul 7.

Senior Department of Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.

Human adenovirus (HAdV) infection causes excessive inflammation associated with severe tissue injury, such as pneumonia. The molecules involved in the underlying inflammatory mechanisms remain to be elucidated. Receptor for advanced glycation end product (RAGE) is mainly expressed on immune cells and lung tissues, and it is a key factor in the initiation and development of inflammation. RAGE can be cleaved by metalloprotease 9 (MMP9) to release the extracellular segment, which is named soluble RAGE (sRAGE), into the intercellular space, where it can bind to RAGE ligands and block RAGE activation and subsequent inflammation. In our study, we enrolled HAdV-infected patients and their contacts to examine the relationship between sRAGE and inflammation induced by HAdV infection. The results showed that HAdV infection stimulated inflammatory cytokine secretion, increased such as high mobility group box 1 (HMGB1) levels, and suppressed sRAGE expression. sRAGE levels were significantly different between patients with or without pneumonia. We also found that MMP9 was significantly lower in patients with pneumonia, and it was positively correlated with sRAGE levels over 7 days after disease onset. The mitogen-activated protein kinase (MAPK) pathway is an important immune activation signaling pathway that is regulated by RAGE. We observed the activation of the MAPK pathway in the peripheral blood mononuclear cells (PBMCs) of patients. Negative correlations between sRAGE and phosphorylated JNK and p38 were observed. These results suggest that sRAGE is involved in HAdV-induced inflammatory responses, and might be a potential therapeutic target to alleviate the HAdV-induced excessive inflammation.
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http://dx.doi.org/10.3389/fmicb.2022.923215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301492PMC
July 2022

Characterization of the complete chloroplast genome of orchid family species .

Mitochondrial DNA B Resour 2022 18;7(7):1310-1312. Epub 2022 Jul 18.

College of Life Sciences, Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an, China.

The genus is well known as the lady's slipper orchid in Orchidaceae family (Rchb.f.) Stein 1892, has important medicinal and ornamental value, which occurs in the tropical Asia. However, in recent decades, it was threatened with extinction by significantly reduced small population size. In this study, we sequenced and characterized the complete chloroplast genome of based on the Illumina Hiseq platform. The size of chloroplast genome was 156,567 bp, including a large single-copy (LSC) region of 88,243 bp, a small single-copy (SSC) region of 3652 bp, and two inverted repeat regions (IRs) of 32,336 bp. The overall GC contents of the chloroplast genome were 35.71%. A total of 122 genes were annotated, including 76 protein-coding genes, 38 transfer RNAs (tRNAs), and eight ribosomal RNAs (rRNAs). The phylogenetic analysis indicated that formed a close relationship with another species . The results will provide helpful genetic resource for further phylogenetic studies of the genus .
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http://dx.doi.org/10.1080/23802359.2022.2096417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297714PMC
July 2022

Genomic Characterization of CIAV Detected in Contaminated Attenuated NDV Vaccine: Epidemiological Evidence of Source and Vertical Transmission From SPF Chicken Embryos in China.

Front Vet Sci 2022 6;9:930887. Epub 2022 Jul 6.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an, China.

Live attenuated vaccines have been extensively used to prevent infectious disease in poultry flocks. Freedom from exogenous virus is a high priority for any veterinary vaccines. Recently, attenuated Newcastle disease virus (NDV) vaccines were detected to be contaminated with chicken infectious anemia virus (CIAV) in a routine screening for exogenous viruses. To investigate the possible source of the contamination, we conducted virological tests on a specific-pathogen-free (SPF) layer breeder flock that provide the raw materials for vaccines in this manufacturer. Firstly, CIAV antibodies in serum and egg yolks samples of the SPF laying hens were detected by ELISA assays. The results showed that CIAV antibodies in serum and egg yolks were 62% positive and 57% positive, respectively. Then, DNA was extracted from the NDV vaccines and SPF chicken embryonated eggs, and detected by molecular virology assays. The results showed that three assays for pathogens in embryonated eggs had similar positive rates (35.8%). And the sequences of CIAV from SPF embryos and NDV vaccines consisted of 2,298 nucleotides (nt) with 100% homology. The new full-length genome of CIAV was designated SDSPF2020 (Genbank accession number: MW660821). Data showed SDSPF2020 had the sequence similarities of 95.8-99.6% with reference strains, and shared the highest homology with the Chinese strain HLJ15125. These results strongly suggested that exogenous CIAV contamination is most likely caused by wild virus infection in SPF flocks and vertical transmission to chicken embryos. Collectively, this study illustrated that vertical transmission of CIAV from a SPF layer breeder flock to embryos was a non-neglible way for exogenous virus contamination in vaccine production.
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http://dx.doi.org/10.3389/fvets.2022.930887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298830PMC
July 2022

Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis.

Front Genet 2022 7;13:856692. Epub 2022 Jul 7.

Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Increasing studies have revealed significant associations between with oncogenesis and prognosis of human cancers; however, pan-cancer analysis has not been reported. Here, we explored the potential carcinogenic function and the association with clinical outcomes of in 33 different human cancers. The results showed that was amplified in 31 investigated cancers; expression was significantly associated with metastasis of six different cancers and significantly associated with the survival of patients in ten different cancers; TOP2A-encoded protein was obviously upregulated in five available cancers; phosphorylated TOP2A protein at S1106 was significantly upregulated in all six available cancers. Moreover, expression was found to be associated with the cancer-associated immune cell infiltration, including fibroblasts, Tregs, and macrophages. In addition, the Kyoto encyclopedia of genes and genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses revealed a most significant association between with the Wnt signaling pathway and DNA conformation change. This work provides a comprehensive knowledge of in different cancers, including carcinogenic function, prognostic values for metastasis, and clinical outcomes.
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http://dx.doi.org/10.3389/fgene.2022.856692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301266PMC
July 2022

Effects of composite environmental materials on the passivation and biochemical effectiveness of Pb and Cd in soil: Analyses at the ex-planta of the Pak-choi root and leave.

Environ Pollut 2022 Jul 20;309:119812. Epub 2022 Jul 20.

School of Chemical and Environmental Engineering, China University of Mining and Technology-Beijing, Beijing, 100083, China. Electronic address:

Passivation of soil heavy metals using environmental materials is an important method or important in situ remediation measure. There are more studies on inorganic environmental materials for heavy metal passivation, but not enough studies on organic and their composite environmental materials with inorganic ones. In order to reveal the passivation effect of coal-based ammoniated humic acid (CAHA), biochemical humic acid (BHA), biochar (BC) and other organic types and inorganic environmental materials such as zeolites (ZL) on soil heavy metals and their biological effectiveness. The microstructures of these materials were analyzed by Scanning electron microscope (SEM). The main components of the environmental materials were analyzed by Energy dispersive spectrometer (EDS), Fourier transforms infrared spectroscopy (FT-IR) and X-ray diffraction spectrum (XRD) to elucidate the mechanism of passivation of heavy metals in soil by these environmental materials. The study was conducted to investigate the effects of different types of environmental materials and their combinations on the passivation effect and biological effectiveness of Pb and Cd complex contamination in soil by means of soil incubation and pot experiments using single-factor and multifactor multilevel orthogonal experimental designs. Soil incubation experiments proved that the effective state of soil Pb and Cd in T was reduced by 13.40% and 11.07%, respectively. The extreme difference analysis determined the optimized formulation of soil lead and cadmium passivation as BHA: CAHA: BC: ZL = 3.5:5:20:10. The pot experiment proved that the application of composite environmental materials led to the reduction of lead and cadmium content and increase of biomass of Pak-choi, and the optimal dosage of optimized composite environmental materials was 23.1 g/kg.
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http://dx.doi.org/10.1016/j.envpol.2022.119812DOI Listing
July 2022

Development and validation of a meta-learning-based multi-modal deep learning algorithm for detection of peritoneal metastasis.

Int J Comput Assist Radiol Surg 2022 Jul 22. Epub 2022 Jul 22.

Institute of Information Science and Electronic Engineering, Zhejiang University, Yuquan Campus, Hangzhou, Zhejiang, China.

Purpose: The existing medical imaging tools have a detection accuracy of 97% for peritoneal metastasis(PM) bigger than 0.5 cm, but only 29% for that smaller than 0.5 cm, the early detection of PM is still a difficult problem. This study is aiming at constructing a deep convolution neural network classifier based on meta-learning to predict PM.

Method: Peritoneal metastases are delineated on enhanced CT. The model is trained based on meta-learning, and features are extracted using multi-modal deep Convolutional Neural Network(CNN) with enhanced CT to classify PM. Besides, we evaluate the performance on the test dataset, and compare it with other PM prediction algorithm.

Results: The training datasets are consisted of 9574 images from 43 patients with PM and 67 patients without PM. The testing datasets are consisted of 1834 images from 21 testing patients. To increase the accuracy of the prediction, we combine the multi-modal inputs of plain scan phase, portal venous phase and arterial phase to build a meta-learning-based multi-modal PM predictor. The classifier shows an accuracy of 87.5% with Area Under Curve(AUC) of 0.877, sensitivity of 73.4%, specificity of 95.2% on the testing datasets. The performance is superior to routine PM classify based on logistic regression (AUC: 0.795), a deep learning method named ResNet3D (AUC: 0.827), and a domain generalization (DG) method named MADDG (AUC: 0.834).

Conclusions: we proposed a novel training strategy based on meta-learning to improve the model's robustness to "unseen" samples. The experiments shows that our meta-learning-based multi-modal PM predicting classifier obtain more competitive results in synchronous PM prediction compared to existing algorithms and the model's improvements of generalization ability even with limited data.
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http://dx.doi.org/10.1007/s11548-022-02698-wDOI Listing
July 2022

Membranous and nuclear staining of CLDN18 in HPV-independent and HPV-associated endocervical adenocarcinomas.

Cancer Med 2022 Jul 21. Epub 2022 Jul 21.

Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Objectives: A classification system for endocervical adenocarcinoma (ECA) based on high-risk human papillomavirus (HPV) status has been established; however, the immunohistochemical markers distinguishing HPV-independent and HPV-associated ECAs have not been fully described. Here, we aimed to characterize ECA immunopathological features.

Methods: We evaluated the immunohistochemical profile of CLDN18, CDX2, PAX8, p16, p53, and CEA in 60 ECAs comprising 10 HPV-independent ECAs and 50 HPV-associated ECAs. Both the membranous and nuclear expression levels of CLDN18 were analyzed.

Results: Membranous CLDN18 (CLDN18 [M]) was found to be expressed in the mucinous epithelium of all HPV-independent ECAs, including eight gastric-type ECAs (G-ECAs), one endometrioid ECA, and one clear cell ECA, but no nuclear CLDN18 (CLDN18 [N]) expression was detected in HPV-independent ECAs. Among HPV-associated ECAs, CLDN18 (M) expression levels in intestinal-type (I-ECAs) and usual-type ECAs (U-ECAs) were significantly different from those in invasive stratified mucin-producing (iSMILE) carcinomas (p = 0.036). Positive CLDN18 (M) staining was present in 55.6% (5/9) of intestinal-type and 39.4% (13/33) of usual-type ECAs and was not present in iSMILE ECAs. Silva pattern C cancers expressed higher levels of CLDN18 (M) than Silva pattern A and B cancers (p = 0.004), whereas the CLDN18 (N) expression levels in cancers showing Silva pattern A were significantly higher than those in cancers exhibiting Silva patterns B and C (p < 0.001).

Conclusion: Membranous CLDN18 is expressed in ECAs and is particularly frequently expressed in HPV-independent ECAs, and membranous CLDN18 expression has potential as a therapeutic target. Nuclear staining of CLDN18 is a new immunohistochemical marker for diagnosing Silva pattern A HPV-associated ECAs and is associated with a good prognosis. Further studies should investigate the therapeutic and prognostic significance of membranous and nuclear CLDN18 expression and develop a related test that can be implemented in the clinical evaluation of ECAs.
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http://dx.doi.org/10.1002/cam4.5029DOI Listing
July 2022

Discovery of Novel Pyrazolopyrimidines as Potent, Selective, and Orally Bioavailable Inhibitors of ALK2.

ACS Med Chem Lett 2022 Jul 22;13(7):1159-1164. Epub 2022 Jun 22.

Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States.

Activin receptor-like kinase 2 (ALK2) is a transmembrane kinase receptor that mediates the signaling of the members of the TGF-β superfamily. The aberrant activation of ALK2 has been linked to the rare genetic disorder fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG) that are associated with severely reduced life expectancy in pediatric patients. ALK2 has also been shown to play an essential role in iron metabolism by regulating hepcidin levels and affecting anemia of chronic disease. Thus, selective inhibition of ALK2 has emerged as a promising strategy for the treatment of multiple disorders. Herein, we report the discovery of a novel pyrazolopyrimidines series as highly potent, selective, and orally bioavailable inhibitors of ALK2. Structure-based drug design and systematic structure-activity relationship studies were employed to identify potent inhibitors displaying high selectivity against other ALK subtypes with good pharmacokinetic profiles.
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http://dx.doi.org/10.1021/acsmedchemlett.2c00206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290007PMC
July 2022

Chiral resolution of racemic phenylpropanoids with tyrosinase inhibitory activities from the fruits of Crataegus pinnatifida Bge.

J Food Biochem 2022 Jul 19:e14304. Epub 2022 Jul 19.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Shenyang Pharmaceutical University, Shenyang, China.

Seven pairs of enantiomeric phenylpropanoids (1a/1b-7a/7b), including eight undescribed phenylpropanoids (1a, 2a/2b, 3a, 5a, 6a/6b, and 7b) were found in the fruits of Crataegus pinnatifida Bge. The enantiomers were separated using chiral column and elucidated through various spectroscopic methods and quantum chemical ECD calculations. The tyrosinase inhibitory activity of enantiomers was tested in vitro. Among them, enantiomers 1a/1b displayed moderate tyrosinase inhibitory activities. The interaction patterns were further studied by molecular docking, and the results indicated compounds 1a/1b may bind in the active site near the copper atom and interacted with the hydrophobic areas in the active pocket. PRACTICAL APPLICATIONS: Melanins exist widely in organisms and will be produced more against environmental stresses. Without th enzymatic action of tyrosinase, melanin biosynthesis would be blocked. Thus, tyrosinase inhibitors have been developed to modulate melanin formation. In this study, the enantiomeric phenylpropanoid isolated from the fruits of C. pinnatifida Bge displayed moderate tyrosinase inhibitory activities. This work may provide foundations for further research on tyrosinase inhibitor from natural sources.
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http://dx.doi.org/10.1111/jfbc.14304DOI Listing
July 2022
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