Publications by authors named "Jingjing Sun"

260 Publications

Study on the formation mechanism of isoniazid crystal defects and defect elimination strategy based on ultrasound.

Ultrason Sonochem 2021 Jul 19;77:105674. Epub 2021 Jul 19.

School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300072, People's Republic of China; The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin 300072, People's Republic of China; Chemistry and Chemical Engineering Guangdong Laboratory, Shantou 515031, People's Republic of China.

In crystallization, crystal growth defects may reduce the strength and purity of crystals, which are not welcomed in the industry. Herein, isoniazid (INH) crystals were chosen as an example to investigate the formation of crystal defects at the molecular scale by combining experiments and molecular dynamics simulations. It was found that the strong interaction between the solvent and the crystal surface, high temperature, small stirring rate, and low supersaturation can lead to more pronounced crystal defects. The bulk severity of INH crystal defects was reflected by N adsorption-desorption measurement. Besides, the single-crystal growth experiments manifested the rough growth mechanism for the (110) surface in the axial direction and the stepwise growth mechanism for the (002) surface in the radial direction. For the (110) surface, cavities occurred under the condition where the growth rate of the crystal edges and corners was greater than that of the surface center due to the starvation phenomenon of diffusion. While for the (002) surface, when the solvent removal rate was lower than the solute insertion rate, liquid inclusions were formed, which was verified by Raman microscopy. Furthermore, the ultrasonic strategy was successfully proposed to eliminate INH crystal defects and prepare perfect INH crystals. Moreover, the mechanism of ultrasound to reduce the crystal defect was proposed. We believe this work can provide insights into the design and preparation of defect-free crystals in crystallization.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105674DOI Listing
July 2021

Knockdown of GPSM1 Inhibits the Proliferation and Promotes the Apoptosis of B-Cell Acute Lymphoblastic Leukemia Cells by Suppressing the ADCY6-RAPGEF3-JNK Signaling Pathway.

Pathol Oncol Res 2021 7;27:643376. Epub 2021 Apr 7.

Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of Education, China Medical University, Shenyang, China.

B-cell acute lymphoblastic leukemia (B-ALL) is the common type of blood cancer. Although the remission rate has increased, the current treatment options for B-ALL are usually related to adverse reactions and recurrence, so it is necessary to find other treatment options. G protein signaling modulator 1 (GPSM1) is one of several factors that affect the basic activity of the G protein signaling system, but its role in B-ALL has not yet been clarified. In this study, we analyzed the expression of GPSM1 in the Oncomine database and found that the GPSM1 levels were higher in B-ALL cells than in peripheral blood mononuclear cells (PBMCs). Analyses of the Gene Expression Profiling Interactive Analysis (GEPIA) demonstrated that patients with high GPSM1 levels had shorter survival times than those with low levels. Additionally, gene set enrichment analysis (GSEA) suggested that GPSM1 was positively correlated with proliferation, G protein-coupled receptor (GPCR) ligand binding, Gαs signaling and calcium signaling pathways. In further experiments, GPSM1 was found to be highly expressed in Acute lymphoblastic leukemia (ALL) cell lines, and downregulation of GPSM1 inhibited proliferation and promoted cell cycle arrest and apoptosis in BALL-1 and Reh cells. Moreover, knockdown of GPSM1 suppressed ADCY6 and RAPGEF3 expression in BALL-1 and Reh cells. Furthermore, we reported that GPSM1 regulated JNK expression via ADCY6-RAPGEF3. The present study demonstrates that GPSM1 promotes tumor growth in BALL-1 and Reh cells by modulating ADCY6-RAPGEF3-JNK signaling.
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http://dx.doi.org/10.3389/pore.2021.643376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262160PMC
April 2021

Two novel variants in PLOD1 causing hydrocephalus in female newborn with kyphoscoliotic Ehlers-Danlos syndrome.

Eur J Med Genet 2021 Jun 20;64(9):104269. Epub 2021 Jun 20.

Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

The kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is a rare autosomal recessive connective tissue disorder characterized by hyperextensible skin and joints, kyphoscoliosis, and severe muscle hypotonia at birth. Causal variants have been identified in PLOD1 resulting in lysyl hydroxylase deficiency responsible for kEDS. However, the detailed phenotype of kEDS during the perinatal period is still poorly recognized. Here, we describe a case of a female newborn presenting with prenatal hydrocephalus and severe hypotonia after birth with two novel compound heterozygous variants, c.2T > C (p.?) and c.1462del (p. Arg488Glyfs*9) in the PLOD1 gene. Our case suggests that in addition to the reported phenotype during the neonatal period, prenatal hydrocephalus should also be differentially diagnosed to exclude the potential of kEDS.
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http://dx.doi.org/10.1016/j.ejmg.2021.104269DOI Listing
June 2021

Carcinoma ex pleomorphic adenoma of major salivary glands: CT and MR imaging findings.

Dentomaxillofac Radiol 2021 Jun 23:20200485. Epub 2021 Jun 23.

Department of radiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.

Objectives: To describe the CT and MR imaging characteristics of primary carcinoma ex pleomorphic adenoma (Ca-ex-PA) in major salivary glands and present more information for recognizing this malignancy.

Methods: 212 patients with primary Ca-ex-PA in major salivary glands (169 in the parotid gland, 36 in the submandibular gland, 7 in the sublingual gland) underwent CT and MR imaging (plain and contrast-enhanced scans) prior to surgical management and histopathological examination. The CT and MR imaging findings of this condition were retrospectively reviewed and correlated with their pathological types: non-invasive carcinoma (Type I, 37 cases), minimally invasive carcinoma (Type II, 18 cases), and widely invasive carcinoma (TypeIII, 157 cases). The binary logistic regression analysis was used to analyze the independent influencing factors of morphology and boundary for differentiating between Type I/II and Type III of Ca-ex-PA, and the sensitivity, specificity and positive predictive value were calculated. Differences in apparent diffusion coefficient (ADC) values between Type I/II and Type III of Ca-ex-PA were calculated by independent sample -tests.

Results: On CT and MR imaging, there were 190/212 cases (89.6%) identified as lobular, 203/212 cases (95.8%) with enhancement, and 173/212 cases (81.6%) with inhomogeneous after contrast administration.Calcification within the mass was shown in 76 of 192 cases (39.6%) on plain CT examination. Of 55 neoplasms with Type I and II, 38 (69.1%) were presented as round or oval and 42 (76.4%) as well-defined margins. Of 157 neoplasms with Type III, 103 (65.6%) were presented as irregular form and 110 (70.1%) as uneven margins or with partial uneven margins.The sensitivity, specificity and positive predictive value for distinguishing Type I/II and Type III tumors according to the morphology and boundary were 78.34%, 63.64% and 86.01%, respectively. The mean ADC value of Ca-ex-PA (22 cases) in major salivary glands was about 0.93 × 10 mm s, and there was no significant difference in mean ADC value between Type I/II and Type III of this neoplasm. Cervical lymph node metastasis and distance metastasis were found in 67 patients (31.6%, Type III) and 32 patients (15.1%, Type I in 1; Type II in 1; and Type III in 30), respectively.

Conclusions: Most Ca-ex-PA is characterized by an irregular, lobular, and inhomogeneous enhanced neoplasm with uneven margin or partial uneven margin on CT and MR imaging, which is frequently corresponding with Type III. And a round or oval mass with well-defined margin usually correlates with Type I and II. Morphology and boundary are important basis for distinguishing Type I/II and Type III tumors. Calcification within the neoplasm shown on CT may be regarded as a specific sign for indicating this malignancy. Low ADC value is an important manifestation of this neoplasm.Ca-ex-PA with Type III is more likely to have cervical lymph node metastasis and distant metastasis.
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http://dx.doi.org/10.1259/dmfr.20200485DOI Listing
June 2021

Heterologous Expression of Cyclodextrin Glycosyltransferase 20 in and Its Application in 2--α-D-Glucopyranosyl-L-Ascorbic Acid Production.

Front Microbiol 2021 28;12:664339. Epub 2021 May 28.

Key Laboratory of Sustainable Development of Polar Fishery, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China.

In this study, the cgt gene 20, which encodes cyclodextrin glycosyltransferase (CGTase) and was obtained by the metagenome sequencing of marine microorganisms from the Mariana Trench, was codon optimized and connected to pET-24a for heterologous expression in BL21(DE3). Through shaking flask fermentation, the optimized condition for recombinant CGTase expression was identified as 20°C for 18 h with 0.4 mM of isopropyl β-D-L-thiogalactopyranoside. The recombinant CGTase was purified by Ni-NTA resin, and the optimum pH and temperature were identified as pH 7 and 80°C, respectively. Activity was stable over wide temperature and pH ranges. After purification by Ni-NTA resin, the specific activity of the CGTase was 63.3 U/mg after 67.3-fold purification, with a final yield of 43.7%. In addition, the enzyme was used to transform L-ascorbic acid into 2--α-D-glucopyranosyl-L-ascorbic acid (AA-2G). The maximal AA-2G production reached 28 g/L, at 40°C, pH 4, 24 h reaction time, 50 g/L donor concentration, and 50 U/g enzyme dosage. The superior properties of recombinant CGTase strongly facilitate the industrial production of AA-2G.
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http://dx.doi.org/10.3389/fmicb.2021.664339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195388PMC
May 2021

Mn as the "spearhead" preventing the trap of Zn in layered Mn inserted hydrated vanadium pentoxide enables high rate capacity.

J Colloid Interface Sci 2021 May 30;602:14-22. Epub 2021 May 30.

State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China. Electronic address:

Vanadium oxides attract much attention and are concerned as one of the most promising cathodes for aqueous zinc-ion batteries (AZIBs) owing to the layered structures. However, their intensive development is limited by the fragile structures and laggard ion-transferring. Herein, Mn inserted hydrated vanadium pentoxide nanobelts/reduced graphene oxide (MnVO·nHO/rGO, abbreviated as MnVOH/rGO) was prepared by a simple one-pot hydrothermal process, delivering excellent electrochemical properties for AZIBs. The Zn//MnVOH/rGO cell operates well even at changing current densities over 45 cycles, behaving 361 mAh·g at 0.1 A·g, 323 mAh·g as the current density gradually increasing to 2 A·g and 350 mAh·g when gradually back to 0.1 A·g (∼97% of initial capacity). Such a superb cycling and rate performance is ascribed to the unique stable structure with the compact electrostatic attraction between Mn and VO·nHO (VOH) laminate. On the one hand, Mn generates electrostatic network with [VO] polyhedrons and suppresses the following electrostatic trap for the moving Zn. On the other hand, rGO improves the conductivity, endowing the high capacity and energy density. The performance of the MnVOH/rGO cathode exceeds most of vanadium-based cathodes applying in AZIBs and paves the way to the ideal energy storage system.
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http://dx.doi.org/10.1016/j.jcis.2021.05.163DOI Listing
May 2021

Mechanisms of the Effects of Parental Emotional Warmth on Extraversion in Children and Adolescents.

Neuroscience 2021 07 24;467:134-141. Epub 2021 May 24.

Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China; Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China; MDT Center for Cognitive Impairment and Sleep Disorders, First Hospital of Shanxi Medical University, Taiyuan, China. Electronic address:

The purpose of this study is to probe into the influence mechanism of parental emotional warmth (PEW) on extraversion for children and adolescents, as well as the moderating and mediating role of brain functional activity. Thirty-two children and adolescents underwent functional magnetic resonance imaging (fMRI) scans and completed Egna Minnen av Barndoms Uppfostran (EMBU) and Eysenck Personality Questionnaire (EPQ). Small-worldness (SW) of brain networks, fractional amplitude of low-frequency fluctuations (fALFF), and region-of-interest to region-of-interest (ROI-ROI) functional connectivity were calculated to study intrinsic neuronal activity. We found that PEW had a positive direct effect on extraversion, and all participants in the current study showed an efficient small-world structure. The positive association between PEW and extraversion was mediated by SW. Furthermore, the fALFF and extraversion were significantly and negatively correlated in the right precuneus and dorsolateral superior frontal gyrus. The mediating effect of SW was moderated by the functional connectivity between the right precuneus and the right dorsolateral superior frontal gyrus. The indirect effect was significant with lower level of the functional connectivity between the right precuneus and the right dorsolateral superior frontal gyrus. These findings indicate that SW of brain networks may be a key factor that accounts for the positive association between PEW and extraversion in children and adolescents and the level of the functional connectivity between the right precuneus and the right dorsolateral superior frontal gyrus could moderate the relationship.
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http://dx.doi.org/10.1016/j.neuroscience.2021.05.021DOI Listing
July 2021

Preoperative Assessment for Event-Free Survival With Hepatoblastoma in Pediatric Patients by Developing a CT-Based Radiomics Model.

Front Oncol 2021 16;11:644994. Epub 2021 Apr 16.

West China Second University Hospital, Sichuan University, Chengdu, China.

To explore a CT-based radiomics model for preoperative prediction of event-free survival (EFS) in patients with hepatoblastoma and to compare its performance with that of a clinicopathologic model. Eighty-eight patients with histologically confirmed hepatoblastoma (mean age: 2.28 ± 2.72 years) were recruited from two institutions between 2002 and 2019 for this retrospective study. They were divided into a training cohort (65 patients from institution A) and a validation cohort (23 patients from institution B). Radiomics features were extracted manually from pretreatment CT images in the portal venous (PV) phase. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied to construct a "radiomics signature" and radiomics score (Rad-score) for EFS prediction. Then, a nomogram incorporating the Rad-score, updated staging system, and significant variables of clinicopathologic risk (age, alpha-fetoprotein (AFP) level, histology subtype, tumor diameter) as the radiomic model, clinicopathologic model, and combined clinicopathologic-radiomic model were built for EFS estimation in the training cohort, the performance of which was assessed in an external-validation cohort with respect to clinical usefulness, discrimination, and calibration. Nine survival-relevant features were selected for a radiomics signature and Rad-score building. Multivariable analysis revealed that histology subtype ( = 0.01), PV ( = 0.001) invasion, and metastasis ( = 0.047) were independent risk factors of EFS. Patients were divided into low- and high-risk groups based on the Rad-score with a cutoff of 0.08 according to survival outcome. The radiomics signature-incorporated nomogram showed good performance ( < 0.001) for EFS estimation (C-Index: 0.810; 95% CI: 0.738-0.882), which was comparable with that of the clinicopathological model for EFS estimation (C-Index: 0.81 vs. 0.85). The radiomics-based nomogram failed to show incremental prognostic value compared with that using the clinicopathologic model. The combined model (radiomics signature plus clinicopathologic parameters) showed significant improvement in the discriminatory accuracy, along with good calibration and greater net clinical benefit, of EFS (C-Index: 0.88; 95% CI: 0.829-0.933). The radiomics signature can be used as a prognostic indicator for EFS in patients with hepatoblastoma. A combination of the radiomics signature and clinicopathologic risk factors showed better performance in terms of EFS prediction in patients with hepatoblastoma, which enabled precise clinical decision-making.
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http://dx.doi.org/10.3389/fonc.2021.644994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086552PMC
April 2021

Nine cases of soft tissue keratocysts arising from buccal mucosa and lateral fascial deep region: Clinicopathological and immunohistochemical study.

Indian J Pathol Microbiol 2021 Apr-Jun;64(2):339-342

Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Centre of Stomatology, China.

Background: Soft tissue keratocysts (SKC) are extremely rare and show similar microscopic morphology to keratocystic odontogenic tumor. The aim was to investigate immunohistochemical (IHC) features and origin of SKCs developing in buccal mucosa and lateral facial deep region.

Material And Methods: Expression of CK19, CK10/13, Ki67, Cyclin D1 and Osteopontin (OPN) of 9 SKCS were investigated using IHC. Forty different types of cysts in jaw/soft tissue were used as control. Follow-up was performed.

Results: CK10/13 positivity occurred more frequently and intensely in SKC and intraosseous parakeratinized odontogenic keratocysts (COKC). However, OPN positivity was observed only in COKC.

Conclusion: This is the largest case series of SKCs; along with first attempt to investigate the expression of OPN on SKC. Given the microscopic and immunohistochemical features, we prefer the view that SKC is odontogenic origin but represents the soft tissue counterpart of COKC, since their expressions of OPN were extremely different.
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http://dx.doi.org/10.4103/IJPM.IJPM_423_20DOI Listing
April 2021

Establishment of patient-derived xenograft models of adenoid cystic carcinoma to assess pre-clinical efficacy of combination therapy of a PI3K inhibitor and retinoic acid.

Am J Cancer Res 2021 1;11(3):773-792. Epub 2021 Mar 1.

Department of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine Shanghai 200011, P. R. China.

Due to the difficulties and long periods of establishment, preclinical animal models of adenoid cystic carcinoma (ACC) are scarce but imperative. The researches involving molecular features and therapeutic targets of ACC require an integrated group of preclinical animal models which can credibly retain the heterogeneity of this tumor. Currently chemotherapies and targeting therapies have modest efficacy in ACC and the overall response rate is rather low. Therefore, novel therapeutic regimen of ACC is urgently needed and remains a major clinical challenge. We transplanted a group of tumor samples from human salivary ACC into immunodeficient mice to establish patient-derived xenografts (PDXs). Patient tumors and their matched PDXs were conducted histological analyses, whole-exome sequencing (WES) and RNA-seq respectively. 13 PDXs were successfully established from 34 ACC, involved in 3 histological types, including cribriform, tubular, and solid. These ACC PDXs generally reflected the histopathological and molecular features of their corresponding original tumors. MYB/MYBL1-NFIB fusion (53.85%) and high-frequency mutation genes, such as KDM6A, KMT2C, KMT2D, NOTCH1, NOTCH2, SMARCA4 and PIK3CA were mainly conserved in PDXs. Guided by the genetic alterations, the efficiencies of retinoic acid (RA) and a PI3K inhibitor were evaluated in ACC PDX models harboring both MYB fusion and PIK3CA amplification/mutation. Combination treatment of the PI3K inhibitor and RA demonstrated remarkable inhibition of tumors in PDXs harboring both PIK3CA mutation/amplification and MYB-NFIB fusion gene in vivo and in vitro. In this study, we displayed the morphologically and genetic featured PDXs which recapitulated the heterogeneity of original ACC tumors, indicating that the models could be used as a platform for drug screening for therapy response. The feasibility of combination treatment approaches for dual targets were confirmed, providing new regimens for personalized therapies in ACC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994170PMC
March 2021

Primary immunodeficiency-related genes in neonatal intensive care unit patients with various genetic immune abnormalities: a multicentre study in China.

Clin Transl Immunology 2021 22;10(3):e1266. Epub 2021 Mar 22.

Department of Neonatology Xinhua Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.

Objectives: The present phenotype-based disease classification causes ambiguity in diagnosing and determining timely, effective treatment options for primary immunodeficiency (PID). In this study, we aimed to examine the characteristics of early-onset PID and proposed a JAK-STATopathy subgroup based on their molecular defects.

Methods: We reviewed 72 patients (< 100 days) retrospectively. These patients exhibited various immune-related phenotypes and received a definitive molecular diagnosis by next-generation sequencing (NGS)-based tests. We evaluated the PID-causing genes and clinical parameters. We assessed the genes that shared the JAK-STAT signalling pathway. We also examined the potential high risks related to the 180-day death rate.

Results: We identified PID disorders in 25 patients (34.72%, 25/72). The 180-day mortality was 26.39% (19/72). Early onset of disease (cut-off value of 3.5 days of age) was associated with a high 180-day death rate ( = 0.009). Combined immunodeficiency with associated or syndromic features comprised the most common PID class (60.00%, 15/25). Patients who presented life-threatening infections were most likely to exhibit PID (odds ratio [OR] = 2.864; 95% confidence interval [CI]: 1.047-7.836). Twelve out of 72 patients shared JAK-STAT pathway defects. Seven JAK-STATopathy patients were categorised as PID. They were admitted to NICUs as immunological emergencies. Most of them experienced severe infections and thrombocytopenia, with 4 succumbing to an early death.

Conclusions: This study confirmed that NGS can be utilised as an aetiological diagnostic method of complex immune-related conditions in early life. Through the classification of PID as pathway-based subtypes, we see an opportunity to dissect the heterogeneity and to direct targeted therapies.
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http://dx.doi.org/10.1002/cti2.1266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984964PMC
March 2021

Clinicopathological aspects of primary mucosa-associated lymphoid tissue lymphoma of the salivary gland: A retrospective single-center analysis of 72 cases.

J Oral Pathol Med 2021 Mar 17. Epub 2021 Mar 17.

Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Department of Oral Pathology, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Ninth People's Hospital, Shanghai, China.

Background: Salivary gland extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) is uncommon and has not been studied extensively. We aimed to investigate the features of clinicopathological and molecular changes of salivary MALT lymphoma.

Methods: Seventy-two cases of primary salivary MALT lymphoma that had clinicopathological information available were utilized in this study. MALT1 gene translocation, trisomy 3, and trisomy 18 were detected by interphase fluorescence in situ hybridization (FISH). The data were analyzed using SPSS 17.0 software package.

Results: The ratio of male to female was 1:2.8, and the median age was 57.0 years. 12.5% (9/72) of the patients presented with multiple swellings. Among the others with solitary mass, the parotid gland was involved most frequently (47/63,74.6%), followed by the palate (7/63, 11.1%). 34.7% of patients had an autoimmune disease, with Sjögren syndrome (SS) being the most common. Among the 70 cases successfully performed, it was identified that trisomy 3 was the most frequent molecular change (41/70, 58.6%), followed by trisomy 18 (7/70, 10%) and MALT1 translocation (5/70, 7.1%). The tumor tissue tended to exhibit trisomy 3 in patients without SS (p = 0.038). The 5-year overall survival was 94.1%, and the 5-year disease-free survival was 85.3% (mean follow-up time: 104.7 months). The patients without SS and trisomy 18 had a prolonged recurrence-free survival (p = 0.015, p = 0.001 respectively).

Conclusion: Salivary gland MALT lymphoma is associated with autoimmune diseases, and trisomy 3 is the most common genetic change. Trisomy 18 can be used to predict the possibility of tumor relapse.
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http://dx.doi.org/10.1111/jop.13168DOI Listing
March 2021

A Chinese newborn with Zellweger syndrome and compound heterozygous mutations novel in the gene: a case report and literature review.

Transl Pediatr 2021 Feb;10(2):446-453

Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.

In this study, we report a male newborn with severe Zellweger spectrum disorder (ZSDs) presenting asphyxia, hypotonia, poor feeding, and dysmorphic facial features. Despite intensive supportive treatment, the boy's condition deteriorated progressively. The patient's diagnosis was made by delayed results after his death. His genetic analysis showed that the boy carried novel compound heterozygous mutation in gene (c.2050C > T and c.782_783del). We conducted a literature search and identified 316 patients with ZSD caused by mutations in the gene. The p.G843D and p.I700Yfs*42 were the most commonly reported mutations. Among the 316 patients, clinical manifestations were available in 265 patients. The segregation of these patients' manifestation showed that patients with missense mutations have a milder phenotype than those with truncating mutations, while the common p.G843D mutations are milder than other missense mutations. Nearly all truncating mutations in except for those with premature stop codons near the end of the gene were associated with a severe disease phenotype. These results indicated that all domains of were important in the maintenance of normal peroxisome function. The correlation between severity of the disease and type of mutations in can be helpful in predicting prognosis among patients with ZSD caused by mutated .
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http://dx.doi.org/10.21037/tp-20-167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944177PMC
February 2021

Phytochrome-interacting factors interact with transcription factor CONSTANS to suppress flowering in rose.

Plant Physiol 2021 Mar 8. Epub 2021 Mar 8.

College of Horticulture, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.

As day-neutral woody perennial plants, the flowering time of roses (Rosa spp.) is assumed to be independent of the photoperiodic conditions; however, light responses of rose plants are not well understood. Chinese rose (Rosa chinensis) plants were grown under two light intensities (low light (LL), 92 μmol·m-2·s-1; or high light (HL), 278 μmol·m-2·s-1), and either with or without an end-of-day far-red (EOD-FR) treatment. Flowering was significantly delayed in the LL condition compared with the HL, but was not affected by EOD-FR treatment. The time until flowering positively corresponded with the mRNA and protein levels of Phytochrome-interacting factors (RcPIFs). The heterologous expression of RcPIF1, RcPIF3 or RcPIF4 in the Arabidopsis (Arabidopsis thaliana) pifq quadruple mutant partially rescued the mutant's shorter hypocotyl length. Simultaneous silencing of three RcPIFs in Rosa chinensis accelerated flowering under both LL and HL, with a more robust effect in LL, establishing RcPIFs as flowering suppressors in response to light intensity. The RcPIFs interacted with the transcription factor CONSTANS (RcCO) to form a RcPIFs-RcCO complex, which interfered with the binding of RcCO to the promoter of FLOWERING LOCUS T (RcFT), thereby inhibiting its expression. Furthermore, this inhibition was enhanced when RcPIFs were stabilized by LL, leading to delayed flowering under LL compared to HL. Our results not only revealed another layer of PIF functioning in the flowering of woody perennial plants, but also established a mechanism of light response in day-neutral plants.
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http://dx.doi.org/10.1093/plphys/kiab109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195524PMC
March 2021

Queuine Is a Nutritional Regulator of Entamoeba histolytica Response to Oxidative Stress and a Virulence Attenuator.

mBio 2021 03 9;12(2). Epub 2021 Mar 9.

Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

Queuosine is a naturally occurring modified ribonucleoside found in the first position of the anticodon of the transfer RNAs for Asp, Asn, His, and Tyr. Eukaryotes lack pathways to synthesize queuine, the nucleobase precursor to queuosine, and must obtain it from diet or gut microbiota. Here, we describe the effects of queuine on the physiology of the eukaryotic parasite , the causative agent of amebic dysentery. Queuine is efficiently incorporated into tRNAs by a tRNA-guanine transglycosylase (EhTGT) and this incorporation stimulates the methylation of C38 in [Formula: see text] Queuine protects the parasite against oxidative stress (OS) and antagonizes the negative effect that oxidation has on translation by inducing the expression of genes involved in the OS response, such as heat shock protein 70 (Hsp70), antioxidant enzymes, and enzymes involved in DNA repair. On the other hand, queuine impairs virulence by downregulating the expression of genes previously associated with virulence, including cysteine proteases, cytoskeletal proteins, and small GTPases. Silencing of EhTGT prevents incorporation of queuine into tRNAs and strongly impairs methylation of C38 in [Formula: see text], parasite growth, resistance to OS, and cytopathic activity. Overall, our data reveal that queuine plays a dual role in promoting OS resistance and reducing parasite virulence. is a unicellular parasite that causes amebiasis. The parasite resides in the colon and feeds on the colonic microbiota. The gut flora is implicated in the onset of symptomatic amebiasis due to alterations in the composition of bacteria. These bacteria modulate the physiology of the parasite and affect the virulence of the parasite through unknown mechanisms. Queuine, a modified nucleobase of queuosine, is exclusively produced by the gut bacteria and leads to tRNA modification at the anticodon loops of specific tRNAs. We found that queuine induces mild oxidative stress resistance in the parasite and attenuates its virulence. Our study highlights the importance of bacterially derived products in shaping the physiology of the parasite. The fact that queuine inhibits the virulence of may lead to new strategies for preventing and/or treating amebiasis by providing to the host queuine directly or via probiotics.
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http://dx.doi.org/10.1128/mBio.03549-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092309PMC
March 2021

Expanding the Toolbox for Peptide Disulfide Bond Formation l-Methionine Selenoxide Oxidation.

J Org Chem 2021 03 23;86(5):4035-4044. Epub 2021 Feb 23.

College of Chemistry and Environmental Science, Key Laboratory of Analytical Science and Technology of Hebei Province, and MOE Key Laboratory of Medicinal Chemistry and Molecular Diagnostics, Hebei University, Baoding 071002, Hebei Province, P. R. China.

In this study, l-methionine selenoxide (MetSeO) was used as an oxidant for the construction of peptide disulfide bonds. Excellent yields for various disulfide-containing peptides were achieved the MetSeO oxidation method in different solvents and on a resin. Most importantly, the construction of disulfide bonds can be performed in the trifluoroacetic acid cocktail used for the cleavage of peptides from the resin, which obviates the steps of peptide purification and lyophilization. This facilitates and simplifies the synthesis of disulfide-containing peptides. Kinetic and mechanistic studies of the reaction between MetSeO and dithiothreitol (DTT, a model compound of dicysteine-containing peptide) show that the reaction is first order in both [MetSeO] and [DTT], and a reaction mechanism is proposed that can help us gain insights into the reaction of the oxidative synthesis of disulfide bonds MetSeO oxidation.
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http://dx.doi.org/10.1021/acs.joc.0c02877DOI Listing
March 2021

The Immune Cell Landscape in Renal Allografts.

Cell Transplant 2021 Jan-Dec;30:963689721995458

Fujian Provincial Key Laboratory of Transplant Biology, Dongfang Hospital (900th Hospital of the Joint Logistics Team), Xiamen University, China.

Immune cell infiltration plays an important role in the pathophysiology of kidney grafts, but the composition of immune cells is ill-defined. Here, we aimed at evaluating the levels and composition of infiltrating immune cells in kidney grafts. We used CIBERSORT, an established algorithm, to estimate the proportions of 22 immune cell types based on gene expression profiles. We found that non-rejecting kidney grafts were characteristic with high rates of M2 macrophages and resting mast cells. The proportion of M1 macrophages and activated NK cells were increased in antibody-mediated rejection (ABMR). In T cell-mediated rejection (TCMR), a significant increase in CD8 T cell and γδT cell infiltration was observed. CD8 positive T cells were dramatically increased in mixed-ABMR/TCMR. Then, the function of ABMR and TCMR prognostic molecular biomarkers were identified. Finally, we described the gene expression of molecular markers for ABMR diagnosis was elevated and related to the ratio of monocytes and M1 macrophages in ABMR biopsies, while the expression of TCMR diagnosis markers was increased too and positively correlated with γδT cells and activated CD4 memory T cells in TCMR biopsies. Our data suggest that CIBERSORT's deconvolution analysis of gene expression data provides valuable information on the composition of immune cells in renal allografts.
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http://dx.doi.org/10.1177/0963689721995458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894583PMC
February 2021

A novel immunochemotherapy based on targeting of cyclooxygenase and induction of immunogenic cell death.

Biomaterials 2021 03 4;270:120708. Epub 2021 Feb 4.

Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, 15261, USA; University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA. Electronic address:

Cyclooxygenase (COX) plays a crucial role in the "inflammogenesis of cancer", which leads to tumor progression, metastasis, and immunotherapy resistance. Therefore, reducing "inflammogenesis" by COX inhibition may be a key perspective for cancer therapy. However, the role of tumor-derived COX in the actions of COX inhibitors remains incompletely understood. In this study, applying "old drug new tricks" to repurpose 5-aminosalicylic acid (5-ASA), a COX inhibitor, we examined the effect of 5-ASA, alone or in combination with doxorubicin (DOX), in several cancer cell lines with different levels of COX expression. To facilitate the evaluation of the combination effect on tumors in vivo, a new micellar carrier based on PEG-b-PNHS polymer-conjugated 5-ASA (PASA) was developed to enhance codelivery of 5-ASA and DOX. Folate was also introduced to the polymer (folate-PEG-NH-conjugated PASA (FASA)) to further improve delivery to tumors via targeting both tumor cells and tumor macrophages. An unprecedented high DOX loading capacity of 42.28% was achieved through various mechanisms of carrier/drug interactions. FASA was highly effective in targeting to and in inhibiting the growth of both 4T1.2 and CT26 tumors in BALB/c mice. However, FASA was more effective in CT26 tumor that has a high level of COX expression. Codelivery of DOX via PASA and FASA led to a further improvement in antitumor activity. Mechanistic studies suggest that inhibition of COX in vivo led to a more active tumor immune microenvironment. Interestingly, treatment with FASA led to upregulation of PD-1 on T cells, likely due to repressing the inhibitory effect of prostaglandin E2 (PGE) on PD-1 expression on T cells. Combination of FASA/DOX with anti-PD-1 antibody led to a drastic improvement in the overall antitumor activity including regression of some established tumors at a suboptimal dose of FASA/DOX. Our data suggest that FASA/DOX may represent a new and effective immunochemotherapy for various types of cancers, particularly those cancers with high levels of COX expression.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910750PMC
March 2021

Metformin-conjugated micellar system with intratumoral pH responsive de-shielding for co-delivery of doxorubicin and nucleic acid.

Biochem Pharmacol 2021 Jul 3;189:114453. Epub 2021 Feb 3.

Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, United States. Electronic address:

A novel PMet-P(cdmPEG) polymeric micellar carrier was developed for tumor-targeted co-delivery of DOX and nucleic acids (NA), based on polymetformin and a structure designed to lose the PEG shell in response to the acidic extracellular tumor environment. NA/DOX co-loaded micelleplexes exhibited enhanced inhibition of cell proliferation compared to DOX-loaded micelles, and displayed a higher level of cytotoxicity at an acidic pH (6.8) which mimicks the tumor microenvironment. The PMet-P(cdmPEG) micelles achieved significantly improved transfection with either a reporter plasmid or Cy3-siRNA, and enhanced DOX intracellular uptake in 4T1.2 cells at pH 6.8. Importantly, PMet-P(cdmPEG) micelles showed excellent pEGFP (EGFP expression plasmid) transfection in an aggressive murine breast cancer (4T1.2) model. By using a plasmid encoding IL-12 (pIL-12), we investigated the combined effect of chemotherapy and gene therapy. PMet-P(cdmPEG) micelles co-loaded with DOX and pIL-12 were more effective at inhibiting tumor growth compared to micelles loaded with DOX or pIL-12 alone. In addition, this micellar system was effective in co-delivery of siRNA and DOX into tumor cells. Our results suggest that PMet-P(cdmPEG) has the potential for chemo and nucleic acid combined cancer therapy.
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http://dx.doi.org/10.1016/j.bcp.2021.114453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187262PMC
July 2021

KSN heterozygosity is associated with continuous flowering of Rosa rugosa Purple branch.

Hortic Res 2021 Feb 1;8(1):26. Epub 2021 Feb 1.

College of Horticulture, Nanjing Agricultural University, Nanjing, 210095, China.

Rose (Rosa spp.) plants flower via two contrasting methods: once flowering (OF) and continuous flowering (CF). Purple branch is a rare continuously flowering variety of Rosa rugosa that is extensively cultivated in China. However, the genetic basis of its CF behavior is unknown. We demonstrated that Purple branch is heterozygous for the TFL1 homolog KSN. One KSN allele with a 9 kb Copia insertion was found to be identical to that from continuously flowering Rosa chinensis Old blush. The other allele was found to be a functional wild-type allele. The overall expression of KSN was closely linked to the floral transition, and it was significantly repressed in continuously flowering Purple branch compared with OF Plena. The promoter region of the normal KSN allele was hypermethylated, and histone methylation at H3H4, H3K9, and H3K27 of the KSN gene locus was modified in continuously flowering Purple branch. Silencing of the DNA methyltransferase genes MET1 and CMT3 and the histone methyltransferase gene SUVR5 in Purple branch led to enhanced KSN expression, but silencing of the histone demethylase gene JMJ12 suppressed KSN expression. Therefore, the CF habit of Purple branch may be due to reduced expression of KSN caused by the halved dose and may be associated with epigenetic modifications together with retrotransposon insertions along the chromosome. Our study revealed a novel mechanism underlying the CF behavior of rose plants.
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http://dx.doi.org/10.1038/s41438-021-00464-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848002PMC
February 2021

Bortezomib activation of mTORC1 pathway mediated by NOX2-drived reactive oxygen species results in apoptosis in primary dorsal root ganglion neurons.

Exp Cell Res 2021 Mar 27;400(2):112494. Epub 2021 Jan 27.

Department of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China; Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, Jiangsu, China. Electronic address:

Bortezomib (Bort), a chemotherapeutic agent, is widely used for the clinical treatment of cancers. However, Bort-induced peripheral neurotoxicity (BIPN) significantly restricts its clinical application, which is difficult to deal with since the underlying mechanisms of BIPN are unclear. Here, we showed that Bort activates mTORC1 pathway leading to dorsal root ganglion (DRG) neuronal apoptosis. Inhibition of mTORC1 with rapamycin or knockdown of raptor, regulatory-associated protein of mTORC1, with shRNA dramatically rescued the cells from Bort-caused apoptosis. In addition, we found that Bort-activated mTORC1 pathway was attributed to Bort elevation of reactive oxygen species (ROS). This is supported by the evidence that using ROS scavenger N-acetyl cysteine (NAC) significantly alleviated Bort-activated mTORC1 pathway. Furthermore, we revealed that upregulation of NOX2 contributed to Bort-elicited ROS overproduction, leading to mTORC1 pathway-dependent apoptosis in DRG neurons. Inhibition of NOX2 with apocynin remarkably diminished Bort-induced overgeneration of ROS, activation of mTORC1 pathway and apoptosis in the cells. Taken together, these results indicate that Bort activation of mTORC1 pathway mediated by NOX2-drived ROS leads to apoptotic death in DRG neurons. Our findings highlight that manipulation of intracellular ROS level or NOX2 or mTORC1 activity may be exploited for prevention of BIPN.
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http://dx.doi.org/10.1016/j.yexcr.2021.112494DOI Listing
March 2021

Prognostic relevance of SMC family gene expression in human sarcoma.

Aging (Albany NY) 2020 12 30;13(1):1473-1487. Epub 2020 Dec 30.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.

Objective: To explore the prognostic value of the expression of genes encoding structural maintenance of chromosomes (SMCs) in human sarcoma.

Results: We found that the levels of SMC1A, SMC2, SMC3, SMC4, SMC5 and SMC6 mRNA were all higher in most tumors compared to normal tissues, and especially in sarcoma. According to the Cancer Cell Line Encyclopedia (CCLE), SMC1A, SMC2, SMC3, SMC4, SMC5 and SMC6 are also highly expressed in sarcoma cell lines. Results of Gene Expression Profiling Interactive Analysis (GEPIA) indicated that high expression of SMC1A was significantly related to poor overall survival (OS) (p<0.05) and disease-free survival (DFS) in sarcoma (p<0.05). Additionally, strong expression of SMC2 was significantly related to poor OS in sarcoma (p<0.05). In contrast, SMC3, SMC4, SMC5, and SMC6 expression had no significant impact on OS or DFS in sarcoma.

Conclusions: Expression of SMC family members is significantly different in sarcoma relative to normal tissues, and SMC1A and SMC2 may be useful as prognostic biomarkers.

Methods: We performed a detailed comparison of cancer and normal tissues regarding the expression levels of mRNA for SMC family members in various cancers including sarcoma through ONCOMINE and GEPIA (Gene Expression Profile Interactive Analysis) databases.
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http://dx.doi.org/10.18632/aging.202455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835044PMC
December 2020

Time-restricted feeding attenuates gluconeogenic activity through inhibition of PGC-1α expression and activity.

Physiol Behav 2021 03 4;231:113313. Epub 2021 Jan 4.

Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, China. Electronic address:

Background: Time-restricted feeding (TRF), a key component of intermittent fasting regimens, has gained considerable attention in recent years due to reversing obesity and insulin resistance. To the best of our knowledge, here, we reported for the first time the underlying mechanistic therapeutic efficacy of TRF against hepatic gluconeogenic activity in obese mice.

Methods: The obese mice were subjected to either ad lib or TRF of a high fat diet for 8 h per day for 4 weeks. Western blotting, qRT-PCR, and plasma biochemical analyses were applied.

Results: The present findings showed that TRF regimen reduced food intake, and reversed high fat diet-induced glucose intolerance, hyperglycemia and insulin resistance in mice of high fat diet-induced obesity. Mechanistically, we confirmed that TRF regimen protected against hyperglycemia and ameliorated hepatic gluconeogenic activity through inhibition of p38 MAPK/SIRT1/PGC-1α signal pathway.

Conclusion: Our findings suggest that TRF regimen might be a potential novel nonpharmacological strategy against obesity/diabetes-induced hyperglycemia and insulin resistance.
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http://dx.doi.org/10.1016/j.physbeh.2021.113313DOI Listing
March 2021

Tumor size-dependent abscopal effect of polydopamine-coated all-in-one nanoparticles for immunochemo-photothermal therapy of early- and late-stage metastatic cancer.

Biomaterials 2021 02 26;269:120629. Epub 2020 Dec 26.

Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, 15261, USA; University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA. Electronic address:

Metastatic cancer is a persistent clinical enigma, which requires combination of several treatment modules. Here, we developed an all-in-one nanomedicine strategy to systemically co-deliver photosensitive, chemotherapeutic, and immunomodulating agents for effective immunochemo-photothermal therapy (PTT) to inhibit both primary tumor and distal metastatic tumor. Two types of polydopamine (dp)-coated nanoparticles (NPs) (N/PGEM/dp-5 and N/PGEM/dp-16) co-loaded with gemcitabine (GEM) and NLG919, a potent indoleamine-2, 3-dioxygenase (IDO) inhibitor, were prepared. N/PGEM/dp-16 NPs with a thicker dp coating layer showed higher photothermal conversion ability, more favorable biodistribution profile and better tumor inhibition effect compared to N/PGEM/dp-5 NPs with a thinner coating layer. Combination with laser irradiation further enhanced the tumor inhibition effect of N/PGEM/dp-16 NPs. In an "early metastatic" pancreatic cancer PANC02 model with small distal tumors, introduction of NLG and dp coating improved the inhibition effect on both primary and distal tumors. Compared to N/PGEM/dp-16, N/PGEM/dp-16 plus laser irradiation further enhanced the inhibition effect on primary tumor, but didn't improve the abscopal antitumor effect. When the initial volume of distal tumor was sufficiently large in a "late metastasis" model, a more dramatic abscopal antitumor effect was achieved, resulting in a significant growth inhibition of both primary tumor and the unirradiated distal tumor. Furthermore, laser irradiation can amplify the immunochemo-NPs-mediated innate and adaptive immune responses in both tumors. This work demonstrated a distal tumor-size dependent abscopal effect, and provided a perspective for future design of more effective immunochemo-PTT nano-formulations for early- and late-stage metastatic tumors.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120629DOI Listing
February 2021

Targeting nerve growth factor, a new option for treatment of osteoarthritis: a network meta-analysis of comparative efficacy and safety with traditional drugs.

Aging (Albany NY) 2020 12 3;13(1):1051-1070. Epub 2020 Dec 3.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Objective: Osteoarthritis (OA) is the most common joint disease and leading cause of pain and disability in the elderly population. Most guidelines recommend the use of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids for the non-operative treatment of OA. Monoclonal nerve growth factor (NGF) antibodies are new drugs with the potential to provide pain relief and functional improvement in OA. We compared the efficacy (pain reduction and functional improvement), and safety of monoclonal NGF antibodies with NSAIDs and opioids in the treatment of OA with a Bayesian network meta-analysis.

Results: 38 articles, comprising 41 trials and 20489 patients with OA were included. Overall from the network meta-analysis, anti-NGFs were the most effective drugs for pain relief (Standardized Mean Difference or SMD compared with placebo 4.25, 95% CI 2.87 to 5.63, Surface Under the Cumulative RAnking curve or SUCRA=93.7%) and for functional improvement (SMD 4.90, 95% CI 3.46 to 6.33, SUCRA=98.3%). Although anti-NGFs were associated with higher risk of peripheral sensation abnormality (paresthesia and pruritus), they were not associated with higher risk of other AEs (headaches and nausea) or with higher withdrawal rates related to AEs.

Conclusions: Monoclonal NGF antibodies provide significantly greater pain relief and functional improvement in OA compared to NSAIDs and opioids. Monoclonal NGF antibodies are not associated with severe AEs. More studies are needed to confirm these findings.

Methods: PubMed, CNKI, Web of Science, Scopus, Embase and Cochrane Library databases were searched for relevant studies (OA treated with anti-NGFs, opioids, selective COX-2 inhibitors or NSAIDs) published between January 1999 to January 2020. Bayesian network and conventional meta-analyses were conducted. Pain relief, functional improvement and AEs were assessed.
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http://dx.doi.org/10.18632/aging.202232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835067PMC
December 2020

Evolution of a Superhydrophobic H59 Brass Surface by Using Laser Texturing via Post Thermal Annealing.

Micromachines (Basel) 2020 Nov 29;11(12). Epub 2020 Nov 29.

College of Mechanical Engineering and Automation, Huaqiao University, Xiamen 361021, China.

To fabricate an industrial and highly efficient super-hydrophobic brass surface, annealed H59 brass samples have here been textured by using a 1064 nm wavelength nanosecond fiber laser. The effects of different laser parameters (such as laser fluence, scanning speed, and repetition frequency), on the translation to super-hydrophobic surfaces, have been of special interest to study. As a result of these studies, hydrophobic properties, with larger water contact angles (WCA), were observed to appear faster than for samples that had not been heat-treated (after an evolution time of 4 days). This wettability transition, as well as the evolution of surface texture and nanograins, were caused by thermal annealing treatments, in combination with laser texturing. At first, the H59 brass samples were annealed in a Muffle furnace at temperatures of 350 °C, 600 °C, and 800 °C. As a result of these treatments, there were rapid formations of coarse surface morphologies, containing particles of both micro/nano-level dimensions, as well as enlarged distances between the laser-induced grooves. A large number of nanograins were formed on the brass metal surfaces, onto which an increased number of exceedingly small nanoparticles were attached. This combination of fine nanoparticles, with a scattered distribution of nanograins, created a hierarchic Lotus leaf-like morphology containing both micro-and nanostructured material (i.e., micro/nanostructured material). Furthermore, the distances between the nano-clusters and the size of nano-grains were observed, analyzed, and strongly coupled to the wettability transition time. Hence, the formation and evolution of functional groups on the brass surfaces were influenced by the micro/nanostructure formations on the surfaces. As a direct consequence, the surface energies became reduced, which affected the speed of the wettability transition-which became enhanced. The micro/nanostructures on the H59 brass surfaces were analyzed by using Field Emission Scanning Electron Microscopy (FESEM). The chemical compositions of these surfaces were characterized by using an Energy Dispersive Analysis System (EDS). In addition to the wettability, the surface energy was thereby analyzed with respect to the different surface micro/nanostructures as well as to the roughness characteristics. This study has provided a facile method (with an experimental proof thereof) by which it is possible to construct textured H59 brass surfaces with tunable wetting behaviors. It is also expected that these results will effectively extend the industrial applications of brass material.
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http://dx.doi.org/10.3390/mi11121057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760971PMC
November 2020

Hydrated vanadium pentoxide/reduced graphene oxide-polyvinyl alcohol (VO⋅nHO/rGO-PVA) film as a binder-free electrode for solid-state Zn-ion batteries.

J Colloid Interface Sci 2021 Apr 24;587:845-854. Epub 2020 Nov 24.

State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China.

Recently, solid-state aqueous Zn-ion batteries (ZIBs) have become the most promising wearable storage systems to replace Li-ion batteries owing to their advantages such as high safety and environmental friendliness. However, the critical challenge is to develop stable and robust cathode materials for excellent Zn storage. In this study, a hydrated vanadium pentoxide/reduced graphene oxide-polyvinyl alcohol (VO⋅nHO/rGO-PVA, abbreviated as VOH/rGO-P) film was synthesized as a binder-free cathode for solid-state aqueous ZIBs. The addition of PVA not only increases the layer spacing of VOH and forms a strong hydrogen bond network with GO and water molecules, but also enhances the mechanical properties of the film. As a binder-free cathode for solid-state aqueous ZIBs, the VOH/rGO-P film attains excellent electrochemical capacity as high as 481 mAh∙g at 0.1 A∙g. Such a high specific capacity indicates that the VOH/rGO-P film shows great potential for the next generation solid-state aqueous ZIBs.
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http://dx.doi.org/10.1016/j.jcis.2020.10.148DOI Listing
April 2021

Research Note: Effects of organic zinc on broiler intestinal permeability and integrity in Clostridium perfringens-challenged condition.

Poult Sci 2020 Dec 25;99(12):6653-6656. Epub 2020 Sep 25.

State Key Laboratory of Animal Nutrition, Key Laboratory of Feed Safety and Bioavailability, College of Animal Science and Technology, China Agricultural University, Ministry of Agriculture, Beijing 100193, China. Electronic address:

This study evaluates the effects of a zinc-amino acid complex on broiler's intestinal permeability and integrity challenged with Clostridium perfringens. A total of 180 Arbor Acres 1-day-old male broilers were assigned to 6 treatments in a completely randomized 2 × 3 factorial design. The experiment investigated the comparative effects of inorganic and organic zinc supplements, that is (ZnSO treatment: 80 mg zinc/kg from ZnSO; iso-dose replacement group. (ISO) treatment:40 mg zinc/kg from ZnSO plus 40 mg zinc/kg from a zinc-amino acid complex; and organic treatment: 40 mg zinc/kg from a zinc-amino acid complex) on C. perfringens-challenged broilers. C. perfringens, on the one hand, compromised intestinal mucosal barrier function by increasing the intestinal permeability of fluorescein isothiocyanate-labeled dextran (P < 0.05) and plasma endotoxin level, on the other hand, decreased both the transepithelial electrical resistance and the relative expression of occludin levels in the ileum at day 21 (P < 0.05). However, zinc supplement alleviates C. perfringens-induced pathologic changes in the intestinal permeability. ISO treatment, in particular, enhanced the villus height-to-crypt depth ratio and transepithelial electrical resistance and also reduced plasma endotoxin levels. In addition, zinc supplement relatively enhanced the expression of occludin levels in the ileum compared with the C. perfringens-challenged group. ISO treatment had the highest relative expression of occludin levels in the ileum. Thereby, the results indicated that partial replacement of ZnSO with a zinc-amino acid complex in the broiler diet could promote intestinal mucosal barrier function during C. perfringens infection via increased expression of occludin in the ileum.
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http://dx.doi.org/10.1016/j.psj.2020.09.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704963PMC
December 2020

Probing the drug delivery strategies in ischemic stroke therapy.

Drug Deliv 2020 Nov;27(1):1644-1655

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, P. R. China.

Ischemic stroke, which is caused by a sudden clot in the blood vessels, may cause severe brain tissue damage and has become a leading cause of death globally. Currently, thrombolysis is the gold standard primary treatment of ischemic stroke in clinics. However, the short therapeutic window of opportunity limits thrombolysis utility. Secondary cerebral damage caused by stroke is also an urgent problem. In this review, we discuss the present methods of treating ischemic stroke in clinics and their limitations. Various new drug delivery strategies targeting ischemic stroke lesions have also been summarized, including pharmaceutical methods, diagnostic approaches and other routes. These strategies could change the pharmacokinetic behavior, improve targeted delivery or minimize side effects. A better understanding of the novel approaches utilized to facilitate drug delivery in ischemic stroke would improve outcomes.
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http://dx.doi.org/10.1080/10717544.2020.1850918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717707PMC
November 2020

Application of Next-Generation Sequencing for Genetic Diagnosis in Neonatal Intensive Care Units: Results of a Multicenter Study in China.

Front Genet 2020 6;11:565078. Epub 2020 Nov 6.

Department of Neonatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

To identify next-generation-sequencing (NGS) clinical usability and to propose a standard diagnostic routine for critically ill infants, aged less than 100 days and suspected of having a genetically heterogeneous condition, a retrospective study was conducted between January 2016 and December 2018 at neonatal intensive care units (NICUs) of three tertiary hospitals in Shanghai, China. Whole-exome sequencing (WES) or panel sequencing was performed on 307 patients. Trio-WES, trio-panel, proband-WES, and proband-panel diagnostic yields were 39.71% (83/209), 68.75% (22/32), 59.09% (26/44), and 33.33% (4/12), respectively. Definitive molecular diagnoses of 142 infants (46.25%) uncovered 99 disorders; 21 disorders displayed on 44.37% of the diagnosed patients. Genetic etiologies were identified for 61.73% (50/81) of the deceased infants. One in three (29.58%) diagnosed infants exhibited one of the following four clinical traits which had a higher odds of diagnostic rate: integument abnormality (adjusted odds ratio [aOR], 19.7; 95% confidence interval [CI], 2.5-156.3), complex immune-related phenotypes (aOR, 9.2; 95% CI, 1.4-83.5), mixed nervous system phenotypes and congenital anomalies (aOR, 5.0; 95% CI, 1.3-19.1), or mixed metabolism and nervous system phenotypes (aOR, 4.5; 95% CI, 1.0-21.5). Our results demonstrated that NGS was an effective diagnostic tool. Infants exhibiting integument, complex immune-related conditions, metabolism, and nervous signs have higher chances of carrying variants in known disease-causing genes. The number of specific phenotypes could be used as an independent predictor of a positive molecular diagnosis, rather than an isolated abnormality. We developed a molecular diagnostic procedure for the use of NGS for diagnosis in Chinese NICU population based on individual characteristics.
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http://dx.doi.org/10.3389/fgene.2020.565078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677510PMC
November 2020
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