Publications by authors named "Lian Zhang"

364 Publications

RAD gene family analysis in cotton provides some key genes for flowering and stress tolerance in upland cotton G. hirsutum.

BMC Genomics 2022 Jan 10;23(1):40. Epub 2022 Jan 10.

Zhengzhou Research Base, State Key Laboratory of Cotton Biology, Zhengzhou University, Henan, 450001, Zhengzhou, China.

Background: RADIALIS (RAD), belongs to the MYB gene family and regulates a variety of functions including floral dorsoventral asymmetry in Antirrhinum majus and development of fruit proteins in Solanum lycopersicum. RAD genes contain an SNF2_N superfamily domain. Here, we comprehensively identified 68 RAD genes from six different species including Arabidopsis and five species of cotton.

Results: Phylogenetic analysis classified RAD genes into five groups. Gene structure, protein motifs and conserved amino acid residues indicated that GhRAD genes were highly conserved during the evolutionary process. Chromosomal location information showed that GhRAD genes were distributed unevenly on different chromosomes. Collinearity and selection pressure analysis indicated RAD gene family expansion in G. hirsutum and G. barbadense with purifying selection pressure. Further, various growth and stress related promotor cis-acting elements were observed. Tissue specific expression level indicated that most GhRAD genes were highly expressed in roots and flowers (GhRAD2, GhRAD3, GhRAD4 and GhRAD11). Next, GhRAD genes were regulated by phytohormonal stresses (JA, BL and IAA). Moreover, Ghi-miRN1496, Ghi-miR1440, Ghi-miR2111b, Ghi-miR2950a, Ghi-miR390a, Ghi-miR390b and Ghi-miR7495 were the miRNAs targeting most of GhRAD genes.

Conclusions: Our study revealed that RAD genes are evolutionary conserved and might be involved in different developmental processes and hormonal stress response. Data presented in our study could be used as the basis for future studies of RAD genes in cotton.
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http://dx.doi.org/10.1186/s12864-021-08248-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744286PMC
January 2022

PRR11 induces filopodia formation and promotes cell motility via recruiting ARP2/3 complex in non-small cell lung cancer cells.

Genes Dis 2022 Jan 2;9(1):230-244. Epub 2021 Mar 2.

Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, PR China.

Filopodia, a finger-like structure and actin-rich plasma-membrane protrusion at the leading edge of the cell, has important roles in cell motility. However, the mechanisms of filopodia generation are not well-understood via the actin-related protein 2/3 (ARP2/3) complex in Non-Small Cell Lung Cancer (NSCLC) cells. We previously have demonstrated that PRR11 associates with the ARP2/3 complex to regulate cytoskeleton-nucleoskeleton assembly and chromatin remodeling. In this study, we further demonstrate that PRR11 involves in filopodia formation, focal adhesion turnover and cell motility through ARP2/3 complex. Cell phenotype assays revealed that the silencing of PRR11 increased cellular size and inhibited cell motility in NSCLC cells. Mechanistically, PRR11 recruited and co-localized with Arp2 at the membrane protrusion to promote filopodia formation but not lamellipodia formation. Notably, PRR11 mutant deletion of the proline-rich region 2 (amino acid residues 185-200) abrogated the effect of filopodia formation. In addition, PRR11-depletion inhibited filopodial actin filaments assembly and increased the level of active integrin β1 in the cell surface, whereas reduced the phosphorylation level of focal adhesion kinase (FAK) to repress focal adhesion turnover and cell motility in NSCLC cells. Taken together, our findings indicate that PRR11 has critical roles in controlling filopodia formation, focal adhesion turnover and cell motility by recruiting ARP2/3 complex, thus dysregualted expression of PRR11 potentially facilitates tumor metastasis in NSCLC cells.
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http://dx.doi.org/10.1016/j.gendis.2021.02.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720695PMC
January 2022

associated aberrant methylation genes in blood leukocyte and gastric mucosa.

J Cancer 2021 28;12(24):7326-7333. Epub 2021 Oct 28.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.

Methylation alterations may be involved in -associated gastric carcinogenesis. This study aims to explore the potential associated methylation biomarkers in blood leukocyte and gastric mucosa. Five candidate -associated aberrant methylation genes were selected from the previous genome-wide profiling panels and validated in blood leukocyte and gastric mucosa in multi-stages (case-control validation between positive and negative subjects and self-control validation before and after anti- treatment). methylation level was decreased in blood leukocyte (62.07% 46.33%, <0.001) and gastric mucosa (56.30% 32.42%, <0.001) of positive subjects compared to negative controls. While, methylation level was increased significantly in blood leukocyte (29.57% 56.02%, <0.001) and gastric mucosa (31.10% 47.50%, <0.001) of positive subjects compared to controls. After successful eradication, the methylation levels were increased from 44.87% to 60.88% (<0.001) for and decreased from 46.19% to 34.56% (<0.001) for in blood leukocyte. Similar increasing and decreasing methylation alterations were also found for the two genes after successful eradication in paired gastric mucosa. In TCGA database, an inverse relationship was found between methylation and mRNA expression (=-0.12, =0.027). The GC cases with higher expression levels showed significantly worse survival (HR, 2.09, 95%CI, 1.22-3.57, =0.007) compared to lower expression subjects. and methylation levels may be affected by infection in gastric mucosa and blood leukocyte. may be involved in advanced stage of GC development, although the possible mechanism still needs further study in precancerous lesions.
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http://dx.doi.org/10.7150/jca.64613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8734399PMC
October 2021

Carbonic anhydrase 10 functions as a tumor suppressor in renal cell carcinoma and its methylation is a risk factor for survival outcome.

Urol Oncol 2022 Jan 1. Epub 2022 Jan 1.

Department of Urology, Peking University First Hospital, Institute of Urology, National Research Center for Genitourinary Oncology, Peking University, Beijing, China. Electronic address:

Carbonic anhydrase 10 (CA10), one of the carbonic anhydrase isozymes, is explored to be downregulated in several tumor types, which indicates its critical role in tumorigenesis. However, its biologic and pathological function remains elusive in the pathogenesis of renal cell carcinoma (RCC). We examined expressions and functions of CA10 in RCC primary tumors and cell lines, assessed its tumor suppressive functions and further explored its impact on survival outcome of RCC patients. We found that CA10 was down-expressed in RCC primary tumors compared with adjacent non-malignant renal tissues. Promoter CpG methylation seemed to directly suppress the transcription of CA10 in RCC cells, which could be reversed by demethylation treatment. Restoration of CA10 in 786-O and Caki-2 cell lines inhibited their cell proliferation and promoted their apoptosis by regulating relevant apoptosis factors. Kaplan-Meier curve identified that CA10 methylation status was associated with progression-free survival in RCC (P = 0.021). Multivariate Cox regression analyses indicated the CA10 methylation status [HR, 4.724; 95% CI, 1.056-21.136; P = 0.042] was an independent predictor of disease progression. Collectively, our study demonstrates that CA10 as a tumor suppressor is frequently inactivated by promoter CpG methylation in RCC and its methylation is a risk factor for the prognosis of RCC.
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http://dx.doi.org/10.1016/j.urolonc.2021.09.020DOI Listing
January 2022

Directionally In Situ Self-Assembled, High-Density, Macropore-Oriented, CoP-Impregnated, 3D Hierarchical Porous Carbon Sheet Nanostructure for Superior Electrocatalysis in the Hydrogen Evolution Reaction.

Small 2022 Jan 5;18(2):e2103866. Epub 2021 Dec 5.

Institute for Clean Energy and Advanced Materials, School of Materials & Energy, Southwest University, Chongqing, 400715, China.

3D ZIF-67-particles-impregnated cellulose-nanofiber nanosheets with oriented macropores are synthesized via directional-freezing-assisted in situ self-assembly, and converted to 3D CoP-nanoparticle (NP)-embedded hierarchical, but macropores-oriented, N-doped carbon nanosheets via calcination and phosphidation. The obtained nanoarchitecture delivers overpotentials at 10 and 50 mA cm and Tafel slope of 82.1 and 113.4 mV and 40.8 mV dec in 0.5 M H SO , and of 97.1 and 136.6 mV and 51.2 mV dec in 1 M KOH, all of which are superior to those of the most reported non-noble-metal-based hydrogen evolution reaction (HER) catalysts. This catalyst even surpasses commercial Pt/C for a much lower overpotential at high current densities, which is essential for large-scale hydrogen production. Its catalytic activity can be further optimized to become one of the best in both 0.5 M H SO and 1 M KOH. The outstanding catalytic activity is ascribed to the uniformly-dispersed small CoP NPs in the 3D carbon sheets and the hierarchical nanostructure with rich oriented pores. This work develops a facile, economical, and universal self-assembly strategy to fabricate uniquely nanostructured hybrids to simultaneously promote charge transfer and mass transport, and also offers an inexpensive and high-performance HER catalyst toward industry-scale water splitting.
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http://dx.doi.org/10.1002/smll.202103866DOI Listing
January 2022

Identification, evolutionary analysis and functional diversification of RAV gene family in cotton (G. hirsutum L.).

Planta 2021 Dec 4;255(1):14. Epub 2021 Dec 4.

Zhengzhou Research Base, State Key Laboratory of Cotton Biology, Zhengzhou University, Zhengzhou, 450001, Henan, China.

Main Conclusion: Genome wide analysis, expression pattern analysis, and functional characterization of RAV genes highlight their roles in roots, stem development and hormonal response. RAV (Related to ABI3 and VP1) gene family members have been involved in tissues/organs growth and hormone signaling in various plant species. Here, we identified 247 RAVs from 12 different species with 33 RAV genes from G. hirsutum. Phylogenetic analysis classified RAV genes into four distinct groups. Analysis of gene structure showed that most GhRAVs lack introns. Motif distribution pattern and protein sequence logos indicated that GhRAV genes were highly conserved during the process of evolution. Promotor cis-acting elements revealed that promotor regions of GhRAV genes encode numerous elements related to plant growth, abiotic stresses and phytohormones. Chromosomal location information showed uneven distribution of 33 GhRAV genes on different chromosomes. Collinearity analysis identified 628 and 52 orthologous/ paralogous gene pairs in G. hirsutum and G. barbadense, respectively. Ka/Ks values indicated that GhRAV and GbRAV genes underwent strong purifying selection pressure. Selecton model and codon model selection revealed that GhRAV amino acids were under purifying selection and adaptive evolution exists among GhRAV proteins. Three dimensional structure of GhRAVs indicated the presence of numerous alpha helix and beta-barrels. Expression level revealed that some GhRAV genes exhibited high expression in roots (GhRAV3, GhRAV4, GhRAV11, GhRAV18, GhRAV20 and GhRAV30) and stem (GhRAV3 and GhRAV18), indicating their potential role in roots and stem development. GhRAV genes can be regulated by phytohormonal stresses (BL, JA and IAA). Our study provides a reference for future studies related to the functional analysis of GhRAVs in cotton.
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http://dx.doi.org/10.1007/s00425-021-03782-2DOI Listing
December 2021

self-assembled N-rich carbon on pristine graphene as a highly effective support and cocatalyst of short Pt nanoparticle chains for superior electrocatalytic activity toward methanol oxidation.

Nanoscale 2021 Nov 11;13(43):18332-18339. Epub 2021 Nov 11.

Institute for Clean energy and Advanced Materials, College of Materials & Energy, Southwest University, Chongqing 400715, China.

Highly conductive cocatalysts with great promotion effects are critical for the development of pristine graphene supported Pt-based catalysts for the methanol oxidation reaction (MOR) in direct methanol fuel cells (DMFCs). However, identification of these cocatalysts and controlled fabrication of Pt/cocatalyst/graphene hybrids with superior catalytic performance present great challenges. For the first time, pristine graphene supported N-rich carbon (NC) has been controllably fabricated ionic-liquid-based self-assembly for growth of small and uniformly dispersed Pt NP chains to improve the MOR catalytic activity. It is discovered that the NC serves simultaneously as a linker to facilitate nucleation of Pt, a stabilizer to restrict its growth and aggregation, and a structure-directing agent to induce the formation of Pt NP chains. The obtained nanohybrid shows a much higher forward peak current density than commercial Pt/C and most reported noncovalently functionalized carbon (NFC) supported Pt catalysts, a lower onset potential than almost all commercial Pt/C and NFC supported Pt, and greatly enhanced durability compared to graphene supported Pt NPs and commercial Pt/C. The superior catalytic performance is ascribed to the uniformly dispersed, small-diameter, and short Pt NP chains supported on highly conductive [email protected] providing high ECSA and improved CO tolerance and the NC with high content of graphitic N greatly enhancing the intrinsic activity and CO tolerance of Pt and offering numerous binding sites for robustly attaching Pt. This work not only identifies and controllably fabricates a novel cocatalyst to significantly promote the catalytic activity of pristine graphene supported Pt but provides a facile and economical strategy for the controlled synthesis of high-performance integrated catalysts for the MOR in DMFCs.
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http://dx.doi.org/10.1039/d1nr05988bDOI Listing
November 2021

Irinotecan Plus Doxorubicin Hydrochloride Liposomes for Relapsed or Refractory Wilms Tumor.

Front Oncol 2021 21;11:721564. Epub 2021 Sep 21.

Department of Pediatric Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

Purpose: The prognosis of relapsed or refractory pediatric Wilms tumor (WT) is dismal, and new salvage therapies are needed. This study aimed to evaluate the efficacy of the combination of irinotecan and a doxorubicin hydrochloride liposome regimen for relapsed or refractory pediatric WT.

Patients And Methods: The present study enrolled relapsed or refractory pediatric WT patients who were treated with the AI regimen (doxorubicin hydrochloride liposomes 40 mg/m per day, day 1, and irinotecan 50 mg/m per day with 90-min infusion, days 1-5; this regimen was repeated every 3 weeks) at Sun Yat-sen University Cancer Center from July 2018 to September 2020. The response was defined as the best-observed response after at least two cycles according to the Response Evaluation Criteria of Solid Tumors (RECIST 1.1), and toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 4.03).

Results: A total of 16 patients (male:female, 8:8) with a median age of 4.2 years (0.5-11 years) with relapsed or refractory disease were enrolled in this study, including 14 patients with relapsed disease and two patients with refractory disease. These patients received 1-8 courses (median, 3 courses) of the AI regimen. Fourteen patients were assessable for response: two with complete response (CR), five with partial response (PR), two with stable disease (SD), and five with progressive disease (PD). The objective response rate was 50% (two CR, five PR), and the disease control rate was 64% (two CR, five PR, and two SD). Seven out of 14 patients (50%) were alive at the last follow-up, ranging from 2.6 to 32.4 months. The median progression-free survival and median overall survival were 3.5 months (range 0.5-12 months) and 8 months (range 1-28 months), respectively. Sixteen patients were assessable for toxicity, with the most common grade 3 or 4 adverse events being alopecia (62%), leukopenia (40%), abdominal pain (38%), diarrhea (23%), and mucositis (16%), etc. No fatal adverse events have been observed, and modest adverse effects can be administered.

Conclusion: Irinotecan and doxorubicin hydrochloride liposome regimens have positive efficacy on relapsed or refractory pediatric WT with well-tolerated toxicity. A prospective clinical trial is warranted.
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http://dx.doi.org/10.3389/fonc.2021.721564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490759PMC
September 2021

Regulation of Hole Concentration and Mobility and First-Principle Analysis of Mg-Doping in InGaN Grown by MOCVD.

Materials (Basel) 2021 Sep 16;14(18). Epub 2021 Sep 16.

Department of Physics, School of Science, Wuhan University of Technology, Wuhan 430070, China.

This work studied the regulation of hole concentration and mobility in p-InGaN layers grown by metalorganic chemical vapor deposition (MOCVD) under an N-rich environment. By adjusting the growth temperature, the hole concentration can be controlled between 6 × 10/cm and 3 × 10/cm with adjustable hole mobility from 3 to 16 cm/V.s. These p-InGaN layers can meet different requirements of devices for hole concentration and mobility. First-principles defect calculations indicate that the p-type doping of InGaN at the N-rich limiting condition mainly originated from Mg substituting In (Mg). In contrast with the compensation of nitrogen vacancy in p-type InGaN grown in a Ga-rich environment, the holes in p-type InGaN grown in an N-rich environment were mainly compensated by interstitial Mg (Mg), which has very low formation energy.
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http://dx.doi.org/10.3390/ma14185339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467921PMC
September 2021

The Alteration human of gut microbiota and metabolites before and after renal transplantation.

Microb Pathog 2021 Nov 24;160:105191. Epub 2021 Sep 24.

Department of Transplantation, Third Xiangya Hospital of Central South University, Changsha, 410013, PR China. Electronic address:

Background: Recent studies have revealed that gut microbiota play an important part in the regulation of the immune function. With the development of newer detection methods, our cognition of the human gut microbiota continues to evolve with startling speed, but our understanding of the changes in the structure and function of gut microbiota before and after renal transplantation and the practical applications of this knowledge are still in their infancy.

Methods: We prospectively recruited 10 renal transplant recipients and collected serial fecal specimens (N = 30) before the operation, and on the 7th and 30th day after the operation, and characterized their gut microbiota structure through deep sequencing of the 16S rRNA V4-V5 variable region and analyzed the presence of metabolites using LC-MS methods.

Results: A decrease in the relative abundance of overall gut microbiota was detected in post-transplantation samples compared to that in pre-transplantation samples. Principal coordinate analysis (PCoA) inhibited a obvious separation between the three groups, and the linear discriminant analysis effect size (LEfSe) method showed that Clostridiales, Clostridia, Ruminococcaceae, Faecalibacterium, and Veillonellaceae were all significantly more abundant in the fecal specimens from the pre-transplantation group while Bacilli, Enterococcaceae, and Enterococcus were significantly more abundant in the fecal specimens from the four weeks post-transplantation group. Anaerostipes and Clostridia-bacterium were detected in the fecal samples from the one week post-transplantation group. Analysis of community composition did not reveal any significant difference between the pre-transplantation group and the post-transplantation group. The metabolic profiling of the volunteers before renal transplantation were distinct from the post-transplantation profiling, which gather together in PCA (Fig. 4A). After renal transplantation, the metabolic profiling of post-transplantation specimens revealed marked diversity and complexity.

Conclusions: Our research indicated remarkable variations in the gut microbiota and metabolites following renal transplantation, and that the gut microbiota and metabolites of patients with uremia were relatively stable and showed reasonable concordance. Distinct microbial compositions and metabolites were observed in patients after transplantation.
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http://dx.doi.org/10.1016/j.micpath.2021.105191DOI Listing
November 2021

XRD and TEM analyses of a simulated leached rare earth ore deposit: Implications for clay mineral contents and structural evolution.

Ecotoxicol Environ Saf 2021 Dec 6;225:112728. Epub 2021 Sep 6.

College of Sciences, Guangdong University of Petrochemical Technology, Maoming 525000, China. Electronic address:

The types, contents, and microstructures of clay minerals play important roles in controlling the adsorption and desorption of ion-absorbed type rare earth ores and heavy metals. By selecting a typical rare earth ore profile, we conducted a leaching experiment and used XRD (X-ray diffraction) and TEM (Transmission electron microscopy) analyses to determine the clay mineral types and microstructural changes after various leaching periods. The XRD phase analyses showed that the main minerals in the simulated rare earth ore were quartz, potassium feldspar, kaolinite, and illite. TEM images showed that the mineral aggregates were broken, disintegrated, and transformed by the leaching process, and a large number of moire fringes were visible. With continuous leaching, REEs (Rare Earth Elements) were gradually re-solved and leached. The results of the leaching experiment indicate that fine-grained minerals in rare earth ores, such as potassium feldspar and clay minerals, migrated downward with the leaching solution. Leaching also promoted the alteration of potassium feldspar to clay minerals, as well as mutual alteration of clay minerals. Under acidic or neutral conditions during the early stage, potassium feldspar was altered to kaolinite or illite, whereas during the middle and late stages of leaching it was altered as follows: illite → mixed-layer illite-kaolinite → kaolinite → mixed-layer kaolinite-illite → illite. This transformation has an important effect on the release of REEs and heavy metals and provides insights into improving the leaching process and explaining heavy metal pollution in rare earth mining areas.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112728DOI Listing
December 2021

Ultrasound-guided high intensity focused ultrasound ablation for uterine fibroids: long-term outcomes and factors affecting local recurrence.

Int J Hyperthermia 2021 ;38(1):1341-1348

State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.

Objective: To assess the long-term outcomes and the factors affecting local recurrence of uterine fibroids after ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation.

Materials And Methods: 629 patients with a solitary uterine fibroid smaller than 10 cm in diameter treated with USgHIFU at our institutes between January 2011 and December 2016 were retrospectively analyzed. The patients were requested to take pre-HIFU and one day post-HIFU MRI. The patients were asked to return to the hospital every 3 months until January 2020, for imaging evaluation and to check on improvement in symptoms.

Results: Five hundred and thirty-six patients completed follow-up according to our protocol. The median follow-up time was 69 (interquartile range: 48 to 89) months. Among them, local recurrence was detected in 110 patients. 18 (16.4%) patients required additional treatment between 12 and 24 months after USgHIFU treatment, 59 (53.6%) patients required additional treatment 24 months after USgHIFU. Therefore, in total, 77 patients required additional treatment, of which 32 received USgHIFU and 45 underwent myomectomy. The median non-perfused volume (NPV) ratio in patients with recurrence was 73%, compared to 89% among patients without recurrence. Multivariate analysis showed that NPV ratio, maximum fibroid diameter and fibroid enhancement type were the independent factors affecting the recurrence of fibroids after USgHIFU treatment.

Conclusions: Achievement of NPV ratio higher than 70% has led to acceptable re-intervention rate during the follow-up period after USgHIFU. NPV ratio, maximum fibroid diameter, and fibroid enhancement type were the independent factors affecting the recurrence of fibroids after USgHIFU treatment.
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http://dx.doi.org/10.1080/02656736.2021.1973585DOI Listing
September 2021

MRI features and clinical outcomes of unexpected uterine sarcomas in patients who underwent high-intensity focused ultrasound ablation for presumed uterine fibroids.

Int J Hyperthermia 2021 09;38(2):39-45

State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.

Objective: To investigate the MRI features and clinical outcomes of unexpected uterine sarcomas in patients after high-intensity focused ultrasound (HIFU) ablation for presumed uterine fibroids.

Materials And Methods: 15,759 consecutive patients who came for HIFU treatment, from November 2008 to September 2019, for presumed uterine fibroids were retrospectively reviewed. All the patients had completed a pre-HIFU MRI. All MRI images were independently analyzed and interpreted by two radiologists in every center.

Results: According to the T2WI MRI features of hyperintensity, accompanied by irregular margins, necrosis or cystic degeneration, multi-lobulated lesion with internal septation, 46 patients were suspected to be uterine sarcomas before HIFU. Eleven patients were histologically diagnosed as uterine sarcomas after laparotomy. Among the 15713 patients who received HIFU treatment for presumed uterine fibroids, 8 patients were found to have occult recurrence during the follow-up period, and 6 were confirmed histologically as uterine sarcomas after laparotomy. The incidence rate of uterine sarcomas was 0.108% (17/15759). Among them, 12 cases were low-grade endometrial stromal sarcoma (LG-ESS) and 5 cases were uterine leiomyosarcoma (LMS). No histological dissemination of the sarcoma was detected in patients with unexpected uterine sarcomas.

Conclusion: Although some MRI features of uterine sarcomas and uterine fibroids overlapped, MRI is valuable in distinguishing between uterine fibroids and uterine sarcomas. HIFU does not seem to cause histological dissemination of the sarcoma, but follow-up visits should be strictly adhered to in order to detect unexpected uterine sarcomas at an early stage and to treat them in a timely manner.
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http://dx.doi.org/10.1080/02656736.2021.1921288DOI Listing
September 2021

The safety and ablation efficacy of ultrasound-guided high-intensity focused ultrasound ablation for desmoid tumors.

Int J Hyperthermia 2021 09;38(2):89-95

State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, PR China.

Objective: To evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for desmoid tumors (DTs).

Method: A total of 111 patients with histologically proven DTs were included and treated by USgHIFU ablation. Adverse events were continuously evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 until 3 months after treatment. The incidence of non-perfused areas within the treated tumors, non-perfused volume rate (NPVR) and tumor volume reduction were evaluated using contrast-enhanced MRI before and one week and 3 months after the procedure.

Results: The enrolled patients (32 male, 79 female, mean age 29.5 ± 1.0 years) with 145 DTs (118 extra-abdominal, 16 abdominal wall, 11 intra-abdominal; median maximum diameter: 9.6 cm, range: 3-34.5 cm) underwent 188 sessions of HIFU ablation, and the mean number of ablations was 1.7 (range, 1-7) per patient. In majority of cases (143/145 cases, 98.6%), no serious adverse events were observed. There was no significant difference in the incidence of adverse events between patients who received a single treatment and those who received multiple treatments. Non-perfused area was observed within every treated tumor, and the median NPVR was 84.9% (range, 1.9-100%). The tumor volume reduction rate was 36.1 ± 4.2% at 3 months after treatment.

Conclusion: USgHIFU ablation, as a noninvasive and easily repeatable local treatment, is a promising treatment for DTs.
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http://dx.doi.org/10.1080/02656736.2021.1894359DOI Listing
September 2021

Gene therapy rescues olfactory perception in a clinically relevant ciliopathy model of Bardet-Biedl syndrome.

FASEB J 2021 09;35(9):e21766

Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA.

Bardet-Biedl syndrome (BBS) is a hereditary genetic disorder that results in numerous clinical manifestations including olfactory dysfunction. Of at least 21 BBS-related genes that can carry multiple mutations, a pathogenic mutation, BBS1M390R, is the single most common mutation of clinically diagnosed BBS outcomes. While the deletion of BBS-related genes in mice can cause variable penetrance in different organ systems, the impact of the Bbs1M390R mutation in the olfactory system remains unclear. Using a clinically relevant knock-in mouse model homozygous for Bbs1M390R, we investigated the impact of the mutation on the olfactory system and tested the potential of viral-mediated, wildtype gene replacement therapy to rescue smell loss. The cilia of olfactory sensory neurons (OSNs) in Bbs1 mice were significantly shorter and fewer than those of wild-type mice. Also, both peripheral cellular odor detection and synaptic-dependent activity in the olfactory bulb were significantly decreased in the mutant mice. Furthermore, to gain insight into the degree to which perceptual features are impaired in the mutant mice, we used whole-body plethysmography to quantitatively measure odor-evoked sniffing. The Bbs1 mice showed significantly higher odor detection thresholds (reduced odor sensitivity) compared to wild-type mice; however, their odor discrimination acuity was still well maintained. Importantly, adenoviral expression of Bbs1 in OSNs restored cilia length and re-established both peripheral odorant detection and odor perception. Together, our findings further expand our understanding for the development of gene therapeutic treatment for congenital ciliopathies in the olfactory system.
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http://dx.doi.org/10.1096/fj.202100627RDOI Listing
September 2021

Combination Therapy With Anti-PD-1 or PD-1 Antibody Alone in Asian Pediatric Patients With Relapsed or Refractory Cancer.

Front Immunol 2021 6;12:647733. Epub 2021 Jul 6.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

There is limited experience of PD-1 antibody combined with other therapies in children. We aimed to explore the antitumor activity and safety of PD-1 antibody monotherapy or combination with other regimens in relapsed or refractory pediatric cancer. This is a retrospective-case study conducted in two Chinese expert centers. The primary objective of this study was to describe the overall response rate (ORR) and disease control rate (DCR). Secondary objectives included characterizing toxicities. Of the 22 pediatric patients with cancer who received PD-1 inhibitors, the median follow-up for all patients after the commencement of PD-1 therapy with or without other regimens was 12.3 months (0 - 43 months). PD-1 antibody monotherapy demonstrated antitumor activity in a population of pediatric patients with Hodgkin lymphoma (HL), with an objective response rate (ORR) and disease control rate (DCR) of 83.3% (3CR and 2PR) and 100%, respectively. However, no objective response was observed in patients with melanoma or Burkitt lymphoma evaluated in this study. We reviewed responses for patients with chemotherapy, decitabine or everolimus combination therapies with PD-1 antibodies, and found that PD-1 antibody combined with decitabine showed potential efficacy in pediatric patients with advanced embryonal rhabdomyosarcoma and lymphoepitheliomatoid-like carcinoma. There were no severe treatment-related adverse events (TRAEs) directly attributed to PD-1 antibody monotherapy in Asian pediatric patients with lower incidence of hematologic toxicity and nonhematologic toxicity. The Grade ≥3 TRAEs were attributed to the combination chemotherapy.
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http://dx.doi.org/10.3389/fimmu.2021.647733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290852PMC
October 2021

ISL1 promoted tumorigenesis and EMT via Aurora kinase A-induced activation of PI3K/AKT signaling pathway in neuroblastoma.

Cell Death Dis 2021 06 15;12(6):620. Epub 2021 Jun 15.

Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China.

Neuroblastoma (NB) is the most common extracranial solid malignancy in children and its mortality rate is relatively high. However, driver genes of NB are not clearly identified. Using bioinformatics analysis, we determined the top 8 differentially expressed genes (DEGs) in NB, including GFAP, PAX6, FOXG1, GAD1, PTPRC, ISL1, GRM5, and GATA3. Insulin gene enhancer binding protein 1 (ISL1) is a LIM homeodomain transcription factor which has been found to be highly expressed in a variety of malignant tumors, but the function of ISL1 in NB has not been fully elucidated. We identified ISL1 as an oncogene in NB. ISL1 is preferentially upregulated in NB tissues compared with normal tissues. High ISL1 expression is significantly associated with poor outcome of NB patients. Knockdown of ISL1 markedly represses proliferation and induces cell apoptosis in vitro, and suppresses tumorigenicity in vivo, while overexpression of ISL1 has the opposite effects. Mechanistically, we demonstrate that ISL1 promotes cell proliferation and EMT transformation through PI3K/AKT signaling pathway by upregulating Aurora kinase A (AURKA), a serine-threonine kinase that is essential for the survival of NB cells. The blockade of AURKA attenuates the function of ISL1 overexpression in the regulation of cell proliferation and migration, Conclusively, this study showed that ISL1 targeted AURKA to facilitate the development of NB, which provided new insights into the tumorigenesis of NB. Thus, ISL1 may be a promising therapeutic target in the future.
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http://dx.doi.org/10.1038/s41419-021-03894-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206128PMC
June 2021

5-Aminolevulinic acid induced photodynamic therapy (ALA-PDT) for erosive adenomatosis of the nipple: A case report.

Photodiagnosis Photodyn Ther 2021 Sep 7;35:102387. Epub 2021 Jun 7.

Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China. Electronic address:

Erosive adenomatosis of the nipple (EAN) is an uncommon, benign neoplasm that involves the nipple. Traditional treatments include complete surgical excision, limited forms of complete surgical excision and Mohs micrographic surgery. Here, we report a case of a 40-year-old woman with a 2-year history of asymptomatic erosion, papillomatous hyperplasia and intermittent serosanguineous discharge on her right nipple. Histopathological examination confirmed the diagnosis of EAN. She was treated with 5-aminolevulinic acid induced photodynamic therapy (ALA-PDT) for 2 sessions with 2 weeks intervals. No recurrence occurred within 6 months. Therefore, our report suggested that ALA-PDT is a possible method to treat EAN, especially in patients who have the need of breastfeeding and cosmetic appearance, but this needs to be examined in a larger clinical trial.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102387DOI Listing
September 2021

MiR-22 regulated T cell differentiation and hepatocellular carcinoma growth by directly targeting Jarid2.

Am J Cancer Res 2021 15;11(5):2159-2173. Epub 2021 May 15.

Department of Oncology, Affiliated Eighth People's Hospital, Jiangsu University Shanghai, China.

MiR-22 has been demonstrated to inhibits tumor growth in several cancers. However, its function in the tumor microenvironment is still unclear, especially for T cell differentiation. Here, miR-22 expression in the circulating T cells from hepatocellular carcinoma (HCC) patients and healthy controls was analyzed with quantitative polymerase chain reaction (qPCR). Diethylnitrosamine (DEN)/phenobarbital (PB)-mediated primary HCC and Hepa1-6 subcutaneous tumor mouse models were established and subjected to lenti-miR-22 injection. Mice immunoreconstituted with miR-22-overexpressing T cells were employed to investigate the antitumor effect of miR-22 in mice. Luciferase assay, immunofluorescent staining, in vitro Th17 cell differentiation assay, and rescue experiments were employed to investigate the mechanism underlying the miR-22-mediated regulation of Th17 cell differentiation and liver tumor growth. Results confirmed the dramatic downregulation of miR-22 expression in malignant tissues and circulating T cells from patients with HCC. MiR-22 expression correlated with good prognosis of patients. Overexpression of miR-22 impaired the DEN/PB-induced primary HCC formation and the growth of Hepa1-6 subcutaneous tumors by promoting Th17 differentiation. Injection of miR-22-overexpressing T cells in irradiated mice resulted in the inhibition of Hepa1-6 subcutaneous tumor growth via Th17 differentiation promotion. MiR-22 could directly bind to Jarid2, which played an important role during the miR-22-mediated regulation of Th17 differentiation. Taken together, our study expands the understanding of miR-22 function and provides a therapy target for HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167680PMC
May 2021

E/D-Mode GaN Inverter on a 150-mm Si Wafer Based on p-GaN Gate E-Mode HEMT Technology.

Micromachines (Basel) 2021 May 27;12(6). Epub 2021 May 27.

Laboratory of Solid State Optoelectronics Information Technology, Institute of Semiconductors, CAS, Beijing 100083, China.

AlGaN/GaN E/D-mode GaN inverters are successfully fabricated on a 150-mm Si wafer. P-GaN gate technology is applied to be compatible with the commercial E-mode GaN power device technology platform and a systematic study of E/D-mode GaN inverters has been conducted with detail. The key electrical characters have been analyzed from room temperature (RT) to 200 °C. Small variations of the inverters are observed at different temperatures. The logic swing voltage of 2.91 V and 2.89 V are observed at RT and 200 °C at a supply voltage of 3 V. Correspondingly, low/high input noise margins of 0.78 V/1.67 V and 0.68 V/1.72 V are observed at RT and 200 °C. The inverters also demonstrate small rising edge time of the output signal. The results show great potential for GaN smart power integrated circuit (IC) application.
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http://dx.doi.org/10.3390/mi12060617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230248PMC
May 2021

A predictive study of multivariate factors affecting goal attainment of INR after anticoagulation in patients with nonvalvular atrial fibrillation.

Ann Palliat Med 2021 Apr;10(4):4532-4538

Department of Cardiovascular Medicine, Xinqiao Hospital Affiliated to Army Military Medical University, Chonqing, China.

Background: Non-valvular atrial fibrillation (NVAF) is a common type of AF, and patients with NVAF have a higher risk of ischemic stroke than non-AF patients. This study aims to investigate the goal attainment of international normalized ratio (INR) in patients with NVAF after anticoagulation therapy, and to analyze the risk factors that affect the goal attainment of INR.

Methods: NVAF patients who were admitted to our hospital from December 2019 to December 2020 and received anticoagulation therapy were selected as the research subjects. The INR goal attainment of patients was assessed, the risk factors affecting INR goal attainment were analyzed, and a ROC curve was drawn to evaluate the predictive value of risk factors for INR goal attainment in NVAF patients.

Results: After anticoagulation treatment, the INR of 42 cases reached the target (INR value ≥0.2, the goal attainment group), and the INR of 74 cases did not reach the target (INR value <2.0, the non-goal attainment group). The age, mean platelet volume (MPV), platelet distribution width (PDW), and large platelet ratio (P-LCR) levels of patients in the goal attainment group were significantly lower than those in the non-goal attainment group, and the platelet count (PLT) level was higher than that of the non-goal attainment group (P<0.05). The results of multivariate logistic regression analysis showed that MPV, PDW, and P-LCR were independent risk factors that affected the failure in INR goal attainment in patients with NVAF after anticoagulation therapy. The ROC curve showed that the AUC values of MPV, PDW, and P-LCR were 0.711, 0.748, 0.867, respectively, and the combined AUC was 0.876, which was higher than that of the single detection.

Conclusions: MPV, PDW, and P-LCR are important factors that affect the goal attainment of INR after anticoagulant therapy in NVAF patients. For patients with risk factors, clinicians can formulate a reasonable individualized anticoagulant drug regimen based on the above-mentioned index levels.
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http://dx.doi.org/10.21037/apm-21-549DOI Listing
April 2021

Wild-type IDH1 inhibits the tumor growth through degrading HIF-α in renal cell carcinoma.

Int J Biol Sci 2021 25;17(5):1250-1262. Epub 2021 Mar 25.

Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

The purpose of our study was to explore the effect and intrinsic mechanism of wild-type IDH1 and its substrate α-KG on renal cell carcinoma (RCC). IDH1 was observed lower expression in RCC cell lines. Phenotype experiment was carried out in the wild-type IDH1 and mutant IDH1 plasmid treated cell line. The results showed that the wild-type IDH1 could significantly inhibit the proliferation, migration and promote the apoptosis of RCC cell lines, which were consistent with the IDH1's substrate α-KG. The mutant IDH1 was found to lose this biological function of IDH1. Moreover, we verified the proliferation inhibition of IDH1 . In addition, we verified the correlation between IDH1 and hypoxia signal-related proteins and , specifically, IDH1 overexpression could significantly reduce the expression of HIF-1α and HIF-2α proteins and its downstream proteins (VEGF, TGF-α). Furthermore, we preliminarily verified the possibility of α-KG in the RCC's treatment by injecting α-KG into the xenograft model. α-KG significantly reduced tumor size and weight in tumor-bearing mice. This study provided a new therapeutic target and small molecule for the study of the treatment and mechanism of RCC.
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http://dx.doi.org/10.7150/ijbs.54401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040470PMC
March 2021

A comparison of the mechanisms and performances of Acorus calamus, Pontederia cordata and Alisma plantagoaquatica in removing nitrogen from farmland wastewater.

Bioresour Technol 2021 Jul 6;332:125105. Epub 2021 Apr 6.

College of Resources and Environment, Hunan Agricultural University, Changsha 410128, PR China; Hunan Provincial Key Laboratory of Farmland Pollution Control and Agricultural Resources Use, Hunan Provincial Key Laboratory of Nutrition in Common University, National Engineering Laboratory on Soil and Fertilizer Resources Efficient Utilization, Changsha 410128, PR China. Electronic address:

This study examined the performances of Acorus calamus, Pontederia cordata, and Alisma plantagoaquatica in removing nitrogen (N) from farmland wastewater. P. cordata showed the fastest rate of N removal, followed by A. plantagoaquatica, whereas that of A. calamus was slowest. P. cordata and A. plantagoaquatica achieving a greater rate of TN reduction in soil than that by A. calamus. A. plantagoaquatica demonstrated the highest N adsorption capacity, 32.6% and 392.1% higher than that of P. cordata and A. calamus, respectively. The higher potential nitrification and denitrification rate, and abundance of functional genes in the P. cordata microcosm resulted in a stronger process of nitrification-denitrification, which accounted for 65.99% of TN loss. Plant uptake and nitrification-denitrification were responsible for 50.06% and 49.94% of TN removed within the A. plantagoaquatica. Nitrification-denitrification accounted for 86.35% of TN loss in A. calamus. These findings helped to insight into N removal mechanisms in different plants.
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http://dx.doi.org/10.1016/j.biortech.2021.125105DOI Listing
July 2021

A comparison of results following the treatment of placenta accreta and placenta increta using high-intensity focused ultrasound followed by hysteroscopic resection.

Int J Hyperthermia 2021 ;38(1):576-581

State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.

Objective: To compare the safety and efficacy of high-intensity focused ultrasound (HIFU) followed by hysteroscopic resection for different placenta accreta spectrum disorders.

Materials And Methods: Thirty-four patients with placenta accreta, placenta increta, or placenta percreta were treated with USgHIFU from January 2016 to December 2019 and were retrospectively reviewed. The patients were classified into three categories according to the relationship between the trophoblastic villi and the myometrium, based on magnetic resonance imaging (MRI). Fifteen patients were classified as placenta accreta, 17 patients were classified as placenta increta, and 2 were classified as placenta percreta. All patients completed follow-up. Treatment efficacy and safety were evaluated.

Results: No significant differences in baseline characteristics and results of HIFU ablation were observed between the patients with placenta accreta and those with placenta increta. The return of HCG levels to normal was longer in patients with placenta accreta compared with patients with placenta increta, while no significant difference was observed in the amount of intraoperative blood loss, the return of normal menstruation and the length of hospital stay.

Conclusions: HIFU treatment followed by hysteroscopic resection is safe and effective in the treatment of patients with placenta accreta and placenta increta.
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http://dx.doi.org/10.1080/02656736.2021.1909149DOI Listing
July 2021

Influence of UGT1A1 *6/*28 Polymorphisms on Irinotecan-Related Toxicity and Survival in Pediatric Patients with Relapsed/Refractory Solid Tumors Treated with the VIT Regimen.

Pharmgenomics Pers Med 2021 23;14:369-377. Epub 2021 Mar 23.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.

Objective: The association between UGT1A1*6/*28 polymorphisms and treatment outcomes of irinotecan in children remains unknown. This retrospective study investigated the influence of UGT1A1*6/*28 polymorphisms on irinotecan toxicity and survival of pediatric patients with relapsed/refractory solid tumors.

Methods: The present study enrolled a total of 44 patients aged younger than 18 years at Sun Yat-sen University Cancer Center between 2014 and 2017.

Results: There were 26 boys and 18 girls; the median age at first VIT course was six years (range: 1-18 years). The tumor types included neuroblastoma (n = 25), rhabdomyosarcoma (n = 11), Wilm's tumor (n = 4), medulloblastoma (n = 2), and desmoplastic small round cell tumor (n = 2). Overall, 203 courses of VIT regimens were prescribed. Neither UGT1A1*6 nor *28 polymorphisms were associated with the incidence rates of severe (grade III-IV) irinotecan-related toxicities, but tended to reduce the patient overall survival (UGT1A1*6, = 0.146; UGT1A1*28, = 0.195). Moreover, patients with mutant UGT1A1*6 genotypes were more likely to develop grade I-IV irinotecan-related diarrhea ( = 0.043) and anemia ( = 0.002). Overall, the UGT1A1*28 polymorphism may play a protective role against irinotecan-related diarrhea and abdominal pain.

Conclusion: In relapsed/refractory pediatric solid tumors, the UGT1A1*6 polymorphism was a risk factor of irinotecan-related diarrhea and anemia. The UGT1A1*28 polymorphism may serve a protective role in irinotecan-related abdominal pain and diarrhea. Both mutations had a tendency to be risk factors for survival. Nevertheless, prospective studies are required to verify such conclusions.
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http://dx.doi.org/10.2147/PGPM.S292556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001723PMC
March 2021

Magnetic resonance imaging parameters in predicting the ablative efficiency of high-intensity focused ultrasound for uterine fibroids.

Int J Hyperthermia 2021 ;38(1):523-531

State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.

Objective: To evaluate the role of quantitative MRI parameters in predicting HIFU ablation results for uterine fibroids.

Material And Methods: A total of 245 patients with uterine fibroids who underwent HIFU treatment in Chongqing Haifu Hospital were reviewed retrospectively. The patients were divided into two groups according to the non-perfused volume (NPV) ratio which was either higher or lower than 80%. The MRI parameters were measured, and a logistical regression analysis was performed to investigate the potential predictors associated with the NPV ratio. Receiver operating characteristics (ROC) analysis was used to determine the cut off value for MRI parameters in predicting a high NPV ratio.

Results: The subcutaneous fat thickness in the group of patients with an NPV ratio over 80% was significantly thinner than that in the group of patients with an NPV ratio less than 80% (15 mm versus 21 mm). The signal intensity ratio of fibroids to skeletal muscle on T2WI was significantly lower in the group of patients with an NPV ratio over 80% compared with the group with an NPV ratio lower than 80% (2.46 versus 3.23). The signal intensity ratio of fibroid to skeletal muscle correlated negatively with the NPV ratio and positively with the energy efficiency factor (EEF). The cut off value of signal intensity ratio of fibroid to muscle for predicting the NPV ratio over 80% is 3.045.

Conclusion: The signal intensity ratio of fibroid to skeletal muscle on T2WI can be used as a factor for predicting the effectiveness of HIFU ablation of uterine fibroids.
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http://dx.doi.org/10.1080/02656736.2021.1904152DOI Listing
July 2021

INPP5E controls ciliary localization of phospholipids and the odor response in olfactory sensory neurons.

J Cell Sci 2022 03 7;135(5). Epub 2021 May 7.

University of Florida, Department of Pharmacology and Therapeutics, Gainesville, FL 32603, USA.

The lipid composition of the primary cilia membrane is emerging as a critical regulator of cilia formation, maintenance and function. Here, we show that conditional deletion of the phosphoinositide 5'-phosphatase gene Inpp5e, mutation of which is causative of Joubert syndrome, in terminally developed mouse olfactory sensory neurons (OSNs), leads to a dramatic remodeling of ciliary phospholipids that is accompanied by marked elongation of cilia. Phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2], which is normally restricted to the proximal segment redistributed to the entire length of cilia in Inpp5e knockout mice with a reduction in phosphatidylinositol (3,4)-bisphosphate [PI(3,4)P2] and elevation of phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3] in the dendritic knob. The redistribution of phosphoinositides impaired odor adaptation, resulting in less efficient recovery and altered inactivation kinetics of the odor-evoked electrical response and the odor-induced elevation of cytoplasmic Ca2+. Gene replacement of Inpp5e through adenoviral expression restored the ciliary localization of PI(4,5)P2 and odor response kinetics in OSNs. Our findings support the role of phosphoinositides as a modulator of the odor response and in ciliary biology of native multi-ciliated OSNs.
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http://dx.doi.org/10.1242/jcs.258364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126451PMC
March 2022

Microbiota alteration at different stages in gastric lesion progression: a population-based study in Linqu, China.

Am J Cancer Res 2021 1;11(2):561-575. Epub 2021 Feb 1.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute Beijing, China.

In addition to Helicobacter pylori (H.pylori), gastric microbiota may be involved in carcinogenesis process. However, the longitudinal study to assess changes in the gastric microbiota associated with the development of gastric carcinogenesis is still limited. The aim of this study is to explore dynamic microbial alterations in gastric cancer (GC) development based on a 4-year endoscopic follow-up cohort in Linqu County, China. Microbial alterations were investigated by deep sequencing of the microbial 16S ribosomal RNA gene in 179 subjects with various gastric lesions, and validated in paired gastric biopsies prospectively collected before and after lesion progression and in non-progression controls. Significant differences were found in microbial diversity and community structure across various gastric lesions, with 62 candidate differential taxa between at least two lesion groups. Further validations identified Helicobacter, Bacillus, Capnocytophaga and Prevotella to be associated with lesion progression-to-dysplasia (DYS)/GC (all P < 0.05), especially for subjects progressing from intestinal metaplasia (IM) to DYS/GC. The combination of the four genera in a microbial dysbiosis index showed a significant difference after lesion progression-to-DYS/GC compared to controls (P = 0.027). The panel including the four genera identified subjects after progression-to-DYS/GC with an area under the receiver-operating curve (AUC) of 0.941. Predictive significance was found before lesion progression-to-DYS/GC with an AUC = 0.776 and an even better AUC (0.927) for subjects progressing from IM to DYS/GC. Microbiota may play different roles at different stages in gastric carcinogenesis. A panel of bacterial genera associated with gastric lesions may help to assess gastric microbial dysbiosis and show potential predictive values for lesion progression. Our findings provide new clues for the microbial mechanism of H.pylori-associated carcinogenesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868750PMC
February 2021
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