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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 341-347, 2024 Jun.
Article in Zh | MEDLINE | ID: mdl-38953258

ABSTRACT

Objective To demonstrate the feasibility of oblique lumbar interbody fusion (OLIF) combined with 4-screw fixation for treating two-level lumbar degenerative diseases.Methods An intact finite element model of L3-S1 (M0) was constructed and validated.Then,we constructed the M1 model by simulating OLIF surgery at L3/4 and L4/5 segments on the M0 model.By attachment of posterior 4-screw or 6-screw fixation to the M1 model,three 4-screw fixation models (M2-M4) and one 6-screw fixation model (M5) were established.The segmental and overall range of motion (ROM) and the peak von Mises stresses of superior endplate,cage,and posterior screw-rod were investigated under each implanted condition.Results Under the motion modes of forward flexion,backward extension,bilateral (left and right) flexion,and left and right rotation,the L3/4 ROM of M2 model and L4/5 ROM of M3 model increased,while the L3/4 and L4/5 ROM of M4 and M5 models significantly decreased compared with those of M1 model.Under all motion modes,the L4 superior endplate in M2 model and the L5 superior endplate in M3 model showed the maximum peak von Mises stress,and the peak von Mises stresses of L4 and L5 superior endplates in M4 and M5 models were close.The L3/4 cage in M2 model and the L4/5 cage in M3 model showcased the largest peak von Mises stress,and the peak von Mises stresses of cages in M4 and M5 models were close.The peak stresses of internal fixation in M2-M5 models were close.Conclusion Four-screw fixation can replace 6-screw fixation in the OLIF surgery for treating two-level degenerative lumbar diseases.


Subject(s)
Bone Screws , Finite Element Analysis , Lumbar Vertebrae , Spinal Fusion , Spinal Fusion/methods , Spinal Fusion/instrumentation , Humans , Lumbar Vertebrae/surgery
2.
Phys Rev Lett ; 130(22): 228101, 2023 Jun 02.
Article in English | MEDLINE | ID: mdl-37327427

ABSTRACT

An associative polymer carries many stickers that can form reversible associations. For more than 30 years, the understanding has been that reversible associations change the shape of linear viscoelastic spectra by adding a rubbery plateau in the intermediate frequency range, at which associations have not yet relaxed and thus effectively act as crosslinks. Here, we design and synthesize new classes of unentangled associative polymers carrying unprecedentedly high fractions of stickers, up to eight per Kuhn segment, that can form strong pairwise hydrogen bonding of ∼20k_{B}T without microphase separation. We experimentally show that reversible bonds significantly slow down the polymer dynamics but nearly do not change the shape of linear viscoelastic spectra. This behavior can be explained by a renormalized Rouse model that highlights an unexpected influence of reversible bonds on the structural relaxation of associative polymers.


Subject(s)
Polymers , Polymers/chemistry , Hydrogen Bonding
3.
BMC Vet Res ; 19(1): 32, 2023 Feb 02.
Article in English | MEDLINE | ID: mdl-36732756

ABSTRACT

Higher dietary energy is often used to achieve better animal performance in mutton sheep production. Notably, changing the diet formula affects rumen fermentation and the microbiota of ruminants. In this study, we investigated the effect of dietary energy on rumen fermentation and ruminal microbiota in fattening sheep. Fifteen 2-month-old white-headed Suffolk sheep (♂) × Hu sheep (♀) crossbred lambs were randomly divided into three treatments based on the dietary energy of the feeds fed: 8.67 MJ/kg (Low energy (LE); n = 5), 10.38 MJ/kg (standard energy (CON); n = 5), and 12.31 MJ/kg (high energy (HE); n = 5) groups. After 70 days of feeding, sheep were slaughtered and the ruminal fluids were collected and analyzed to determine fermentation parameters. Microbiota was determined using metagenomics sequencing. Notably, the microbial cell protein (MCP) and butyric acid concentrations were significantly high in the HE group. Metagenomic sequencing revealed that ACE and Chao indexes of the HE group were significantly decreased. Four genera among the major classified taxa across all the kingdoms differed in relative abundance in the three dietary energy levels. The relative abundances of Prevotella_brevis, Succiniclasticum_ruminis, Prevotellace-ae_bacterium, and Lachnospiraceae_bacterium were significantly correlated with rumen fermentation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis further revealed that a high-energy diet increased lipid metabolism of microbiota. The Carbohydrate Active enzymes (CAZy) gene, which participates in energy metabolism, was upregulated, while genes regulating plant cell wall degradation were downregulated in the HE group. These results suggest that a high-energy diet had minimal influence on the rumen fermentation pattern but altered the composition of the rumen microbiota, enhancing microbial lipid metabolism and limiting crude fiber metabolism. The findings of this study provide scientific evidence of the effect of dietary energy on ruminant fermentation and fattening sheep production.


Subject(s)
Animal Feed , Rumen , Sheep , Animals , Rumen/metabolism , Animal Feed/analysis , Diet/veterinary , Butyrates , Energy Metabolism , Fermentation
4.
Perfusion ; 38(8): 1697-1704, 2023 11.
Article in English | MEDLINE | ID: mdl-36173344

ABSTRACT

OBJECTIVE: To determine the efficacy of sacubitril/valsartan plus dapagliflozin in the treatment of patients with pulmonary arterial hypertension (PAH) due to left heart disease and to explore new treatment regimen for PAH due to left heart disease. METHODS: This study is a randomized controlled trial (RCT) study of 120 patients with PAH due to left heart disease admitted to the cardiovascular department of our hospital from Dec. 2019 to Dec. 2021. The patients were randomized 1:1 to the study group and control group. All patients were given baseline treatments targeting left heart disease and symptoms of PAH. In addition to the baseline treatments, patients in the control group were given sacubitril/valsartan tablets, while patients in the study group were given sacubitril/valsartan tablets plus dapagliflozin tablets. After 6 months of treatment, parameters including left heart function and exercise tolerance, Hemodynamics (left ventricular end systolic diameter [LVSED], left ventricular end diastolic diameter [LVEDD], left ventricular ejection fraction [LVEF], 6 min walk distance (6MWD), mean pulmonary artery pressure (mPAP) and pulmonary artery systolic pressure (PASP)), vascular endothelial function (plasma endothelin (ET) -1 and nitric oxide [NO]), heart failure markers (plasma N-terminal pro-brain natriuretic peptide (NT-proBNP)], inflammatory factors (serum C reactive protein [CRP], interleukin (IL)-6, and tumor necrosis factor (TNF)-α], and adverse drug reactions (ADRs) were assessed in both groups. RESULTS: Both groups had reduced LVESD and LVEDD, increased LVEF, and extended 6MWD after 6 months of treatment. The improvements in these parameters were significantly greater in the study group than in the control group (all P < 0.05). In addition, both the mPAP and PASP showed a decrease, and the mPAP and PASP in the study group were lower than those in the control group (p<0.05). Furthermore, both groups had decreased plasma ET-1 and NT-proBNP but increased plasma NO after 6 months of treatment. The improvements in these parameters were significantly greater in the study group than in the control group (all P < 0.05). Serum CRP, IL-6 and TNF-α levels were decreased in both groups after 6 months of treatment, and were significantly lower in the study group than in the control group (all P < 0.05). There was no significant difference in the overall incidence of ADRs between the two groups (P > 0.05). CONCLUSION: Sacubitril/valsartan plus dapagliflozin in the treatment with PAH due to left heart disease can improve left heart function of patients by improving vascular endothelial functions and alleviating inflammation, which helps to reduce the PAH process. Therefore, this combination treatment is safe and effective in PAH due to left heart disease.


Subject(s)
Heart Diseases , Heart Failure , Pulmonary Arterial Hypertension , Humans , Heart Diseases/chemically induced , Heart Diseases/drug therapy , Heart Failure/complications , Heart Failure/drug therapy , Pulmonary Arterial Hypertension/chemically induced , Pulmonary Arterial Hypertension/drug therapy , Stroke Volume , Valsartan/therapeutic use , Valsartan/pharmacology , Ventricular Function, Left
5.
J Community Psychol ; 51(2): 531-538, 2023 03.
Article in English | MEDLINE | ID: mdl-36571799

ABSTRACT

Despite the remarkable improvements that have been achieved in the field of child development in contemporary China, there remain daunting challenges. To explore and address these issues, we organize this special issue "Child development in contemporary China: Toward a multisystems perspective." In this collection, we introduce theoretically-informed empirical research conducted by scholars worldwide and organize these research articles into four general themes: policy/program intervention regarding child development, migration status and child development, parenting/grandparenting and child development, and school/after-school engagement and child development. These articles keep abreast of theoretical, methodological, and practical innovations in the field, aiming to provide new evidence to enrich the understanding of the patterns and potential mechanisms that would lead to a (dis)advantaged childhood in China.


Subject(s)
Child Development , Schools , Child , Humans , China
6.
Pak J Pharm Sci ; 36(5): 1457-1466, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37869922

ABSTRACT

The effect of sericin in high glucose (HG)-induced podocyte injury and the mechanisms involving Snai1 and miR-30a-5p were investigated. Bioinformatics and dual-luciferase reporter assay evaluated the relationship of Snai1 with miR-31a-5p. Podocyte injury mouse induced by HG were randomly divided into control (5.5mmol/L D-glucose), HG (30mmol/L D-glucose), HG + Sericin (30mmol/L D-glucose+600µg/ml sericin), miR-30a-5p inhibitor NC (sericin+30mmol/L D-glucose+miR-30a-5p inhibitor negative control) and miR-30a-5p inhibitor groups (sericin+30mmol/L D-glucose+miR-30a-5p inhibitor). The migration ability of podocytes was detected by Transwell assay. The expressions of Snai1, podocin, E-cadherin, FSP-1, ZO-1, α-SMA, Desmin, and miR-30a-5p were assessed with RT-qPCR and Western blot. Snai1 was one direct target of miR-30a-5p. HG group had significantly larger number of migrated podocytes and higher levels of Snai1, FSP-1, α-SMA and Desmin, but significantly lower levels of podocin, ZO-1 and E-cadherin than control and HG + Sericin group. These effects of sericin were reversed by miR-30a-5p inhibitor, as evidenced by increased podocyte migration and increased expressions of Snai1, α-SMA, FSP-1 and Desmin, whereas decreased expressions of podocin, ZO-1 and E-cadherin. Sericin may protect podocytes from damage caused by HG via up-regulating epithelial phenotype markers, down-regulating mesenchymal phenotype markers, and reducing migration of podocytes. The mechanism may be through targeting miR-30a-5p and its target Snai1.


Subject(s)
Epithelial-Mesenchymal Transition , MicroRNAs , Podocytes , Sericins , Animals , Mice , Cadherins/metabolism , Desmin , Glucose/toxicity , MicroRNAs/metabolism , Podocytes/metabolism , Sericins/pharmacology
7.
Phys Rev Lett ; 128(23): 237801, 2022 Jun 10.
Article in English | MEDLINE | ID: mdl-35749195

ABSTRACT

The stretchability of polymeric materials is critical to many applications such as flexible electronics and soft robotics, yet the stretchability of conventional cross-linked linear polymers is limited by the entanglements between polymer chains. We show using molecular dynamics simulations that cross-linked ring polymers are significantly more stretchable than cross-linked linear polymers. Compared to linear polymers, the entanglements between ring polymers do not act as effective cross-links. As a result, the stretchability of cross-linked ring polymers is determined by the maximum extension of polymer strands between cross-links, rather than between trapped entanglements as in cross-linked linear polymers. The more compact conformation of ring polymers before deformation also contributes to the increase in stretchability.


Subject(s)
Elastomers , Polymers , Molecular Conformation , Molecular Dynamics Simulation
8.
Soft Matter ; 18(35): 6582-6591, 2022 Sep 14.
Article in English | MEDLINE | ID: mdl-35968884

ABSTRACT

Recent advances in the functional material and biomedical applications of nanorods call for a fundamental understanding of the active motion of nanorods in a viscoelastic medium. Molecular dynamics simulations are performed to investigate a model system consisting of force-driven active thin nanorods in a melt of unentangled polymers. The activeness of a thin nanorod arises from a constant external force applied uniformly along the rod. The simulations demonstrate that the active force overcomes the randomness of the diffusive motion and results in a ballistic motion along the direction of the applied force at long timescales. The constant speed of the force-driven ballistic motion is determined by the balance of the active force and the friction from the coupling of the nanorod with the polymer viscosity. The friction coefficient, which is computed as the ratio of the active force and the speed, decreases as the active force increases. The origin of the reduction in the friction coefficient is the high speed that allows the nanorod to renew its local environment faster than the relaxation time of melt chains. A scaling theory is developed to quantify the dependence of the friction coefficient on the strength of the active force. The simulations also demonstrate that the force-driven ballistic motion suppresses the rotational diffusion of the rod and cuts off the de-correlation of the rod axis with time. On the scaling level, the long-time trajectory of a force-driven active nanorod piercing through unentangled polymers may be described as a stretched array of "active blobs", where the short-time random-walk trajectory within an active blob is unperturbed by the active force.

9.
Exp Parasitol ; 235: 108234, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35218759

ABSTRACT

Cysteine proteases are involved in the digestion of host blood and the degradation of yolk proteins of arthropod ectoparasites. In this study, a cathepsin L-like cysteine proteinase gene (HasCPL) of Hyalomma asiaticum was cloned, and recombinant (r)HasCPL protein was generated for immunization study. Bioinformatic analysis confirmed HasCPL was a member of the papain family (clan CA) and have high sequence identities with CPLs of other Ixodid ticks. The efficacy of immunization against H. asiaticum infestations in rabbits was assessed. Rabbits (n = 3) were immunized three times with rHasCPL before challenged with 250 larvae per rabbit four weeks post-immunization. A high antibody titer was detected in immunized rabbits in comparison to control. Western blot analysis detected CPLs in midgut, salivary gland, and ovary. Increase of rejection percentage of larvae were noted in ticks fed on immunized animals in comparison to control. Overall, a 55.09% protection against larva ticks was noted.


Subject(s)
Cysteine Proteases , Ixodidae , Tick Infestations , Animals , Cysteine Proteases/genetics , Female , Immunization , Rabbits , Salivary Glands , Tick Infestations/prevention & control , Tick Infestations/veterinary
10.
BMC Nephrol ; 23(1): 228, 2022 06 27.
Article in English | MEDLINE | ID: mdl-35761207

ABSTRACT

BACKGROUND: Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare disease with a high mortality rate caused by VPS33B or VIPAS39 mutations. ARC syndrome typically presents with arthrogryposis, renal tubular leak and neonatal cholestatic jaundice, and most patients with this disease do not survive beyond one year. CASE PRESENTATION: Here, we report the case of a 13-year-old girl with ARC featuring an incomplete and mild phenotype with novel compound heterozygous mutations of VPS33B. The patient presented with arthrogryposis (claw-shaped limbs), ichthyosis, jaundice, and pruritus. Laboratory tests revealed highly evaluated levels of total bilirubin (TB), direct bilirubin (DB), and total bile acid (TBA) as well as normal levels of gamma-glutamyltransferase (GGT). However, signs of renal dysfunction, as well as other manifestations of ARC syndrome, including nervous system abnormalities, deafness, and failure to thrive, were not observed. The patient's clinical symptoms of jaundice and pruritus were significantly alleviated by administration of ursodeoxycholic acid. Whole-exome sequencing (WES) revealed novel compound heterozygous mutations of VPS33B, c.1081 C > T (p.Q361X,257)/c.244 T > C (p.C82R). Both variants were predicted to be pathogenic in silico and have never been reported previously. To date, the patients' cholestatic jaundice has been well controlled with continuous treatment of ursodeoxycholic acid. CONCLUSIONS: We report the case of a Chinese female with ARC including novel compound heterozygous mutations of VPS33B and an incomplete and mild phenotype. Early diagnosis and suitable symptomatic therapies are critical for the management of ARC patients with mild manifestations and prolonged lifespan.


Subject(s)
Arthrogryposis , Cholestasis , Jaundice, Obstructive , Renal Insufficiency , Arthrogryposis/diagnosis , Arthrogryposis/genetics , Bilirubin , Cholestasis/diagnosis , Cholestasis/genetics , Female , Humans , Mutation/genetics , Phenotype , Pruritus , Renal Insufficiency/diagnosis , Renal Insufficiency/genetics , Ursodeoxycholic Acid , Vesicular Transport Proteins/genetics
11.
Exp Appl Acarol ; 86(2): 283-298, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35133525

ABSTRACT

Hyalomma asiaticum and H. anatolicum are tick species in Eurasia and Africa with major medical and veterinary significance. Beside their direct pathogenic effects, H. asiaticum and H. anatolicum are vectors of important diseases of livestock and in some instances of zoonoses. In search of ways to address the increasing incidence of global acaricide resistance, tick control through vaccination is regarded as a sustainable alternative approach. Cathepsin L-like cysteine protease (CPL) is a potent hemoglobinase, and plays important roles in the digestion of blood acquired from a host. CPL from H. anatolicum (HanCPL) with high similarity (> 90%) for H. asiaticum CPL (HasCPL) were aligned by in silico analysis. After further in vitro validation, the anti-HasCPL sera have cross-reactivity between the different total native protein of life stages and tissues for H. asiaticum and H. anatolicum. Furthermore, we further confirmed that recombinant HasCPL (rHasCPL) immunized rabbits were partially cross-protected (54.8%) by H. anatolicum infestation.


Subject(s)
Acaricides , Ixodidae , Tick Infestations , Ticks , Animals , Antigens , Cathepsin L , Rabbits , Tick Infestations/veterinary
12.
J Community Psychol ; 50(7): 2808-2828, 2022 09.
Article in English | MEDLINE | ID: mdl-35060137

ABSTRACT

In recent years, research has begun to touch upon the associations between the natural environment and individuals' subjective wellbeing; however, whether such associations would vary among different groups of people remains under-studied. Using four waves (2010-2013) of data from the Chinese General Social Survey, we investigate the group-specific correlation between environment-specifically, greenspace exposure-and individuals' happiness in contemporary urban China. For this study, the normalized difference vegetation index at the county level is a proxy for greenspace exposure. The results from the ordered logit model indicate that county-level green vegetation is associated with individuals' happiness level, but such effects vary with a household's relative deprivation. While greenspace exposure is positively associated with happiness among individuals from less deprived families, it is negatively associated with happiness among those from deprived households. These findings contribute to the body of knowledge of the heterogeneous effect of greenspace on residents' subjective well-being.


Subject(s)
Happiness , Parks, Recreational , China , Environment , Humans , Logistic Models
13.
Yi Chuan ; 43(11): 1038-1049, 2021 Nov 20.
Article in English | MEDLINE | ID: mdl-34815207

ABSTRACT

Eukaryotic cilia and flagella are evolutionarily conserved organelles that protrude from the cell surface. The unique location and properties of cilia allow them to function in vital processes such as motility and signaling. Ciliary assembly and maintenance rely on intraflagellar transport (IFT). Bidirectional movement of IFT particles composed of IFT-A and IFT-B complexes is powered by kinesin-2 and dynein-2 motors. IFT delivers building blocks between their site of synthesis in the cell body and the ciliary assembly site at the tip of the cilium. The integrity of the flagellum, a specialized organelle of mammalian sperm to generate the motility, is critical for normal sperm function. Recent findings suggest that IFT is indispensable for sperm flagellum formation and male fertility in mice and human. In this review, we summarize the role and mechanisms of IFT proteins during enflagellation in spermiogenesis, thereby discussing the pathological mechanisms of male infertility and providing theoretical basis for the diagnosis and treatment of male infertility.


Subject(s)
Flagella , Kinesins , Animals , Biological Transport , Cilia/metabolism , Flagella/metabolism , Kinesins/metabolism , Male , Mice , Spermatogenesis
14.
Phys Rev Lett ; 124(2): 027801, 2020 Jan 17.
Article in English | MEDLINE | ID: mdl-32004030

ABSTRACT

Molecular dynamics simulations confirm recent extensional flow experiments showing ring polymer melts exhibit strong extension-rate thickening of the viscosity at Weissenberg numbers Wi≪1. Thickening coincides with the extreme elongation of a minority population of rings that grows with Wi. The large susceptibility of some rings to extend is due to a flow-driven formation of topological links that connect multiple rings into supramolecular chains. Links form spontaneously with a longer delay at lower Wi and are pulled tight and stabilized by the flow. Once linked, these composite objects experience larger drag forces than individual rings, driving their strong elongation. The fraction of linked rings depends nonmonotonically on Wi, increasing to a maximum when Wi∼1 before rapidly decreasing when the strain rate approaches 1/τ_{e}.

15.
Nutr Cancer ; 72(7): 1225-1230, 2020.
Article in English | MEDLINE | ID: mdl-31603353

ABSTRACT

Purpose: The consequences of malnutrition include increased risk of many complications. The assessment and management of nutritional problems are essential in supportive care of patients undergoing therapy. The primary objective of the present study was to assess changes in the nutritional status in lung cancer patients who had undergone chemotherapy.Patients and methods: Preliminary and post-chemotherapy assessments of patients' nutritional status and medical characteristics were conducted using the Patient-Generated Subjective Global Assessment (PG-SGA) from July 2014 to May 2016 at Harbin Medical University Cancer Hospital. Four hundred sixty-five advanced lung cancer patients (51.8% men and 48.2% women with a mean (SD) age of 60.2 ± 9.8 years) participated in the present study. PG-SGA was assessed prior to the initiation of chemotherapy and after four cycles of chemotherapy.Results: We found that 11.4% of the patients were severely malnourished and 65.6% of the patients were moderately malnourished prior to chemotherapy. After chemotherapy, 52.9% of the patients were considered moderately malnourished, whereas 33.8% were severely malnourished. The nutritional status had deteriorated in the majority of patients. After chemotherapy, there was a rise in the prevalence of nutrition impact symptoms.Conclusions: A deteriorated nutritional status was the result of the side effects caused by chemotherapy in the patients of the present study. These findings highlight that more attention should be paid to improve the nutritional status in patients with advanced lung cancer undergoing chemotherapy, and proper nutrition education and nutritional support should be provided to these patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Malnutrition/epidemiology , Nutritional Status , Small Cell Lung Carcinoma/drug therapy , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/epidemiology , Female , Humans , Lung Neoplasms/epidemiology , Male , Middle Aged , Nutrition Assessment , Prevalence , Prospective Studies , Small Cell Lung Carcinoma/epidemiology , Surveys and Questionnaires
16.
BMC Public Health ; 20(1): 293, 2020 Mar 06.
Article in English | MEDLINE | ID: mdl-32138702

ABSTRACT

BACKGROUND: Suicidal ideation is subject to serious underestimation among existing public health studies. While numerous factors have been recognized in affecting suicidal thoughts and behaviors (STB), the associated environmental risks have been poorly understood. Foremost among the various environment risks were air pollution, in particular, the PM2.5. The present study attempted to examine the relationship between PM2.5 level and local weekly index of suicidal ideation (ISI). METHODS: Using Internet search query volumes in Baidu (2017), the largest internet search engine in China, we constructed a prefectural panel data (278 prefectures, 52 weeks) and employed dynamic panel GMM system estimation to analyze the relationship between weekly concentration of PM2.5 (Mean = 87 µg·m- 3) and the index of suicidal ideation (Mean = 49.9). RESULTS: The results indicate that in the spring and winter, a 10 µg·m- 3 increase in the prior week's PM2.5 in a Chinese city is significantly associated with 0.020 increase in ISI in spring and a 0.007 increase in ISI in winter, after taking account other co-pollutants and meteorological conditions. CONCLUSION: We innovatively proposed the measure of suicidal ideation and provided suggestive evidence of a positive association between suicidal ideation and PM2.5 level.


Subject(s)
Environmental Exposure/statistics & numerical data , Particulate Matter/analysis , Suicidal Ideation , China , Cities , Humans , Internet , Search Engine , Seasons
17.
BMC Med Genet ; 20(1): 18, 2019 01 18.
Article in English | MEDLINE | ID: mdl-30658709

ABSTRACT

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a group of genetic autosomal recessive disorders that predominantly affects young children and results in early-onset progressive liver damage. Several types of PFIC were defined based on different genetic aetiologies in last decades. CASE PRESENTATION: Here, we report a Chinese young child diagnosed as PFIC with variants in tight junction protein 2 (TJP2). The patient was affected by a long history of jaundice, pruritus, and failure to thrive. Highly elevated level of serum total bile acid (TBA) and normal levels of gamma-glutamyltransferase (GGT) were observed at hospitalization. The patient's clinical symptoms could be alleviated by administration of ursodeoxycholic acid. Genetic testing by next generation sequencing (NGS) found novel compound heterozygote mutations c.2448 + 1G > C/c.2639delC (p.T880Sfs*12) in TJP2, which were inherited from her mother and father, respectively. Both mutations were predicted to abolish TJP2 protein translation, and neither has previously been identified. CONCLUSION: We report a Chinese female PFIC child with novel compound heterozygous mutations of TJP2. Genetic testing by NGS is valuable in the clinical diagnosis of hereditary liver disease.


Subject(s)
Cholestasis, Intrahepatic/genetics , High-Throughput Nucleotide Sequencing/methods , Mutation , Zonula Occludens-2 Protein/genetics , China , Female , Heterozygote , Humans , Infant , Maternal Inheritance , Paternal Inheritance , Sequence Analysis, DNA/methods
18.
BMC Cancer ; 19(1): 769, 2019 Aug 05.
Article in English | MEDLINE | ID: mdl-31382924

ABSTRACT

BACKGROUND: ROS1 rearrangements are validated drivers in lung cancer, which have been identified in a small subset (1-2%) of patients with non-small cell lung cancer (NSCLC). To date, 18 fusion genes of ROS1 have been identified in NSCLC. The ALK inhibitor (crizotinib) exhibits therapeutic effect against ROS1-rearranged NSCLC. Next-generation sequencing (NGS) technology represents a novel tool for ROS1 detection that covers many fusion genes. CASE PRESENTATION: A 55-year-old female with EGFR mutation (L858R) was diagnosed with lung adenocarcinoma, who was responsive to first-generation EGFR-tyrosine kinase inhibitor (TKI). Afterwards, she developed acquired resistance accompanied with a ROS1 rearrangement. A NGS assay showed that the tumor had a novel ROS1-ADGRG6 rearrangement generated by the fusion of exons of 1-33 of ROS1 on chr6: q22.1 to exons of 2-26 of ADGRG6 on chr6: q24.2. The patient was obviously responsive to crizotinib. CONCLUSION: We firstly identified ROS1-ADGRG6 fusion variant in NSCLC by NGS, which should be considered in further ROS1 detecting assays.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Crizotinib/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Oncogene Proteins, Fusion/genetics , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/genetics , Chromosomes, Human, Pair 6/genetics , Crizotinib/pharmacology , Drug Resistance, Neoplasm/genetics , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Exons/genetics , Female , Follow-Up Studies , Gene Rearrangement/genetics , High-Throughput Nucleotide Sequencing , Humans , Middle Aged , Mutation , Precision Medicine , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , Treatment Outcome
19.
Plant Physiol ; 173(2): 1342-1354, 2017 02.
Article in English | MEDLINE | ID: mdl-27999084

ABSTRACT

Ca2+ is absorbed by roots and transported upward through the xylem to the apoplastic space of the leaf, after which it is deposited into the leaf cell. In Arabidopsis (Arabidopsis thaliana), the tonoplast-localized Ca2+/H+ transporters CATION EXCHANGER1 (CAX1) and CAX3 sequester Ca2+ from the cytosol into the vacuole, but it is not known what transporter mediates the initial Ca2+ influx from the apoplast to the cytosol. Here, we report that Arabidopsis CYCLIC NUCLEOTIDE-GATED CHANNEL2 (CNGC2) encodes a protein with Ca2+ influx channel activity and is expressed in the leaf areas surrounding the free endings of minor veins, which is the primary site for Ca2+ unloading from the vasculature and influx into leaf cells. Under hydroponic growth conditions, with 0.1 mm Ca2+, both Arabidopsis cngc2 and cax1cax3 loss-of-function mutants grew normally. Increasing the Ca2+ concentration to 10 mm induced H2O2 accumulation, cell death, and leaf senescence and partially suppressed the hypersensitive response to avirulent pathogens in the mutants but not in the wild type. In vivo apoplastic Ca2+ overaccumulation was found in the leaves of cngc2 and cax1cax3 but not the wild type under the 10 mm Ca2+ condition, as monitored by Oregon Green BAPTA 488 5N, a low-affinity and membrane-impermeable Ca2+ probe. Our results indicate that CNGC2 likely has no direct roles in leaf development or the hypersensitive response but, instead, that CNGC2 could mediate Ca2+ influx into leaf cells. Finally, the in vivo extracellular Ca2+ imaging method developed in this study provides a new tool for investigating Ca2+ dynamics in plant cells.


Subject(s)
Arabidopsis/metabolism , Calcium/metabolism , Cyclic Nucleotide-Gated Cation Channels/metabolism , Plant Leaves/metabolism , Antiporters/genetics , Antiporters/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Calcium/analysis , Cation Transport Proteins/genetics , Cation Transport Proteins/metabolism , Cyclic Nucleotide-Gated Cation Channels/genetics , HEK293 Cells , Humans , Molecular Imaging/methods , Mutation , Plant Leaves/growth & development , Plants, Genetically Modified
20.
Phys Rev Lett ; 120(5): 057801, 2018 Feb 02.
Article in English | MEDLINE | ID: mdl-29481209

ABSTRACT

We use molecular simulations to probe the local viscoelasticity of an entangled polymer melt by tracking the motion of embedded nonsticky nanoparticles (NPs). As in conventional microrheology, the generalized Stokes-Einstein relation is employed to extract an effective stress relaxation function G_{GSE}(t) from the mean square displacement of NPs. G_{GSE}(t) for different NP diameters d are compared with the stress relaxation function G(t) of a pure polymer melt. The deviation of G_{GSE}(t) from G(t) reflects the incomplete coupling between NPs and the dynamic modes of the melt. For linear polymers, a plateau in G_{GSE}(t) emerges as d exceeds the entanglement mesh size a and approaches the entanglement plateau in G(t) for a pure melt with increasing d. For ring polymers, as d increases towards the spanning size R of ring polymers, G_{GSE}(t) approaches G(t) of the ring melt with no entanglement plateau.

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