Current Status of Liverwort Herbaria Specimens and Geographical Distribution in China.

Specimen data play a crucial role in geographical distribution research. In this study, the collection information of liverwort specimens in China was compiled and analyzed to investigate the history, current status, and limitations of liverwort research in China. By utilizing the latest systematic research findings and corresponding environmental data, a niche model was developed to offer theoretical support for exploring the potential geographical distribution and diversity of liverwort resources. A total of 55,427 liverwort specimens were collected in China, resulting in the recording of 1212 species belonging to 169 genera and 63 families. However, there are imbalances in the distributions of liverwort data among different groups, collection units, and geographical areas, with families such as Lejeuneaceae, Porellaceae, and Plagiochilaceae having the highest number of specimens. Similarly, genera such as Porella, Frullania, and Horikawaella were well represented. Remarkably, 125 species had specimen counts exceeding 100. Unfortunately, approximately 51.77% of the species had fewer than 10 recorded specimens. There were four obvious peaks in the collection years of the bryophyte specimens in China, among which the largest collection occurred from 2010 to 2023. Notably, the number of specimens collected at different stages closely aligned with the history of taxonomic research on liverworts in China. The results of the integrity of the liverwort collection indicate that there is insufficient representation of some families and genera, with a concentration of common and widely distributed large families and genera. Tropical and subtropical humid areas are key regions for liverwort diversity, with water and temperature being the primary environmental factors influencing their geographical distribution. The specific temporal and spatial data of species recorded from plant specimens will enhance the study of species diversity, comprehensive protection, and sustainable utilization. Additionally, these data will contribute to the investigation of large-scale biodiversity distribution patterns and the impact of global change on diversity.

Pathobiological characterization of a novel duck picornavirus in duck in China.

A novel strain of duck picornavirus was isolated from duck tissue in Taian, Shandong Province, in 2017 in our laboratory. The virus was amplified in specific-pathogen-free (SPF) chicken embryos, purified and then analyzed by whole genome sequencing, which revealed a new duck-derived small RNA virus that was designated as Duck/FC22/China/2017 (FC22, GenBank accession no. MN102111) based on its genome structure and phylogenetic relationship. An in-depth study revealed that the virus grew well on the Leghorn male hepatoma (LMH) cell line. After propagation of the virus, SPF ducks were inoculated for pathogenicity tests, and their mental state, growth and development were observed after inoculation; the ducks were dissected to observe the organs and histopathological changes. A TaqMan fluorescence quantitative PCR method was utilized to detect the proliferation and shedding patterns of the virus within the ducks, while the SYBR Green I fluorescence quantitative PCR method was used to assess cytokine expression levels in the organs. The results showed that following inoculation with the FC22 strain, the mental status of the SPF ducks remained unchanged. Mild oedema was observed in some tissue organs during dissection; however, no pathological changes, such as congestion or degeneration, were noted. Histopathological analysis revealed cellular necrosis in organs, including the heart, liver, and bursa of Fabricius, as well as a reduced volume and deep staining of certain neurons in the cerebrum. Following infection, the virus titres in various organs and in cloacal swabs of the SPF ducks peaked on the first day before gradually decreasing daily. By the 10th d, the virus titres in all organs had decreased to less than 101 copies/µL. Additionally, notable alterations were observed in the expression levels of the cytokines IFNα, IL6, IL10, and TNFα. This indicates that the FC22 strain does not cause significant disease in ducks. This report presents the initial study on a recently discovered picornavirus, offering a thorough and methodical examination of its pathogenic characteristics and provides a reference for the clinical evaluation and scientific strategies for the prevention and treatment of this particular picornavirus.

Physiological effects of field concentrations and sublethal concentrations of sulfoxaflor on Apis mellifera.

BACKGROUND: Bees (Apis mellifera), as important pollinators of agricultural crops, are at risk when pesticides are used. Sulfoxaflor is a new insecticide which acts on the nicotinic acetylcholine receptor (nAChR) in a similar way to neonicotinoids. The goal of this study is to evaluate the toxicity of sulfoxaflor and its effect on the A. mellifera exposure. RESULTS: Initially, developmental indicators such as larval survival, pupation, and eclosion were inhibited by 5.0 mg/L (field concentration) sulfoxaflor. In the pupal stage, fat content was significantly increased, while the glycogen content decreased. In addition, A. mellifera heads were treated with 2.0 mg/L (sublethal concentration) of sulfoxaflor and analyzed by RNA sequencing. The transcriptome results indicated that 2.0 mg/L amounts of sulfoxaflor have adverse effects on the immune, digestive, and nervous systems. Sulfoxaflor down-regulated the expression of many genes involved in immunity, detoxification, the myosin cytoskeleton, sensory neurons, and odor-binding proteins. CONCLUSION: Field concentration and sublethal concentration were used for the combined analysis of honeybees. The effect of sublethal concentration of sulfoxaflor on honeybees was studied for the first time from the perspective of transcriptome sequencing of honeybee head. A preliminary study was carried out on the stress of sulfoxaflor at sublethal concentration on honeybee workers, which has certain research significance and can provide theoretical basis for the use of sulfoxaflor in the field environment. © 2024 Society of Chemical Industry.

A key ABA biosynthetic gene OsNCED3 is a positive regulator in resistance to Nilaparvata lugens in Oryza sativa.

The gene encoding 9-cis-epoxycarotenoid dioxygenase 3 (NCED3) functions in abscisic acid (ABA) biosynthesis, plant growth and development, and tolerance to adverse temperatures, drought and saline conditions. In this study, three rice lines were used to explore the function of OsNCED3, these included an OsNCED3-overexpressing line (OsNCED3-OE), a knockdown line (osnced3-RNAi) and wild-type rice (WT). These rice lines were infested with the brown plant hopper (BPH; Nilaparvata lugens) and examined for physiological and biochemical changes, hormone content, and defense gene expression. The results showed that OsNCED3 activated rice defense mechanisms, which led to an increased defense enzyme activity of superoxide dismutase, peroxidase, and polyphenol oxidase. The overexpression of OsNCED3 decreased the number of planthoppers and reduced oviposition and BPH hatching rates. Furthermore, the overexpression of OsNCED3 increased the concentrations of jasmonic acid, jasmonyl-isoleucine and ABA relative to WT rice and the osnced3-RNAi line. These results indicate that OsNCED3 improved the stress tolerance in rice and support a role for both jasmonates and ABA as defense compounds in the rice-BPH interaction.

Response to Climate Change and GAP Analysis of Thuja koraiensis Nakai.

Due to global warming and increased human activity, the wild population of Thuja koraiensis Nakai (T. koraiensis) has dropped, placing it in danger. An understanding of the response of T. koraiensis to climate change and the determination of priority conservation areas are tremendously critical for proper conservation. Using sixty-nine T. koraiensis distribution points and seven environmental factors, the Maxent model was used to predict potentially suitable areas and spatial variation patterns of T. koraiensis and the Marxan conservation planning model was used to evaluate conservation gap areas. Research shows that the dominant environmental factors affecting the distribution of potentially suitable areas for T. koraiensis included elevation, precipitation of the driest month, isothermality and precipitation of the wettest quarter. Under the current climatic conditions, highly suitable areas for T. koraiensis are mainly distributed in the Changbai Mountains within Samjiyon County and Baishan City, the Hamgyong Mountains within the western part of Hamgyong-Bukto Province, and the T'aeback-Sanmaek Mountains within Gangwon-do, Kumgangsan Special Administrative Region and Kangwon-do. Under future climate conditions, suitable areas for T. koraiensis show a decreasing trend, and the suitable area will be reduced to higher elevations, and the Hamgyong Mountains may become a refuge. Based on GAP analysis, 69.69% of the priority conservation areas of T. koraiensis are located outside of the nature reserve, and these conservation gap areas are primarily in the southern part of the Changbai Mountains and Kangwon-do.

Efficacy and Safety of DPP-4 Inhibitors and Metformin Combinations in Type 2 Diabetes: A Systematic Literature Review and Network Meta-Analysis.

Objective: Several oral antidiabetic regimens are available for treating type 2 diabetes mellitus (T2DM), dipeptidyl peptidase-4 inhibitors (DPP4i) being one of them. We conducted a network meta-analysis (NMA) comparing DPP4i plus metformin (Met) combination with other Met-based oral antidiabetic drug (OAD) combinations used in treating patients with T2DM. Methods: We searched PubMed and Embase from inception until 19th April, 2022 for phase II and phase III trials in patients with T2DM on Met-based traditional OADs. The primary outcome was assessed by change in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and 2-hour post-prandial blood glucose (2h-PPG). The secondary safety outcomes assessed were hypoglycemic events, serious adverse events (SAEs), cardiovascular (CV) events, and gastrointestinal (GI) events. Results: Sixty-two trials were included in the analysis. The combination of DPP4i + Met revealed a comparable mean reduction in HbA1c levels to the glinides (Gli) + Met combination (mean difference [MD]: -0.03%, 95% CI: 0.69, -0.65), although the difference was not statistically significant. The mean HbA1c reduction with DPP4i + Met was greater than with sulfonylureas (SU) + Met (MD: -0.05, 95% CI: -0.29, 0.39), thiazolidinedione (TZD) + Met (MD: -0.69, 95% CI: -1.39, -0.02), and SU + TZD (MD: 0.21; 95% CI: -1.30, 1.71), with no statistical significance. DPP4i + Met demonstrated a non-significant lower incidence of CV events in comparison to TZD + Met (RR: 1.01, 95% CI: 0.46, 2.45) and SU + Met (RR: 1.06, 95% CI: 0.61, 2.06). Conclusion: DPP4i in combination with Met was efficacious and had a well-tolerated safety profile compared with other traditional OADs. This combination can be considered as a suitable treatment option for patients with T2DM.

CNOT7 regulates lipid deposition in nonalcoholic fatty liver disease.

BACKGROUND: In recent years, the incidence rate of nonalcoholic fatty liver disease (NAFLD) has ascended with the increasing number of metabolic diseases such as obesity and diabetes, which will bring great medical burden to society. At present, multiple scientific experiments have found that the CCR4-NOT complex can participate in regulating obesity and energy metabolism. This study is designed to explore the role and mechanism of CCR4-NOT transcription complex subunit 7 (CNOT7), a subunit of the CCR4-NOT complex in liver lipid deposition. METHODS: To establish the NAFLD cell model, palmitic acid (PA) was utilized to stimulate HepG2 cells and LO2 cells, promoting intracellular lipid deposition. CNOT7 was knockdown by siRNA and lentivirus to evaluate the effect of CNOT7 in NAFLD. RESULTS: Our results demonstrated that the expression of CNOT7 was increased in the NAFLD cell model. After knocking down CNOT7, the lipid deposition declined in HepG2 or LO2 cells treated by PA reduced. We found the lipid synthesis genes and the lipid uptake and transport factors in the CNOT7 knockdown group were significantly downregulated compared to the non-knockdown group. Furthermore, knockdown of CNOT7 might promote fatty acid oxidation. CONCLUSION: Knocking down CNOT7 can improve lipid deposition and CNOT7 may be a potential therapeutic target for NAFLD.

[Expansion of the genotypic and phenotypic spectrum and treatment of four children with Steroid-resistant nephrotic syndrome due to variants of TRPC6 gene].

OBJECTIVE: To summarize the clinical and genetic characteristics, treatment and prognosis of four children with Steroid-resistant nephrotic syndrome (SRNS) due to variants of TRPC6 gene. METHODS: Clinical data of four children with SRNS admitted to Children's Hospital Affiliated to Zhengzhou University between May 2020 and August 2022 were collected. Peripheral blood samples were collected from the children and their parents, and whole exome sequencing was carried out. Sanger sequencing was used to verify the pathogenicity of the candidate variants among the children and their parents. RESULTS: All of the four children were found to harbor heterozygous variants of the TRPC6 gene, including c.523C>T (p.R175W), c.1327T>A (p.F443I), c.430G>C (p.E144Q) (unreported previously), and c.523C>T (p.R175W), which were all missense variants. Two of the children have shown a simple type, whilst two have shown a nephritis type, none had extrarenal phenotype. Comprehensive renal pathology of three children revealed focal segmental glomerulosclerosis (FSGS). Two children were treated with steroids combined with calcineurin inhibitors (CNIs), among whom one showed significant improvement in symptoms. CONCLUSION: Discoveries of the novel c.430G>C variant and the new SRNS phenotype of the c.1327T>A variant have expanded the mutational and phenotypic spectrum of the TRPC6 gene, which has provided a reference for clinical diagnosis and genetic counseling for the families.

Exogenous ABA promotes resistance to Sitobion avenae (Fabricius) in rice seedlings.

BACKGROUND: Over the course of evolution, plants have developed various sophisticated defense mechanisms to resist pests and diseases. The phytohormone abscisic acid (ABA) has an important role in the growth and development of plants and confers tolerance to selected abiotic stressors, such as drought. Previous studies have shown that ABA promotes the deposit of callose in response to piercing/sucking insect pests. The English grain aphid, Sitobion avenae Fabricius, causes huge losses in rice and is especially harmful to rice seedlings. RESULTS: Exogenous ABA promoted growth and reduced the feeding behavior of S. avenae nymphs in rice. Our results suggested that enhanced trichome density and increased expression of related genes may be associated with rice resistance to aphids. An analysis of volatiles revealed the production of seven compounds associated with pest resistance. CONCLUSION: These results indicate that ABA reduces aphid feeding in rice. Our findings provide a basis for understanding ABA-mediated defense responses in rice and provide insights on more environmentally-friendly approaches to control. © 2024 Society of Chemical Industry.

[COL4A5 genotypes and clinical characteristics of children with Alport syndrome]. / 儿童Alport综合征COL4A5åŸºå› åž‹åŠä¸´åºŠç‰¹ç‚¹åˆ†æž.

OBJECTIVES: To investigate the genotypes of the pathogenic gene COL4A5 and the characteristics of clinical phenotypes in children with Alport syndrome (AS). METHODS: A retrospective analysis was performed for the genetic testing results and clinical data of 19 AS children with COL4A5 gene mutations. RESULTS: Among the 19 children with AS caused by COL4A5 gene mutations, 1 (5%) carried a new mutation of the COL4A5 gene, i.e., c.3372A>G(p.P1124=) and presented with AS coexisting with IgA vasculitis nephritis; 3 children (16%) had large fragment deletion of the COL4A5 gene, among whom 2 children (case 7 had a new mutation site of loss51-53) had gross hematuria and albuminuria at the onset, and 1 child (case 13 had a new mutation site of loss3-53) only had microscopic hematuria, while the other 15 children (79%) had common clinical phenotypes of AS, among whom 7 carried new mutations of the COL4A5 gene. Among all 19 children, 3 children (16%) who carried COL4A5 gene mutations also had COL4A4 gene mutations, and 1 child (5%) had COL4A3 gene mutations. Among these children with double gene mutations, 2 had gross hematuria and proteinuria at the onset. CONCLUSIONS: This study expands the genotype and phenotype spectrums of the pathogenic gene COL4A5 for AS. Children with large fragment deletion of the COL4A5 gene or double gene mutations of COL4A5 with COL4A3 or COL4A4 tend to have more serious clinical manifestations.

Novel compound heterozygous WDR35 variants in a Chinese patient associated with cranioectodermal dysplasia and ectopic testis: a case report and review of the literature.

BACKGROUND: WDR35 variants are known to cause a rare autosomal recessive disorder-Cranioectodermal dysplasia (CED). The CED patients are commonly present with facial dysmorphisms (frontal bossing and low-set ears), sagittal craniosynostosis, growth retardation, dolichocephaly, skeletal deformities (brachydactyly, terminal hypoplasia of the fingers and narrow thorax), ectodermal abnormalities (sparse hair, and finger/toe nail dysplasia), nephronophthisis, retinal dystrophy and hepatic fibrosis. Diagnosis of CED can be difficult because it presents with high genetic heterogeneity. However, our understanding of the phenotype of CED caused by WDR35 variants could be more explicit, and the correlation between genotype and phenotype needs further improvement. CASE PRESENTATION: We report a case of the first Chinses patient of CED caused by WDR35 variants, a 3-year-and-3-month-old patient, who was admitted to our hospital with frontal bossing, growth retardation, low set ears, dolichocephaly, sparse hair, and small limbs, abnormal renal function, and moderate anemia. The child showed a novel phenotype of the ectopic testis except for presenting typical CED characteristics, and he was identified with novel compound heterozygous WDR35 variants (c.2590 C > T, p.Gln864* and c.2408_2416del, p.Asn803_Ala805del; NM_001006657). He was given iron succinate and erythropoietin to improve anemia and to inhibit repeated metabolic acidosis and hyperkalemia through acid correction, diuretic, and potassium-lowering treatments. The parents refused to accept renal replacement therapy for their child and were discharged voluntarily. CONCLUSIONS: This is the first reported case of the WDR35 variants that can lead to CED and ectopic testis, which is also the first Chinese patient associated with WDR35 variants. This study expands our understanding of genotype-phenotype association in patients with WDR35 variants and provides genetic counseling for prevention and intervention in this genetic disorder. Neonatal carriers should be followed up for kidney and CED-related diseases to detect warning signs.

Transcriptome profiling in rice reveals a positive role for OsNCED3 in defense against the brown planthopper, Nilaparvata lugens.

9-cis-epoxycarotenoid dioxygenase (NCED) is the rate-limiting enzyme for abscisic acid (ABA) biosynthesis in higher plants. In rice, OsNCED3 was shown to promote ABA synthesis, and improve abiotic stress tolerance, but the function of OsNCED3 in regulating rice defense against the brown planthopper (Nilaparvata lugens; BPH) has been unclear. In this study, several parameters were used to assess rice resistance to BPH, including the average injury level, the functional plant loss index, and electrical penetration graph analysis. Rice lines overexpressing OsNCED3 (OE) were more resistant to BPH than the wild-type cv. Zhonghua11 (WT). Transcriptome analysis was performed on WT, OE, and a RNAi transgenic line silenced for OsNCED3; these three lines were either infested or non-infested with BPH. Seventeen RNA libraries were compared, and most of the differentially expressed genes (DEGs) were upregulated. The number of DEGs in the RNAi line infested with BPH was significantly higher than the OE, and WT lines, and many DEGs were related to the stress response, and biosynthesis of jasmonic acid. This study shows that overexpression of OsNCED3 in rice improves resistance to BPH, and has potential merit in rice breeding programs.

Transcriptome Analysis Reveals Crosstalk between the Abscisic Acid and Jasmonic Acid Signaling Pathways in Rice-Mediated Defense against Nilaparvata lugens.

The brown planthopper (BPH) impacts both rice yield and quality. The exogenous application of abscisic acid (ABA) and jasmonic acid (JA) has been previously shown to induce rice resistance to BPH; however, the regulation of rice-mediated defense by these plant growth regulators is unclear. We applied exogenous JA and ABA to rice and analyzed molecular responses to BPH infestation. Nine RNA libraries were sequenced, and 6218 differentially expressed genes (DEGs) were generated and annotated. After ABA + BPH and JA + BPH treatments, 3491 and 2727 DEGs, respectively, were identified when compared with the control (BPH alone). GO enrichment and KEGG pathway analysis showed that the expression of several JA pathway genes (OsAOS2, encoding allene oxide synthase; OsOPR, 12-oxo-phytodienoic acid reductase; and OsACOX, acy1-CoA oxidase) were significantly up-regulated after ABA + BPH treatment. Furthermore, exogenous JA increased the expression of genes involved in ABA synthesis. Meanwhile, the expression levels of genes encoding WRKY transcription factors, myelocytomatosis protein 2 (MYC2) and basic leucine zippers (bZIPs) were up-regulated significantly, indicating that ABA and JA might function together to increase the expression of transcription factors during the rice defense response. The DEGs identified in this study provide vital insights into the synergism between ABA and JA and further contribute to the mechanistic basis of rice resistance to BPH.

The mechanism and effects of remdesivir-induced developmental toxicity in zebrafish: Blood flow dysfunction and behavioral alterations.

The antiviral drug remdesivir has been used to treat the growing number of coronavirus disease 2019 (COVID-19) patients. However, the drug is mainly excreted through urine and feces and introduced into the environment to affect non-target organisms, including fish, which has raised concerns about potential ecotoxicological effects on aquatic organisms. Moreover, studies on the ecological impacts of remdesivir on aquatic environments have not been reported. Here, we aimed to explore the toxicological impacts of microinjection of remdesivir on zebrafish early embryonic development and larvae and the associated mechanism. We found that 100 µM remdesivir delayed epiboly and impaired convergent movement of embryos during gastrulation, and dose-dependent increases in mortality and malformation were observed in remdesivir-treated embryos. Moreover, 10-100 µM remdesivir decreased blood flow and swimming velocity and altered the behavior of larvae. In terms of molecular mechanisms, 80 differentially expressed genes (DEGs) were identified by transcriptome analysis in the remdesivir-treated group. Some of these DEGs, such as manf, kif3a, hnf1ba, rgn, prkcz, egr1, fosab, nr4a1, and ptgs2b, were mainly involved in early embryonic development, neuronal developmental disorders, vascular disease and the blood flow pathway. These data reveal that remdesivir can impair early embryonic development, blood flow and behavior of zebrafish embryos/larvae, probably due to alterations at the transcriptome level. This study suggests that it is important to avoid the discharge of remdesivir to aquatic ecosystems and provides a theoretical foundation to hinder remdesivir-induced ecotoxicity to aquatic environments.

Physiological and Population Responses of Nilaparvata lugens after Feeding on Drought-Stressed Rice.

Drought stress greatly impacts insect development and population growth. Some studies have demonstrated increased reproductive capacity in drought-stressed insects; however, physiological changes in the brown planthopper (BPH), Nilaparvata lugens (Stål), during periods of drought are unclear. In this study, BPH fed on drought- stressed rice had lower population numbers than BPH feeding on non-stressed rice. Water content, osmotic pressure of hemolymph and total amino acid content of BPH were significantly lower when BPH fed on drought-stressed rice compared to the non-stressed control; however, glucose content and glutathione S-transferase (GST) activity were significantly higher in BPH fed on drought-stressed rice. The expression of Vitellogenin and Exuperantia in BPH fed on drought-stressed rice was higher than that in BPH feeding on non-stressed control plants. The size of myofibrils and the abundance of mitochondria in BPH flight muscles were significantly lower in BPH fed on drought-stressed rice compared to non-stressed plants. These results indicate that water management impacts the physiology of BPH, which may be useful in understanding the relationship between drought stress and this damaging herbivore.

An aspartic protease 47 causes quantitative recessive resistance to rice black-streaked dwarf virus disease and southern rice black-streaked dwarf virus disease.

Rice black-streaked dwarf virus disease (RBSDVD) and southern rice black-streaked dwarf virus disease (SRBSDVD) are the most destructive viral diseases in rice. Progress is limited in breeding due to lack of resistance resource and inadequate knowledge on the underlying functional gene. Using genome-wide association study (GWAS), linkage disequilibrium (LD) decay analyses, RNA-sequencing, and genome editing, we identified a highly RBSDVD-resistant variety and its first functional gene. A highly RBSDVD-resistant variety W44 was identified through extensive evaluation of a diverse international rice panel. Seventeen quantitative trait loci (QTLs) were identified among which qRBSDV6-1 had the largest phenotypic effect. It was finely mapped to a 0.8-1.2 Mb region on chromosome 6, with 62 annotated genes. Analysis of the candidate genes underlying qRBSDV6-1 showed high expression of aspartic proteinase 47 (OsAP47) in a susceptible variety, W122, and a low resistance variety, W44. OsAP47 overexpressing lines exhibited significantly reduced resistance, while the knockout mutants exhibited significantly reduced SRBSDVD and RBSDVD severity. Furthermore, the resistant allele Hap1 of OsAP47 is almost exclusive to Indica, but rare in Japonica. Results suggest that OsAP47 knockout by editing is effective for improving RBSDVD and SRBSDVD resistance. This study provides genetic information for breeding resistant cultivars.

Diagnosis, treatment and genetic analysis of 11ß -hydroxylase deficiency caused by CYP11B gene mutation.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive hereditary disease, and the 11ß- hydroxylase deficiency is the second most common syndrome in different types of CAH. The occurrence of 11ß- hydroxylase deficiency is related to the mutation of CYP11B gene on human autosome 8. In this report, we detected the gene mutation sites of a 14-year-old patient with 11ß-hydroxylase deficiency by whole exon sequencing (WES), verified the suspected mutation by Sanger sequencing, and analyzed its characteristics. Gene sequencing revealed that homozygous missense mutation of c.1226C>T appeared on the 8th exon of CYP11B1 gene, which resulted in the mutation of the encoding protein Ser409 to phenylalanine (p. Ser409Phe), affecting the binding of heme and enzyme and resulting in the loss of CYP11B1 enzyme activity and a series of clinical symptoms. This mutation has not been reported at home and abroad. This case enriches the variation spectrum of CYP11B1 gene and provides clinical data and genetic resources for further research on the pathogenesis of 11ß-hydroxylase deficiency.

Graphene oxide promoted chromium uptake by zebrafish embryos with multiple effects: Adsorption, bioenergetic flux and metabolism.

The increasing production and application of graphene oxide (GO, a popular carbon nanomaterial), makes their release into aqueous environment inevitably. The capability of GO to enhance the toxicity of background contaminants has been widely concerned. However, the effect of GO on heavy metal accumulation in fish embryos remains unclear. Here, we show that GO-promoted chromium (Cr) uptake by zebrafish embryos with multiple effects. The adsorption accelerated the aggregation and settlement of Cr6+-adsorbed GO and decreased the Cr6+ concentration in the upper water, which enhanced the interaction of chorions and contaminants (Cr6+, GO and Cr6+-adsorbed GO). In the presence of GO, the Cr content in chorions and intra-chorion embryos was increased by four times and 57% respectively, compared to that of the single Cr6+ exposure. Furthermore, GO+Cr6+ increased the oxygen consumption rates, embryonic acid extrusion rates and ATP production, induced more serious oxidative stress, and disturbed amino acid metabolism, fatty acid metabolism and TCA cycle. These findings provide new insights into the effect of GO on heavy metal bioaccumulation and toxicity during embryogenesis.

The Adaptor Protein Lurap1 Is Required for Cell Cohesion during Epiboly Movement in Zebrafish.

Cell adhesion and polarized cellular behaviors play critical roles in a wide variety of morphogenetic events. In the zebrafish embryo, epiboly represents an important process of epithelial morphogenesis that involves differential cell adhesion and dynamic cell shape changes for coordinated movements of different cell populations, but the underlying mechanism remains poorly understood. The adaptor protein Lurap1 functions to link myotonic dystrophy kinase-related Rac/Cdc42-binding kinase with MYO18A for actomyosin retrograde flow in cell migration. We previously reported that it interacts with Dishevelled in convergence and extension movements during gastrulation. Here, we show that it regulates blastoderm cell adhesion and radial cell intercalation during epiboly. In zebrafish mutant embryos with loss of both maternal and zygotic Lurap1 function, deep cell multilayer of the blastoderm exhibit delayed epiboly with respect to the superficial layer. Time-lapse imaging reveals that these deep cells undergo unstable intercalation, which impedes their expansion over the yolk cell. Cell sorting and adhesion assays indicate reduced cellular cohesion of the blastoderm. These defects are correlated with disrupted cytoskeletal organization in the cortex of blastoderm cells. Thus, the present results extend our previous works by demonstrating that Lurap1 is required for cell adhesion and cell behavior changes to coordinate cell movements during epithelial morphogenesis. They provide insights for a further understanding of the regulation of cytoskeletal organization during gastrulation cell movements.

Prognosis of radiotherapy in medullary thyroid carcinoma patients without distant metastasis.

BACKGROUND: Medullary thyroid carcinoma (MTC) is an advanced disease with a poor prognosis. Although radiotherapy is widely utilized to treat MTC, it is still controversial. MTC patients without distant metastases have not been investigated to explore indications for adjuvant radiotherapy. This study aims to investigate the impact of radiotherapy on the survival of MTC patients without distant metastases. METHODS: Data of MTC patients without distant metastasis who underwent total thyroidectomy between 2010 and 2015 were obtained from the Surveillance, Epidemiology and End Results (SEER) database. Propensity score matching was performed to analyze the relationship between radiotherapy and cancer-specific survival (CSS). RESULTS: Seventy-four of 718 MTC patients without distant metastases received radiotherapy and underwent total thyroidectomy. A total of 148 patients were screened via propensity score matching analysis. Multivariate Cox regression indicated that factors including age, sex, radiotherapy and chemotherapy were independent predictors of CSS. Based on these factors, MTC patients without distant metastasis were classified into two risk groups using a nomogram and risk classification system. The C-index of the nomogram was 0.791. The calibration curves showed good consistency of CSS between the actual observation and the nomogram prediction, and decision curve analysis (DCA) showed great clinical usefulness of the nomogram. The three-year CSS of the radiotherapy group was 85.3%, and that of the surgery group was 95%. Particularly, compared with the surgery group, the three-year CSS of subgroups of the radiotherapy group, including male patients and those aged >48 years, was decreased. CONCLUSIONS: Radiotherapy results in worse CSS for MTC patients without distant metastases. To maximize benefits, decisions about individual radiotherapy should weigh its advantages and disadvantages.