Uncertainty quantification of CO2 emissions from China's civil aviation industry to 2050.

To mitigate aviation's carbon emissions of the aviation industry, the following steps are vital: accurately quantifying the carbon emission path by considering uncertainty factors, including transportation demand in the post-COVID-19 pandemic period; identifying gaps between this path and emission reduction targets; and providing mitigation measures. Some mitigation measures that can be employed by China's civil aviation industry include the gradual realization of large-scale production of sustainable aviation fuels and transition to 100% sustainable and low-carbon sources of energy. This study identified the key driving factors of carbon emissions by using the Delphi Method and set scenarios that consider uncertainty, such as aviation development and emission reduction policies. A backpropagation neural network and Monte Carlo simulation were used to quantify the carbon emission path. The study results show that China's civil aviation industry can effectively help the country achieve its carbon peak and carbon neutrality goals. However, to achieve the net-zero carbon emissions goal of global aviation, China needs to reduce its emissions by approximately 82%-91% based on the optimal emission scenario. Thus, under the international net-zero target, China's civil aviation industry will face significant pressure to reduce its emissions. The use of sustainable aviation fuels is the best way to reduce aviation emissions by 2050. Moreover, in addition to the application of sustainable aviation fuel, it will be necessary to develop a new generation of aircraft introducing new materials and upgrading technology, implement additional carbon absorption measures, and make use of carbon trading markets to facilitate China's civil aviation industry's contribution to reduce climate change.

Is diabetes mellitus a risk factor for low bone density: a systematic review and meta-analysis.

BACKGROUND: This systematic review aimed to investigate whether diabetes mellitus is a risk factor for low bone density, as this might be important and necessary for doctors specialized in treating patients with low bone density. METHODS: PubMed, Embase, CINAHL, and SciELO were searched for cohort, case-control, and cross-sectional studies that investigated the effects of diabetes mellitus on bone mineral density till January 2020. Data screening and extraction are done independently, whereas the methodological quality of the studies was assessed according to the Newcastle-Ottawa Scale (NOS). RESULTS: A total of 14 studies that met the eligibility criteria including 24,340 participants were enrolled. The overall quality of the studies had a scale of over 6 points. The overall odds ratio (OR) regarding the risk of diabetes mellitus in low bone density patients was 1.20 [95% confidence interval (CI)0.80-1.79, P = 0.30], and type 2 diabetes mellitus (T2DM) (OR = 0.69 [0.11, 4.55], P = 0.70). Subgroup analysis revealed that whether females or males, developed or developing countries, T2DM, studies after 2015, and quality over 7 points (all P values > 0.05) showed no significant differences with the risk of low bone density, except type 1 diabetes mellitus (T1DM) (OR = 3.83 [1.64, 8.96], P = 0.002), and studies before 2015 (OR = 1.76 [1.06, 2.92], P = 0.03), and quality below 7 points (OR = 2.27 [1.50, 3.43], P = 0.0001). Funnel plot showed no significant asymmetry. CONCLUSIONS: These findings revealed no relationship between T2DM and low bone density, and also, the evidence between T1DM and low bone density is inadequate, requiring further analysis of well-designed cohort studies.

Hepatic steroid sulfatase critically determines estrogenic activities of conjugated equine estrogens in human cells in vitro and in mice.

Conjugated equine estrogens (CEEs), whose brand name is Premarin, are widely used as a hormone-replacement therapy (HRT) drug to manage postmenopausal symptoms in women. Extracted from pregnant mare urine, CEEs are composed of nearly a dozen estrogens existing in an inactive sulfated form. To determine whether the hepatic steroid sulfatase (STS) is a key contributor to the efficacy of CEEs in HRT, we performed estrogen-responsive element (ERE) reporter gene assay, real-time PCR, and UPLC-MS/MS to assess the STS-dependent and inflammation-responsive estrogenic activity of CEEs in HepG2 cells and human primary hepatocytes. Using liver-specific STS-expressing transgenic mice, we also evaluated the effect of STS on the estrogenic activity of CEEs in vivo We observed that CEEs induce activity of the ERE reporter gene in an STS-dependent manner and that genetic or pharmacological inhibition of STS attenuates CEE estrogenic activity. In hepatocytes, inflammation enhanced CEE estrogenic activity by inducing STS gene expression. The inflammation-responsive estrogenic activity of CEEs, in turn, attenuated inflammation through the anti-inflammatory activity of the active estrogens. In vivo, transgenic mice with liver-specific STS expression exhibited markedly increased sensitivity to CEE-induced estrogenic activity in the uterus resulting from increased levels of liver-derived and circulating estrogens. Our results reveal a critical role of hepatic STS in mediating the hormone-replacing activity of CEEs. We propose that caution needs to be applied when Premarin is used in patients with chronic inflammatory liver diseases because such patients may have heightened sensitivity to CEEs due to the inflammatory induction of STS activity.

Isolated Langerhans cell histiocytosis in the hypothalamic-pituitary region: a case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease that mainly affects children, but this disease is significantly rarer in patients who are older than 15 years. In this disease, any organ can be involved. The skeleton, skin and lung are commonly affected, and isolated hypothalamic-pituitary (HP) involvement is relatively rare. Here we report a 17-year-old adolescent with isolated HP-LCH of enlarged pituitary stalk presented with central diabetes insipidus (CDI). CASE PRESENTATION: A 17-year-old male adolescent with polydipsia and polyuria accompanied with elevated serum sodium level and low urine osmolality for 3 weeks was referred to our hospital. After admission, hormonal evaluation showed that his growth hormone (GH) was slightly elevated, and serum osmolality and glucose were normal. The fluid deprivation-vasopressin test demonstrated CDI. Imaging examination showed an obvious thickening of the pituitary stalk. Lymphocytic hypophysitis, sarcoidosis and granulation tissue lesions were suspected. After oral 1-deamino-8-Darginine vasopressin (DDAVP) and prednisone were administered for 2 months, symptoms were relieved, and he discontinued taking the drugs by himself. On reexamination, imaging revealed changes in the size and shape of the pituitary stalk, with thickened nodules. Then, a diagnostic biopsy of the pituitary stalk lesion was performed. Immunohistochemistry confirmed the definitive diagnosis of LCH. The clinical symptoms subsided with oral hormone replacements. CONCLUSION: CDI is a rare symptom in children and adolescents. Most of the causes are idiopathic, while others are caused by central nervous system (CNS) disorders. Meanwhile, lymphocytic hypophysitis, germinoma, LCH and other CNS disorders can all present as thickening of the pituitary stalk, diffuse enlargement of the pituitary gland, and weakening of high signal intensity in the neurohypophysis on magnetic resonance imaging (MRI). The differential diagnosis among these diseases depends on immunohistochemistry evidence.

A rare case of pure testosterone-secreting adrenal adenoma in a postmenopausal elderly woman.

BACKGROUND: Hyperandrogenemia is more common in puberty and reproductive age, but relatively rare in postmenopausal women. Postmenopausal virilization may result from androgen-producing tumors. Androgen-secreting adrenal tumors are rare in clinical practice and are diagnosed as adrenocortical carcinoma, most of which can co-secrete androgen and cortisol. Highly elevated serum testosterone level with normal adrenal androgens such as dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS) and androstenedione is usually regarded as ovary origin. Here we describe an unusual case of a postmenopausal woman with markedly elevated serum testosterone level, while DHEAS, androstenedione, 17-hydroxyprogesterone and cortisol were within the normal range. CASE PRESENTATION: A 67-year-old postmenopausal woman with hirsutism in the upper lip and armpit, accompanied by clitoromegaly for 5 months. Hormonal evaluation showed markedly elevated serum testosterone level (714.8 ng/ml), whereas DHEAS, androstenedione, 17-hydroxyprogesterone, and cortisol were within the normal range. Imaging examination showed a mass of 1.5 cm in diameter in the left adrenal gland and normal appearance of both ovaries. PET-CT indicated that it was a case of benign adrenal adenoma and excluded ovarian abnormalities and other ectopic tumors. Thus, a pure testosterone-secreting adrenal tumor was suspected and then adrenalectomy was performed. Histology and immunohistochemistry furtherly confirmed the benign adrenocortical adenoma with immunohistochemistry positive for inhibin α, melan A, ß-captenin, SYN (focal), Ki-67(< 3%), and negative for chromogranin (CgA), cytokeratin (CK), S-100, P53. After surgery, the level of testosterone returned to normal range and the clinical symptoms also subsided. CONCLUSIONS: Pure testosterone-secreting adrenal adenomas are extremely rare, but it can induce severe hyperandrogenism and virilization. The source identification of hyperandrogenemia only based on the levels of testosterone, DHEAS and androstenedione is limited. It is important to evaluate not only ovaries but also adrenals in all women with virilization particularly during menopause, even their androstenedione, DHEA and DHEAS level are normal.

Metabolic Profiling of Plasma in Gestational Diabetes Mellitus Using Liquid Chromatography and Q-TOF Mass Spectrometry.

BACKGROUND: To delineate the metabolomic profiling and identify early diagnostic biomarkers in maternal plasma from the pregnant women who subsequently developed gestational diabetes mellitus (GDM) using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-Q-TOF MS). METHODS: Plasma samples were collected from GDM pregnant women (n = 30) and healthy controls (n = 30) at the 20th gestational week in Huzhou Central Hospital and Huzhou Maternal and Child Health Hospital. The principle component analysis (PCA), partial least-squares discriminant analysis (PLS-DA), and orthogonal PLS (OPLS) were sequentially applied to discover the differential metabolites for GDM diagnosis. Further, we analyzed the identified biomarkers in the MetPA database in order to reveal the key relevant metabolism in GDM. RESULTS: Twenty-four out of 975 aligned metabolites were distinguished among GDM plasma and healthy controls. In particular, the level of linolenic acid and arachidonic acid was significantly elevated in GDM. CONCLUSIONS: The linolenic acid and arachidonic acid could be selected as new potent biomarkers for GDM diagnosis and prognosis in early pregnancy; however, they still need to be confirmed from large samples in future.

Effects of endocrine therapy on the prognosis of elderly patients after surgery for papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is a common thyroid malignancy. Elderly patients have more severe disease and more complications following postoperative endocrine therapy to control thyroid-stimulating hormone (TSH) levels. We aimed to identify optimal postoperative serum TSH levels in elderly patients to prevent recurrence and metastasis and minimize complications. This retrospective cohort study collected data of 87 consecutive elderly patients (age >75) who underwent surgery for PTC with postoperative levothyroxine therapy (50-150 µg/d) between January 2006 and June 2008 and were followed until 2013. After 24 patients with TSH fluctuations and incomplete data were excluded, 73 patients were grouped based on postoperative TSH levels: Group A, 0.3-0.5 mIU/mL; Group B, 0.1-0.3 mIU/mL; and Group C <0.1 mIU/mL (n = 24, 25, 24, respectively). Subjects' baseline, preoperative data, postoperative complications and 1-, 3- and 5-year follow-up data were compared between groups. No significant differences in gender, age (median age of 80 years old), surgery type or clinical characteristics were found between groups (all p value >0.05). Postoperatively, all subjects had normal ECG and neck ultrasound, no osteoporosis, and no differences in survival rate or metastasis. Five-year follow-up revealed significant differences in development of arrhythmias, osteoporosis, insomnia and anxiety between Groups B (0.1-0.3 mIU/mL) and C (<0.1 mIU/mL) compared to Group A (0.3-0.5 mIU/mL). Postoperative incidence of PTC recurrence and metastasis remained stable in elderly patients undergoing thyroid surgery and endocrine therapy but complications increased significantly with increasing TSH levels. Controlling TSH to lower limits of normal may help prevent PTC recurrence and metastasis and reduce complications in this high-risk population.

[Efficacy and safety of alogliptin in treatment of type 2 diabetes mellitus: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial in mainland China].

OBJECTIVE: To evaluate the efficacy and safety of alogliptin in Chinese patients with type 2 diabetes (T2DM). METHODS: This was a multicenter, randomized, double-blind, placebo-controlled phase III trial. A total of 491 subjects with T2DM were randomized in a 1:1 ratio to receive alogliptin (25 mg once daily) or placebo for 16 weeks. Among them, 181 were in the monotherapy group (group A), 186 were in the add-on to metformin group (group B), and 124 were in the add-on to pioglitazone group (group C). RESULTS: After 16 weeks of therapy, glycosylated hemoglobin A1c (HbA1c) levels decreased in both alogliptin and placebo groups. The mean changes in HbA1c for alogliptin and placebo were 1.00% and 0.43% (P<0.001), 0.91% and 0.23% (P<0.001), and 0.76% and 0.25% (P<0.001) in group A, B and C, respectively. Compared with placebo, alogliptin treatment led to a greater decrease in fasting plasma glucose (FPG) and a higher percentage of subjects who achieved HbA1c targets of ≤ 6.5% and ≤ 7.0%. The percentage of subjects who experienced all adverse events including hypoglycemia with alogliptin were comparable to those with placebo. CONCLUSIONS: Alogliptin 25 mg once daily reduced HbA1c and FPG, and increased a greater proportion of subjects achieving HbA1c goals of ≤6.5% and ≤7.0% compared with placebo when used as a monotherapy, add-on to metformin, or add-on to pioglitazone. The hypoglycemia rates and safety profiles with alogliptin were similar to those with placebo.

Targeting SMAD3 for inhibiting prostate cancer metastasis.

Although SMAD3 signaling has been suggested to play a role in the metastasis of various cancers, its possible involvement as well as the underlying mechanism in the pathogenesis in prostate cancer remains unclear. Here, we found that the MMP9 level, an indicator of the invasiveness of cancer cells, negatively correlates with the activity of phosphorylated SMAD3 levels in the prostate cancer patients. Moreover, the phosphorylated SMAD3 also appeared to regulate the MMP9 level in a prostate cancer cell line, PC3. Augmented phosphorylated SMAD3 inhibited MMP9 and invasiveness of PC3 cells, while inhibition of phosphorylated SMAD3 activated MMP9 and promoted PC3 cell invasiveness. Furthermore, forced MMP9 inhibition abolished the effect of phosphorylated SMAD3 on the invasiveness of PC3 cells, while forced MMP9 activation abolished the effect of phosphorylated SMAD3 on the invasiveness of PC3 cells. Taken together, our data suggest the possibility of the existence of a unique signaling cascade in which SMAD3 signaling regulates MMP9 during cancer metastasis.

ABCA1 and ABCG1 expression in the small intestine of type 2 diabetic rats.

OBJECTIVE: Inflammation of the small intestine may occur in type 2 diabetes. This study aimed to investigate whether ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) were altered in chronic inflammation of the small intestine of type 2 diabetic rats. METHODS: Thirty-two male Sprague-Dawley rats were used. Eight rats in the control group were fed with regular chow, and 24 rats were fed a high-fat diet and injected with a single low dose of streptozotocin. All of the control rats and diabetic rats were bred for 10 months. Immunohistochemistry detected ABCA1 and ABCG1 in the small intestine in all the rats. RESULTS: Hematoxylin-eosin staining showed chronic inflammation in the small intestine of the diabetic rats. Immunohistochemistry staining showed that alteration of ABCA1 and ABCG1 was different in the inflammatory and epithelial cells. Quantitative analysis showed that the overall expression of ABCA1 and ABCG1 increased in the diabetic rats compared to the control rats. Both ABCA1 and ABCG1 were enriched in the inflammatory cells of the small intestine in diabetic rats. In the epithelial cells, ABCA1, but not ABCG1, was detected in significantly more diabetic rats than control rats. CONCLUSION: Both ABCA1 and ABCG1 are enriched in chronic inflammation of the small intestine of type 2 diabetic rats. ABCA1, but not ABCG1, is activated in the intestinal epithelial cells of type 2 diabetic rats.

Electrostatic-Interaction-Aided Microneedle Patch for Enhanced Glucose-Responsive Insulin Delivery and Three-Meal-Per-Day Blood-Glucose Regulation.

The phenylborate-ester-cross-linked hydrogel microneedle patch (MNP) was promising in the diabetic field for the glucose-responsive insulin-delivering property and simple fabrication process. However, the unfit design of the charging microneedle network limited the improvement of blood-glucose regulating performances. In this work, insulin-loaded phenylborate-ester-cross-linked MNPs, with the polyzwitterion property, were constructed based on the modified ε-polylysine and poly(vinyl alcohol). The relationship between the charging nature of the MNP network and insulin release was verified by regulating the content of postprotonated positively charged amino groups. The elaborately designed MNP possessed improved glucose-responsive insulin-delivering performance. The in vivo study revealed the satisfactory results on blood-glucose regulation by the optimized MNP under the mimic three-meal-per-day mode. Moreover, the insulin bioactivity in the MNP could be maintained for 2 weeks under 25 °C. In summary, this work developed an effective strategy to improve the glucose-responsive phenylborate-ester-cross-linked MNP and enhance its potential for clinical transformation.

A missense mutation in the arginine-vasopressin neurophysin-II gene causes autosomal dominant neurohypophyseal diabetes insipidus in a Chinese family.

BACKGROUND: Familial neurohypophyseal diabetes insipidus, an autosomal dominant disorder, is mostly caused by mutations in the genes that encode AVP or its intracellular binding protein, neurophysin-II. The mutations lead to aberrant preprohormone processing and progressive destruction of AVP-secreting cells, which gradually manifests a progressive polyuria and polydipsia during early childhood, and a disorder of water homeostasis. OBJECTIVE: We characterized the clinical and biochemical features, and sequenced the AVP neurophysin-II(AVP-NPII) gene of the affected individuals with autosomal dominant neurohypophyseal diabetes insipidus(ADNDI)to determine whether this disease was genetically determined. PATIENTS AND METHODS: We obtained the histories of eight affected and four unaffected family individuals. The diagnosis of ADNDI was established using a water deprivation test and exogenous AVP administration. For molecular analysis, genomic DNA was extracted and the AVP-NPII gene was amplified using polymerase chain reaction and sequenced. RESULTS: The eight affected individuals showed different spectra of age of onsets (7-15 years) and urine volumes (132-253 ml/kg/24 h). All affected individuals responded to vasopressin administration, with a resolution of symptoms and an increase in urine osmolality by more than 50%. The characteristic hyperintense signal in the posterior pituitary on T1-weighted magnetic resonance imaging was absent in six family members and present in one. Sequencing analysis revealed a missense heterozygous mutation 1516G > T (Gly17Val) in exon 2 of the AVP-NPII gene among the ADNDI individuals. CONCLUSIONS: We identified a missense mutation in the AVP-NPII gene and the same mutation showed different spectra of age of onsets and urine volumes in a new Chinese family with ADNDI. The mutation may provide a molecular basis for understanding the characteristics of NPII and add to our knowledge of the pathogenesis of ADNDI, which would allow the presymptomatic diagnosis of asymptomatic subjects.

[The design and baseline characteristics of a phase III study to evaluate the efficacy and safety of alogliptin versus placebo in type 2 diabetes mellitus in Mainland China].

OBJECTIVE: To assess the design and the Mainland China subgroup baseline characteristics of the study to evaluate the efficacy and safety of alogliptin versus placebo in subjects with type 2 diabetes (T2DM) as monotherapy, add-on to metformin or add-on to pioglitazone. METHODS: This was a multi-center, randomized, double-blind, placebo-controlled, 16-week study comparing alogliptin (ALO, 25 mg, 1/d) versus placebo (PLA) as monotherapy (A), add-on to metformin (B) or add-on to pioglitazone ± metformin (C). The T2DM subjects with glycosylated hemoglobin A1c(HbA1c) between 7% and 10% and aged between 18 years and 75 years were enrolled and randomized to the alogliptin group and the placebo group in 1: 1 ratio with 16 weeks treatment. All patients were followed up every 4 weeks. The safety endpoints consisted of the incidence of hypoglycemia and other adverse events. RESULTS: A total of 491 patients were enrolled in the Mainland China subgroup of the study (181 in group A, 186 in group B and 124 in group C). In each treatment group, the baseline characteristics including age, gender, body mass index, diabetes duration, HbA1c, fasting plasma glucose, body weight, daily dosage of metformin and daily dosage of pioglitazone were all well balanced. CONCLUSION: The demographic data, medical history, glycemic profile and treatment regimen at baseline in Mainland China subgroup are well balanced. The result of this study will provide the clinical evidence for the use of alogliptin in Chinese T2DM patients.

Medical service pricing and pharmaceutical supply chain coordination contracts under the zero-markup drug policy.

To implement state policies of zero-markup drug policy and medical service fee adjustment for public hospitals, this study constructed game models of the pharmaceutical supply chain, consisting of a drug supplier and a public hospital. The study obtained the optimal medical service level and pricing under the new state drug policies. In addition, it analyzed the impacts of the degree of public benefit of hospitals on the medical service level, the medical service price, and the drug price. Finally, from the perspective of cooperation between drug suppliers and public hospitals, the specialized coordination contract was designed to maximize overall social welfare. This study found an anomalous but meaningful conclusion: in the background of the zero-markup drug policy, a higher public benefit of hospitals could increase the drug prices, but it could reduce the medical service prices further to cut down on the overall treatment fees for the patients. The novel coordination contract can optimize the pharmaceutical supply chain and achieve a win-win situation for the drug suppliers, public hospitals, and patients. When the public benefit of hospitals is higher, the profit of a decentralized decision-making supply chain is greater than a centralized one, while the pharmaceutical supply chain will not coordinate itself.

Molecular Docking-Guided Design on Glucose-Responsive Nanoparticles for Microneedle Fabrication and "Three-Meal-per-Day" Blood-Glucose Regulation.

It was greatly significant, but difficult, to develop stimulus-responsive polymeric nanoparticles with efficient protein-loading and protein-delivering properties. Crucial obstacles were the ambiguous protein/nanoparticle-interacting mechanisms and the corresponding inefficient trial-and-error strategies, which brought large quantities of experiments in design and optimization. In this work, a molecular docking-guided universal "segment-functional group-polymer" process was proposed to simplify the previous laborious experimental step. The insulin-delivering glucose-responsive polymeric nanoparticles for diabetic treatments were taken as the examples. The molecular docking study obtained insights from the insulin/segment interactions. It was then experimentally confirmed in six functional groups for insulin-loading performances of their corresponding polymers. The optimization formulation was further proved effective in blood-glucose stabilization on the diabetic rats under the "three-meal-per-day" mode. It was believed that the molecular docking-guided designing process was promising in the protein-delivering field.

Adoption of mobile health services using the unified theory of acceptance and use of technology model: Self-efficacy and privacy concerns.

Mobile health (mHealth) services have been widely used in medical services and health management through mobile devices and multiple channels, such as smartphones, wearable equipment, healthcare applications (Apps), and medical platforms. However, the number of the users who are currently receiving the mHealth services is small. In China, more than 70% of internet users have never used mHealth services. Such imbalanced situation could be attributed to users' traditional concept of medical treatment, psychological factors (such as low self-efficacy) and privacy concerns. The purpose of this study is to explore the direct and indirect effects of mHealth users' self-efficacy and privacy concerns on their intention to adopt mHealth services, providing guidelines for mHealth service providers to enhance users' intention of adoption. A questionnaire was designed by the research team and 386 valid responses were collected from domestic participants in China. Based on the unified theory of acceptance and use of technology (UTAUT) model, a research model integrated self-efficacy and privacy concerns was constructed to investigate their effects on users' intention to adopt mobile mHealth services. The results show that self-efficacy could facilitate users' intention to adopt mHealth services, and had a significantly positive effect on perceived ubiquity, effort expectancy, performance expectancy and subjective norm. This study verifies the direct and indirect effects of self-efficacy and privacy concerns on users' intention to adopt mHealth services, providing a different perspective for studying mHealth adoption behavior. The findings could provide guidelines for mHealth service providers to improve their service quality and enhance users' intention of adoption.

Detection of Chromosomal Segments Introgressed from Wild Species of Carrot into Cultivars: Quantitative Trait Loci Mapping for Morphological Features in Backcross Inbred Lines.

Cultivated carrot is thought to have been domesticated from a wild species, and various phenotypes developed through human domestication and selection over the past several centuries. Little is known about the genomic contribution of wild species to the phenotypes of present-day cultivars, although several studies have focused on identifying genetic loci that contribute to the morphology of storage roots. A backcross inbred line (BIL) population derived from a cross between the wild species Daucus carota ssp. carota "Songzi" and the orange cultivar "Amsterdam forcing" was developed. The morphological features in the BIL population became more diverse after several generations of selfing BC2F1 plants. Only few lines retained features of wild parent. Genomic resequencing of the two parental lines and the BILs resulted in 3,223,651 single nucleotide polymorphisms (SNPs), and 13,445 bin markers were generated using a sliding window approach. We constructed a genetic map with 2027 bins containing 154,776 SNPs; the total genetic distance was 1436.43 cM and the average interval between the bins was 0.71 cm. Five stable QTLs related to root length, root shoulder width, dry material content of root, and ratio of root shoulder width to root middle width were consistently detected on chromosome 2 in both years and explained 23.4-66.9% of the phenotypic variance. The effects of introgressed genomic segments from the wild species on the storage root are reported and will enable the identification of functional genes that control root morphological traits in carrot.

Roles of sulfonylurea receptor 1 and multidrug resistance protein 1 in modulating insulin secretion in human insulinoma.

BACKGROUND: Sulfonylurea receptor 1 (SUR1) and multidrug resistance protein 1 (MRP1) are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate their expression in insulinomas and their sole and synergistic effects in modulating abnormal insulin secretion. METHODS: Fasting glucose, insulin and C-peptide were measured in 11 insulinoma patients and 11 healthy controls. Prolonged oral glucose tolerance tests were performed in 6 insulinoma patients. Insulin content, SUR1 and MRP1 were detected in 11 insulinoma patients by immunohistochemistry. SUR1 and MRP1 were also detected in 6 insulinoma patients by immunofluorescence. RESULTS: Insulinoma patients presented the typical demonstrations of Whipple's triad. Fasting glucose of each insulinoma patient was lower than 2.8 mmol/L, and simultaneous insulin and C-peptide were increased in insulinoma patients. Prolonged oral glucose tolerance tests showed that insulin secretion in insulinoma patients were also stimulated by high glucose. Immunohistochemistry and immunofluorescence staining showed that SUR1 increased, but MRP1 decreased in insulinoma compared with the adjacent islets. CONCLUSIONS: The hypersecretion of insulin in insulinomas might be, at least partially, due to the enrichment of SUR1. In contrast, MRP1, which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion.

Cross-Linking-Density-Changeable Microneedle Patch Prepared from a Glucose-Responsive Hydrogel for Insulin Delivery.

To simplify the preparation process of a glucose-responsive microneedle patch, a cross-linking-density changeable microneedle patch was designed. The microneedle patch was made up of a hydrogel formed by phenylboronic acid-grafted polyallylamine and poly(vinyl alcohol) (PVA). The gel was cross-linked by boronate ester bonds between phenylboronic acid groups and PVA. It still had fluidity and could be filled into a mold to prepare microneedle patches. Moreover, insulin could be directly loaded into the microneedle patch by mixing with the gel. The boronate ester bond would be broken in the presence of glucose, resulting in a decrease in the cross-linking density. Therefore, the gel could achieve a greater swelling degree and insulin could be released faster. In addition, PVA chains were crystallized by repeatedly freezing and thawing to improve the mechanical strength of the microneedle patch. In terms of glucose-dependent insulin release, the gel showed good glucose-responsive insulin-release ability. Through additional ion cross-linking, the microneedle patch could also control the insulin release according to glucose concentration. In the hypoglycemic experiment of diabetic rats, the microneedle patch effectively pierced the skin and slowly released insulin.

Familial syndrome resembling Aarskog syndrome.

Aarskog(-Scott) syndrome (AAS) is characterized by short stature, and facial, limb, and genital anomalies. AAS can be an X-linked condition caused by mutations in the FGD1 gene, but there is evidence that an autosomal dominant or recessive form also exists. We report on a Chinese family in whom several members have manifestations of AAS, but differ in limb anomalies and show additional characteristics. FGD1 sequencing and linkage analysis excluded FGD1 as the cause in this family. A common known submicroscopic chromosome imbalance is less likely. Both autosomal dominant and recessive patterns of inheritance remain possible.