Molecular evolution and interaction of 14-3-3 proteins with H+-ATPases in plant abiotic stresses.

Environmental stresses severely affect plant growth and crop productivity. Regulated by 14-3-3 proteins (14-3-3s), H+-ATPases (AHAs) are important proton pumps that can induce diverse secondary transport via channels and co-transporters for the abiotic stress response of plants. Many studies demonstrated the roles of 14-3-3s and AHAs in coordinating the processes of plant growth, phytohormone signaling, and stress responses. However, the molecular evolution of 14-3-3s and AHAs has not been summarized in parallel with evolutionary insights across multiple plant species. Here, we comprehensively review the roles of 14-3-3s and AHAs in cell signaling to enhance plant responses to diverse environmental stresses. We analyzed the molecular evolution of key proteins and functional domains that are associated with 14-3-3s and AHAs in plant growth and hormone signaling. The results revealed evolution, duplication, contraction, and expansion of 14-3-3s and AHAs in green plants. We also discussed the stress-specific expression of those 14-3-3and AHA genes in a eudicotyledon (Arabidopsis thaliana), a monocotyledon (Hordeum vulgare), and a moss (Physcomitrium patens) under abiotic stresses. We propose that 14-3-3s and AHAs respond to abiotic stresses through many important targets and signaling components of phytohormones, which could be promising to improve plant tolerance to single or multiple environmental stresses.

Clinical characteristics and predictive factors of delayed diagnosis in patients with sellar germ cell tumors.

PURPOSE: To investigate the clinical characteristics and predictive factors associated with delayed diagnosis in patients with sellar germ cell tumors (GCTs), aiming for early diagnosis. METHODS: A total of 345 patients with sellar GCTs were retrospectively collected. Patients were classified into a delayed diagnosis group (> 6 months from onset to diagnosis) and a non-delayed diagnosis group (≤ 6 months). We compared general characteristics, clinical symptoms, diagnostic methods, treatment strategies, tumor prognosis, and pituitary function between the two groups. Predictive factors for delayed diagnosis were explored using multivariate logistic regression analysis. RESULTS: 225 patients (65.2%) experienced delayed diagnosis. Although there was no association between delayed diagnosis and survival rates or tumor recurrence rates, the delayed diagnosis group had a higher incidence of central diabetes insipidus, central adrenal insufficiency, central hypothyroidism, central hypogonadism, and growth hormone deficiency. Moreover, polyuria/polydipsia (OR 5.46; 95% CI 2.33-12.81), slow growth (OR 5.86; 95% CI 2.61-13.14), amenorrhea (OR 6.82; 95% CI 2.68-17.37), and germinoma (OR 4.99; 95% CI 1.08-3.61) were associated with a higher risk of delayed diagnosis, while older age of onset (OR 0.88; 95% CI 0.84-0.94) and nausea/vomiting (OR 0.31; 95% CI 0.15-0.63) contributed to earlier diagnosis. CONCLUSION: In patients with sellar GCTs, delayed diagnosis is common and linked to increased pituitary dysfunction. The initial symptoms of slow growth, polyuria/polydipsia, and amenorrhea, as well as germinoma with negative tumor markers, predict the possibility of a delayed diagnosis. Early diagnosis is crucial to minimize the impact of sellar GCTs on pituitary function.

Clinical Characteristics and Management of Cosecreting Thyroid Stimulating Hormone or Prolactin Pituitary Growth Hormone Adenomas: A Case-Control Study.

OBJECTIVE: Cosecreting thyroid stimulating hormone (TSH) or prolactin (PRL) in patients with pituitary growth hormone (GH) adenomas has been rarely reported. Our study aimed to elucidate their clinical characteristics. METHODS: We retrospectively collected data of 22 cases of cosecreting GH and TSH pituitary adenomas [(GH+TSH)oma] and 10 cases of cosecreting GH and PRL pituitary adenomas [(GH+PRL)oma] from Beijing Tiantan Hospital, Capital Medical University between January 2009 and January 2023. The clinical manifestation, preoperative hormone levels, imaging features, pathologic characteristics, and biochemical remission rates were compared among 335 patients with solo-secreting GH adenomas (GHoma) and 49 patients with solo-secreting TSH adenoma (TSHoma). Patients with (GH+TSH)oma and (GH+PRL)oma were grouped according to biochemical remission to explore the risk factors leading to biochemical nonremission. RESULTS: Cosecreting pituitary GH adenomas had various clinical manifestations and a larger tumor volume and were more likely to invade the cavernous sinus bilaterally and compress the optic chiasm. GH and TSH levels were lower in (GH+TSH)oma than in GHoma or TSHoma. Solo part remission was observed both in (GH+TSH)oma and (GH+PRL)oma. Cavernous sinus invasion was an independent risk factor for biochemical nonremission in patients with (GH+TSH)oma and (GH+PRL)oma. CONCLUSIONS: The clinical manifestation of (GH+TSH)oma and (GH+PRL)oma may be atypical. When screening for pituitary adenomas, a comprehensive evaluation of all pituitary target gland hormones is needed. Cosecreting pituitary GH adenomas are more aggressive and surgery is often unable to completely remove the tumor, requiring pharmacologic or radiological treatment if necessary. Clinicians should give high priority to biochemical remission, although solo part remission may occur.

Differential effects of four laboratory animal control diets on gut microbiota in mice.

BACKGROUND: The gut microbiota is intricate and susceptible to multiple factors, with diet being a major contributor. The present study aimed to investigate the impact of four commonly used laboratory animal control diets, namely Keao Xieli's maintenance diet (KX), HFK's 1025 (HF), Research Diets' D12450B (RD), and Lab Diet's 5CC4 (LD), on the gut microbiota of mice. RESULTS: A total of 40 mice were randomly assigned to four groups, and each group was fed one of the four diets for a duration of 8 weeks. The assessment of gut microbiota was conducted using 16S rRNA sequencing both at the beginning of the study (week 0) and the end (week 8), which served as the baseline and endpoint samples, respectively. Following the 8-week feeding period, no significant differences were observed in physiological parameters, including body weight, visceral weight, and blood biochemical indices, across the four groups. Nonetheless, relative to the baseline, discernible alterations in the gut microbiota were observed in all groups, encompassing shifts in beta-diversity, hierarchical clustering, and key genera. Among the four diets, HF diet exhibited a significant influence on alpha-diversity, RD diet brought about notable changes in microbial composition at the phylum level, and LD diet demonstrated an interconnected co-occurrence network. Mantel analysis indicated no significant correlation between physiological parameters and gut microbiota in the four groups. CONCLUSION: Overall, our study demonstrated that the four control diets had a minimal impact on physiological parameters, while exerting a distinct influence on the gut microbiota after 8 weeks. © 2024 Society of Chemical Industry.

Dietary supplementation of ark clams protects gut health and modifies gut microbiota in d-galactose-induced aging rats.

BACKGROUND: Ark clams, a seafood abundant in various nutrients, are widely consumed worldwide. This study aimed to investigate the protective benefits of two common ark clams in Korea, Scapharca subcrenata (SS) and Tegillarca granosa (TG), on gut health in d-galactose (d-gal)-induced aging rats. RESULTS: Thirty-two Wistar rats (11 weeks old) were randomly allocated into four groups: a CON group (normal diet + saline intraperitoneal (i.p.) injection), a CD group (normal diet + d-gal i.p. injection), an SS group (normal diet with 5% SS supplementation + d-gal i.p. injection), and a TG group (normal diet with 5% TG supplementation + d-gal i.p. injection). After 12 weeks of treatment, histopathological results showed that gut barrier damage was alleviated in rats of the SS and TG groups, as evidenced by increases in mucus layer thickness and goblet cell numbers. Meanwhile, the two groups supplemented with ark clams showed an evident reduction in oxidative stress biomarkers (malondialdehyde and protein carbonyl content levels in the colon) and an increase in the immune-related factor (immunoglobulin A level in the plasma) in rats. The 16S ribosomal RNA analysis revealed that SS and TG ark clams significantly increased the proliferations of Bacteroidetes at the phylum level and Parabacteroides at the genus level. Additionally, the levels of the three main short-chain fatty acids in the cecal contents were also significantly increased in the SS and TG groups. CONCLUSION: Our results indicated a potent preventive effect of SS and TG ark clams on d-gal-induced gut injury, suggesting that ark clams may be a promising dietary component for intervening in aging. © 2023 Society of Chemical Industry.

Molecular Evolution of Plant 14-3-3 Proteins and Function of Hv14-3-3A in Stomatal Regulation and Drought Tolerance.

Drought significantly affects stomatal regulation, leading to the reduced growth and productivity of plants. Plant 14-3-3 proteins were reported to participate in drought response by regulating the activities of a wide array of target proteins. However, the molecular evolution, expression pattern and physiological functions of 14-3-3s under drought stress remain unclear. In this study, a comparative genomic analysis and the tissue-specific expression of 14-3-3s revealed the highly conserved and early evolution of 14-3-3s in green plants and duplication and expansion of the 14-3-3s family members in angiosperms. Using barley (Hordeum vulgare) for the functional characterization of 14-3-3 proteins, the transcripts of five members out of six Hv14-3-3s were highly induced by drought in the drought-tolerant line, XZ141. Suppression of the expression of Hv14-3-3A through barley stripe mosaic virus-virus induced gene silencing resulted in significantly increased drought sensitivity and stomatal density as well as significantly reduced net CO2 assimilation (A) and stomatal conductance (gs) in barley. Moreover, we showed the functional interactions between Hv14-3-3s and key proteins in drought and stomatal responses in plants-such as Open Stomata 1 (HvOST1), Slow Anion Channel 1 (HvSLAC1), three Heat Shock Proteins (HvHSP90-1/2/5) and Dehydration-Responsive Element-Binding 3 (HvDREB3). Taken together, we propose that 14-3-3s are highly evolutionarily conserved proteins and that Hv14-3-3s represent a group of the core regulatory components for the rapid stomatal response to drought in barley. This study will provide important evolutionary and molecular evidence for future applications of 14-3-3 proteins in breeding drought-tolerant crops in a changing global climate.

Acupuncture exerts preventive effects in rats of chronic unpredictable mild stress: The involvement of inflammation in amygdala and brain-spleen axis.

BACKGROUND: Acupuncture has shown the preventive effects on depression in rats with chronic unpredictable mild stress (CUMS). However, the mechanisms of acupuncture for preventing depression still need to be explored. In the study, acupuncture was applied to a rat depression model of CUMS, high-mobility group box 1(HMGB1)/toll-like receptor 4 (TLR4) and brain-spleen axis were assessed. METHODS: Male Sprague Dawley (SD) rats were exposed to CUMS with two stressors per day for 28 days. In the meantime, manual acupuncture (at GV16 and GV23 acupoints, once every other day) and fluoxetine gavage (2.1 mg/kg, 0.21 mg/mL) were administered daily post CUMS stressors. Behavioral tests and biological detection methods were conducted in sequence to evaluate depression-like phenotypes in rats. RESULTS: The results showed CUMS induced depression-like behaviors, hyper-activation of HMGB1/TLR4 signaling pathway, elevated inflammation in amygdala and peripheral blood, and hyperactivation of hypothalamic-pituitary-adrenal (HPA) axis. These changes could be prevented and reversed by acupuncture to varying extents. CONCLUSION: Acupuncture prevented and ameliorated depression-like symptoms induced by CUMS, possibly via regulating inflammation through brain-spleen axis mediated by HMGB1/TLR4 signaling pathway and HPA axis regulation.

Ectopic odorant receptors responding to flavor compounds in skin health and disease: Current insights and future perspectives.

Skin, the largest organ of human body, acts as a barrier to protect body from the external environment and is exposed to a myriad of flavor compounds, especially food- and plant essential oil-derived odorant compounds. Skin cells are known to express various chemosensory receptors, such as transient potential receptors, adenosine triphosphate receptors, taste receptors, and odorant receptors (ORs). We aim to provide a review of this rapidly developing field and discuss latest discoveries related to the skin ORs activated by flavor compounds, their impacts on skin health and disease, odorant ligands interacting with ORs exerting specific biological effects, and the mechanisms involved. ORs are recently found to be expressed in skin tissue and cells, such as keratinocytes, melanocytes, and fibroblasts. To date, several ectopic skin ORs responding to flavor compounds, are involved in different skin biological processes, such as wound healing, hair growth, melanin regulation, pressure stress, skin barrier function, atopic dermatitis, and psoriasis. The recognition of physiological role of skin ORs, combined with the fact that ORs belong to a highly druggable protein family (G protein-coupled receptors), underscores the potential of skin ORs responding to flavor compounds as a novel regulating strategy for skin health and disease.

The gut odorant receptor and taste receptor make sense of dietary components: A focus on gut hormone secretion.

Odorant receptors (ORs) and taste receptors (TRs) are expressed primarily in the nose and tongue in which they transduce electrical signals to the brain. Advances in deciphering the dietary component-sensing mechanisms in the nose and tongue prompted research on the role of gut chemosensory cells. Acting as the pivotal interface between the body and dietary cues, gut cells "smell" and "taste" dietary components and metabolites by taking advantage of chemoreceptors-ORs and TRs, to maintain physiological homeostasis. Here, we reviewed this novel field, highlighting the latest discoveries pertinent to gut ORs and TRs responding to dietary components, their impacts on gut hormone secretion, and the mechanisms involved. Recent studies indicate that gut cells sense dietary components including fatty acid, carbohydrate, and phytochemical by activating relevant ORs, thereby modulating GLP-1, PYY, CCK, and 5-HT secretion. Similarly, gut sweet, umami, and bitter receptors can regulate the gut hormone secretion and maintain homeostasis in response to dietary components. A deeper understanding of the favorable influence of dietary components on gut hormone secretion via gut ORs and TRs, coupled with the facts that gut hormones are involved in diverse physiological or pathophysiological phenomena, may ultimately lead to a promising treatment for various human diseases.

Understanding the mechanism underlying the anti-diabetic effect of dietary component: a focus on gut microbiota.

Diabetes has become one of the biggest non-communicable diseases and threatens human health worldwide. The management of diabetes is a complex and multifaceted process including drug therapy and lifestyle interventions. Dietary components are essential for both diabetes management and health and survival of trillions of the gut microbiota (GM). Herein, we will discuss the relationship between diets and GM, the mechanism linking diabetes and gut dysbiosis, and the effects of dietary components (nutrients, phytochemicals, probiotics, food additives, etc.) on diabetes from the perspective of modulating GM. The GM of diabetic patients differs from that of health individuals and GM disorder contributes to the onset and maintenance of diabetes. Studies in humans and animal models consolidate that dietary component is a key regulator of diabetes and increasing evidence suggests that the alteration of GM plays a salient role in dietary interventions for diabetes. Given that diabetes is a major public health issue, especially that diabetes is linked with a high risk of mortality from COVID-19, this review provides compelling evidence for that targeting GM by dietary components is a promising strategy, and offers new insights into potential preventive or therapeutic approaches (dietary and pharmacological intervention) for the clinical management of diabetes.

Acupuncture Alleviates CUMS-Induced Depression-Like Behaviors by Restoring Prefrontal Cortex Neuroplasticity.

Purpose: To explore the therapeutic efficiency of acupuncture and the related molecular mechanism of neural plasticity in depression. Methods: Chronic unpredictable mild stress- (CUMS-) induced rats were established for the depression animal model. There were a total of four rat groups, including the control group, the CUMS group, the CUMS+acupuncture group, and the CUMS+fluoxetine group. The acupuncture group and the fluoxetine group were given a 3-week treatment after the modeling intervention. The researcher performed the open-field, elevated plus maze, and sucrose preference tests to evaluate depressive behaviors. The number of nerve cells, dendrites' length, and the prefrontal cortex's spine density were detected using Golgi staining. The prefrontal cortex expression, such as BDNF, PSD95, SYN, and PKMZ protein, was detected using the western blot and RT-PCR. Results: Acupuncture could alleviate depressive-like behaviors and promote the recovery of the neural plasticity functions in the prefrontal cortex, showing the increasing cell numbers, prolonging the length of the dendrites, and enhancing the spine density. The neural plasticity-related proteins in the prefrontal cortex, including BDNF, PSD95, SYN, and PKMZ, were all downregulated in the CUMS-induced group; however, these effects could be partly reversed after being treated by acupuncture and fluoxetine (P < 0.05). Conclusion: Acupuncture can ameliorate depressive-like behaviors by promoting the recovery of neural plasticity functions and neural plasticity-related protein upregulation in the prefrontal cortex of CUMS-induced depressed rats. Our study provides new insights into the antidepressant approach, and further studies are warranted to elucidate the mechanisms of acupuncture involved in depression treatment.

Molecular response and evolution of plant anion transport systems to abiotic stress.

KEY MESSAGE: We propose that anion channels are essential players for green plants to respond and adapt to the abiotic stresses associated changing climate via reviewing the literature and analyzing the molecular evolution, comparative genetic analysis, and bioinformatics analysis of the key anion channel gene families. Climate change-induced abiotic stresses including heatwave, elevated CO2, drought, and flooding, had a major impact on plant growth in the last few decades. This scenario could lead to the exposure of plants to various stresses. Anion channels are confirmed as the key factors in plant stress responses, which exist in the green lineage plants. Numerous studies on anion channels have shed light on their protein structure, ion selectivity and permeability, gating characteristics, and regulatory mechanisms, but a great quantity of questions remain poorly understand. Here, we review function of plant anion channels in cell signaling to improve plant response to environmental stresses, focusing on climate change related abiotic stresses. We investigate the molecular response and evolution of plant slow anion channel, aluminum-activated malate transporter, chloride channel, voltage-dependent anion channel, and mechanosensitive-like anion channel in green plant. Furthermore, comparative genetic and bioinformatic analysis reveal the conservation of these anion channel gene families. We also discuss the tissue and stress specific expression, molecular regulation, and signaling transduction of those anion channels. We propose that anion channels are essential players for green plants to adapt in a diverse environment, calling for more fundamental and practical studies on those anion channels towards sustainable food production and ecosystem health in the future.

Three-Dimensional Imaging Provides Detailed Atherosclerotic Plaque Morphology and Reveals Angiogenesis After Carotid Artery Ligation.

RATIONALE: Remodeling of the vessel wall and the formation of vascular networks are dynamic processes that occur during mammalian embryonic development and in adulthood. Plaque development and excessive neointima formation are hallmarks of atherosclerosis and vascular injury. As our understanding of these complex processes evolves, there is a need to develop new imaging techniques to study underlying mechanisms. OBJECTIVE: We used tissue clearing and light-sheet microscopy for 3-dimensional (3D) profiling of the vascular response to carotid artery ligation and induction of atherosclerosis in mouse models. METHODS AND RESULTS: Adipo-Clear and immunolabeling in combination with light-sheet microscopy were applied to image carotid arteries and brachiocephalic arteries, allowing for 3D reconstruction of vessel architecture. Entire 3D neointima formations with different geometries were observed within the carotid artery and scored by volumetric analysis. Additionally, we identified a CD31-positive adventitial plexus after ligation of the carotid artery that evolved and matured over time. We also used this method to characterize plaque extent and composition in the brachiocephalic arteries of ApoE-deficient mice on high-fat diet. The plaques exhibited inter-animal differences in terms of plaque volume, geometry, and ratio of acellular core to plaque volume. A 3D reconstruction of the endothelium overlying the plaque was also generated. CONCLUSIONS: We present a novel approach to characterize vascular remodeling in adult mice using Adipo-Clear in combination with light-sheet microscopy. Our method reconstructs 3D neointima formation after arterial injury and allows for volumetric analysis of remodeling, in addition to revealing angiogenesis and maturation of a plexus surrounding the carotid artery. This method generates complete 3D reconstructions of atherosclerotic plaques and uncovers their volume, geometry, acellular component, surface, and spatial position within the brachiocephalic arteries. Our approach may be used in a number of mouse models of cardiovascular disease to assess vessel geometry and volume. Visual Overview: An online visual overview is available for this article.

Local adrenomedullin gene delivery inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo.

Adrenomedullin (ADM) has beneficial effects on Leydig cells under pathological conditions, including lipopolysaccharide (LPS)-induced orchitis. Our previous studies demonstrated that ADM exerts a restorative effect on steroidogenesis in LPS-treated primary rat Leydig cells by attenuating oxidative stress, inflammation and apoptosis. In this study, we aim to investigate whether ADM inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo. Rats were administered with LPS and injected with Ad-ADM, an adeno-associated virus vector that expressed ADM. Then, rat testes were collected for 3ß-hydroxysteroid dehydrogenase (3ß-HSD) immunofluorescence staining. Steroidogenic enzymes or steroidogenic regulatory factors or protein, including steroidogenic factor-1 (SF-1), liver receptor homologue-1 (LRH1), Nur77, steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc), 3ß-HSD, cytochrome P450 17α-hydroxylase/17, 20 lyase (CYP17) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD), were detected via gene expression profiling and western blot analysis. Plasma testosterone concentrations were measured. Results showed that ADM may inhibit Leydig cell dysfunction by rescuing steroidogenic enzymes and steroidogenic regulatory factors in vivo. The reduction in the number of Leydig cells after LPS exposure was reversed by ADM. ADM rescued the gene or protein levels of SF-1, LRH1, Nur77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD and plasma testosterone concentrations. To summarize ADM could rescue some important steroidogenic enzymes, steroidogenic regulatory factors and testosterone production in Leydig cells in vivo.

Molecular Evolution of Calcium Signaling and Transport in Plant Adaptation to Abiotic Stress.

Adaptation to unfavorable abiotic stresses is one of the key processes in the evolution of plants. Calcium (Ca2+) signaling is characterized by the spatiotemporal pattern of Ca2+ distribution and the activities of multi-domain proteins in integrating environmental stimuli and cellular responses, which are crucial early events in abiotic stress responses in plants. However, a comprehensive summary and explanation for evolutionary and functional synergies in Ca2+ signaling remains elusive in green plants. We review mechanisms of Ca2+ membrane transporters and intracellular Ca2+ sensors with evolutionary imprinting and structural clues. These may provide molecular and bioinformatics insights for the functional analysis of some non-model species in the evolutionarily important green plant lineages. We summarize the chronological order, spatial location, and characteristics of Ca2+ functional proteins. Furthermore, we highlight the integral functions of calcium-signaling components in various nodes of the Ca2+ signaling pathway through conserved or variant evolutionary processes. These ultimately bridge the Ca2+ cascade reactions into regulatory networks, particularly in the hormonal signaling pathways. In summary, this review provides new perspectives towards a better understanding of the evolution, interaction and integration of Ca2+ signaling components in green plants, which is likely to benefit future research in agriculture, evolutionary biology, ecology and the environment.

One-Pot Synthesis of Benzimidazo[2,1-b]thiazoline Derivatives through an Addition/Cyclization/Oxidative Coupling Reaction.

A novel and efficient approach to the synthesis of benzimidazo[2,1-b]thiazoline derivatives has been developed through an addition/cyclization/intramolecular oxidative C-H functionalization process. A variety of alkylene benzimidazo[2,1-b] thiazolines were conveniently assembled from the reaction of aryl isothiocyanate and propargylic amine in the presence of Cu(OAc)2 and PIFA at room temperature. The product could be further converted to substituted benzimidazo[2,1-b]thiazole derivatives.

Erratum: Tong, T., et al. α-Ionone Protects Against UVB-Induced Photoaging in Human Dermal Fibroblasts. Molecules 2019, 24, 1804.

The authors wish to make the following change to their paper [...].

Genetic variation of HvXYN1 associated with endoxylanase activity and TAX content in barley (Hordeum vulgare L.).

BACKGROUND: Endo-ß-1,4-xylanase1 (EA), the key endoxylanase in plants, is involved in the degradation of arabinoxylan during grain germination. In barley (Hordeum vulgare L.), one gene (HvXYN-1) that encode a endo-beta-1,4-xylanase, has been cloned. However, the single nucleotide polymorphisms (SNPs) that affect the endoxylanase activity and total arabinoxylan (TAX) content have yet to be characterized. The investigation of genetic variation in HvXYN1 may facilitate a better understanding of the relationship between TAX content and EA activity in barley. RESULTS: In the current study, 56 polymorphisms were detected in HvXYN1 among 210 barley accessions collected from 34 countries, with 10 distinct haplotypes identified. The SNPs at positions 110, 305, 1045, 1417, 1504, 1597, 1880 bp in the genomic region of HvXYN1 were significantly associated with EA activity (P < 0.0001), and the sites 110, 305, and 1045 were highly significantly associated with TAX content. The amount of phenotypic variation in a given trait explained by each associated polymorphism ranged from 6.96 to 9.85%. Most notably, we found two variants at positions 1504 bp and 1880 bp in the second exon that significantly (P < 0.0001) affected EA activity; this result could be used in breeding programs to improve beer quality. In addition, African accessions had the highest EA activity and TAX content, and the richest germplasm resources were from Asia, indicating the high potential value of Asian barley. CONCLUSION: This study provided insight into understanding the relationship, EA activity, TAX content with the SNPs of HvXYN1 in barley. These SNPs can be applied as DNA markers in breeding programs to improve the quality of barley for beer brewing after further validation.

α-Cedrene protects rodents from high-fat diet-induced adiposity via adenylyl cyclase 3.

OBJECTIVE: The increasing global prevalence of obesity and its associated disorders points to an urgent need for the development of novel and effective strategies for the prevention of weight gain. Here, we investigated the potential of α-cedrene, a volatile sesquiterpene compound derived from cedarwood oil, in regulation of obesity and delineated the mechanisms involved. METHODS: For the prevention of obesity, C57BL/6 N mice were fed a high-fat diet (HFD) and were orally administered either with vehicle or α-cedrene for 8 weeks. For the therapy of obesity, obese Sprague Dawley rats, induced by a HFD for 8 weeks, were orally treated either with vehicle or α-cedrene for 12 weeks. To determine whether the action of α-cedrene was Adcy3 dependent, Adcy3 heterozygous null mice (Adcy3+/-) and wild-type controls were fed either HFD or α-cedrene supplemented HFD for 17 weeks. RESULTS: Oral α-cedrene administration prevented or reversed HFD-induced obesity and abnormal metabolic aberrations in rodents, without affecting their food intake. Downregulation of Adcy3 expression by small interfering RNA abrogated the beneficial effects of α-cedrene on the oxygen consumption rate and intracellular lipid accumulation in 3T3-L1 adipocytes. Similarly, in Adcy3+/- mice, the α-cedrene-driven suppression of body weight gain observed in wild-type mice was substantially (~50%) attenuated. Expression of thermogenic and lipid oxidation genes was increased in adipose tissues of α-cedrene-treated mice, with concomitant downregulation of adipogenic gene expression. These beneficial molecular changes elicited by α-cedrene were blunted in adipose tissues of Adcy3+/- mice. CONCLUSIONS: Our results highlight the potential of α-cedrene for antiobesity interventions and suggest that the antiobesity effect of α-cedrene is mediated by Adcy3 in adipose tissues.

Novel mutations in CYP4V2 in Bietti corneoretinal crystalline dystrophy: Next-generation sequencing technology and genotype-phenotype correlations.

Purpose: To identify any novel mutations in CYP4V2 in 85 Chinese families with Bietti corneoretinal crystalline dystrophy (BCD) by using next-generation sequencing, and to summarize the mutation spectrum in this population, along with any genotype-phenotype correlations. Methods: A total of 90 patients with BCD from 85 unrelated Chinese families were recruited. All probands were analyzed by using gene chip-based next-generation sequencing, to capture and sequence all the exons of 57 known hereditary retinal degeneration-associated genes. The candidate variants were validated with PCR and Sanger sequencing. Results: Twenty-eight mutations were detected in all patients, including thirteen novel mutations (five missense, six deletions, one splicing and one frame-shift mutations) and 15 previously reported mutations. Mutations in 64 patients were inherited from their parents, while three patients had de novo mutations. c.802-8_810del17insGC was the most common mutation, accounting for 78% of the mutations. Although 16 patients were homozygous at this site, the clinical features of all 16 patients were highly heterogeneous. Conclusions: These results expand the spectrum of mutations in CYP4V2, and suggest that mutations in CYP4V2 may be common in the Chinese population. The phenotype of patients with the homozygous mutation (hom.c.802-8_810del17insGC) is highly heterogeneous.