AKT/FOXM1/STMN1 signaling pathway activation by SMC1A promotes tumor growth in breast cancer.

BACKGROUND: Upregulation of SMC1A (Structural maintenance of chromosomes 1A) is linked with many types of cancer and its oncogenic function, which has been associated with crucial cellular mechanisms (cell division, cell cycle checkpoints regulation and DNA repair). Recent studies have shown that SMC1A was involved in breast cancer, although the exact mechanisms of SMC1A remain to be determined. METHODS: Using The Cancer Genome Atlas (TCGA) database, we examined SMC1A expression and its relation to other genes, including FOXM1 and STMN1. Short hairpin RNA was used to subsequently examine the biological roles of SMC1A in MDA-MB-231 and MDA-MB-468 cell lines. Bioinformatics were performed to identify the SMC1A-related gene FOXM1. RESULTS: Here, we used the TCGA database to show that SMC1A is overexpressed in breast cancer. Later investigations showed SMC1A's role in breast cancer cell survival, apoptosis and invasion. Using bioinformatics and western blot assays, we confirmed that FOXM1 acted as the downstream of SMC1A, and SMC1A knockdown significantly downregulated the FOXM1 expression via the AKT signal pathway. Interestingly, the inhibition effects induced by SMC1A downregulation could be reversed by FOXM1 overexpression. In the clinic, SMC1A expression is favorably linked with FOXM1 expression in breast cancer tumor tissues. CONCLUSIONS: Collectively, our results not only enhance our knowledge of SMC1A's molecular pathways in breast cancer, but also suggest a potential new therapeutic target.

Right ventricular-pulmonary arterial coupling ratio derived from 3-dimensional echocardiography predicts outcomes in systemic lupus erythematosus-associated pulmonary arterial hypertension patients.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune connective tissue disease (CTD) that is an important cause of devastating pulmonary arterial hypertension (PAH), and persistent progression of PAH can lead to right heart failure, predicting a poor prognosis for SLE patients. Right ventricular-pulmonary arterial (RV-PA) coupling with echocardiography has been demonstrated to be a noninvasive alternative method for evaluating PAH patients' predictive outcomes. Whether the ratio of right ventricular stroke volume (RVSV) to right ventricular end-systolic volume (RVESV) measured by three-dimensional echocardiography (3DE) is a new index of RV-PA coupling has not been discussed as a new predictor for the clinical outcome of systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). METHODS: From June 2019 to February 2023, 46 consecutive patients with SLE-PAH were enrolled prospectively, and their clinical data and echocardiographs were studied and analyzed. The control group consisted of 30 healthy subjects matched for age, sex, and body surface area (BSA). The main endpoints of this study were a composite of all-cause mortality and adverse clinical events. Baseline clinical characteristics and echocardiographic assessments were analyzed. RESULTS: During a median of 24 months (IQR 18-31), 16 of 46 SLE-PAH patients (34.7%) experienced endpoint-related events. At baseline, patients who experienced mortality or adverse events had a worse WHO functional class (WHO FC) and lower anti-double-stranded DNA (dsDNA) antibody levels. The right ventricular (RV) systolic dysfunction in SLE-PAH subjects was significantly worse than that in the healthy control group, especially in SLE-PAH patients in the endpoint event group. Compared to controls, patients with SLE-PAH had a lower RVSV/RVESV ratio. In the group comparison, patients who had experienced an endpoint event had a sequentially worse ratio (1.86 (1.65-2.3) versus 1.30 (1.09-1.46) versus 0.64 (0.59-0.67), p < .001). There were statistically significant associations between the RVSV/RVESV ratio to routine RV systolic function and clinical parameters. The RVSV/RVESV ratio was negatively correlated with the WHO FC (r = -0.621, p < .001) and positively correlated with the anti-dsDNA level. The ROC curve showed that the optimal cutoff for RVSV/RVESV < 0.712 determined a higher risk of poor prognosis. Kaplan‒Meier survival curves showed that an RVSV/RVESV ratio >0.712 was associated with more favorable long-term outcomes. CONCLUSIONS: The 3DE-derived SV/ESV ratio as a noninvasive alternative surrogate of RV-PA coupling was an eximious indicator for identifying endpoint events in SLE-PAH patients and can provide a diagnostic basis for clinical intervention.

DIA-Based Quantitative Proteomics in the Flower Buds of Two Malus sieversii (Ledeb.) M. Roem Subtypes at Different Overwintering Stages.

Malus sieversii is considered the ancestor of the modern cultivated apple, with a high value for apple tolerance breeding. Despite studies on the temperature adaptability of M. sieversii carried out at a physiological response and the genome level, information on the proteome changes of M. sieversii during dormancy is limited, especially about the M. sieversii subtypes. In this study, a DIA-based approach was employed to screen and identify differential proteins involved in three overwintering periods of flower buds in two M. sieversii subtypes (Malus sieversii f. luteolus, GL; Malus sieversii f. aromaticus, HC) with different overwintering adaptabilities. The proteomic analysis revealed that the number of the down-regulated differential expression proteins (DEPs) was obviously higher than that of the up-regulated DEPs in the HC vs. GL groups, especially at the dormancy stage and dormancy-release stage. Through functional classification of those DEPs, the majority of the DEPs in the HC vs. GL groups were associated with protein processing in the endoplasmic reticulum, oxidative phosphorylation, starch and sucrose metabolism and ribosomes. Through WGCNA analysis, tricarboxylic acid cycle and pyruvate metabolism were highly correlated with the overwintering stages; oxidative phosphorylation and starch and sucrose metabolism were highly correlated with the Malus sieversii subtypes. This result suggests that the down-regulation of DEPs, which are predominantly enriched in these pathways, could potentially contribute to the lower cold tolerance observed in HC during overwintering stage.

[Consistency evaluation of multidimensional quality attributes of Atractylodis Macrocephalae Rhizoma by fusion of multi-source information].

The quality control of Chinese medicinal decoction pieces is one of the key tasks in the traditional Chinese medicine industry. In this study, multi-source information fusion was employed to fuse the data from near-infrared spectroscopy, electronic tongues, and other tests and establish an overall quality consistency evaluation method for Atractylodis Macrocephalae Rhizoma, which provided methodological support for the overall quality evaluation of Atractylodis Macrocephalae Rhizoma. The near-infrared spectroscopy information was measured in both static and dynamic states for 23 batches of Atractylodis Macrocephalae Rhizoma samples from different sources, and the electronic tongue sensory information, moisture content, and leachate content were measured. The overall quality of Atractylodis Macrocephalae Rhizoma was evaluated by multi-source information fusion. The results showed that the near-infrared spectroscopy information of 16122103, 801000509, 801000352, 701003656, HX21L01, and 160956 was different from that of other batches of Atractylodis Macrocephalae Rhizoma powder in the static state, and 701003298, 16122103, 701003656, 701003107, 801000229, and 18090404 were the different batches in the dynamic state. The moisture content showed no significant difference between batches. The leachate content in the batch 801000509 was different from that in other batches. The electronic tongue sensory information of 150721004, 151237, 160703004, HX21M01, HX21K04, HX21K01, and 601003516 was different from that of other batches. Furthermore, data layer fusion was employed to analyze the overall quality of Atractylodis Macrocephalae Rhizoma. Four batches, 150721004, HX21M01, HX21K04, and HX21K01, showed the parameters exceeding the 95% control limits and differed from the other samples in terms of the overall quality. This study integrated the information of moisture, near-infrared spectroscopy, and other sources to evaluate the quality consistency among 23 batches of Atractylodis Macrocephalae Rhizoma samples, which provides a reference for the quality consistency evaluation of Chinese medicinal decoction pieces.

PRDX6-mediated pulmonary artery endothelial cell ferroptosis contributes to monocrotaline-induced pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening cardiopulmonary disorder whose underlying pathogenesis is unknown. Our previous study showed that pulmonary endothelial cell (PAEC) ferroptosis is involved in the progression of PH by releasing High-mobility group box 1 (HMGB1) and activating Toll-like receptor 4/NOD-like receptor family pyrin domain containing 3 (TLR4/NLRP3) inflammasome signalling. The precise mechanisms that regulate ferroptosis in PH are unclear. This study aimed to investigate the effect of peroxiredoxin 6 (PRDX6) on PAEC ferroptosis in PH. METHODS: A rat model of PH was established with monocrotaline (MCT), and the distribution and expression of PRDX6 in the pulmonary artery were examined. Lentiviral vectors carrying PRDX6 (LV-PRDX6) were transfected into PAECs and injected into MCT-induced PH rats. Cell viability, MDA levels, reactive oxygen species (ROS) levels, labile iron pool (LIP) levels and mitochondrial morphology were examined. Ferroptosis-related proteins (NADPH oxidase-4 (NOX4), glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1(FTH1)), TLR4, NLRP3 inflammasome markers, HMGB1 and inflammatory cytokines were examined. Pulmonary vascular remodelling and right ventricular structure and function were measured. RESULTS: PRDX6 was expressed in PAECs and was significantly decreased in PH. PRDX6 overexpression significantly inhibited ferroptosis in PAECs under PH conditions in vitro and in vivo, as indicated by increased cell viability, decreased MDA, ROS and LIP levels, inhibited mitochondrial damage, upregulated GPX4 and FTH1 expression, and downregulated NOX4 expression. PRDX6 overexpression attenuated pulmonary vascular remodelling and changes in right ventricle structure and function in MCT-induced PH rats. Moreover, PRDX6 overexpression prevented HMGB1 release by PAECs and decreased TLR4 and NLRP3 inflammasome expression and inflammatory cytokine release in macrophages, while RSL3, a specific activator of ferroptosis, reversed these effects. CONCLUSIONS: Taken together, these findings indicate that PRDX6 regulates PAEC ferroptosis through the release of HMGB1 and activation of the TLR4/NLRP3 inflammasome signalling pathway, providing novel therapeutic targets for the treatment of PH.

Isolation of new compounds related to xyloketals biosynthesis implies an alternative pathway for furan-fused-chromene formation.

In fungi, there is a rare group of natural products harboring the 2,3,3a,9a-tetrahydro-4H-furo[2,3-b]chromene skeleton, represented by xyloketal B, which display a wide range of biological activities and have drawn significant attention. In this work, four new analogues simpliketals A-D (1-4), as well as two other new compounds simplilactones A and B (5 and 6), were isolated from Simplicillium sp. AHK071-01. Their structures were elucidated by extensive NMR spectroscopic methods, 13C NMR calculation, single-crystal X-ray diffraction, and ECD calculation. In addition, five known compounds (7-11) including alboatrin (7) were also obtained. Based on the structural similarity of the above compounds, we inferred that compounds 5, 6, and 8-11 might be biosynthetically related with 1-4 and 7, which allowed us to propose an alternative biosynthetic route to generate the furan-fused chromene skeleton of this class of compounds, instead of a previously presumed polyketide-terpenoid hybrid pathway. Finally, cytotoxicity assays showed that 1-4 exhibited weak inhibitory activity on PANC-1 cells and that 2 and 3 possessed moderate activity against SH-SY5Y cells.

Acute and chronic effects of sublethal neonicotinoid thiacloprid to Asian honey bee (Apis cerana cerana).

Pesticide pollution is one of the most important factors for global bee declines. Despite many studies have revealed that the most important Chinese indigenous species，Apis cerana, is presenting a high risk on exposure to neonicotinoids, the toxicology information on Apis cerana remain limited. This study was aimed to determine the acute and chronic toxic effects of thiacloprid (IUPAC name: {(2Z)-3-[(6-Chloro-3-pyridinyl)methyl]-1,3-thiazolidin-2-ylidene}cyanamide) on behavioral and physiological performance as well as genome-wide transcriptome in A. cerana. We found the 1/5 LC50 of thiacloprid significantly impaired learning and memory abilities after both acute and chronic exposure, nevertheless, has no effects on the sucrose responsiveness and phototaxis climbing ability of A. cerana. Moreover, activities of detoxification enzyme P450 monooxygenases and CarE were increased by short-term exposure to thiacloprid, while prolonged exposure caused suppression of CarE activity. Neither acute nor chronic exposure to thiacloprid altered honey bee AChE activities. To further study the potential defense molecular mechanisms in Asian honey bee under pesticide stress, we analyzed the transcriptomes of honeybees in response to thiacloprid stress. The transcriptomic profiles revealed consistent upregulation of immune- and stress-related genes by both acute or chronic treatments. Our results suggest that the chronic exposure to thiacloprid produced greater toxic effects than a single administration to A. cerana. Altogether, our study deepens the understanding of the toxicological characteristic of A. cerana against thiacloprid, and could be used to further investigate the complex molecular mechanisms in Asian honey bee under pesticide stress.

Mitochondrial Energy Metabolism in the Regulation of Thermogenic Brown Fats and Human Metabolic Diseases.

Brown fats specialize in thermogenesis by increasing the utilization of circulating blood glucose and fatty acids. Emerging evidence suggests that brown adipose tissue (BAT) prevents the incidence of obesity-associated metabolic diseases and several types of cancers in humans. Mitochondrial energy metabolism in brown/beige adipocytes regulates both uncoupling protein 1 (UCP1)-dependent and -independent thermogenesis for cold adaptation and the utilization of excess nutrients and energy. Many studies on the quantification of human BAT indicate that mass and activity are inversely correlated with the body mass index (BMI) and visceral adiposity. Repression is caused by obesity-associated positive and negative factors that control adipocyte browning, de novo adipogenesis, mitochondrial energy metabolism, UCP1 expression and activity, and noradrenergic response. Systemic and local factors whose levels vary between lean and obese conditions include growth factors, inflammatory cytokines, neurotransmitters, and metal ions such as selenium and iron. Modulation of obesity-associated repression in human brown fats is a promising strategy to counteract obesity and related metabolic diseases through the activation of thermogenic capacity. In this review, we highlight recent advances in mitochondrial metabolism, thermogenic regulation of brown fats, and human metabolic diseases.

Transplantation of Chemical Compound-Induced Cells from Human Fibroblasts Improves Locomotor Recovery in a Spinal Cord Injury Rat Model.

The development of regenerative medicine using cell therapy is eagerly awaited for diseases such as spinal cord injury (SCI), for which there has been no radical cure. We previously reported the direct conversion of human fibroblasts into neuronal-like cells using only chemical compounds; however, it is unclear whether chemical compound-induced neuronal-like (CiN) cells are clinically functional. In this study, we partially modified the method of inducing CiN cells (termed immature CiN cells) and examined their therapeutic efficacy, in a rat model of SCI, to investigate whether immature CiN cells are promising for clinical applications. Motor function recovery, after SCI, was assessed using the Basso, Beattie, and Bresnahan (BBB) test, as well as the CatWalk analysis. We found that locomotor recovery, after SCI in the immature CiN cell-transplanted group, was partially improved compared to that in the control group. Consistent with these results, magnetic resonance imaging (MRI) and histopathological analyses revealed that nerve recovery or preservation improved in the immature CiN cell-transplanted group. Furthermore, transcriptome analysis revealed that immature CiN cells highly express hepatocyte growth factor (HGF), which has recently been shown to be a promising therapeutic agent against SCI. Our findings suggest that immature CiN cells may provide an alternative strategy for the regenerative therapy of SCI.

Absent atherosclerotic risk factors are associated with carotid stiffening quantified with ultrafast ultrasound imaging.

OBJECTIVES: To evaluate carotid stiffening in participants without conventional cardiovascular risk factors (CVRFs) by using ultrafast pulse wave velocity (ufPWV). METHODS: The present study enrolled 517 participants without conventional CVRFs (CVRF-Free total population). Subjects in this population were defined as current non-smokers with untreated blood pressure < 140/90 mmHg, fasting blood glucose (FBG) < 7.0 mmol/L, total cholesterol (TC) < 6.2 mmol/L, low-density lipoprotein cholesterol < 4.1 mmol/L, and high-density lipoprotein cholesterol ≥ 1.0 mmol/L. Participants in the subgroup with optimal CVRFs (CVRF-Optimal subgroup; n = 188) were defined as having blood pressure < 120/80 mmHg, TC < 5.2 mmol/L, and FBG < 5.6 mmol/L. Clinical interviews, physical examinations, serum draw, carotid intima-media thickness (cIMT), and ufPWV were evaluated. Adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression models were used. RESULTS: Carotid stiffening was present in 46.2-54.5% of CVRF-Free subjects. Age, male sex, and body mass index (BMI) were independently associated with carotid stiffening in both the CVRF-Free total population and CVRF-Optimal subgroup (OR for age = 1.10-1.11, OR for male sex = 2.65-7.19, OR for BMI = 1.34-1.62; p < 0.05). Carotid stiffening was associated with TC only in the CVRF-Free total population (OR for TC = 1.84; p = 0.034). CONCLUSIONS: Many CVRF-Free individuals have carotid stiffening. ufPWV for atherosclerotic stiffening aids the assessment of early atherogenesis and may further clarify the true status of healthy adults without CVRFs. KEY POINTS: • CVRF-Optimal individuals have a lower carotid stiffness than CVRF-Free populations. • ufPWV is a quantitative predictor for the early assessment of AS. • Absent major CVRFs cannot be considered low risk for carotid stiffening and atherosclerosis.

Comparing four methods of rearing Varroa destructor in vitro.

The parasitic mite Varroa destructor Anderson and Trueman continues to devastate western honey bee (Apis mellifera L.) colonies throughout most of the world where they are managed. The development of a method to rear Varroa in vitro would allow for year-round Varroa research, rapidly advancing our progress towards controlling the mite. We created two separate experiments to address this objective. First, we determined which of four in vitro rearing methods yields the greatest number of Varroa offspring. Second, we attempted to improve the rearing rates achieved with that method. The four methods tested included (1) rearing Varroa on honey bee pupae in gelatin capsules, (2) rearing Varroa on in vitro-reared honey bees, (3) group rearing Varroa on honey bee pupae in Petri dishes, and (4) providing Varroa a bee-derived diet. The number of reproducing females and the number of fully mature offspring were significantly higher in the gelatin capsules maintained at 75% RH than in any other method. A 2 × 3 full factorial design was used to test combinations of gelatin capsule size (6 and 7 mm diameter) and relative humidity (65, 75, or 85%) on Varroa rearing success. Varroa reproduction and survival were significantly higher in 7-mm-diameter gelatin capsules maintained at 75% RH than in those maintained in 6-mm capsules and at the other humidities. By identifying factors that influence Varroa reproductive success in vitro, this work provides an important foundation for the development of future rearing protocols.

Intramolecular Imino-ene Reaction of Azirines: Regioselectivity, Diastereoselectivity, and Computational Insights.

Intramolecular imino-ene reaction of 2 H-aziridine has been studied experimentally and computationally, demonstrating that (1) the concerted process takes place regioselectively on the alkene E-CH group; (2) the geometry of the N-linker impacts the reaction activation energy and diastereoselectivity significantly, with pyramidal alkyl amine as the linkage, an exclusive cis-product is achieved; (3) when the reaction has to occur with the Z-CH group, the cis-diastereoselectivity is solely observed regardless of the nature of the N-linkage.

Insights into the molecular basis of immunosuppression and increasing pathogen infection severity of ammonia toxicity by transcriptome analysis in pacific white shrimp Litopenaeus vannamei.

The high concentration of ammonia resulting from intensive culture system and environmental pollution could cause disease occurrence in shrimp, but little information is available on its molecular mechanisms. In this study, we performed comparative transcriptome analysis among WSSV-infected shrimp under ammonia stress (LAV), WSSV-infected shrimp under normal water (LV), and normal shrimp under ammonia stress (LA) groups to identify the key genes and pathways involved in immunosuppression and increasing pathogen infection severity caused by ammonia toxicity in Litopenaeus vannamei. Totally, 526 significantly differential expressed genes (DEGs) were identified in LAV group compared to LV and LA groups, among which 270 genes were lost expressed and 67 genes uniquely expressed in the LAV group. According to the public functional reports for the annotated DEGs, they potentially involved in the following functions: (1) accelerating pathogen adhesion, invasion and multiplication; (2) reducing the ability for pathogen defense and immune response; (3) inhibiting positive regulation of apoptotic and antioxidant defense for host homeostasis; (4) inhibiting transcription and protein transport; (5) and increasing protein methylation and ubiquitination, etc. A total of 13 pathways were obtained mainly involving in this process, which mainly led to the following changes: (1) increasing the immunosuppression, anemia, endocrine dysfunction, neurotoxic effect and neuroinvasion, atherosclerosis and thrombogenesis, blood-brain barrier penetration, thyroid disorder, necrosis, inflammation, and circadian disturbance; (2) reducing the ability of vascular remodeling, angiogenesis, cell survival, migration, apoptosis, and lymph transferred to blood stream; (3) leading to cell hypertrophy, cellular shape changes, and mesangial matrix expansion. The present results firstly supplied molecular mechanisms for the ammonia toxicity inhibiting the immune system and increasing pathogen infection severity in shrimp, which is a prerequisite for better understanding the pathogenesis caused by ammonia toxicity.

Mechanistic Insights into Cyclopropenes-Involved Carbonylative Carbocyclization Catalyzed by Rh(I) Catalyst: A DFT Study.

Computational studies were carried out to provide mechanistic insights into the Rh(I)-catalyzed activation of cyclopropenes and the detailed mechanistic pathways of [3+2+1] carbonylative carbocyclization of tethered ene- and yne-cyclopropenes. Computational results suggest that it is more favorable for the cyclopropene moiety of tethered ene-cyclopropenes to initially undergo heterolytic cleavage of a C-C σ-bond to form a vinyl Rh(I) carbenoid intermediate than to proceed through homolytic C-C σ-bond cleavage to generate a rhodacyclobutene intermediate. The yielded vinyl Rh(I) carbenoid intermediate could undergo cyclization to generate a Rh(III) metallacyclobutene intermediate, which could further lead to a thermodynamically more stable six-coordinated Rh(III) metallacycle intermediate in the presence of additional CO. Afterward, it is more feasible for the yielded six-coordinated Rh(III) metallacycle to sequentially undergo CO migratory insertion, cyclization, and reductive elimination to furnish the final cyclohexenone product. The origin of stereoselectivity of the product was also discussed. The proposed mechanistic pathway can also be applied to the Rh(I)-catalyzed carbonylative carbocyclization of tethered yne-cyclopropenes and vinyl cyclopropenes to produce phenol derivatives. The main mechanistic difference for the vinyl cyclopropene substrate is that the conversion of Rh(I) carbenoid intermediate to the Rh(III) metallacycle proceeds via intramolecular 6π electrocyclization.

iTRAQ-based comparative proteome analysis for molecular mechanism of defense against acute ammonia toxicity in Pacific White shrimp Litopenaeus vannamei.

In the practical farming of Litopenaeus vannamei, the intensive culture system and environmental pollution usually results in a high concentration of ammonia, which brings large detrimental effects to shrimp, such as increasing the susceptibility to pathogens and even causing high mortality. We have revealed that the survival time under acute ammonia stress varied substantially among different families and obtained ammonia-tolerant (LV_T) and ammonia-sensitive (LV_S) families. In order to understand the molecular mechanism of defense against ammonia toxicity in shrimp, we performed iTRAQ LC-MS/MS proteomic analysis between LV_T and LV_S groups of L. vannamei under acute ammonia stress to identify the key proteins and pathways that play an effective role for against ammonia toxicity. By comparative proteome analysis, 202 significantly differentially proteins (DEPs) were identified in LV_T compared to LV_S, and most of the DEPs (60%) were up-regulated. Excepting for the proteins without function reporting, the meaningful finding is that 77.8% of the DEPs have been reported mainly involving in immune defense and stress tolerant in crustacean species, such as hemocyanin, Rab7, Rab GTPase, Rac1, alpha 2 macroglobulin, Bip, peroxiredoxin, Cu/Zn SOD, glutathione peroxidase, thioredoxin, calreticulin, and Elongation Factor 1-alpha, etc. These DEPs might potentially play important role in against ammonia toxicity, and it also reflected a relation between ammonia tolerance and pathogen resistance. In addition, a total of 10 significantly changed KEGG pathways were detected, and the network diagram of these KEGG pathways showed that more critical nodes were up-regulated, which involved in protein synthesis and transport, and against stress stimuli. This study provided important information for understanding the molecular mechanism of defense against ammonia toxicity in shrimp at whole protein level.

Identification of SNP markers associated with tolerance to ammonia toxicity by selective genotyping from de novo assembled transcriptome in Litopenaeus vannamei.

The high concentration of ammonia from deteriorated aquaculture environments and the intensive culture system could increase the susceptibility to pathogens and even cause high mortality in Litopenaeus vannamei. In addition, we have revealed that the ammonia-tolerant shrimp also have high disease resistance in L. vannamei. In the present study, in order to identify SNP markers associated with tolerance to ammonia toxicity, we developed and characterized SNPs from our previous transcriptome sequencing data of ammonia-stressed and control groups, and a marker-trait association analysis was performed for marker-assisted selection (MAS) to increase production in L. vannamei. A total of 318,919 SNPs were identified from the transcriptome sequences, and 25,772 SNPs were found from the 1826 ammonia-responsive genes with functional annotation. We selected 49 SNPs from 26 ammonia-responsive genes that had strong homologies to known genes in the shrimp and probably involved in immune function as candidate markers for genotyping, among which 39 SNPs were polymorphic for further marker-trait association analysis with the ammonia-tolerant (AT) and ammonia-sensitive (AS) groups. Finally, 12 out of the 49 SNP markers were identified to be associated with ammonia tolerance, containing 10 loci with significantly different allele frequencies and 10 loci with significantly different genotyping frequencies between the AT and AS groups. Among the associated markers, the G allele of TSP-1 (the first locus from the thrombospondin gene), the A allele of TSP-3, and the C allele of XBP1-5 (the fifth locus from X-box binding protein 1) only presented in the AT groups, but they were absent from the AS groups, which would be the preference of the MAS for the ammonia-tolerant shrimp. In addition, when the 12 associated SNP markers were used for analysis, the genetic diversity of the AT groups were significantly higher than that of the AS groups, but when the 39 loci were used there was no difference. This is the first report for the markers associated with ammonia tolerance in this species, indirectly with disease resistance, which provided important potential for genetic selection to increase survival rate and production in shrimp farming.

Highly efficient hydroboration of carbonyl compounds catalyzed by tris(methylcyclopentadienyl)lanthanide complexes.

Homoleptic lanthanide complexes coordinated by a Me-substituted Cp ligand [(MeCp)3Ln] demonstrate unprecedentedly high efficiency in catalyzing the hydroboration of aldehydes and ketones with pinacolborane. This protocol is also applicable for the hydroboration of aryl-substituted imines. In addition, broad functional group compatibility and excellent chemoselectivity is also achieved. DFT calculations are employed to shed light on the reaction mechanism.

Characterization of Methyltransferase AlmCII in Chalcomycin Biosynthesis: The First TylF Family O-Methyltransferase Works on a 4'-Deoxysugar.

Sugar O-methylation is a ubiquitous modification in natural products and plays diverse roles. This realization has inspired many attempts to search for novel methyltransferases. Chalcomycins are a group of 16-membered macrolides containing two methylated sugars that require three methyltransferases for their biosynthesis. Here, we identified that AlmCII, a sugar O-methyltransferase belonging to the TylF family that was previously only known to methylate sugars with a 4'-hydroxy group, can methylate a 4',6'-dideoxysugar during the biosynthesis of chalcomycins. An in vitro enzymatic assay revealed that AlmCII is divalent metal-dependent with an optimal pH of 8.0 and optimal temperature of 42 °C. Moreover, the 3'-O-demethylated chalcomycins exhibit less than 6 % of the antibacterial activity of their parent compounds. This is the first report demonstrating that a TylF family O-methyltransferase can use a 4'-deoxy sugar as a substrate and highlighting the importance of this methylation for the antibacterial activity of chalcomycins.

Genetic assessment of residual feed intake as a feed efficiency trait in the Pacific white shrimp Litopenaeus vannamei.

BACKGROUND: Residual feed intake (RFI) was investigated as a measure of feed efficiency in a breeding population of Litopenaeus vannamei. Shrimp from 34 families were housed individually and feed efficiency and growth traits were recorded during two successive growth periods. The objectives of this study were (1) to estimate the heritability of RFI and related traits, including feed efficiency ratio (FER), average daily gain (ADG) and daily feed intake (DFI), (2) to determine the relationships between RFI and other traits, and (3) to evaluate the variation of these traits across two growth periods. RESULTS: Shrimp displayed large inter-individual variation in RFI, FER, ADG and DFI during each growth period. Heritability estimates of all these traits during both periods reached high values (0.577 ± 0.232 to 0.707 ± 0.252). RFI showed weak and no genetic correlations with ADG during the two growth periods between days 1 to 21 (0.135 ± 0.204) and 22 to 42 (-0.018 ± 0.128), respectively, but high positive genetic correlations with DFI (>0.8). Weak and moderate negative genetic correlations were observed between RFI and FER during the two periods (-0.126 ± 0.208 and -0.387 ± 0.183). As evidenced by the high genetic correlations between the two periods for each trait (>0.6), trait performance of the shrimp tended to be consistent across periods. CONCLUSIONS: For the first time, accurate measurement of individual feed efficiency on a large scale was achieved in shrimp. Although the estimated heritability reported here for RFI may be overestimated, it is a heritable trait in L. vannamei that can be improved by genetic improvement. For L. vannamei, the biggest potential advantage in using RFI as a measure of feed efficiency is that it is independent of growth rate, and thus genetic selection on RFI has the potential to improve feed efficiency and reduce feed intake, without compromising growth performance.

Microbial transformation of the anti-diabetic agent corosolic acid by Cunninghamella echinulata.

The pentacyclic triterpenoid corosolic acid was metabolized by Cunninghamella echinulata CGMCC 3.2000 to its C-24 aldehyde group metabolite and five other hydroxylated metabolites: madasiatic acid (2), 2α, 3ß, 7ß-trihydroxyurs-12-en-28-oic acid (3), 2α, 3ß, 15α-trihydroxyurs-12-en-28-oic acid (4), 2α, 3ß, 6ß, 7ß-tetrahydroxyurs-12-en-28-oic acid (5), 2α, 3ß, 7ß, 15α-tetrahydroxyurs-12-en-28-oic acid (6), and 2α, 3ß,7ß-trihydroxy-24-al-urs-12-en-28-oic acid (7); compounds 3, 5, and 7 were new compounds. The α-glucosidase inhibitory effects of the metabolites were also evaluated.