The construction of carbon–heteroatom bonds is one of the most active areas of research in organic chemistry because the function of organic molecules is often derived from the presence of ...heteroatoms. Although considerable advances have recently been achieved in radical-involved catalytic asymmetric C–N bond formation, there has been little progress in the corresponding C–O bond-forming processes. Here, we describe a photoinduced copper-catalyzed cross-coupling of readily available oxime esters and 1,3-dienes to generate diversely substituted allylic esters with high regio- and enantioselectivity (>75 examples; up to 95% ee). The reaction proceeds at room temperature under excitation by purple light-emitting diodes (LEDs) and features the use of a single, earth-abundant copper-based chiral catalyst as both the photoredox catalyst for radical generation and the source of asymmetric induction in C–O coupling. Combined experimental and density functional theory (DFT) computational studies suggest the formation of π-allylcopper complexes from redox-active oxime esters as bifunctional reagents and 1,3-dienes through a radical–polar crossover process.
Aims
To evaluate the association between glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and the risk of bone fracture in patients with type 2 diabetes mellitus (T2DM).
Materials and methods
We ...conducted a systematic literature search in PubMed, Embase, the Cochrane Library, and Web of Science from inception to 28 February 2018 and identified eligible randomized controlled trials. The following data were extracted from each study: first author, year of publication, sample size, patient characteristics, study design, intervention drug, control drug, follow‐up time, and incident bone fracture events. A meta‐analysis was conducted using Review Manager 5.3 software to calculate the odds ratio (OR) and 95% confidence intervals (CI) for dichotomous variables.
Results
A total of 38 studies with 39 795 patients with T2DM were included. There were 241 incident bone fracture cases (107 in the GLP‐1 RAs group and 134 in the control group). Compared with patients who received placebo and other anti‐diabetic drugs, those who received GLP‐1 RAs treatment showed a pooled OR of 0.71 (95% CI, 0.56‐0.91) for bone fracture. Subgroup analysis showed that treatments with liraglutide and lixisenatide were associated with significantly reduced risk of bone fractures (ORs, 0.56; 95% CI, 0.38‐0.81 and 0.55; 95% CI, 0.31‐0.97, respectively). However, other GLP‐1 RAs did not show superiority to placebo or other anti‐diabetic drugs. Moreover, these beneficial effects were dependent on the duration of GLP‐1 RAs treatment, only a GLP‐1 RAs treatment period of more than 52 weeks could significantly lower the risk of bone fracture in patients with T2DM (OR, 0.71; 95% CI, 0.56‐0.91).
Conclusions
Compared with placebo and other anti‐diabetic drugs, liraglutide and lixisenatide were associated with a significant reduction in the risk of bone fractures, and the beneficial effects were dependent on the duration of treatment.
To investigate the potential impact of complications in gastric cancer patients who survive the initial postoperative period.
Between January 1, 2005 and December 31, 2006, 432 patients who received ...curative gastrectomy with D2 lymph node dissection for gastric cancer at our department were studied. Associations between clinicopathological factors age, sex, American Society of Anesthesiologists grade, body mass index, tumor-node-metastases (TNM) stage and tumor grade, including postoperative complications (defined as any deviation from an uneventful postoperative course within 30 d of the operation and survival rates) and treatment-specific factors (blood transfusion, neoadjuvant therapy and duration of surgery). Patients were divided into 2 groups: with (n = 54) or without (n = 378) complications. Survival curves were compared between the groups, and univariate and multivariate models were conducted to identify independent prognostic factors.
Among the 432 patients evaluated, 61 complications occurred affecting 54 patients (12.50%). Complications included anastomotic leakages, gastric motility disorders, anastomotic block, wound infections, intra-abdominal abscesses, infectious diarrhea, bleeding, bowel obstructions, arrhythmias, angina pectoris, pneumonia, atelectasis, thrombosis, unexplained fever, delirium, ocular fungal infection and multiple organ failure. American Society of Anesthesiologists grade, body mass index, combined organ resection and median duration of operation were associated with higher postoperative complications. The 1-, 3- and 5-year survival rates were 83.3%, 53.2% and 37.5%, respectively. In the univariate analysis, the size of lesions, TNM stage, blood transfusion, lymphovascular invasion, perineural invasion, neoadjuvant chemotherapy, and postoperative complications were significant predictors of overall survival. In the multivariate analysis, only TNM stage and the presence of complications remained significant predictors of reduced survival.
The occurrence of in-hospital postoperative complications was an independent predictor of worse 5-year overall survival rate after radical resection of gastric cancer.
Aridity and heat are significant environmental stressors that affect sheep adaptation and adaptability, thus influencing immunity, growth, reproduction, production performance, and profitability. The ...aim of this study was to profile mRNA expression levels in the spleen of indigenous Kazakh sheep breed for comparative analysis with the exotic Suffolk breed. Spleen histomorphology was observed in indigenous Kazakh sheep and exotic Suffolk sheep raised in Xinjiang China. Transcriptome sequencing of spleen tissue from the two breeds were performed via Illumina high-throughput sequencing technology and validated by RT-qPCR. Blood cytokine and IgG levels differed between the two breeds and IgG and IL-1β were significantly higher in Kazakh sheep than in Suffolk sheep (p < 0.05), though spleen tissue morphology was the same. A total of 52.04 Gb clean reads were obtained and the clean reads were assembled into 67,271 unigenes using bioinformatics analysis. Profiling analysis of differential gene expression showed that 1158 differentially expressed genes were found when comparing Suffolk with Kazakh sheep, including 246 up-regulated genes and 912 down-regulated genes. Utilizing gene ontology annotation and pathway analysis, 21 immune- responsive genes were identified as spleen-specific genes associated with adaptive traits and were significantly enriched in hematopoietic cell lineage, natural killer cell-mediated cytotoxicity, complement and coagulation cascades, and in the intestinal immune network for IgA production. Four pathways and up-regulated genes associated with immune responses in indigenous sheep played indispensable and promoting roles in arid and hot environments. Overall, this study provides valuable transcriptome data on the immunological mechanisms related to adaptive traits in indigenous and exotic sheep and offers a foundation for research into adaptive evolution.
Vacuolar ATPase (vATPase) is an important proton pump in insect tissues including gut and Malpighian tubule. Subunit F, one of the 16 subunits of the vATPase holoenzyme, is not well characterized. ...Here, we found that two HvvATPaseF isoforms were highly expressed in the hindgut and Malpighian tubules (MT) in the 28‐spotted lady‐beetle Henosepilachna vigintioctopunctata, an agricultural pest that feeds on Solanaceae and Cucurbitaceae. Knockdown of both HvvATPaseF variants by RNA interference (RNAi) delayed larval growth and negatively affected ecdysis and adult emergence. In the midgut, RNAi treatment resulted in the disappearance of peritrophic membrane, the reduction in the size and the impaired integrity of the gut, which was associated with sparse principle cells and an increase in TUNEL‐ and EdU‐positive cells. Whereas the MT were opaque and the tubule lumens were full of urine in dsegfp‐fed larvae, the tubules were clear and the tubule lumens were empty in the dsvATPaseF‐fed larvae. HvvATPaseF knockdown was also associated with a decrease in the abundance of the fat body and the levels of glucose, trehalose, triglyceride, total soluble amino acids and proteins, and an increase in glycogen. Consistent with the known effects of sugars on chitin formation, both the expression level of a chitin biosynthesis gene and the thickness of the head capsule cuticle were reduced in the HvvATPaseF‐depleted beetles. Our results demonstrated that subunit F plays an essential role in H. vigintioctopunctata development.
HvvATPaseF is highly expressed in the hindgut and Malpighian tubules. RNAi of HvvATPaseF impairs ecdysis and adult emergence. Silencing HvvATPaseF inhibits growth and compromises integrity of the midguts. Knockdown of HvvATPaseF dysfunctions Malpighian tubules. Silencing HvvATPaseF lowers contents of nutrients and depletes fat body.
In insects, the expression of 20E response genes that initiate metamorphosis is triggered by a pulse of 20‐hydroxyecdysone (20E). The 20E pulse is generated through two processes: synthesis, which ...increases its level, and inactivation, which decreases its titer. CYP18A1 functions as an ecdysteroid 26‐hydroxylase and plays a role in 20E removal in several representative insects. However, applying 20E degradation activity of CYP18A1 to other insects remains a significant challenge. In this study, we discovered high levels of Hvcyp18a1 during the larval and late pupal stages, particularly in the larval epidermis and fat body of Henosepilachna vigintioctopunctata, a damaging Coleopteran pest of potatoes. RNA interference (RNAi) targeting Hvcyp18a1 disrupted the pupation. Approximately 75% of the Hvcyp18a1 RNAi larvae experienced developmental arrest and remained as stunted prepupae. Subsequently, they gradually turned black and eventually died. Among the Hvcyp18a1‐depleted animals that successfully pupated, around half became malformed pupae with swollen elytra and hindwings. The emerged adults from these deformed pupae appeared misshapen, with shriveled elytra and hindwings, and were wrapped in the pupal exuviae. Furthermore, RNAi of Hvcyp18a1 increased the expression of a 20E receptor gene (HvEcR) and four 20E response transcripts (HvE75, HvHR3, HvBrC, and HvαFTZ‐F1), while decreased the transcription of HvβFTZ‐F1. Our findings confirm the vital role of CYP18A1 in the pupation, potentially involved in the degradation of 20E in H. vigintioctopunctata.
RNA interference (RNAi) targeting Hvcyp18a1 disrupted the pupation. The emerged adults from the deformed pupae appeared misshapen, with shriveled elytra and hindwings. Our findings confirm the vital role of CYP18A1 in the pupation, potentially involved in the degradation of 20E in Henosepilachna vigintioctopunctata.
Research Highlights
RNA interference (RNAi) targeting Hvcyp18a1 disrupted the pupation.
The emerged adults from the deformed pupae appeared misshapen, with shriveled elytra and hindwings.
RNAi of Hvcyp18a1 upregulated the expression of a 20E receptor gene (HvEcR) and four 20E response transcripts (HvE75, HvHR3, HvBrC, and HvαFTZ‐F1), while downregulating the transcription of HvβFTZ‐F1.
Although muscle development has been widely studied in Drosophila melanogaster, it was a great challenge to apply to developmental processes of other insect muscles. This study was focused on the ...functional characterization of a basic helix‐loop‐helix transcription factor gene twist in an herbivorous ladybird Henosepilachna vigintioctopunctata. Its transcript (Hvtwist) levels were detected in all developmental stages. RNA interference (RNAi)‐aided knockdown of Hvtwist at the penultimate larval instar stage impaired pupation, and caused a deformed adult in the legs. The tarsi were malformed and did not support the bodies in an upright position. The climbing ability was impaired. Moreover, around 50% of the impaired adults had a malformed elytrum. In addition, they consumed less foliage and did not lay eggs. A hematoxylin–eosin staining of the leg demonstrated that the tibial extensor (TE) and the tibial flexor (TF) muscles were originated from the femurs while levator and depressor muscles of the tarsus (TL and TD) were located in the tibia in the control adults, in which tarsal segments were devoid of muscles. RNAi treatment specific to Hvtwist expression markedly impaired TE and TF muscles in the femurs, and prevented the development of TL and TD muscles in the tibia. Therefore, our findings demonstrate Twist plays a vital role in the myogenesis in H. vigintioctopunctata adult legs.
RNA interference (RNAi) of Hvtwist inhibits reduced pupation and caused deformed adults. All the Hvtwist RNAi adults possessed deformed legs and undeveloped muscles. The climbing ability of the Hvtwist RNAi adults was impaired.
Highlights
Previtellogenesis occurs in 4‐day‐old H. vigintioctopunctata ovarioles.
The vitellogenesis happens in the 5–7‐day‐old ovaries.
The choriogenesis take places at 8 and 9 days posteclosion.
The copulation and oviposition comes about from 8 days postemergence.
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•Previtellogenesis occurs in 4-day-old H. vigintioctopunctata ovarioles.•The vitellogenesis happens in the 5- to 7-day-old ovaries.•The choriogenesis take places at 8 and 9 days post ...eclosion.•The copulation and oviposition comes about from 8 days post emergence.
In order to provide a biological basis for the development of population management strategies, a critical need is to better understand the reproduction of agricultural pests. In the current paper, we timed the previtellogenesis, vitellogenesis and choriogenesis processes in Henosepilachna vigintioctopunctata (Fabricius), (Coleoptera, Coccinellidae), a serious polyphagous defoliator damaging a wide range of crops in Solanaceae and Cucurbitaceae. The female reproductive system was comprised of two ovaries, two lateral oviducts, a median oviduct, a spermathecal sac and a genital chamber. Each ovary had an average of 28 (±0.4) telotrophic meroistic ovarioles. In the ovarioles of 4-day-old females, only previtellogenesis process was observed. The vitellogenesis occurred at 5 to 7 days after female emergence, while the choriogenesis took place at 8 and 9 days post eclosion. Copulation and oviposition occurred before and at 8 days post emergence. In order to confirm the observation, HvVgR and HvVg were identified and their expression was examined. HvVgR was abundantly transcribed in the ovary, whereas HvVg was richly expressed in the fat body. The temporal expression profiles showed that the high levels of HvVgR and HvVg were accompanied with the active accumulation of yolk proteins and the occurrence of intercellular spaces among follicle cells. Moreover, only one oocyte was observed per ovariole in active vitellogenesis. The observation demonstrates that oocytes are continuously matured and the oviposition persists in females from 8 days to at least 13 days post eclosion.
During choriogenesis in insects, chorion (eggshell) is formed by surrounding follicular epithelial cells in ovarioles. However, the regulatory endocrine factor(s) activating choriogenesis and the ...effect of chemical components on eggshell deserve further exploration. In two representative coleopterans, a coccinellid
and a chrysomelid
, genes encoding the 20-hydroxyecdysone (20E) receptor heterodimer, ecdysone receptor (EcR) and ultraspiracle (USP), and two chitin biosynthesis enzymes UDP-N-acetylglucosamine pyrophosphorylase (UAP) and chitin synthase (ChS1), were highly expressed in ovaries of the young females. RNA interference (RNAi)-aided knockdown of either
or
in
inhibited oviposition, suppressed the expression of
, and lessened the positive signal of Calcofluor staining on the chorions, which suggests the reduction of a chitin-like substance (CLS) deposited on eggshells. Similarly, RNAi of
or
in
constrained oviposition, decreased the expression of
and
, and reduced CLS contents in the resultant ovaries. Knockdown of
or
caused similar defective phenotypes, i.e., reduced oviposition and CLS contents in the
ovaries. These results, for the first time, indicate that 20E signaling activates choriogenesis in two coleopteran species. Moreover, our findings suggest the deposition of a CLS on the chorions.
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