Rescue of bmp15 deficiency in zebrafish by mutation of inha reveals mechanisms of BMP15 regulation of folliculogenesis.

As an oocyte-specific growth factor, bone morphogenetic protein 15 (BMP15) plays a critical role in controlling folliculogenesis. However, the mechanism of BMP15 action remains elusive. Using zebrafish as the model, we created a bmp15 mutant using CRISPR/Cas9 and demonstrated that bmp15 deficiency caused a significant delay in follicle activation and puberty onset followed by a complete arrest of follicle development at previtellogenic (PV) stage without yolk accumulation. The mutant females eventually underwent female-to-male sex reversal to become functional males, which was accompanied by a series of changes in secondary sexual characteristics. Interestingly, the blockade of folliculogenesis and sex reversal in bmp15 mutant could be partially rescued by the loss of inhibin (inha-/-). The follicles of double mutant (bmp15-/-;inha-/-) could progress to mid-vitellogenic (MV) stage with yolk accumulation and the fish maintained their femaleness without sex reversal. Transcriptome analysis revealed up-regulation of pathways related to TGF-ß signaling and endocytosis in the double mutant follicles. Interestingly, the expression of inhibin/activin ßAa subunit (inhbaa) increased significantly in the double mutant ovary. Further knockout of inhbaa in the triple mutant (bmp15-/-;inha-/-;inhbaa-/-) resulted in the loss of yolk granules again. The serum levels of estradiol (E2) and vitellogenin (Vtg) both decreased significantly in bmp15 single mutant females (bmp15-/-), returned to normal in the double mutant (bmp15-/-;inha-/-), but reduced again significantly in the triple mutant (bmp15-/-;inha-/-;inhbaa-/-). E2 treatment could rescue the arrested follicles in bmp15-/-, and fadrozole (a nonsteroidal aromatase inhibitor) treatment blocked yolk accumulation in bmp15-/-;inha-/- fish. The loss of inhbaa also caused a reduction of Vtg receptor-like molecules (e.g., lrp1ab and lrp2a). In summary, the present study provided comprehensive genetic evidence that Bmp15 acts together with the activin-inhibin system in the follicle to control E2 production from the follicle, Vtg biosynthesis in the liver and its uptake by the developing oocytes.

Genetic analysis of activin/inhibin ß subunits in zebrafish development and reproduction.

Activin and inhibin are both dimeric proteins sharing the same ß subunits that belong to the TGF-ß superfamily. They are well known for stimulating and inhibiting pituitary FSH secretion, respectively, in mammals. In addition, activin also acts as a mesoderm-inducing factor in frogs. However, their functions in development and reproduction of other species are poorly defined. In this study, we disrupted all three activin/inhibin ß subunits (ßAa, inhbaa; ßAb, inhbab; and ßB, inhbb) in zebrafish using CRISPR/Cas9. The loss of ßAa/b but not ßB led to a high mortality rate in the post-hatching stage. Surprisingly, the expression of fshb but not lhb in the pituitary increased in the female ßA mutant together with aromatase (cyp19a1a) in the ovary. The single mutant of ßAa/b showed normal folliculogenesis in young females; however, their double mutant (inhbaa-/-;inhbab-/-) showed delayed follicle activation, granulosa cell hypertrophy, stromal cell accumulation and tissue fibrosis. The ovary of inhbaa-/- deteriorated progressively after 180 dpf with reduced fecundity and the folliculogenesis ceased completely around 540 dpf. In addition, tumor- or cyst-like tissues started to appear in the inhbaa-/- ovary after about one year. In contrast to females, activin ßAa/b mutant males showed normal spermatogenesis and fertility. As for activin ßB subunit, the inhbb-/- mutant exhibited normal folliculogenesis, spermatogenesis and fertility in both sexes; however, the fecundity of mutant females decreased dramatically at 270 dpf with accumulation of early follicles. In summary, the activin-inhibin system plays an indispensable role in fish reproduction, in particular folliculogenesis and ovarian homeostasis.

Loss of growth differentiation factor 9 causes an arrest of early folliculogenesis in zebrafish-A novel insight into its action mechanism.

Growth differentiation factor 9 (GDF9) was the first oocyte-specific growth factor identified; however, most information about GDF9 functions comes from studies in the mouse model. In this study, we created a mutant for Gdf9 gene (gdf9-/-) in zebrafish using TALEN approach. The loss of Gdf9 caused a complete arrest of follicle development at primary growth (PG) stage. These follicles eventually degenerated, and all mutant females gradually changed to males through sex reversal, which could be prevented by mutation of the male-promoting gene dmrt1. Interestingly, the phenotypes of gdf9-/- could be rescued by simultaneous mutation of inhibin α (inha-/-) but not estradiol treatment, suggesting a potential role for the activin-inhibin system or its signaling pathway in Gdf9 actions. In gdf9-null follicles, the expression of activin ßAa (inhbaa), but not ßAb (inhbab) and ßB (inhbb), decreased dramatically; however, its expression rebounded in the double mutant (gdf9-/-;inha-/-). These results indicate clearly that the activation of PG follicles to enter the secondary growth (SG) requires intrinsic factors from the oocyte, such as Gdf9, which in turn works on the neighboring follicle cells to trigger follicle activation, probably involving activins. In addition, our data also support the view that estrogens are not involved in follicle activation as recently reported.

Place of concordance-discordance model in evaluating NGS performance.

INTRODUCTION: Ideally, evaluating NGS performance requires a gold standard; in its absence, concordance between replicates is often used as substitute standard. However, the appropriateness of the concordance-discordance criterion has been rarely evaluated. This study analyzes the relationship between the probability of discordance and the probability of error under different conditions. METHODS: This study used a conditional probability approach under conditional dependence then conditional independence between two sequencing results and compares the probabilities of discordance and error in different theoretical conditions of sensitivity, specificity, and correlation between replicates, then on real results of sequencing genome NA12878. The study examines also covariate effects on discordance and error using generalized additive models with smooth functions. RESULTS: With 99% sensitivity and 99.9% specificity under conditional independence, the probability of error for a positive concordant pair of calls is 0.1%. With additional hypotheses of 0.1% prevalence and 0.9 correlation between replicates, the probability of error for a positive concordant pair is 47.4%. With real data, the estimated sensitivity, specificity, and correlation between tests for variants are around 98.98%, 99.996%, and 93%, respectively, and the error rate for positive concordant calls approximates 2.5%. In covariate effect analyses, the effects' functional form are close between discordance and error models, though the parts of deviance explained by the covariates differ between discordance and error models. CONCLUSION: With conditional independence of two sequencing results, the concordance-discordance criterion seems acceptable as substitute standard. However, with high correlation, the criterion becomes questionable because a high percentage of false concordant results appears among concordant results.

Both Resilience and Adhesivity Define Solid Electrolyte Interphases for a High Performance Anode.

Solid electrolyte interphases (SEIs) are sought to protect high-capacity anodes, which suffer from severe volume changes and fast degradations. The previously proposed effective SEIs were of high strength yet abhesive, inducing a yolk-shell structure to decouple the rigid SEI from the anode for accommodating the volume change. Ambivalently, the interfacial void-evolved electro-chemo-mechanical vulnerabilities become inherent defects. Here, we establish a new rationale for SEIs that resilience and adhesivity are both requirements and pioneer a design of a resilient yet adhesive SEI (re-ad-SEI), integrated into a conjugated surface bilayer structure. The re-ad-SEI and its protected particles exhibit excellent stability almost free from the thickening of SEI and the particle pulverization during cycling. More promisingly, the dynamically bonded intact SEI-anode interfaces enable a high-efficiency ion transport and provide a unique mechanical confinement effect for structural integrity of anodes. The high Coulombic efficiency (>99.8%), excellent cycling stability (500 cycles), and superior rate performance have been demonstrated in microsized Si-based anodes.

ISRIB alleviates aging-associated brown fat UCP1 translational repression and thermogenic deficiency.

Upon cold exposure, aged people with lower metabolic rate cannot rapidly increase the higher levels of heat production, and are seriously threatened by the hypothermia, extensive cold stress responses and risk of mortality. Here, we show that brown fat thermogenic activity is obviously deficient in aged mice, associating with reduction of UCP1 expression and inhibition of its mRNA translation. As we considered, aging aggravates brown fat oxidative stress and activates the integrated stress response (ISR), inducing the phosphorylation of eIF2α to block the global mRNA translation. Therefore, small-molecule ISR inhibitor (ISRIB) treatment attenuates the higher level of eIF2α phosphorylation, restores the repression of Ucp1 mRNA translation and improves UCP1-mediated thermogenic function to defend cold stress in aged mice. Furthermore, ISRIB treatment increases the relative lower metabolic rates, and alleviates glucose intolerance and insulin resistance in aged mice. Thus, we have uncovered a promising drug that reverses the aged-related the deficiency of UCP1-mediated thermogenesis to combat cold stress and associated metabolic diseases.

Rubidium ions doping to improve the photoluminescence properties of Mn doped CsPbCl3perovskite quantum dots.

All-inorganic cesium lead halide CsPbX3(X = Cl, Br, I) perovskite quantum dots (PQDs) have shown promising potential in current Mini/Micro-LED display applications due to their excellent photoluminescence performance. However, lead ions in PQDs are easily to leak owing to the unstable structure of PQDs, which hinders their commercial applications. Herein, we adopt Rb+ions co-doping strategy to regulate the doping characteristics of Mn2+ions in CsPbCl3PQDs. The synthesized CsPbCl3:(Rb+, Mn2+) PQDs possess enhanced photoluminescence quantum yield of 71.1% due to the reduction of intrinsic defect states and Mn-Mn or Mn-traps in co-doped PQDs. Moreover, the white light emission of CsPb(Cl/Br)3:(Rb+, Mn2+) PQDs is achieved by anion exchange reaction and the constructed WLED exhibits the CIE coordinate of (0.33, 0.29) and the correlated color temperature of 5497 K. Benefiting from the substitution strategy, these doped CsPbX3PQDs can be widely used as fluorescence conversion materials for the construction of Mini/Micro-LED.

Extending the optical temperature sensing range of Cr3+ by synchronously tuning 2E and 4T2 emission.

Due to the different sensitivities of the 2E and 4T2 energy levels of Cr3+ to the local environment, Cr3+-doped fluorescent materials appear as excellent candidates for highly sensitive temperature sensing based on luminescence intensity ratio technology. However, a way to broaden the strict Boltzmann temperature measuring range is rarely reported. In this work, through Al3+ alloying strategy, a series of SrGa12-xAlxO19:0.5%Cr3+(x = 0, 2, 4, and 6) solid-solution phosphors were synthesized. Remarkably, the introduction of Al3+ can play a role in regulating the crystal field around Cr3+ and the symmetry of [Ga/AlO6] octahedron, realizing the synchronous tuning of 2E and 4T2 energy levels when the temperature changes in a wide range, achieving the purpose of increasing the intensity difference of 2E → 4A2 and 4T2 → 4A2 transitions, so as to extend the temperature sensing range. Among all samples, SrGa6Al6O19:0.5%Cr3+ showed the widest temperature measuring range from 130 K to 423 K with Sa of 0.0066 K-1 and Sr of 1% K-1@130 K. This work proposed a feasible way to extend the temperature sensing range for transition metal-doped LIR-mode thermometers.

Phase stability and electronic structure of CsPbCl3 under hydrostatic stress and anion substitution.

Perovskites based on CsPbX3 (X = Cl, Br, I) have promising applications in solar cells, light-emitting diodes, and photodetectors. In this paper, the phase stability of inorganic metal halide perovskite CsPbCl3 under hydrostatic pressure and anion substitution is studied using density functional theory (DFT), and this modification is explained by the interaction of the octahedrons and transformation of the bond-orbital coupling. In addition, two space groups, P4/mbm and Amm2, which are stable under stress, are subjected to anion substitution; then, the structural stability and band gap change of CsPbCl3-yXy (X = Br, I; y = 0, 1, 2, 3) are analyzed after applying stress; finally, the electronic structures and optical properties of the six most stable components are presented. The effect of stress and anions on the components' optoelectronic properties is closely linked with the crystal's structural alteration mechanism. These results show that stress and anion modulation can significantly change the optoelectronic properties of materials, which make these materials have broad application prospects. Furthermore, stress can be used as an effective tool for screening the most stable material structure.

The relationships between organizational culture and thriving at work among nurses: The mediating role of affective commitment and work engagement.

AIM: Guided by the social embeddedness model of thriving at work, this paper explores how nursing organizational culture, work engagement and affective commitment affect nurses' thriving at work. BACKGROUND: Thriving at work has implications for better employee and organization outcomes. The antecedents of thriving at work among the nursing population needs to be expanded by analysing the cross-level impact of organizational and individual characteristics. METHODS: A cross-sectional design was used to collect data from 1437 frontline nurses in a tertiary teaching hospital in China between April and May 2020 through an online survey about perceived nursing culture, work engagement, affective commitment and thriving at work. Data were analysed using SPSS, and a structural equation model was established using the PROCESS macro. RESULTS: Our results showed that work engagement and affective commitment mediated the relationship between nurses' perceived nursing culture and their thriving at work. Among nurses, work engagement was positively correlated to affective commitment. CONCLUSION: Our study confirmed the social embeddedness model of thriving at work by showing that both contextual and dispositional factors can influence nurses' thriving at work. Nurse leaders can foster nursing staff's thriving at work by building an inclusive work environment and by providing adequate resources to staff. Future research is needed to elaborate on employee and organizational outcomes associated with thriving at work. IMPACT: Nurse leaders should be the advocate for nurses to improve their organizational identification, fostering their thriving at work. Individual nurses can also take an active role in developing work-related resources to sustain their thriving through self-adaption processes. Collective thriving in the nursing workforce is needed to overcome adversity and hardship in the ever-changing and increasingly demanding health care industry and to further contribute to the vitality of the broader social and public environments. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. This study did not involve patients, service users, caregivers or members of the public.

How Nurses Develop Standardized Care Plans Under a Clinical Decision Support System: A Mixed-Methods Study.

Standardized care plans are being increasingly introduced to health facilities; however, their level of adoption remains unsatisfactory. Little is known about nurses' use of standardized care plans in China. This study aims to investigate acute care nurses' practices and experiences of care planning within a clinical decision support system embedded with standardized nursing languages. We explored the importance and performance of nursing interventions by retrospective analysis of 400 standardized care plans (performance) and a survey among nurses (importance). Semistructured interviews were conducted to supplement quantitative findings and delve deeper into nurses' experience with standardized care plans. A total of six core nursing diagnoses were determined, each corresponding to seven to 15 nursing interventions. The correlations between nurses' perceived importance and actual performance of nursing interventions in the care plan were weak. Qualitative interviews identified three themes: negative attitudes toward the care plan, uncertainty regarding care planning, and new routines with the care plan. Our findings indicate that nurses' care planning may not reflect their professional judgments. Effective leadership from nurse administrators is warranted to engage nurses with standardized care plan implementation. The content of the standardized nursing language embedded-knowledge base should be continuously adapted to clinical needs to facilitate nurses' care planning practices.

Does dental caries play a role on the asthma development?-systematic review and meta-analysis.

Asthma and dental caries are the two most common diseases in children, and the relationship between them has been a focus of research. Whether dental caries affects the development of asthma has long been controversial. The aim of this study was to conduct a systematic review of the literature to assess the effect of dental caries on the development of asthma and provide new ideas for the pathogenesis and promoting factors of asthma. For a systematic review and meta-analysis, we systematically searched three databases (PubMed, Web of Science, and Embase) for studies published from database inception to 22 May 2022. We included observational studies that investigated the effect of dental caries on the development of asthma. Studies were critically appraised and a meta-analysis was performed to estimate a pooled effect. From the 845 studies initially identified, 7 of these were included in the meta-analysis. Included studies originated from America (n = 5) and Asia (n = 2). A meta-analysis of data from seven selected studies suggested that dental caries was positively associated with the risk of asthma development (The odds ratio for the pooled effect was 1.06, 95% confidence interval: 1.01, 1.10). In addition, the effect of dental caries on asthma risk varied in different geographic locations according to subgroup analyses. This study suggests that dental caries may affect the development of asthma and emphasizes the importance of increased awareness of dental care and caries prevention in patients with asthma.

QKI regulates adipose tissue metabolism by acting as a brake on thermogenesis and promoting obesity.

Adipose tissue controls numerous physiological processes, and its dysfunction has a causative role in the development of systemic metabolic disorders. The role of posttranscriptional regulation in adipose metabolism has yet to be fully understood. Here, we show that the RNA-binding protein quaking (QKI) plays an important role in controlling metabolic homeostasis of the adipose tissue. QKI-deficient mice are resistant to high-fat-diet (HFD)-induced obesity. Additionally, QKI depletion increased brown fat energy dissipation and browning of subcutaneous white fat. Adipose tissue-specific depletion of QKI in mice enhances cold-induced thermogenesis, thereby preventing hypothermia in response to cold stimulus. Further mechanistic analysis reveals that QKI is transcriptionally induced by the cAMP-cAMP response element-binding protein (CREB) axis and restricts adipose tissue energy consumption by decreasing stability, nuclear export, and translation of mRNAs encoding UCP1 and PGC1α. These findings extend our knowledge of the significance of posttranscriptional regulation in adipose metabolic homeostasis and provide a potential therapeutic target to defend against obesity and its related metabolic diseases.

The impact of left truncation of exposure in environmental case-control studies: evidence from breast cancer risk associated with airborne dioxin.

In epidemiology, left-truncated data may bias exposure effect estimates. We analyzed the bias induced by left truncation in estimating breast cancer risk associated with exposure to airborne dioxins. Simulations were run with exposure estimates from a Geographic Information System (GIS)-based metric and considered two hypotheses for historical exposure, three scenarios for intra-individual correlation of annual exposures, and three exposure-effect models. For each correlation/model combination, 500 nested matched case-control studies were simulated and data fitted using a conditional logistic regression model. Bias magnitude was assessed by estimated odds-ratios (ORs) versus theoretical relative risks (TRRs) comparisons. With strong intra-individual correlation and continuous exposure, left truncation overestimated the Beta parameter associated with cumulative dioxin exposure. Versus a theoretical Beta of 4.17, the estimated mean Beta (5%; 95%) was 73.2 (67.7; 78.8) with left-truncated exposure and 4.37 (4.05; 4.66) with lifetime exposure. With exposure categorized in quintiles, the TRR was 2.0, the estimated ORQ5 vs. Q1 2.19 (2.04; 2.33) with truncated exposure versus 2.17 (2.02; 2.32) with lifetime exposure. However, the difference in exposure between Q5 and Q1 was 18× smaller with truncated data, indicating an important overestimation of the dose effect. No intra-individual correlation resulted in effect dilution and statistical power loss. Left truncation induced substantial bias in estimating breast cancer risk associated with exposure with continuous and categorical models. With strong intra-individual exposure correlation, both models detected associations, but categorical models provided better estimates of effect trends. This calls for careful consideration of left truncation-induced bias in interpreting environmental epidemiological data.

Cadmium exposure reprograms energy metabolism of hematopoietic stem cells to promote myelopoiesis at the expense of lymphopoiesis in mice.

Cadmium (Cd) is a highly toxic heavy metal in our living environment. Hematopoietic stem cells (HSC) are ancestors for all blood cells. Therefore understanding the impact of Cd on HSC is significant for public health. The aim of this study was to investigate the impact of Cd2+ on energy metabolism of HSC and its involvement in hematopoiesis. Wild-type C57BL/6 mice were treated with 10 ppm of Cd2+ via drinking water for 3 months, and thereafter glycolysis and mitochondrial (MT) oxidative phosphorylation (OXPHOS) of HSC in the bone marrow (BM) and their impact on hematopoiesis were evaluated. After Cd2+ treatment, HSC had reduced lactate dehydrogenase (LDH) activity and lactate production while having increased pyruvate dehydrogenase (PDH) activity, MT membrane potential, ATP production, oxygen (O2) consumption and reactive oxygen species (ROS), indicating that Cd2+ switched the pattern of energy metabolism from glycolysis to OXPHOS in HSC. Moreover, Cd2+ switch of HSC energy metabolism was critically dependent on Wnt5a/Cdc42/calcium (Ca2+) signaling triggered by a direct action of Cd2+ on HSC. To test the biological significance of Cd2+ impact on HSC energy metabolism, HSC were intervened for Ca2+, OXPHOS, or ROS in vitro, and thereafter the HSC were transplanted into lethally irradiated recipients to reconstitute the immune system; the transplantation assay indicated that Ca2+-dependent MT OXPHOS dominated the skewed myelopoiesis of HSC by Cd2+ exposure. Collectively, we revealed that Cd2+ exposure activated Wnt5a/Cdc42/Ca2+ signaling to reprogram the energy metabolism of HSC to drive myelopoiesis at the expense of lymphopoiesis.

Lead suppresses interferon γ to induce splenomegaly via modification on splenic endothelial cells and lymphoid tissue organizer cells in mice.

Splenomegaly is a symptom characterized by the presence of an enlarged spleen. The impact of environmental factors on splenomegaly is largely unknown. In this study, C57BL/6 mice were treated with 125 ppm or 1250 ppm lead (Pb) via drinking water for 8 wk, and the process of splenomegaly was evaluated. Treatment with 1250 ppm Pb, but not 125 ppm Pb, caused splenomegaly, which was associated with increased capacity for erythrocyte clearance. Intriguingly, Pb-caused splenomegaly was independent of lymphoid tissue inducer (LTi) cells, which produce lymphotoxins α and ß (LTα/ß) to activate endothelial cells and LT organizer (LTo) cells and drive the development of spleen physiologically. A direct action of Pb on endothelial cells and LTo cells did not impact their proliferation. On the other hand, during steady state, a tonic level of interferon (IFN)γ acted on endothelial cells and LTo cells to suppress splenomegaly, as IFNγ receptor (IFNγR)-deficient mice had enlarged spleens relative to wild-type mice; during Pb exposure, splenic IFNγ production was suppressed, thus leading to a loss of the inhibitory effect of IFNγ on splenomegaly. Mechanically, Pb acted on splenic CD4+ T cells to suppress IFNγ production, which impaired the Janus kinase (Jak)1/ signal transducer and activator of transcription (STAT)1 signaling in endothelial cells and LTo cells; the weakened Jak1/STAT1 signaling resulted in the enhanced nuclear factor-κB (NF-κB) signaling in endothelial cells and LTo cells, which drove their proliferation and caused splenomegaly. The present study reveals a previously unrecognized mechanism for the immunotoxicity of Pb, which may extend our current understanding for Pb toxicology.

Transition to a new nursing information system embedded with clinical decision support: a mixed-method study using the HOT-fit framework.

BACKGROUND: Nursing information systems embedded with standardized nursing language and clinical decision support have been increasingly introduced in health care settings. User experience is key to the adoption of health information technologies. Despite extensive research into the user experience with nursing information systems, few studies have focused on the interaction between user, technology and organizational attributes during its implementation. Guided by the human, organization and technology-fit framework, this study aimed to investigate nurses' perceptions and experiences with transition to a new nursing information system (Care Direct) 2 years after its first introduction. METHODS: This is a mixed-method study using an embedded design. An online survey was launched to collect nurses' self-reported use of the new system, perceived system effectiveness and experience of participation in system optimization. Twenty-two semi structured interviews were conducted with twenty nurses with clinical or administrative roles. The quantitative and qualitative data were merged using the Pillar Integration Process. RESULTS: The average score of system use behavior was 3.76 ± 0.79. Regarding perceived system effectiveness, the score of each dimension ranged 3.07-3.34 out of 5. Despite large variations in approaches to participating in system optimization, nurses had generally positive experiences with management and technical support. Eight main categories emerged from the integrated findings, which were further condensed into three themes: perceptions on system content, structure, and functionality; perceptions on interdisciplinary and cross-level cooperation; and embracing and accepting the change. CONCLUSIONS: Effective collaboration between clinicians, administrators and technical staff is required during system promotion to enhance system usability and user experience. Clear communication of organizational missions to staff and support from top management is needed to smooth the system implementation process and achieve broader system adoption.

Elucidation of the dimeric interplay of dual MRAP2 proteins in the zebrafish.

The melanocortin receptor accessory protein 2 (MRAP2) plays an essential role in the regulation of metabolic homeostasis and deletion of which results in severe obesity syndrome in mice and human. Mammalian MRAP2 is recognized as an endogenous physiological mediator through the potentiation of the MC4R signaling in vivo. Two isoforms of MRAP2 are identified in zebrafish genome, zMRAP2a and zMRAP2b. However, the mechanism of assembling dual topology and the regulatory roles of each complex on the melanocortin cascades remains unclear. In this study, we showed the bidirectional homo- and hetero-dimeric topologies of two zebrafish MRAP2 isoforms on the plasma membrane. Orientation fixed chimeric proteins could affect the trafficking and pharmacological properties of zMC4R signaling. Reciprocal replacement of zMRAP2a and zMRAP2b proteins elucidated the major participation of the carboxyl terminal as the functional domain for modulating zMC4R signaling. Our findings revealed the complex and dynamic conformational regulation of dual zebrafish MRAP2 proteins in vitro.

Optimized Design of a Pump Laser System for a Spin Exchange Relaxation Free Inertial Measurement Device.

In order to improve the precision and beam quality of a pump laser for a spin exchange relaxation free inertial measurement device, we applied one scheme to achieve the square wave modulation and power stability control of the pump laser and another one to obtain the uniform intensity distribution of the laser beam, in which the acousto-optic modulator (AOM) and proportion integration differentiation (PID) controller were used to achieve the former, and the freeform surface lens was designed and optimized to achieve the latter based on the TracePro software. In experiments, the first-order diffraction light beam coming through the AOM had a spot size of about 1.1×0.7 mm2, and a spherical vapor cell with a radius of 7 mm was placed behind the freeform surface lens. Results show that the uniformity of the reshaped intensity distribution is higher than 90% within the target area with a radius of 7 mm both in the simulation and the experiment, which ensure that the uniform laser beam covers the area of cell. On the other hand, the power stability of the pump laser is controlled to be less than 0.05%. Compared with traditional methods, the complicated calculation process in optical design is better solved, and a higher uniformity with slight energy loss is achieved.

Rational design, synthesis and structure-activity relationship of novel substituted oxazole isoxazole carboxamides as herbicide safener.

A series of novel substituted oxazole isoxazole carboxamides derivatives were designed on the basis of active subunit combination. Forty-four novel compounds were synthesized by an efficient one-pot procedure under microwave irradiation. The bioactivity was evaluated as herbicide safener against the injury of chlorsulfuron. It was found that most of the synthesized compounds displayed remarkable protection against chlorsulfuron via enhanced glutathione content and glutathione S transferase activity. Especially compound I-11 exhibited better bioactivity than the safeners isoxadifen-ethyl and R-28725. Molecular docking simulations suggested that the target compounds could compete with chlorsulfuron in the active site of acetolactate synthase, which could explain the protective effects of safeners. The present work demonstrates that the target compounds containing oxazole isoxazole groups could be considered as potential candidates for developing novel safeners in the future.