Search

Uncertainty exists about whether lowering systolic blood pressure to less than 120 mm Hg is superior to that of less than 140 mm Hg, particularly in patients with diabetes and patients with previous stroke.

ObjectiveThe correlation between cholangiocarcinoma (CCA) progression and bile is rarely studied. Here, we aimed to identify differential metabolites in benign and malignant bile ducts and elucidate the generation, function and degradation of bile metabolites.DesignDifferential metabolites in the bile from CCA and benign biliary stenosis were identified by metabonomics. Biliary molecules able to induce mast cell (MC) degranulation were revealed by in vitro and in vivo experiments, including liquid chromatography-mass spectrometry (MS)/MS and bioluminescence resonance energy transfer assays. Histamine (HA) receptor expression in CCA was mapped using a single-cell mRNA sequence. HA receptor functions were elucidated by patient-derived xenografts (PDX) in humanised mice and orthotopic models in MC-deficient mice. Genes involved in HA-induced proliferation were screened by CRISPR/Cas9.ResultsBile HA was elevated in CCA and indicated poorer prognoses. Cancer-associated fibroblasts (CAFs)-derived stem cell factor (SCF) recruited MCs, and bile N,N-dimethyl-1,4-phenylenediamine (DMPD) stimulated MCs to release HA through G protein-coupled receptor subtype 2 (MRGPRX2)-Gαq signalling. Bile-induced MCs released platelet-derived growth factor subunit B (PDGF-B) and angiopoietin 1/2 (ANGPT1/2), which enhanced CCA angiogenesis and lymphangiogenesis. Histamine receptor H1 (HRH1) and HRH2 were predominantly expressed in CCA cells and CAFs, respectively. HA promoted CCA cell proliferation by activating HRH1-Gαq signalling and hastened CAFs to secrete hepatocyte growth factor by stimulating HRH2-Gαs signalling. Solute carrier family 22 member 3 (SLC22A3) inhibited HA-induced CCA proliferation by importing bile HA into cells for degradation, and SLC22A3deletion resulted in HA accumulation.ConclusionBile HA is released from MCs through DMPD stimulation and degraded via SLC22A3 import. Different HA receptors exhibit a distinct expression profile in CCA and produce different oncogenic effects. MCs promote CCA progression in a CCA-bile interplay pattern.

As an important mechanical transmission device, the camshafts with highly reflective surface (HRS) are widely used in various automobiles. The automobile manufacturers have increasingly strict requirements for the processing quality of camshafts. However, affected by multiple processing steps, it is impossible to achieve 100% defect-free products, which even tiny defects on their surfaces can significantly impact the performance, accuracy, and longevity of the camshaft. Therefore, precise inspection of camshaft defects in HRS becomes a necessary means of quality control, that reliable inspection methods still cannot meet the requirements. To address these issues, based on a multitask learning (MTL) framework, a lightweight fine-grained perceptual defect inspection network is proposed that is able to optimize both the saliency detection and classification tasks. The network uses a reparameterization technique and a lightweight bottleneck layer that can encode and fuse multiscale features efficiently, while a fine-grained feature-aware module combined with spatial attention and channel attention mechanisms effectively improved the classification accuracy. Based on the experimental validation, the proposed method can achieve a high Mathews correlation coefficient (MCC) of 0.951 and real-time speed of 190 fps on a single GPU, meanwhile demonstrate excellent performance and interpretability in HRS defect inspection and classification.

Binocular camera is widely used in high-accuracy 3-D measurement and the systematic error is critically determined by the calibration of camera parameters. This article proposes a binocular camera calibration method based on planar target with different orientations translating along single axis. The translation of planar target composes a calibration grid, which is localized in an affine coordinate system (ACS). In addition, nonhomogeneous projection equations of binocular camera indicate the relationship between ACS and image projection coordinate system (IPCS). Therefore, a linear estimation of binocular camera parameters is obtained. In addition, we collect multiple calibration grids with different orientations to improve the estimation accuracy of principal points. Finally, we minimize reprojection error to optimize these camera parameters. Simulation and application experiments demonstrate that our method achieves less focal length error (0.063 pixel) than traditional calibration method using arbitrary placed planar target (0.123 pixel), and less principal point error (0.220 pixel) than pure translation method (0.271 pixel).

A metal-free Meerwein arylation reaction from aryl(alkyl)idenemalononitriles and diazonium salts for the synthesis of 2-(aryl(alkyl)/arylmethylene)malononitrile derivatives under mild conditions was well developed. Different from the general addition reactions between alkenes and diazonium salts, this study performed the traditional coupling reaction for the formation of C(sp2)–C(sp2) bond arylation products. The radical reaction mechanism was well verified in the control experiments. The other advantages of the approach are broad-scope substrates and good group tolerance. Moreover, the obtained products can be readily converted into high-value asymmetric ketones and hydrogenation reactions.

Human skeletal stem cells (hSSCs) hold tremendous therapeutic potential for developing new clinical strategies to effectively combat congenital and age-related musculoskeletal disorders. Unfortunately, refined methodologies for the proper isolation of bona fide hSSCs and the development of functional assays that accurately recapitulate their physiology within the skeleton have been lacking. Bone marrow-derived mesenchymal stromal cells (BMSCs), commonly used to describe the source of precursors for osteoblasts, chondrocytes, adipocytes and stroma, have held great promise as the basis of various approaches for cell therapy. However, the reproducibility and clinical efficacy of these attempts have been obscured by the heterogeneous nature of BMSCs due to their isolation by plastic adherence techniques. To address these limitations, our group has refined the purity of individual progenitor populations that are encompassed by BMSCs by identifying defined populations of bona fide hSSCs and their downstream progenitors that strictly give rise to skeletally restricted cell lineages. Here, we describe an advanced flow cytometric approach that utilizes an extensive panel of eight cell surface markers to define hSSCs; bone, cartilage and stromal progenitors; and more differentiated unipotent subtypes, including an osteogenic subset and three chondroprogenitors. We provide detailed instructions for the FACS-based isolation of hSSCs from various tissue sources, in vitro and in vivo skeletogenic functional assays, human xenograft mouse models and single-cell RNA sequencing analysis. This application of hSSC isolation can be performed by any researcher with basic skills in biology and flow cytometry within 1–2 days. The downstream functional assays can be performed within a range of 1–2 months.

The most abundant human milk oligosaccharide 2′‐fucosyllactose (2′‐FL) is a valuable component that has gained significant attention from the food industry. To biosynthesize 2′‐FL, various Escherichia coliK12 derivatives have been genetically modified. To further enhance the application performance of E. coliK12, a novel E. coliK12 derivative BL27 was used as a chassis cell in this study, and modular pathway enhancement was performed to achieve de novo synthesis of 2′‐FL. The futCgene encoding α‐1,2‐fucosyltransferase was introduced, and the wcaJgene was knocked out to prevent the conversion of GDP‐ l‐fucose to colanic acid. Next, the effects of overexpressing transcriptional regulators rcsAand rcsBand knocking out transcriptional regulators mcbRand waaFwere evaluated to optimize the colanic acid pathway. The expression level, solubility, and activity of FutC were improved through genomic integration, TrxA‐tag fusion, and double mutation in F40S/Q237S. Fermentation conditions were optimized to achieve maximum 2′‐FL titers of 3.86 and 23.56 g/L in shake‐flask and fed‐batch cultivation, respectively. Over 85% of the products were successfully excreted into extracellular and almost no byproduct 2′,3‐difucosyllactose was generated. This study has explored a new microbial platform and modification strategies for the synthesis of 2′‐FL and provides opportunities for its commercial production. A novel Escherichia coliK12 derivative was used as a chassis for 2′‐FL biosynthesis. Inactivation of transcriptional regulator McbR can improve 2′‐FL production. Double mutation F40S/Q237S of FutC‐J166 increased 2′‐FL titer by 1.55‐fold.

Graphical abstract:

Chitin oligosaccharides (CHOS), high-value-added oligomers linked by N-acetyl-d-glucosamine (GlcNAc, NAG), and a small amount of d-glucosamine (GlcN, GA), have aroused increasing interest due to their excellent biological properties, including antibacterial, anti-inflammatory, and immunoprotective activities, and intestinal regulation. The efficient production and utilization of CHOS with high performance can solve problems from chitin as biowaste. However, the large-scale production of well-defined CHOS has not been fully accomplished due to the limited biotechnology and separation methods, thus impeding the research on their biological functions as well as their accurate applications. In this review, we comprehensively summarize the current preparation methods of CHOS, including the chemical, physical, enzymatic and biosynthetic methods. The advantages and disadvantages of the methods are discussed in terms of efficiency, economy, and environmental effects. Furthermore, the applications of CHOS in the food industry and their contributions to human health based on their excellent bioactivities are expounded. It is hoped that this review will help in providing new insights into the production of CHOS with high precision, and support the application of CHOS in serving the food industry as nutritional supplements or foods for special medical purposes.

The development of biodegradable packaging materials focuses on their barrier properties and mechanical properties, which are critical parameters for food protection. Synthetic biodegradable material polyamide 4 (PA4) may offer outstanding capacities for packaging due to its rigid molecular structure. The current study originally reveals the various physical properties of PA4 films and explores the influence of its internal structure, molecular weight, and external environment, environmental humidity, on its performance to provide further guidance for PA4 application. PA4 (Mη= 18,000 g/mol) films showed tensile strength (TS) of 47.5 ± 1.3 MPa, elongation at break (EB) of 228% ± 30%, oxygen permeability of 7.83 ± 3.32 × 10−17cm3m−1s−1Pa−1, and water vapor permeability of 4.34 ± 0.06 × 10−11g m−1s−1Pa−1. The TS and EB of PA4 improved slightly with increasing molecular weight, while the barrier characteristic remained unchanged. The moisture adsorption capabilities of PA4 films were similar to natural hydrophilic polymers. The mechanical characteristic of PA4 changed from brittle to ductile with the increase in relative humidity. Overall, PA4 can be considered to be a promising food packaging material since it presented better mechanical and oxygen barrier properties than those of commercial food packaging polymers. Colorless and translucent polyamide 4 (PA4) films, which are both bio‐based and biodegradable, were prepared by the solution casting method in a dual‐solvent system. The physical properties of single PA4 films were originally characterized, and the effects of molecular weight and environmental humidity on PA4 were investigated.

Sand fences made of punched steel plate (PSP) have recently been applied to control wind-blown sand in desertified and Gobi areas due to their strong wind resistance and convenient in situconstruction. However, few studies have assessed the protective effect of PSP sand fences, especially through field observations. This study analyzes the effects of double-row PSP sand fences on wind and sand resistance using field observations and a computational fluid dynamics (CFD) numerical simulation. The results of field observations showed that the average windproof efficiencies of the first-row and second-row sand fences were 79.8% and 70.8%, respectively. Moreover, the average windproof efficiencies of the numerical simulation behind the first-row and second-row sand fences were 89.8% and 81.1%, respectively. The sand-resistance efficiency of the double-row PSP sand fences was 65.4%. Sand deposition occurred close to the first-row sand fence; however, there was relatively little sand on the leeward side of the second-row sand fence. The length of sand accumulation near PSP sand fences obtained by numerical simulation was basically consistent with that through field observations, indicating that field observations combined with numerical simulation can provide insight into the complex wind-blown sand field over PSP sand fences. This study indicates that the protection efficiency of the double-row PSP sand fences is sufficient for effective control of sand hazards associated with extremely strong wind in the Gobi areas. The output of this work is expected to improve the future application of PSP sand fences.

Benefiting from the abundant solar energy and the emergence of photothermal conversion equipment, solar-driven water evaporation has shown great potential in seawater desalination. One common problem for solar–thermal evaporation is that the salt crystallized on the surface of solar absorbers during the seawater evaporation process will significantly deteriorate the continuity and efficiency of the evaporation process. In most reports, efforts have been made to transfer the accumulated salts, while the studies on preventing salt crystallization, which leads to better continuity of the production, are limited. Herein, a spontaneous salt-preventing solar–thermal water evaporator was designed, utilizing a dual-mode water transfer structure consisting of in-plane diffusion and in-tube migration. The dual-mode structural system gave rise to uniform and continuous water transfer, efficiently suppressing the salt concentration in the evaporator. As a result, salt crystallization was scarcely found on the surface of the evaporator under 1 sun irradiation for an ultralong time (200 h), demonstrating its high efficiency in inhibiting salt crystallization. In addition, the small contact area between the water and the evaporator could reduce the heat loss during the solar–thermal evaporation process, which further improved the water evaporation rate (1.64 kg m–2h–1).

Background: Medium-chain triglyceride ketogenic diet (MCTKD) is  previously less commonly used in China. This study was aimed to assess the efficacy and safety of the modified MCTKD in the treatment of drug-resistant epilepsy in Chinese patients. Methods: Patients with drug-resistant epilepsy were enrolled to receive treatment with modified MCTKD in Guangdong Sanjiu Brain Hospital during December 2020 and September 2022. The modified MCTKD contained fat that provided 50–70% of the total energy, as well as proteins and carbohydrates that provided 20–30% and 20% of energy, respectively. The fat component was composed of 20–30% medium-chain triglycerides (MCTs) and 30–40% long-chain triglycerides. The efficacy and safety of the diet were assessed at 1, 3 and 6 months. Results: A total of 123 patients aged 2.5 to 65 years, were included in this study. The response rates at 1, 3 and 6 months were 49.6%, 43.1%, and 30.9%, respectively. The seizure freedom rates at 1, 3 and 6 months were 12.2%, 10.6%, and 6.5%, respectively. The retention rates at 1, 3 and 6 months were 98.4%, 65.0% and 33.3% respectively. Side effects occurred in 21.14% of patients, which were predominantly gastrointestinal symptoms such as abdominal pain, diarrhea, vomiting, and constipation, and most of them resolved after dietary adjustments. A total of 82 patients (66.7%) discontinued the treatment with the reason of refusing to eat (8.1%), poor efficacy (35.0%), poor compliance (4.9%), and inability to follow-up (9.8%). Only 4 patients (3.3%) withdrew the diet due to side effects. Conclusions: The modified MCTKD with MCTs providing 20–30% of energy has a good safety in patients with drug-resistant epilepsy, but its effectiveness needs to be enhanced. Further modifications of MCTKD with an optimal energy ratio are required to achieve a better efficacy and safety.

Cholangiocarcinoma (CCA) is a type of highly malignant tumor originating from bile ducts. The prognosis of CCA is poor and the treatment options are limited. The biomarker study of CCA has made little progresses in recent years because of the difficulty to obtain CCA specimens. SOX9 is an important regulator of cholangiocyte proliferation and differentiation. We performed mRNA sequencing of CCA, retrieved TCGA data, and detected SOX9 expression in a large CCA cohort. With WNT3A stimulation, SOX9 expression and transcription was elevated by TCF7. Moreover, SOX9 was substantially up-regulated in CCA tissues and was identified as a prognostic biomarker of CCA. With mRNA sequencing and in vitro/vivovalidation, we demonstrated that SOX9 enhanced the transcription and expression of FGF7 and FGFR2. FGF7 was significantly up-regulated in the bile and serum of CCA patients, and may promote CCA proliferation by activating FGFR2 in an autocrine pathway. co-expression of FGF7 and FGFR2 was a more sensitive marker for poor prognosis. SOX9-induced overexpression of FGF7 and FGFR2 was the key reason of SOX9-involved pemigatinib resistance. In conclusion, SOX9 and FGF7 were prognostic biomarkers of CCA. WNT3A-TCF7-SOX9 axis could induce pemigatinib resistance in two independent pathways: (1)SOX9 directly promotes FGFR2 transcription and expression; (2)SOX9 elevates FGF7 expression, which could be secreted from CCA cells and activates FGFR2 phosphorylation in an autocrine pathway.

Objectives: The purpose of this study is to explore the curative effect of open surgical excision and endoscopic radiofrequency ablation (RA) in the treatment of piriform fossa fistula (PSF).Methods: Retrospective study of 80 cases of PSF in the Department of Otolaryngology-Head and Neck Surgery, Shanghai Children’s Hospital, from June 2009 to June 2017.Results: In this series, there were 43 males and 37 females, and the mean age was 5.2 years (17 days to 12 years). Surgical excision was performed for 62 patients. Radiofrequency ablation was performed for 18 patients. Six cases of postoperative temporary hoarseness occurred, and the hoarseness rates were not significantly different between the excision and RA groups (6.4% vs 11.1%, respectively, P= .88). Two cases of temporary neck abscess occurred in the RA group. After the mean follow-up period of 3.1 years (1-8 years), no recurrence was found between the excision and RA groups.Conclusions: The curative effect of excision and RA for PSF is not significantly different; each of the 2 methods has its advantages and disadvantages. However, RA for PSF has the merit of being minimally invasive, easy to operate, and safe; this procedure seems to be more suitable in the clinic.

2,7-Bis(2-phenyl-1H-imidazol-4-yl)fluorenone (BPIFO) was synthesized as a new fluorenone derivative bearing two imidazole moieties, and it exhibited remarkable and reversible changes in photo physical properties through two-step deprotonation with a base and back protonation with an acid in dimethylsulfoxide, which were interpreted by DFT calculations.2,7-Bis(2-phenyl-1H-imidazol-4-yl)fluorenone (BPIFO) was synthesized as a new fluorenone derivative bearing imidazole moieties, and it exhibited remarkable and reversible changes in photo physical properties through two-step deprotonation with a base and back protonation with an acid in dimethylsulfoxide, which were interpreted by DFT calculations.

Networking with outside organizations provide new ventures with stronger resources, allowing for more favorable competition in the marketplace. Three of six Chinese entrepreneurial companies studied were high-growth and reported a greater intensity and range of networking with external organizations than the three low-growth entrepreneurial firms.

The social exchange theory was applied to an examination of the social and cultural factors in international technology transfer (ITT). ITT negotiations between Chinese and US firms were studied by conducting interviews with Chinese and US executives who were involved in the negotiations. The negotiations were characterized by the interdependence and the expectation of rewards by both parties. The exchange elements which were emphasized in the negotiations were the issues of power, perception of resources, expectations and perception, reward/cost ratio and conflict and satisfaction.

The emerging interface solar-thermal water evaporation has been widely studied to solve fresh water shortage because of its high solar-thermal conversion efficiency, environmental friendliness, and low cost. However, traditional water evaporation systems inevitably lose heat to the environment, which not only greatly affects the water evaporation rate but also hinders their practical applications. In this work, an interface solar-thermal water evaporation system with enhanced heat localization, which is combined by a hydrophobic carbon nanotube (CNT) film (heating layer) and hydrophilic polyvinyl alcohol (PVA)/CNT foam (evaporating layer), is demonstrated. Under solar irradiation, the temperature of the hydrophobic CNT film is higher than that of the hydrophilic PVA/CNT foam due to the differences in wettability, so the thermal energy in the CNT film can be continuously transferred to the PVA/CNT foam evaporator, forming a gradient heating effect and greatly increasing the water evaporation rate. As a result, the water evaporation rate can reach 4.2 kg m–2h–1under a solar illumination of 1 kW m–2, which is among the highest water evaporation rate levels. More importantly, this water evaporation system structure is simple, can be easily scaled up, and has gradient applicability to other photothermal materials, which provides a route to improve the interfacial solar steam evaporation rate.

Purpose: Triglyceride–glucose (TyG) index is an emerging surrogate predictor of incident type 2 diabetes mellitus (T2DM). The study aimed to examine the association between TyG index and incident T2DM in a prospective Chinese cohort. Methods: The data were collected in 1992 and recollected in 2007 from the same group of 687 participants. The association between TyG index and T2DM was analysed. Results: During follow-up, 74 participants developed T2DM and the risk of T2DM increased with TyG index. The adjusted hazard ratio (HR) was 3.36 (95% CI: 1.52–7.39, P< 0.001) comparing the top TyG quartile to the bottom quartile. Smooth curve fitting revealed a nonlinear association and threshold effect between TyG index and incident T2DM with a nadir of risk when TyG index was around 8.51. For TyG ≤ 8.51, the risk of incident T2DM tended to decrease with per SD increase in TyG but no statistical significance was achieved (adjusted HR: 0.69, 95% CI: 0.43–1.12, P= 0.133). For TyG > 8.51, the risk of incident T2DM significantly increased by 38% with per SD increase in TyG (adjusted HR: 1.38, 95% CI: 1.14–1.67, P= 0.001). Time-dependent receiver operating curve suggested helpful discriminative power of TyG index for T2DM. It also significantly promoted the reclassification ability beyond the baseline risk model with net reclassification index of 0.159 (P= 0.020). Sensitivity analysis excluding participants with prediabetes demonstrated similar results. Conclusions: The TyG index was a significant and independent predictor for future T2DM development. The shape of relationship will require further studies.

The low-cost and efficient bifunctional electrocatalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is critical for advanced rechargeable Zn–air batteries (ZABs). Herein, we designed and fabricated a bifunctional m-Fe2.04Ni0.66@GCFs catalyst using a sustainable physical upcycling strategy involving spent artificial diamond accelerants. Experiments and theoretical calculations verified that dual-metal active-site synergy between *Fe2.04Ni0.66@GC and Fe2.04*Ni0.66@GC enhances the rapid adsorption/desorption of *OOH/*OH species, thereby improving ORR/OER performance. In situ Raman technique confirmed that ORR/OER activities are dependent on the FeOOH, Fe(OH)2, and β-NiOOH intermediates formed during the reaction. Impressively, the m-Fe2.04Ni0.66@GCFs catalyst exhibited outstanding ORR/OER activities with a small potential difference of only 0.73 V in alkaline media. The assembled rechargeable ZAB exhibited high peak power density (115.2 mW cm−2), large specific capacity (786.9 mA h g−1), and long-term charge-discharge cycling stability of more than 1200 cycles. These results not only contribute to the design of efficient bifunctional catalysts, but also provide a new approach to the high-value utilisation of waste catalyst resources.

Investigating genetic markers and key genes associated with sheep growth rate using integrated multi-omics approaches could provide valuable insights for the sheep industry. Based on the average daily gain (ADG), fast-growing (Ncase=70) and slow-growing (Ncontrol=70) Hu sheep were selected for a genome-wide association study (GWAS). Ten Hu sheep (fast-growing, n= 5; slow-growing, n= 5) and ten Dorper sheep (fast-growing, n= 5; slow-growing, n=5) were selected for comparative transcriptome analysis. We identified hub genes and tissue-specific genes (TSGs) using weighted gene co-expression network analysis (WGCNA) and RNA sequencing (RNA-Seq) data from ten tissues, respectively. Ten genes were found within 50 kb distances of the significant single nucleotide polymorphisms (SNPs). Based on a comparative transcriptomic analysis, a total of 501 and 441 differentially expressed genes (DEGs) were identified in the HF vs.HS and DF vs.DS comparisons, respectively. We found some important signaling pathways closely associated with fat metabolism and energy metabolism, such as “regulation of lipolysis in adipocytes”, “Oxidative phosphorylation”, and “Thermogenesis”. Several DEGs play a crucial role in fat deposition (such as ADRB3, PDE3B, FABP4, SERPINE1, PLIN1, and FOXO6) and muscle development (MYL3). Using the WGCNA analysis, 15 genes were considered as hub genes associated with ADG. Integration of GWAS and RNA-Seq data indicates that BRINP3and PENKmay further influence the growth rate by regulating feeding behavior in sheep. Association analysis of 1,071 Hu sheep populations revealed that mutations in the BRINP3(BRINP3g.16903465 T>C) and PENK(PENKg.39289926 T>C) genes were significantly related to the growth traits (P< 0.05). Our research provides novel insights into understanding the molecular mechanisms underlying growth traits in sheep. BRINP3and PENKgenes may be potential key candidate genes related to sheep growth rate.

The phenotypic diversity resulting from artificial or natural selection of sheep has made a significant contribution to human civilization. Hu sheep are a local sheep breed unique to China with high reproductive rates and rapid growth. Genome selection signatures have been widely used to investigate the genetic mechanisms underlying phenotypic variation in livestock. Here, we conduct whole-genome sequencing of 207 Hu sheep and compare them with the wild ancestors of domestic sheep (Asiatic mouflon) to investigate the genetic characteristics and selection signatures of Hu sheep. Based on six signatures of selection approaches, we detect genomic regions containing genes related to reproduction (BMPR1B, BMP2, PGFS, CYP19, CAMK4, GGT5, and GNAQ), vision (ALDH1A2, SAG, and PDE6B), nervous system (NAV1), and immune response (GPR35, SH2B2, PIK3R3, and HRAS). Association analysis with a population of 1299 Hu sheep reveal those missense mutations in the GPR35(GPR35g.952651 A > G; GPR35g.952496 C > T) and NAV1(NAV1g.84216190 C > T; NAV1g.84227412 G > A) genes are significantly associated (P < 0.05) with immune and growth traits in Hu sheep, respectively. This research offers unique insights into the selection characteristics of Hu sheep and facilitates further genetic improvement and molecular investigations.

Although demographic characteristics are the most analyzed variables in the literature on workplace friendship, their effects on its formation and development remain unclear, owing to conflicting results. To draw generalizable conclusions, this study employed meta-analytical techniques to examine the relationships between employees’ demographic characteristics and their workplace friendship, and investigated whether collectivism and year of data collection moderated this relationship. Seventy-seven empirical pieces of literature and 219 correlations (N = 34,856) were included in the final meta-analysis. Our findings revealed that male employees acquired more workplace friendships than female employees, and that organizational tenure, hierarchical position, and education were positively related to workplace friendships. However, employees’ age and marital status had no significant effect on workplace friendships. Furthermore, the results of the moderating effects analysis suggested that, as collectivism diminished and data collection was delayed, the impact of certain demographic characteristics on workplace friendships became weaker.

Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of articular cartilage1. The etiology of OA is complex and involves a variety of factors, including genetic predisposition, acute injury and chronic inflammation2–4. Here we investigate the ability of resident skeletal stem-cell (SSC) populations to regenerate cartilage in relation to age, a possible contributor to the development of osteoarthritis5–7. We demonstrate that aging is associated with progressive loss of SSCs and diminished chondrogenesis in the joints of both mice and humans. However, a local expansion of SSCs could still be triggered in the chondral surface of adult limb joints in mice by stimulating a regenerative response using microfracture (MF) surgery. Although MF-activated SSCs tended to form fibrous tissues, localized co-delivery of BMP2 and soluble VEGFR1 (sVEGFR1), a VEGF receptor antagonist, in a hydrogel skewed differentiation of MF-activated SSCs toward articular cartilage. These data indicate that following MF, a resident stem-cell population can be induced to generate cartilage for treatment of localized chondral disease in OA.

A “time-economical” radical cascade cyclization/haloazidation of 1,6-enynes provides a direct approach to access highly functional succinimide compounds. Moderate to excellent yields along with excellent Z/Eratio were obtained under the reaction features of broad substrate scope, good functional group tolerance, and mild reaction conditions.

Electrically bistable devices play an important role in the next generation of information materials. Plasmonic noble metal nanoparticles (Au and Ag NPs) with diameters <6 nm were embedded into 3-D Cd-based metal–organic framework (MOF) matrixes via the photoreduction method to generate Au (Ag) NPs@MOF composites. Electrical bistability measurements on the sandwiched ITO/NPs@MOF/silver devices indicate that two switchable conductivity states with nonvolatile memory behaviors can be observed. The ITO/Au NP@2/Ag device with neutral matrix possesses the highest ON/OFF current ratio of 104, which can be attributed to its higher electron tunneling efficiency because of the better dispersity of Au NPs in the MOF matrix. A mechanism regarding the electric-field-induced charge-transfer process assisted by conformational change in the active layer was proposed.

Insufficient blood vessel supply is a primary limiting factor for regenerative approaches to large bone defect repair. Recombinant bone morphogenetic protein-2 (BMP-2) delivery induces robust bone formation and has been observed to enhance neovascularization, but whether the angiogenic effects of BMP-2 are due to direct endothelial cell stimulation or due to indirect paracrine signaling remain unclear. In this study, we evaluated the effects of BMP-2 delivery on vascularized bone regeneration and tested whether BMP-2 induces neovascularization directly or indirectly. We found that delivery of BMP-2 (5 μg) enhanced both bone formation and neovascularization in critically sized (8 mm) rat femoral bone defects; however, BMP-2 did not directly stimulate angiogenesis in vitro. In contrast, conditioned medium from both mesenchymal progenitor cells and osteoblasts induced endothelial cell migration in vitro, suggesting a paracrine mechanism of BMP-2 action. Consistent with this inference, codelivery of BMP-2 with endothelial colony forming cells to a heterotopic site, distant from the skeletal stem cell-rich bone marrow niche, induced ossification but had no effect on neovascularization. Taken together, these data suggest that paracrine activation of osteoprogenitor cells is an important contributor to neovascularization during BMP-2-mediated bone regeneration.Impact StatementIn this study, we show that bone morphogenetic protein-2 (BMP-2) robustly induces neovascularization during tissue-engineered large bone defect regeneration, and we found that BMP-2 induced angiogenesis, in part, through paracrine signaling from osteoprogenitor cells.

Oxygen-respirable sponge was constructed by carbon dots-assisted synthesis strategy.The hydrophilicity and aerophilicity of Co@C–O–Cs active sites boost oxygen diffusion and the bifunctional oxygen reduction reaction and oxygen evolution reaction activities.Co@C–O–Cs-based Zn-air battery (ZAB) displays excellent specific capacity and stability, and the all-solid-state Co@C–O–Cs-based ZAB exhibits excellent flexibility.

K-doped MnO2is regarded as an efficient catalyst for HCHO oxidation. A combined study of density functional theory (DFT) and microkinetic modeling was implemented to investigate the role of potassium doping in the catalytic reactivity of MnO2towards HCHO oxidation. The DFT-derived thermodynamic stability analysis indicates that the K-doped MnO2surface is more stable than the pristine MnO2surface under the practical experimental conditions. The introduction of K ion is energetically beneficial to the adsorption of HCHO and O2by charge transfer from potassium to the catalyst surface. The HCHO oxidation paths show that the rate-determining step is the second dehydrogenation reaction. The best catalytic activity of MnO2@K-1 is associated with the abundant Mn atom with a high chemical valence on the catalyst surface. Specially, K doping has little effect on the adsorption of water, but promotes the production of OH group by reducing the energy barrier of hydrolysis. The hydroxylated surface is favorable for the two-step cleavage of the C-H bond. The overall reaction rate of HCHO oxidation on the K-doped MnO2catalyst is much higher than that on the pristine MnO2. At low temperatures, the reaction rate is relatively insensitive to the pressure change, while the oxidation rate gradually rises with the increasing of pressure at high temperatures. K doping is conducive to boosting the reaction rate of HCHO oxidation, which is associated with the stronger interaction of reactants with K-doped catalysts.

Reaction mechanisms of hydrosilylation of ketone and alkene with tertiary silane using the Wilkinson-type catalyst were theoretically investigated on the basis of density functional calculations using ωB97XD functional. Previously proposed three mechanisms, the Chalk–Harrod (CH) mechanism, the modified Chalk–Harrod (mCH) mechanism, and the outer-sphere mechanism were examined. Besides, we also found two mechanisms, the alternative CH (aCH) mechanism and the double hydride (DH) mechanism. In the aCH mechanism, a four-coordinate rhodium hydride complex formed through the elimination of R3Si–Cl is a catalytically active species. In the DH mechanism, the active species is a six-coordinate complex with two Rh–H bonds. For the C═O double bond hydrosilylation, the rate-determining steps of the aCH and DH mechanisms are both acetone insertion into the Rh–H bond, and the order of the activation barrier is DH < aCH ≈ CH < mCH. For the C═C double bond hydrosilylation, except for the mCH pathway whose rate-determining step is the hydrosilane addition reaction, the rate-determining steps of the CH, aCH, and DH pathways are Si–C reductive elimination reactions. The order of the energy barrier is DH ≈ mCH < aCH ≈ CH. In the outer-sphere mechanism, no stable intermediate or transition state was found. Consequently, we concluded that the DH mechanism is adopted as the mechanism for the Rh-catalyzed hydrosilylation of the carbonyl group while the mCH or DH mechanism is adopted as the mechanism for alkenes under conditions where their active intermediates are formed. The present result revises a hypothesis that the hydrosilylation of the carbonyl group is in general accomplished by the mCH mechanism. The active species in the DH mechanism has one more extra Rh–H bond compared to that of the other pathways, and its interaction with a silyl group, trans-influence, and small steric effect are the origin of the highly efficient catalytic activity, which was not reported before.

An optical fiber microdisplacement sensor based on symmetric Mach-Zehnder interferometer (MZI) with a seven-core fiber and two single-mode fiber balls is proposed. The rationality and manufacturing process of the MZI sensing structure are analyzed. The fabrication mechanism of the Mach-Zehnder sensor by CO2laser is described in detail. Experimental results show that temperature sensitivities of the two dips are 98.65 pm/°C and 89.72 pm/°C, respectively. The microdisplacement sensitivities are 2017.71 pm/mm and 2457.92 pm/mm, respectively. The simultaneous measurement of temperature and microdisplacement is demonstrated based on the sensitive matrix. The proposed Mach-Zehnder interference sensor exhibits the advantages of compact structure, simple manufacturing process, and high reliability.

Chitooligosaccharide has been reported to possess diverse bioactivities. The development of novel strategies for obtaining optimum degree of polymerization (DP) chitooligosaccharides has become increasingly important. In this study, two glycoside hydrolase family 46 chitosanases were studied for immobilization on curdlan (insoluble β-1,3-glucan) using a novel carbohydrate binding module (CBM) family 56 domain from a β-1,3-glucanase. The CBM56 domain provided a spontaneous and specific sorption of the fusion proteins onto a curdlan carrier, and two fusion enzymes showed increased enzyme stability in comparison with native enzymes. Furthermore, a continuous packed-bed reactor was constructed with chitosanase immobilized on a curdlan carrier to control the enzymatic hydrolysis of chitosan. Three chitooligosaccharide products with different molecular weights were prepared in optimized reaction conditions. This study provides a novel CBM tag for the stabilization and immobilization of enzymes. The controllable hydrolysis strategy offers potential for the industrial-scale preparation of chitooligosaccharides with different desired DPs.

AbstractUsing the stress–strain oscillation method, we conducted experiments on a sandstone over a frequency range of 1–100 Hz at a differential pressure of 5 MPa to investigate the effects of oil saturation and oil/water substitution on modulus dispersion and attenuation. We first saturated the sandstone with a low viscosity oil (2#) at different saturation degrees, then replaced the 2# oil with a more viscous oil (68#) and finally injected distilled water in the oil-saturated sample. Young’s modulus, Poisson’s ratio and extensional attenuation were measured during these saturation processes. The measured moduli of this sandstone, when saturated with the 2# oil at different saturation degrees (0% to 100%) or when fully saturated with the 68# oil, manifest little dispersion over the frequency range of 1–100 Hz, and low attenuation was observed. The measured bulk modulus for the oil-saturated sandstone agrees well with the prediction of Gassmann’s fluid-substitution theory, suggesting that wave-induced fluid flow (WIFF) plays an insignificant role in control of the bulk modulus when the sandstone is filled with oil. However, as oil saturation and viscosity increase, the shear modulus keeps increasing, violating the Gassmann’s fluid-substitution theory, which may be caused by the viscous coupling mechanism. When water was injected into sandstone fully saturated with the 68# oil, distinct modulus dispersion and attenuation were observed. The characteristics of the modulus dispersion and attenuation are consistent with mesoscopic WIFF theory, indicating that mesoscopic WIFF is the main cause of modulus dispersion and attenuation for this sandstone saturated with oil–water mixture at seismic frequencies.

The everted gut sacs and Caco-2 cell models were used to investigate the intestinal absorptive characteristics and subcellular localization of chitobiose and chitopentaose in this study. In everted gut sacs, the absorptive pattern showed no concentration-dependent manner when the concentration was lower than 10 mM. In the presence of phlorizin (100 μM) and phloretin (100 μM), the chitobiose absorption rates decreased by (4.97 ± 0.89)% and (19.2 ± 2.77)%, and they were (10.4 ± 2.43)% and (27.5 ± 1.68)% for chitopentaose. In Caco-2 cells, the concentration showed influences similar to those with the everted gut sacs results. After adding phlorizin and phloretin in the apical side, the PappAP–BLof chitobiose and chitopentaose significantly decreased. Considering the translocation, they were enriched in endoplasmic reticulum and mitochondrion. This study indicated that concentration and active transporter were capable of mediating the absorption of chitobiose and chitopentaose, and the subcellular localization of them could help to study the mechanisms of their effects.

GLP-1 analogs suffer from the main disadvantage of a short in vivo half-life. Lithocholic acid (LCA), one of the four main bile acids in the human body, possesses a high albumin binding rate. We therefore envisioned that a LCA-based peptide delivery system could extend the half-life of GLP-1 analogs by facilitating the noncovalent binding of peptides to human serum albumin. On the basis of our previously identified XenopusGLP-1 analogs (1–3), a series of LCA-modified XenopusGLP-1 conjugates were designed (4a–4r), and the bioactivity studies of these conjugates were performed to identify compounds with balanced in vitro receptor activation potency and plasma stability. 4c, 4i, and 4rwere selected, and their LCA side chains were optimized to further increase their stability, affording 5a–5c. Compound 5bshowed a more increased albumin affinity and prolonged in vitro stability than that of 4iand liraglutide. In db/dbmice, 5bexhibited comparable hypoglycemic and insulinotropic activity to liraglutide and semaglutide. Importantly, the enhanced albumin affinity of 5bresulted in a prolonged in vivo antidiabetic duration. Finally, chronic treatment investigations of 5bdemonstrated the therapeutic effects of 5bon HbA1c, body weight, blood glucose, and pancreatic endocrine deficiencies on db/dbmice. Our studies revealed 5bas a promising antidiabetic candidate. Furthermore, our study suggests the derivatization of XenopusGLP-1 analogs with LCA represents an effective strategy to develop potent long-acting GLP-1 receptor agonists for the treatment of type 2 diabetes.

ABSTRACTThe taste of umami peptide H-Lys-Gly-Asp-Glu-Glu-Ser-Leu-Ala-OH (LGAGGSLA) is controversial. One possible reason for this controversy is the use of chemically synthesized LGAGGSLA to confirm its taste. To explore other ways to further confirm the flavor of LGAGGSLA, we developed a new strategy to prepare a bio-source peptide by adopting a gene engineering method to express LGAGGSLA in recombinant Escherichia coli. In our previous work, we structured the LGAGGSLA recombinant expression system and optimized the culturing conditions for preparing a fusion protein. However, the fusion protein was not cleaved by enterokinase to obtain LGAGGSLA. Because the cleavage conditions of commercial enterokinase were not specific and recombinant engineered bacteria had the potential to be used in industrial processes, in this addendum, we calculated the mass and volume yields of key processing steps in the preparation of LGAGGSLA, and established a model of cleavage conditions with the cleavage ratio of LGAGGSLA. When the LGAGGSLA was confirmed to show umami taste, it is considered as a new umami or umami enhancer. The gene information of LGAGGSLA should have a great potential in the development of new flavor product and food product containing high umami flavor.

We developed a system to explore the effects of pressure and fluid viscosity on the dispersion and attenuation of fully saturated tight sandstones, especially at seismic frequencies. Calibration of the new system revealed that the system can operate reliably at frequencies of [2–200, 106] Hz. Tight sandstone with a “crack–pore” microstructure was tested under nitrogen gas (dry), brine, and glycerin saturation. A frequency‐dependent effect was not found for the dry case. However, apparent dispersion and attenuation for the undrained/unrelaxed transition was clearly observed for sample under brine or glycerin saturation, the magnitude of which was largely suppressed by increasing effective pressure. The measurement results illustrated that increasing the fluid viscosity or the effective pressure will shift the dispersion curve to the lower frequency range. A simple squirt‐flow model with dual‐porosity scheme was used to compare with the measurement results. Although the estimated values deviated slightly from the data, the trend fitted the saturated data relatively well, especially at low effective pressures. Therefore, considering the crack–pore microstructure of the tight sandstone, dispersion and attenuation are induced predominantly by the squirt‐flow stiffening effect from cracks to pores. A system for measurement of elastic moduli across a wide frequency bandInvestigate effects of pressure and fluid viscosity on frequency‐dependent elastic properties of tight sandstoneSquirt flow is the dominant mechanism for the dispersion and attenuation at seismic frequency for this tight sandstone

Aedes aegypti(L.) is the vector responsible for transmitting dengue, chikungunya, yellow fever, and Zika viruses, as well as other pathogens. Microbial larvicides based on Bacillus thuringiensisBerliner israelensis(Bti) and Saccharopolyspora spinosaMertz and Yao, such as VectoBac 12AS and Natular 2EC, have been shown to be effective in reducing larval populations of Ae. aegypti. We examined the gene expression of two detoxification enzymes, glucosyl and glucuronosyl transferases (AaeGGT1and AaeGGT2), through developmental stages and a time course study in response to larvicide exposure using qualitative real-time polymerase chain reaction (qPCR). AaeGGT1and AaeGGT2gene expressions were differentially regulated during development of the immature stages. We also found that male adults had higher expression than female adults after controlling for age effects. AaeGGT1and AaeGGT2gene expression were both upregulated in response to VectoBac 12AS and Natular 2EC treatments with the maximum level of expression occurring 24 h after treatment applications. This information sheds light on larvicide-induced changes in the physiology of Ae. aegyptiwith implications for development of mosquito control strategies.

To evaluate the feasibility of isomer separation by nanofiltration (NF), the effects of different monosaccharide stereo-structures on separation performance of xylose and arabinose nanofiltration were studied in this work. An NF250 membrane was used to study xylose and arabinose rejection under different physical conditions. The retention differences between xylose and arabinose were investigated under different solution conditions during NF processing. Furthermore, the influences of physical conditions on molecular computational radius (rc) and diffusion coefficient of the solute (Dp) were analyzed. The STERIMOL model was introduced to describe the theoretical sizes of monosaccharide molecules. Dpwas applied to calculate the degree of rejections. The results showed that the rejection ratio of xylose to arabinose increased as Dpexceeded 5.0. Maintaining the trans-membrane pressure (TMP) between 8.0 and 12.0 bar, elevating the operation temperature and reducing the concentration of the bulk solution helped increase the rejection ratio of xylose to arabinose. This study presents a potential approach for monosaccharide isomers separation by solution physical properties regulating.

The regeneration of alveolar bone is still clinical challenge, particularly accompanied with diabetes, causing metabolic disorder with a protracted low-grade inflammatory phenotype and thus retards angiogenesis and osteogenesis. As a result, the anticipated loading of biomaterials is highly suspicious in spontaneous modulation of cells function, which is mostly disturbed by constant inflammation. In this study, we developed glucose and hydrogen peroxide dual-responsive borosilicate glass (BSG) scaffolds loaded with epigallocatechin gallate (EGCG) to synergistically modulate the abnormal inflammation of diabetic alveolar bone defects. It was found that the release of EGCG by BSG could directly regulate the shift of macrophages from M1 to the M2 phenotype by promoting autophagy and lessening the inhibition of autophagic flux. Moreover, EGCG can also indirectly regulate the polarization phenotype of macrophages by reducing the activation of NF-κb in stem cells and restoring its immunoregulatory capacity. Therefore, the addition of EGCG to BSG scaffold in diabetes allows for a more striking modulation of the macrophage phenotype in a timely manner. The altered macrophage phenotype reduces local inflammation and thus increases the ability to repair diabetic alveolar bone, showing promise for the treatment of alveolar defect in diabetic patients.

Inspired by biological ion channels, numerous artificial asymmetric ion channels have been synthesized to facilitate the fabrication of ionic circuits. Nevertheless, the creation of biomimetic asymmetric ion channels necessitates expensive scientific apparatus and intricate material processing procedures, which constrains its advancement within the realm of ionic devices. In this study, we have devised dynamic asymmetric ion channels with mechanical responsiveness by combining polymers of varying elastic modulus along the longitudinal axis of carbon nanotube fiber (CNTF). The ion rectification can be modulated viathe disparate response of CNTF-based ion channels to mechanical stress. We have effectively employed these asymmetric ion channels with mechanical sensitivity in the design of a logic gate device, achieving logic operations such as “AND” and “OR”. The conception of these dynamic asymmetric ion channels with mechanical sensitivity offers a straightforward, cost-effective, and versatile approach for generating ion channels, highlighting their potential application in intricate, highly integrated ionic circuits.

Feed efficiency is an important indicator in the sheep production process, which plays an important role in improving economic benefits and strengthening energy conservation and emission reduction. Compared with the rumen, the fermentation of the hindgut microorganisms can also provide part of the energy for the host, and the composition of the hindgut microorganisms will affect the feed efficiency. Therefore, we hope to find new ways to regulate sheep feed efficiency by studying the sheep gut microbes. In this study, male Hu sheep with the same birth date were raised under the same conditions until 180 d old. The sheep were divided into high and low groups according to the feed conversion ratio (FCR) at 80 to 180 d old, and the differences in rectal microorganisms between the two groups were compared. The permutational multivariate analysis (PERMANOVA) test showed that there were differences in microorganisms between the two groups (P< 0.05). Combined with linear fitting analysis, a total of six biomarkers were identified, including Ruminobacter, Eubacterium_xylanophilum_group, Romboutsia, etc. Functional enrichment analysis showed that microorganisms may affect FCR through volatile fatty acids synthesis and inflammatory response. At the same time, we conducted a longitudinal analysis of the hindgut microbes, sampling nine-time points throughout the sheep birth to market stages. The microbiota is clearly divided into two parts: before weaning and after weaning, and after weaning microbes are less affected by before weaning microbial composition.The relationship between rectal microbes and feed conversion ratio in sheep was explored, and the longitudinal development of microbes was elucidated.The level of feed efficiency determines the input of sheep production costs and the income of economic benefits. Improving sheep feed efficiency can effectively save energy and reduce emissions. Gut microbes play an important role in the process of feed fermentation. In this study, biomarkers associated with feed efficiency were identified by exploring the relationship between microbes and feed conversion ratio. At the same time, the longitudinal development of microorganisms was explored. It provides a basis for the regulation of intestinal microbes in sheep.

Cottonseed meal has been one of the predominant protein feedstuffs used in aqua feed, which contains gossypol. It is well known that gossypol, a natural polyphenolic compound found in seeds, can be toxic to fish. The toxicity of gossypol persists even after a recovery period; however, the underlying mechanism remains largely unknown. To investigate the toxic mechanism of gossypol after the recovery period, Cyprinus carpiowere administered a continuous oral dose of 20mg/kg·d gossypol (gossypol acetate dose/fish weight·d) for one week, followed by a two-week recovery period. The spleen index, spleen morphology, lysozyme (LZM) activity, acid phosphatase (ACP) activity and nitric oxide (NO) concentration were obviously changed in the spleens of C. carpioafter two weeks of recovery. Then, miRNA sequencing identified 22 differentially expressed miRNAs in the spleens of C. carpiotwo weeks after the gossypol treatment. The mRNA expression levels of immune-associated genes were significantly increased in the spleens after recovery. MiR-194 was chosen for future study through a search of existing literature and an analysis of miRNA and mRNA expression levels. To further characterize the potential target of miR-194, we identified putative miR-194 binding sites in the 3'UTR of myeloid differentiation factor 88a (MyD88a). Dual-luciferase reporter assays revealed that miR-194 downregulated the expression level of MyD88a through binding to seed-matching sequence in the 3′ UTR of MyD88a. Moreover, C. carpiowere intraperitoneally administered with miR-194 antagomir. Furthermore, down-regulation of miR-194 increased the expression levels of MyD88a and some pro-inflammatory cytokines and anti-inflammatory cytokines. Altogether, the results demonstrate miR-194 can target MyD88a to regulate the immune response of C. carpioafter a two-week recovery period following gossypol administration.

Animal growth traits are important and complex traits that determine the productivity of animal husbandry. There are many factors that affect growth traits, among which diet digestion is the key factor. In the process of animal digestion and absorption, the role of gastrointestinal microbes is essential. In this study, we transplanted two groups of sheep intestinal microorganisms with different body weights into the intestines of mice of the same age to observe the effect of fecal bacteria transplantation on the growth characteristics of the mouse model. The results showed that receiving fecal microbiota transplantation (FMT) had an effect on the growth traits of recipient mice (P< 0.05). Interestingly, only mice receiving high-weight donor microorganisms showed differences. Use 16S rDNA sequencing technology to analyze the stool microorganisms of sheep and mice. The microbial analysis of mouse feces showed that receiving FMT could improve the diversity and richness of microorganisms (P< 0.05), and the microbial composition of mouse feces receiving low-weight donor microorganisms was similar to that of the control group, which was consistent with the change trend of growth traits. The feces of high-weight sheep may have higher colonization ability. The same five biomarkers were identified in the donor and recipient, all belonging to Firmicutes, and were positively correlated with the body weight of mice at each stage. These results suggest that FMT affects the growth traits of receptors by remodeling their gut microflora.Elucidating the process by which fecal microbiota transplantation alters growth traits by altering recipient gut microbes.The rate of development of growth traits determines the productivity of sheep. Shortening the fattening cycle of sheep can effectively improve economic efficiency. Gut microbes have important effects on host growth traits. In this study, the method of fecal microbiota transplantation (FMT) was used to transplant the intestinal microbes of sheep into the mouse model, and the changes of the growth traits and intestinal microbes of the mice were observed. The results suggest that FMT can effectively affect growth traits by altering recipient gut microbes. This provides a new idea for the regulation of sheep growth traits.