RGD-p21Ras-scFv expressed prokaryotically on a pilot scale inhibits ras-driven colorectal cancer growth by blocking p21Ras-GTP.

BACKGROUND: Ras gene mutation and/or overexpression are drivers in the progression of cancers, including colorectal cancer. Blocking the Ras signaling has become a significant strategy for cancer therapy. Previously, we constructed a recombinant scFv, RGD-p21Ras-scFv by linking RGD membrane-penetrating peptide gene with the anti-p21Ras scFv gene. Here, we expressed prokaryotically RGD-p21Ras-scFv on a pilot scale, then investigated the anti-tumor effect and the mechanism of blocking Ras signaling. METHODS: The E. coli bacteria which could highly express RGD-p21Ras-scFv was screened and grown in 100 L fermentation tank to produce RGD-p21Ras-scFv on optimized induced expression conditions. The scFv was purified from E. coli bacteria using His Ni-NTA column. ELISA was adopted to test the immunoreactivity of RGD-p21Ras-scFv against p21Ras proteins, and the IC50 of RGD-p21Ras-scFv was analyzed by CCK-8. Immunofluorescence colocalization and pull-down assays were used to determine the localization and binding between RGD-p21Ras-scFv and p21Ras. The interaction forces between RGD-p21Ras-scFv and p21Ras after binding were analyzed by molecular docking, and the stability after binding was determined by molecular dynamics simulations. p21Ras-GTP interaction was detected by Ras pull-down. Changes in the MEK-ERK /PI3K-AKT signaling paths downstream of Ras were detected by WB assays. The anti-tumor activity of RGD-p21Ras-scFv was investigated by nude mouse xenograft models. RESULTS: The technique of RGD-p21Ras-scFv expression on a pilot scale was established. The wet weight of the harvested bacteria was 31.064 g/L, and 31.6 mg RGD-p21Ras-scFv was obtained from 1 L of bacterial medium. The purity of the recombinant antibody was above 85%, we found that the prepared on a pilot scale RGD-p21Ras-scFv could penetrate the cell membrane of colon cancer cells and bind to p21Ras, then led to reduce of p21Ras-GTP (active p21Ras). The phosphorylation of downstream effectors MEK-ERK /PI3K-AKT was downregulated. In vivo antitumor activity assays showed that the RGD-p21Ras-scFv inhibited the proliferation of colorectal cancer cell lines. CONCLUSION: RGD-p21Ras-scFv prokaryotic expressed on pilot-scale could inhibited Ras-driven colorectal cancer growth by partially blocking p21Ras-GTP and might be able to be a hidden therapeutic antibody for treating RAS-driven tumors.

Regulating the crystal orientation of vapor-transport-deposited GeSe thin films by a post-annealing treatment.

Recently, GeSe has emerged as a highly promising photovoltaic absorber material due to its excellent optoelectronic properties, nontoxicity, and high stability. Although many advantages make GeSe well suited for thin-film solar cells, the power conversion efficiency of the GeSe thin-film solar cell is still much below the theoretical maximum efficiency. One of the challenges lies in controlling the crystal orientation of GeSe to enhance solar cell performance. The two-step preparation of GeSe thin films has not yet been reported to grow along the [111] orientation. In this work, we study the effect of a post-annealing treatment on the GeSe thin films and the performance of the solar cells. It was found that amorphous GeSe films can be converted into polycrystalline films with different orientations by changing the post-annealing temperature. [111]-oriented and [100]-oriented GeSe thin films were successfully prepared on the same substrate by optimizing the annealing conditions. With the structure of Au/GeSe/CdS/ITO cell devices, PCEs of 0.14% and 0.16% were ultimately achieved.

Recent advances in Zizania latifolia: A comprehensive review on phytochemical, health benefits and applications that maximize its value.

Zizania latifolia is an aquatic and medicinal plant with a long history of development in China and the East Asian region. The smut fungus "Ustilago esculenta" parasitizes Z. latifolia and induces culm expansion to form a vegetable named Jiaobai, which has a unique taste and nutritional attributes. However, the postharvest quality of water bamboo shoots is still a big challenge for farmers and merchants. This paper traced the origin, development process, and morphological characteristics of Z. latifolia. Subsequently, the compilation of the primary nutrients and bioactive substances are presented in context to their effects on ecology a postharvest storage and preservation methods. Furthermore, the industrial, environmental, and material science applications of Z. latifolia in the fields of industry were discussed. Finally, the primary objective of the review proposes future directions for research to support the development of Z. latifolia industry and aid in maximizing its value. To sum up, Z. latifolia, aside from its potential as material it can be utilized to make different productions and improve the existing applications. This paper provides an emerging strategy for researchers undertaking Z. latifolia.

Recent advances in the tumor-penetrating peptide internalizing RGD for cancer treatment and diagnosis.

Cancer has become a prominent disease that seriously endangers human health. The complexity of the biological characteristics of the tumor makes it challenging for traditional therapeutic drugs to penetrate tumor tissues and exert their antitumor effects. Internalizing RGD peptide (iRGD) is a novel tumor-homing peptide that binds to αvß3 and αvß5 integrins on the surface of tumor vessels through the C-end rule (CendR) motif. The CendR motif binds to the neuropilin-1 (NRP-1) receptor on tumor cells, initiating NRP-1-mediated transcytosis to facilitate drug entry into the tumor tissue. Multiple studies demonstrated that iRGD improved the penetration and targeting of antitumor drugs, thereby enhancing their antitumor efficacy. In this review, we initially described the origins of iRGD and its penetration mechanism. Furthermore, we presented updates on the application of iRGD in cancer chemotherapy, photodynamic therapy, gene therapy, immunotherapy, treatment with antibodies or protein-based biologics, and tumor imaging.

Inhibiting pyroptosis: novel immune evasion strategies for pathogens.

Pyroptosis is a type of programmed cell death mediated by the Gasdermin family. It is triggered in response to pathogen infection or other danger signals. The activation of Gasdermins leads to pyroptosis and the release of large amounts of inflammatory cytokines. Pyroptosis plays a crucial role in combating pathogen infections, as it helps to eliminate infected cells and activate the immune system. However, pathogens have already developed sophisticated strategies to evade or inhibit pyroptosis, allowing them to persist and facilitate infection. This review provides an overview of the discovery of pyroptosis and its importance in anti-infectious immunity. We also discuss several new strategies for inhibiting pyroptosis by pathogens. A thorough learning of the occurrence and regulation of pyroptosis may reveal the pathogenesis of related infectious diseases and contribute to developing effective anti-infective therapeutic strategies.

Switching Adaptive Control with Applications on Robot Manipulators.

This paper concentrates on the study of logic-based switching adaptive control. Two different cases will be considered. In the first case, the finite time stabilization problem for a class of nonlinear system is studied. Based on the recently developed adding a barrier power integrator technique, a new logic-based switching adaptive control method is proposed. In contrast with the existing results, finite time stability can be achieved when the considered systems contain both fully unknown nonlinearties and unknown control direction. Moreover, the proposed controller has a very simple structure and no approximation methods, e.g., neural networks/fuzzy logic, are needed. In the second case, the sampled-data control for a class of nonlinear system is investigated. New sampled-data logic-based switching mechanism is proposed. Compared with previous works, the considered nonlinear system has an uncertain linear growth rate. The control parameters and the sampling time can be adjusted adaptively to render the exponential stability of the closed loop system. Applications in robot manipulators are conducted to verify the proposed results.

Asynchronous Stabilization for Two Classes of Stochastic Switching Systems with Applications on Servo Motors.

This paper addresses the asynchronous stabilization problem of two typical stochastic switching systems, i.e., dual switching systems and semi-Markov jump systems. By dual switching, it means that the systems contain both deterministic and stochastic switching dynamics. New stability criteria are firstly proposed for these two switched systems, which can well handle the asynchronous phenomenon. The conditional expectation of Lyapunov functions is allowed to increase during some unmatched interval to reduce the conservatism. Next, we present numerically testable asynchronous controller design methods for the dual switching systems. The proposed method is suitable for the situation where the asynchronous modes come from both inaccurate mode detection and time varying delay. Meanwhile, the transition probabilities are both uncertain and partly accessible. Finally, novel asynchronous controller design methods are proposed for the semi-Markov jump systems. The sojourn time of the semi-Markov jump systems can have both lower and upper bounds, which could be more practical than previous scenarios. Examples are utilized to demonstrate the effectiveness of the proposed methods.

Effects of working pressure and power on photovoltaic and defect properties of magnetron sputtered Sb2Se3 thin-film solar cells.

Antimony selenide (${\text{Sb}_2}{\text{Se}_3}$Sb2Se3) is an emerging material with potential applications in photovoltaics, while magnetron sputtering is an important method in material growth. In this study, ${\text{Sb}_2}{\text{Se}_3}$Sb2Se3 thin films, prepared by the magnetron sputtering technique with varied working pressures and sputtering powers, were fabricated into solar cells with a structure of $\text{glass}/\text{ITO}/\text{CdS}/{\text{Sb}_2}{\text{Se}_3}/\text{Au}$glass/ITO/CdS/Sb2Se3/Au. The current density versus voltage measurements and x-ray diffraction were introduced to compare the photovoltaic and structural properties of the cell samples. Characterization and identification of the defects in ${\text{Sb}_2}{\text{Se}_3}$Sb2Se3 thin films were investigated by admittance measurements. The ${\text{Sb}_2}{\text{Se}_3}$Sb2Se3 cell samples prepared with appropriate sputtering power (about 60 W) or working pressure (about 0.4 Pa) were found to own better crystal qualities and lower defect densities, which may be the reason for better efficiency.

Robust Lateral Stabilization Control of In-Wheel-Motor-Driven Mobile Robots via Active Disturbance Suppression Approach.

Due to the praiseworthy maneuverability and actuation flexibility, the in-wheel-motor-driven mobile robots (IWMD-MR) are widely employed in various industrial fields. However, the active estimation and rejection of unknown disturbances/uncertainties remain a tough work for formulating a stable lateral motion controller. To address the challenge, this paper proposes a robust lateral stabilization control (RLSC) scheme for the developed IWMD-MR by designing an active disturbance suppression mechanism. The distinctive features of the proposed RLSC method are threefold: (i) With a fuzzy estimator, a modified super-twisting sliding mode method is designed to eliminate the system perturbations and time-varying lumped disturbances in an active manner; (ii) The resultant system trajectory is forced into a bounded switching region within finite time, which can be maintained therein for subsequent periods; (iii) Employing the Lyapunov function, new adaption rules for multivariable gains are derived to preserve the lateral motion stability and robustness. Finally, under the direct yaw moment control framework, simulation experiments of real-life IWMD-MR are offered to verify the effectiveness of the presented RLSC method.

A newly isolated human intestinal bacterium strain capable of deglycosylating flavone C-glycosides and its functional properties.

BACKGROUND: Flavone C-glycosides are difficult to be deglycosylated using traditional chemical methods due to their solid carbon-carbon bond between sugar moieties and aglycones; however, some bacteria may easily cleave this bond because they generate various specific enzymes. RESULTS: A bacterial strain, named W12-1, capable of deglycosylating orientin, vitexin, and isovitexin to their aglycones, was isolated from human intestinal bacteria in this study and identified as Enterococcus faecalis based on morphological examination, physiological and biochemical identification, and 16S rDNA sequencing. The strain was shown to preferentially deglycosylate the flavone C-glycosides on condition that the culture medium was short of carbon nutrition sources such as glucose and starch, and its deglycosylation efficiency was negatively correlated with the content of the latter two substances. CONCLUSION: This study provided a new bacterial resource for the cleavage of C-glycosidic bond of flavone C-glycosides and reported the carbon nutrition sources reduction induced deglycosylation for the first time.

Overexpression of the neuronal human (pro)renin receptor mediates angiotensin II-independent blood pressure regulation in the central nervous system.

Despite advances in antihypertensive therapeutics, at least 15-20% of hypertensive patients have resistant hypertension through mechanisms that remain poorly understood. In this study, we provide a new mechanism for the regulation of blood pressure (BP) in the central nervous system (CNS) by the (pro)renin receptor (PRR), a recently identified component of the renin-angiotensin system that mediates ANG II formation in the CNS. Although PRR also mediates ANG II-independent signaling, the importance of these pathways in BP regulation is unknown. Here, we developed a unique transgenic mouse model overexpressing human PRR (hPRR) specifically in neurons (Syn-hPRR). Intracerebroventricular infusion of human prorenin caused increased BP in Syn-hPRR mice. This BP response was attenuated by a NADPH oxidase (NOX) inhibitor but not by antihypertensive agents that target the renin-angiotensin system. Using a brain-targeted genetic knockdown approach, we found that NOX4 was the key isoform responsible for the prorenin-induced elevation of BP in Syn-hPRR mice. Moreover, inhibition of ERK significantly attenuated the increase in NOX activity and BP induced by human prorenin. Collectively, our findings indicate that an ANG II-independent, PRR-mediated signaling pathway regulates BP in the CNS by a PRR-ERK-NOX4 mechanism. NEW & NOTEWORTHY This study characterizes a new transgenic mouse model with overexpression of the human (pro)renin receptor in neurons and demonstrated a novel angiotensin II-independent mechanism mediated by human prorenin and the (pro)renin receptor in the central regulation of blood pressure.

Investigation of the effective components of the flowers of Trollius chinensis from the perspectives of intestinal bacterial transformation and intestinal absorption.

CONTEXT: The flowers of Trollius chinensis Bunge (Ranunculaceae), used for respiratory tract infections, mainly contain flavonoids, phenolic acids, and alkaloids; however, the effective components are debatable because of their unclear in vivo activities. OBJECTIVE: This study investigates the effective components from the perspectives of biotransformation and absorption. MATERIALS AND METHODS: Both single person derived- and multiple people-derived intestinal florae were used to investigate the biotransformation of aqueous extract of the flowers of T. chinensis (AEOF) at the concentrations of 15.0, 30.0, and 60.0 mg/mL, respectively, for 72 h. Both human colon adenocarcinoma cell line (Caco-2) monolayers and everted gut sacs were employed to evaluate the intestinal absorption of the intestinal bacterial transformed AEOF at the concentrations of 10, 20, and 30 mg/mL, respectively, for 180 min. RESULTS: 2″-O-ß-l-Galactopyranosylorientin, orientin, vitexin, quercetin, veratric acid, proglobeflowery acid, and trolline in AEOF were not transformed by intestinal bacteria, while isoquercetin and trollioside were completely transformed. The Papp values of 2″-O-ß-l-galactopyranosylorientin, orientin, and vitexin calculated based on the experimental data of intestinal absorption were at the levels of 10-5, whereas those of veratric acid, proglobeflowery acid, and trolline were at 10-4. The mass ratio of flavonoids to phenolic acids to alkaloids changed from 16:10:7 to 9:12:8 before and after absorption. DISCUSSION AND CONCLUSION: The dominant position of flavonoids was replaced by phenolic acids after absorption. In addition to flavonoids which are usually considered as the dominant effective ones, phenolic acids and alkaloids should be also very important for the efficacy of these flowers.

Adaptive Neural Consensus for Fractional-Order Multi-Agent Systems With Faults and Delays.

This article investigates the consensus control for a class of fractional-order (FO) nonlinear multi-agent systems (MASs). Severe sensor/actuator faults and time-varying delays are both considered in the FO MASs. The severe faults may cause unknown control directions in MASs. A new adaptive controller, which is composed of a distributed FO Nussbaum gain, an FO filter, and an auxiliary function, is presented to deal with the severe faults. To cope with the time-varying delays, two different methods are proposed based on barrier Lyapunov function and Lyapunov-Krasovskii function, respectively. Meanwhile, the radial basis function neural network (RBF NN) is applied to approximate the unknown nonlinear functions during the design procedures. This can result in a low-complexity controller. Finally, two simulation examples are used to verify the validity of the proposed schemes.

Integrated thrust ripple identification and compensation for linear servo system using an MP algorithm.

Generally there are two methods for the thrust ripple modeling: one is to identify the eigenvalues and the model parameters of thrust ripple sequentially under rigorous operating conditions; another is to treat thrust ripple as a general and inaccurate disturbance. To get rid of the constraints and further enhance the tracking accuracy of the linear servo system, a novel integrated identification and compensation scheme using an improved matching pursuit algorithm is proposed in this paper. First, the dynamics of the linear motor is formulated, and the cause of thrust ripple is analyzed. Then, a time-frequency atomic library of thrust ripple is constructed with the consideration of the frequency characteristics of position command, and meanwhile, the two optimal atoms are obtained successively by maximizing the inner product for the thrust ripple reconstruction. Based on the above, the eigenvalues and model parameters of thrust ripple can be simultaneously identified in an online manner. Finally, the feedforward compensation component is devised by the identification results to suppress thrust ripple. In order to verify the superiority of the proposed scheme, simulations and experiments are conducted compared with the conventional methods.

Establishment of a N1-methyladenosine-related risk signature for breast carcinoma by bioinformatics analysis and experimental validation.

OBJECTIVES: Breast carcinoma (BRCA) has resulted in a huge health burden globally. N1-methyladenosine (m1A) RNA methylation has been proven to play key roles in tumorigenesis. Nevertheless, the function of m1A RNA methylation-related genes in BRCA is indistinct. METHODS: The RNA sequencing (RNA-seq), copy-number variation (CNV), single-nucleotide variant (SNV), and clinical data of BRCA were acquired via The Cancer Genome Atlas (TCGA) database. In addition, the GSE20685 dataset, the external validation set, was acquired from the Gene Expression Omnibus (GEO) database. 10 m1A RNA methylation regulators were obtained from the previous literature, and further analyzed through differential expression analysis by rank-sum test, mutation by SNV data, and mutual correlation by Pearson Correlation Analysis. Furthermore, the differentially expressed m1A-related genes were selected through overlapping m1A-related module genes obtained by weighted gene co-expression network analysis (WGCNA), differentially expressed genes (DEGs) in BRCA and DEGs between high- and low- m1A score subgroups. The m1A-related model genes in the risk signature were derived by univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. In addition, a nomogram was built through univariate and multivariate Cox analyses. After that, the immune infiltration between the high- and low-risk groups was investigated through ESTIMATE and CIBERSORT. Finally, the expression trends of model genes in clinical BRCA samples were further confirmed by quantitative real-time PCR (RT‒qPCR). RESULTS: Eighty-five differentially expressed m1A-related genes were obtained. Among them, six genes were selected as prognostic biomarkers to build the risk model. The validation results of the risk model showed that its prediction was reliable. In addition, Cox independent prognosis analysis revealed that age, risk score, and stage were independent prognostic factors for BRCA. Moreover, 13 types of immune cells were different between the high- and low-risk groups and the immune checkpoint molecules TIGIT, IDO1, LAG3, ICOS, PDCD1LG2, PDCD1, CD27, and CD274 were significantly different between the two risk groups. Ultimately, RT-qPCR results confirmed that the model genes MEOX1, COL17A1, FREM1, TNN, and SLIT3 were significantly up-regulated in BRCA tissues versus normal tissues. CONCLUSIONS: An m1A RNA methylation regulator-related prognostic model was constructed, and a nomogram based on the prognostic model was constructed to provide a theoretical reference for individual counseling and clinical preventive intervention in BRCA.

Impermeability and Durability of Self-Compacting Concrete Prepared with Aeolian Sand and Recycled Coarse Aggregate.

Self-compacting concrete has seen extensive application in both engineering and construction. In order to save building resources, aeolian sand-recycled coarse aggregate self-compacting concrete (ARSCC) is created by partially substituting recycled coarse aggregates (RCA) and aeolian sand (AS) for natural coarse aggregates. For ten groups with different mechanical and durable properties, this study examined the effects of sulfate erosion, chloride penetration resistance, and related impermeability, as well as AS replacement ratios of 20%, 40%, and 60% and RCA replacement ratios of 25%, 50%, and 75% in ARSCC and a control group (A0-R0). According to the study's findings, after sulfate attack, the highest relative dynamic elastic modulus and corrosion resistance factor were obtained with the 20% AS replacement ratio and 50% RCA replacement ratio (A20-R50). The highest impermeability grade and lowest electric flux were obtained with the 20% AS replacement ratio and 25% RCA replacement ratio (A20-R25). X-ray diffraction (XRD) and mercury intrusion porosimetry (MIP) revealed that the addition of aeolian sand and recycled coarse aggregates improved the pore structure of the SCC and increased the densification of the self-compacting concrete, particularly following sulfate attack. This study highlights the importance of recycled aggregates and aeolian sand in engineering applications and the sustainable growth of the concrete industry, both of which support resource conservation and environmental protection.

DeCOOC Deconvoluted Hi-C Map Characterizes the Chromatin Architecture of Cells in Physiologically Distinctive Tissues.

Deciphering variations in chromosome conformations based on bulk three-dimensional (3D) genomic data from heterogenous tissues is a key to understanding cell-type specific genome architecture and dynamics. Surprisingly, computational deconvolution methods for high-throughput chromosome conformation capture (Hi-C) data remain very rare in the literature. Here, a deep convolutional neural network (CNN), deconvolve bulk Hi-C data (deCOOC) that remarkably outperformed all the state-of-the-art tools in the deconvolution task is developed. Interestingly, it is noticed that the chromatin accessibility or the Hi-C contact frequency alone is insufficient to explain the power of deCOOC, suggesting the existence of a latent embedded layer of information pertaining to the cell type specific 3D genome architecture. By applying deCOOC to in-house-generated bulk Hi-C data from visceral and subcutaneous adipose tissues, it is found that the characteristic chromatin features of M2 cells in the two anatomical loci are distinctively bound to different physiological functionalities. Taken together, deCOOC is both a reliable Hi-C data deconvolution method and a powerful tool for functional extraction of 3D genome architecture.

Effect of different dietary energy/protein ratios on growth performance, reproductive performance of breeding pigeons and slaughter performance, meat quality of squabs in summer.

Large-scale pigeon farming in China is gradually increasing. However, studies on the basic nutritional requirements of breeding pigeons during lactation, which greatly influence the productivity and economic benefits of pigeon breeding, remain scanty. The objective of this study was to determine the optimal dietary energy/protein ratio requirements for lactating pigeons in summer. A total of 576 pairs of Mimas breeding pigeons were randomly divided into 12 groups (n = 48 per treatment), and each pair bred 4 squabs. A two-way ANOVA design with different protein levels (15%, 16%, 17%, and 18%) for factor A and different energy levels (12.6 MJ/kg, 12.8 MJ/kg, and 13.0 MJ/kg) for factor B was used to design 12 groups of experimental diets for feeding. The experiment lasted for 28 d. We found that ME level had little effect on breeding pigeons, but the CP level and dietary energy/protein ratio significantly affected the reproductive and growth performance of the pigeons. The lowest total weight loss (P < 0.01), and the highest egg production (P < 0.01) were observed in group 11 (18% CP, 12.8 MJ/kg). It had no effect on egg quality. Both ME and CP levels significantly affected the growth performance, slaughter performance and meat quality of squabs, and there was a strong interaction between CP and ME. The fastest growth rate (P < 0.01) was observed in group 11 (18% CP, 12.8 MJ/kg). The best CP and ME combination for the eviscerated weight, pectoral muscle weight, organ weight, 45 min meat color (L⁎, a⁎, b⁎), pH, and muscle fiber characteristics were also group 11. Finally, the regression model revealed that the best dietary energy/protein ratio was 17.92 to 19.02 kcal/g for squabs and 16.72 kcal/g for the breeding pigeons. There was a strong interaction between energy and protein levels in breeding pigeons during the lactation period, and the best production performance was at 18% CP 12.8 MJ/kg. And this is recommended to be applied as the energy/protein ratio dietary requirement for breeding pigeons during lactation in the summer "2 + 4" pattern.

Optimal dietary energy and protein levels for breeding pigeons in the winter "2 + 3" lactation pattern.

The nutritional requirements of breeding pigeons depend on their physiological period, breeding pattern, and environmental conditions. Despite works on reduced litter size in winter production to combat high mortality and the poor welfare of squabs, there are few studies on the related nutritional requirements of these pigeons. A total of 432 pairs of European Mimas pigeons were randomly divided into 9 groups in which 3 crude protein (CP) levels (15, 16.5, and 18%) and 3 metabolizable energy (ME) levels (12.2 MJ/kg, 12.4 MJ/kg, and 12.6 MJ/kg) were tested to determine the optimal energy and protein requirements of breeding pigeons in the winter "2 + 3" breeding pattern. The results showed that ME and CP levels had little effect on the body weight, feed intake, and egg quality of breeding pigeons during the lactation period. An 18% CP diet significantly increased the laying rate and hatchability (P < 0.05), but there was no difference in the laying rate with 18% CP and 16.5% CP during the whole reproductive cycle (P > 0.05). There was a significant interaction between ME and CP levels, and the laying interval of breeding pigeons in group 9 (18% CP; 12.6 MJ/kg) was significantly shortened (P < 0.05). For squabs, the ME level had no effect on growth performance, slaughter performance, or meat quality. The body weight of 21-day-old squabs in the 18% CP group increased by 3.16% compared with that of the 15% CP group, but there was no difference between the 18% CP and 16.5% CP groups. Compared with other experimental groups, group 7 (18% CP; 12.2 MJ/kg) had the fastest growth rate in squabs (P < 0.05), and the corresponding slaughter weight was also the heaviest (P < 0.05). We further found that the height of the squab intestinal epithelium was significantly increased in both the 16.5% CP and 18% CP groups of squabs (P < 0.01), but male breeding pigeons showed a certain degree of oxidative stress with an increase in CP level. In conclusion, the effects of 15 to 18% CP levels and 12.2 to 12.6 MJ/kg ME levels on the reproductive metabolism of breeding pigeons and the growth and development of squabs in the "2 + 3" breeding pattern during winter are small. For economic efficiency, we suggest that the CP level can be reduced to 16.5% while the ME level should not be less than 12.2 MJ/kg in practical production.

Effects of granular feed on reproductive metabolism of breeding pigeons, intestinal development and microbiota of squab pigeons-A double-edged sword.

Pigeons like to eat raw grains, but meat pigeon enterprises often use compound feeds instead of raw grains to feed breeding pigeons to increase economic efficiency, which may change the pigeon's dietary behavior, and consequently lead to health and welfare problems. The purpose of this study was to investigate the effect of granular feeds on the health of high-yielding breeding pigeons and squabs in lactation. The results showed that, compared with raw grain group, the provision of granular feed resulted in lower total feed intake without affecting the weight of lactating breeding pigeons. Meanwhile, reproductive metabolism was improved and no oxidative stress was observed, which indicated that granular feeds had a positive effect on breeding pigeon's health. However, granular feed adversely affected jejunum development in squabs, compare wtih raw grain group, the growth rate of squab was reduced. Sequencing of the 16 s rRNA gene revealed that granular feed induced intestinal microbiota dysbiosis in the squabs. The use of granular feed reduced the relative abundance of gut microorganisms in functional categories related to lipid and energy metabolism, resulting in a decrease in the relative abundance of beneficial bacteria such as Bifidobacterium, Ligilactobacillus, Atopobium, and an increase in that of inflammation-related Limosilactobacillus, which likely inhibited squab intestinal development and growth. Although the use of granular feed can improve breeder metabolism, it affect the composition of the microbial community and gut development of squabs. Therefore, the use of granular feed in production should be more careful to avoid causing growth obstruction of squab.