The antioxidant effects of butylated hydroxytoluene on cryopreserved goat sperm from a proteomic perspective.

At present, there are few reports about the proteomics changes provoked by butylated hydroxytoluene (BHT) supplementation on cryopreserved semen in mammals. Thus, we aimed to evaluate the effects of different concentrations of BHT on goat sperm and to investigate the proteomics changes of adding BHT to cryopreserved goat (Capra hircus) sperm. Firstly, semen samples were collected from four goats, and frozen in the basic extenders containing different concentrations of BHT (0.5 mM, 1.0 mM, 2.0 mM) and a control without BHT, respectively. After thawing, the protective effects of dose-dependent replenished BHT to the freezing medium on post-thaw sperm motility, integrities of plasma membrane and acrosome, reactive oxygen species levels were confirmed, with 0.5 mM BHT being the best (B group) as compared to the control (without BHT, C group). Afterwards, TMT-based quantitative proteomic technique was performed to profile proteome of the goat sperm between C group and B group. Parallel reaction monitoring was used to confirm reliability of the data. Overall, 2,476 proteins were identified and quantified via this approach. Comparing the C and B groups directly (C vs. B), there were 17 differentially abundant proteins (DAPs) po-tentially associated with sperm characteristics and functions were identified, wherein three were upregulated and 14 were downregulated, respectively. GO annotation analysis demonstrated the potential involvement of the identified DAPs in metabolic process, multi-organism process, reproduction, reproductive process, and cellular process. KEGG enrichment analysis further indicated their potential roles in renin-angiotensin system and glutathione metabolism pathways. Together, this novel study clearly shows that BHT can effectively improve quality parameters and fertility potential of post-thawed goat sperm at the optimal concentration, and its cryoprotection may be realized through regulation of sperm metabolism and antioxidative capability from the perspective of sperm proteomic modification.

Impact of Varying Dietary Calcium Contents on the Gut Metabolomics of Yunnan Semi-Fine Wool Sheep (Ovis aries).

Yunnan semi-fine wool (YSFW) is a recently developed dual-purpose (meat and wool) sheep breed mainly found in Yunnan Province, China. Moreover, dietary calcium is essential for animal health and productivity. The current experiment aimed to investigate the impact of dietary calcium on sheep gut metabolite profile. For this, thirty YSFW rams (male, age = 10 months, and body weight = 40.37 ± 0.49 kg) were randomized into three groups (n = 10 rams/group), followed by a completely randomized design, and the groups were allotted to one of three dietary calcium levels (Q_1 = 0.50%, Q_3 = 0.73%, and Q_5 = 0.98% on a dry basis). The rams were fed ad libitum by feeding twice a day (at 08:00 and 17:00 h/day) throughout the experimental period (44 day). On the 21st day of the experiment, fecal samples were collected from 27 rams (9/group) and untargeted metabolite profiling was performed by using ultra-performance liquid chromatography. The PCA plot showed that the Q_5 group metabolites were clustered more tightly than for Q_1 and Q_3, respectively. The tightly clustering molecules were mainly alkaloids and their derivatives, benzenoids, lignans and related compounds, lipids, nucleotides, organic acids, and nitrogenous-based derivatives. According to the Kyoto Encyclopedia of Genes and Genomes pathway analysis, these molecules potentially contribute to metabolic pathways, biosynthesis of secondary metabolites, proteinaceous compounds, and the metabolism of the protein derivatives, particularly amino acids. The PLS-DA plots revealed a significant difference between the Q_1, Q_3, and Q_5 groups, suggesting that Q_5 had a clear separation across the groups. Based on the metabolomic analysis, feeding different levels of dietary calcium significantly changed the metabolomic profile of YSFW rams, which primarily entails metabolic pathways such as energy, protein, and lipid metabolism.

Dietary Energy and Protein Levels Influence the Mutton Quality and Metabolomic Profile of the Yunshang Black Goat.

This study aimed to evaluate the impact of dietary energy and protein levels on the meat quality and metabolomic profile of Yunshang black goats. For this, 80 Yunshang black goats (male, 6 months old, with a mean live body weight of 35.82 ± 2.79 kg) were used in a completely randomized design with a 2 × 2 factorial dietary arrangement. The dietary treatments were (1) high energy (9.74 MJ/kg) with high protein (12.99%) (HEHP), (2) high energy (9.76 MJ/kg) with low protein (10.01%) (HELP), (3) low energy (8.18 MJ/kg) with high protein (13.04%) (LEHP), and (4) low energy (8.14 MJ/kg) with low protein (10.05%) (LELP). The experiment lasted 64 days, including 14 days for dietary adaptation and a 50-day feeding trial. At the end of the experiment, four animals from each treatment were slaughtered to assess their meat quality and metabolomic profiles. The pH value was greater for the goats fed the LELP diet compared with the other treatments. The LEHP-fed group's meat was brighter (L*) than that of the other three groups. The HEHP-fed group had considerably more tender meat (p < 0.05) compared with the LEHP-fed group. Moreover, 72 and 183 differentiated metabolites were detected in the longissimus muscle samples by using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, respectively. The hydropathy and volatilities of raw meat were different (p < 0.05), suggesting changes in the meat flavor because of the dietary treatments. Based on the results, it can be concluded that feeding a high-energy- and high-protein-containing diet improved the tenderness, flavor, and fatty acid contents of mutton.

Association of litter size with the ruminal microbiome structure and metabolomic profile in goats.

The Yunshang black goat is a renowned mutton specialist breed mainly originating from China that has excellent breeding ability with varying litter sizes. Litter size is an important factor in the economics of goat farming. However, ruminal microbiome structure might be directly or indirectly regulated by pregnancy-associated factors, including litter sizes. Therefore, the current experiment aimed to evaluate the association of different litter sizes (low versus high) with ruminal microbiome structure by 16S rRNA gene sequencing and metabolomic profiling of Yunshang black does. A total of twenty does of the Yunshang Black breed, approximately aged between 3 and 4 years, were grouped (n = 10 goats/group) into low (D-l) and high (D-h) litter groups according to their litter size (the lower group has ≤ 2 kids/litter and the high group has ≧ 3 kids/litter, respectively). All goats were sacrificed, and collected ruminal fluid samples were subjected to 16S rRNA sequencing and LC-MS/MC Analysis for ruminal microbiome and metabolomic profiling respectively. According to PCoA analysis, the ruminal microbiota was not significantly changed by the litter sizes among the groups. The Firmicutes and Bacteroidetes were the most dominant phyla, with an abundance of 55.34% and 39.62%, respectively. However, Ruminococcaceae_UCG-009, Sediminispirochaeta, and Paraprevotella were significantly increased in the D-h group, whereas Ruminococcaceae_UCG-010 and Howardella were found to be significantly decreased in the D-l group. The metabolic profiling analysis revealed that litter size impacts metabolites as 29 and 50 metabolites in positive and negative ionic modes respectively had significant differences in their regulation. From them, 16 and 24 metabolites of the D-h group were significantly down-regulated in the positive ionic mode, while 26 metabolites were up-regulated in the negative ionic mode for the same group. The most vibrant identified metabolites, including methyl linoleate, acetylursolic acid, O-desmethyl venlafaxine glucuronide, melanostatin, and arginyl-hydroxyproline, are involved in multiple biochemical processes relevant to rumen roles. The identified differential metabolites were significantly enriched in 12 different pathways including protein digestion and absorption, glycerophospholipid metabolism, regulation of lipolysis in adipocytes, and the mTOR signaling pathway. Spearman's correlation coefficient analysis indicated that metabolites and microbial communities were tightly correlated and had significant differences between the D-l and D-h groups. Based on the results, the present study provides novel insights into the regulation mechanisms of the rumen microbiota and metabolomic profiles leading to different fertility in goats, which can give breeders some enlightenments to further improve the fertility of Yunshang Black goats.

Remodeling the hepatic immune microenvironment and demolishing T cell traps to enhance immunotherapy efficacy in liver metastasis.

Immune checkpoint inhibitors (ICIs) exhibit compromised therapeutic efficacy in many patients with advanced cancers, particularly those with liver metastases. Much of this incapability can be ascribed as an irresponsiveness resulting from the "cold" hepatic tumor microenvironment that acts as T cell "traps" for which there currently lack countermeasures. We report a novel nanomedicine that converts the hepatic immune microenvironment to a "hot" phenotype by targeting hepatic macrophage-centric T cell elimination. Using the nanomedicine, composed of KIRA6 (an endothelium reticulum stress inhibitor), α-Tocopherol nanoemulsions, and anti-PD1 antibodies, we found its potency in murine models of orthotopic colorectal tumors and hepatic metastases, restoring immune responses and enhancing anti-tumor effects. A post-treatment scrutiny of the immune microenvironment landscape in the liver reveals repolarization of immunosuppressive hepatic macrophages, upregulation of Th1-like effector CD4+ T cells, and rejuvenation of dendritic cells along with CD8+ T cells. These findings suggest adaptations of liver-centric immune milieu modulation strategies to improve the efficacy of ICIs for a variety of "cold" tumors and their liver metastases.

Calcium Requirement of Yunnan Semi-fine Wool Rams (Ovis aries) Based on Growth Performance, Calcium Utilization, and Selected Serum Biochemical Indexes.

Calcium (Ca) is required for the growth and development of sheep, but the requirement of Yunnan semi-fine wool (YSW) rams remains uncovered. The current study aims to estimate the Ca requirement of growing YSW rams based on their growth performance, Ca utilization, and serum biochemical indexes. Forty-five YSW rams (10-month-olds) were randomly allocated to five dietary treatments with varying Ca levels of 0.50% (D1), 0.68% (D2), 0.73% (D3), 0.89% (D4), and 0.98% (D5). A higher value for average daily gain and a lower value for the feed conversion ratio were observed in the D3 group compared to the D5 group (p < 0.05). The dry matter intake amount changed quadratically with the increased Ca levels (p < 0.05). The levels of Ca intake, fecal Ca, and excreted Ca were significantly higher in the D5 group than those in the D1 group (p < 0.05). The apparent Ca digestibility rate and the Ca retention rate were significantly higher in the D4 group than in the D1 group (p < 0.05). The serum Ca concentration increased linearly with the incremental levels of dietary Ca (p < 0.05). The activity of alkaline phosphatase was significantly higher in the D1 group than in the D2 group (p < 0.05). The serum levels of hydroxyproline, osteocalcin, and calcitonin decreased from the D1 group to the D2 group, and then significantly ascended (p < 0.05) with the dietary Ca levels from the D3 group to the D5 group. The serum parathyroid hormone content was elevated from the D1 group to the D3 group and then decreased from the D4 group to the D5 group. After calculation, the daily net Ca requirement for the maintenance of YSW rams was 0.073 g/kg of BW0.75, and the daily total Ca requirement was 0.676 g/kg of BW0.75. To optimize the growth performance and the Ca utilization of YSW rams, the recommended dietary Ca level ranges from 0.73% to 0.89% based on this study.

ZoomNeXt: A Unified Collaborative Pyramid Network for Camouflaged Object Detection.

Recent camouflaged object detection (COD) attempts to segment objects visually blended into their surroundings, which is extremely complex and difficult in real-world scenarios. Apart from the high intrinsic similarity between camouflaged objects and their background, objects are usually diverse in scale, fuzzy in appearance, and even severely occluded. To this end, we propose an effective unified collaborative pyramid network that mimics human behavior when observing vague images and videos, i.e. zooming in and out. Specifically, our approach employs the zooming strategy to learn discriminative mixed-scale semantics by the multi-head scale integration and rich granularity perception units, which are designed to fully explore imperceptible clues between candidate objects and background surroundings. The former's intrinsic multi-head aggregation provides more diverse visual patterns. The latter's routing mechanism can effectively propagate inter-frame differences in spatiotemporal scenarios and be adaptively deactivated and output all-zero results for static representations. They provide a solid foundation for realizing a unified architecture for static and dynamic COD. Moreover, considering the uncertainty and ambiguity derived from indistinguishable textures, we construct a simple yet effective regularization, uncertainty awareness loss, to encourage predictions with higher confidence in candidate regions. Our highly task-friendly framework consistently outperforms existing state-of-the-art methods in image and video COD benchmarks.

Multi-organ developmental toxicity and its characteristics in fetal mice induced by dexamethasone at different doses, stages, and courses during pregnancy.

Dexamethasone is widely used in pregnant women at risk of preterm birth to reduce the occurrence of neonatal respiratory distress syndrome and subsequently reduce neonatal mortality. Studies have suggested that dexamethasone has developmental toxicity, but there is a notable absence of systematic investigations about its characteristics. In this study, we examined the effects of prenatal dexamethasone exposure (PDE) on mother/fetal mice at different doses (0.2, 0.4, or 0.8 mg/kg b.i.d), stages (gestational day 14-15 or 16-17) and courses (single- or double-course) based on the clinical practice. Results showed that PDE increased intrauterine growth retardation rate, and disordered the serum glucose, lipid and cholesterol metabolic phenotypes, and sex hormone level of mother/fetal mice. PDE was further discovered to interfere with the development of fetal lung, hippocampus and bone, inhibits steroid synthesis in adrenal and testis, and promotes steroid synthesis in the ovary and lipid synthesis in the liver, with significant effects observed at high dose, early stage and double course. The order of severity might be: ovary > lung > hippocampus/bone > others. Correlation analysis revealed that the decreased serum corticosterone and insulin-like growth factor 1 (IGF1) levels were closely related to PDE-induced low birth weight and abnormal multi-organ development in offspring. In conclusion, this study systematically confirmed PDE-induced multi-organ developmental toxicity, elucidated its characteristics, and proposed the potential "glucocorticoid (GC)-IGF1" axis programming mechanism. This research provided an experimental foundation for a comprehensive understanding of the effect and characteristics of dexamethasone on fetal multi-organ development, thereby guiding the application of "precision medicine" during pregnancy.

A Long-Acting Lyotropic Liquid Crystalline Implant Promotes the Drainage of Macromolecules by Brain-Related Lymphatic System in Treating Aged Alzheimer's Disease.

Numerous evidence has demonstrated that the brain is not an immune-privileged organ but possesses a whole set of lymphatic transport system, which facilitates the drainage of harmful waste from brains to maintain cerebral homeostasis. However, as individuals age, the shrinkage and dysfunction of meningeal and deep cervical lymphatic networks lead to reduced waste outflow and elevated neurotoxic molecules deposition, further inducing aging-associated cognitive decline, which act as one of the pathological mechanisms of Alzheimer's disease. Consequently, recovering the function of meningeal and deep cervical lymph node (dCLNs) networks (as an important part of the brain waste removal system (BWRS)) of aged brains might be a feasible strategy. Herein we showed that the drug brain-entering efficiency was highly related to administration routes (oral, subcutaneous, or dCLN delivery). Besides, by injecting a long-acting lyotropic liquid crystalline implant encapsulating cilostazol (an FDA-approved selective PDE-3 inhibitor) and donepezil hydrochloride (a commonly used symptomatic relief agent to inhibit acetylcholinesterase for Alzheimer's disease) near the deep cervical lymph nodes of aged mice (about 20 months), an increase of lymphatic vessel coverage in the nodes and meninges was observed, along with accelerated drainage of macromolecules from brains. Compared with daily oral delivery of cilostazol and donepezil hydrochloride, a single administered dual drugs-loaded long-acting implants releasing for more than one month not only elevated drug concentrations in brains, improved the clearing efficiency of brain macromolecules, reduced Aß accumulation, enhanced cognitive functions of the aged mice, but improved patient compliance as well, which provided a clinically accessible therapeutic strategy toward aged Alzheimer's diseases.

Ultralong Stability of Ti3 C2 Tx -MXene Dispersion Through Synergistic Regulation of Storage Environment and Defect Capping with Tris-HCl Buffering.

Aqueous MXene dispersion suffers from a bottleneck issue of oxidation, leading to its gradual deterioration and ultimately compromised physicochemical characteristics. Herein, Tris-HCl buffer is employed to stabilize the diluted Ti3 C2 Tx -MXene dispersion (0.05 mg mL-1 ) through the synergy of its potent pH-regulation capability and capping effect toward oxidation-susceptible defects/edges. Tris-HCl functionalized Ti3 C2 Tx maintained its original morphology, structure, and favorable dispersity even after 150 days of aging under naturally aerated conditions. The pH-regulation nature of Tris-HCl is elucidated through solution monitoring of Ti3 C2 Tx dispersion, while the adsorption of Tris-HCl onto defects/edges is revealed by spectral analysis and multi-scale simulations. Tris-HCl at the neutral pH can bind to the negatively charged basal plane of Ti3 C2 Tx via + HTris moiety, while the other moiety (Tris) interacts with the exposed edge-based Ti atoms and/or intrinsic defects, forming a Ti─N bond that prevents MXene from attack by H2 O and O2 . Besides, Tris-HCl stabilized Ti3 C2 Tx exhibited nearly identical capacitive characteristics to its freshly-etched counterpart, indicating the minimal impact of Tris-HCl on electrochemical performance of Ti3 C2 Tx during long-term storage. This study provides practical guidance for stabilizing MXene in their native aqueous dispersion without compromising the inherent properties.

High-Performance Engineered Composites Biofabrication Using Fungi.

Various natural polymers offer sustainable alternatives to petroleum-based adhesives, enabling the creation of high-performance engineered materials. However, additional chemical modifications and complicated manufacturing procedures remain unavoidable. Here, a sustainable high-performance engineered composite that benefits from bonding strategies with multiple energy dissipation mechanisms dominated by chemical adhesion and mechanical interlocking is demonstrated via the fungal smart creative platform. Chemical adhesion is predominantly facilitated by the extracellular polymeric substrates and glycosylated proteins present in the fungal outer cell walls. The dynamic feature of non-covalent interactions represented by hydrogen bonding endows the composite with extensive unique properties including healing, recyclability, and scalable manufacturing. Mechanical interlocking involves multiple mycelial networks (elastic modulus of 2.8 GPa) binding substrates, and the fungal inner wall skeleton composed of chitin and ß-glucan imparts product stability. The physicochemical properties of composite (modulus of elasticity of 1455.3 MPa, internal bond strength of 0.55 MPa, hardness of 82.8, and contact angle of 110.2°) are comparable or even superior to those of engineered lignocellulosic materials created using petroleum-based polymers or bioadhesives. High-performance composite biofabrication using fungi may inspire the creation of other sustainable engineered materials with the assistance of the extraordinary capabilities of living organisms.

A physiologically based toxicokinetic model of P-glycoprotein transporter-mediated placenta perfusion of dexamethasone in the pregnant rat.

The present dosage of Dexamethasone (DEX) administered to pregnant women may pose a risk of toxicity to their unborn offspring. We aimed to develop a maternal-fetal physiologically based toxicokinetic (PBTK) model for DEX in pregnant rats, with a specific focus on the role of the P-glycoprotein (P-gp) transporter in placenta perfusion, and finally facilitate the optimization of clinical DEX dosage. We conducted animal experiments to determine DEX concentrations in various rat tissues, and constructed the PBTK model using MATLAB software. Sensitivity analysis was performed to assess input parameters and the model stability, with fold error (FE) values serving as evaluation indices. Our results indicate the successful construction of the PBTK model, with the fitting key parameters such as the absorption rate constant (Ka), intrinsic hepatic clearance (CLh,int) and intrinsic P-gp clearance (CLint,P-gp). The median concentration of DEX in maternal plasma, fetal plasma, fetal lung, and fetal brain were determined, which allowed us to fit the tissue-to-plasma partition coefficients for the fetal lung (Kp,lung,f) and fetal brain (Kp,brain,f). After making adjustments, all calculated FE values were found to be less than 2, demonstrating the acceptability and accuracy of our model's predictions. Our model integrated external literature data and internal animal experimentation to comprehensively evaluate the maternal-fetal PK characteristics of DEX. These findings provide valuable support for the optimization of clinical DEX dosing.

Perioperative neurocognitive disorder changes in elderly diabetes patients within 30 days after surgery: a retrospective cohort study.

BACKGROUND: Perioperative neurocognitive disorders (PND) are a common central nervous system complication that predominantly affects the elderly. PND after surgery includes postoperative delirium (POD), delayed neurocognitive recovery up to 30 days (DNR), and postoperative neurocognitive disorder up to 12 months. Diabetes is an important independent risk factor for PND. Over the years, few studies have assessed the incidence of PND and the difference in serum biomarkers between diabetic and non-diabetic patients. We sought to examine the difference in the incidence of PND between elderly diabetic and non-diabetic patients in China and identify the risk factors of PND in elderly diabetics. METHODS: We conducted a secondary and exploratory data analysis from our prior studies, including patients aged 65 years or older who underwent non-cardiac elective surgery with general anesthesia. We used the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and Montreal Cognitive Assessment (MoCA) to assess patient cognition. RESULTS: A total of 236 patients were analyzed; the incidence of PND was significantly higher in diabetic than in non-diabetic patients within 30 days (59.2% vs. 36.8%) (P = 0.022). Multivariate logistic regression analysis showed that the preoperative MoCA was an independent risk factor for PND (odds ratio, 0.88 [0.8 to 0.97]; P = 0.014), and Hosmer-Lemeshow tests showed that it could predict PND in diabetic patients (P = 0.360). According to the maximum Youden index, the optimal cutoff for preoperative MoCA was 21.5 points, yielding a specificity and sensitivity of 88.0% and 55.2% for PND. The levels of glial fibrillary acidic protein (GFAP) and Tau in diabetic patients before and after surgery were significantly higher than in non-diabetic patients among cases of PND (P = 0.002 and 0.011, respectively). CONCLUSION: The incidence of PND is higher in diabetic than in non-diabetic patients in China, and preoperative MoCA is an independent risk factor for PND in diabetics. Meanwhile, the changes in GFAP and p-Tau in diabetic patients who experienced PND were significantly higher than in non-diabetic ones.

Solvent exchange-motivated and tunable in situ forming implants sustaining triamcinolone acetonide release for arthritis treatment.

Arthritis is a syndrome characterized by inflammation in the joints. Triamcinolone acetonide (TA) was used as an anti-inflammatory agent in the treatment of this disease. However, there are limitations to its clinical application, including rapid clearance from the joint cavity, potential joint damage from multiple injections, and adverse joint events. To address these drawbacks, we developed a tunable in situ forming implant loaded with TA. This injectable polymer solution utilized poly (lactic-co-glycolic acid) (PLGA) as an extended-release material. When injected into the joints, the solution solidifies into implants through a solvent exchange in the aqueous environment. The implants demonstrated robust retention at the injection site and released TA over several weeks even months through diffusion and erosion. By adding different proportions of low water-miscible plasticizers, the release period of the drug could be precisely adjusted. The plasticizers-optimized implants exhibited a tough texture, enhancing the therapeutic efficiency and drug safety in vivo. In arthritic model studies, the tunable TA-loaded implants significantly reduced swelling, pain, and motor discoordination, and also showed suppression of arthritis progression to some extent. These findings suggested that TA-loaded ISFI holds promise for managing inflammatory disorders in individuals with arthritis.

Dietary protein levels modulate the gut microbiome composition through fecal samples derived from lactating ewes.

In ruminants, the digestion and utilization of dietary proteins are closely linked to the bacterial populations that are present in the gastrointestinal tract. In the present study, 16S rDNA sequencing, together with a metagenomic strategy was used to characterize the fecal bacteria of ewes in the early lactation stage after feeding with three levels of dietary proteins 8.58%, 10.34%, and 13.93%, in three different groups (H_1), (H_m) and (H_h), respectively. A total of 376,278,516 clean data-points were obtained by metagenomic sequencing. Firmicutes and Bacteroidetes were the dominant phyla, regardless of the dietary protein levels. In the H_h group, the phyla Proteobacteria, Caldiserica, and Candidatus_Cryosericota were less abundant than those in the H_I group. In contrast, Lentisphaerae, Chlamydiae, and Planctomycetes were significantly more abundant in the H_h group. Some genera, such as Prevotella, Roseburia, and Firmicutes_unclassified, were less abundant in the H_h group than those in the H_I group. In contrast, Ruminococcus, Ruminococcaceae_noname, Anaerotruncus, Thermotalae, Lentisphaerae_noname, and Paraprevotella were enriched in the H_h group. The acquired microbial genes were mainly clustered into biological processes; molecular functions; cytosol; cellular components; cytoplasm; structural constituents of ribosomes; plasma membranes; translation; and catalytic activities. 205987 genes were significantly enriched in the H_h group. In contrast, 108129 genes were more abundant in the H_I group. Our findings reveal that dynamic changes in fecal bacteria and their genes are strongly influenced by the levels of dietary proteins. We discovered that differentially expressed genes mainly regulate metabolic activity and KEGG demonstrated the primary involvement of these genes in the metabolism of carbohydrates, amino acids, nucleotides, and vitamins. Additionally, genes responsible for metabolism were more abundant in the H_h group. Investigating fecal bacterial characteristics may help researchers develop a dietary formula for lactating ewes to optimize the growth and health of ewes and lambs.

Effects of graded levels of dietary protein supplementation on milk yield, body weight gain, blood biochemical parameters, and gut microbiota in lactating ewes.

Diet-associated characteristics such as dietary protein levels can modulate the composition and diversity of the gut microbiota, leading to effects on the productive performance and overall health of animals. The objective of this study was to see how changes in dietary protein levels affect milk yield, body weight gain, blood biochemical parameters, and gut microbiota in lactating ewes. In a completely randomized design, eighteen ewes were randomly assigned to three groups (n = 6 ewes/group), and each group was assigned to one of three dietary treatments with different protein contents. The ewes' groups were fed on 8.38% (S-I), 10.42% (S-m), and 13.93% (S-h) dietary protein levels on a dry basis. The body weight gain and milk yield were greater (p < 0.05) in ewes fed the S-h dietary treatment than in those fed the S-m and S-1 diets, respectively. However, milk protein contents were similar (p > 0.05) across the treatments. The blood glucose, total protein, cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, lactate, creatinine, and C-reactive protein contents of lactating ewes were not influenced (p > 0.05) by different dietary protein levels. The alanine transaminase, aminotransferase, and lactate dehydrogenase activities were also not changed (p > 0.05) across the groups. However, blood urea nitrogen and albumin contents of lactating ewes were changed (p < 0.05) with increasing levels of dietary protein, and these metabolite concentrations were higher (p < 0.05) for S-h than the rest of the treatments. In the different treatment groups, Firmicutes and Bacteroidetes were found to be the most dominant phyla. However, the abundance of Lachnospiraceae species decreased as dietary protein levels increased. Within the Bacteroidetes phylum, Rikenellaceae were more abundant, followed by Prevotellaceae, in ewes fed the S-m diet compared to those fed the other diets. Based on the results, feeding at an optimal protein level improved milk yield and body weight gain through modifying the digestive tract's beneficial bacterial communities. The results of blood metabolites suggested that feeding higher-protein diets has no negative impact on health.

Effect of Sodium Dodecyl Sulfate on Stability of MXene Aqueous Dispersion.

MXenes suffer from severe oxidation and progressive degradation in aqueous media due to its poor chemical stability. Herein, sodium dodecyl sulfate (SDS) is employed as an efficient protectant for long-term storage of Ti3 C2 Tx -MXene aqueous dispersion. Experimental data support SDS's capability to protect oxidation-prone sites on Ti3 C2 Tx nanosheets, providing extended colloidal stability of up to 213 days. Concentration-dependent anti-oxidation effect articulates that 1.5 mg mL-1 is deemed as an ideal SDS dose for Ti3 C2 Tx to achieve optimal oxidation-resistance in aqueous solution. Additionally, a chroma strategy is developed to instantly and precisely measure the oxidation degree of Ti3 C2 Tx . Adsorption-driven anti-oxidation efficacy of SDS is further confirmed by optimized conformations with interaction energies of SDS on termination-free and surface-defective Ti3 C2 Tx through multiscale simulations. This proposed route is a step forward in broadening the horizons of experimental and theoretical investigations of MXenes with promising implications for long-term storage and reliable applications.

Oridonin attenuates the progression of atherosclerosis by inhibiting NLRP3 and activating Nrf2 in apolipoprotein E-deficient mice.

Oridonin, a well-known traditional Chinese herbal medicinal product isolated from Isodon rubescens (Hemsl.) H.Hara, has many potential properties, including anti-inflammatory and antioxidant activities. However, there is no evidence whether oridonin have a protective effect on atherosclerosis. This study focused on the effects of oridonin on oxidative stress and inflammation generated from atherosclerosis. The therapeutic effect on atherosclerosis was evaluated by intraperitoneal injection of oridonin in a high-fat fed ApoE-/- mouse model. We isolated mouse peritoneal macrophages and detected the effect of oridonin on oxidized low-density lipoprotein-induced lipid deposition. Oil red O staining, Masson's staining, dihydroethidium fluorescence staining, immunohistochemical staining, western blotting analysis, immunofluorescence, enzyme-linked immunosorbent assay and quantitative real-time PCR were used to evaluate the effect on atherosclerosis and explore the mechanisms. Oridonin treatment significantly alleviated the progression of atherosclerosis, reduced macrophage infiltration and stabilized plaques. Oridonin could significantly inhibit inflammation associated with NLRP3 activation. Oridonin significantly reduced oxidative stress by blocking Nrf2 ubiquitination and degradation. We also found that oridonin could prevent the formation of foam cells by increasing lipid efflux protein and reducing lipid uptake protein in macrophages. Oridonin has a protective effect on atherosclerosis in ApoE-/- mice, which may be related to the inhibition of NLRP3 and the stabilization of Nrf2. Therefore, oridonin may be a potential therapeutic agent for atherosclerosis.

CAVER: Cross-Modal View-Mixed Transformer for Bi-Modal Salient Object Detection.

Most of the existing bi-modal (RGB-D and RGB-T) salient object detection methods utilize the convolution operation and construct complex interweave fusion structures to achieve cross-modal information integration. The inherent local connectivity of the convolution operation constrains the performance of the convolution-based methods to a ceiling. In this work, we rethink these tasks from the perspective of global information alignment and transformation. Specifically, the proposed cross-modal view-mixed transformer (CAVER) cascades several cross-modal integration units to construct a top-down transformer-based information propagation path. CAVER treats the multi-scale and multi-modal feature integration as a sequence-to-sequence context propagation and update process built on a novel view-mixed attention mechanism. Besides, considering the quadratic complexity w.r.t. the number of input tokens, we design a parameter-free patch-wise token re-embedding strategy to simplify operations. Extensive experimental results on RGB-D and RGB-T SOD datasets demonstrate that such a simple two-stream encoder-decoder framework can surpass recent state-of-the-art methods when it is equipped with the proposed components.

The role of chondrocyte-to-osteoblast trans-differentiation in fetal bone dysplasia of mice caused by prenatal exposure to dexamethasone.

Maternal exposure to dexamethasone can cause developmental toxicity of long bones in offspring. However, the effect of dexamethasone on the trans-differentiation of growth plate chondrocytes into osteoblasts and its role in bone dysplasia of fetuses caused by prenatal dexamethasone exposure (PDE) remains unclear. In this study, pregnant mice were treated with different doses, stages, and courses of dexamethasone according to clinical practice to reveal the phenomenon. Further, growth plate chondrocytes were treated with dexamethasone in vitro to clarify the phenomenon and mechanism. The results showed that PDE caused dysplasia of fetal long bones in female and male mice, accompanied by the delayed formation of the primary ossification center and the widening hypertrophic zone of growth plate cartilage. Meanwhile, PDE increased the number of hypertrophic chondrocytes at growth plate cartilage and decreased the number of osteoblasts at the primary ossification center. Moreover, PDE significantly decreased the expression of osteogenic transcription factor Runx2 but increased the expression of hypertrophic chondrocytes marker Col10. These above phenomena were more significant in the high dose, early stage, and double courses of dexamethasone exposure groups, and the male fetal mice showed more obvious than the female fetal mice. In vitro, dexamethasone significantly inhibited the trans-differentiation of growth plate chondrocytes into osteoblasts, accompanied by a decrease in Runx2 expression and an increase in Col10 expression. In conclusion, this study revealed the phenomenon and mechanism of fetal bone dysplasia caused by PDE from the new perspective of trans-differentiation disorder of growth plate chondrocytes to osteoblasts.