Head and Neck Osteosarcoma: Perineural Invasion is Associated With Disease-Free Survival and Tumor Metastasis.

BACKGROUND: Head and neck osteosarcoma (HNOS) is the most common bone malignancy in the head and neck region, accounting for 10% of all osteosarcoma cases. Perineural invasion (PNI) is a notable indication of aggressive tumor behavior, which includes the phenomenon of tumor cells invading any of the 3 layers of the nerve sheath or tumor cells gathering, encircling one-third of the nerve circumference, and infiltrating and metastasizing along the nerve. PNI has been reported in various malignant tumors and is considered to be linked to poor prognosis. PURPOSE: The study's purpose is to measure the association between PNI and survival outcomes in patients with HNOS. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study focused on HNOS patients who underwent surgery at the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital School of Medicine, Shanghai Jiao Tong University, from January 1, 2019 to December 31, 2021. Patients who did not undergo complete surgical resection of the tumor, did not receive a conventional osteosarcoma diagnosis, and had positive surgical margins were eliminated. PREDICTOR VARIABLE: The predictor variable is PNI status. The pathological section of the tumor was consistent with any of the PNI features, which was considered PNI-positive. MAIN OUTCOME VARIABLE(S): The primary outcome variables were 3-year disease-free survival (DFS) and 3-year overall survival. Secondary outcomes were 3-year tumor local recurrence and 3-year metastasis (MT). COVARIATES: Covariates were categorized into the following categories: demographic variables (age, sex), clinical variables (tumor region, primary tumor), and treatment variables (chemotherapy, radiotherapy). ANALYSES: Analytic statistical methods were used for the data analysis. Pearson χ2 or Fisher's exact test was used to describe the baseline data. Kaplan-Meier is used to calculate survival rates. The Cox regression model was adapted for univariate and multivariate analysis. A P value less than .05 indicated statistical significance. RESULTS: The study sample comprised 70 patients; 33 (47.1%) were male, and the mean age was 42.2 (standard deviation: 16.7) years. There were 15 (21.4%) cases of PNI. The 3-year DSF rate and OS rate were 67.3% and 82.0%, respectively. PNI-positive resulted in higher risk for MT (P ＜ .01, hazard ratio: 5.95, 95% confidence interval: 1.62-21.86) and negative impact on DFS (P < .01, hazard ratio: 6.35, 95% confidence interval: 2.11-19.17) for HNOS patients. CONCLUSION AND RELEVANCE: Positive PNI status was associated with decreased DFS and increased risk of MT.

CRB3 navigates Rab11 trafficking vesicles to promote γTuRC assembly during ciliogenesis.

The primary cilium plays important roles in regulating cell differentiation, signal transduction, and tissue organization. Dysfunction of the primary cilium can lead to ciliopathies and cancer. The formation and organization of the primary cilium are highly associated with cell polarity proteins, such as the apical polarity protein CRB3. However, the molecular mechanisms by which CRB3 regulates ciliogenesis and the location of CRB3 remain unknown. Here, we show that CRB3, as a navigator, regulates vesicle trafficking in γ-tubulin ring complex (γTuRC) assembly during ciliogenesis and cilium-related Hh and Wnt signaling pathways in tumorigenesis. Crb3 knockout mice display severe defects of the primary cilium in the mammary ductal lumen and renal tubule, while mammary epithelial-specific Crb3 knockout mice exhibit the promotion of ductal epithelial hyperplasia and tumorigenesis. CRB3 is essential for lumen formation and ciliary assembly in the mammary epithelium. We demonstrate that CRB3 localizes to the basal body and that CRB3 trafficking is mediated by Rab11-positive endosomes. Significantly, CRB3 interacts with Rab11 to navigate GCP6/Rab11 trafficking vesicles to CEP290, resulting in intact γTuRC assembly. In addition, CRB3-depleted cells are unresponsive to the activation of the Hh signaling pathway, while CRB3 regulates the Wnt signaling pathway. Therefore, our studies reveal the molecular mechanisms by which CRB3 recognizes Rab11-positive endosomes to facilitate ciliogenesis and regulates cilium-related signaling pathways in tumorigenesis.

Bta-miR-484 Targets SFRP1 and Affects Preadipocytes Proliferation, Differentiation, and Apoptosis.

MicroRNAs (miRNAs) are essential regulators of numerous biological processes in animals, including adipogenesis. Despite the abundance of miRNAs associated with adipogenesis, their exact mechanisms of action remain largely unknown. Our study highlights the role of bta-miR-484 as a major regulator of adipocyte proliferation, apoptosis, and differentiation. Here, we demonstrated that the expression of bta-miR-484 initially increased during adipogenesis before decreasing. Overexpression of bta-miR-484 in adipocytes ultimately inhibited cell proliferation and differentiation, reduced the number of EdU fluorescence-stained cells, increased the number of G1 phase cells, reduced the number of G2 and S phase cells, and downregulated the expression of proliferation markers (CDK2 and PCNA) and differentiation markers (CEBPA, FABP4, and LPL). Additionally, overexpression of bta-miR-484 promoted the expression of apoptosis-related genes (Caspase 3, Caspase 9, and BAX), and increased the number of apoptotic cells observed via flow cytometry. In contrast, bta-miR-484 inhibition in adipocytes yielded opposite effects to those observed during bta-miR-484 overexpression. Moreover, luciferase reporter assays confirmed SFRP1 as a target gene of bta-miR-484, and revealed that bta-miR-484 downregulates SFRP1 mRNA expression. These findings offer compelling evidence that bta-miR-484 targets SFRP1, inhibits proliferation and differentiation, and promotes apoptosis. Therefore, these results offer novel insights into the bta-miR-484 regulation of adipocyte growth and development.

Effects of different starch structures on energy metabolism in pigs.

BACKGROUND: Starch is a major component of carbohydrates and a major energy source for monogastric animals. Starch is composed of amylose and amylopectin and has different physiological functions due to its different structure. It has been shown that the energy supply efficiency of amylose is lower than that of amylopectin. However, there are few studies on the effect of starch structure on the available energy of pigs. The purpose of this study was to measure the effect of different structures of starch in the diet on the net energy (NE) of pigs using a comparative slaughter method and to establish a prediction equation to estimate the NE of starch with different structures. Fifty-six barrows (initial BW 10.18 ± 0.11 kg) were used, and they were housed and fed individually. Pigs were divided into 7 treatments, with 8 replicates for each treatment and 1 pig for each replicate. One of the treatments was randomly selected as the initial slaughter group (ISG). Pigs in the remaining treatments were assigned to 6 diets, fed with basic diet and semi-pure diets with amylose/amylopectin ratio (AR) of 3.09, 1.47, 0.25, 0.15 and 0.12, respectively. The experiment lasted for 28 d. RESULTS: Results showed that compared with the high amylose (AM) groups (AR 3.09 and 1.47), the high amylopectin (AP) group (AR 0.15) significantly increased the final BW, average daily weight gain and average daily feed intake of pigs (P < 0.05), but the F:G of the AM group was lower (P < 0.01). In addition, AR 0.15 and 0.12 groups have higher (P < 0.01) nutrient digestibility of dry matter, crude protein, gross energy and crude ash. Meanwhile, compared with other groups, AR 0.15 group has a higher (P < 0.05) NE intake and energy retention (RE). The regressive equation for predicting with starch structures was established as RE = 1,235.243 - 48.298AM/AP (R2 = 0.657, P = 0.05). CONCLUSIONS: In conclusion, NE intake and RE of pigs augmented with the increase of dietary amylopectin content, indicating that diets high in amylopectin were more conducive to promoting the growth of pigs in the late conservation period.

Discovery of drug lead compounds for Anti-Alzheimer's disease on the basis of synaptic plasticity.

Alzheimer's disease (AD) is a progressive neurodegenerative disease commonly seen in the middle-aged and the elder. Its clinical presentations are mainly memory impairment and cognitive impairment. Its cardinal pathological features are the deposition of extracellular Amyloid-ß (Aß), intracellular neurofibrillary tangles and synaptic dysfunction. The etiology of AD is complex and the pathogenesis remains unclear. Having AD would lead to awful living experience of it's patients, which may be a burden to the patient even to the public health care system. However, there are no certain cure for AD. Thus it's significant for both medical value and social meaning to find the way to cure or prevent AD and to research on the pathogenesis of AD. In this work, the molecular docking technology, pharmacokinetic analysis and pharmacological experiments were employed to analyse the natural active compounds and the mechanisms against AD based on the synaptic plasticity. A total of seven target proteins related to the synaptic plasticity and 44 natural active compounds with potential to enhance the synaptic plasticity were obtained through a literature review and network pharmacological analysis. Computer-Aided Drug Design (CADD) method was used to dock the anti-AD key target proteins with the 44 compounds. The compounds with good binding effect were screened. Three anti-AD active compounds based on the synaptic plasticity were obtained, including Curcumin, Withaferin A and Withanolide A. In addition, pharmacological experiments were carried out on Withaferin A and Withanolide A based on its good docking results. The experimental results showed that Withaferin A has good anti-AD potential and great potential to enhance synaptic plasticity. The anti-AD effect can be achieved through a multi-target synergistic mechanism.

The sustainable production of succinic anhydride from renewable biomass.

The selective production of C4 bulk chemicals from biomass is significant to replace the traditional method from petroleum resource. In this work, the succinic anhydride (SAN) is directly prepared from bio-based furanic platform compounds utilizing the visible light-induced oxygenation process, in which m-tetraphenyl porphyrin (H2TPP) and molecular oxygen was employed as the photocatalyst and terminal oxidant, respectively. Under optimal conditions, a 99.9% conversion with 97.8% selectivity of SAN was obtained from furoic acid (FAC) at room temperature. Moreover, the transformation of furfural and furfuryl alcohol with this system can also generate SAN, and the product selectivity is controllable by tuning light intensity and time. Furthermore, the EPR detection, isotope labeling, and control experiments exhibited that the generation of singlet oxygen plays a crucial role and 5-hydroxy-2(5H)-furanone is the main intermediate during the reaction. Finally, a possible reaction mechanism for the production of SAN from furanic compound is proposed.

KLF2 is a clinical diagnostic and treatment biomarker of breast cancer.

Background: As a highly prevalent malignancy among women worldwide, breast cancer, remains a critical public health issue necessitating the development of novel therapeutics and biomarkers. Kruppel Like Factor 2 (KLF2), a member of the Kruppel family of transcription factors, has been implicated in various types of cancer due to its diminished expression; however, the potential implications of KLF2 expression in relation to breast cancer progression, prognosis, and therapy remain unclear. Methods: The present study employed the Tumor Immune Estimation Resource (TIMER) and The Human Protein Atlas databases to investigate the expression pattern of KLF2 in pan-cancer. The relationship between KLF2 expression and clinical features or immune infiltration of The Cancer Genome Atlas (TCGA) breast cancer samples was evaluated using Breast Cancer Integrative Platform (BCIP) and TIMER. The expression levels of KLF2 in breast cancer were validated via immunohistochemical staining analysis. Gene Set Enrichment Analysis (GSEA) to study the KLF2-related gene ontology. STRING database was employed to construct a protein-protein interaction (PPI) network of KLF2 in relation to vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor 1α (HIF1α). The expression of KLF2 following diverse breast cancer therapies was analyzed in the Gene Expression Omnibus (GEO) databases. The expression of KLF2 following treatment with simvastatin was validated via immunofluorescence and western blotting. Results: Our study reveals that KLF2 displays significantly reduced expression in cancerous tissues compared to non-cancerous controls. Patients with low KLF2 expression levels exhibited poor prognosis across multiple cancer types. KLF2 expression levels were found to be reduced in advanced cancer stages and grades, while positively correlated with the expression of estrogen receptor (ER), progesterone receptor (PR), and tumor size in breast cancer. KLF2 expression is associated with diverse immune infiltration cells, and may impact the breast tumor immune microenvironment by regulating dendritic cell activation. Additionally, we observed a negative correlation between KLF2 expression levels and angiogenesis, as well as the expression of VEGFA and HIF1α. Notably, the anticancer drug simvastatin could induce KLF2 expression in both breast cancer. Conclusion: Based on our observations, KLF2 has potential as a diagnostic, prognostic, and therapeutic biomarker for breast cancer.

Relationship between plasma glutamate and cardiovascular disease risk in Chinese patients with type 2 diabetes mellitus by gender.

Objectives: This study aimed to assess the association between plasma glutamate (Glu) and the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) and whether this association differs by gender. Material and methods: We retrieved clinical information on 1032 consecutive patients with T2DM from a same tertiary care center from May 2015 to August 2016. Glu was quantified by liquid chromatography-tandem mass spectrometry analysis. Glu was converted into a categorical variable based on the median concentration in the whole population, while logistic regression was used to obtain the odds ratio (OR) and 95% confidence interval (CI), and the correlation between Glu and various biochemical indices was analyzed. Results: We found that Glu was positively associated with the risk of CVD in patients with T2DM. This correlation was more significant in women. In T2DM patients, the higher the age, body mass index (BMI), weight and systolic blood pressure (SBP), the lower the glycosylated hemoglobin (HbA1C) concentration and the higher the Glu. In female patients, the correlation between age, weight, BMI, SBP, and plasma Triglycerides (TG), and Glu was also statistically significant. Conclusion: In conclusion, female T2DM patients with high levels of Glu have a higher risk of developing CVD.

Establishment and validation of a nomogram to predict structural incomplete response in papillary thyroid carcinoma patients: a retrospective study.

OBJECTIVE: To identify risk factors related to structural incomplete response (SIR) in papillary thyroid carcinoma (PTC) and develop a nomogram for PTC patients. METHODS: In this respective study, clinical, ultrasonic, and pathological data of PTC patients treated at our institute between 2016 and 2020 were analyzed. Patients were randomly split into training and validation sets at a ratio of 7:3. Multivariate Cox regression analysis was conducted to determine independent prognostic factors. On the basis of these factors, a nomogram was built to predict SIR. P value, concordance index, calibration plots and decision curve analysis were used to evaluate the model. RESULTS: Multivariate Cox regression analysis showed that BRAF V600E status, lymph node metastasis, sex, tumor size, margin, and surgical procedure were independent prognostic factors. In the validation set, the concordance index of the nomogram was 0.774 (95% confidence interval: 0.703-0.845). Calibration plots at 3 and 5 years showed no apparent difference between predicted SIR probability and the actual SIR proportion. Additionally, the nomogram had good net clinical benefit according to the decision curve analysis compared with cases that were treat-all or treat-none. CONCLUSION: We build a nomogram to predict individualized outcomes and help postoperative surveillance in PTC patients.

Metformin and simvastatin synergistically suppress endothelin 1-induced hypoxia and angiogenesis in multiple cancer types.

Multiple cancers have been reported to be associated with angiogenesis and are sensitive to anti-angiogenic therapies. Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments. However, the underlying anticancer mechanisms of antiangiogenic drugs are still unknown. Metformin (MET) and simvastatin (SVA), two metabolic-related drugs, have been shown to play important roles in modulating the hypoxic tumor microenvironment and angiogenesis. Whether the combination of MET and SVA could exert a more effective antitumor effect than individual treatments has not been examined. The antitumor effect of the synergism of SVA and MET was detected in mouse models, breast cancer patient-derived organoids, and multiple tumor cell lines compared with untreated, SVA, or MET alone. RNA sequencing revealed that the combination of MET and SVA (but not MET or SVA alone) inhibited the expression of endothelin 1 (ET-1), an important regulator of angiogenesis and the hypoxia-related pathway. We demonstrate that the MET and SVA combination showed synergistic effects on inhibiting tumor cell proliferation, promoting apoptosis, alleviating hypoxia, decreasing angiogenesis, and increasing vessel normalization compared with the use of a single agent alone. The MET and SVA combination suppressed ET-1-induced hypoxia-inducible factor 1α expression by increasing prolyl hydroxylase 2 (PHD2) expression. Furthermore, the MET and SVA combination showed a more potent anticancer effect compared with bosentan. Together, our findings suggest the potential application of the MET and SVA combination in antitumor therapy.

Arachidonic acid is associated with dyslipidemia and cholesterol-related lipoprotein metabolism signatures.

Introduction: Abnormal lipoprotein metabolism is associated with a variety of diseases, cardiovascular disease in particular. Free fatty acids (FAs) and triglycerides (TGs) are the principal lipid species in adipocytes and are the major components of lipoproteins. However, in routine clinical laboratory testing, only the total plasma concentrations of FAs and TGs are typically measured. Methods: We collected 965 individuals with hyperlipidemia plasma and clinical characteristics; high-throughput metabolomics permits the accurate qualitative and quantitative assessment of a variety of specific FAs and TGs and their association with lipoproteins; through regression analysis, the correlation between multiple metabolites and routine measured lipid parameters was found. Mice were fed a diet containing AA, and the concentrations of TC and TG in the plasma of mice were detected by enzyme method, western blot and qRT-PCR detected the protein and mRNA levels of cholesterol synthesis and metabolism in mice. Result: Using LC-MS/MS identified eight free FA and 27 TG species in plasma samples, the plasma concentrations of free arachidonic acid (AA) and AA-enriched TG species were significantly associated with the plasma low-density lipoprotein-cholesterol, apolipoprotein B (ApoB), and total cholesterol (TC) concentrations after adjustment for age, sex, the use of lipid-lowering therapy, and body mass index. AA-rich diet significantly increased the plasma concentrations of TC and ApoB and the liver expression of ApoB protein and reduced the protein expression of ATP binding cassette subfamily G members 5 and 8 in mice. Discussion: In this study, it was clarified that the plasma concentrations of free AA- and AA-enriched TG species were significantly associated with the plasma low-density lipoprotein-cholesterol, ApoB, and TC concentrations in individuals with hyperlipidemia, and it was verified that AA could increase the plasma TC level in mice. Taken together, these findings suggest a potential role of AA in the regulation of plasma cholesterol and lipoprotein concentrations.

DPP4 Is a Potential Prognostic Marker of Thyroid Carcinoma and a Target for Immunotherapy.

DPP4 (dipeptidyl peptidase 4) is expressed in many cancers, but the relationship between DPP4 and thyroid carcinoma (THCA) is incompletely understood. We aim to explore the expression of DPP4 in THCA and the correlation between DPP4 expression with the prognosis of THCA and antitumor immunity. We systematically analyzed data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases and explored DPP4 expression, its impact on prognosis, and its relationship with antitumor immunity in THCA. Next, we collected 18 pairs of fresh THCA and adjacent paracancerous tissues and performed RT-qPCR to validate the DPP4 mRNA level. Concurrently, immunohistochemistry (IHC) analysis was performed on 12 pairs of paraffin-embedded tissues of medullary thyroid carcinoma (MTC) and paracancerous tissues to validate the DPP4 protein level. Bioinformatics analysis showed that DPP4 mRNA expression in THCA was significantly higher than that in paracancerous tissues (p < 0.01). DPP4 was expressed at the highest levels in MTC than in other pathological types. The DPP4 expression level was different between groups with different clinical characteristics. The higher the DPP4 expressed in THCA, the lower the disease-free survival (DFS) was (HR = 1.8, p=0.048). DPP4 was significantly correlated with immune cell infiltration and immune response and was positively associated with 21 immune checkpoint genes (ICGs) in THCA (p < 0.05). The results of RT-qPCR showed that the relative mRNA expression of DPP4 was significantly upregulated in 18 THCA tissues compared to that in paracancerous tissues (p=0.011). IHC results showed that the DPP4 protein level was higher in 12 MTC tissues than in paracancerous tissues (p=0.011). In conclusion, DPP4 is a potential prognostic marker of THCA and may become an effective target for immunotherapy.

Identification of necroptosis-related subtypes and prognosis model in triple negative breast cancer.

Background: Necroptosis is considered to be a new form of programmed necrotic cell death, which is associated with metastasis, progression and prognosis of various types of tumors. However, the potential role of necroptosis-related genes (NRGs) in the triple negative breast cancer (TNBC) is unclear. Methods: We extracted the gene expression and relevant clinicopathological data of TNBC from The Cancer Genome Atlas (TCGA) databases and the Gene Expression Omnibus (GEO) databases. We analyzed the expression, somatic mutation, and copy number variation (CNV) of 67 NRGs in TNBC, and then observed their interaction, biological functions, and prognosis value. By performing Lasso and COX regression analysis, a NRGs-related risk model for predicting overall survival (OS) was constructed and its predictive capabilities were verified. Finally, the relationship between risk_score and immune cell infiltration, tumor microenvironment (TME), immune checkpoint, and tumor mutation burden (TMB), cancer stem cell (CSC) index, and drug sensitivity were analyzed. Results: A total 67 NRGs were identified in our analysis. A small number of genes (23.81%) detected somatic mutation, most genes appeared to have a high frequency of CNV, and there was a close interaction between them. These genes were remarkably enriched in immune-related process. A seven-gene risk_score was generated, containing TPSG1, KRT6A, GPR19, EIF4EBP1, TLE1, SLC4A7, ESPN. The low-risk group has a better OS, higher immune score, TMB and CSC index, and lower IC50 value of common therapeutic agents in TNBC. To improve clinical practicability, we added age, stage_T and stage_N to the risk_score and construct a more comprehensive nomogram for predicting OS. It was verified that nomogram had good predictive capability, the AUC values for 1-, 3-, and 5-year OS were 0.847, 0.908, and 0.942. Conclusion: Our research identified the significant impact of NRGs on immunity and prognosis in TNBC. These findings were expected to provide a new strategy for personalize the treatment of TNBC and improve its clinical benefit.

Boosting the Electrocatalytic CO2 Reduction Reaction by Nanostructured Metal Materials via Defects Engineering.

Electrocatalytic CO2 reduction reaction (CO2RR) is one of the most effective methods to convert CO2 into useful fuels. Introducing defects into metal nanostructures can effectively improve the catalytic activity and selectivity towards CO2RR. This review provides the recent progress on the use of metal nanomaterials with defects towards electrochemical CO2RR and defects engineering methods. Accompanying these ideas, we introduce the structure of defects characterized by electron microscopy techniques as the characterization and analysis of defects are relatively difficult. Subsequently, we present the intrinsic mechanism of how the defects affect CO2RR performance. Finally, to promote a wide and deep study in this field, the perspectives and challenges concerning defects engineering in metal nanomaterials towards CO2RR are put forward.

The Association of Homocysteine and Diabetic Retinopathy in Homocysteine Cycle in Chinese Patients With Type 2 Diabetes.

Objective: This study aimed to explore the relationship between homocysteine (Hcy) and diabetic retinopathy (DR) and the impacts of the Hcy pathway on this relationship against this background. Methods: This study retrieved 1979 patients with type 2 diabetes (T2D) from the First Affiliated Hospital of Liaoning Medical University in Jinzhou, Liaoning Province, China. Multiple logistic regression was used to analyze the effects of Hcy cycle on the relationship between Hcy and DR. Spearman's rank correlation analysis was used to analyze the correlation between risk factors related to DR progression and Hcy. Finally, the results of logistic regression were supplemented by mediation analysis. Results: We found there was a negative correlation between low concentration of Hcy and DR (OR : 0.83, 95%CI: 0.69-1). After stratifying all patients by cysteine (Cys) or Methionine (Met), this relationship remained significant only in low concentration of Cys (OR: 0.75, 95%CI: 0.61-0.94). Through the RCS curve, we found that the effect of Hcy on DR presents a U-shaped curve relationship. Mediating effect in Met and Hcy cycles was also significant [Total effect c (OR: 0.968, 95%CI: 0.938-0.998), Direct effect path c' (OR: 0.969, 95%CI: 0.940-0.999), Path a (OR: 1.047, 95%CI: 1.004-1.091), Path b (OR: 0.964, 95%CI: 0.932-0.998)]. Conclusions: The relationship between Hcy and DR presents a U-shaped curve and the homocysteine cycle pathway has an impact on it. And too low concentration of Hcy indicates a lack of other substances, such as vitamins. It is suggested that the progression of DR is the result of a combination of many risk factors. Further prospective studies are needed to determine the role of Hcy in the pathogenesis of DR.

Developmental Profiling of Dietary Carbohydrate Digestion in Piglets.

Carbohydrates are the main source of energy in the diet, accounting for the largest proportion in the diets of humans and monogastric animals. Although recent progress has been made in the study of intestinal carbohydrate digestion in piglets, there is a lack of comprehensive study on the dynamic changes in intestinal carbohydrate digestion with age in the early growth stage of piglets. To fill in this gap of knowledge, we collected samples of the small intestine, pancreatic tissues, and colonic digesta from 42 piglets during newborn [day (d) 0], lactation (d 7, 14), weaning (d 21), and nursery (d 28, 35, and 42) stages. Intestinal and pancreatic tissues and colonic digesta were collected at necropsy and analyzed for morphology, digestive enzyme activities, short-chain fatty acids (SCFA), and microbial abundance. Villus height reached a maximum at 1 week (d 7) in the duodenum and jejunum (P <0.01), and a higher ratio of villus height to crypt depth and lactase activity were observed on d 0 and 7 (P < 0.001) compared to other ages. However, the sucrase and maltase activities were increased with piglets' age. Similar activities of sucrase and maltase were found in the small intestine. In addition, amylase, lipase, and protease activities were assayed in the pancreas. The activity of amylase increased with age, while lipase and protease decreased gradually from birth to weaning (d 21, 28) and then increased after weaning (d 35, 42). Compared with d 0, d 42 increased the abundance of Firmicutes and Bacteroidetes with a higher concentration of total SCFA (P < 0.001) and decreased the abundance of Proteobacteria, but weaning (d 21, 28) increased the abundance of Proteobacteria in the colon. These results indicate that with the increase in piglet age, the carbohydrate digestive function gradually increased, but weaning hindered the development of intestinal function. These results provide us with new insights into the healthy development of piglets' intestines, which may help us to better regulate the physiological health of piglets in the future.

Engineering the degree of concavity of one-dimensional Au-Cu alloy nanorods with partial intermetallic compounds by facile wet chemical synthesis.

Finely modulating the morphology of bimetallic nanomaterials plays a vital role in enhancing their catalytic activities. Among the various morphologies, concave structures have received considerable attention due to the three advantageous features of high-index facets, high surface areas, and high curvatures, which contribute greatly to enhancing the catalytic performance. However, concave morphologies are not the products generated from thermodynamically controlled growth with minimized surface energy. Additionally, most nanocrystals with concave shapes are currently in the state of mono-metals or alloys with disordered arrangements of atoms. The synthesis of alloy structures with ordered atom arrangements, intermetallic compounds, which tend to display superior catalytic performance on account of their optimal geometric and electronic effects, has rarely been reported as high-temperature annealing is usually needed, which constrains the modulation of morphology and surface structure. In this work, concave one-dimensional Au-Cu nanorods with a partially ordered intermetallic structure were synthesized via a facile wet chemical method. By simply adjusting the reaction kinetics via the concentrations of the corresponding metal precursors, the degree of concavity of the one-dimensional Au-Cu nanorods could be regulated. In both the p-nitrophenol reduction and CO2 electro-reduction reactions, the concave-shaped Au-Cu nanorods demonstrated superior catalytic activity compared to corresponding non-concave samples with the same structure due to the morphological advantages provided by the concave structure.

Relationship Between Acylcarnitine and the Risk of Retinopathy in Type 2 Diabetes Mellitus.

Objective: Diabetic retinopathy is a common complication of type 2 diabetes mellitus (T2DM). Due to the limited effectiveness of current prevention and treatment methods, new biomarkers are urgently needed for the prevention and diagnosis of DR. This study aimed to explore the relationships between plasma acylcarnitine with DR in T2DM. Methods: From May 2015 to August 2016, data of 1032 T2DM patients were extracted from tertiary hospitals. Potential non-linear associations were tested by binary logistic regression models, and ORs and 95% CIs of the research variables were obtained. Correlation heat map was used to analyze the correlation between variables. The change of predictive ability was judged by the area under the receiver operating characteristic curve. Results: Of the 1032 patients with T2DM, 162 suffered from DR. After adjusting for several confounding variables, C2 (OR:0.55, 95%CI:0.39-0.76), C14DC (OR:0.64, 95%CI:0.49-0.84), C16 (OR:0.64, 95%CI:0.49-0.84), C18:1OH (OR:0.51, 95%CI:0.36-0.71) and C18:1 (OR:0.60, 95%CI:0.44-0.83) were negatively correlated with DR. The area under the curve increased from 0.794 (95% CI 0.745 to 0.842) to 0.840 (95% CI 0.797 to 0.833) when C2, C14DC, C18:1OH and C18:1 added to the traditional risk factor model. Conclusion: There was a negative correlation between C2, C14DC, C16, C18:1OH, and C18:1 and the risk of retinopathy in patients with T2DM. C2, C14DC, C18:1OH, and C18:1 may be new predictors and diagnostic markers of DR.

Short chain fatty acids for the risk of diabetic nephropathy in type 2 diabetes patients.

AIMS: This study aimed to explore relationships short chain fatty acids with diabetic nephropathy (DN) in type 2 diabetes (T2D) patients. METHODS: We extracted the clinical and omics data of 100 T2D patients and 100 DN patients from April 2018 to April 2019 from a tertiary hospital. Restricted cubic splines were used to examine full-range associations of short chain fatty acids with DN in T2D.Query Logistic regression was used to obtain odds ratio (OR) and confidence interval (CI). RESULTS: Acetate, butyrate and isovalerate were negatively correlated with DN. Isobutyrate was positively correlated with DN. Propionate ≥ 4.4 µg/mL and isobutyrate ≥ 1.4 µg/mL had threshold effects and their increasing levels above the cutoff points were associated with rapid rises in the risk of DN. The additive interaction between high propionate and high isobutyrate in serum significantly increased the risk of DN (OR34.35; 95%CI 7.11 to 166.08). Presence of hypertension further increased the OR of high propionate for DN to 8.27(95%CI 1.82 to 37.57) with a significant additive interaction. The additive interaction of the high isobutyrate and hypertension was not significant. CONCLUSIONS: Acetate, butyrate and isovalerate were negatively associated with DN. Isobutyrate was positively associated with DN. Serum high propionate and high isobutyrate worked independently and synergistically to increase the risk of DN in T2D. Presence of hypertension further amplified the effect of copresence of high propionate on DN risk.

The HVCN1 voltage-gated proton channel contributes to pH regulation in canine ventricular myocytes.

Regulation of intracellular pH (pHi ) in cardiomyocytes is crucial for cardiac function; however, currently known mechanisms for direct or indirect extrusion of acid from cardiomyocytes seem insufficient for energetically efficient extrusion of the massive H+ loads generated under in vivo conditions. In cardiomyocytes, voltage-sensitive H+ channel activity mediated by the HVCN1 proton channel would be a highly efficient means of disposing of H+ , while avoiding Na+ loading, as occurs during direct acid extrusion via Na+ /H+ exchange or indirect acid extrusion via Na+ -HCO3- cotransport. PCR and immunoblotting demonstrated expression of HVCN1 mRNA and protein in canine heart. Patch clamp analysis of canine ventricular myocytes revealed a voltage-gated H+ current that was highly H+ -selective. The current was blocked by external Zn2+ and the HVCN1 blocker 5-chloro-2-guanidinobenzimidazole. Both the gating and Zn2+ blockade of the current were strongly influenced by the pH gradient across the membrane. All characteristics of the observed current were consistent with the known hallmarks of HVCN1-mediated H+ current. Inhibition of HVCN1 and the NHE1 Na+ /H+ exchanger, singly and in combination, showed that either mechanism is largely sufficient to maintain pHi in beating cardiomyocytes, but that inhibition of both activities causes rapid acidification. These results show that HVCN1 is expressed in canine ventricular myocytes and provides a major H+ extrusion activity, with a capacity similar to that of NHE1. In the beating heart in vivo, this activity would allow Na+ -independent extrusion of H+ during each action potential and, when functionally coupled with anion transport mechanisms, could facilitate transport-mediated CO2 disposal. KEY POINTS: Intracellular pH (pHi ) regulation is crucial for cardiac function, as acidification depresses contractility and causes arrhythmias. H+ ions are generated in cardiomyocytes from metabolic processes and particularly from CO2 hydration, which has been shown to facilitate CO2 venting from mitochondria. Currently, the NHE1 Na+ /H+ exchanger is viewed as the dominant H+ extrusion mechanism in cardiac muscle. We show that the HVCN1 voltage-gated proton channel is present and functional in canine ventricular myocytes, and that HVCN1 and NHE1 both contribute to pHi regulation. HVCN1 provides an energetically efficient mechanism of H+ extrusion that would not cause Na+ loading, which can cause pathology, and that could contribute to transport-mediated CO2 disposal. These results provide a major advance in our understanding of pHi regulation in cardiac muscle.