Distinct invasive patterns in situ between estrogen receptor-positive and triple-negative breast cancer through the intraductal tracking of carbon nanoparticles.

Given that the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer (BC) is crucial during the BC progression, the mechanism involved in the invasion transition behind triple-negative breast cancer (TNBC) and estrogen receptor-positive (ER-positive) subtype has remained elusive. This article detected distinct invasion patterns of BC cells between the ER-positive and TNBC using intraductal murine models with intraductal administration of carbon nanoparticles (CNPs). First, the feasibility of the utility of CNPs as a tracer was proved. The area ratio of CNPs and tumor cells invading the stroma at the late stage was found significantly higher than that in the early stage in MNU-induced ER-positive BC. However, opposite results were obtained in the triple-negative model. Consequently, we proposed that the ER-positive phenotype cells behave differently between different stages during tumor progression while there is no such difference in the invasion process of TNBC cells. The analysis regarding the duct integrity along with immunohistochemical characteristics further explained the distinct invasion features between the ER-positive and triple-negative subtypes. Last, the relationship between the duct thickness and the duct integrity suggested that ER-positive tumors gradually increased in size within the lumen before the invasion. Overall, this study suggested the different invasion characteristics of ER-positive BC and TNBC in vivo.

Theoretical Analyses of Multiobjective Evolutionary Algorithms on Multimodal Objectives.

Multiobjective evolutionary algorithms are successfully applied in many real-world multiobjective optimization problems. As for many other AI methods, the theoretical understanding of these algorithms is lagging far behind their success in practice. In particular, previous theory work considers mostly easy problems that are composed of unimodal objectives. As a first step towards a deeper understanding of how evolutionary algorithms solve multimodal multiobjective problems, we propose the OneJumpZeroJump problem, a bi-objective problem composed of two objectives isomorphic to the classic jump function benchmark. We prove that the simple evolutionary multiobjective optimizer (SEMO) with probability one does not compute the full Pareto front, regardless of the runtime. In contrast, for all problem sizes n and all jump sizes k∈[4..n2-1], the global SEMO (GSEMO) covers the Pareto front in an expected number of Θ((n-2k)nk) iterations. For k=o(n), we also show the tighter bound 32enk+1±o(nk+1), which might be the first runtime bound for an MOEA that is tight apart from lower-order terms. We also combine the GSEMO with two approaches that showed advantages in single-objective multimodal problems. When using the GSEMO with a heavy-tailed mutation operator, the expected runtime improves by a factor of at least kΩ(k). When adapting the recent stagnation-detection strategy of Rajabi and Witt (2022) to the GSEMO, the expected runtime also improves by a factor of at least kΩ(k) and surpasses the heavy-tailed GSEMO by a small polynomial factor in k. Via an experimental analysis, we show that these asymptotic differences are visible already for small problem sizes: A factor-5 speed-up from heavy-tailed mutation and a factor-10 speed-up from stagnation detection can be observed already for jump size 4 and problem sizes between 10 and 50. Overall, our results show that the ideas recently developed to aid single-objective evolutionary algorithms to cope with local optima can be effectively employed also in multiobjective optimization.

Dihydromyricetin resists inflammation-induced muscle atrophy via ryanodine receptor-CaMKK-AMPK signal pathway.

Skeletal muscle plays a pivotal role in the maintenance of physical and metabolic health. Skeletal muscle atrophy usually results in physical disability, inferior quality of life and higher health care costs. The higher incidence of muscle atrophy in obese and ageing groups is due to increased levels of inflammatory factors during obesity and ageing. Dihydromyricetin, as a bioactive polyphenol, has been used for anti-inflammatory, anti-tumour and improving insulin sensitivity. However, there are no published reports demonstrated the dihydromyricetin effect on inflammation-induced skeletal muscle atrophy. In this study, we first confirmed the role of dihydromyricetin in inflammation-induced skeletal muscle atrophy in vivo and in vitro. Then, we demonstrated that dihydromyricetin resisted inflammation-induced skeletal muscle atrophy by activating Ca2+ -CaMKK-AMPK through signal pathway blockers, Ca2+ probes and immunofluorescence. Finally, we clarified that dihydromyricetin activated Ca2+ -CaMKK-AMPK signalling pathway through interaction with the ryanodine receptor, its target protein, by drug affinity responsive target stability (DARTS). Our results not only demonstrated that dihydromyricetin resisted inflammation-induced muscle atrophy via the ryanodine receptor-CaMKK-AMPK signal pathway but also discovered that the target protein of dihydromyricetin is the ryanodine receptor. Our results provided experimental data for the development of dihydromyricetin as a functional food and new therapeutic strategies for treating or preventing skeletal muscle atrophy.

Searching for essential genes and drug discovery in breast cancer and periodontitis via text mining and bioinformatics analysis.

The primary purpose of the study was (1) to search for the essential genes associated with breast cancer and periodontitis, and (2) to identify candidate drugs targeted to these genes for expanding the potential drug indications. The genes related to both breast cancer and periodontitis were determined by text mining. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were performed on these genes, and protein-protein interaction analysis was carried out to export significant module genes. Drug-gene interaction database was employed for potential drug discovery. We identified 221 genes common to both breast cancer and periodontitis. The top six significant enrichment terms and 15 enriched signal pathways were selected. Among 24 significant genes demonstrated as a gene cluster, we found SERPINA1 and TF were significantly related to poor overall survival between the relatively high and low groups in patients. Using the final two genes, 12 drugs were identified that had potential therapeutic effects. SERPINA1 and TF were screened out as essential genes related to both breast cancer and periodontitis, targeting 12 candidate drugs that may expand drug indications. Drug discovery using text mining and analysis of different databases can promote the identification of existing drugs that have the potential of administration to improve treatment in breast cancer.

The MyD88 inhibitor TJ-M2010-2 suppresses proliferation, migration and invasion of breast cancer cells by regulating MyD88/GSK-3ß and MyD88/NF-κB signalling pathways.

MyD88 has been implicated in the tumourigenesis, metastasis and recurrence of breast cancer (BC). Here we utilized TJ-M2010-2 (TJ), an inhibitor of MyD88 homodimerimerization, and siMyD88 to suppress the function of MyD88 in MCF-7 and MDA-MB-231 cells. BC cells were treated in vitro and xenografted into nude mice to generate a model in vivo. TJ inhibited BC cell growth by impeding proliferation rather than by promoting apoptosis in vitro. Additionally, TJ and siMyD88 significantly attenuated cell migration and invasion, inhibited EMT-like progression and reduced cytokine (IL-6, IL-8, TGF-ß1 and TNF-α) secretion induced by LPS. In vivo, TJ significantly hindered tumour growth in mice. Notably, TJ also decreased the secretion of IL-6, IL-8, TGF-ß1, and TNF-α and M2 macrophage infiltration in the tumour microenvironment. The expression of MyD88, TRAF6, NF-κB p65, Snail, MMP-2, MMP-9, p-GSK-3ß and p-Akt was significantly downregulated by TJ in BC cells and tumour tissues. Collectively, these results suggest that a MyD88 inhibitor (TJ) may be a promising therapeutic modality for treating BC patients.

Ag2 O-TiO2 -NTs enhance osteogenic activity in vitro by modulating TNF-α/ß-catenin signaling in bone marrow-derived mesenchymal stem cells.

The toxic effects of nanoparticles-silver oxide (Ag2 O) limited its use. However, loading Ag2 O nanoparticles into titanium dioxide (TiO2 ) nanotubes (Ag2 O-TiO2 -NTs) has more efficient biological activity and safety. The aim of this study was to observe the effect of Ag2 O-TiO2 -NTs on osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and its mechanism. The enzyme activity of lactate dehydrogenase (LDH) and the expression of RUNX family transcription factor 2 (Runx2), OPN, OCN in BMSCs were detected by quantitative real time polymerase chain reaction. At 14 days of induction, the mineralization ability and alkaline phosphatase (ALP) activity of cells in each group were observed by Alizarin Red S staining and ALP staining. In addition, the protein levels of tumor necrosis factor-α (TNF-α) and ß-catenin in BMSCs of each group were observed by western blot. After 14 days of the induction, the mineralization ability and ALP activity of BMSCs in the Ag2 O-TiO2 -NTs group were significantly enhanced compared with those in the Ag2 O and TiO2 groups. Western blot analysis showed that the BMSCs in the Ag2 O-TiO2 -NTs group exhibited much lower protein level of TNF-α and higher protein level of ß-catenin than those in the Ag2 O and TiO2 groups.Ag2 O-TiO2 -NTs enhance the osteogenic activity of BMSCs by modulating TNF-α/ß-catenin signaling.

Based on whole-exome sequencing to explore the rule of Herceptin and TKI resistance in breast cancer patients.

BACKGROUND: Breast cancer is the second leading cause of cancer-related death in women, and drug resistance during treatment is a major challenge. However, the mechanisms underlying drug resistance are not fully understood. Here we applied whole-exome sequencing (WES) to clarify resistant rules to Herceptin and tyrosine kinase inhibitors (TKIs). METHODS: There are 12 HER2+ breast cancer patients who were done WES. Samples from tumor and surrounding tissues underwent DNA sequencing and analysis. Various experimental and bioinformatics techniques were employed, including genomic capture, mutation analysis (Genome Analysis Toolkit (GATK), etc.), bioinformatics assessments, and drug-gene interaction investigations. Ultimately, the study explored the association of APOB gene expression with breast cancer recurrence rates, immune cell infiltration, and drug response. RESULTS: The C > T mutation frequency was highest in the Herceptin-insensitive (HI) and verification groups, codenamed YI, contrasting with the Herceptin-sensitive (HE) group. No microsatellite instability (MSI)-H patients were in the HE group, but both HI and YI groups had 1 each. Significant differences in transition-transversion (TiTv) were observed in the HI and YI groups rather than the HE group. In the TKI- insensitive (TI) group, C > T mutations were highest, differing from the TKI-sensitive (TE) group. TE group included 2 MSI-H patients. Significant differences in TiTv were found in the TI group rather than the TE group. Mutated APOB may resist Herceptin and TKI, increasing immune infiltration. We identified potential drugs targeting it. CONCLUSIONS: Our study suggested that a higher percentage of C > T mutations, significant differences in TiTv, and MSI-H status may indicate Herceptin resistance, while a higher percentage of C > T mutations, significant differences in TiTv, and the absence of MSI-H may indicate TKI resistance in breast cancer patients. For patients resistant to both Herceptin and TKI, mutated APOB may play a crucial role in resistance.

Risk model for predicting mortality in patients with necrotizing soft tissue infections in the intensive care unit.

BACKGROUND: The goal of this study is to look into the factors that lead to death in patients with necrotizing soft tissue infections（NSTIs） in the intensive care unit and create a mortality risk model. METHODS: The clinical data of 106 patients with necrotizing soft tissue infections admitted to intensive care unit(ICU) of the First Affiliated Hospital of Wenzhou Medical University between January 2008 and December 2021 were retrospectively analyzed. Univariate analysis and multivariate analysis were performed to evaluate the risk factors impacting patient mortality. The regression coefficient in binary logistic regression analysis was converted into the item score in the model, and then the model score of each patient was calculated. Finally, an ROC curve was constructed to evaluate the efficiency of the model for predicting mortality. Thirteen patients with NSTIs admitted to ICU between January 2022 and November 2022 were used to validate the model. RESULTS: The death group had 44 patients, while the survival group had 62 patients. The overall mortality was 41.5%. Binary logistic regression analysis showed that risk factors for mortality were age≥ 60 years(OR:4.419; 95%CI:1.093-17.862; P = 0.037), creatinine ≥ 132µmol/L(OR:11.166; 95%CI:2.234-55.816; P = 0.003), creatine kinase ≥ 1104 U/L(OR:4.019; 95%CI:1.134-14.250; P = 0.031), prothrombin time ≥ 24.4 s(OR:11.589; 95%CI:2.510-53.506; P = 0.002), and invasive mechanical ventilation (OR:17.404; 95%CI:4.586-66.052; P＜0.000). The AUC of the model for predicting mortality was 0.940 (95% CI:0.894-0.986). When the cut-off value for the model was 4 points, the sensitivity was 95.5% and the specificity was 83.9%. CONCLUSION: The death risk model in this study for NSTIs patients in the intensive care unit shows high sensitivity and specificity. Patients with a score of ≥ 4 points have a higher risk of mortality.

NEATmap: a high-efficiency deep learning approach for whole mouse brain neuronal activity trace mapping.

Quantitative analysis of activated neurons in mouse brains by a specific stimulation is usually a primary step to locate the responsive neurons throughout the brain. However, it is challenging to comprehensively and consistently analyze the neuronal activity trace in whole brains of a large cohort of mice from many terabytes of volumetric imaging data. Here, we introduce NEATmap, a deep learning-based high-efficiency, high-precision and user-friendly software for whole-brain neuronal activity trace mapping by automated segmentation and quantitative analysis of immunofluorescence labeled c-Fos+ neurons. We applied NEATmap to study the brain-wide differentiated neuronal activation in response to physical and psychological stressors in cohorts of mice.

A facile strategy for constructing lightweight, fire safety and compression resistance poly(vinylalcohol) aerogels with highly-efficient expansible graphene oxide/layered double hydroxides hybrid synergistic flame retardant.

Poly(vinyl alcohol) (PVA) aerogels with excellent environmentally friendly properties have been considered to replace undegradable polymer foams. However, due to highly flammable, hydrophilic, and worse compression resistance performance, PVA aerogels have always been excluded from practical. Herein, a fire safety and compression resistance PVA/expansible graphene oxide (EGO)/Layered double hydroxides (LDHs) (PGL) aerogel was prepared via the freeze-drying method and electrostatic adsorption of flame retardant. The ice crystals from aerogels were sublimated and left a mass of tree-like pore tunnel structures. Meantime, the compound of EGO and LDHs rendered PGL aerogels high compressive strength of 6.0917 MPa (at 80% of strains), a high specific modulus of 19.16 m2/s2, and an ultra-low density of 0.059 g/cm3. Especially, the as-prepared PGL aerogels showed heat release reduced by 55.4%, smoke release reduced by 54.3%, and the limiting oxygen index reaching up to 31%. Moreover, LDHs also enhanced the interface with PVA/EGO resulting in hydrophobic performance improvement. The proposed enhancements mechanism suggested that (i) chemical reactions between EGO and PVA matrix; (ii) a mass of negative potential sites from the interface of PVA/EGO composites made LDHs sheets easily adsorbing; (iii) oxygen-containing groups from EGO and LDHs absorbed mass of heat during combustion; (iv) the compact char residues on the surface of aerogels acting as barriers suppressed smoke and prevented PVA matrix from further combustion. Therefore, electrostatic adsorption as a facile production process was paved for meeting the compression resistance, flame-retardant, heat-insulating, and smoke-suppressed requirements of PVA aerogels in this work.

Dynamic Changes in Egg Quality, Heritability and Correlation of These Traits and Yolk Nutrient throughout the Entire Laying Cycle.

Egg quality and nutritional value are becoming increasingly important to consumers, offering a new direction for the development of high-quality eggs. In this study, we conducted a comprehensive analysis of egg quality and nutrient profiles in native breeds at different ages, integrating pedigree data. Our results reveal dynamic changes in egg qualities, stronger associations among eggshell-related traits, and the effect of onset production and body weight on egg qualities. The heritability of different traits was estimated, ranging from 0.05 to 0.62. Subsequently, we elucidated that the moisture and nutritional content in the egg yolk were not influenced by the percentage of yolk but were indeed subject to age regulation. There was a notable decrease in moisture, an elevation in crude fat, and an increase in the diversity of fatty acids of yolk with advancing age. In summary, investigating the trends and interrelationships in egg quality, nutrient content, and heritability across the whole laying cycle offers valuable insights for breeders to optimize feeding management strategies and aids consumers in meeting their expectations of egg quality.

Searching for Essential Genes and Targeted Drugs Common to Breast Cancer and Osteoarthritis.

BACKGROUND: It is documented that osteoarthritis can promote the progression of breast cancer (BC). OBJECTIVE: This study aims to search for the essential genes associated with breast cancer (BC) and osteoarthritis (OA), explore the relationship between epithelial-mesenchymal transition (EMT)-related genes and the two diseases, and identify the candidate drugs. METHODS: The genes related to both BC and OA were determined by text mining. Protein-protein Interaction (PPI) analysis was carried out, and as a result, the exported genes were found to be related to EMT. PPI and the correlation of mRNA of these genes were also analyzed. Different kinds of enrichment analyses were performed on these genes. A prognostic analysis was performed on these genes for examining their expression levels at different pathological stages, in different tissues, and in different immune cells. Drug-gene interaction database was employed for potential drug discovery. RESULTS: A total number of 1422 genes were identified as common to BC and OA and 58 genes were found to be related to EMT. We found that HDAC2 and TGFBR1 were significantly poor in overall survival. High expression of HDAC2 plays a vital role in the increase of pathological stages. Four immune cells might play a role in this process. Fifty-seven drugs were identified that could potentially have therapeutic effects. CONCLUSION: EMT may be one of the mechanisms by which OA affects BC. Using the drugs can have potential therapeutic effects, which may benefit patients with both diseases and broaden the indications for drug use.

Breast cancer heterogeneity and its implication in personalized precision therapy.

Breast cancer heterogeneity determines cancer progression, treatment effects, and prognosis. However, the precise mechanism for this heterogeneity remains unknown owing to its complexity. Here, we summarize the origins of breast cancer heterogeneity and its influence on disease progression, recurrence, and therapeutic resistance. We review the possible mechanisms of heterogeneity and the research methods used to analyze it. We also highlight the importance of cell interactions for the origins of breast cancer heterogeneity, which can be further categorized into cooperative and competitive interactions. Finally, we provide new insights into precise individual treatments based on heterogeneity.

Identification of genetic associations and functional SNPs of bovine KLF6 gene on milk production traits in Chinese holstein.

BACKGROUND: Our previous research identified the Kruppel like factor 6 (KLF6) gene as a prospective candidate for milk production traits in dairy cattle. The expression of KLF6 in the livers of Holstein cows during the peak of lactation was significantly higher than that during the dry and early lactation periods. Notably, it plays an essential role in activating peroxisome proliferator-activated receptor α (PPARα) signaling pathways. The primary aim of this study was to further substantiate whether the KLF6 gene has significant genetic effects on milk traits in dairy cattle. RESULTS: Through direct sequencing of PCR products with pooled DNA, we totally identified 12 single nucleotide polymorphisms (SNPs) within the KLF6 gene. The set of SNPs encompasses 7 located in 5' flanking region, 2 located in exon 2 and 3 located in 3' untranslated region (UTR). Of these, the g.44601035G > A is a missense mutation that resulting in the replacement of arginine (CGG) with glutamine (CAG), consequently leading to alterations in the secondary structure of the KLF6 protein, as predicted by SOPMA. The remaining 7 regulatory SNPs significantly impacted the transcriptional activity of KLF6 following mutation (P < 0.005), manifesting as changes in transcription factor binding sites. Additionally, 4 SNPs located in both the UTR and exons were predicted to influence the secondary structure of KLF6 mRNA using the RNAfold web server. Furthermore, we performed the genotype-phenotype association analysis using SAS 9.2 which found all the 12 SNPs were significantly correlated to milk yield, fat yield, fat percentage, protein yield and protein percentage within both the first and second lactations (P < 0.0001 ~ 0.0441). Also, with Haploview 4.2 software, we found the 12 SNPs linked closely and formed a haplotype block, which was strongly associated with five milk traits (P < 0.0001 ~ 0.0203). CONCLUSIONS: In summary, our study represented the KLF6 gene has significant impacts on milk yield and composition traits in dairy cattle. Among the identified SNPs, 7 were implicated in modulating milk traits by impacting transcriptional activity, 4 by altering mRNA secondary structure, and 1 by affecting the protein secondary structure of KLF6. These findings provided valuable molecular insights for genomic selection program of dairy cattle.

Structure-evolution-designed amorphous oxides for dielectric energy storage.

Recently, rapidly increased demands of integration and miniaturization continuously challenge energy densities of dielectric capacitors. New materials with high recoverable energy storage densities become highly desirable. Here, by structure evolution between fluorite HfO2 and perovskite hafnate, we create an amorphous hafnium-based oxide that exhibits the energy density of ~155 J/cm3 with an efficiency of 87%, which is state-of-the-art in emergingly capacitive energy-storage materials. The amorphous structure is owing to oxygen instability in between the two energetically-favorable crystalline forms, in which not only the long-range periodicities of fluorite and perovskite are collapsed but also more than one symmetry, i.e., the monoclinic and orthorhombic, coexist in short range, giving rise to a strong structure disordering. As a result, the carrier avalanche is impeded and an ultrahigh breakdown strength up to 12 MV/cm is achieved, which, accompanying with a large permittivity, remarkably enhances the energy storage density. Our study provides a new and widely applicable platform for designing high-performance dielectric energy storage with the strategy exploring the boundary among different categories of materials.

Organic-Inorganic Double-Gel System Thermally Insulating and Hydrophobic Polyimide Aerogel.

Aerogel materials are used in various fields, but there is a shortage of aerogel materials with an excellent combination of mechanical properties, thermal stability, and easy preparation. In this study, polyimide aerogel materials with superior mechanical properties, thermal stability, and low thermal conductivity were prepared by forming a double-gel system in the liquid phase. The amino-modified gel, prepared by coating SiO2 nano-microspheres with GO through a modified sol-gel method (SiO2@GO-NH2), was subsequently homogeneously dispersed with PAA wet gel in water to form a double-gel system. The construction of a double-gel system enabled the PI aerogel to shape a unique honeycomb porous structure and a multi-layered interface of PI/SiO2/GO. The final obtained PI aerogel possessed effective thermal conductivity (0.0309 W/m·K) and a high specific modulus (46.19 m2/s2). In addition, the high thermal stability (543.80 °C in Ar atmosphere) and the ability to retain properties under heat treatment proved its durability in high thermal environments. The hydrophobicity (131.55°) proves its resistance to water from the environment. The excellent performance of this PI aerogel and its durability in thermal working environments make it possible to be applied in varied industrial and research fields, such as construction and energy, where heat and thermal insulation are required.

"Oxynitride trap" over N/S co-doped graphene-supported catalysts promoting low temperature NH3-SCR performance: Insight into the structure and mechanisms.

A series of nitrogen and sulfur (N/S) co-doped graphene supported catalysts (Mn-Ce-SnOx/NSG) were synthesized using an in situ method for enhancing selective catalytic reduction of NOx with NH3 (NH3-SCR) performance. The changes in catalysts' structure, morphology, and active sites were systematically researched to explore the promoting effect of N/S co-doped on catalytic performance. The prepared Mn-Ce-SnOx/NSG-0.3 catalyst achieves an excellent SCR activity at a low temperature, which is comparable to previous graphene-based catalysts. The Ce3+/(Ce3+ + Ce4+), Mn4+/Mn3+, and Oα/(Oα + Oß) ratios in the catalyst are improved by N/S co-doping, which closely related to excellent SCR activity. Meanwhile, the unpaired electrons on N/S functional groups are effective in promoting the adsorption and further oxidation of gaseous NO. The ability to adsorb NH3 has also been promoted result of numerous Lewis acid sites over Mn-Ce-SnOx/NSG-0.3. In-situ DRIFTS and reaction kinetic results suggest that the Eley-Rideal mechanism should be the most significant pathway in the temperature range of ≥ 200 °C, where coordinated NH3 has higher activity than ionic NH4+. The Langmuir-Hinshelwood (L-H) mechanism is the main route of the low-temperature (L-T) (< 200 °C) SCR reaction. Particularly, the L-T SCR activity improves because the N/S functional groups act as an additional "oxynitride trap" (based on the L-H mechanism).

Weakly supervised learning analysis of Aß plaque distribution in the whole rat brain.

Alzheimer's disease (AD) is a great challenge for the world and hardly to be cured, partly because of the lack of animal models that fully mimic pathological progress. Recently, a rat model exhibiting the most pathological symptoms of AD has been reported. However, high-resolution imaging and accurate quantification of beta-amyloid (Aß) plaques in the whole rat brain have not been fulfilled due to substantial technical challenges. In this paper, a high-efficiency data analysis pipeline is proposed to quantify Aß plaques in whole rat brain through several terabytes of image data acquired by a high-speed volumetric imaging approach we have developed previously. A novel segmentation framework applying a high-performance weakly supervised learning method which can dramatically reduce the human labeling consumption is described in this study. The effectiveness of our segmentation framework is validated with different metrics. The segmented Aß plaques were mapped to a standard rat brain atlas for quantitative analysis of the Aß distribution in each brain area. This pipeline may also be applied to the segmentation and accurate quantification of other non-specific morphology objects.

Identification of Genetic Effects of ACADVL and IRF6 Genes with Milk Production Traits of Holstein Cattle in China.

With the development of high-throughput sequencing, RNA sequencing has been widely used in the identification of candidate genes for complex traits in livestock, and the functional genes and mutations with large genetic effects on milk production traits can provide molecular information for marker-assisted selection to increase the selection accuracy and accelerate genetic gain in dairy cattle. Our previous study on the liver transcriptome of Holstein cows found that acyl-CoA dehydrogenase (ACADVL) and interferon regulatory factor 6 (IRF6) are differentially expressed between dry and peak lactation periods, as well as that they are involved in lipid metabolism and the proliferation and differentiation of mammary epithelial cells. Thus, the two genes were considered candidates for milk traits. Hence, this study further collected 1186 Holstein cows from 110 sire families to investigate their genetic associations with milk yield and composition traits. By resequencing the entire exons and 2000 bp of the 5' and 3' flanking regions of the two genes, we identified eight SNPs in ACADVL and eight SNPs in IRF6. Subsequent single-locus association analyses showed that the eight SNPs in ACADVL were all significantly associated with milk fat yield, fat percentage, and protein yield (p values ≤ 0.0001-0.0414), and the eight SNPs in IRF6 were associated with milk, fat, and protein yields in the first or second lactation (p values ≤ 0.0001-0.0467). Using Haploview 4.2, one haplotype block with eight of the SNPs in ACADVL (D' = 0.99-1.00) and two haplotype blocks in IRF6 with three of the SNPs in each were observed (D' = 0.98-1.00). Similarly, the haplotype combinations of ACADVL were significantly associated with milk yield, fat percentage, fat yield, and protein yield in the two lactations (p values ≤ 0.0001-0.0125), and those of IRF6 were associated with five milk traits (p values ≤ 0.0001-0.0263). Furthermore, with the JASPAR software, it was predicted that the SNPs 19:g.26933503T>C in ACADVL and 16:g.73501985G>A in IRF6 changed the transcription factor binding sites of ZEB1, PLAGL2, and RHOXF1, implying their impacts on the expressions of the corresponding genes. Our findings demonstrated that the ACADVL and IRF6 genes have significant genetic effects on milk yield and composition traits, and the valuable SNPs might be used as genetic markers for genomic selection programs in dairy cattle.

Novel application of microdissection tungsten needle in total thyroidectomy with central neck dissection for papillary thyroid carcinoma.

Background: Energy-based devices (EBD) have been popularized in thyroidectomy worldwide. Microdissection tungsten needle (MDTN) is characterized by the ultra-sharp tip providing safe and meticulous dissection with effective hemostasis. However, little study has applied MDTN in thyroidectomy. Methods: This retrospective study compared clinical data of the patients who underwent total thyroidectomy (TT) with central neck dissection (CND) using MDTN, harmonic scalpel (HS), and conventional electrocautery (CE). We assessed outcomes related to surgical efficacy and safety. The injury degree of tissue was assessed by biochemical indicators and early-stage inflammatory factors in the drainage fluid. Histological sections of the thyroid specimens were evaluated to compare levels of thermal damage by the three EBD. Results: There was a significant decrease in the intraoperative blood loss, operation time and 24-hour drainage volume in the MDTN group compared to the CE group. The total drainage volume, duration of drainage, and average length of stay of the MDTN group were less compared to the CE group though they did not reach statistical significance. No disparity was observed between the MDTN group and HS group in these variables. Total costs were not significantly different among these groups. The incidence of recurrent laryngeal nerve (RLN) injury was the lowest using MDTN compared to the CE (P = 0.034) and HS (not significant). No statistical differences were observed among these groups regarding postoperative wound pain and infection, hypoparathyroidism, and postoperative hemorrhage. Analysis of biochemical indicators showed a lower level of hemoglobin in the MDTN and HS group than the CE group (P = 0.046 and 0.038, respectively) and less triglyceride in the HS group than the MDTN and CE group (P = 0.002 and 0.029, respectively) but no significant difference in cholesterol level in these groups. Early-stage inflammatory factors including TNF-α and IL-6 showed significantly higher concentration in the CE group than the MDTN and HS group. Histological sections of thyroid specimens revealed that MDTN caused the lowest degree of thermal damage followed by HS then CE. Conclusion: MDTN exhibited comparable surgical efficacy and safety outcomes as HS in thyroidectomy. Therefore, MDTN is a safe and viable alternative for hemostasis in thyroidectomy.