Comprehensive assessment of drought resistance and recovery in kiwifruit genotypes using multivariate analysis.

As global climate change persists, ongoing warming exposes plants, including kiwifruit, to repeated cycles of drought stress and rewatering, necessitating the identification of drought-resistant genotypes for breeding purposes. To better understand the physiological mechanisms underlying drought resistance and recovery in kiwifruit, moderate (40-45% field capacity) and severe (25-30% field capacity) drought stresses were applied, followed by rewatering (80-85% field capacity) to eight kiwifruit rootstocks in this study. We then conducted a multivariate analysis of 20 indices for the assessment of drought resistance and recovery capabilities. Additionally, we identified four principal components, each playing a vital role in coping with diverse water conditions. Three optimal indicator groups were pinpointed, enhancing precision in kiwifruit drought resistance and recovery assessment and simplifying the evaluation system. Finally, MX-1 and HW were identified as representative rootstocks for future research on kiwifruit's responses to moderate and severe drought stresses. This study not only enhances our understanding of the response mechanisms of kiwifruit rootstocks to progressive drought stress and recovery but also provides theoretical guidance for reliable screening of drought-adaptive kiwifruit genotypes.

Circ_0002395 promotes aerobic glycolysis and proliferation in pancreatic adenocarcinoma cells via miR-548c-3p/PDK1 axis.

Circular RNAs (circRNAs) showing unusual expressions have been discovered in pancreatic adenocarcinoma (PAAD). However, the functions and underlying mechanisms of these circRNAs still remain largely unclear. Our current study discovered a notable increase in the expression of circRNA hsa_circ_0002395 (circ_0002395) in both PAAD tissues and cell lines. This up-regulation of circ_0002395 was found to be associated with larger tumor sizes and lymph node metastasis. Furthermore, our findings showed that circ_0002395 facilitated aerobic glycolysis and cell proliferation in PAAD cells by regulating the miR-548c-3p/PDK1 axis. Mechanistically, we identified circ_0002395 as a competing endogenous RNA (ceRNA) that sponged miR-548c-3p, thereby promoting PDK1 expression and aerobic glycolysis, and ultimately resulting in the enhancement of cell proliferation. Our findings found that circ_0002395 promoted proliferation of PAAD cells by enhancing PDK1 expression and aerobic glycolysis by sponging miR-548c-3p.

Identification of carbohydrate gene clusters obtained from in vitro fermentations as predictive biomarkers of prebiotic responses.

BACKGROUND: Prebiotic fibers are non-digestible substrates that modulate the gut microbiome by promoting expansion of microbes having the genetic and physiological potential to utilize those molecules. Although several prebiotic substrates have been consistently shown to provide health benefits in human clinical trials, responder and non-responder phenotypes are often reported. These observations had led to interest in identifying, a priori, prebiotic responders and non-responders as a basis for personalized nutrition. In this study, we conducted in vitro fecal enrichments and applied shotgun metagenomics and machine learning tools to identify microbial gene signatures from adult subjects that could be used to predict prebiotic responders and non-responders. RESULTS: Using short chain fatty acids as a targeted response, we identified genetic features, consisting of carbohydrate active enzymes, transcription factors and sugar transporters, from metagenomic sequencing of in vitro fermentations for three prebiotic substrates: xylooligosacharides, fructooligosacharides, and inulin. A machine learning approach was then used to select substrate-specific gene signatures as predictive features. These features were found to be predictive for XOS responders with respect to SCFA production in an in vivo trial. CONCLUSIONS: Our results confirm the bifidogenic effect of commonly used prebiotic substrates along with inter-individual microbial responses towards these substrates. We successfully trained classifiers for the prediction of prebiotic responders towards XOS and inulin with robust accuracy (≥ AUC 0.9) and demonstrated its utility in a human feeding trial. Overall, the findings from this study highlight the practical implementation of pre-intervention targeted profiling of individual microbiomes to stratify responders and non-responders.

Site-directed mutagenesis leads to the optimized transglycosylation activity of endo-beta-N-acetylglucosaminidase from Trypanosoma brucei.

Endo-ß-N-acetylglucosaminidases (ENGases) are pivotal enzymes in the degradation and remodeling of glycoproteins, which catalyze the cleavage or formation of ß-1,4-glycosidic bond between two N-acetylglucosamine (GlcNAc) residues in N-linked glycan chains. It was investigated that targeted mutations of amino acids in ENGases active site may modulate their hydrolytic and transglycosylation activities. Endo-Tb, the ENGase derived from Trypanosoma brucei, belongs to the glycoside hydrolase family 85 (GH85). Our group previously demonstrated that Endo-Tb exhibits hydrolytic activity toward high-mannose and complex type N-glycans and preliminarily confirmed its transglycosylation potential. In this study, we further optimized the transglycosylation activity of recombinant Endo-Tb by focusing on the N536A, E538A and Y576F mutants. A comparative analysis of their transglycosylation activity with that of the wild-type enzyme revealed that all mutants exhibited enhanced transglycosylation capacity. The N536A mutant exhibited the most pronounced improvement in transglycosylation activity with a significant reduction in hydrolytic activity. It is suggested that Endo-Tb N536A possesses the potential as a tool for synthesizing a wide array of glycoconjugates bearing high-mannose and complex type N-glycans.

V-Based MXene/MAX Heterostructure Composites with Enhancing Dielectric Loss for Broadband Microwave Absorption.

Electromagnetic wave absorption performance is strictly dependent on attenuation and impedance matching, which are directly influenced by the ratio of MXene/MAX in the multilayer structured MXene/MAX composites. However, there is still a challenge to achieve collaborative optimization of dielectric loss and impedance matching by precisely regulating the proportional relationship of MXene/MAX. Herein, V-based MXene/MAX heterostructure composites with different V2C/V2AlC ratios were successfully synthesized by rationally controlling the temperature and time of the hydrothermal reaction. Experimental results indicated that V2C-100 °C-1 harvested the balance between reduced impedance matching and enhanced dielectric losses, which was attributed to the mildly enhanced conduction loss and polarization loss. The first principles indicated that abundant electrons migrate from the V atoms of the MXene to the C atoms of the MAX phase. The charge redistributed and accumulated at the interface, exciting the increase in the dielectric loss of V2C-100 °C-1. As a result, the V2C-100 °C-1 heterostructure composite had an excellent electromagnetic absorption effect with a minimum reflection loss of -50.06 dB and a wide effective absorption bandwidth of 4.0 GHz (12.72-16.72 GHz). This work provides a valuable experience for the development of efficient MXene-based microwave absorbing materials.

Antibacterial Indole-Diterpenoid Alkaloids from the Marine Fungus Penicillium sp. ZYX-Z-718.

Two new indole-diterpenoids, penpaxilloids F and G (1 and 2), along with 11 known analogues (3-13), were isolated from the marine fungus Penicillium sp. ZYX-Z-718. The structures of the new compounds were identified by extensive spectroscopic analyses including HR-ESI-MS, UV, and NMR, as well as theoretical NMR chemical shifts and ECD calculations. Compounds 6 and 10 showed antibacterial activity against Gram-positive bacteria including Staphylococcus aureus, Bacillus subtilis, and MRSA with MIC values ranging from 16.0-32.0 µg/mL.

Diaporchalasins A-E, New Cytochalasins from the Endophytic Fungus Diaporthe sp. BMX12 Isolated from Aquilaria sinensis.

Five new cytochalasins, diaporchalasins A-E (1-5), together with 14 known congeners (6-19) were isolated from the endophytic fungus Diaporthe sp. BMX12, which was isolated from the branches of Aquilaria sinensis. The structures of the new compounds were elucidated by extensive spectroscopic analyses including high-resolution electron spray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR). Their absolute configurations were assigned by theoretical electronic circular dichroism (ECD) calculations. Compounds 11 and 12 featuring a keto carbonyl at C-21 displayed cytotoxicity toward K562, BEL-7402, SGC-7901, A549, and HeLa cell lines with IC50 values ranging from 4.4 to 47.4 µM.

Best Evidence Summary for the Prevention of Pressure Injuries in Orthopaedic Patients.

AIM: To systematically search, evaluate and synthesise the most robust evidence regarding pressure injury prevention in orthopaedic patients admitted to general wards. DESIGN: The present study provides an evidence-based summary of the most robust findings, adhering to the evidence guidelines established by the Center for Evidence-Based Nursing of Fudan University. METHOD: According to the "6S" model, a systematic search was conducted for literature on pressure injury prevention among orthopaedic patients in general wards. The types of literature included guidelines, clinical decisions, expert Consensus, evidence summaries, etc. The search period covered the time from the beginning of the database up to December 2023. DATA SOURCES: The following databases and resources were systematically searched: Up To Date, JBI, NICE, WOCN, NZWCS, etc. RESULTS: Fifteen literature sources were included, comprising one clinical decision, eight guidelines, one systematic review, and one expert Consensus. In these sources, a comprehensive collection of 34 pieces of best evidence was formed across six key topics: risk assessment, position management, skin care, device used for device-related pressure injury, nutritional assessment, and support, as well as health education and training. Among the evidence gathered, a strong recommendation was made for 18 pieces, while the remaining 16 received a weak recommendation. CONCLUSION: This study provides a comprehensive synthesis of the most robust evidence on pressure injury prevention in orthopaedic patients, encompassing 34 pieces of evidence that can serve as valuable references for clinical practice. Before implementing this evidence, it is crucial to evaluate the specific contextual factors within different countries and medical institutions, as well as the facilitators and barriers influencing its application by healthcare professionals and patient's preferences. Furthermore, targeted evidence selection should be conducted through careful screening and subsequent adjustments in implementation, thereby offering a more scientifically grounded basis for clinical nursing practice. Future research endeavours should prioritise investigating strategies for effective evidence utilisation. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: The prevention of pressure injuries poses a significant challenge for orthopaedic patients. This study presents a synthesis of 34 pieces of best evidence to provide guidance on preventive measures for pressure injuries in orthopaedic patients. Adhering to and implementing these 34 pieces of evidence can effectively aid in preventing pressure injuries in clinical practice. This evidence encompasses risk assessment, position management, skin care, device usage for device-related pressure injuries, nutritional support and evaluation, and health education and training, establishing a comprehensive and systematic implementation process. Assessing the risk of pressure injuries during interventions serves as an essential prerequisite for developing effective strategies to prevent such injuries among orthopaedic patients. Ultimately, this study will offer valuable guidance to healthcare professionals worldwide regarding preventing pressure injuries in orthopaedic patients. IMPACT: Upon admission to the hospital, it is essential to conduct a risk assessment and implement evidence-based, individualised prevention measures for pressure ulcers in patients to prevent their occurrence. This study will provide valuable insights into preventing pressure injuries in orthopaedic patients admitted to orthopaedic wards for healthcare workers worldwide. STATE: The PRIMA manifest is utilised during the text preparation process. TRAIL REGISTRATION: ES20245365.

MicroRNAs in Pancreatic Cancer: Advances in Biomarker Discovery and Therapeutic Implications.

Pancreatic cancer remains a formidable malignancy characterized by high mortality rates, primarily attributable to late-stage diagnosis and a dearth of effective therapeutic interventions. The identification of reliable biomarkers holds paramount importance in enhancing early detection, prognostic evaluation, and targeted treatment modalities. Small non-coding RNAs, particularly microRNAs, have emerged as promising candidates for pancreatic cancer biomarkers in recent years. In this review, we delve into the evolving role of cellular and circulating miRNAs, including exosomal miRNAs, in the diagnosis, prognosis, and therapeutic targeting of pancreatic cancer. Drawing upon the latest research advancements in omics data-driven biomarker discovery, we also perform a case study using public datasets and address commonly identified research discrepancies, challenges, and limitations. Lastly, we discuss analytical approaches that integrate multimodal analyses incorporating clinical and molecular features, presenting new insights into identifying robust miRNA-centric biomarkers.

Quantile difference estimation with censoring indicators missing at random.

In this paper, we define estimators of distribution functions when the data are right-censored and the censoring indicators are missing at random, and establish their strong representations and asymptotic normality. Besides, based on empirical likelihood method, we define maximum empirical likelihood estimators and smoothed log-empirical likelihood ratios of two-sample quantile difference in the presence and absence of auxiliary information, respectively, and prove their asymptotic distributions. Simulation study and real data analysis are conducted to investigate the finite sample behavior of the proposed methods.

[Buyang Huanwu Decoction promotes arteriogenesis after hindlimb ischemia in mice by activating PDGF signaling pathway].

This study aims to investigate the effect of Buyang Huanwu Decoction on blood flow recovery and arteriogenesis after hindlimb ischemia in mice via the platelet-derived growth factor(PDGF) signaling pathway. Forty C57BL/6 mice were randomized into model(clean water, 10 mL·kg~(-1)·d~(-1)), beraprost sodium(positive control, 18 µg·kg~(-1)·d~(-1)), and low-, medium-, and high-dose(10, 20, and 40 g·kg~(-1)·d~(-1), respectively) Buyang Huanwu Decoction groups(n=8). The hindlimb ischemia model was established by femoral artery ligation. The mice were administrated with corresponding agents by gavage daily for 14 days after ligation. For laser Doppler perfusion imaging, the mice were anesthetized and measured under a Periscan PSI imager. The density of capillary and arterio-le in the ischemic gastrocnemius was measured using immunofluorescence staining of the frozen tissue sections. Western blot was employed to determine the expression of PDGF subunit B(PDGFB), phosphorylated mitogen extracellular kinase(p-MEK), MEK, phosphorylated extracellular signal-regulated kinase(p-ERK), and ERK. Real-time PCR was employed to determine the mRNA level of PDGFB. The Buyang Huanwu Decoction-containing serum was used to treat the vascular smooth muscle cells(VSMCs) in hypoxia at doses of 10% and 20%. The proliferation and migration of VSMCs was assessed in vitro. The results showed that compared with the model group, beraprost sodium and Buyang Huanwu Decoction enhanced the blood flow recovery, increased the capillary and arteriole density, and up-regulated the protein levels of PDGFB, p-MEK, p-ERK, and mRNA levels of PDGFB, with the medium-dose Buyang Huanwu Decoction demonstrating the most significant effect. The 10% Buyang Huanwu Decoction-containing serum enhanced the proliferation and migration of VSMCs. Our findings demonstrate that Buyang Huanwu Decoction up-regulates PDGFB transcription and activates PDGF signaling pathway to promote arteriogenesis and blood flow recovery in ischemic gastrocnemius.

The absorption of bovine milk small extracellular vesicles largely depends on galectin 3 and galactose ligands in human intestinal cells and C57BL/6J mice.

Small extracellular vesicles in milk (sMEVs) have attracted attention in drug delivery and as bioactive food compounds. Previous studies implicate galactose residues on the sMEV surface in sMEV transport across intestinal and endothelial barriers in humans, but details of glycoprotein-dependent transport are unknown. We used a combination of cell biology and genetics protocols to identify glycoproteins on the sMEV surface that facilitate sMEV absorption. We identified 256 proteins on the bovine sMEVs surface by using LC-MS/MS, and bioinformatics analysis suggested that 42, 13, and 13 surface proteins were N-, O-, and 13 C-glycosylated, respectively. Lectin blots confirmed the presence of mannose, galactose, N-acetyl galactose, fucose, and neuraminate. When surface proteins were removed by various treatment with various proteases, sMEV uptake decreased by up to 58% and 67% in FHs-74 Int and Caco-2 cells, respectively, compared with controls (P < 0.05). When glycans were removed by treatment with various glycosidases, sMEV uptake decreased by up to 54% and 74% in FHs-74 Int and Caco-2 cells, respectively (P < 0.05). When galactose and N-acetyl galactosamine residues were blocked with agglutinins, sMEV uptake decreased by more than 50% in FHs-74 Int cells (P < 0.05). When bovine sMEVs were administered to Galectin-3 knockout mice by oral gavage, hepatic sMEV accumulation decreased by 56% compared with wild-type mice (P < 0.05), consistent with a role of ß-galactoside glycan structures in the absorption of sMEVs. We conclude that sMEVs are decorated with glycoproteins, and Galectin-3 and its galactose ligands are particularly important for sMEV absorption.NEW & NOTEWORTHY This is the first paper to assess the role of unique glycans and their Galectin-3 receptor in the transport and distribution of small extracellular vesicles ("exosomes") from milk in mammals. The research assessed milk exosome transport and distribution by using multiple approaches and platforms including cell cultures, various exosome labels, knockout and mutant mice, enzymatic removal of surface proteins and glycans, and lectin blocking of glycans.

Elucidation of dynamic microRNA regulations in cancer progression using integrative machine learning.

MOTIVATION: Empowered by advanced genomics discovery tools, recent biomedical research has produced a massive amount of genomic data on (post-)transcriptional regulations related to transcription factors, microRNAs, long non-coding RNAs, epigenetic modifications and genetic variations. Computational modeling, as an essential research method, has generated promising testable quantitative models that represent complex interplay among different gene regulatory mechanisms based on these data in many biological systems. However, given the dynamic changes of interactome in chaotic systems such as cancers, and the dramatic growth of heterogeneous data on this topic, such promise has encountered unprecedented challenges in terms of model complexity and scalability. In this study, we introduce a new integrative machine learning approach that can infer multifaceted gene regulations in cancers with a particular focus on microRNA regulation. In addition to new strategies for data integration and graphical model fusion, a supervised deep learning model was integrated to identify conditional microRNA-mRNA interactions across different cancer stages. RESULTS: In a case study of human breast cancer, we have identified distinct gene regulatory networks associated with four progressive stages. The subsequent functional analysis focusing on microRNA-mediated dysregulation across stages has revealed significant changes in major cancer hallmarks, as well as novel pathological signaling and metabolic processes, which shed light on microRNAs' regulatory roles in breast cancer progression. We believe this integrative model can be a robust and effective discovery tool to understand key regulatory characteristics in complex biological systems. AVAILABILITY: http://sbbi-panda.unl.edu/pin/.

Human body-fluid proteome: quantitative profiling and computational prediction.

Empowered by the advancement of high-throughput bio technologies, recent research on body-fluid proteomes has led to the discoveries of numerous novel disease biomarkers and therapeutic drugs. In the meantime, a tremendous progress in disclosing the body-fluid proteomes was made, resulting in a collection of over 15 000 different proteins detected in major human body fluids. However, common challenges remain with current proteomics technologies about how to effectively handle the large variety of protein modifications in those fluids. To this end, computational effort utilizing statistical and machine-learning approaches has shown early successes in identifying biomarker proteins in specific human diseases. In this article, we first summarized the experimental progresses using a combination of conventional and high-throughput technologies, along with the major discoveries, and focused on current research status of 16 types of body-fluid proteins. Next, the emerging computational work on protein prediction based on support vector machine, ranking algorithm, and protein-protein interaction network were also surveyed, followed by algorithm and application discussion. At last, we discuss additional critical concerns about these topics and close the review by providing future perspectives especially toward the realization of clinical disease biomarker discovery.

Comparison of outcomes between single- and multiple-perforator-based free perforator flaps: A systematic review and meta-analysis.

BACKGROUND: Perforator-based free perforator flaps have become an important tool for the reconstruction of tissue defects. The effect of the number of perforators on the outcomes of perforator flaps has been widely debated. This study aimed to compare the outcomes of single- and multiple-perforator-based free perforator flaps in free-flap reconstruction. METHODS: We searched PubMed, Web of Science, EMBASE, Chinese BioMedical Literature Database (CBM), Cochrane Library, and clinicaltrials.gov between January 2000 and June 2021 to identify studies that reported data on the outcomes of free perforator flaps. Two authors individually extracted data and performed quality assessment. Outcomes, including partial flap loss, total loss, fat necrosis, arterial insufficiency, venous insufficiency, hemorrhage and hematoma, wound dehiscence at recipient sites and donor site complications, were evaluated. RESULTS: Thirty-two studies with 2498 flaps were included in our analysis. No significant difference was found in the rates of partial loss and arterial insufficiency of flaps, hemorrhage and hematoma, wound dehiscence at recipient sites and donor site complications. However, the multiple-perforator group showed significantly lower rates of total loss (relative risk [RR] = 1.08, 95% confidence interval [CI]: 0.78-1.79, p = .754), fat necrosis (RR = 1.79, 95% [CI]: 1.36-2.36, p = .000) and venous insufficiency (RR = 1.72, 95% CI: 1.07-2.79, p = .026) than the single-perforator group. CONCLUSION: The rates of total loss, fat necrosis and venous insufficiency in the multiple-perforator group were lower than those in the single-perforator group. Hence, we recommend that multiple perforators be included in the free perforator flap when appropriate, to yield better clinical outcomes in reconstruction.

Circulating microRNA trafficking and regulation: computational principles and practice.

Rapid advances in genomics discovery tools and a growing realization of microRNA's implication in intercellular communication have led to a proliferation of studies of circulating microRNA sorting and regulation across cells and different species. Although sometimes, reaching controversial scientific discoveries and conclusions, these studies have yielded new insights in the functional roles of circulating microRNA and a plethora of analytical methods and tools. Here, we consider this body of work in light of key computational principles underpinning discovery of circulating microRNAs in terms of their sorting and targeting, with the goal of providing practical guidance for applications that is focused on the design and analysis of circulating microRNAs and their context-dependent regulation. We survey a broad range of informatics methods and tools that are available to the researcher, discuss their key features, applications and various unsolved problems and close this review with prospects and broader implication of this field.

DeepSec: a deep learning framework for secreted protein discovery in human body fluids.

MOTIVATION: Human proteins that are secreted into different body fluids from various cells and tissues can be promising disease indicators. Modern proteomics research empowered by both qualitative and quantitative profiling techniques has made great progress in protein discovery in various human fluids. However, due to the large number of proteins and diverse modifications present in the fluids, as well as the existing technical limits of major proteomics platforms (e.g. mass spectrometry), large discrepancies are often generated from different experimental studies. As a result, a comprehensive proteomics landscape across major human fluids are not well determined. RESULTS: To bridge this gap, we have developed a deep learning framework, named DeepSec, to identify secreted proteins in 12 types of human body fluids. DeepSec adopts an end-to-end sequence-based approach, where a Convolutional Neural Network is built to learn the abstract sequence features followed by a Bidirectional Gated Recurrent Unit with fully connected layer for protein classification. DeepSec has demonstrated promising performances with average area under the ROC curves of 0.85-0.94 on testing datasets in each type of fluids, which outperforms existing state-of-the-art methods available mostly on blood proteins. As an illustration of how to apply DeepSec in biomarker discovery research, we conducted a case study on kidney cancer by using genomics data from the cancer genome atlas and have identified 104 possible marker proteins. AVAILABILITY: DeepSec is available at https://bmbl.bmi.osumc.edu/deepsec/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Circ_0001093 promotes glutamine metabolism and cancer progression of esophageal squamous cell carcinoma by targeting miR-579-3p/glutaminase axis.

Increasing studies indicate that circular RNAs (circRNAs) play critical roles in tumor metabolism of multiple cancers. However, the contribution of circRNAs in glutamine metabolism of esophageal squamous cell carcinoma (ESCC) remains elusive. The objective of this research was to investigate the role and mechanism of circRNA hsa_circ_0001093 (circ_0001093) in the glutamine metabolism and tumorigenesis of ESCC. Circ_0001093, microRNA-579-3p (miR-579-3p) and glutaminase (GLS) expressions in ESCC tissues and cell lines were measured by qRT-PCR, tissue array or Western blot. Cell proliferation, invasion and migration were assessed by CCK-8 or transwell assays. Glutamine consumption, glutamate and ATP production were detected by indicated assay kits. The relationships between circ_0001093 and miR-579-3p or GLS mRNA were investigated by bioinformatics analysis, RNA pull-down, luciferase reporter and RNA immunoprecipitation (RIP) assays. Here, we found that circ_0001093 expression was up-regulated in ESCC tissues and cell lines. Increased circ_0001093 expression predicted an unfavourable prognosis, and was associated with the lymph node metastasis, TNM staging and tumor size in ESCC tissues. Circ_0001093 knockdown suppressed cell proliferation, invasion, migration and glutamine metabolism of ESCC cells, while circ_0001093 over-expression showed the opposite effects. Mechanistically, circ_0001093 acted as a competing endogenous RNA (ceRNA) by sponging miR-579-3p, thereby increasing GLS expression. Furthermore, the inhibitory effects of circ_0001093 knockdown on the invasion, migration and glutamine metabolism were partly rescued by miR-579-3p inhibition or GLS over-expression in ESCC cells. Additionally, miR-579-3p expression was down-regulated in ESCC tissues, while GLS expression was up-regulated. In conclusion, this study first provides evidence that the circ_0001093/miR-579-3p/GLS regulatory network can affect glutamine metabolism and malignant phenotype of ESCC, which can further impact ESCC progression.

ΔI=2 Bifurcation as a Characteristic Feature of Scissors Rotational Bands.

We report microscopic many-body calculations indicating that rotational bands based on nuclear scissors vibrations exhibit systematic splitting between neighboring spin states (ΔI=2 bifurcation) in which the magnitude of the moment of inertia oscillates between states having even and odd spins. We show that this unexpected result is caused by self-organization of the deformed proton and neutron bodies in the scissors motion, which is further amplified by the K^{π}=1^{+} two-quasiparticle configurations near the scissors states. We propose that the puzzling excited state found above the 1^{+} scissors state in ^{156}Gd [Phys. Rev. Lett. 118, 212502 (2017)PRLTAO0031-900710.1103/PhysRevLett.118.212502] is the first evidence of this effect, and predict that bifurcation may generally appear in all other scissors rotational bands of deformed nuclei, and possibly in other systems exhibiting collective scissors vibrations.

Ultrasonication of Milk Decreases the Content of Exosomes and MicroRNAs in an Exosome-Defined Rodent Diet.

BACKGROUND: Bovine milk exosomes (BMEs) harbor regulatory proteins, lipids, and microRNAs. Consumption of an exosome- and RNA-depleted (ERD) diet elicited phenotypes compared with controls fed an exosome- and RNA-sufficient (ERS) diet in mice. All other ingredients were identical in the diets. ERD and ERS diets were prepared by substituting ultrasonicated and nonultrasonicated milk, respectively, for casein in the AIN-93G formulation. OBJECTIVES: The objective of this study was to assess the effect of ultrasonication of milk on exosome content and bioavailability, and cargo content. METHODS: Bovine milk was ultrasonicated and exosomes were isolated by ultracentrifugation [ultrasonicated exosomes (USEs)]; controls were not ultrasonicated [nonultrasonicated exosomes (NSEs)]. Exosome count, size, and morphology were assessed using a nanoparticle tracker and electron microscopy. RNAs, lipids, and proteins were analyzed by RNA sequencing and MS. Intestinal transport, bioavailability, and distribution were measured by using fluorophore-labeled USEs and NSEs in Caco-2 cells, FHs 74 Int cells, and C57BL/6J mice (n = 3; age: 6-8 wk). RESULTS: The exosome count was 76% ± 22% lower in USEs than in NSEs (P < 0.05). Ultrasonication caused a degradation of ≤100% of microRNAs. USEs and NSEs contained 145 and 332 unique lipid signatures, respectively (P < 0.05). We detected a total of 525 and 484 proteins in USEs and NSEs, respectively. The uptake of USEs decreased by 46% ± 30% and 40% ± 27% compared with NSEs in Caco-2 and FHs 74 Int cells, respectively (P < 0.05). The hepatic accumulation of USEs was 48% ± 28% lower than the accumulation of NSEs in mice (P < 0.05). CONCLUSIONS: Ultrasonication of milk depletes bioavailable BMEs in studies of Caco-2 cells, FHs 74 Int cells, and C57BL/6J mice and causes a near-complete degradation of microRNA cargos.