An Emerging Era: Conformable Ultrasound Electronics.

Conformable electronics are regarded as the next generation of personal healthcare monitoring and remote diagnosis devices. In recent years, piezoelectric-based conformable ultrasound electronics (cUSE) have been intensively studied due to their unique capabilities, including nonradiative monitoring, soft tissue imaging, deep signal decoding, wireless power transfer, portability, and compatibility. This review provides a comprehensive understanding of cUSE for use in biomedical and healthcare monitoring systems and a summary of their recent advancements. Following an introduction to the fundamentals of piezoelectrics and ultrasound transducers, the critical parameters for transducer design are discussed. Next, five types of cUSE with their advantages and limitations are highlighted, and the fabrication of cUSE using advanced technologies is discussed. In addition, the working function, acoustic performance, and accomplishments in various applications are thoroughly summarized. It is noted that application considerations must be given to the tradeoffs between material selection, manufacturing processes, acoustic performance, mechanical integrity, and the entire integrated system. Finally, current challenges and directions for the development of cUSE are highlighted, and research flow is provided as the roadmap for future research. In conclusion, these advances in the fields of piezoelectric materials, ultrasound transducers, and conformable electronics spark an emerging era of biomedicine and personal healthcare.

NK-derived exosome miR-1249-3p inhibits Mycobacterium tuberculosis survival in macrophages by targeting SKOR1.

Murine Natural Killer cells were cultivated in vitro to isolate NK-derived exosomes. Subsequent quantification via qPCR confirmed enrichment of miR-1249-3p. Ana-1 murine macrophages were cultured in vitro and subsequently inoculated with Mycobacterium tuberculosis (MTB) strain H37Rv. NK-exo and NK-exo miR-1249-3p were separately applied to the infection model, followed by immunological assays conducted post-48-hour co-culture. Western blot analyses corroborated that NK-exo exhibited exosomal marker proteins Granzyme A (GzmA), Granzyme B (GzmB), and Perforin (PFN), alongside a notable enrichment of miR-1249-3p. Functionally, NK-exo augmented the expression levels of Caspase-9,-8, and -3, as well as PARP, while attenuating the expression of NLRP3, ASC, and Cleaved-Caspase-1. Furthermore, qPCR demonstrated an up-regulation of Caspase-9, -8, and -3, along with pro-apoptotic factors Bax and Bid, and a concomitant down-regulation of the anti-apoptotic factor Bcl-2. The expression levels of inflammatory markers ASC, NLRP3, Cleaved-Caspase-1, and IL-1ß were concomitantly decreased. ELISA findings indicated diminished levels of TNF-α and ROS secretion. NK-exo miR-1249-3p specifically targeted and attenuated the expression of SKOR-1, engendering up-regulation of apoptosis-associated proteins and down-regulation of inflammation-related proteins, consequently affecting cellular fate.Our empirical evidence substantiates that NK-exo induces macrophage apoptosis, thereby mitigating MTB survival. Furthermore, NK-exo miR-1249-3p directly targets and inhibits SKOR-1 expression, leading to macrophage apoptosis and consequently hampering the proliferation of MTB. The data implicate the potential therapeutic relevance of NK-exo and miR-1249-3p in managing drug-resistant tuberculosis.

Human Toll-like receptor 2 genetic polymorphisms with tuberculosis susceptibility: A systematic review and meta-analysis.

BACKGROUND: Toll-like receptor 2 (TLR2) is a crucial factor in the development of tuberculosis. However, no studies have explored the association between TLR2 polymorphisms and tuberculosis susceptibility. OBJECTIVES: This study aimed to explore the correlation between tuberculosis susceptibility and TLR2 polymorphisms (rs3804099, rs3804100, rs1898830, rs5743708, rs121917864, and (-196-174) del). METHODS: All relevant online databases including PubMed, CNKI, WANFANG DATA, and METSTR-FMRS were systematically searched. STATA17.0 (Stata Corp LP, College Station, Texas, USA) was used. RESULTS: A total of 37 studies, covering six polymorphisms and comprising 9,474 cases and 10,295 controls, were included in this analysis. rs3804099(C vs T: OR = 1.00, 95 % CI: 0.93-1.08, CC + TC vs TT: OR = 1.04, 95 % CI: 0.98-1.10), rs3804100 (C vs T: OR = 1.19, 95 % CI: 0.93-1.07, CC + TC vs TT: OR = 0.97, 95 % CI: 0.89-1.06), rs1898830(G vs A: OR = 0.90, 95 % CI: 0.81-1.00, GG + AG vs AA: OR = 0.87, 95 % CI: 0.67-1.12), (-196 ∼174) del polymorphism (Del vs Ins: OR = 0.93,95 % CI: 0.76-1.14, DD + DI vs II: OR = 0.92,95 % CI: 0.72-1.17). CONCLUSIONS: This study indicated that only the TLR2 rs5743708 polymorphism exhibited a significant association with a higher tuberculosis risk, while TLR2 rs3804099, rs3804100, rs1898830, rs121917864, and (-196-174) del polymorphisms were not associated with tuberculosis susceptibility.

Conformable ultrasound breast patch for deep tissue scanning and imaging.

Ultrasound is widely used for tissue imaging such as breast cancer diagnosis; however, fundamental challenges limit its integration with wearable technologies, namely, imaging over large-area curvilinear organs. We introduced a wearable, conformable ultrasound breast patch (cUSBr-Patch) that enables standardized and reproducible image acquisition over the entire breast with less reliance on operator training and applied transducer compression. A nature-inspired honeycomb-shaped patch combined with a phased array is guided by an easy-to-operate tracker that provides for large-area, deep scanning, and multiangle breast imaging capability. The in vitro studies and clinical trials reveal that the array using a piezoelectric crystal [Yb/Bi-Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3] (Yb/Bi-PIN-PMN-PT) exhibits a sufficient contrast resolution (~3 dB) and axial/lateral resolutions of 0.25/1.0 mm at 30 mm depth, allowing the observation of small cysts (~0.3 cm) in the breast. This research develops a first-of-its-kind ultrasound technology for breast tissue scanning and imaging that offers a noninvasive method for tracking real-time dynamic changes of soft tissue.

An RCT-reticulated meta-analysis of six MBE therapies affecting college students' negative psychology.

The positive impact of mind-body movement therapy on mental health has been confirmed, but the current effect of various mind-body movement-specific therapies on improving the negative psychology of college students is controversial. This study compared the effects of six mind-body exercise (MBE) therapies on improving negative psychological symptoms in college students. The study found that Tai Chi (standardized mean difference [SMD] = -0.87, 95% confidence interval [CI] (-1.59, -0.15), p < 0.05), yoga (SMD = -0.95, 95% CI (-1.74, -0.15), p < 0.05), Yi Jin Jing (SMD = -1.15, 95% CI (-2.36, -0.05), p=<0.05), Five Animal Play (SMD = -1.1, 95% CI (-2.09, -0.02), p < 0.05), and Qigong Meditation (SMD = -1.31, 95% CI (-2.2, -0.4), p < 0.05) improved depressive symptoms in college students (p < 0.05). Tai Chi (SMD = -7.18, 95% CI (-13.18, -1.17), p = 0.019), yoga (SMD = -6.8, 95% CI (-11.79, -1.81), p = 0.008), and Yi Jin Jing (SMD = -9.21, 95% CI (-17.55, -0.87), p = 0.03) improved college students' anxiety symptoms. It shows that the six MBE therapies are effective in improving anxiety and depression in college students.

Identification of genes involved in regulating the development of feathered feet in chicken embryo.

The genetic and developmental factors driving the diverse distribution and morphogenesis of feathers and scales on bird feet are yet unclear. Within a single species, Guangxi domestic chickens exhibit dramatic variety in feathered feet, making them an accessible model for research into the molecular basis of variations in skin appendages. In this study, we used H&E staining to observe the morphogenesis of feathered feet, scaled feet and wings skin at different embryonic stages in Longsheng-Feng chickens and Guangxi Partridge chickens. We selected 4 periods (E6, E7, E8, and E12) that play an important role in feather development and performed transcriptome sequencing to screen for candidate genes associated with feathered feet. Through comparison and analysis of transcriptome data, we identified a set of differently expressed genes (DGEs), which were enriched in appendage organ development, hindlimb morphogenesis, activation of transcription factor binding, and binding of sequence-specific DNA in the cis-regulatory region. In addition, we identified some feathered feet-related genes by analyzing the classical signaling pathways that regulate feather development. Finally, we identified candidate genes that regulate feathered feet formation, which include TBX5, PITX1, ZIC1, FGF20, WNT11, WNT7A, WNT16, and SHH. Interestingly, we found that TBX5 was significantly overexpressed in the skin of the feathered feet and had the highest expression at E7 (P < 0.01), whereas PITX1 expression was significantly reduced at E7(P < 0.01). It is hypothesized that TBX5 and PITX1 regulate the development of hair follicles through the Wnt/ß-catenin signaling pathway at E7. Our results provide a theoretical basis for investigating the molecular regulatory mechanisms underlying the formation of chicken feathered feet.

Corrigendum: The effect of topical airway anesthesia on hemodynamic profile during the induction period in patients undergoing cardiac surgery: Study protocol for a randomized controlled trial.

[This corrects the article DOI: 10.3389/fcvm.2022.992534.].

Clinical observation of concentrated growth factor (CGF) combined with iliac cancellous bone and composite bone material graft on postoperative osteogenesis and inflammation in the repair of extensive mandibular defects.

PURPOSE: To evaluate the effects of concentrated growth factor (CGF), combined with a mixture of iliac cancellous and composite bone materials, on the repair of extensive mandibular defects. PATIENTS AND METHODS: This clinical trial involved patients with mandibular defects caused by large cystic lesions. The test group comprised 16 patients who underwent CGF combined with iliac cancellous bone and composite bone materials to repair extensive mandibular defects, whereas the control group comprised eight patients who underwent vascularised free fibula grafts for mandibular segmental defects. Postoperative exudatum was collected from patients on the 1st, 2nd, 3rd, and 4th days postoperatively, and osteogenic factor, including alkaline phosphatase (ALP), osteocalcin (BGP), and procollagen type I N-terminal propeptide (PINP), and inflammatory cytokines were performed. Additionally, regular cone beam computed tomography (CBCT) scans were conducted before and after surgery. RESULTS: On postoperative days 1-4, the expression levels of ALP, BGP, and PINP were higher in the test group, while those of IL-1α, IL-1ß, IL-6, IL-8, and TNF-α, which were identified as co-differentially expressing inflammatory cytokines, were all down-regulated in the exudatum of the test group. Regular CBCT radiological scans revealed a significant osteogenic effect in the test group. CONCLUSION: The use of CGF combined with iliac cancellous bone and composite bone materials to repair extensive mandibular jaw defects facilitates bone formation and reductions in inflammation in the defect area in the short term, which deserves further research in clinical practice.

Corrigendum: Comparison of out-of-plane short axis with in-plane long axis for ultrasound-guided radial arterial cannulation: A systematic review with trial sequential analysis of randomised controlled trials.

[This corrects the article DOI: 10.3389/fcvm.2022.983532.].

Recent Progress on Hydrogel-Based Piezoelectric Devices for Biomedical Applications.

Flexible electronics have great potential in the application of wearable and implantable devices. Through suitable chemical alteration, hydrogels, which are three-dimensional polymeric networks, demonstrate amazing stretchability and flexibility. Hydrogel-based electronics have been widely used in wearable sensing devices because of their biomimetic structure, biocompatibility, and stimuli-responsive electrical properties. Recently, hydrogel-based piezoelectric devices have attracted intensive attention because of the combination of their unique piezoelectric performance and conductive hydrogel configuration. This mini review is to give a summary of this exciting topic with a new insight into the design and strategy of hydrogel-based piezoelectric devices. We first briefly review the representative synthesis methods and strategies of hydrogels. Subsequently, this review provides several promising biomedical applications, such as bio-signal sensing, energy harvesting, wound healing, and ultrasonic stimulation. In the end, we also provide a personal perspective on the future strategies and address the remaining challenges on hydrogel-based piezoelectric electronics.

The effect of pituitrin on postoperative outcomes in patients with pulmonary hypertension undergoing cardiac surgery: a study protocol for a randomized controlled trial.

Background: The vasoplegic syndrome is one of the major consequences of cardiac surgery. If pulmonary hypertension is additionally involved with vasoplegic syndrome, circulation management becomes much more complicated. According to previous studies, pituitrin (a substitute for vasopressin, which contains vasopressin and oxytocin) not only constricts systemic circulation vessels and increases systemic circulation pressure but also likely decreases pulmonary artery pressure and pulmonary vascular resistance. The aim of this study is to investigate whether pituitrin is beneficial for the postoperative outcomes in patients with pulmonary hypertension undergoing cardiac surgery. Methods and analysis: The randomized controlled trial will include an intervention group continuously infused with 0.04 U/(kg h) of pituitrin and a control group. Adult patients with pulmonary hypertension undergoing elective cardiac surgery will be included in this study. Patients who meet the conditions and give their consent will be randomly assigned to the intervention group or the control group. The primary outcome is the composite endpoint of all-cause mortality within 30 days after surgery or common complications after cardiac surgery. Secondary outcomes include the incidence of other postoperative complications, length of hospital stay, and so on. Discussion: Pituitrin constricts systemic circulation vessels, increases systemic circulation pressure, and may reduce pulmonary artery pressure and pulmonary vascular resistance, which makes it a potentially promising vasopressor during the perioperative period in patients with pulmonary hypertension. Therefore, evidence from randomized controlled trials is necessary to elucidate whether pituitrin influences outcomes in patients with pulmonary hypertension following cardiac surgery.

Intensive versus conservative glycemic control in patients undergoing coronary artery bypass graft surgery: A protocol for systematic review of randomised controlled trials.

INTRODUCTION: Hyperglycemia and hypoglycemia are common during coronary artery bypass graft (CABG) and are associated with a variety of postoperative outcomes. Therefore, the strategy of intraoperative glycemic control is an important issue for the patients undergoing CABG. This systematic review aims to evaluate the effect of different intraoperative glycemic control strategies on postoperative outcomes. METHODS AND ANALYSES: We will perform this systematic review of randomised controlled trials (RCTs) according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Relevant studies will be searched in Medline, Embase, Cochrane Library and Web of Science. Two independent reviewers will conduct study selection, data extraction, risk of bias and quality assessment. The primary outcome is postoperative mortality, and the secondary outcomes include the duration of mechanical ventilation in the intensive care unit (ICU), the incidence of postoperative myocardial infarction (MI), the incidence of postoperative atrial fibrillation (AF), the type and volume of blood product transfusion, the rate of rehospitalization, the rate of cerebrovascular accident, the rate of significant postoperative bleeding, the rate of infection, the incidence of acute kidney failure (AKF), hospital and ICU lengths of stay (LOS). ReviewManager 5.4 will be used for data management and statistical analysis. The Cochrane risk-of -bias tool 2.0 and GRADEpro will be applied for risk of bias and quality assessment of the evidence. DISCUSSION: There is no consensus that which strategy of glycemic control is better for improving postoperative complications of patients undergoing CABG. The results of our study might provide some evidence for the relationship between intraoperative glycemic control strategies and postoperative outcomes in patients undergoing CABG.

The effect of topical airway anesthesia on hemodynamic profiles during the induction period in patients undergoing cardiac surgery: Study protocol for a randomized controlled trial.

Background: Patients scheduled for cardiac surgery are often accompanied by cardiac dysfunction and hemodynamic instability. However, the conventional induction strategy for anesthesia using high-dose intravenous anesthetics is often associated with persistent and recurrent hypotension after tracheal intubation. The purpose of this study is to investigate the effects of topical airway anesthesia on the hemodynamic profile of patients undergoing cardiac surgery during the induction period. Methods: This is a superiority, single-blind, randomized controlled study with two parallel groups. Participants scheduled to undergo elective cardiac surgery will be allocated into two blocks according to the New York Heart Association (NYHA) classification and then randomly assigned to the following two groups at a 1:1 ratio: the conventional induction group and the combined topical airway anesthesia induction group. The combined topical airway anesthesia induction strategy includes aerosol inhalation airway anesthesia, subglottic airway anesthesia, and general anesthesia induction using low-dose intravenous anesthetics. The primary outcome is the area under the curve (AUC) of blood pressure below baseline mean arterial pressure (MAP) from 3 to 15 min after endotracheal intubation. Secondary outcomes include the AUC above baseline MAP and below baseline MAP at other time points, the highest and lowest arterial blood pressure values during the induction period, type and dose of vasoactive drugs, incidence of arrhythmias, cardiac function, and the incidence of postoperative hoarseness and sore throat. Discussion: The study will explore whether aerosol inhalation airway anesthesia and subglottic airway anesthesia could reduce the incidence and duration of hypotension during the induction period in patients undergoing cardiac surgery. Clinical Trial Registration: This trial was registered on www.ClinicalTrials.gov (NCT05323786).

Comparison of out-of-plane short axis with in-plane long axis for ultrasound-guided radial arterial cannulation: A systematic review with trial sequential analysis of randomised controlled trials.

Background: It is controversial whether the short-axis out-of-plane or long-axis in-plane approach is a better needling technique for ultrasound-guidance radial artery cannulation. We aimed to compare the efficacy and safety of the two approaches for ultrasound-guided radial artery cannulation. Methods: A systematic search of Medline, Embase, the Cochrane Library, and Web of Science for relevant articles published until 1 May 2021 was conducted. Randomised controlled trials comparing the long-axis in-plane with short-axis out-of-plane approaches were included. Review Manager software version 5.4, STATA version 14.2, and trial sequential analysis (TSA) version 0.9.5.10 Beta were used for statistical analysis. Risk of bias and methodological quality of all studies included in this review were assessed according to the Cochrane Collaboration tool for the risk of bias. Subgroup analyses and meta-regression were performed to explore sources of heterogeneity. Results: The rate of cannula insertion success on the first attempt was similar between the short-axis out-of-plane and long-axis in-plane approaches (RR = 1.03; 95% CI: 0.83 to 1.28; P = 0.79; I 2 = 83.0%). No significant differences were observed in total time to successful cannulation between the two approaches (MD = -3.9; 95% CI:-18.30 to 10.49; P = 0.6; I 2 = 97%). However, the required information size for the success rate of the first attempt and total time to successful cannulation was not reached. Conclusion: It remains inconclusive whether short-axis out-of-plane is a better choice for radial arterial cannulation than the long-axis in-plane approach. Inexperienced operators may need more attempts and longer ultrasound location time with the short-axis out-of-plane technique. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021236098].

RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to have devastating consequences worldwide. Recently, great efforts have been made to identify SARS-CoV-2 host factors, but the regulatory mechanisms of these host molecules, as well as the virus per se, remain elusive. Here we report a role of RNA G-quadruplex (RG4) in SARS-CoV-2 infection. Combining bioinformatics, biochemical and biophysical assays, we demonstrate the presence of RG4s in both SARS-CoV-2 genome and host factors. The biological and pathological importance of these RG4s is then exemplified by a canonical 3-quartet RG4 within Tmprss2, which can inhibit Tmprss2 translation and prevent SARS-CoV-2 entry. Intriguingly, G-quadruplex (G4)-specific stabilizers attenuate SARS-CoV-2 infection in pseudovirus cell systems and mouse models. Consistently, the protein level of TMPRSS2 is increased in lungs of COVID-19 patients. Our findings reveal a previously unknown mechanism underlying SARS-CoV-2 infection and suggest RG4 as a potential target for COVID-19 prevention and treatment.

A microRNA checkpoint for Ca2+ signaling and overload in acute pancreatitis.

Acute pancreatitis (AP) is a common digestive disease without specific treatment, and its pathogenesis features multiple deleterious amplification loops dependent on translation, triggered by cytosolic Ca2+ ([Ca2+]i) overload; however, the underlying mechanisms in Ca2+ overload of AP remains incompletely understood. Here we show that microRNA-26a (miR-26a) inhibits pancreatic acinar cell (PAC) store-operated Ca2+ entry (SOCE) channel expression, Ca2+ overload, and AP. We find that major SOCE channels are post-transcriptionally induced in PACs during AP, whereas miR-26a expression is reduced in experimental and human AP and correlated with AP severity. Mechanistically, miR-26a simultaneously targets Trpc3 and Trpc6 SOCE channels and attenuates physiological oscillations and pathological elevations of [Ca2+]i in PACs. MiR-26a deficiency increases SOCE channel expression and [Ca2+]i overload, and significantly exacerbates AP. Conversely, global or PAC-specific overexpression of miR-26a in mice ameliorates pancreatic edema, neutrophil infiltration, acinar necrosis, and systemic inflammation, accompanied with remarkable improvements on pathological determinants related with [Ca2+]i overload. Moreover, pancreatic or systemic administration of an miR-26a mimic to mice significantly alleviates experimental AP. These findings reveal a previously unknown mechanism underlying AP pathogenesis, establish a critical role for miR-26a in Ca2+ signaling in the exocrine pancreas, and identify a potential target for the treatment of AP.

Optimization of miR-22 expression cassette for rAAV delivery on diabetes.

MicroRNA-22 (miR-22) was suggested to be important for type 2 diabetes but its functions for this disease remained unclear. Recombinant adeno-associated virus (rAAV)-mediated miR delivery is a powerful approach to study miR functions in vivo, however, the overexpression of miR-22 by rAAV remains challenging because it is one of the most abundant miRs in the liver. In this study, a series of expression cassettes were designed and compared. It was shown that different lengths of primary miR-22 were overexpressed in HEK293 and HeLa cells but the longer ones were more efficiently expressed. miR-22 may be placed in either introns or the 3' UTR of a transgene for efficient overexpression. RNA polymerase III or II promoters were successfully utilized for miR expression but the latter showed higher expression levels in cell lines. Specifically, miR-22 was expressed efficiently together with an EGFP gene. After screening, a liver-specific TTR promoter was chosen to overexpress miR-22 in diabetic mice fed a high-fat diet. It was shown that miR-22 was overexpressed 2-3 folds which improved the insulin sensitivity significantly. The approach utilized in this study to optimize miR overexpression is a powerful tool for the creation of efficient rAAV vectors for the other miRs.

Transcriptome analysis reveals key genes and pathways associated with egg production in Nandan-Yao domestic chicken.

BACKGROUND: Egg production is a very important economic trait in chicken breeding, but its molecular mechanism is unclear until now. Nandan-Yao chicken (Gallus gallus domesticus) is a native breed in Guangxi province, China, which is famous for good meet quality, but with low egg production. METHODS: To explore the molecular regulation related to egg production, high egg production (HEP) and low egg production (LEP) were divided according to the total egg number at 55 weeks, and the concentration of serum sex hormones was tested to evaluate the physiological function of ovary and uterus. RNA sequencing (RNA-Seq) was used to explore the transcriptome from the ovary and uterus of Nandan-Yao chicken. RESULTS: The levels of serum sex hormone showed that concentrations of estradiol (E2), follicle-stimulating hormone (FSH), and luteotropic hormone (LH) were significantly higher in HEP than those in LEP (P < 0.01), while the concentration of testosterone (T) was significantly lower in HEP (P < 0.01). RNA-Seq analysis identified 901 and 2763 differentially expressed genes (DEGs) in ovary and uterus, respectively. Enrichment analysis showed that DEGs were significantly involved in the regulation of tight junction in the ovary (P < 0.05), while in uterus, DEGs were mainly enriched in the phagosome, ECM-receptor interaction, cell adhesion molecules (CAMs), focal adhesion, cardiac muscle contraction, cytokine-cytokine receptor interaction, and the regulation of MAPK signaling pathway (P < 0.05). Protein network interaction and function analyses revealed that FN1, FGF7, SOX2 identified from the ovary, and UQCRH, COX5A, FN1 from the uterus might be key candidate genes for egg production in Nandan-Yao chicken. CONCLUSIONS: Our study provided key candidate genes and pathways involved in the egg-laying process of Nandan-Yao chicken and could help to further understand the molecular mechanisms of chicken reproduction.

Metagenomic analysis reveals linkages between cecal microbiota and feed efficiency in Xiayan chickens.

The cecal microbiota plays a critical role in energy harvest and nutrient digestion, influencing intestinal health and the performance of chickens. Feed efficiency (FE) is essential for improving economic efficiency and saving social resources in chicken production and may be affected by the cecal microbiota. Therefore, to investigate the composition and functional capacity of cecum microbes related to FE in Xiayan chicken, an indigenous breed in Guangxi province, metagenome sequencing was performed on chicken cecal contents. 173 male and 167 female chickens were divided into high and low FE groups according to the residual feed intake. The cecal microbial genome was extracted and sequenced. The results showed that the genera Bacteroides, Prevotella, and Alistipes were the 3 most abundant in each cecal microbiome. The linear discriminant analysis effect size revealed 6 potential biomarkers in male and 14 in female chickens. Notably, the relative abundance of Lactobacillus in the high FE group was higher than that of the low FE group both in the male and female chickens, and the species Limosilactobacillus oris has a higher score in the high FE group of male chickens. In contrast, some potentially pathogenic microorganisms such as Campylobacter avium in females and Helicobacter pullorum in males were enriched in the low FE group. Predictive functional analysis showed that the high FE group in male chickens had a greater ability of xenobiotics biodegradation and metabolism and signaling molecules and interaction. In addition, the host sex was found to exert effects on the cecal microbial composition and function associated with FE. These results increased our understanding of the cecal microbial composition and identified many potential biomarkers related to FE, which may be used to improve the FE of the chickens.

RNA G-quadruplex regulates microRNA-26a biogenesis and function.

BACKGROUND & AIMS: RNA G-quadruplexes (RG4s) appear to be important in post-transcriptional gene regulation, but their pathophysiological functions remain unknown. MicroRNA-26a (miR-26a) is emerging as a therapeutic target for various human diseases, however the mechanisms underlying endogenous miR-26a regulation are poorly understood. Herein, we study the role of RG4 in miR-26a expression and function in vitro and in vivo. METHODS: Putative RG4s within liver-enriched miRNAs were predicted by bioinformatic analysis, and the presence of an RG4 structure in the miR-26a-1 precursor (pre-miR-26a-1) was further analyzed by biophysical and biochemical methods. RG4 stabilizers, pre-miR-26a-1 overexpression plasmids, and luciferase reporter assays were used to assess the effect of RG4 on pre-miR-26a-1 maturation. Both miR-26a knock-in and knockout mouse models were employed to investigate the influence of this RG4 on miR-26a expression and function. Moreover, the interaction between RG4 in pre-miR-26a-1 and DEAH-box helicase 36 (DHX36) was determined by biophysical and molecular methods. Finally, miR-26a processing and DHX36 expression were quantified in the livers of obese mice. RESULTS: We identify a guanine-rich sequence in pre-miR-26a-1 that can fold into an RG4 structure. This RG4 impairs pre-miR-26a-1 maturation, resulting in a decrease in miR-26a expression and subsequently an increase in miR-26a cognate targets. In line with known miR-26a functions, this RG4 can regulate hepatic insulin sensitivity and lipid metabolism in vitro and in vivo. Furthermore, we reveal that DHX36 can bind and unwind this RG4 structure, thereby enhancing miR-26a maturation. Intriguingly, there is a concordant decrease of miR-26a maturation and DHX36 expression in obese mouse livers. CONCLUSIONS: Our findings define a dynamic DHX36/RG4/miR-26a regulatory axis during obesity, highlighting an important role of RG4 in physiology and pathology. LAY SUMMARY: Specific RNA sequences called G-quadruplexes (or RG4) appear to be important in post-transcriptional gene regulation. Obesity leads to the formation of these RG4 structures in pre-miR-26a-1 molecules, impairing the maturation and function of miR-26a, which has emerged as a therapeutic target in several diseases. This contributes to hepatic insulin resistance and the dysregulation of liver metabolism.