Association of sleep duration and prevalence of sarcopenia: A large cross-sectional study.

Background: The purpose of this study was to examine the relationship between sleep duration and risk of sarcopenia in in general U.S. population. Methods: Utilizing publicly available data from the National Health and Nutrition Examination Survey spanning from 2011 to 2014, we explored the association between sleep duration and prevalence of sarcopenia. To investigate their relationship, we conducted weighted multivariate logistic regression analysis, restricted cubic splines (RCS) curve, and subgroup analysis. Results: The study included 8,200 individuals, among whom 99 (0.9 %) had sarcopenia. The RCS curve revealed a U-shaped association of sarcopenia with sleep duration (P for nonlinearity = 0.020), showing that the risk of sarcopenia decreases with increasing sleep duration, reaching the lowest risk around 6.67 h. After controlling for underlying cofounders, compared to individuals with sleep duration < 5 h, the odds ratios with 95 % confidence intervals of sarcopenia were 0.64 (0.27, 1.49), 0.50 (0.20, 1.26), 0.65 (0.27, 1.60), and 2.31 (0.73, 7.30) for < 5-6, 6.5-7.5, 8-9, and > 9 h group. The U-shaped association between sleep time and prevalence of sarcopenia also was observed in the subjects who aged < 40 or ≥ 40 years, were male or female, with or without hypertension, and diabetes mellitus. Conclusions: In summary, both short and long sleep durations increased prevalence of sarcopenia. Further studies are needed to explore the underlying mechanisms.

One Stone Two Birds: Anomalously Enhancing the Cross-Plane and In-Plane Heat Transfer in 2D/3D Heterostructures by Defects Engineering.

This study addresses a crucial challenge in two-dimensional (2D) material-based electronic devices-inefficient heat dissipation across the van der Waals (vdW) interface connecting the 2D material to its three-dimensional (3D) substrate. The objective is to enhance the interfacial thermal conductance (ITC) of 2D/3D heterostructures without compromising the intrinsic thermal conductivities (κ) of 2D materials. Using 2D-MoS2/3D-GaN as an example, a novel strategy to enhance both the ITC across 2D/3D interface and κ of 2D material is proposed by introducing a controlled concentration (ρ) of vacancy defects to substrate's bottom surface. Molecular dynamics simulations demonstrate a notable 2.1-fold higher ITC of MoS2/GaN at ρ = 4% compared to the no-defective counterpart, along with an impressive 56% enhancement in κ of MoS2 compared to the conventional upper surface modification approaches. Phonon dynamics analysis attributes the ITC enhancement to increased phonon coupling between MoS2 and GaN, resulting from polarization conversion and hybridization of phonons at the defective surface. Spectral energy density analysis affirms that the improved κ of MoS2 directly results from the proposed strategy, effectively reducing phonon scattering at the interface. This work provides an effective approach for enhancing heat transfer in 2D/3D vdW heterostructures, promisingly advancing electronics' heat dissipation.

Neuroinflammation generated by HIV-infected microglia promotes dysfunction and death of neurons in human brain organoids.

Despite the success of combination antiretroviral therapy (ART) for individuals living with HIV, mild forms of HIV-associated neurocognitive disorder (HAND) continue to occur. Brain microglia form the principal target for HIV infection in the brain. It remains unknown how infection of these cells leads to neuroinflammation, neuronal dysfunction, and/or death observed in HAND. Utilizing two different inducible pluripotent stem cell-derived brain organoid models (cerebral and choroid plexus [ChP] organoids) containing microglia, we investigated the pathogenic changes associated with HIV infection. Infection of microglia was associated with a sharp increase in CCL2 and CXCL10 chemokine gene expression and the activation of many type I interferon stimulated genes (MX1, ISG15, ISG20, IFI27, IFITM3 and others). Production of the proinflammatory chemokines persisted at low levels after treatment of the cell cultures with ART, consistent with the persistence of mild HAND following clinical introduction of ART. Expression of multiple members of the S100 family of inflammatory genes sharply increased following HIV infection of microglia measured by single-cell RNA-seq. However, S100 gene expression was not limited to microglia but was also detected more broadly in uninfected stromal cells, mature and immature ChP cells, neural progenitor cells and importantly in bystander neurons suggesting propagation of the inflammatory response to bystander cells. Neurotransmitter transporter expression declined in uninfected neurons, accompanied by increased expression of genes promoting cellular senescence and cell death. Together, these studies underscore how an inflammatory response generated in HIV-infected microglia is propagated to multiple uninfected bystander cells ultimately resulting in the dysfunction and death of bystander neurons.

Oral Administration Properties Evaluation of Three Milk-derived Extracellular Vesicles Based on Ultracentrifugation Extraction Methods.

Milk-derived extracellular vesicles (M-EVs) are low-cost, can be prepared in large quantities, and can cross the gastrointestinal barrier for oral administration. However, the composition of milk is complex, and M-EVs obtained by different extraction methods may affect their oral delivery. Based on this, we propose a new method for extracting M-EVs based on cryogenic freezing treatment (Cryo-M-EVs) and compare this method with the previously reported acetic acid treatment (Acid-M-EVs) method and the conventional ultracentrifugation method (Ulltr-M-EVs). The new method simplifies the pretreatment step and achieves 25-fold and 2-fold higher yields than Acid-M-EVs and Ulltr-M-EVs. And it was interesting to note that Cryo-M-EVs and Acid-M-EVs had higher cellular uptake efficiency, and Cryo-M-EVs presented the best transepithelial transport effect. After oral administration of the three M-EVs extracted by three methods in mice, Cryo-M-EVs effectively successfully crossed the gastrointestinal barrier and achieved hepatic accumulation, whereas Acid-M-EVs and Ultr-M-EVs mostly resided in the intestine. The M-EVs obtained by the three extraction methods showed a favorable safety profile at the cellular as well as animal level. Therefore, when M-EVs obtained by different extraction methods are used for oral drug delivery, we can utilize their accumulation properties at different sites to better deal with different diseases. This article is protected by copyright. All rights reserved.

Process of mercury accumulation in urban strip river artificial wetland ecosystems: a case study of Changchun, a typical industrial city in Northeast China.

Mercury (Hg), as a global pollutant, is persistent, migratory, insidious, highly biotoxic and highly enriched, and is widely distributed in the atmosphere, hydrosphere, biosphere and lithosphere. Wetland ecosystems, as active mercury reservoirs, have become the most important sources and sinks of heavy metal mercury. Distinguished from natural wetlands, artificial wetlands located in urban sections of rivers face problems such as diverse urban pollution sources and complex spatial and temporal changes. Therefore, in this study, five intermittently distributed artificial wetlands were selected from the upstream to the downstream of the Changchun section of the Yitong River, a tributary of the Songhua River basin in the old industrial base of Northeast China. The mercury levels in the water bodies, sediments and plants of the artificial wetlands were collected and tested in four quarters from April 2023 to analyse the spatial and temporal distribution characteristics of total mercury. The results showed that the mercury levels in the water bodies, sediments and plants of the five wetlands showed a fluctuating trend with the river flow direction and had certain spatial and temporal distribution characteristics. This phenomenon was attributed to the sinking of external mercury pollution sources. In general, the wetland ecosystems showed a decreasing trend in the total Hg output of the downstream watershed. This may be due to the retention of particulate matter by aquatic plants in artificial wetlands to regular salvage of dead aquatic plants. At the same time urbanization and industrialization affect mercury levels in aquatic environments, so the risk of residential exposure needs to be looked at.

Plastic Clamp Versus Conventional Surgical Dissection Technique in Pediatric Circumcision: A Systematic Review and Meta-Analysis.

PURPOSE: Phimosis is a common condition of the urinary system in children and often requires surgical treatment. However, the optimal method of circumcision for children has not been determined. We conducted a systematic review and meta-analysis to compare the safety and effectiveness of plastic clamp with conventional surgical circumcision in pediatric circumcision. METHODS: A literature search was carried out to compare the plastic clamp and conventional dissection technique in the pediatric population. The following search terms were used: "circumcision", "plastic clamp", "conventional", "plastibell", "children" and etc. Meta-analysis was used to pool and evaluate variables such as operative time, blood loss, wound infection, bleeding, edema, and total postoperative complications. RESULTS: The plastic clamp technique (PCT) was used in 10,412 of the 17,325 participants in the nine studies, while the conventional surgical dissection technique (CST) was used on 6913 patients. When compared to the CST approach, the PCT approach resulted in shorter operative times (mean difference (MD) -17.48, 95% CI -22 to -12.96; P < 0.001), less blood loss (MD -4.25, 95% CI -7.75 to -0.77; P = 0.02), and a higher incidence of postoperative edema (OR 2.33, 95% CI 1.34 to 4.08; P = 0.003). However, no significant difference was found in the incidence of postoperative complications, including wound infection and bleeding between PCT and CST. CONCLUSIONS: PCT is a safe and time-saving option in the pediatric population. However, this method appeared to have a significant greater rate of postoperative edema.

Activation of the cGMP/PKG/ERK signaling pathway associated with PDE5Is inhibits fibroblast activation by downregulating autophagy in early progressive benign prostatic hyperplasia.

PURPOSE: Benign prostatic hyperplasia (BPH) is one of the most prevalent diseases affecting aging males. However, approximately, 8% of the BPH patients under 50-year-old experience remarkably early progression, for reasons that remain elusive. Among the various factors implicated in promoting BPH advancement, the activation of fibroblasts and autophagy hold particular importance. Our research endeavors to explore the mechanisms behind the accelerated progression in these patients. METHODS: Immunohistochemistry and immunofluorescence were performed to detect the expression levels of LC3, p62, PDE5, and α-SMA in diverse BPH tissues and prostate stromal cells. The autophagy activator rapamycin, the autophagy suppressor chloroquine, and siRNA transfection were used to identify the impact of autophagy on fibroblast activation. RESULTS: Prostatic stromal fibroblasts in early progressive BPH tissues displayed activation of autophagy with an upregulation of LC3 and a concurrent downregulation of p62. After starvation or rapamycin treatment to a heightened level of autophagy, fibroblasts exhibited activation. Conversely, chloroquine treatment and ATG-7-knockdown effectively suppressed the level of autophagy and fibroblast activation. High expression of PDE5 was found in early progressive BPH stromal cells. The administration of PDE5 inhibitors (PDE5Is) hindered fibroblast activation through suppressing autophagy by inhibiting the ERK signaling pathway. CONCLUSION: Our findings suggest that autophagy plays a pivotal role in promoting BPH progression through fibroblast activation, while PDE5Is effectively suppress autophagy and fibroblast activation via the ERK signaling pathway. Nevertheless, further investigations are warranted to comprehensively elucidate the role of autophagy in BPH progression.

Circular RNA circHIPK2 inhibits colon cancer cells through miR-373-3p/RGMA axis.

Circular RNAs (circRNAs) have been implicated in cancer development. However, their regulation, function, and underlying mechanisms of action remain unclear. We found that circHIPK2 was downregulated in colon cancer, and low expression levels of circHIPK2 were associated with high tumor grade and poor patient survival. The expression of circHIPK2 was observed to be regulated by the transcription factor HOXD10, which was downregulated in colon cancer. Consequently, low circHIPK2 expression promoted colon cancer cell proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, circHIPK2 sponges miR-373-3p to upregulate the expression of the tumor suppressor RGMA, leading to the activation of BMP/Smad signaling and, ultimately, the inhibition of colon cancer cells, indicating that circHIPK2 inhibits colon cancer cells through the miR-373-3p/RGMA/BMP pathway. These findings revealed a previously unknown regulation, function, and underlying mechanism of circHIPK2 in cancer cells. Hence, circHIPK2 may have a prognostic value and serve as a potential target for colon cancer treatment.

Simultaneous detection of bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BoHV-1) using recombinase polymerase amplification.

Bovine viral diarrhea virus (BVDV) is considered to be the most common agent of severe diarrhea in cattle worldwide, causing fever, diarrhea, ulcers, and abortion. Bovine herpesvirus 1 (BoHV-1) is also a major bovine respiratory disease agent that spreads worldwide and causes extensive damage to the livestock industry. Recombinase polymerase amplification (RPA) is a novel nucleic acid amplification method with the advantages of high efficiency, rapidity and sensitivity, which has been widely used in the diagnosis of infectious diseases. A dual RPA assay was developed for the simultaneous detection of BVDV and BoHV-1. The assay was completed at a constant temperature of 37 °C for 30 min. It was highly sensitive and had no cross-reactivity with other common bovine viruses. The detection rate of BVDV RPA in clinical samples (36.67%) was higher than that of PCR (33.33%), the detection rate of BoHV-1 RPA and PCR were equal. Therefore, the established dual RPA assay for BVDV and BoHV-1 could be a potential candidate for use as an immediate diagnostic.

Impact of English-Speaking Environments and Chinese Language Pronunciation on the Speaking Proficiency of English Learners in China: A Comprehensive Study.

English is widely regarded as a global language, and it has become increasingly important for global communication. As a result, the demand for English language education has been on the rise. In China, a significant number of individuals are engaged in learning the English language. However, many English learners in China encounter challenges when it comes to developing their speaking skills. This study aims to investigate the factors influencing the speaking skills of English learners in China. Employing a mixed-methods approach, data were collected through a questionnaire from 455 college students from three different courses (arts, science & business, and commerce) in China. The study findings identified several factors impacting the speaking skills of English learners in China, including limited opportunities for speaking practice, fear of making mistakes, limited exposure to English-speaking environments, inadequate teacher training, and the influence of the Chinese language on English pronunciation. Additionally, the study highlighted that learners who have greater exposure to English-speaking environments and more opportunities for speaking practice tend to demonstrate better speaking skills. The novelty of this study lies in its valuable insights into the factors influencing the speaking skills of English learners in China. Based on the findings, it is recommended that English teachers receive enhanced training to effectively teach speaking skills, and learners should be provided with increased opportunities for speaking practice, such as participating in group discussions or engaging in speaking activities.

Nonlinear error elimination using the fusion of PGC-DCM, geometric fitting, and Atan algorithms.

A phase generated carrier (PGC) demodulation scheme is always accompanied by nonlinear errors. We propose a fusion of PGC differential and cross multiplying (PGC-DCM), geometric fitting, and arctangent (Atan) algorithms for fiber optic interferometric sensors to eliminate nonlinear errors. The output amplitude of the PGC-DCM algorithm is used to judge whether the Lissajous figure of quadrature signals is larger than 1/2 ellipse arc. When the Lissajous figure exceeds 1/2 ellipse arc, the contaminated quadrature signals are corrected by the ellipse correction parameters calculated from the geometric fitting; otherwise, the previous fitting parameters are employed for correction. Geometric fitting is realized by minimizing the Sampson error, and its failure problem under small signals is solved by using the temporary stability of fitting results. Finally, desired signals are extracted from the corrected quadrature signals by the Atan algorithm. Experimental results show that the fusion combines the merits of the three algorithms and expands the application of the geometric fitting in PGC demodulation schemes.

Formation of Nitrogen-Doped Positively Curved Molecules by π-Extension.

Two nitrogen-doped positively curved aromatic molecules bearing doubly fused pentagonal rings were synthesized and characterized. Crystallographic analysis confirms the formation of a bowl-shaped structure, which is induced by the fusion of adjacent pentagons to the rigid aromatic planes. Both compounds demonstrate good photoluminescence. These electron-rich bowl-shaped molecules can associate with C60 to form complexes in 2:1 ratio in toluene with different association constants depending on the molecular dimension of the hosts.

Chondroprotective effects of Apolipoprotein D in knee osteoarthritis mice through the PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Because the pathophysiology of osteoarthritis (OA) has not been fully elucidated, targeted treatments are lacking. In this study, we assessed the role and underlying mechanism apolipoprotein D (APOD) on the development of OA. METHODS: To establish an in vitro OA model, we extracted primary chondrocytes from the cartilage of C57BL/6 mice and stimulated the chondrocytes with IL-1ß. After APOD intervention or incubation with an overexpressing plasmid, we detected inflammatory-related markers using RT-qPCR, Western blotting, and ELISA. To detect apoptosis and autophagy-related markers, we used flow cytometry, immunofluorescence, and transmission electron microscopy (TEM). Finally, we measured the level of oxidative stress. We also used RNA-seq to identify the APOD-regulated downstream signaling pathways. We used an in vivo mice OA model of the anterior cruciate ligament transection (ACLT) and administered intra-articular adenovirus overexpressing APOD. To examine cartilage damage severity, we used immunohistochemical analysis (IHC), micro-CT, scanning electron microscopy (SEM), and Safranin O-fast green staining. RESULTS: Our results showed that APOD inhibited chondrocyte inflammation, degeneration, and apoptosis induced by IL-1ß. Additionally, APOD reversed autophagy inhibition and oxidative stress and also blocked activation of the PI3K/AKT/mTOR signaling pathway induced by IL-1ß. Finally, overexpression of the APOD gene through adenovirus was sufficient to mitigate OA progression. CONCLUSIONS: Our findings revealed that APOD had a chondroprotective role in OA progression by the PI3K/AKT/mTOR signaling pathway.

Escaping from CRISPR-Cas-mediated knockout: the facts, mechanisms, and applications.

Clustered regularly interspaced short palindromic repeats and associated Cas protein (CRISPR-Cas), a powerful genome editing tool, has revolutionized gene function investigation and exhibits huge potential for clinical applications. CRISPR-Cas-mediated gene knockout has already become a routine method in research laboratories. However, in the last few years, accumulating evidences have demonstrated that genes knocked out by CRISPR-Cas may not be truly silenced. Functional residual proteins could be generated in such knockout organisms to compensate the putative loss of function, termed herein knockout escaping. In line with this, several CRISPR-Cas-mediated knockout screenings have discovered much less abnormal phenotypes than expected. How does knockout escaping happen and how often does it happen have not been systematically reviewed yet. Without knowing this, knockout results could easily be misinterpreted. In this review, we summarize these evidences and propose two main mechanisms allowing knockout escaping. To avoid the confusion caused by knockout escaping, several strategies are discussed as well as their advantages and disadvantages. On the other hand, knockout escaping also provides convenient tools for studying essential genes and treating monogenic disorders such as Duchenne muscular dystrophy, which are discussed in the end.

Rejuvenating fecal microbiota transplant enhances peripheral nerve repair in aged mice by modulating endoneurial inflammation.

Peripheral nerve injury (PNI) resulting from trauma or neuropathies can cause significant disability, and its prognosis deteriorates with age. Emerging evidence suggests that gut dysbiosis and reduced fecal short-chain fatty acids (SCFAs) contribute to an age-related systemic hyperinflammation (inflammaging), which hinders nerve recovery after injury. This study thus aimed to evaluate the pro-regenerative effects of a rejuvenating fecal microbiota transplant (FMT) in a preclinical PNI model using aged mice. Aged C57BL/6 mice underwent bilateral crush injuries to their sciatic nerves. Subsequently, they either received FMT from young donors at three and four days after the injury or retained their aged gut microbiota. We analyzed gut microbiome composition and SCFA concentrations in fecal samples. The integrity of the ileac mucosal barrier was assessed by immunofluorescence staining of Claudin-1. Flow cytometry was utilized to examine immune cells and cytokine production in the ileum, spleen, and sciatic nerve. Various assessments, including behavioural tests, electrophysiological studies, and morphometrical analyses, were conducted to evaluate peripheral nerve function and repair following injury. Rejuvenating FMT reversed age-related gut dysbiosis by increasing Actinobacteria, especially Bifidobacteriales genera. This intervention also led to an elevation of gut SCFA levels and mitigated age-related ileac mucosal leakiness in aged recipients. Additionally, it augmented the number of T-helper 2 (Th2) and regulatory T (Treg) cells in the ileum and spleen, with the majority being positive for anti-inflammatory interleukin-10 (IL-10). In sciatic nerves, rejuvenating FMT resulted in increased M2 macrophage counts and a higher IL-10 production by IL-10+TNF-α- M2 macrophage subsets. Ultimately, restoring a youthful gut microbiome in aged mice led to improved nerve repair and enhanced functional recovery after PNI. Considering that FMT is already a clinically available technique, exploring novel translational strategies targeting the gut microbiome to enhance nerve repair in the elderly seems promising and warrants further evaluation.

SC-Net: Symmetrical conical network for colorectal pathology image segmentation.

BACKGROUND AND OBJECTIVE: Image segmentation of histopathology of colorectal cancer is a core task of computer aided medical image diagnosis system. Existing convolutional neural networks generally extract multi-scale information in linear flow structures by inserting multi-branch modules, which is difficult to extract heterogeneous semantic information under multi-level and different receptive field and tough to establish context dependency among different receptive field features. METHODS: To address these issues, we propose a symmetric spiral progressive feature fusion encoder-decoder network called the Symmetric Conical Network (SC-Net). First, we design a Multi-scale Feature Extraction Block (MFEB) matching with the Symmetric Conical Network to obtain multi-branch heterogeneous semantic information under different receptive fields, so as to enrich the diversity of extracted feature information. The encoder is composed of MFEB through spiral and multi-branch arrangement to enhance context dependence between different information flow. Secondly, the information loss of contour, color and others in high-level semantic information through causally stacking MFEB, the Feature Mapping Layer (FML) is designed to map low-level features to high-level semantic features along the down-sampling branch and solve the problem of insufficient global feature extraction in deep levels. RESULTS: The SC-Net was evaluated on our self-constructed colorectal cancer dataset, a publicly available breast cancer dataset and a polyp dataset. The results revealed that the mDice of segmentation reached 0.8611, 0.7259 and 0.7144. We compare our model with the state-of-art semantic segmentation UNet++, PSPNet, Attention U-Net, R2U-Net and other advanced segmentation networks. The experimental results demonstrate that we achieve the most advanced performance. CONCLUSIONS: The results indicate that the proposed SC-Net excels in segmenting H&E stained pathology images, effectively preserving morphological features and spatial information even in scenarios with weak texture, poor contrast, and variations in appearance.

Lipidomics reveals new lipid-based lung adenocarcinoma early diagnosis model.

Lung adenocarcinoma (LUAD) continues to pose a significant mortality risk with a lack of dependable biomarkers for early noninvasive cancer detection. Here, we find that aberrant lipid metabolism is significantly enriched in lung cancer cells. Further, we identified four signature lipids highly associated with LUAD and developed a lipid signature-based scoring model (LSRscore). Evaluation of LSRscore in a discovery cohort reveals a robust predictive capability for LUAD (AUC: 0.972), a result further validated in an independent cohort (AUC: 0.92). We highlight one lipid signature biomarker, PE(18:0/18:1), consistently exhibiting altered levels both in cancer tissue and in plasma of LUAD patients, demonstrating significant predictive power for early-stage LUAD. Transcriptome analysis reveals an association between increased PE(18:0/18:1) levels and dysregulated glycerophospholipid metabolism, which consistently displays strong prognostic value across two LUAD cohorts. The combined utility of LSRscore and PE(18:0/18:1) holds promise for early-stage diagnosis and prognosis of LUAD.