Chemical Cross-Linking Cellulose Aerogel-Based Triboelectric Nanogenerators for Energy Harvesting and Sensing Human Activities.

Zinc oxide (ZnO) is a widely employed material for enhancing the performance of cellulose-based triboelectric nanogenerators (C-TENGs). Our study provides a novel chemical interpretation for the improved output efficiency of ZnO in C-TENGs. C-TENGs exhibit excellent flexibility and integration, achieving a maximum open-circuit voltage (Voc) of 210 V. The peak power density is 54.4 µW/cm2 with a load resistance of 107 Ω, enabling the direct powering of 191 light-emitting diodes with the generated electrical output. Moreover, when deployed as self-powered sensors, C-TENGs exhibit prolonged operational viability and responsiveness, adeptly discerning bending and motion induced by human interaction. The device's sensitivity, flexibility, and stability position it as a promising candidate for a diverse array of energy-harvesting applications and advanced healthcare endeavors. Specifically, envisaging sensitized wearable sensors for human activities underscores the multifaceted potential of C-TENGs in enhancing both energy-harvesting technologies and healthcare practices.

Density Analysis of Adsorption Phase in the Thermodynamic Study of Shale Gas Adsorption.

Understanding the adsorption mechanism and precisely predicting the thermodynamic adsorption properties of methane at high pressure are crucial while very challenging for shale gas development. In this study, we demonstrated that the Langmuir adsorption model combining with different empirical methods to determine the adsorption phase density makes the calculated isothermal adsorption heat violate Henry's law at low pressure. For instance, the isothermal adsorption heat calculated by the Langmuir-Freundlich model contradicts Henry's law when the absolute adsorption quantity is zero. Given the current challenge in accurately calculating the adsorption phase density, it is necessary to impose constraints on the parameters of the adsorption model by adhering to Henry's law to maintain thermodynamic consistency. We found that the adsorption phase volume of methane molecules lies between the micropore volume and the total pore volume when shale adsorption reaches saturation. The adsorption mechanism involves not only filling micropores but also monolayer adsorption in meso-macro pores. The high-energy adsorption sites for methane are primarily concentrated in organic matter, while within these methane adsorption areas in shale, the high-energy adsorption sites for water are mainly located in kaolinite within clay minerals. The zero-pressure heat of adsorption is a temperature-independent thermodynamic index, yet it is influenced by the water content. It can therefore be selected as a quantitative measure to evaluate the impact of methane adsorption on water.

Development and performance assessment of novel machine learning models for predicting postoperative pneumonia in aneurysmal subarachnoid hemorrhage patients: external validation in MIMIC-IV.

Background: Postoperative pneumonia (POP) is one of the primary complications after aneurysmal subarachnoid hemorrhage (aSAH) and is associated with postoperative mortality, extended hospital stay, and increased medical fee. Early identification of pneumonia and more aggressive treatment can improve patient outcomes. We aimed to develop a model to predict POP in aSAH patients using machine learning (ML) methods. Methods: This internal cohort study included 706 patients with aSAH undergoing intracranial aneurysm embolization or aneurysm clipping. The cohort was randomly split into a train set (80%) and a testing set (20%). Perioperative information was collected from participants to establish 6 machine learning models for predicting POP after surgical treatment. The area under the receiver operating characteristic curve (AUC), precision-recall curve were used to assess the accuracy, discriminative power, and clinical validity of the predictions. The final model was validated using an external validation set of 97 samples from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Results: In this study, 15.01% of patients in the training set and 12.06% in the testing set with POP after underwent surgery. Multivariate logistic regression analysis showed that mechanical ventilation time (MVT), Glasgow Coma Scale (GCS), Smoking history, albumin level, neutrophil-to-albumin Ratio (NAR), c-reactive protein (CRP)-to-albumin ratio (CAR) were independent predictors of POP. The logistic regression (LR) model presented significantly better predictive performance (AUC: 0.91) than other models and also performed well in the external validation set (AUC: 0.89). Conclusion: A machine learning model for predicting POP in aSAH patients was successfully developed using a machine learning algorithm based on six perioperative variables, which could guide high-risk POP patients to take appropriate preventive measures.

Association between serum α-Klotho levels and osteoarthritis prevalence among middle-aged and older adults: an analysis of the NHANES 2007-2016.

BACKGROUND: As individuals age, the prevalence of osteoarthritis tends to increase gradually. α-Klotho is a hormone renowned for its anti-aging properties. However, the precise role of serum α-Klotho in osteoarthritis is still not fully comprehended. METHODS: We conducted a cross-sectional study utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016. Serum α-Klotho levels were measured using an enzyme-linked immunosorbent assay (ELISA). Osteoarthritis was assessed through self-reported questionnaires. Through univariate and multivariate logistic regression analyses, smooth curve fitting, threshold effect analysis, and subgroup analyses, we delved into the potential association between them. RESULTS: The study encompassed a cohort of 10,265 participants. In fully adjusted models of multivariate logistic regression analysis, we identified a negative correlation between serum ln α-Klotho and OA (OR = 0.77, 95% CI: 0.65-0.91, p = 0.003). When stratifying serum α-Klotho levels into tertiles, individuals in the highest tertile exhibited a 26% reduced risk of OA compared to those in the lowest tertile (OR = 0.84, 95% CI: 0.73-0.97, p = 0.014). Subsequent analyses indicated a linearly negative association. In subgroup analyses, we explored the relationship between serum ln α-Klotho and osteoarthritis across diverse populations, revealing the persistence of this association in the majority of subgroups. CONCLUSION: Serum α-Klotho levels exhibit a significant negative linear correlation with the prevalence of osteoarthritis in middle-aged and elderly populations in the United States.

Inhibition of MAGL attenuates Intervertebral Disc Degeneration by Delaying nucleus pulposus senescence through STING.

Intervertebral disc degeneration (IVDD) stands as the primary cause of low back pain (LBP). A significant contributor to IVDD is nucleus pulposus cell (NPC) senescence. However, the precise mechanisms underlying NPC senescence remain unclear. Monoacylglycerol lipase (MAGL) serves as the primary enzyme responsible for the hydrolysis of 2-arachidonoylglycerol (2-AG), breaking down monoglycerides into glycerol and fatty acids. It plays a crucial role in various pathological processes, including pain, inflammation, and oxidative stress. In this study, we utilized a lipopolysaccharide (LPS)-induced NPC senescence model and a rat acupuncture-induced IVDD model to investigate the role of MAGL in IVDD both in vitro and in vivo. Initially, our results showed that MAGL expression was increased 2.41-fold and 1.52-fold within NP tissues from IVDD patients and rats induced with acupuncture, respectively. This increase in MAGL expression was accompanied by elevated expression of p16INK4α. Following this, it was noted that the suppression of MAGL resulted in a notable decrease in the quantity of SA-ß-gal-positive cells and hindered the manifestation of p16INK4α and the inflammatory factor IL-1ß in NPCs. MAGL inhibition promotes type II collagen (Col-2) expression and inhibits matrix metalloproteinase 13 (MMP13), thereby restoring the balance of extracellular matrix (ECM) metabolism both in vitro and in vivo. A significant role for STING has also been demonstrated in the regulation of NPC senescence by MAGL. The expression of the STING protein was reduced by 57% upon the inhibition of MAGL. STING activation can replicate the effects of MAGL and substantially increase LPS-induced inflammation while accelerating the senescence of NPCs. These results strongly indicate that the inhibition of MAGL can significantly suppress nucleus pulposus senescence via its interaction with STING, consequently restoring the balance of ECM metabolism. This insight provides new perspectives for potential treatments for IVDD.

Albumin promoter-driven FlpO expression induces efficient genetic recombination in mouse liver.

Tissue-specific gene manipulations are widely used in genetically engineered mouse models. A single recombinase system, such as the one using Alb-Cre, has been commonly used for liver-specific genetic manipulations. However, most diseases are complex, involving multiple genetic changes and various cell types. A dual recombinase system is required for conditionally modifying different genes sequentially in the same cell or inducing genetic changes in different cell types within the same organism. A FlpO cDNA was inserted between the last exon and 3'-UTR of the mouse albumin gene in a bacterial artificial chromosome (BAC-Alb-FlpO). The founders were crossed with various reporter mice to examine the efficiency of recombination. Liver cancer tumorigenesis was investigated by crossing the FlpO mice with FSF-KrasG12D mice and p53frt mice (KPF mice). BAC-Alb-FlpO mice exhibited highly efficient recombination capability in both hepatocytes and intrahepatic cholangiocytes. No recombination was observed in the duodenum and pancreatic cells. BAC-Alb-FlpO-mediated liver-specific expression of mutant KrasG12D and conditional deletion of p53 gene caused the development of liver cancer. Remarkably, liver cancer in these KPF mice manifested a distinctive mixed hepatocellular carcinoma and cholangiocarcinoma phenotype. A highly efficient and liver-specific BAC-Alb-FlpO mouse model was developed. In combination with other Cre lines, different genes can be manipulated sequentially in the same cell, or distinct genetic changes can be induced in different cell types of the same organism.NEW & NOTEWORTHY A liver-specific Alb-FlpO mouse line was generated. By coupling it with other existing CreERT or Cre lines, the dual recombinase approach can enable sequential gene modifications within the same cell or across various cell types in an organism for liver research through temporal and spatial gene manipulations.

Impact of salinity and organic matter on the ammonia-oxidizing archaea and bacteria in treating hypersaline industrial wastewater: amoA gene abundance and ammonia removal contributions.

Studies published recently proposed that ammonia-oxidizing archaea (AOA) may be beneficial for hypersaline (salinity > 50 g NaCl L-1) industrial wastewater treatment. However, knowledge of AOA activity in hypersaline bioreactors is limited. This study investigated the effects of salinity, organic matter, and practical pickled mustard tuber wastewater (PMTW) on AOA and ammonia-oxidizing bacteria (AOB) in two sequencing batch biofilm reactors (SBBRs). Results showed that despite observed salinity inhibition (p < 0.05), both AOA and AOB contributed to high ammonia removal efficiency at a salinity of 70 g NaCl L-1 in the two SBBRs. The ammonia removal efficiency of SBBR2 did not significantly differ from that of SBBR1 in the absence of organic matter (p > 0.05). Batch tests and quantitative real-time PCR (qPCR) reveal that salinity and organic matter inhibition resulted in a sharp decline in specific ammonia oxidation rates and amoA gene copy numbers of AOA and AOB (p < 0.05). AOA demonstrated higher abundance and more active ammonia oxidation activity in hypersaline and high organic matter environments. Salinity was positively correlated with the potential ammonia oxidation contribution of AOA (p < 0.05), resulting in a potential transition from AOB dominance to AOA dominance in SBBR1 as salinity levels rose. Moreover, autochthonous AOA in PMTW promoted the abundance and ammonia oxidation activities of AOA in SBBR2, further elevating the nitrification removal efficiency after feeding the practical PMTW. AOA demonstrates greater tolerance to the challenging hypersaline environment, making it a valuable candidate for the treatment of practical industrial wastewater with high salinity and organic content.

PTEN Deficiency Induces an Extrahepatic Cholangitis-Cholangiocarcinoma Continuum via Aurora kinase A in Mice.

BACKGROUND & AIMS: The PTEN-AKT pathway is frequently altered in extrahepatic cholangiocarcinoma (eCCA). We aim to evaluate the role of PTEN in the pathogenesis of eCCA and find novel therapies for this disease. METHODS: The Pten gene in the biliary epithelial cells were genetically deleted using the Cre-loxp system. The pathologies were evaluated both macroscopically and histologically. The characteristics were further analyzed by immunohistochemistry (IHC), RT-PCR, cell culture, and RNAseq. Some features were compared to those in human eCCA samples. Further mechanistic studies utilized the conditional knockout of Trp53 and Aurora kinase A (Aurka) genes. Experimental therapy was tested using an Aurka inhibitor. RESULTS: We observed that genetic deletion of the Pten gene in the extrahepatic biliary epithelium and peri-ductal glands initiated sclerosing cholangitis-like lesions in mice, resulting in enlarged and distorted extrahepatic bile ducts in mice as early as one month old. Histologically, these lesions exhibited increased epithelial proliferation, inflammatory cell infiltration, and fibrosis. With aging, the lesions progressed from low-grade dysplasia to invasive carcinoma. Trp53 inactivation further accelerated the disease progression, potentially through downregulating senescence. Further mechanistic studies showed that both human and mouse eCCA showed high expressions of AURKA. Notably, the genetic deletion of Aurka completely eliminated Pten deficiency-induced extrahepatic bile duct lesions. Furthermore, pharmacological inhibition of Aurka alleviated disease progression. CONCLUSIONS: Pten deficiency in extrahepatic cholangiocytes and peribiliary glands led to a cholangitis-to-cholangiocarcinoma continuum through an Aurka-dependent manner. These findings offer new insights into preventive and therapeutic interventions for extrahepatic CCA. IMPACT AND IMPLICATIONS: The aberrant PTEN-PI3K-AKT signaling pathway is commonly observed in human extrahepatic cholangiocarcinoma (eCCA), a disease with a poor prognosis. In our study, we developed a mouse model mimicking cholangitis to eCCA progression by conditionally deleting the Pten gene via Pdx1-Cre in epithelial cells and peribiliary glands of the extrahepatic biliary duct. The conditional Pten deletion in these cells led to cholangitis, which gradually advanced to dysplasia, ultimately resulting in eCCA. The loss of Pten heightened Akt signaling, cell proliferation, inflammation, fibrosis, DNA damage, epigenetic signaling, epithelial-mesenchymal transition (EMT), cell dysplasia, and cellular senescence. Genetic deletion or pharmacological inhibition of Aurka successfully halted the disease progression. This model shall be valuable for testing novel therapies and unraveling the mechanisms of eCCA tumorigenesis.

Hydrogel-Based Therapy for Age-Related Macular Degeneration: Current Innovations, Impediments, and Future Perspectives.

Age-related macular degeneration (AMD) is an ocular disease that leads to progressive photoreceptor death and visual impairment. Currently, the most common therapeutic strategy is to deliver anti-vascular endothelial growth factor (anti-VEGF) agents into the eyes of patients with wet AMD. However, this treatment method requires repeated injections, which potentially results in surgical complications and unwanted side effects for patients. An effective therapeutic approach for dry AMD also remains elusive. Therefore, there is a surge of enthusiasm for the developing the biodegradable drug delivery systems with sustained release capability and develop a promising therapeutic strategy. Notably, the strides made in hydrogels which possess intricate three-dimensional polymer networks have profoundly facilitated the treatments of AMD. Researchers have established diverse hydrogel-based delivery systems with marvelous biocompatibility and efficacy. Advantageously, these hydrogel-based transplantation therapies provide promising opportunities for vision restoration. Herein, we provide an overview of the properties and potential of hydrogels for ocular delivery. We introduce recent advances in the utilization of hydrogels for the delivery of anti-VEGF and in cell implantation. Further refinements of these findings would lay the basis for developing more rational and curative therapies for AMD.

Encapsulated cell technology: Delivering cytokines to treat posterior ocular diseases.

Encapsulated cell technology (ECT) is a targeted delivery method that uses the genetically engineered cells in semipermeable polymer capsules to deliver cytokines. Thus far, ECT has been extensively utilized in pharmacologic research, and shows enormous potentials in the treatment of posterior segment diseases. Due to the biological barriers within the eyeball, it is difficult to attain effective therapeutic concentration in the posterior segment through topical administration of drug molecules. Encouragingly, therapeutic cytokines provided by ECT can cross these biological barriers and achieve sustained release at the desired location. The encapsulation system uses permeable materials that allow growth factors and cytokines to diffuse efficiently into retinal tissue. Moreover, the ECT based treatment can be terminated timely when we need to retrieve the implant, which makes the therapy reversible and provides a safer alternative for intraocular gene therapy. Meanwhile, we also place special emphasis on optimizing encapsulation materials and enhancing preservation techniques to achieve the stable release of growth factors and cytokines in the eyeball. This technology holds great promise for the treatment of patients with dry AMD, RP, glaucoma and MacTel. These findings would enrich our understandings of ECT and promote its future applications in treatment of degenerative retinopathy. This review comprises articles evaluating the exactness of artificial intelligence-based formulas published from 2000 to March 2024. The papers were identified by a literature search of various databases (PubMed/MEDLINE, Google Scholar, Cochrane Library and Web of Science).

A simple and effective genotyping workflow for rapid detection of CRISPR genome editing.

Genetically engineered mouse models play a pivotal role in the modeling of diseases, exploration of gene functions, and the development of novel therapies. In recent years, clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated genome editing technology has revolutionized the process of developing such models by enabling precise genome modifications of the multiple interested genes simultaneously. Following genome editing, an efficient genotyping methodology is crucial for subsequent characterization. However, current genotyping methods are laborious, time-consuming, and costly. Here, using targeting the mouse trypsinogen genes as an example, we introduced common applications of CRISPR-Cas9 editing and a streamlined cost-effective genotyping workflow for CRISPR-edited mouse models, in which Sanger sequencing is required only at the initial steps. In the F0 mice, we focused on identifying the presence of positive editing by PCR followed by Sanger sequencing without the need to know the exact sequences, simplifying the initial screening. In the F1 mice, Sanger sequencing and algorithms decoding were used to identify the precise editing. Once the edited sequence was established, a simple and effective genotyping strategy was established to distinguish homozygous and heterozygous status by PCR from tail DNA. The genotyping workflow applies to deletions as small as one nucleotide, multiple-gene knockout, and knockin studies. This simplified, efficient, and cost-effective genotyping shall be instructive to new investigators who are unfamiliar with characterizing CRISPR-Cas9-edited mouse strains.NEW & NOTEWORTHY This study presents a streamlined, cost-effective genotyping workflow for clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) edited mouse models, focusing on trypsinogen genes. It simplifies initial F0 mouse screening using PCR and Sanger sequencing without needing exact sequences. For F1 mice, precise editing is identified through Sanger sequencing and algorithm decoding. The workflow includes a novel PCR strategy for distinguishing homozygous and heterozygous statuses in subsequent generations, effective for small deletions, multiple-gene knockouts, and knockins.

Low-frequency rTMS modulated the excitability and high-frequency firing in hippocampal neurons of the Alzheimer's disease mouse model.

Repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, holds potential for applications in the treatment of Alzheimer's disease (AD). This study aims to compare the therapeutic effects of rTMS at different frequencies on Alzheimer's disease and explore the alterations in neuronal electrophysiological properties throughout this process. APP/PS1 AD mice were subjected to two rTMS treatments at 0.5 Hz and 20 Hz, followed by assessments of therapeutic outcomes through the Novel Object Recognition (NOR) and Morris Water Maze (MWM) tests. Following this, whole-cell patch-clamp techniques were used to record action potential, voltage-gated sodium channel currents, and voltage-gated potassium channel currents in dentate gyrus granule neurons. The results show that AD mice exhibit significant cognitive decline compared to normal mice, along with a pronounced reduction in neuronal excitability and ion channel activity. Both frequencies of rTMS treatment partially reversed these changes, demonstrating similar therapeutic efficacy. Furthermore, the investigation indicates that low-frequency magnetic stimulation inhibited the concentrated firing of early action potentials in AD.

Catalytic Intermolecular Deoxygenative Coupling of Carbonyl Compounds with Alkynes by a Cp*Mo(II)-Catalyst.

Carbonyl is highly accessible and acts as an essential functional group in chemical synthesis. However, the direct catalytic deoxygenative functionalization of carbonyl compounds via a putative metal carbene intermediate is a formidable challenge due to the requirement of a high activation energy for the cleavage of strong C═O double bonds. Here, we report a class of bench stable and readily available Cp*Mo(II)-complexes as efficient deoxygenation catalysts that could catalyze the direct intermolecular deoxygenative coupling of carbonyl compounds with alkynes. Enabled by this powerful Cp*Mo(II)-catalyst, various valuable heteroarenes (10 different classes) were obtained in generally good yields and remarkable chemo- and regioselectivities. Mechanistic studies suggested that this reaction might proceed via a sequence of C═O double bonds cleavage, carbene-alkyne metathesis, cyclization, and aromatization processes. This strategy not only provided a general catalytic platform for the rapid preparation of heteroarenes but also opened a new window for the applications of Cp*Mo(II)-catalysts in organic synthesis.

Higher diagnostic value of metagenomic next-generation sequencing in acute infection than chronic infection: a multicenter retrospective study.

Background: The aim of this study is to compare the diagnostic value of metagenomic next-generation sequencing (mNGS) vs. conventional culture methods (CM) in chronic infection and acute infection. Methods: We retrospectively analyzed the bronchoalveolar lavage fluid (BALF) of 88 patients with acute infection and 105 patients with chronic infection admitted to three hospitals from 2017 to 2022. Results: The results showed that the sensitivity and specificity of mNGS were higher than those of CM. The number of patients who changed the antibiotic treatment in the mNGS positive group was larger than that of patients in the mNGS negative group in both the acute infection group (60.5 vs. 28.0%, P = 0.0022) and chronic infection group (46.2 vs. 22.6%, P = 0.01112). High levels of temperature (OR: 2.02, 95% CI: 1.18-3.70, P: 0.015), C-reactive protein (CRP) (OR: 15, 95% CI: 2.74-280.69, P: 0.011), neutrophil count (OR: 3.09, 95% CI: 1.19-8.43, P: 0.023), and low levels of lymphocyte count (OR: 3.43, 95% CI:1.26-10.21, P: 0.020) may lead to positive mNGS results in the acute infection group while no significant factor was identified to predict positive results in the chronic infection group. Conclusion: mNGS could provide useful guidance on antibiotic strategies in infectious diseases and may be more valuable for the diagnosis and treatment of acute infection vs. chronic infection.

Genetic evidence for the causal relations between metabolic syndrome and psychiatric disorders: a Mendelian randomization study.

Emerging evidence reveals associations between metabolic syndrome (MetS) and psychiatric disorders (PDs), although causality remains uncertain. Consequently, we conducted Mendelian randomization (MR) to systematically evaluate the causality between MetS and PDs. Linkage disequilibrium score regression estimated the heritability of PDs and their genetic correlations with MetS. In primary analyses, the main model employed inverse variance weighting method, with sensitivity analyses using various MR models to ensure robustness. Replication MR analyses, involving cohorts distinct from those in the primary analyses, were performed to validate the generalizability of the findings. Multivariable MR analyses were carried out to account for genetically predicted body mass index (BMI). As a result, genetic correlations of MetS with attention-deficit/hyperactivity disorder(ADHD), anorexia nervosa(ANO), major depressive disorder(MDD), and schizophrenia were identified. Causal effects of MetS on ADHD (OR: 1.59 [95% CI:1.45-1.74]), ANO (OR: 1.42 [95% CI:1.25-1.61]), MDD(OR: 1.23 [95% CI: 1.13-1.33]), and the effects of ADHD (OR: 1.03 [95% CI: 1.02-1.04]) and ANO (OR: 1.01 [95% CI: 1.01-1.02]) on MetS were observed in primary analyses. Results from sensitivity analyses and replication analyses were generally consistent with the primary analyses, confirming the robustness and generalizability of the findings. Associations between MetS and ADHD, as well as ANO persisted after adjusting for BMI, whereas the statistical significance of the association between MetS and MDD was no longer observable. These results contribute to a deeper understanding of the mechanisms underlying PDs, suggesting potential modifiable targets for public prevention and clinical intervention in specific PDs related to metabolic pathways.

Necroptosis-related genes allow novel insights into predicting graft loss and diagnosing delayed graft function in renal transplantation.

Ischemia-reperfusion injury (IRI) is an inevitable pathophysiological phenomenon in kidney transplantation. Necroptosis is an undoubtedly important contributing mechanism in renal IRI. We first screened differentially expressed necroptosis-related genes (DENRGs) from public databases. Eight DENRGs were validated by independent datasets and verified by qRT-PCR in a rat IRI model. We used univariate and multivariate Cox regression analyses to establish a prognostic signature, and graft survival analysis was performed. Immune infiltrating landscape analysis and gene set enrichment analysis (GSEA) were performed to understand the underlying mechanisms of graft loss, which suggested that necroptosis may aggravate the immune response, resulting in graft loss. Subsequently, a delayed graft function (DGF) diagnostic signature was constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) and exhibited robust efficacy in validation datasets. After comprehensively analyzing DENRGs during IRI, we successfully constructed a prognostic signature and DGF predictive signature, which may provide clinical insights for kidney transplant.

Follicle-stimulating hormone accelerates osteoclast migration by enhancing methyltransferase-like 3-mediated m6A methylation of cathepsin K.

Follicle-stimulating hormone (FSH) accelerates osteoporosis in postmenopausal women, while the underlying mechanism remains uncharacterized. N6-methyladenosine (m6A) is one of the most important regulations in the development of osteoporosis. In this study, we aimed to investigate the role of FSH in m6A modification and osteoclast function. Here, we showed that FSH upregulated m6A levels in osteoclasts via stimulating methyltransferase-like 3 (METTL3) protein expression. FSH enhanced osteoclast migration, while the knockdown of METTL3 eliminated this enhancement. Both MeRIP-seq and RNA sequencing identified that cathepsin K (CTSK) is the potential downstream target of METTL3. Knockdown of CTSK reduced FSH-upregulated osteoclast migration. Furthermore, silencing METTL3 decreased CTSK mRNA stability. Finally, FSH induced phosphorylation of cyclic-AMP response element-binding protein (CREB), while silencing of CREB attenuated the effects of FSH on the promoter transcriptional activity of Mettl3 and CTSK/METTL3 protein. Taken together, these findings indicate that FSH promotes osteoclast migration via the CREB/METTL3/CTSK signaling pathway, which may provide a potential target for suppressing osteoclast mobility and postmenopausal osteoporosis therapy.

Unraveling the effect of combined heat and high-pressure homogenization treatment on the improvement of chickpea protein solubility from the perspectives of colloidal state change and structural characteristic modification.

Chickpea protein (CP) is a promising plant protein ingredient, but the poor solubility has limited its broad application. In this study, heating followed by high-pressure homogenization (HPH) was used to improve the solubility of CP. The results showed that combined heat (80℃, 30 min) and HPH (80 MPa, 2 cycles) treatment exhibited an additive effect in improving the solubility of CP. This improvement could be attributed to the dissociation and the rearrangement of large insoluble protein aggregates into small-sized soluble protein aggregates, the increased exposure of hydrophobic residues and reactive sulfhydryl groups, the transformation of α-helices to ß-sheets and ß-turns. Moreover, the 11S subunits of CP could form reinforced disulfide covalent cross-links under heating + HPH, which may provide steric hindrance preventing the reassembly of large protein bodies. This work proposes an interesting approach to enhance the physicochemical properties of CP for tailoring techno-functional plant protein ingredients in food formulations.

Low-intensity focused ultrasound modulation of the paraventricular nucleus to prevent myocardial infarction-induced ventricular arrhythmia.

BACKGROUND: Our previous study showed that light-emitting diode modulation of the hypothalamic paraventricular nucleus (PVN), which is the control center of the sympathetic nervous system, might attenuate neuroinflammation in the PVN and prevent ventricular arrhythmias (VAs) after myocardial infarction (MI). Low-intensity focused ultrasound (LIFU) has deeper penetration than does light-emitting diode, while its effect on the PVN has not been reported. OBJECTIVE: This study aimed to explore the effect of LIFU modulation of the PVN on the inducibility of post-MI VAs. METHODS: Fifty-four Sprague-Dawley rats were randomly divided into acute control (n = 12, 22.22%), acute MI (AMI, n = 12, 22.22%), AMI + LIFU (n = 12, 22.22%), chronic control (n = 6, 11.11%), chronic MI (CMI, n = 6, 11.11%), and CMI + LIFU (n = 6, 11.11%) groups. MI was induced by left anterior artery ligation, and electrocardiographic recording for 0.5 hours after MI and programmed electrophysiological stimulation were used to test the vulnerability of VAs. Peripheral sympathetic neural activity was assessed by measuring left stellate ganglion neural activity. Finally, hearts and brains were extracted for Western blotting and histopathological analysis, respectively. RESULTS: Compared with the AMI group, AMI-induced VAs (P < .05) and left stellate ganglion neural activity (P < .05) were significantly attenuated in the AMI + LIFU group. In addition, LIFU resulted in a significant reduction of microglial activation in the PVN and expression of inflammatory cytokines in the peri-ischemic myocardium. In the CMI + LIFU group, there was no obvious tissue damage in the brain. CONCLUSION: LIFU modulation of the PVN may prevent the incidence of post-MI VAs by attenuating MI-induced sympathetic neural activation and inflammatory response.

[Retracted] Interaction of S100A1 with LATS1 promotes cell growth through regulation of the Hippo pathway in hepatocellular carcinoma.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the western blotting data shown in Figs. 2B and 3E were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to International Journal of Oncology, or were under consideration for publication at around the same time. In view of the fact that certain of these data had already apparently been published previously, the Editor of International Journal of Oncology has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 53: 592­602, 2018; DOI: 10.3892/ijo.2018.4431].