MiR-4769-3p suppresses adipogenesis in systemic sclerosis by negatively regulating the USP18/VDAC2 pathway.

Systemic sclerosis (SSc) is an autoimmune disease affecting multiple tissues. The underlying causes and mechanisms of subcutaneous adipose tissue (SAT) loss in SSc remain unclear. Recent studies have highlighted the role of microRNAs in adipogenesis. Our study found that miR-4769-3p was upregulated in SSc patients and its silencing promoted SAT recovery in bleomycin-induced SSc mice, suggesting that miR-4769-3p might affect adipogenesis in SSc. Manipulating miR-4769-3p expression in 3T3-L1 cells revealed that its inhibition enhanced adipogenesis, while its overexpression weakened it. Further investigations showed that miR-4769-3p bound to 3'UTR of ubiquitin-specific protease-18 (USP18), inhibiting its expression, while USP18 interacted with voltage-dependent anion channel-2 (VDAC2), both of which were reduced in SSc. Silencing either USP18 or VDAC2 attenuated adipogenesis. Notably, USP18 inhibited VDAC2 ubiquitination and degradation, whereas miR-4769-3p reversed the VDAC2-induced elevation of adipogenesis, suggesting that miR-4769-3p inhibited adipogenesis by negatively regulating the USP18/VDAC2 pathway, providing a potential therapeutic target for SSc.

Mechanically induced M2 macrophages are involved in bone remodeling of the midpalatal suture during palatal expansion.

BACKGROUND: Palatal expansion is a common way of treating maxillary transverse deficiency. Under mechanical force, the midpalatal suture is expanded, causing local immune responses. This study aimed to determine whether macrophages participate in bone remodeling of the midpalatal suture during palatal expansion and the effects on bone remodeling. METHODS: Palatal expansion model and macrophage depletion model were established. Micro-CT, histological staining, and immunohistochemical staining were used to investigate the changes in the number and phenotype of macrophages during palatal expansion as well as the effects on bone remodeling of the midpalatal suture. Additionally, the effect of mechanically induced M2 macrophages on palatal osteoblasts was also elucidated in vitro. RESULTS: The number of macrophages increased significantly and polarized toward M2 phenotype with the increase of the expansion time, which was consistent with the trend of bone remodeling. After macrophage depletion, the function of osteoblasts and bone formation at the midpalatal suture were impaired during palatal expansion. In vitro, conditioned medium derived from M2 macrophages facilitated osteogenic differentiation of osteoblasts and decreased the RANKL/OPG ratio. CONCLUSIONS: Macrophages through polarizing toward M2 phenotype participated in midpalatal suture bone remodeling during palatal expansion, which may provide a new idea for promoting bone remodeling from the perspective of regulating macrophage polarization.

Nano titanium dioxide alleviates the toxic effects of tris (2-chloropropyl) phosphate on the digestive gland and hemolymph of thick-shell mussel Mytilus coruscus.

In the marine environment, nanoparticles play a role in adsorbing and catalytically degrading organic pollutants, thereby mitigating their toxic effects on aquatic organisms. This study aimed to investigate the impact of nano titanium dioxide (nTiO2) and tris (2-chloropropyl) phosphate (TCPP) on the hemolymph and digestive function of the thick-shell mussel Mytilus coruscus. Mussels were divided into a control group, a group exposed to TCPP alone, a group exposed to a combination of TCPP and 0.5 mg/L nTiO2, and a group exposed to a combination of TCPP and 1 mg/L nTiO2. After 14 days of exposure, oxidative stress responses, including superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, immune defense responses, including acid phosphatase (ACP) and alkaline phosphatase (AKP) activities, and gene expression, including HSP70 expression, were measured in the hemolymph and digestive glands of the mussels. Compared to the control group, mussels solely exposed to 100 µg/L TCPP exhibited a significant reduction in SOD activity in the hemolymph. When TCPP was co-exposed with 0.5 mg/L nTiO2, there were significant increases in MDA content and AKP activity in both the digestive gland and hemolymph compared to the control group. Upon co-exposure of TCPP with 1 mg/L nTiO2, MDA content and AKP activity in the digestive gland significantly decreased, while SOD, ACP, and AKP activity in the hemolymph significantly increased and MDA content significantly decreased, returning to the control group levels. Furthermore, in the combined exposure, HSP70 gene expression significantly decreased as the nTiO2 concentration increased from 0.5 mg/L to 1 mg/L. In summary, TCPP impacted the hemolymph and digestive function of mussels, whereas a concentration of 1 mg/L nTiO2 effectively alleviated the toxic effects of TCPP. This study is crucial for assessing the ecological risks of nanoparticles and emerging organic pollutants in marine environments, and provides new insights into the interaction between nTiO2 and TCPP, as well as the influence of nTiO2 concentration on mitigating TCPP toxicity.

Molecular detection and genetic variability of Cryptosporidium spp. in wild Asian house shrews (Suncus murinus) from southern Zhejiang province, China.

Shrews play a crucial role as repositories for diverse pathogens linked to zoonotic infectious diseases. However, the genetic information regarding Cryptosporidium in Chinese shrews remains unexplored. The objectives of this study were twofold: to determine the occurrence rate of Cryptosporidium spp. in wild shrews residing in the southern part of Zhejiang Province, China, and to investigate their genetic characteristics. A total of 282 wild shrews were captured between April and October of 2023. The detection of Cryptosporidium in fecal samples, collected from each animal's rectum, was performed using PCR and sequencing of the partial small subunit of ribosomal RNA (SSU rRNA) gene. The 60-kDa glycoprotein (gp60) gene was utilized to further subtype the positive samples of C. viatorum and C. parvum. All animals were identified as Suncus murinus, and a positive result for Cryptosporidium was obtained in 14.2 % (40/282) of the samples. The following species and genotypes were identified: C. ratti (n = 19), C. parvum (n = 2), C. viatorum (n = 1), Cryptosporidium rat genotype IV (n = 13), and Cryptosporidium skunk genotype (n = 5). Furthermore, the subtypes IIdA15G1 and XVdA3 were detected within C. parvum and C. viatorum, respectively. Molecular evidence indicates that S. murinus is concurrently infected with rodent-adapted and zoonotic species/genotypes, actively contributing to the dissemination of cryptosporidiosis.

Brain metastasis magnetic resonance imaging-based deep learning for predicting epidermal growth factor receptor (EGFR) mutation and subtypes in metastatic non-small cell lung cancer.

Background: The preoperative identification of epidermal growth factor receptor (EGFR) mutations and subtypes based on magnetic resonance imaging (MRI) of brain metastases (BM) is necessary to facilitate individualized therapy. This study aimed to develop a deep learning model to preoperatively detect EGFR mutations and identify the location of EGFR mutations in patients with non-small cell lung cancer (NSCLC) and BM. Methods: We included 160 and 72 patients who underwent contrast-enhanced T1-weighted (T1w-CE) and T2-weighted (T2W) MRI at Liaoning Cancer Hospital and Institute (center 1) and Shengjing Hospital of China Medical University (center 2) to form a training cohort and an external validation cohort, respectively. A multiscale feature fusion network (MSF-Net) was developed by adaptively integrating features based on different stages of residual network (ResNet) 50 and by introducing channel and spatial attention modules. The external validation set from center 2 was used to assess the performance of MSF-Net and to compare it with that of handcrafted radiomics features. Receiver operating characteristic (ROC) curves, accuracy, precision, recall, and F1-score were used to evaluate the effectiveness of the models. Gradient-weighted class activation mapping (Grad-CAM) was used to demonstrate the attention of the MSF-Net model. Results: The developed MSF-Net generated a better diagnostic performance than did the handcrafted radiomics in terms of the microaveraged area under the curve (AUC) (MSF-Net: 0.91; radiomics: 0.80) and macroaveraged AUC (MSF-Net: 0.90; radiomics: 0.81) for predicting EGFR mutations and subtypes. Conclusions: This study provides an end-to-end and noninvasive imaging tool for the preoperative prediction of EGFR mutation status and subtypes based on BM, which may be helpful for facilitating individualized clinical treatment plans.

Nitrogen-Doped Porous Carbons Derived from Peanut Shells as Efficient Electrodes for High-Performance Supercapacitors.

The doping of porous carbon materials with nitrogen is an effective approach to enhance the electrochemical performance of electrode materials. In this study, nitrogen-doped porous carbon derived from peanut shells was prepared as an electrode for supercapacitors. Melamine, urea, urea phosphate, and ammonium dihydrogen phosphate were employed as different nitrogen dopants. The optimized electrode material PA-1-1 prepared by peanut shells, with ammonium dihydrogen phosphate as a nitrogen dopant, exhibited a N content of 3.11% and a specific surface area of 602.7 m2/g. In 6 M KOH, the PA-1-1 electrode delivered a high specific capacitance of 208.3 F/g at a current density of 1 A/g. Furthermore, the PA-1-1 electrode demonstrated an excellent rate performance with a specific capacitance of 170.0 F/g (retention rate of 81.6%) maintained at 20 A/g. It delivered a capacitance of PA-1-1 with a specific capacitance retention of 98.8% at 20 A/g after 5000 cycles, indicating excellent cycling stability. The PA-1-1//PA-1-1 symmetric supercapacitor exhibited an energy density of 17.7 Wh/kg at a power density of 2467.0 W/kg. This work not only presents attractive N-doped porous carbon materials for supercapacitors but also offers a novel insight into the rational design of biochar carbon derived from waste peelings.

Cross-species transmission of Cryptosporidium in wild rodents from the southern region of Zhejiang Province of China and its possible impact on public health.

Wild rodents serve as reservoirs for Cryptosporidium and are overpopulated globally. However, genetic data regarding Cryptosporidium in these animals from China are limited. Here, we have determined the prevalence and genetic characteristics of Cryptosporidium among 370 wild rodents captured from three distinct locations in the southern region of Zhejiang Province, China. Fresh feces were collected from the rectum of each rodent, and DNA was extracted from them. The rodent species was identified by PCR amplifying the vertebrate cytochrome b gene. Cryptosporidium was detected by PCR amplification and amplicon sequencing the small subunit of ribosomal RNA gene. Positive samples of C. viatorum and C. parvum were further subtyped by analyzing the 60-kDa glycoprotein gene. A positive Cryptosporidium result was found in 7% (26/370) of samples, involving five rodent species: Apodemus agrarius (36), Niviventer niviventer (75), Rattus losea (18), R. norvegicus (155), and R. tanezumi (86). Their respective Cryptosporidium positive rates were 8.3%, 5.3%, 11.1%, 7.1%, and 7.0%. Sequence analysis confirmed the presence of three Cryptosporidium species: C. parvum (4), C. viatorum (1), and C. muris (1), and two genotypes: Cryptosporidium rat genotype IV (16) and C. mortiferum-like (4). Additionally, two subtypes of C. parvum (IIdA15G1 and IIpA19) and one subtype of C. viatorum (XVdA3) were detected. These results demonstrate that various wild rodent species in Zhejiang were concurrently infected with rodent-adapted and zoonotic species/genotypes of Cryptosporidium, indicating that these rodents can play a role in maintaining and dispersing this parasite into the environment and other hosts, including humans.

Title: Transmission interspécifique de Cryptosporidium chez les rongeurs sauvages de la région sud de la province chinoise du Zhejiang et son impact possible sur la santé publique. Abstract: Les rongeurs sauvages servent de réservoirs à Cryptosporidium et ont des grandes populations à l'échelle mondiale. Cependant, les données génétiques concernant Cryptosporidium chez ces animaux en Chine sont limitées. Ici, nous avons déterminé la prévalence et les caractéristiques génétiques de Cryptosporidium parmi 370 rongeurs sauvages capturés dans trois endroits distincts de la région sud de la province du Zhejiang, en Chine. Des excréments frais ont été collectés dans le rectum de chaque rongeur et l'ADN en a été extrait. L'espèce de rongeur a été identifiée par amplification par PCR du gène du cytochrome b des vertébrés. Cryptosporidium a été détecté par amplification PCR et séquençage d'amplicons de la petite sous-unité du gène de l'ARN ribosomal. Les échantillons positifs de C. viatorum et C. parvum ont ensuite été sous-typés en analysant le gène de la glycoprotéine de 60 kDa. Un résultat positif pour Cryptosporidium a été trouvé dans 7 % (26/370) des échantillons, impliquant cinq espèces de rongeurs : Apodemus agrarius (36), Niviventer niviventer (75), Rattus losea (18), R. norvegicus (155) et R. tanezumi (86). Leurs taux respectifs de positivité pour Cryptosporidium étaient de 8,3 %, 5,3 %, 11,1 %, 7,1 % et 7,0 %. L'analyse des séquences a confirmé la présence de trois espèces de Cryptosporidium : C. parvum (4), C. viatorum (1) et C. muris (1), et de deux génotypes : Cryptosporidium génotype IV de rat (16) et C. mortiferum-like (4). De plus, deux sous-types de C. parvum (IIdA15G1 et IIpA19) et un sous-type de C. viatorum (XVdA3) ont été détectés. Ces résultats démontrent que diverses espèces de rongeurs sauvages du Zhejiang sont simultanément infectées par des espèces/génotypes de Cryptosporidium zoonotiques et adaptés aux rongeurs, ce qui indique que ces rongeurs peuvent jouer un rôle dans le maintien et la dispersion de ce parasite dans l'environnement et d'autres hôtes, y compris les humains.

Maternal bisphenols exposure and thyroid function in children: a systematic review and meta-analysis.

Background: Evidence from animal experiments and epidemiological studies has reported controversial results about the effects of prenatal bisphenols (BPs) exposure on childhood thyroid function. This study aims to explore the associations of prenatal exposure to BPs with thyroid-related hormones (THs) in newborns and early childhood, with a particular focus on the sex-dependent and exposure level effects. Methods: Correlated studies were systematically searched from PubMed, Web of Science, Medline, Cochrane, and Embase until February 21, 2024. The exposures assessed include bisphenol A (BPA), bisphenol F (BPF), bisphenol S (BPS), bisphenol AF (BPAF), and tetrachlorobisphenol A (TCBPA). THs measured were thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), free tri-iothyronine (FT3), and free thyroxine (FT4). Effect estimates were quantified using coefficients from multivariable regression models. Statistical analyses were completed using Stata 16.0. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). Results: Eleven cohort studies comprising 5,363 children were included in our meta-analysis. Prenatal bisphenol concentrations were statistically significant related to alterations in thyroid hormones in children, exclusively in female offspring, including reduced TSH (ß = -0.020, 95% CI: -0.036, -0.005) and increased TT3 levels (ß = 0.011, 95% CI: 0.001, 0.021), and exposure to high concentration of bisphenols (>1.5 ug/g creatinine) significantly reduced FT3 levels in children (ß = -0.011, 95% CI: -0.020, -0.003). Conclusion: Prenatal bisphenol exposure is linked to alterations in thyroid hormone levels in girls, necessitating enhanced measures to control bisphenol exposure levels during pregnancy for child health protection. Systematic Review Registration: https://inplasy.com, identifier INPLASY202450129.

Complete chloroplast genome and phylogenetic analysis of Amorphophallus paeoniifolius (Araceae).

Amorphophallus paeoniifolius (Dennst.) Nicolson, 1885, often known as elephant foot yam, is a tropical tuber crop that originates from south-east Asia and belongs to the Araceae family. It is known for its high production potential and popularity as a medicinal plant. However, the phylogeny and genes for this species are still unavailable. In this study, the first complete chloroplast genome of A. paeoniifolius was reported and phylogenetic analysis was conducted with Araceae species. The chloroplast genome was 176,258 bp in length with 34.80% overall GC content and includes a large single-copy (LSC) region (93,951 bp), a small single-copy (SSC) region (15,013 bp), and a pair of inverted repeat (IRs) regions (33,647 bp). The chloroplast genome has 130 genes, which include 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. A maximum-likelihood (ML) phylogenetic analysis indicated that all Amorphophallus species formed a single monophyletic clade with a high bootstrap value and A. paeoniifolius was closely related to A. konjac, A. albus, A. krausei, and A. titanum. The chloroplast genome reported in this study will be useful for further taxonomic and evolutionary studies of Amorphophallus.

An Overview on the Adhesion Mechanisms of Typical Aquatic Organisms and the Applications of Biomimetic Adhesives in Aquatic Environments.

Water molecules pose a significant obstacle to conventional adhesive materials. Nevertheless, some marine organisms can secrete bioadhesives with remarkable adhesion properties. For instance, mussels resist sea waves using byssal threads, sandcastle worms secrete sandcastle glue to construct shelters, and barnacles adhere to various surfaces using their barnacle cement. This work initially elucidates the process of underwater adhesion and the microstructure of bioadhesives in these three exemplary marine organisms. The formation of bioadhesive microstructures is intimately related to the aquatic environment. Subsequently, the adhesion mechanisms employed by mussel byssal threads, sandcastle glue, and barnacle cement are demonstrated at the molecular level. The comprehension of adhesion mechanisms has promoted various biomimetic adhesive systems: DOPA-based biomimetic adhesives inspired by the chemical composition of mussel byssal proteins; polyelectrolyte hydrogels enlightened by sandcastle glue and phase transitions; and novel biomimetic adhesives derived from the multiple interactions and nanofiber-like structures within barnacle cement. Underwater biomimetic adhesion continues to encounter multifaceted challenges despite notable advancements. Hence, this work examines the current challenges confronting underwater biomimetic adhesion in the last part, which provides novel perspectives and directions for future research.

Exergaming and cognitive functions in people with mild cognitive impairment and dementia: a meta-analysis.

Exergaming is a combination of exercise and gaming. Evidence shows an association between exercise and cognition in older people. However, previous studies showed inconsistent results on the cognitive benefits of exergaming in people with cognitive impairment. Therefore, this study aims to examine the effect of exergaming intervention on cognitive functions in people with MCI or dementia. A systematic literature search was conducted via OVID databases. Randomized controlled trials (RCTs) examined the effect of an exergaming intervention on cognitive functions in people with MCI or dementia were included. Subgroup analyses were conducted according to the type of intervention and training duration. Twenty RCTs with 1152 participants were identified, including 14 trials for MCI and 6 trials for dementia. In people with MCI, 13 studies used virtual-reality (VR)-based exergaming. Those who received VR-based exergaming showed significantly better global cognitive function [SMD (95%CI) = 0.67 (0.23-1.11)], learning and memory [immediate recall test: 0.79 (0.31-1.27); delayed recall test: 0.75 (0.20-1.31)], working memory [5.83 (2.27-9.39)], verbal fluency [0.58 (0.12-1.03)], and faster in executive function than the controls. For people with dementia, all studies used video-based exergaming intervention. Participants with exergaming intervention showed significantly better global cognitive function than the controls [0.38 (0.10-0.67)]. Subgroup analyses showed that longer training duration generated larger effects. The findings suggest that exergaming impacts cognitive functions in people with MCI and dementia. Cognitive benefits are demonstrated for those with a longer training duration. With technological advancement, VR-based exergaming attracts the attention of people with MCI and performs well in improving cognitive functions.

Investigating Enterocytozoon bieneusi in pigs farmed in Zhejiang Province, China: Occurrence, genotype identification, evolutionary analysis, and zoonotic risk assessment.

Enterocytozoon bieneusi is a widespread intracellular fungus that can infect both humans and animals, making it a significant zoonotic threat. In the current study, a total of 208 fecal samples were assayed to investigate the prevalence of E. bieneusi in pigs reared in Zhejiang Province, China. Employing polymerase chain reaction (PCR) amplification techniques specifically designed to target the internal transcribed spacer (ITS) region of the small subunit ribosomal RNA (rRNA) gene, the results revealed that 78 samples (37.5 %) tested positive for the presence of E. bieneusi. A total of 19 different genotypes of E. bieneusi were detected. Nine of these genotypes were already known: EbpC (n = 36), KIN-1 (n = 10), PigEbITS7 (n = 8), EbpA (n = 6), Henan III (n = 3), PigEbITS5 (n = 2), Henan-IV (n = 1), EbpD (n = 1), and TypeIV (n = 1), and 10 were novel: ZJP-I to ZJP-X (one each). The present investigation revealed that all the nine known genotypes identified in pigs here, have also been previously discovered in humans. Additionally, the novel genotypes of E. bieneusi discovered here were all classified as belonging to Group 1. These findings suggest the potential for cross-species transmission between humans and pigs.

Silica's silent threat: Contributing to skin fibrosis in systemic sclerosis by targeting the HDAC4/Smad2/3 pathway.

Nowadays, silica products are widely used in daily life, especially in skin applications, which inevitably increases the risk of silica exposure in general population. However, inadequate awareness of silica's potential hazards and lack of self-protection are of concern. Systemic sclerosis (SSc) is characterized by progressive tissue fibrosis under environmental and genetic interactions. Silica exposure is considered an important causative factor for SSc, but its pathogenesis remains unclear. Within this study, we showed that lower doses of silica significantly promoted the proliferation, migration, and activation of human skin fibroblasts (HSFs) within 24 h. Silica injected subcutaneously into mice induced and exacerbated skin fibrosis. Notably, silica increased histone deacetylase-4 (HDAC4) expression by inducing its DNA hypomethylation in normal HSFs. The elevated HDAC4 expression was also confirmed in SSc HSFs. Furthermore, HDAC4 was positively correlated with Smad2/3 phosphorylation and COL1, α-SMA, and CTGF expression. The HDAC4 inhibitor LMK235 mitigated silica-induced upregulation of these factors and alleviated skin fibrosis in SSc mice. Taken together, silica induces and exacerbates skin fibrosis in SSc patients by targeting the HDAC4/Smad2/3 pathway. Our findings provide new insights for evaluating the health hazards of silica exposure and identify HDAC4 as a potential interventional target for silica-induced SSc skin fibrosis.

PGC-1α/LDHA signaling facilitates glycolysis initiation to regulate mechanically induced bone remodeling under inflammatory microenvironment.

The mechanosensitivity of inflammation can alter cellular mechanotransduction. However, the underlying mechanism remains unclear. This study aims to investigate the metabolic mechanism of inflammation under mechanical force to guide tissue remodeling better. Herein, we found that inflammation hindered bone remodeling under mechanical force, accompanied by a simultaneous enhancement of oxidative phosphorylation (OXPHOS) and glycolysis. The control of metabolism direction through GNE-140 and Visomitin revealed that enhanced glycolysis might act as a compensatory mechanism to resist OXPHOS-induced osteoclastogenesis by promoting osteogenesis. The inhibited osteogenesis induced by inflammatory mechanical stimuli was concomitant with a reduced expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). PGC-1α knockdown impeded osteogenesis under mechanical force and facilitated osteoclastogenesis by enhancing OXPHOS. Conversely, PGC-1α overexpression attenuated the impairment of bone remodeling by inflammatory mechanical signals through promoting glycolysis. This process benefited from the PGC-1α regulation on the transcriptional and translational activity of lactate dehydrogenase A (LDHA) and the tight control of the extracellular acidic environment. Additionally, the increased binding between PGC-1α and LDHA proteins might contribute to the glycolysis promotion within the inflammatory mechanical environment. Notably, LDHA suppression effectively eliminated the bone repair effect mediated by PGC-1α overexpression within inflammatory mechanical environments. In conclusion, this study demonstrated a novel molecular mechanism illustrating how inflammation orchestrated glucose metabolism through glycolysis and OXPHOS to affect mechanically induced bone remodeling.

Corrigendum: Phenylpropane biosynthesis and alkaloid metabolism pathways involved in resistance of Amorphophallus spp. against soft rot disease.

[This corrects the article DOI: 10.3389/fpls.2024.1334996.].

m6A RNA methylation: The latent string-puller in fibrosis.

Fibrosis is a pathological phenomenon characterized by the aberrant accumulation of extracellular matrix (ECM) in tissues. Fibrosis is a universally age-related disease involving that many organs and is the final stage of many chronic inflammatory diseases, which often threaten the patient's health. Undoubtedly, fibrosis has become a serious economic and health burden worldwide, However, the pathogenesis of fibrosis is complex. Further, the key molecules still remain to be unraveled. Hence, so far, there have been no effective treatments designed against the key targets of fibrosis. The methylation modification on the nitrogen atom at position 6 of adenine (m6A) is the most common mRNA modification in mammals. There is increasing evidence that m6A is actively involved in the pathogenesis of fibrosis. This review aims to highlight m6A-associated mechanisms and functions in several organic fibrosis, which implies that m6A is universal and critical for fibrosis and summarize the outlook of m6A in the treatment of fibrosis. This may light up the unknown aspects of this condition for researchers interested to explore fibrosis further.

CircPRKD3/miR-6783-3p responds to mechanical force to facilitate the osteogenesis of stretched periodontal ligament stem cells.

BACKGROUND: The mechanotransduction mechanisms by which cells regulate tissue remodeling are not fully deciphered. Circular RNAs (circRNAs) are crucial to various physiological processes, including cell cycle, differentiation, and polarization. However, the effects of mechanical force on circRNAs and the role of circRNAs in the mechanobiology of differentiation and remodeling in stretched periodontal ligament stem cells (PDLSCs) remain unclear. This article aims to explore the osteogenic function of mechanically sensitive circular RNA protein kinase D3 (circPRKD3) and elucidate its underlying mechanotransduction mechanism. MATERIALS AND METHODS: PDLSCs were elongated with 8% stretch at 0.5 Hz for 24 h using the Flexcell® FX-6000™ Tension System. CircPRKD3 was knockdown or overexpressed with lentiviral constructs or plasmids. The downstream molecules of circPRKD3 were predicted by bioinformatics analysis. The osteogenic effect of related molecules was evaluated by quantitative real-time PCR (qRT-PCR) and western blot. RESULTS: Mechanical force enhanced the osteogenesis of PDLSCs and increased the expression of circPRKD3. Knockdown of circPRKD3 hindered PDLSCs from osteogenesis under mechanical force, while overexpression of circPRKD3 promoted the early osteogenesis process of PDLSCs. With bioinformatics analysis and multiple software predictions, we identified hsa-miR-6783-3p could act as the sponge of circPRKD3 to indirectly regulate osteogenic differentiation of mechanically stimulated PDLSCs. CONCLUSIONS: Our results first suggested that both circPRKD3 and hsa-miR-6783-3p could enhance osteogenesis of stretched PDLSCs. Furthermore, hsa-miR-6783-3p could sponge circPRKD3 to indirectly regulate RUNX2 during the periodontal tissue remodeling process in orthodontic treatment.

In Situ Synthesis of Self-Assembly Supramolecular Crystal Seeds within Continuous Carbon Nanofibers for Improved Fiber Graphitic Structure.

The utilization of carbon-based fibers as a fundamental constituent holds strong appeal for diverse materials and devices. However, the poor fiber graphitic structure resulting from the heat treatment of atactic polyacrylonitrile (PAN) precursors often leads to a modest performance of carbon-based fibers. This paper takes electrospun carbon nanofibers (CNFs) as the research object and provides a seed-assisted graphitization strategy to improve the fiber graphitic structures. The typical melamine/cyanuric acid self-assembly precursor of graphitic carbon nitride is applied as supramolecular seeds in CNFs and demonstrates significant promotion of fiber graphitization, while it decomposes at elevated temperatures. Further studies show that the higher carbon content contributes to the better heat resistance of seeds; thus, nanoscale 2,6-diaminopyridine/cyanuric acid and 2,4,6-triaminopyrimidine/barbituric acid supramolecular seeds are developed. Both systems can be uniformly distributed in PAN precursors through in situ self-assembly and withstand high-temperature carbonization without severe pyrolysis. The dispersed seeds contribute to the formation of fibrillar PAN crystals and promote their conversion to ordered graphitic domains through nucleation and templating roles. The obtained CNFs exhibit increased crystallinity and graphitization degree with improved orientation and refined size of fiber crystals. As a result, the strength, modulus, and elongation at break of CNFs are comprehensively enhanced.

The endophytic fungal community plays a crucial role in the resistance of host plants to necrotic bacterial pathogens.

Konjac species (Amorphophallus spp.) are the only plant species in the world that are rich in a large amount of konjac glucomannan (KGM). These plants are widely cultivated as cash crops in tropical and subtropical countries in Asia, including China. Pectobacterium carotovorum subsp. carotovorum (Pcc) is one of the most destructive bacterial pathogens of konjac. Here, we analyzed the interactions between Pcc and susceptible and resistant konjac species from multiple perspectives. At the transcriptional and metabolic levels, the susceptible species A. konjac and resistant species A. muelleri exhibit similar molecular responses, activating plant hormone signaling pathways and metabolizing defense compounds such as phenylpropanoids and flavonoids to resist infection. Interestingly, we found that Pcc stress can lead to rapid recombination of endophytic microbial communities within a very short period (96 h). Under conditions of bacterial pathogen infection, the relative abundance of most bacterial communities in konjac tissue decreased sharply compared with that in healthy plants, while the relative abundance of some beneficial fungal communities increased significantly. The relative abundance of Cladosporium increased significantly in both kinds of infected konjac compared to that in healthy plants, and the relative abundance in resistant A. muelleri plants was greater than that in susceptible A. konjac plants. Among the isolated cultivable microorganisms, all three strains of Cladosporium strongly inhibited Pcc growth. Our results further elucidate the potential mechanism underlying konjac resistance to Pcc infection, highlighting the important role of endophytic microbial communities in resisting bacterial pathogen infections, especially the more direct role of fungal communities in inhibiting pathogen growth.

Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway.

Effective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression. Furthermore, the mechanism of cell death caused by NTP is closely related to oxidative stress. NTP increases intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreasing the mitochondrial membrane potential (MMP) and inducing glucose (GSH) consumption. While the death of GC cells can be partially rescued by ROS inhibitor N-acetylcysteine (NAC). Mechanistically, NTP activates the Kelch-like ECH-associated protein (Keap1)-NF-E2-related factor 2 (Nrf2) pathway, which is an important pathway involved in oxidative stress. RNA sequencing and proteomics analysis further revealed molecular changes at the mRNA and protein levels and provided potential targets and pathways through differential gene expression analysis. In addition, NTP can inhibited tumor growth in nude mouse subcutaneous tumor models constructed respectively using AGS and MFC (mouse-derived GC cells), providing preliminary evidence of its effectiveness in vivo. In conclusion, our study demonstrated that NTP exhibits significant anti-GC activity and is anticipated to be a candidate for drug repurposing.