A Novel Peptidomimetic Insecticide: Dippu-AstR-Based Rational Design and Biological Activity of Allatostatin Analogs.

Insect neuropeptides play an essential role in regulating growth, development, reproduction, nerve conduction, metabolism, and behavior in insects; therefore, G protein-coupled receptors of neuropeptides are considered important targets for designing green insecticides. Cockroach-type allatostatins (ASTs) (FGLamides allatostatins) are important insect neuropeptides in Diploptera punctata that inhibit juvenile hormone (JH) synthesis in the corpora allata and affect growth, development, and reproduction of insects. Therefore, the pursuit of novel insecticides targeting the allatostatin receptor (AstR) holds significant importance. Previously, we identified an AST analogue, H17, as a promising candidate for pest control. Herein, we first modeled the 3D structure of AstR in D. punctata (Dippu-AstR) and predicted the binding mode of H17 with Dippu-AstR to study the critical interactions and residues favorable to its bioactivity. Based on this binding mode, we designed and synthesized a series of H17 derivatives and assessed their insecticidal activity against D. punctata. Among them, compound Q6 showed higher insecticidal activity than H17 against D. punctata by inhibiting JH biosynthesis, indicating that Q6 is a potential candidate for a novel insect growth regulator (IGR)-based insecticide. Moreover, Q6 exhibited insecticidal activity against Plutella xylostella, indicating that these AST analogs may have a wider insecticidal spectrum. The underlying mechanisms and molecular conformations mediating the interactions of Q6 with Dippu-AstR were explored to understand its effects on the bioactivity. The present work clarifies how a target-based strategy facilitates the discovery of new peptide mimics with better bioactivity, enabling improved IGR-based insecticide potency in sustainable agriculture.

A bioactive nanocomposite integrated specific TAMs target and synergistic TAMs repolarization for effective cancer immunotherapy.

Reactive oxygen species (ROS) generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages (TAMs) toward the anti-tumor M1 phenotype, representing a promising cancer immunotherapy strategy. Nevertheless, their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers. Here, a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy. Colloidal mesoporous silica nanoparticles (CMSN) are fabricated to encapsulate photosensitizer-Indocyanine Green (ICG) to improve their stability. Then ginseng-derived exosome (GsE) was coated on the surface of ICG/CMSN for targeting TAMs, as well as repolarizing TAMs concurrently, named ICG/CMSN@GsE. As expected, with the synergism of ICG and GsE, ICG/CMSN@GsE exhibited better stability, mild generation of ROS, favorable specificity toward M2-like macrophages, enhancing drug retention in tumors and superior TAMs repolarization potency, then exerted a potent antitumor effect. In vivo, experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage. Taken together, by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform, ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.

Distribution and spatial variation of volatile methylsiloxanes in surface water and wastewater from the Yangtze River Basin, China.

Volatile methylsiloxanes (VMSs) earned serious concerns due to their detection and toxicities after their release to the environments. They were also detected in rivers around the globe, but their distribution remained to be explored in larger rivers with longer length, higher water volume and wider watershed. In the present study, 8 cyclic VMSs (cVMSs) and 7 linear ones (lVMSs) were investigated in 42 water samples (27 surface water (including 7 drinking source water) and 15 wastewater) from the Yangtze River Basin, China. Results showed that VMSs were detected in all sampling sites. In surface water, the concentrations of total cVMSs ranged from 17.3 to 4.57 × 103 ng/L, while those of lVMSs ranged from 1.72 to 81.6 ng/L. In wastewater, the total concentrations of cVMSs and lVMSs showed ranges of 17.6-1.66 × 103 ng/L and 2.59-252 ng/L, respectively. Apparently, cVMSs showed significantly higher concentrations than lVMSs. The concentrations of cVMSs followed an order of lower > upper > middle reaches, while those of lVMSs did not show clear distribution patterns. Among cVMSs, those with less Si numbers were dominant, while those with more Si numbers were dominant in lVMSs. Notably, the VMSs were also detected in 7 surface waters that served as drinking source waters, which earned them further concerns. In addition, the VMSs in surface water showed positive correlation with those in wastewater, which led to necessity in management on industrial emissions in the future.

Small-molecule α-lipoic acid targets ELK1 to balance human neutrophil and erythrocyte differentiation.

BACKGROUND: Erythroid and myeloid differentiation disorders are commonly occurred in leukemia. Given that the relationship between erythroid and myeloid lineages is still unclear. To find the co-regulators in erythroid and myeloid differentiation might help to find new target for therapy of myeloid leukemia. In hematopoiesis, ALA (alpha lipoic acid) is reported to inhibit neutrophil lineage determination by targeting transcription factor ELK1 in granulocyte-monocyte progenitors via splicing factor SF3B1. However, further exploration is needed to determine whether ELK1 is a common regulatory factor for erythroid and myeloid differentiation. METHODS: In vitro culture of isolated CD34+, CMPs (common myeloid progenitors) and CD34+ CD371- HSPCs (hematopoietic stem progenitor cells) were performed to assay the differentiation potential of monocytes, neutrophils, and erythrocytes. Overexpression lentivirus of long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 transduced CD34+ HSPCs were transplanted into NSG mice to assay the human lymphocyte and myeloid differentiation differences 3 months after transplantation. Knocking down of SRSF11, which was high expressed in CD371+GMPs (granulocyte-monocyte progenitors), upregulated by ALA and binding to ELK1-RNA splicing site, was performed to analyze the function in erythroid differentiation derived from CD34+ CD123mid CD38+ CD371- HPCs (hematopoietic progenitor cells). RNA sequencing of L-ELK1 and S-ELK1 overexpressed CD34+ CD123mid CD38+ CD371- HPCs were performed to assay the signals changed by ELK1. RESULTS: Here, we presented new evidence that ALA promoted erythroid differentiation by targeting the transcription factor ELK1 in CD34+ CD371- hematopoietic stem progenitor cells (HSPCs). Overexpression of either the long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 inhibited erythroid-cell differentiation, but knockdown of ELK1 did not affect erythroid-cell differentiation. RNAseq analysis of CD34+ CD123mid CD38+ CD371- HPCs showed that L-ELK1 upregulated the expression of genes related to neutrophil activity, phosphorylation, and hypoxia signals, while S-ELK1 mainly regulated hypoxia-related signals. However, most of the genes that were upregulated by L-ELK1 were only moderately upregulated by S-ELK1, which might be due to a lack of serum response factor interaction and regulation domains in S-ELK1 compared to L-ELK1. In summary, the differentiation of neutrophils and erythrocytes might need to rely on the dose of L-ELK1 and S-ELK1 to achieve precise regulation via RNA splicing signals at early lineage commitment. CONCLUSIONS: ALA and ELK1 are found to regulate both human granulopoiesis and erythropoiesis via RNA spliceosome, and ALA-ELK1 signal might be the target of human leukemia therapy.

Genome-wide identification, characterization and expression of C2H2 zinc finger gene family in Opisthopappus species under salt stress.

BACKGROUND: The C2H2 zinc finger protein family plays important roles in plants. However, precisely how C2H2s function in Opisthopappus (Opisthopappus taihangensis and Opisthopappus longilobus) remains unclear. RESULTS: In this study, a total of 69 OpC2H2 zinc finger protein genes were identified and clustered into five Groups. Seven tandem and ten fragment repeats were found in OpC2H2s, which underwent robust purifying selection. Of the identified motifs, motif 1 was present in all OpC2H2s and conserved at important binding sites. Most OpC2H2s possessed few introns and exons that could rapidly activate and react when faced with stress. The OpC2H2 promoter sequences mainly contained diverse regulatory elements, such as ARE, ABRE, and LTR. Under salt stress, two up-regulated OpC2H2s (OpC2H2-1 and OpC2H2-14) genes and one down-regulated OpC2H2 gene (OpC2H2-7) might serve as key transcription factors through the ABA and JA signaling pathways to regulate the growth and development of Opisthopappus species. CONCLUSION: The above results not only help to understand the function of C2H2 gene family but also drive progress in genetic improvement for the salt tolerance of Opisthopappus species.

The value of the dermal rim sign on nonenhanced magnetic resonance imaging for predicting dermal backflow in patients with primary lower extremity lymphedema.

PURPOSE: The dermal rim sign (DRS) on nonenhanced magnetic resonance imaging has been shown to predict dermal backflow (DBF) in patients with secondary upper limb lymphedema. However, whether the DRS has the same effects on primary lower extremity lymphedema (PLEL) has not been clearly reported. Therefore, this study aimed to explore whether the DRS can be used to diagnose DBF on lymphoscintigraphy in patients with PLEL. METHODS: A total of 94 patients who were diagnosed with PLEL were recruited for this retrospective study from January 2022 to December 2023. All the patients were divided into two groups according to the lymphoscintigraphy findings: no DBF and DBF. The magnetic resonance imaging data of the two groups were recorded and statistically compared for the following indicators: range of lymphedema involvement (left, right, whole lower limbs, only thigh, only calf and ankle), signs of lymphedema (notable thickening of skin, parallel line sign, grid sign, honeycomb sign, band sign, lymph lake sign, crescent sign, DRS), and lymphedema measurement (skin thickness, band width). The DRS is characterized by notable thickening of the skin plus the grid sign and/or honeycomb sign, plus the band sign. RESULTS: The following statistically significant differences in the following indicators were found between the two groups (P < .05): notable skin thickening, parallel line sign, grid sign, honeycomb sign, band sign, DRS, skin thickness, and band width. The sensitivity, specificity, and accuracy for predicting for DBF with the DRS was 82%, 64%, and 77%, respectively. CONCLUSIONS: This study confirmed good consistency between the DRS and DBF from the perspective of imaging. This tool is suitable for children, adolescents, and patients with contraindications to lymphoscintigraphy. The DRS has important value in assessing the severity of PLEL. The DRS is suggested for the clinical use of combined surgical treatment of PLEL.

Blockade of aryl hydrocarbon receptor restricts omeprazole-induced chronic kidney disease.

Chronic kidney disease (CKD) is the 16th leading cause of mortality worldwide. Clinical studies have raised that long-term use of omeprazole (OME) is associated with the morbidity of CKD. OME is commonly used in clinical practice to treat peptic ulcers and gastroesophageal reflux disease. However, the mechanism underlying renal failure following OME treatment remains mostly unknown and the rodent model of OME-induced CKD is yet to be established. We described the process of renal injury after exposure to OME in mice; the early renal injury markers were increased in renal tubular epithelial cells (RTECs). And after long-term OME treatment, the OME-induced CKD mice model was established. Herein, aryl hydrocarbon receptor (AHR) translocation appeared after exposure to OME in HK-2 cells. Then for both in vivo and in vitro, we found that Ahr-knockout (KO) and AHR small interfering RNA (siRNA) substantially alleviated the OME-induced renal function impairment and tubular cell damage. Furthermore, our data demonstrate that antagonists of AHR and CYP1A1 could attenuate OME-induced tubular cell impairment in HK-2 cells. Taken together, these data indicate that OME induces CKD through the activation of the AHR-CYP axis in RTECs. Our findings suggest that blocking the AHR-CYP1A1 pathway acts as a potential strategy for the treatment of CKD caused by OME. KEY MESSAGES: We provide an omeprazole-induced chronic kidney disease (CKD) mice model. AHR activation and translocation process was involved in renal tubular damage and promoted the occurrence of CKD. The process of omeprazole nephrotoxicity can be ameliorated by blockade of the AHR-CYP1A1 axis.

Potential Response Patterns of Endogenous Hormones in Cliff Species Opisthopappus taihangensis and Opisthopappus longilobus under Salt Stress.

When plants are exposed to salt stress, endogenous hormones are essential for their responses through biosynthesis and signal transduction pathways. However, the roles of endogenous hormones in two cliff species (Opisthopappus taihangensis and Opisthopappus longilobus (Opisthopappus genus)) in the Taihang Mountains under salt stress have not been investigated to date. Following different time treatments under 500 mM salt concentrations, 239 differentially expressed gene (DEG)-related endogenous hormones were identified that exhibited four change trends, which in Profile 47 were upregulated in both species. The C-DEG genes of AUX, GA, JA, BR, ETH, and ABA endogenous hormones were significantly enriched in Opisthopappus taihangensis (O. taihangensis) and Opisthopappus longilobus (O. longilobus). During the responsive process, mainly AUX, GA, and JA biosynthesis and signal transduction were triggered in the two species. Subsequently, crosstalk further influenced BR, EHT, ABA, and MAPK signal transduction pathways to improve the salt resistance of the two species. Within the protein-protein interactions (PPI), seven proteins exhibited the highest interactions, which primarily involved two downregulated genes (SAUR and GA3ox) and eight upregulated genes (ACX, MFP2, JAZ, BRI1, BAK1, ETR, EIN2, and SNRK2) of the above pathways. The more upregulated expression of ZEP (in the ABA biosynthesis pathway), DELLA (in the GA signaling pathway), ABF (in the ABA signaling pathway), and ERF1 (in the ETH signaling pathway) in O. taihangensis revealed that it had a relatively higher salt resistance than O. longilobus. This revealed that the responsive patterns to salt stress between the two species had both similarities and differences. The results of this investigation shed light on the potential adaptive mechanisms of O. taihangensis and O. longilobus under cliff environments, while laying a foundation for the study of other cliff species in the Taihang Mountains.

Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells.

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. METHODS: Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. RESULTS: The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation. CONCLUSIONS: A novel method for harvesting MSCs with neural crest origin from 3D human brain organoids under serum-free culture conditions was reported. We demonstrate that the pMSCs support human UCB-HSPC expansion in vitro in a long-term culture and the maintenance of their transplantable ability. RNA and proteomic sequencing indicated that pMSCs provided an improved microenvironment for HSC maintenance via mechanisms involving cell-cell contact and secreted factors and suppression of Wnt signaling. This represents a novel method for large-scale production of MSCs of neural crest origin and provides a potential approach for development of human hematopoietic stromal cell therapy for treatment of dyshematopoiesis.

Characteristics of the presence and migration patterns of DOM between ice and water in the cold and arid Daihai Lake.

Seasonal ice cover plays a crucial role in shaping the physical characteristics of lakes in cold and arid regions. Moreover, the ice significantly affects the level and quality of dissolved organic matter (DOM) in the water column. We utilized spectroscopy and mass spectrometry to analyze the molecular composition and distribution of DOM in ice cores and under-ice water in Daihai Lake. We identified the main environmental factors affecting DOM migration through structural equation modelling (SEM). The freezing process created a repulsive effect on DOM, with water samples demonstrating a greater DOM content than ice. The dominant part of the DOM in the ice cores was mainly comprised of protein-like materials (71.45 %), whereas water consisted of humus-like materials (54.81 %). The average molecular weight of the ice cover DOM (m/z = 396.77) was smaller than in the under-ice water (m/z = 405.42). While low-molecular and low-aromatic protein-like material tended to be trapped in the ice layer during ice formation, large-molecular and highly aromatic humic substances were more easily expelled into the water. Interestingly, condensed aromatic hydrocarbons were found to occur less frequently in the ice phase (11 %) compared to the aqueous phase (13 %). Both the lipid and protein/aliphatic compound structures exhibited slightly higher ratios in the ice (6 % and 8 %, respectively) than in water (1 % and 5 %, respectively). SEM between the ice cover environment and DOM indicated that the ice can influence the distribution pattern of DOM through the regulation of internal solute factors and other chemicals. The nature of the DOM and the rate of ice growth also play critical roles in determining the distribution mechanism of DOM for ice and water. The pollutant distribution characteristics and migration patterns between ice and water are essential for comprehending environmental water pollution and promoting pollution management and protection measures in cold region lakes.

The Use of Eye-Tracking Technology in Dento-Maxillofacial Esthetics: A Systematic Review.

The use of eye-tracking technology in dental esthetics has gained popularity over the past decade because of its ability to assess observers' visual preferences in an objective manner. The goal of this study was to provide a comprehensive review of eye-tracking studies in dentistry, which could provide a reference for the rational and effective application of eye-tracking technology by dentists in the future. A comprehensive search of articles on eye tracking, published from January 1946 to June 2023, was conducted across several databases using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The major criterion for inclusion was that the study evaluated the use of eye-tracking technology in the field of dentistry. Two independent reviewers screened the eligible studies. A total of 67 articles were identified, 41 of which met our inclusion criteria. The most common application of eye tracking was the assessment of perceptions of changes in specific dental conditions among different classes of observers. Overall differences between groups (different classes of observers, different types of conditions) among different areas or regions of interest were analyzed. This systematic review demonstrated the utility of eye-tracking technology as a quantifiable objective assessment and emerging research tool for evaluating outcomes in several domains of dentistry.

Neoteric Semiembedded ß-Tricalcium Phosphate Promotes Osteogenic Differentiation of Mesenchymal Stem Cells under Cyclic Stretch.

ß-Tricalcium phosphate (ß-TCP) is a bioactive material for bone regeneration, but its brittleness limits its use as a standalone scaffold. Therefore, continuous efforts are necessary to effectively integrate ß-TCP into polymers, facilitating a sturdy ion exchange for cell regulation. Herein, a novel semiembedded technique was utilized to anchor ß-TCP nanoparticles onto the surface of the elastic polymer, followed by hydrophilic modification with the polymerization of dopamine. Cell adhesion and osteogenic differentiation of mesenchymal stem cells (MSCs) under static and dynamic uniaxial cyclic stretching conditions were investigated. The results showed that the new strategy was effective in promoting cell adhesion, proliferation, and osteogenic induction by the sustained release of Ca2+ in the vicinity and creating a reasonable roughness. Specifically, released Ca2+ from ß-TCP could activate the calcium signaling pathway, which further upregulated calmodulin and calcium/calmodulin-dependent protein kinase II genes in MSCs. Meanwhile, the roughness of the membrane and the uniaxial cyclic stretching activated the PIEZO1 signaling pathway. Chemical and mechanical stimulation promotes osteogenic differentiation and increases the expression of related genes 2-8-fold. These findings demonstrated that the neoteric semiembedded structure was a promising strategy in controlling both chemical and mechanical factors of biomaterials for cell regulation.

Effect of yeast extract on microbiologically influenced corrosion of X70 pipeline steel by Desulfovibrio bizertensis SY-1.

Microbiologically influenced corrosion (MIC) is a complicated process that happens ubiquitously and quietly in many fields. As a useful nutritional ingredient in microbial culture media, yeast extract (YE) is a routinely added in the MIC field. However, how the YE participated in MIC is not fully clarified. In the present work, the effect of YE on the growth of sulfate reducing prokaryotes (SRP) Desulfovibrio bizertensis SY-1 and corrosion behavior of X70 pipeline steel were studied. It was found that the weight loss of steel coupons in sterile media was doubled when YE was removed from culture media. However, in the SRP assays without YE the number of planktonic cells decreased, but the attachment of bacteria on steel surfaces was enhanced significantly. Besides, the corrosion rate of steel in SRP assays increased fourfold after removing YE from culture media. MIC was not determined for assays with planktonic SRP but only for biofilm assays. The results confirm the effect of YE on D. bizertensis SY-1 growth and also the inhibitory role of YE on MIC.

Molecular subgroup establishment and signature creation of lncRNAs associated with acetylation in lung adenocarcinoma.

BACKGROUND: The significance of long non-coding RNAs (lncRNAs) as pivotal mediators of histone acetylation and their influential role in predicting the prognosis of lung adenocarcinoma (LUAD) has been increasingly recognized. However, there remains uncertainty regarding the potential utility of acetylation-related lncRNAs (ARLs) in prognosticating the overall survival (OS) of LUAD specimens. METHODS: The RNA-Seq and clinical information were downloaded from The Cancer Genome Atlas (TCGA). Through the differential analysis, weighted correlation network analysis (WGCNA), Pearson correlation test and univariate Cox regression, we found out the prognosis associated ARLs and divided LUAD specimens into two molecular subclasses. The ARLs were employed to construct a unique signature through the implementation of the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. Subsequently, the predictive performance was evaluated using ROC analysis and Kaplan-Meier survival curve analysis. Finally, ARL expression in LUAD was confirmed by quantitative real-time PCR (qRT-PCR). RESULTS: We triumphantly built a ARLs prognostic model with excellent predictive accuracy for LUAD. Univariate and multivariate Cox analysis illustrated that risk model served as an independent predictor for influencing the overall survival OS of LUAD. Furthermore, a nomogram exhibited strong prognostic validity. Additionally, variations were observed among subgroups in the field of immunity, biological functions, drug sensitivity and gene mutations within the field. CONCLUSIONS: Nine ARLs were identified as promising indicators of personalized prognosis and drug selection for people suffering with LUAD.

YTHDC1 inhibits osteoclast differentiation to alleviate osteoporosis by enhancing PTPN6 mRNA stability in an m6A-HUR dependent manner.

YTH domain containing 1 (YTHDC1) has been confirmed to mediate osteoporosis (OP) progression by regulating osteogenic differentiation. However, whether YTHDC1 mediates osteoclast differentiation and its molecular mechanism remain unclear. Quantitative real-time PCR and western blot analysis were performed to detect the levels of YTHDC1, protein tyrosine phosphatase non-receptor type 6 (PTPN6), nuclear factor of activated T cells 1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), runt-related transcription factor 2 (RUNX2), alkalinephosphatase (ALP) human antigen R (HUR). YTHDC1 knockout (KO) mice was constructed by CRISPR/Cas9 system, and OP mice model was established by ovariectomy (OVX). Hematoxylin and eosin (H&E) staining and micro-CT were used to evaluate bone formation and bone mass. Mouse primary bone marrow macrophages cells (BMMs) were isolated and induced into osteoclasts. TRAP positive cells were detected using TRAP staining. MeRIP-qPCR, RIP-qPCR assay, RNA affinity isolation assay and Co-IP assay were used to confirm the interactions among YTHDC1, PTPN6 and HUR. YTHDC1 expression was reduced and positively correlated with lumbar bone mineral density (BMD) in OP patients. In OVX model of YTHDC1-KO mice, bone formation was reduced, bone histomorphology was changed, and osteoclastic-related factors (NFATc1 and TRAP) levels were enhanced. Overexpression YTHDC1 inhibited osteoclast differentiation. YTHDC1 increased PTPN6 mRNA stability in an m6A dependent manner. Moreover, YTHDC1 interacted with HUR to positively regulate PTPN6 expression. PTPN6 knockdown promoted osteoclast differentiation, and this effect was reversed by overexpressing HUR or YTHDC1. YTHDC1 was involved in regulating OP progression through inhibiting osteoclast differentiation by enhancing PTPN6 mRNA stability in an m6A-HUR dependent manner.

Responsive Alternative Splicing Events of Opisthopappus Species against Salt Stress.

Salt stress profoundly affects plant growth, prompting intricate molecular responses, such as alternative splicing (AS), for environmental adaptation. However, the response of AS events to salt stress in Opisthopappus (Opisthopappus taihangensis and Opisthopappus longilobus) remains unclear, which is a Taihang Mountain cliff-dwelling species. Using RNA-seq data, differentially expressed genes (DEGs) were identified under time and concentration gradients of salt stress. Two types of AS, skipped exon (SE) and mutually exclusive exons (MXE), were found. Differentially alternative splicing (DAS) genes in both species were significantly enriched in "protein phosphorylation", "starch and sucrose metabolism", and "plant hormone signal transduction" pathways. Meanwhile, distinct GO terms and KEGG pathways of DAS occurred between two species. Only a small subset of DAS genes overlapped with DEGs under salt stress. Although both species likely adopted protein phosphorylation to enhance salt stress tolerance, they exhibited distinct responses. The results indicated that the salt stress mechanisms of both Opisthopappus species exhibited similarities and differences in response to salt stress, which suggested that adaptive divergence might have occurred between them. This study initially provides a comprehensive description of salt responsive AS events in Opisthopappus and conveys some insights into the molecular mechanisms behind species tolerance on the Taihang Mountains.

Photocatalytic chitosan-based bactericidal films incorporated with WO3/AgBr/Ag and activated carbon for ethylene removal and application to banana preservation.

Ethylene (C2H4) and pathogenic microorganisms are the two major causes of the deterioration of postharvest fruits and vegetables (F&V). Hence, the development of active packaging with C2H4 scavenging and bactericidal activities is urgently desirable. Herein, a novel photocatalytic active film (CS-PC-AC) is developed for banana preservation by incorporating WO3/AgBr/Ag photocatalyst (PC) and activated carbon (AC) into chitosan (CS). The fabricated PC is a ternary Z-scheme heterojunction and its high photocatalytic activity is achieved by the bridge of Ag between WO3 and AgBr through rapid transfer and separation of photogenerated electrons and holes. AC plays an indispensable role in the photocatalytic reaction through molecule adsorption and transport. PC and AC are hydrogen bonded with chitosan and their incorporation has slight effect on film's thermal stability but decreases the film's mechanical and barrier properties to some extent. CS-PC-AC exhibits strong bactericidal activity (killing ~100 % of Escherichia coli and Staphylococcus aureus within 3 h) and good C2H4 scavenging activity (C2H4 scavenging rate of 49 ± 2 %) under visible light irradiation, which can extend the banana shelf-life by at least 50 % at 25 °C. These results indicate the good perspective of CS-PC-AC in the delay of the deterioration of postharvest F&V.

Facile fluorescence detection of malachite green in fish using molecularly imprinted polymers doped CdTe quantum dots based system.

Malachite green (MG) possesses high toxicity, therefore, the detection of MG in fish tissues is of vital importance. A novel core-shell MIPs doped CdTe quantum dots coated silica nanoparticles (CdTe-MIP/SiO2 NPs) were synthesized via a simple one-pot strategy. The materials were characterized carefully. The resulting CdTe-MIP/SiO2 NPs were coated on the thin layer chromatography plate, and coupled with miniaturized fluorimeter for fluorescence detection of MG in fish samples. The resulting CdTe-MIP/SiO2 NPs based system possessed good linearity (0.01 âˆ¼ 20 µmol/L), high recoveries (98.36 %∼101.45 %) and low detection limit (3.7 nmol/L) for MG. Furthermore, CdTe-MIP/SiO2 NPs based system were employed to measure fish samples spiked with MG, meanwhile, HPLC was utilized to evaluate the accuracy and reliability. And the paired t-test was conducted to evaluate differences between fluorescence method and HPLC, P > 0.05 means no significant difference was observed, the results demonstrated that both fluorescence method and HPLC are suitable for MG analysis.

The association of normal-range serum phosphorus with immunoglobulin A nephropathy progression: a retrospective cohort study.

PURPOSE: The relationship between serum phosphorus and immunoglobulin A (IgA) nephropathy progression remains uncertain, especially normal-range serum phosphorus. Therefore, we herein examined the relationship between the normal-range serum phosphorus and the progression of IgA nephropathy. METHODS: One hundred sixty-two patients with primary IgA nephropathy were divided into three groups according to tertiles of baseline serum phosphorus (first tertile: 0.73-1.04 mmol/L; second tertile: 1.04-1.21 mmol/L; third tertile: 1.21-1.60 mmol/L). Estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration. The composite outcome was defined as a decrease of at least 50% in eGFR from baseline or end-stage kidney disease (ESKD). The association of serum phosphorus with IgA nephropathy progression was estimated using Cox proportional hazards models, adjusting for potential confounders. RESULTS: During a median 16 month follow-up period, 15 patients reached a composite outcome. In the crude Cox proportional hazard model, baseline serum phosphorus as a continuous variable was associated with increased risk for adverse renal outcomes [hazard ratio (HR) = 63.510, 95% confidence interval (CI) = 3.953-1020.284, P = 0.003], and the high tertile of serum phosphorus group had an increased risk of the composite outcome by using the low tertile group as the reference (HR = 11.895, 95% CI = 1.522-92.993, P = 0.018). After adjustment for traditional risk factors, the high tertile of serum phosphorus group was significantly related to IgA nephropathy progression compared with the low tertile group (HR = 9.424, 95% CI = 1.019-87.165, P = 0.048). CONCLUSIONS: Relatively higher serum phosphorus levels within the normal range were significantly associated with the progression of IgA nephropathy.