NAT10/CEBPB/vimentin signalling axis promotes adenoid cystic carcinoma malignant phenotypes in vitro.

OBJECTIVE: To explore the biological function and mechanisms of CEBPB and NAT10-mediated N4-acetylcytidine (ac4c) modification in salivary adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: CEBPB and NAT10 were knocked down in SACC-LM cells by siRNA transfection and overexpressed in SACC-83 cells by plasmid transfection. Malignant phenotypes were evaluated using CCK-8, Transwell migration and colony formation assays. Real-time PCR, western blotting, ChIP and acRIP were used to investigate the molecular mechanisms involved. RESULTS: We found that CEBPB was highly expressed in SACC tissues and correlated with lung metastasis and unfavourable prognosis. Gain- and loss-of-function experiments revealed that CEBPB promoted SACC malignant phenotypes. Mechanistically, CEBPB exerted its oncogenic effect by binding to the vimentin gene promoter region to enhance its expression. Moreover, NAT10-mediated ac4c modification led to stabilization and overexpression of CEBPB in SACC cells. We also found that NAT10, the only known human enzyme responsible for ac4C modification, promoted SACC cell migration, proliferation and colony formation. Moreover, CEBPB overexpression restored the inhibitory effect of NAT10 knockdown on malignant phenotypes. CONCLUSIONS: Our study reveals the critical role of the newly identified NAT10/CEBPB/vimentin axis in SACC malignant progression, and the findings may be applied to improve treatment for SACC.

Long non-coding RNA MRPL23-AS1 suppresses anoikis in salivary adenoid cystic carcinoma in vitro.

Distant lung metastasis is the main factor that affects the survival rate of patients with salivary adenoid cystic carcinoma (SACC). Anoikis resistance is a feature of tumor cells that easily metastasize. The long non-coding RNA (lncRNA) MRPL23 antisense RNA 1 (MPRL23-AS1) is related to lung metastasis in SACC, but its role in anoikis resistance is unknown. After altering MPRL23-AS1 expression in SACC cells, anoikis resistance was detected by calcein AM/PI staining and annexin V/PI flow cytometry. The apoptosis marker activated caspase-3 and the bcl-2/bax ratio were detected by Western blotting. The relationship between MPRL23-AS1 and the promoter of the potential downstream target gene p19INK4D was identified by chromatin immunoprecipitation (ChIP)-PCR assay. p19INK4D expression in patient tissues was determined using qRT-PCR and immunohistochemistry. The functional experiments showed that MPRL23-AS1 could promote anoikis resistance in vitro. MRPL23-AS1 recruited the EZH2 to the promoter region of p19INK4D, inhibited p19INK4D expression, and promoted tumor cell anoikis resistance. p19INK4D overexpression did not affect anoikis in attached cells; however, it attenuated the anoikis resistance effect of MPRL23-AS1 in suspension cells. p19INK4D expression was significantly lower in SACC tissues than in normal tissues. The novel MRPL23-AS1/p19INK4D axis may be a potential SACC biomarker or therapeutic target.

Tailoring Electronic Structure and Size of Ultrastable Metalated Metal-Organic Frameworks with Enhanced Electroconductivity for High-Performance Supercapacitors.

Utilization of metal-organic frameworks (MOFs) as electrodes for energy storage/conversion is challenging because of the low chemical stability and poor electrical conductivity of MOFs in electrolytes. A nanoscale MOF, Co0.24 Ni0.76 -bpa-200, possessing ultrahigh stability with uncommon semiconductor behavior (σ=4.2×10-3  S m-1 ) was fabricated. The MOF comprises a robust hydrophobic paddlewheel and an optimized Co/Ni ratio, with consequent control over MOF size and the degree of conjugation of the coligand. A DFT study revealed that appropriate Ni2+ doping reduces the activation energy of the system, thus providing a higher carrier concentration, and the strongly delocalized N-donor ligand notably increases the metal-ligand orbital overlap to achieve efficient charge migration, leading to continuous through-bond (-CoNi-N-CoNi-)∞ conduction paths. These structural features endow the MOF with a good cycling stability of 86.5 % (10 000 cycles) and a high specific capacitance of 1927.14 F g-1 among pristine MOF-based electrodes.

Stem cells  from exfoliated  deciduous  teeth alleviate hyposalivation caused by Sjögren syndrome.

OBJECTIVES: To evaluate the effect of stem cells  from  exfoliated  deciduous  teeth on the hyposalivation caused by Sjögren syndrome (SS) and investigate the mechanism. METHODS: Stem cells were injected into the tail veins of non-obese diabetic mice, the animal model of SS. The saliva flow was measured after pilocarpine intraperitoneal injection. Apoptosis and autophagy were evaluated by TUNEL and Western blot. Lymphocyte proportions were detected by flow cytometer. RESULTS: Fluid secretion was decreased in 21-week-old mice. Stem cell treatment increased fluid secretion, alleviated inflammation in the submandibular glands and reduced inflammatory cytokine levels in the serum, submandibular glands and saliva. Stem cells decreased the apoptotic cell number and the expressions of ATG5 and Beclin-1 in the submandibular glands. Stem cells have no effect on other organs. Furthermore, the infused stem cells migrated to the spleen and liver, not the submandibular gland. Stem cells directed T cells towards Treg cells and suppressed Th1 and Tfh cells in spleen lymphocytes. CONCLUSION: Stem cells  from  exfoliated  deciduous  teeth alleviate the hyposalivation caused by SS via decreasing the inflammatory cytokines, regulating the inflammatory microenvironment and decreasing the apoptosis and autophagy. The stem cells regulated in T-cell differentiation are involved in the immunomodulatory effects.

Hsa_circRNA_0059655 plays a role in salivary adenoid cystic carcinoma by functioning as a sponge of miR-338-3p.

Circular RNAs(circRNA) are recently demonstrated to have a close relationship with tumors.To investigate the role of circular RNA in the pathogenesis of salivary adenoid cystic carcinoma(SACC), ten SACC tissues and paired normal submandibular gland(SMG) tissues were collected as the tumor group and the control group. Total RNA was extracted and then measured using ceRNA microarray (including mRNA, lncRNA, and circRNA) and miRNA microarray. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis were performed in order to investigate the function of the differential expressing genes. The ceRNA regulatory network was constructed to find the core circRNAs. Then the role of circRNA on proliferation was examined in the SACC cell line SACC-83 using CCK-8,qRT-PCR and western blotting, and its roles on migration and invasion were examined using wound healing assay and transwell assay. The results of the microarrays showed that 3792 mRNAs, 7649 lncRNAs, 11553 circRNAs, and 132 miRNAs expressed differentially. The ceRNA regulatory network analysis showed that hsa_circ_0059655 and other 14circRNAs derived from PYGB target on several similar genes by miR-338-3p.Among the 15 circRNAs derived from PYGB, hsa_circ_0059655has the most relationships in the ceRNA network. Furthermore, after hsa_circ_0059655 was knocked down in SACC-83 cells, the expression of hsa-miR-338-3p was up-regulated while CCND1was down-regulated. The proliferation, migration, and invasion of SACC-83 cells also decreased after hsa_circ_0059655 knock-downed.Taken together, the circRNAs derived from PYGB may regulate the tumorigenesis and development of SACC through competing with miR-338-3p.

Expression of the TetA gene encoding TetA efflux protein in E. coli contributes to its increased bacterial resistance toward berberine.

Berberine (BBR) is a traditional Chinese medicine in various applications due to its antibacterial effect. Here we investigated the increased bacterial resistance of E. coli toward BBR. The median effective concentration (EC50) of BBR against E. coli was increased when TetA efflux protein (TEP) was introduced. Sixty-five percent of the intracellular BBR was expelled and molecular docking demonstrated the intensive interaction of TEP to BBR. Finally, the combined antibacterial experiment identified that BBR acted as an inhibitor of TEP in detoxification of tetracycline. TEP is the first discovered protein that was related to the bacterial susceptibility to BBR.

Evaluation of berberine as a natural fungicide: biodegradation and antimicrobial mechanism.

Berberine (BBR) is a traditional Chinese medicine which recently was applied as a biological pesticide. Here, we studied the antimicrobial mode of BBR and its impact on soil bacterial diversity. BBR was more effective against fungi than bacteria due to the specific interaction between BBR and glucan. Also, BBR was degraded rapidly in soil, leading to the limited effect on soil bacterial diversity. Collectively, BBR is an environment-friendly pesticide and it is promising in dealing with fungal plant diseases.

[Value of Elasticity Contrast Index of Ultrasonography in Differentiating Benign and Malignant Cervical Lymph Nodes].

Objective To investigate the diagnostic value of elasticity contrast index(ECI)in the differential diagnosis between benign and malignant cervical lymph nodes.Methods Cervical lymph nodes of 48 patients were examined by traditional ultrasound and ECI in Peking University Third Hospital between December 2016 and April 2017. Patients were further divided into free-hand group and non-free-hand group according to the use of manual compression or not. With pathological or clinical follow-up results as the gold standard,we compared the diagnostic values of traditional ultrasound,ECI,and their combination in the differential diagnosis between benign and malignant lymph nodes.Results Totally 138 lymph nodes were collected from 46 patients,among which 76 were benign and 62 were malignant. The ECI value of malignant lymph nodes(1.69±0.89)were significantly higher than that of benign lymph nodes(1.32±0.87)(t=-2.46,P=0.015).The area under receiver operating characteristic(ROC)curve for traditional ultrasound in discrimination of malignant cervical lymph nodes with benign ones was 0.899,with an optimal cut-off value of 7,which had a sensitivity of 93.5% and a specificity of 84.2%. The area under ROC curve for ECI was 0.649,with an optimal cut-off value of 1.25,which had a sensitivity of 59.7% and a specificity of 60.5%. For their combination,the area under ROC curve was 0.724,with a sensitivity of 93.5% and a specificity of 51.3%. In the group without using free-hand technique,the mean ECI value was 1.77±0.94 for malignant nodes,which was significantly higher than that(1.26±0.81)for benign nodes(t=-3.09,P=0.003). In the group requiring free-hand technique,the ECI value for malignant nodes was 1.33(1.01,1.44),showing no significant difference with benign ones[1.32(0.78,2.18);z=-0.20,P=0.843].Conclusions Conventional ultrasound has higher diagnostic value than ECI and their combination in differentiating benign and malignant lymph nodes. The role of ECI in evaluating other organs requires further investigations.

Identification of FkpA as a key quality control factor for the biogenesis of outer membrane proteins under heat shock conditions.

The outer membrane proteins (OMPs) of Gram-negative bacterial cells, as well as the mitochondrion and chloroplast organelles, possess unique and highly stable ß-barrel structures. Biogenesis of OMPs in Escherichia coli involves such periplasmic chaperones as SurA and Skp. In this study, we found that the ΔsurA Δskp double-deletion strain of E. coli, although lethal and defective in the biogenesis of OMPs at the normal growth temperature, is viable and effective at the heat shock temperature. We identified FkpA as the multicopy suppressor for the lethal phenotype of the ΔsurA Δskp strain. We also demonstrated that the deletion of fkpA from the ΔsurA cells resulted in only a mild decrease in the levels of folded OMPs at the normal temperature but a severe decrease as well as lethality at the heat shock temperature, whereas the deletion of fkpA from the Δskp cells had no detectable effect on OMP biogenesis at either temperature. These results strongly suggest a functional redundancy between FkpA and SurA for OMP biogenesis under heat shock stress conditions. Mechanistically, we found that FkpA becomes a more efficient chaperone for OMPs under the heat shock condition, with increases in both binding rate and affinity. In light of these observations and earlier reports, we propose a temperature-responsive OMP biogenesis mechanism in which the degrees of functional importance of the three chaperones are such that SurA > Skp > FkpA at the normal temperature but FkpA ≥ SurA > Skp at the heat shock temperature.

Nimotuzumab suppresses epithelial-mesenchymal transition and enhances apoptosis in low-dose UV-C treated salivary adenoid cystic carcinoma cell lines in vitro.

Salivary adenoid cystic carcinoma (SACC), which is one of the most common malignant tumors of the salivary glands, is associated with a poor long-term outcome. There are currently few therapeutic options for patients with SACC. Recent studies have shown the potential of the application of ultraviolet-C (UV-C) irradiation for the treatment of human cancer. In the present study, we investigated the effects of UV-C in the SACC cell lines SACC-83 and SACC-LM. High-dose UV-C (200 J/m) induced apoptosis and inhibited colony formation significantly. However, low-dose UV-C (10 J/m), which had little effect on apoptosis and colony formation, increased the ability of migration in SACC cells accompanied by a decrease in E-cadherin and an increase in vimentin, suggesting the occurrence of epithelial-mesenchymal transition (EMT). Low-dose UV-C (10 J/m) also resulted in upregulation of the phosphorylated forms of epidermal growth factor receptor (EGFR) and Akt (p-EGFR and p-Akt, respectively). Pretreatment with Nimotuzumab, an anti-EGFR monoclonal antibody, reversed the EMT as well as upregulation of p-EGFR/p-Akt induced by UV-C. Moreover, Nimotuzumab enhanced UV-C induced apoptosis and inhibition of colony formation. Our results indicate that EMT exerts a protective effect against apoptosis induced by low-dose UV-C. Thus, the combined application of Nimotuzumab and low-dose UV-C in vitro has an advantageous antitumor effect in SACC compared with the application of UV-C alone.

Insights into 3-hydroxypropionic acid biosynthesis revealed by overexpressing native glycerol dehydrogenase in Klebsiella pneumoniae.

In Klebsiella pneumoniae, glycerol dissimilation involves parallel oxidation and reduction pathways. Oxidation pathway provides adenosine triphosphate (ATP) and cofactors to sustain cell growth, while reduction pathway presents 3-hydroxypropionic acid (3-HP) and 1,3-propanediol(1,3-PDO), which are commercially attractive platform chemicals. Previous metabolic engineering of K. pneumoniae focused on the intensification of reduction pathway; however, it failed to overproduce 3-HP or 1,3-PDO. Contrary to this strategy, here we show that overexpression of glycerol dehydrogenase (dhaD), the first functional enzyme in oxidation pathway, can efficiently stimulate cell growth and facilitate 3-HP accumulation. Under microaerobic conditions, although metabolic burden arising from plasmid replication, the recombinant K. pneumoniae overexpressing dhaD grew actively and showed 60% enhancement of 3-HP compared to the control. In particular, overexpression of dhaD increased the activity of glycerol dehydratase, indicating the concerted action of two enzymes and the interdependence between glycerol oxidation and reduction pathways. Moreover, the strain overexpressing dhaD produced more lactic acid yet less acetic acid than the control, implying the interplay between dhaD expression and the formation of byproducts. Together, not only showing that intensifying glycerol oxidation pathway is beneficial to 3-HP production, this study also reveals the structural rigidity of dha operon that mediates glycerol dissimilation in K. pneumoniae.

Population pharmacokinetics of oxcarbazepine active metabolite in Chinese paediatric patients with epilepsy: Model-based dose optimization.

The pharmacological activity of oxcarbazepine (OXC) is primarily exerted through its active 10-monohydroxy metabolite (MHD). Nonetheless, there is limited pharmacokinetic information available regarding paediatric patients with epilepsy treated with OXC, especially in infants and toddlers. Concurrently, this drug exhibits substantial variability in pharmacokinetics and therapeutic response across different individuals. We aimed to develop a model to quantitatively investigate factors that affect MHD pharmacokinetics to formulate a dosage guideline for OXC in Chinese paediatric patients. A total of 297 MHD trough concentrations were obtained from 287 epileptic children. Six body weight (BW)-based allometric models were used for population pharmacokinetic modelling, while investigating the impact of other covariates on the apparent clearance. The one-compartment model and age cut-off model for the apparent clearance (CL/F) were established to describe the pharmacokinetics of MHD. The probability to obtain target trough concentration ranges (TTCRs) of MHD between 3 and 35 mg/L was determined by Monte Carlo simulations for doses ranging from 8 to 90 mg/kg/day. A new dose optimization strategy combining the dosage guidelines and Bayesian method provides a tailored approach for Chinese paediatric epileptic patients based on their individual BW and desired TTCRs of MHD, and also supports current dose recommendations, with the exception of children weighing ≤5 kg.

Extracellular vesicles containing circMYBL1 induce CD44 in adenoid cystic carcinoma cells and pulmonary endothelial cells to promote lung metastasis.

Adenoid cystic carcinoma (ACC) is a rare malignant epithelial neoplasm that arises in secretory glands and commonly metastasizes to the lungs. MYBL1 is frequently overexpressed in ACC and has been suggested to be a driver of the disease. Here, we identified a circRNA derived from MYBL1 pre-mRNA that accompanied overexpression of MYBL1 in ACC. Overexpression of circMYBL1 was correlated with increased lung metastasis and poor overall survival in ACC patients. Ectopic circMYBL1 overexpression promoted malignant phenotypes and lung metastasis of ACC cells. Mechanistically, circMYBL1 formed a circRNA-protein complex with CCAAT enhancer binding protein beta (CEBPB), which inhibited ubiquitin-mediated degradation and promoted nuclear translocation of CEBPB. In the nucleus, circMYBL1 increased the binding of CEBPB to the CD44 promoter region and enhanced its transcription. In addition, circMYBL1 was enriched in small extracellular vesicles (sEVs) isolated from the plasma of ACC patients. Treatment with sEVs containing circMYBL1 in sEVs enhanced pro-metastatic phenotypes of ACC cells, elevated the expression of CD44 in human pulmonary microvascular endothelial cells (HPMECs), and enhanced the adhesion between HPMECs and ACC cells. Moreover, circMYBL1 encapsulated in sEVs increased the arrest of circulating ACC cells in the lung and enhanced the lung metastatic burden. This data suggests that circMYBL1 is a tumor-promoting circRNA that could serve as a potential biomarker and therapeutic target in ACC.

ALMS1-IT1: A Key Player in the Novel Disulfidptosis-Related LncRNA Prognostic Signature for Head and Neck Squamous Cell Carcinoma.

Disulfidptosis is a newly discovered form of programmed cell death that is induced by disulfide stress. It is closely associated with various cancers, including head and neck squamous cell carcinoma (HNSCC). However, the factors involved in the modulation of disulfidptosis-related genes (DRGs) still remain unknown. In this study, we established and validated a novel risk score model composed of 11 disulfidptosis-related lncRNAs (DRLs) based on 24 DRGs in HNSCC. The results revealed strong correlations between the 11-DRL prognostic signature and clinicopathological features, immune cell infiltration, immune-related functions, and disulfidptosis-associated pathways, including NADPH and disulfide oxidoreductase activities. Furthermore, we studied and verified the involvement of ALMS1-IT1, one of the 11 model DRLs, in the disulfidptosis of HNSCC cell lines. A series of assays demonstrated that ALMS1-IT1 modulated cell death under starvation conditions in a pentose phosphate pathway (PPP)-dependent manner. Knockdown of ALMS1-IT1 inhibited the PPP, contributing to a decline in NADPH levels, which resulted in the formation of multiple intermolecular disulfide bonds between actin cytoskeleton proteins and the collapse of F-actin in the cytoplasm. Therefore, ALMS1-IT1, which is highly expressed in SLC7A11high cells, can be considered a promising therapeutic target for disulfidptosis-focused treatment strategies for cancer and other diseases.

Responses of leaf traits to altitude in Quercus aquifolioides and Sorbus rehderiana on the eastern edge of the Qinghai-Tibet Plateau, China.

As the most senstitive plant organs to environmental changes, leaves serve as crucial indicators of plant survival strategies. We measured the morphology, anatomical traits, gas exchange parameters, and chlorophyll fluorescence parameters of Quercus aquifolioides (evergreen broad-leaved) and Sorbus rehderiana (deciduous broad-leaved) at altitudes of 2600, 2800, 3000, 3200 and 3400 m on the eastern edge of the Qinghai-Tibet Plateau, China. We explored the similarity and difference in their responses to altitude change and the ecological adaptation strategy. The results showed that as the altitude increased, leaf dry matter content of Q. aquifolioides decreased, that of S. rehderiana increased, leaf size for both species gradually decreased, and the palisade coefficient of Q. aquifolioides showed a decreasing trend, contrasting with the increasing trend in S. rehderiana. As the altitude increased, the thickness of leaves, palisade tissue, spongy tissue, upper epidermis, and lower epidermis of both species increased significantly, with the increment of 22.4%, 4.9%, 45.1%, 23.3%, 19.6%, and 28.2%, 46.9%, 8.9%, 25.9%, 20.8% at altitude of 3400 m, respectively, compared with the altitude of 2600 m. The gas exchange and chlorophyll fluorescence parameters of S. rehderiana significantly increased with increasing altitude, while Q. aquifolioides showed the opposite trend. Leaf anatomical traits, gas exchange, and chlorophyll fluorescence parameters of both species displayed considerable plasticity. There were significant correlations among most leaf traits and between leaf traits and altitude. The survival strategy of Q. aquifolioides was more conservative in response to altitude changes, while that of S. rehderiana was more active. Both species adapted to different altitudes by adjusting their own traits.

[Differences and drivers of leaf stable carbon and nitrogen isotope in herbs under different vegetation types on the eastern Qinghai-Tibet Plateau]. / é’è—é«˜åŽŸä¸œç¼˜ä¸åŒæ¤è¢«ç±»åž‹ä¸‹è‰æœ¬æ¤ç‰©å¶ç‰‡ç¢³æ°®ç¨³å®šåŒä½ç´ å·®å¼‚åŠå ¶é©±åŠ¨å› ç´ .

The natural abundance of stable carbon and nitrogen isotopes (δ13C and δ15N) in leaves can provide comprehensive information on the physiological and ecological processes of plants and has been widely used in ecological research. However, recent studies on leaf δ13C and δ15N have focused mainly on woody species, few studies have been conducted on herbs in different vegetation types, and their differences and driving factors are still unclear. In this study, we focused on the herbs in subalpine coniferous forests, alpine shrublands, and alpine mea-dows on the eastern Qinghai-Tibet Plateau, and investigated the differences in leaf δ13C and δ15N of herbs and the driving factors. The results showed that there were significant differences in leaf δ13C and δ15N values of herbs among different vegetation types, with the highest δ13C and δ15N values in alpine meadows, followed by alpine shrublands, and the lowest in subalpine coniferous forests. Using variation partitioning analysis, we revealed that differences in leaf δ13C and δ15N of herbs among various vegetation types were driven by both leaf functional traits and climate factors, with the contribution of leaf functional traits being relatively higher than that of climate factors. Hierarchical partitioning results indicated that mean annual temperature (MAT), chlorophyll content index, leaf nitrogen content per unit area (Narea), and leaf mass per area were the main drivers of leaf δ13C variations of herbs across different vegetation types, while the relative importance of Narea and MAT for variation in leaf δ15N of herbs was much higher than those other variables. There was a strong coupling relationship between leaf δ13C and δ15N as indicated by the result of the ordinary least squares regression. Our findings could provide new insights into understanding the key drivers of leaf δ13C and δ15N variations in herbs across different vegetation types.

A genetically incorporated crosslinker reveals chaperone cooperation in acid resistance.

Acid chaperones are essential factors in preserving the protein homeostasis for enteric pathogens to survive in the extremely acidic mammalian stomach (pH 1-3). The client proteins of these chaperones remain largely unknown, primarily because of the exceeding difficulty of determining protein-protein interactions under low-pH conditions. We developed a genetically encoded, highly efficient protein photocrosslinking probe, which enabled us to profile the in vivo substrates of a major acid-protection chaperone, HdeA, in Escherichia coli periplasm. Among the identified HdeA client proteins, the periplasmic chaperones DegP and SurA were initially found to be protected by HdeA at a low pH, but they subsequently facilitated the HdeA-mediated acid recovery of other client proteins. This unique, ATP-independent chaperone cooperation in the ATP-deprived E. coli periplasm may support the acid resistance of enteric bacteria. The crosslinker would be valuable in unveiling the physiological interaction partners of any given protein and thus their functions under normal and stress conditions.

Applications of Polydopamine in Implant Surface Modification.

There is great clinical demand for orthopedic and dental implant surface modification methods to prevent osseointegration failure and improve implant biological functions. Notably, dopamine (DA) can be polymerized to form polydopamine (PDA), which is similar to the adhesive proteins secreted by mussels, to form a stable bond between the bone surface and implants. Therefore, PDA has the potential to be used as an implant surface modification material with good hydrophilicity, roughness, morphology, mechanical strength, biocompatibility, antibacterial activity, cellular adhesion, and osteogenesis. In addition, PDA degradation releases DA into the surrounding microenvironment, which is found to play an important role in regulating DA receptors on both osteoblasts and osteoclasts during the bone remodeling process. Furthermore, the adhesion properties of PDA suggest its use as an intermediate layer in assisting other functional bone remodeling materials, such as nanoparticles, growth factors, peptides, and hydrogels, to form "dual modifications." The purpose of this review is to summarize the recent progress in research on PDA and its derivatives as orthopedic and dental implant surface modification materials and to analyze the multiple functions of PDA.

The double-edged sword effects of active social media use on loneliness: The roles of interpersonal satisfaction and fear of missing out.

Introduction: Social media' impact on loneliness has attracted widespread scholarly attention. One hypothesis is that active social media use (ASMU) is associated with a decrease in loneliness. However, several empirical studies did not find a significant correlation between ASMU and loneliness, and ASMU may even increase loneliness. This study explored the mechanism of the double-edged sword effects of ASMU on loneliness. Methods: Data were collected through convenience sampling from three universities in China. A total of 454 Chinese college social media users (Mean age 19.75 ± 1.33; 59.92% female) completed an online questionnaire. Results: ASMU was positively related to interpersonal relationship satisfaction, which was negatively related to general trait-fear of missing out (FoMO) and loneliness. Further structural equation modeling (SEM) analysis showed that ASMU could negatively predict loneliness through the mediation pathways of interpersonal satisfaction and "Interpersonal satisfaction → Trait-FoMO." At the same time, ASMU was also positively associated with online-specific state-FoMO, which was positively associated with trait-FoMO and loneliness. Further SEM analysis found no mediation effect of state-FoMO between ASMU and loneliness, but state-FoMO and traitFoMO sequentially mediate the relationship between ASMU and loneliness. Discussion: This study indicates that ASMU may increase and decrease loneliness. Interpersonal satisfaction and FoMO explained the double-edged mechanism of ASMU on loneliness. These findings contribute to dialectically understanding the effectiveness of active social media use and provide theoretical guidance for promoting the beneficial aspects of social media while weakening its harmful consequences.

Effects of slope aspect on soil enzyme activity and microbial nutrient limitation in subalpine region of wes-tern Sichuan, China.

Exploring the resource limitation of soil microbial metabolism is essential to understand ecosystem functions and processes. However, the spatially divergent patterns and drivers of soil microbial nutrient limitation cha-racteristics in montane ecosystems at small scales, especially at the slope aspect scale, are still unclear. In this study, we measured soil enzyme activities involved in carbon (C), nitrogen (N) and phosphorus (P) cycle and quantified the microbial nutrient limitations by enzyme stoichiometry in two representative mountain sites in subalpine region of western Sichuan, including the sunny and shady slopes with different vegetation types (shrubland and forest, respectively) in Miyaluo of Lixian County, and with the same vegetation type (shrubland) in Yakexia of Heishui County. The results showed that soil enzyme activities and their stoichiometric ratios were significantly different between slope aspects in Miyaluo, while the differences were not significant in Yakexia. The stoichiometry ratio of C-, N- and P-acquiring enzymes on the sunny slope of Miyaluo was 1:0.96:0.92, approaching the 1:1:1 ratio at the global scale, but deviated from 1:1:1 on the shady slope of Miyaluo (1:1.39:0.75) and the different slopes of Yakexia (1:1.09:1.35). There was no significant difference in vector length between slope aspects at both sites, indicating no significant effect of slope aspect on the microbial C limitation. The vector angle was significantly higher on the sunny slope (43.6°) than that on the shady slope (28.7°) in Miyaluo, suggesting that the microorganisms were mainly N-limited. Partial least squares path model showed that the vector angle was mainly directly influenced by the soil nutrient ratios. The vector angle ranged from 50.3° to 51.4°, and did not differ between slope aspects in Yakexia. Therefore, differences in vegetation types between slope aspects drove variations in soil enzyme activity and microbial nutrient limitation through soil properties. It would provide a scientific basis for predicting the spatial pattern of soil enzyme activity and microbial nutrient limitation.