Salicin alleviates periodontitis via Tas2r143/gustducin signaling in fibroblasts.

Introduction: Cells expressing taste signaling elements in non-gustatory tissues have been described as solitary chemosensory cells (SCCs) or tuft cells. These "taste-like" cells play a critical role in the maintenance of tissue homeostasis. Although the expression of SCC markers and taste signaling constituents has been identified in mouse gingivae, their role in periodontal homeostasis is still unclear. Methods: Public RNA sequencing datasets were re-analyzed and further validated with RT-PCR/qRT-PCR and immunofluorescent staining to explore the expression of TAS2Rs and downstream signaling constituents in mouse gingival fibroblasts (MGFs). The specific action of salicin on MGFs via Tas2r143 was validated with RNA silence, heterologous expression of taste receptor/Gα-gustducin and calcium imaging. The anti-inflammatory effects of salicin against LPS-induced MGFs were investigated in cell cultures, and were further validated with a ligature-induced periodontitis mouse model using Ga-gustducin-null (Gnat3-/-) mice. Results: The expression of Tas2r143, Gnat3, Plcb2, and TrpM5 was detected in MGFs. Moreover, salicin could activate Tas2r143, elicited taste signaling and thus inhibited LPS-induced chemokines expression (CXCL1, CXCL2, and CXCL5) in MGFs. Consistently, salicin-treatment inhibited periodontal bone loss, inflammatory/chemotactic factors expression, and neutrophil infiltration in periodontitis mice, while these effects were abolished in Gnat3-/- mice. Discussion: Gingival fibroblasts play a critical role in the maintenance of periodontal homeostasis via "SCC-like" activity. Salicin can activate Tas2r143-mediated bitter taste signaling and thus alleviate periodontitis in mouse, indicating a promising approach to the resolution of periodontal inflammation via stimulating the "SCC-like" function of gingival fibroblasts.

Omics for deciphering oral microecology.

The human oral microbiome harbors one of the most diverse microbial communities in the human body, playing critical roles in oral and systemic health. Recent technological innovations are propelling the characterization and manipulation of oral microbiota. High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes. New long-read platforms improve genome assembly from complex samples. Single-cell genomics provides insights into uncultured taxa. Advanced imaging modalities including fluorescence, mass spectrometry, and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution. Fluorescence techniques link phylogenetic identity with localization. Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification. Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches. Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly, gene expression, metabolites, microenvironments, virulence mechanisms, and microbe-host interfaces in the context of health and disease. However, significant knowledge gaps persist regarding community origins, developmental trajectories, homeostasis versus dysbiosis triggers, functional biomarkers, and strategies to deliberately reshape the oral microbiome for therapeutic benefit. The convergence of sequencing, imaging, cultureomics, synthetic systems, and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict, prevent, diagnose, and treat associated oral diseases.

The first record of Tricholathys Chamberlin & Ivie, 1935 (Araneae, Dictynidae) from China, with a new combination and descriptions of seven new species.

The genus Tricholathys, found for the first time in China, is surveyed and seven new species, T.burangensissp. nov. (♂♀, Thibet), T.chenzhenningisp. nov. (♂♀, Qinghai), T.hebeiensissp. nov. (♀, Hebei), T.lhunzeensissp. nov. (♂♀, Tibet), Tricholathysrelictoidessp. nov. (♂♀, Xinjiang), T.serratasp. nov. (♂♀, Tibet), and T.xizangensissp. nov. (♂♀, Tibet), are described. A new combination is proposed for Tricholathysalxa (Tang, 2011) comb. nov., ex. Argenna Thorell, 1870. Descriptions of all new species are provided, together with digital images, illustrations, and a distribution map. The DNA barcode information of four recently collected species is also provided.

Association between Hepatitis B virus and gastric cancer: A systematic review and meta-analysis.

An increasing number of studies are suggesting that hepatitis B virus (HBV) infection may be associated with an increased risk of not only hepatocellular carcinoma but also gastric cancer (GC). Whether HBV infection can be a risk factor for GC remains to be explored. In this study, we systematically searched for all eligible literature in 7 databases (China National Knowledge Infrastructure, WanFang, China Science and Technology Journal, PubMed, Cochrane Library, Web of Science and Embase). Eligible studies were required to have a case-control or cohort design. Sixteen studies were included and a meta-analysis was performed using Stata version 17.0. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. The association between HBV infection and risk of GC was quantified by calculating the odds ratio and 95% confidence interval. The proportion of high-quality studies was 87.5% (14/16). The risk of GC was higher when HBV infection was present than when it was not (combined odds ratio 1.29, 95% confidence interval 1.16-1.44; I2 = 62.7%, p < 0.001). The results of subgroup analyses were consistent with the main results. In conclusion, this systematic review and meta-analysis identified a positive association between HBV infection and an increased risk of GC.

Multifunctional Polymer Restraint of the Agglomeration of SnO2 Nanocrystals for Efficient and Stable Planar Perovskite Solar Cells.

The aggregation of SnO2 nanocrystals due to van der Waals interactions is not conducive to the realization of a compact and pinhole-free electron transport layer (ETL). Herein, we have utilized potassium alginate (PA) to self-assemble SnO2 nanocrystals, forming a PA-SnO2 ETL for perovskite solar cells (PSCs). Through density functional theory (DFT) calculations, PA can be effectively absorbed onto the surface of SnO2. This inhibits the agglomeration of SnO2 nanocrystals in solution, forming a smoother pinhole-free film. This also changes the surface contact potential (CPD) of the SnO2 film, which leads to a reduction in the energy barrier between the ETL and the perovskite layers, promotes effective charge transfer, and reduces trap density. Consequently, the power conversion efficiency (PCE) of PSCs with a PA-SnO2 ETL increased from 19.24% to 22.16%, and the short-circuit current (JSC) was enhanced from 23.52 to 25.21 mA cm-2. Furthermore, the PA-modified unpackaged device demonstrates better humidity stability compared to the original device.

Diagnostic value of triglyceride-glucose index and related parameters in metabolism-associated fatty liver disease in a Chinese population: a cross-sectional study.

OBJECTIVE: Our study aimed to explore the diagnostic value of triglyceride-glucose (TyG) and its related parameters in metabolism-associated fatty liver disease (MAFLD). DESIGN: A cross-sectional study of residents who attended medical checkups at the First Hospital of Nanping City, Fujian Medical University, between 2015 and 2017. SETTING: One participation centre. PARTICIPANTS: 2605 subjects met the inclusion-exclusion criteria and were grouped according to whether they had MAFLD. RESULTS: The TyG index and its associated parameters are positively associated with the risk of developing MAFLD (p<0.001). Restriction cube spline analysis showed a significant dose-response relationship between the TyG index and MAFLD. The risk of developing MAFLD increases significantly with a higher TyG index. After adjusting for confounders, this relationship remains (OR: 4.89, 95% CI 3.98 to 6.00). The areas under the receiver operating characteristic curves of the TyG index for MAFLD detection were 0.793 (0.774 to 0.812). The areas under the curve (AUC) of TyG-related parameters were improved, among which TyG-waist circumference (TyG-WC) showed the largest AUC for MAFLD detection (0.873, 95% CI 0.860 to 0.887). In addition, the best cut-off value of the TyG-WC was 716.743, with a sensitivity and specificity of 88.7% and 71.4%, respectively. CONCLUSION: The TyG index effectively identifies MAFLD, and the TyG-related parameters improved the identification and diagnosis of MAFLD, suggesting that TyG-related parameters, especially TyG-WC, may be a useful marker for diagnosing MAFLD.

Lysine lactylation regulates metabolic pathways and biofilm formation in Streptococcus mutans.

In eukaryotes, lactate produced during glycolysis is involved in regulating multiple metabolic processes through lysine lactylation (Kla). To explore the potential link between metabolism and Kla in prokaryotes, we investigated the distribution of Kla in the cariogenic bacterium Streptococcus mutans during planktonic growth in low-sugar conditions and in biofilm-promoting, high-sugar conditions. We identified 1869 Kla sites in 469 proteins under these two conditions, with the biofilm growth state showing a greater number of lactylated sites and proteins. Although high sugar increased Kla globally, it reduced lactylation of RNA polymerase subunit α (RpoA) at Lys173. Lactylation at this residue inhibited the synthesis of extracellular polysaccharides, a major constituent of the cariogenic biofilm. The Gcn5-related N-acetyltransferase (GNAT) superfamily enzyme GNAT13 exhibited lysine lactyltransferase activity in cells and lactylated Lys173 in RpoA in vitro. Either GNAT13 overexpression or lactylation of Lys173 in RpoA inhibited biofilm formation. These results provide an overview of the distribution and potential functions of Kla and improve our understanding of the role of lactate in the metabolic regulation of prokaryotes.

Association of food intake with a risk of metabolic dysfunction-associated fatty liver disease: a cross-sectional study.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease, the risk of which can be increased by poor diet. The objective of this study was to evaluate the associations between food items and MAFLD, and to propose reasonable dietary recommendations for the prevention of MAFLD. Methods: Physical examination data were collected from April 2015 through August 2017 at Nanping First Hospital (n = 3,563). Dietary intakes were assessed using a semi-quantitative food frequency questionnaire. The association between food intake and the risk of MAFLD was assessed by using the inverse probability weighted propensity score. Results: Beverages (soft drinks and sugar-sweetened beverages) and instant noodles were positively associated with MAFLD risk, adjusting for smoking, drinking, tea intake, and weekly hours of physical activity [adjusted odds ratio (ORadjusted): 1.568; P = 0.044; ORadjusted: 4.363; P = 0.001]. Milk, tubers, and vegetables were negatively associated with MAFLD risk (ORadjusted: 0.912; P = 0.002; ORadjusted: 0.633; P = 0.007; ORadjusted: 0.962; P = 0.028). In subgroup analysis, the results showed that women [odds ratio (OR): 0.341, 95% confidence interval (CI): 0.172-0.676] had a significantly lower risk of MAFLD through consuming more tubers than men (OR: 0.732, 95% CI: 0.564-0.951). Conclusions: These findings suggest that reducing consumption of beverages (soft drinks and sugar-sweetened beverages) and instant noodles, and consuming more milk, vegetables, and tubers may reduce the risk of MAFLD.

Thyroid V40 is a good predictor for subclinical hypothyroidism in patients with nasopharyngeal carcinoma after intensity modulated radiation therapy: a randomized clinical trial.

BACKGROUND: Hypothyroidism (HT) and subclinical HT after radiotherapy is frequent in nasopharyngeal carcinoma (NPC) patients, results in negative impact on patients' quality of life. The percentage of thyroid volume receiving more than 40 Gy (V40) ≤ 85% was reported to be a useful dose constraint to adopt during intensity-modulated radiation therapy (IMRT) planning. This study aims to verify whether V40 ≤ 85% can be used as an effective dose constraint in IMRT planning in a randomized clinical trial. METHODS: This single-center 1:1 randomized clinical trial was conducted in Fujian province hospital between March 2018 and September 2022. All patients were treated with IMRT and randomized to induction chemo followed by concurrent chemo-IMRT or concurrent chemo-IMRT alone. Ninety-two clinically NPC patients were included in this study. The thyroid function tests were performed for all patients before and after radiation at regular intervals. Thyroid dose-constraint was defined as V40 ≤ 85%. The primary outcome in this study was subclinical HT. RESULTS: Median follow up was 34 months. Significant difference in the incidence of subclinical HT between the thyroid dose-constraint group and unrestricted group was observed (P = 0.023). The risk of subclinical HT in the thyroid dose-constraint group was lower than that in the unrestricted group (P = 0.022). Univariate and multivariate cox regression analysis indicated that thyroid dose-constraint was a protective effect of subclinical HT (HR = 0.408, 95% CI 0.184-0.904; HRadjusted = 0.361, 95% CI 0.155-0.841). CONCLUSION: V40 ≤ 85% can be used as an effective dose constraint in IMRT planning to prevent radiation-induced subclinical HT.

Heavy Ion Radiation Directly Induced the Shift of Oral Microbiota and Increased the Cariogenicity of Streptococcus mutans.

Radiation caries is one of the most common complications of head and neck radiotherapy. A shift in the oral microbiota is the main factor of radiation caries. A new form of biosafe radiation, heavy ion radiation, is increasingly being applied in clinical treatment due to its superior depth-dose distribution and biological effects. However, how heavy ion radiation directly impacts the oral microbiota and the progress of radiation caries are unknown. Here, unstimulated saliva samples from both healthy and caries volunteers and caries-related bacteria were directly exposed to therapeutic doses of heavy ion radiation to determine the effects of radiation on oral microbiota composition and bacterial cariogenicity. Heavy ion radiation significantly decreased the richness and diversity of oral microbiota from both healthy and caries volunteers, and a higher percentage of Streptococcus was detected in radiation groups. In addition, heavy ion radiation significantly enhanced the cariogenicity of saliva-derived biofilms, including the ratios of the genus Streptococcus and biofilm formation. In the Streptococcus mutans-Streptococcus sanguinis dual-species biofilms, heavy ion radiation increased the ratio of S. mutans. Next, S. mutans was directly exposed to heavy ions, and the radiation significantly upregulated the gtfC and gtfD cariogenic virulence genes to enhance the biofilm formation and exopolysaccharides synthesis of S. mutans. Our study demonstrated, for the first time, that direct exposure to heavy ion radiation can disrupt the oral microbial diversity and balance of dual-species biofilms by increasing the virulence of S. mutans, increasing its cariogenicity, indicating a potential correlation between heavy ions and radiation caries. IMPORTANCE The oral microbiome is crucial to understanding the pathogenesis of radiation caries. Although heavy ion radiation has been used to treat head and neck cancers in some proton therapy centers, its correlation with dental caries, especially its direct effects on the oral microbiome and cariogenic pathogens, has not been reported previously. Here, we showed that the heavy ion radiation directly shifted the oral microbiota from a balanced state to a caries-associated state by increasing the cariogenic virulence of S. mutans. Our study highlighted the direct effect of heavy ion radiation on oral microbiota and the cariogenicity of oral microbes for the first time.

Valid and reliable diagnostic performance of dual-energy CT in anterior cruciate ligament rupture.

OBJECTIVES: To determine whether dual-energy CT (DECT) can be used to accurately and reliably detect anterior cruciate ligament (ACL) rupture. MATERIALS AND METHODS: Participants with unilateral ACL rupture were prospectively enrolled, and the bilateral knees were scanned by DECT. A tissue-specific mapping algorithm was applied to improve the visualization of the ACLs. The 80-keV CT value, mixed-keV CT value, electron density (Rho), and effective atomic number (Zeff) were measured to quantitatively differentiate torn ACLs from normal ACLs. MRI and arthroscopy served as the reference standards. RESULTS: Fifty-one participants (mean age, 27.0 ± 8.7 years; 31 men) were enrolled. Intact and torn ACLs were explicitly differentiated on color-coded DECT images. The 80-keV CT value, mixed-keV CT value, and Rho were significantly lower for the torn ACLs than for the intact ACLs (p < 0.001). The optimal cutoff values were an 80-keV CT value of 61.8 HU, a mixed-keV CT value of 60.9 HU, and a Rho of 51.8 HU, with AUCs of 98.0% (95% CI: 97.0-98.9%), 99.2% (95% CI: 98.6-99.7%), and 99.8% (95% CI: 99.6-100.0%), respectively. Overall, DECT had almost perfect reliability and validity in detecting ACL integrity (sensitivity = 97.1% [95% CI: 88.1-99.8%]; specificity = 98.0% [95% CI: 89.5-99.9%]; PPV = 98.0% [95% CI: 93.0-99.8%]; NPV = 97.1% [95% CI: 91.7-99.4%]; accuracy = 97.5% [95% CI: 94.3-99.2%]). There was no evidence of a difference between MRI and DECT in the diagnostic performance (p > 0.99). CONCLUSION: DECT has excellent diagnostic accuracy and reliability in qualitatively and quantitatively diagnosing ACL rupture. CLINICAL RELEVANCE STATEMENT: DECT could validly and reliably diagnose ACL rupture using both qualitative and quantitative methods, which may become a promising substitute for MRI to evaluate the integrity of injured ACLs and the maturity of postoperative ACL autografts. KEY POINTS: • On color-coded DECT images, an uncolored ACL was a reliable sign for qualitatively diagnosing ACL rupture. • The 80-keV CT value, mixed-keV CT value, and Rho were significantly lower for the torn ACLs than for the intact ACLs, which contributed to the quantitative diagnosis of ACL rupture. • DECT had an almost perfect diagnostic performance for ACL rupture, and diagnostic capability was comparable between MRI and DECT.

[Application of Droplet-Based Microfluidics in Microbial Research].

Droplet-based microfluidics is a technology that generates and manipulates highly uniform droplets, ranging from picoliter to nanoliter droplets, in microchannels under precise control. In biological research, each droplet can be used to encapsulate a small group of cells or even a single cell, and then serve as an individual container for biochemical reaction, which is well suited for high-throughput and high-resolution biochemical analysis. In the field of microbial research, from cultivation and identification of microbes to the investigation of the spatiotemporal dynamics of microbial communities, from precise quantitation of microbiota to systematic study of microbial interactions, and from the isolation of rare and unculturable microbes to the development of genetically engineered strains, droplet microfluidic technology has played an important promotional role in all these aspects. Droplet microfluidics shows potential for becoming a basic tool for exploring single-cell microbes in microbiological research. In this review, we gave a brief overview of the technical basis of droplet microfluidics. Then, we presented its latest applications in microbial research and had some discussions, aiming to provide a reference for relevant research on microorganisms.

Esophageal mycobiome landscape and interkingdom interactions in esophageal squamous cell carcinoma.

Background: The study purpose was to characterize the mycobiome and its associations with the expression of pathogenic genes in esophageal squamous cell carcinoma (ESCC). Methods: Patients with primary ESCC were recruited from two central hospitals. We performed internal transcribed spacer 1 (ITS1) ribosomal DNA sequencing analysis. We compared differential fungi and explored the ecology of fungi and the interaction of bacteria and fungi. Results: The mycobiota diversity was significantly different between tumors and tumor-adjacent samples. We further analysed the differences between the two groups, at the species level, confirming that Rhodotorula toruloides, Malassezia dermatis, Hanseniaspora lachancei, and Spegazzinia tessarthra were excessively colonized in the tumor samples, whereas Preussia persica, Fusarium solani, Nigrospora oryzae, Acremonium furcatum, Golovinomyces artemisiae, and Tausonia pullulans were significantly more abundant in tumor-adjacent samples. The fungal co-occurrence network in tumor-adjacent samples was larger and denser than that in tumors. Similarly, the more complex bacterial-fungal interactions in tumor-adjacent samples were also detected. The expression of mechanistic target of rapamycin kinase was positively correlated with the abundance of N. oryzae and T. pullulans in tumor-adjacent samples. In tumors, the expression of MET proto-oncogene, receptor tyrosine kinase (MET) had a negative correlation and a positive correlation with the abundance of R. toruloides and S. tessarthra, respectively. Conclusion: This study revealed the landscape of the esophageal mycobiome characterized by an altered fungal composition and bacterial and fungal ecology in ESCC.

Preparation and characterization of a solid dispersion of Hexahydrocolupulone and its application in the preservation of fresh apple juice.

Hops extracts and their derivatives have many important biological activities, among them, excellent antibacterial and antioxidant properties make them a promising food preservative. However, poor water solubility limits their application in the food industry. This work aimed to improve the solubility of Hexahydrocolupulone (HHCL) by preparing solid dispersion (SD) and investigating the application of the obtained products (HHCL-SD) in actual food systems. HHCL-SD was prepared by solvent evaporation with PVPK30 as a carrier. The solubility of HHCL was dramatically increased to 24.72 mg/mL（25 ℃)by preparing HHCL-SD, much higher than that of raw HHCL (0.002 mg/mL). The structure of HHCL-SD and the interaction between HHCL and PVPK30 were analyzed. HHCL-SD was confirmed to have excellent antibacterial and antioxidant activities. Furthermore, the addition of HHCL-SD proved to be beneficial for the sensory, nutritional quality, and microbiological safety of fresh apple juice, hence prolonging its shelf-life.

Two new species of the sac-spider genus Clubiona Latreille, 1804 (Araneae, Clubionidae) and the female of C. subcylindrata from China.

Two new species of the genus Clubiona Latreille, 1804 are described: C. tianpingshan sp. nov. (♂♀) and C. flammaforma sp. nov. (♂♀) from central and south China. The female of C. subcylindrata Wang et al., 2018 is described for the first time. Detailed descriptions, photographs of somatic features and copulatory organs, as well as a distribution map of these three species, are provided.

Pterostilbene could alleviate diabetic cognitive impairment by suppressing TLR4/NF-кB pathway through microbiota-gut-brain axis.

Diabetic cognitive impairment (DCI) is a serious neurodegenerative disorder caused by diabetes, with chronic inflammation being a crucial factor in its pathogenesis. Pterostilbene is a well-known natural stilbene derivative that has excellent anti-inflammatory activity, suggesting its potential medicinal advantages for treating DCI. Therefore, this study is to explore the beneficial effects of pterostilbene for improving cognitive dysfunction in DCI mice. A diabetic model was induced by a high-fat diet plus streptozotocin (40 mg·kg-1 ) for consecutive 5 days. After the animals were confirmed to be in a diabetic state, they were treated with pterostilbene (20 or 60 mg·kg-1 , i.g.) for 10 weeks. Pharmacological evaluation showed pterostilbene could ameliorate cognitive dysfunction, regulate glycolipid metabolism disorders, improve neuronal damage, and reduce the accumulation of ß-amyloid in DCI mice. Pterostilbene alleviated neuroinflammation by suppressing oxidative stress and carbonyl stress damage, astrocyte and microglia activation, and dopaminergic neuronal loss. Further investigations showed that pterostilbene reduced the level of lipopolysaccharide, modulated colon and brain TLR4/NF-κB signaling pathways, and decreased the release of inflammatory factors, which in turn inhibited intestinal inflammation and neuroinflammation. Furthermore, pterostilbene could also improve the homeostasis of intestinal microbiota, increase the levels of short-chain fatty acids and their receptors, and suppress the loss of intestinal tight junction proteins. In addition, the results of plasma non-targeted metabolomics revealed that pterostilbene could modulate differential metabolites and metabolic pathways associated with inflammation, thereby suppressing systemic inflammation in DCI mice. Collectively, our study found for the first time that pterostilbene could alleviate diabetic cognitive dysfunction by inhibiting the TLR4/NF-κB pathway through the microbiota-gut-brain axis, which may be one of the potential mechanisms for its neuroprotective effects.

Small Molecule Attenuates Bacterial Virulence by Targeting Conserved Response Regulator.

Antibiotic tolerance within a biofilm community presents a serious public health challenge. Here, we report the identification of a 2-aminoimidazole derivative that inhibits biofilm formation by two pathogenic Gram-positive bacteria, Streptococcus mutans and Staphylococcus aureus. In S. mutans, the compound binds to VicR, a key response regulator, at the N-terminal receiver domain, and concurrently inhibits expression of vicR and VicR-regulated genes, including the genes that encode the key biofilm matrix producing enzymes, Gtfs. The compound inhibits S. aureus biofilm formation via binding to a Staphylococcal VicR homolog. In addition, the inhibitor effectively attenuates S. mutans virulence in a rat model of dental caries. As the compound targets bacterial biofilms and virulence through a conserved transcriptional factor, it represents a promising new class of anti-infective agents that can be explored to prevent or treat a host of bacterial infections. IMPORTANCE Antibiotic resistance is a major public health issue due to the growing lack of effective anti-infective therapeutics. New alternatives to treat and prevent biofilm-driven microbial infections, which exhibit high tolerance to clinically available antibiotics, are urgently needed. We report the identification of a small molecule that inhibits biofilm formation by two important pathogenic Gram-positive bacteria, Streptococcus mutans and Staphylococcus aureus. The small molecule selectively targets a transcriptional regulator leading to attenuation of a biofilm regulatory cascade and concurrent reduction of bacterial virulence in vivo. As the regulator is highly conserved, the finding has broad implication for the development of antivirulence therapeutics that selectively target biofilms.

Small molecule II-6s synergises with fluconazole against Candida albicans.

BACKGROUND: Candida albicans (C. albicans) is the most common opportunistic fungal species in the oral cavity. The emergence of drug resistance of C. albicans has necessitated the development of novel antifungal agents. OBJECTIVES: This study evaluated the antifungal activity of a previously developed antimicrobial small molecule, namely II-6s, and explored its potential synergism with fluconazole against C. albicans and the underlying mechanisms. METHODS: The antifungal effects of II-6s against C. albicans were evaluated with microdilution and time-killing assays. Synergism of II-6s with fluconazole was determined by calculating the fractional inhibitory concentration index (FICI). The effects of II-6s on efflux pump, mitochondrial function and energy metabolism were examined to investigate the underlying mechanism of synergism. The antifungal mechanism of II-6s against C. albicans was further explored with RNA-seq and validated with specific mutant strains. RESULTS: II-6s exhibited a fungicidal effect against C. albicans with a minimum fungicidal concentration of 31.25 µg/mL. II-6s also inhibited C. albicans biofilm with a sessile minimum inhibitory concentration at 500 µg/mL. More importantly, II-6s showed a synergistic effect with fluconazole against a fluconazole-resistant strain of C. albicans, which expressed elevated levels of CDR1 (FICI < 0.5). II-6s inhibited the efflux pump activity of C. albicans. Consistently, II-6s inhibited energy metabolism of C. albicans by reducing the mitochondrial membrane potential and ATP generation, and inhibited utilisation of the non-fermentable carbon source. II-6s also inhibited the mitogen-activated protein kinase signal pathway, particularly HOG1, which may explain its antifungal activity against C. albicans. CONCLUSION: The small molecule II-6s inhibits the growth of C. albicans by targeting HOG1. II-6s also synergises with fluconazole by inhibiting the drug efflux pump, representing a promising antifungal agent for the control of candidiasis.

pH-responsive DMAEM Monomer for dental caries inhibition.

Previous research indicated that there is an aggregate of microorganism in oral cavity which takes part in promoting the occurrence of dental caries, but few studies on anticaries materials for these 'core microbiome' were developed. And We've found that DMAEM monomer has an obvious inhibitory effect on the growth of Streptococcus mutans and saliva biofilm, but the effect of that on the "core microbiome" of caries need further research. Thus, the objectives of this study were to explore the effect of DMAEM monomer on the core microbiota of dental caries, and to further study its anticaries effect. The changes of microbial structure and metabolic activity of the core microbiota biofilm were detected through measuring lactic acid yield, viable bacteria counts and demineralization depth, et al., and the anticaries potential in vivo of DMAEM monomer was evaluated by rat caries model. Meanwhile, high-throughput sequencing was used to analyze the microbial diversity change of saliva samples of rats. The results showed that DMAEM monomer could inhibit the growth of the core microbiota biofilm, decrease the metabolic activity and the acid production, as well as reduce the ability of demineralization under acidic conditions. Moreover, the degree of caries in the DMAEM group was significantly reduced, and the diversity and the evenness of oral microecology in the rats were statistically higher. In summary, DMAEM monomer could respond to acidic environment, significantly inhibit the cariogenic ability of the 'core microbiome' of caries, and help to maintain the microecological balance of oral cavity.

Development and validation of an online dynamic nomogram based on the atherogenic index of plasma to screen nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), a common liver disease worldwide, can be reversed early in life with lifestyle and medical interventions. This study aimed to develop a noninvasive tool to screen NAFLD accurately. METHODS: Risk factors for NAFLD were identified using multivariate logistic regression analysis, and an online NAFLD screening nomogram was developed. The nomogram was compared with reported models (fatty liver index (FLI), atherogenic index of plasma (AIP), and hepatic steatosis index (HSI)). Nomogram performance was evaluated through internal and external validation (National Health and Nutrition Examination Survey (NHANES) database). RESULTS: The nomogram was developed based on six variables. The diagnostic performance of the present nomogram for NAFLD (area under the receiver operator characteristic curve (AUROC): 0.863, 0.864, and 0.833, respectively) was superior to that of the HSI (AUROC: 0.835, 0.833, and 0.810, respectively) and AIP (AUROC: 0.782, 0.773, and 0.728, respectively) in the training, validation, and NHANES sets. Decision curve analysis and clinical impact curve analysis presented good clinical utility. CONCLUSION: This study establishes a new online dynamic nomogram with excellent diagnostic and clinical performance. It has the potential to be a noninvasive and convenient method for screening individuals at high risk for NAFLD.