The relationship of dietary flavonoids and periodontitis in US population: a cross-sectional NHANES analysis.

OBJECTIVES: We investigated the association between dietary flavonoids intake and periodontitis. MATERIALS AND METHODS: This cross-sectional study analyzed data from the US National Health and Nutrition Examination Survey 2009-2010 on 3025 participants aged between 30 and 80 years who had full-mouth periodontal examination and dietary flavonoids intake data. This study used periodontal pocket depth (PPD) and clinical attachment loss (CAL) as periodontitis markers. Data were analyzed using multivariate linear regression. RESULTS: After adjusting confounders, the middle tertile of total dietary flavonoids was associated with decreased mean PPD (0.06 mm, P = 0.016) and mean CAL (0.13 mm, P = 0.001) and the top tertile of total dietary flavonoids was significantly associated with decreases in mean PPD (0.05 mm, P = 0.029) and mean CAL (0.11 mm, P = 0.010). Both the middle and top tertiles of total flavonoids intake were significantly related with decreased mean CAL in females, those flossing 0 days/week, overweight and non-diabetic population but not in males, smokers, those flossing 1-6 days/week and diabetic population. Higher anthocyanidins, flavones and flavonols intake was significantly associated with decreased mean PPD and mean CAL while higher flavanones intake was only significantly associated with decreased mean CAL. Higher anthocyanidins intake was particularly related with greatest decreases in mean CAL (top tertile: 0.22 mm, middle tertile: 0.17 mm, both P < 0.010). However, no significant associations were found between isoflavones and flavan_3_ols intake and mean CAL. CONCLUSIONS: Higher dietary flavonoids intake may be beneficial for periodontal health. CLINICAL RELEVANCE: Additional anthocyanidins, flavanones, flavones and flavonols intake was associated with improved periodontal health.

A deep-learning-based framework for identifying and localizing multiple abnormalities and assessing cardiomegaly in chest X-ray.

Accurate identification and localization of multiple abnormalities are crucial steps in the interpretation of chest X-rays (CXRs); however, the lack of a large CXR dataset with bounding boxes severely constrains accurate localization research based on deep learning. We created a large CXR dataset named CXR-AL14, containing 165,988 CXRs and 253,844 bounding boxes. On the basis of this dataset, a deep-learning-based framework was developed to identify and localize 14 common abnormalities and calculate the cardiothoracic ratio (CTR) simultaneously. The mean average precision values obtained by the model for 14 abnormalities reached 0.572-0.631 with an intersection-over-union threshold of 0.5, and the intraclass correlation coefficient of the CTR algorithm exceeded 0.95 on the held-out, multicentre and prospective test datasets. This framework shows an excellent performance, good generalization ability and strong clinical applicability, which is superior to senior radiologists and suitable for routine clinical settings.

Chi3l1: New kid on the T cell blockade.

T cell-excluded tumors are less responsive to immunotherapies. In this issue of Immunity, Taifour et al. show that secretion of the cytokine Chi3l1 by tumor cells induces T cell exclusion via neutrophil extracellular trap (NET) formation. Chi3l1 depletion stimulates T cell infiltration and synergizes with PD-1 blockade.

OGD/R-induced ferroptosis and pyroptosis in retinal pigment epithelium cells: Role of PLD1 and PLD2 modulation.

This study investigated the role of phospholipase D (PLD) in retinal ischemia-reperfusion (I/R) injury using an oxygen-glucose deprivation/reperfusion (OGD/R) model commonly used in retinal I/R injury research. To create an in vitro cellular I/R model, pharmacological inhibitors and small interfering RNA (siRNA) were used to target PLD1 and PLD2 in retinal pigment epithelial (RPE) cells. Treatment with PLD inhibitors and siRNA reduced reactive oxygen species (ROS) and malondialdehyde (MDA) induced by OGD/R in RPE cells and increased the levels of superoxide dismutase (SOD) and glutathione (GSH), indicating a reduction in oxidative damage and improvement in the antioxidant system. Next, we showed that inhibiting PLD1 or PLD2 reduced intracellular iron levels and lipid peroxidation, which are critical factors in ferroptosis. Additionally, PLD1 and PLD2 modulated the expression of proteins involved in the regulation of ferroptosis, including GPX4, SLC7A11, FTH1, and ACSL4. We also investigated the roles of PLD1 and PLD2 in preventing pyroptosis, another form of programmed cell death associated with inflammation. Our study found that OGD/R significantly increased the production of pro-inflammatory cytokines and activated caspase-1, NLRP3, ASC, cleaved-caspase 1 (C-caspase-1), and GSDMD-N in RPE cells, indicating pyroptosis induction. However, PLD1 and PLD2 inhibition or knockdown significantly inhibited the production of pro-inflammatory cytokines and activation of the NLRP3 inflammasome, Taken together, our findings support the hypothesis that the PLD signaling pathway plays a key role in OGD/R-induced ferroptosis and pyroptosis induction and may be a potential therapeutic target for preventing or treating retinal dysfunction and degeneration.

Adiposity Reduction by Cucumis melo var. gaettongchamoe Extract in High-Fat Diet-Induced Obese Mice.

This study investigated the anti-obesity effects of Cucumis melo var. gaettongchamoe (CG) in mice fed a high-fat diet (HFD). The mice received CG water extract (CGWE) treatment for 8 weeks, and changes in body weight and serum lipid levels were analyzed. The HFD + vehicle group showed a significant increase in body weight compared to the control group, while the HFD + CGWE and HFD + positive (orlistat) groups exhibited reduced body weight. Lipid profile analysis revealed lower levels of total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol in the HFD + CGWE group compared to the HFD + vehicle group. The HFD + vehicle group had increased abdominal fat weight and fat content, whereas both HFD + CGWE groups showed significant reductions in abdominal fat content and adipocyte size. Additionally, CGWE administration downregulated mRNA expression of key proteins involved in neutral lipid metabolism. CGWE also promoted hepatic lipolysis, reducing lipid droplet accumulation in hepatic tissue and altering neutral lipid metabolism protein expression. Furthermore, CGWE treatment reduced inflammatory mediators and suppressed the activation of the mitogen-activated protein kinase pathway in hepatic tissue. In conclusion, CGWE shows promise as a therapeutic intervention for obesity and associated metabolic dysregulation, including alterations in body weight, serum lipid profiles, adipose tissue accumulation, hepatic lipolysis, and the inflammatory response. CGWE may serve as a potential natural anti-obesity agent.

The association of severely worn dentition resulting from betel nut chewing with temporomandibular disorders: a cross-sectional study.

BACKGROUND: Most studies support parafunctions play an important role in temporomandibular disorders (TMD), whereas the association between tooth wear and TMD remains controversial. Betel nut chewing as a parafunction is popular in South and Southeast Asia. We therefore investigated the association of severely worn dentition resulting from betel nut chewing with TMD. METHODS: A cross-sectional analysis of 408 control participants (male: 380, female: 28, 43.62 ± 9.54 years) and 408 participants with betel nut chewing related severely worn dentition (male: 380, female: 28, 43.73 ± 8.93 years) who received dental and TMD checkup according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) in Health Management Center, Xiangya Hospital was performed. Betel nut chewing related severely worn dentition meant all the natural teeth had moderate to severe tooth wear [Tooth Wear Index (TWI) ≥ 2)] including ≥ 2 severe wear teeth (TWI ≥ 3) due to betel nut chewing. Multivariable logistic regression analysis was used. RESULTS: After adjusting for age, gender, betel nut chewing related severely worn dentition, oral submucosal fibrosis, number of missing teeth, number of dental quadrants with missing teeth, visible third molar and orthodontic history, variables of age, gender and betel nut chewing related severely worn dentition were significant for overall TMD. Multivariable analysis showed betel nut chewing related severely worn dentition was significantly associated with intra-articular TMD [odds ratio and 95% confidence intervals: 1.689 (1.271-2.244), P = 0.001] in a betel nut chewing dose-dependent manner. CONCLUSION: Betel nut chewing related severely worn dentition was associated with intra-articular TMD.

Association of severely damaged endodontically infected tooth with carotid plaque and abnormal carotid intima-media thickness: a retrospective analysis.

OBJECTIVE: We investigated the association of severely damaged endodontically infected tooth with carotid artery plaque and abnormal mean carotid intima-media thickness (CIMT) ≥ 1.0 mm. METHODS: A retrospective analysis of 1502 control participants and 1552 participants with severely damaged endodontically infected tooth who received routine medical and dental checkup in Health Management Center, Xiangya Hospital was performed. Carotid plaque and CIMT were measured with B-mode tomographic ultrasound. Data were analyzed using logistic and linear regression. RESULTS: Severely damaged endodontically infected tooth group had a significantly higher prevalence of carotid plaque (41.62%) compared to 32.22% of carotid plaque in control group. Participants with severely damaged endodontically infected tooth had a significantly higher prevalence of abnormal CIMT (16.17%) and a significantly increased level of CIMT (0.79 ± 0.16 mm) in comparison to 10.79% of abnormal CIMT and 0.77 ± 0.14 mm CIMT in control participants. Severely damaged endodontically infected tooth was significantly related with formation of carotid plaque [1.37(1.18-1.60), P < 0.001], top quartile length [1.21(1.02-1.44), P = 0.029] and top quartile thickness [1.27(1.08-1.51), P = 0.005] of carotid plaque and abnormal CIMT [1.47(1.18-1.83), P < 0.001]. Severely damaged endodontically infected tooth was significantly associated with both single [1.277(1.056-1.546), P = 0.012] and multiple carotid plaques [1.488(1.214-1.825), P < 0.001] and instable carotid plaques [1.380(1.167-1.632), P < 0.001]. Presence of severely damaged endodontically infected tooth increased 0.588 mm of carotid plaque length (P = 0.001), 0.157 mm of carotid plaque thickness (P < 0.001) and 0.015 mm of CIMT (P = 0.005). CONCLUSION: Severely damaged endodontically infected tooth was associated with carotid plaque and abnormal CIMT. CLINICAL RELEVANCE: Early treatment of endodontically infected tooth is warranted.

Association of congenitally missing teeth with adult temporomandibular disorders in the urban health checkup population.

BACKGROUND: Congenitally missing tooth is the most common dental abnormality which leaves spaces in the arch, leads to numerous forms of malocclusion due to the Bolton index discrepancy and is even associated with abnormal craniofacial morphology. Even though the roles of malocclusion and tooth loss in temporomandibular disorders (TMD) development remain controversial, basic researches have found some common molecules are involved in osteoarthritis and dental agenesis. However, the association of congenitally missing teeth with TMD is unknown. We hence investigated the association of congenitally missing teeth with TMD. METHODS: A cross-sectional analysis of 586 control participants (male: 287, female: 299, 38.33 ± 11.65 years) and 583 participants with non-third molar congenitally missing teeth (male: 238, female: 345, 39.13 ± 11.67 years) who consecutively received routine dental and TMD checkup according to Diagnostic Criteria for Temporomandibular Disorders Axis I in Health Management Center, Xiangya Hospital was performed. Logistic regression analysis was used to study the association of congenitally missing teeth with TMD. RESULTS: The congenitally missing teeth group included 581 hypodontia and 2 oligodontia participants. The congenitally missing anterior teeth participants, the congenitally missing posterior teeth participants and participants with both congenitally missing anterior and posterior teeth accounted for 88.34%, 8.40% and 3.26% of the congenitally missing teeth group respectively. Congenitally missing teeth group had greater ratios of females and orthodontic history. Participants with congenitally missing teeth had a significantly higher prevalence of overall TMD (67.24%) in comparison to control participants (45.90%). After adjusting age, gender, presence of congenitally missing teeth, number of congenitally missing teeth, number of non-congenitally missing teeth, number of dental quadrants with missing teeth, visible third molar and orthodontic history, the variables of age, gender, presence of congenitally missing teeth and number of dental quadrants with missing teeth were significant for overall TMD. Multivariable logistic regression analysis showed congenitally missing tooth was significantly related with overall TMD [odds ratio (OR):1.689(1.080-2.642), P = 0.022], intra-articular TMD [OR: 1.711(1.103-2.656), P = 0.017] and pain-related TMD [OR: 3.093(1.321-7.239), P = 0.009]. CONCLUSION: Congenitally missing tooth is a risk factor for TMD. When treating the congenitally missing teeth population, TMJ evaluation and multidisciplinary strategies are necessary.

Edible Vitalmelon Fruit Extract Inhibits Adipogenesis and Ameliorates High-Fat Diet-Induced Obesity.

Conventional breeding of wild (Cucumis melo var. makuwa Makino (CM)) and cultivated (Cucumis melo var. reticulatus (CR)) melons is aimed at improving their biological traits. Here, we prepared a nontoxic, bioactive extract of vitalmelon (F1 hybrid) and evaluated its antiadipogenic and antiobesity effects in fully differentiated 3T3-L1 adipocytes and high-fat diet- (HFD-) induced obese C57BL/6 mice. In fully differentiated 3T3-L1 adipocytes, the vitalmelon extract reduced the DMI- (dexamethasone, 3-isobutyl-1-methylxanthine, and insulin-) induced increases in lipid droplet number and intracellular glucose and triglyceride levels. In addition, the extract inhibited 3T3-L1 preadipocyte differentiation by downregulating PPAR-γ and target genes LPL, CD36, HMGCR, and L-FABP. To investigate the inhibitory effects of the vitalmelon extract on lipid metabolism, we measured serum lipid, hormone, and cytokine concentrations; lipolytic activity; lipid accumulation; and adipogenesis in HFD-fed mice treated with the extract. The HFD+vitalmelon-fed mice showed lower blood cholesterol, free fatty acid, sugar, leptin, and insulin concentrations but higher blood adiponectin concentrations than the HFD-fed mice. Moreover, the HFD+vitalmelon-fed mice showed lower abdominal fat levels, smaller fat cells, lower weight, and fewer lipid droplets in the liver tissue than the HFD-fed mice. Therefore, in HFD-fed mice, vitalmelon regulated lipid metabolism through PPAR-γ, highlighting its potential as a promising antiobesity functional food.

Prevalence of recurrent aphthous stomatitis, oral submucosal fibrosis and oral leukoplakia in doctor/nurse and police officer population.

BACKGROUND: The doctor/nurse and police officer population have some common typical characteristics of great professional pressure and night shift and past studies indicated oral mucosa lesions were closely associated with psychological factors and health-risking behaviors, however the prevalence of recurrent aphthous stomatitis (RAS) and the two commonly seen oral potentially malignant disorders of oral submucosal fibrosis (OSF) and oral leukoplakia in doctor/nurse and police officer in the Betel quid chewing city of Mainland China is unknown The cross-sectional study was to determine the prevalence differences of RAS, oral leukoplakia and OSF among doctor/nurse, police officer and non-doctor/nurse and non-police officer population aged 20-59 years. METHODS: RAS, OSF and oral leukoplakia were examined in doctor/nurse group (male: 659, female: 2439), police officer group (male: 839, female: 262) and non-doctor/nurse and non-police officer group (male: 7576, female: 8129) from 2020-11-01 to 2021-08-31 in Health Management Center, Xiangya Hospital in Changsha city, Hunan province. RESULTS: The prevalence rates of RAS, OSF, oral leukoplakia and oral leukoplakia combined with OSF in male and female non-doctor/nurse and non-police officer group are 8.32‰ and 10.83‰, 58.08‰ and 1.23‰, 11.75‰ and 0.25‰, 7.66‰ and 0.12‰ respectively. Compared with the non-doctor/nurse and non-police officer population, prevalence rates of RAS in male (24.27‰) and female (20.50‰) doctor/nurse population were significantly higher. Prevalence rates of OSF (21.24‰) and oral leukoplakia (3.03‰) in male doctor/nurse population were significantly less but prevalence rates of OSF (93.71‰), oral leukoplakia (20.17‰) and oral leukoplakia combined with OSF (15.42‰) for male police officer were significantly greater in comparison with male non-doctor/nurse and non-police officer group. OSF and oral leukoplakia prevalence rates were obvious lower for the female than the counterpart male group, but there were no significant differences of OSF and oral leukoplakia prevalence rates between the female non-doctor/nurse and non-police officer and female doctor/nurse group. Oral leukoplakia was not found in the female police officers. CONCLUSIONS: Doctor/nurse population have higher prevalence of RAS. Male doctors/nurses have lower prevalence of OSF and oral leukoplakia, while male police officers have higher prevalence of OSF, oral leukoplakia and oral leukoplakia combined with OSF.

The SlTPL3-SlWUS module regulates multi-locule formation in tomato by modulating auxin and gibberellin levels in the shoot apical meristem.

Malformed fruits depreciate a plant's market value. In tomato (Solanum lycopersicum), fruit malformation is associated with the multi-locule trait, which involves genes regulating shoot apical meristem (SAM) development. The expression pattern of TOPLESS3 (SlTPL3) throughout SAM development prompted us to investigate its functional significance via RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (Cas9)-mediated gene editing. Lower SlTPL3 transcript levels resulted in larger fruits with more locules and larger SAMs at the 5 d after germination (DAG5) stage. Differentially expressed genes in the SAM of wild-type (WT) and SlTPL3-RNAi plants, identified by transcriptome deep sequencing (RNA-seq), were enriched in the gibberellin (GA) biosynthesis and plant hormone signaling pathways. Moreover, exogenous auxin and paclobutrazol treatments rescued the multi-locule phenotype, indicating that SlTPL3 affects SAM size by mediating auxin and GA levels in the SAM. Furthermore, SlTPL3 interacted with WUSCHEL (SlWUS), which plays an important role in SAM size maintenance. We conducted RNA-seq and DNA affinity purification followed by sequencing (DAP-seq) analyses to identify the genes regulated by SlTPL3 and SlWUS in the SAM and to determine how they regulate SAM size. We detected 24 overlapping genes regulated by SlTPL3 and SlWUS and harboring an SlWUS-binding motif in their promoters. Furthermore, functional annotation revealed a notable enrichment for functions in auxin transport, auxin signal transduction, and GA biosynthesis. Dual-luciferase assays also revealed that SlTPL3 enhances SlWUS-mediated regulation (repression and activation) of SlPIN3 and SlGA2ox4 transcription, indicating that the SlTPL3-SlWUS module regulates SAM size by mediating auxin distribution and GA levels, and perturbations of this module result in enlarged SAM. These results provide novel insights into the molecular mechanism of SAM maintenance and locule formation in tomato and highlight the SlTPL3-SlWUS module as a key regulator.

BTC as a Novel Biomarker Contributing to EMT via the PI3K-AKT Pathway in OSCC.

Purpose: Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck, while metastasis is the main cause of OSCC-related death. There is an urgent need to explore novel prognostic biomarkers and identify biological targets related to metastasis in OSCC treatment. Methods: Analysis of differential expression was performed using datasets in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Immunohistochemistry (IHC) was conducted to assess the expression of betacellulin (BTC) in OSCC. SCC4 and CAL27 cells were used for in vitro experiments, in which CCK-8, transwell assays, and wounding healing assays were performed to verify the biological functions of BTC. The role of BTC in EMT was analyzed by EMT score and Western blot. Results: Through the analysis of the mRNA expression profile data from TCGA database in OSCC, we found that only low expression of BTC was significantly correlated with a poor prognosis in OSCC patients. The results of IHC assays and TCGA databases showed that the expression level of BTC was related to the tumor stage, histological grade, and metastasis status. In vitro analysis showed that overexpression of BTC significantly suppressed the proliferation and migration of OSCC cells. Furthermore, we confirmed that BTC could affect EMT through the PI3K-AKT signaling pathway. Conclusion: The overexpression of BTC suppresses the proliferation, migration, and EMT of OSCC cells via the PI3K-AKT pathways, leading to a better prognosis in OSCC. BTC may be used as a novel molecular marker to assess the prognosis of OSCC patients.

Combinations of Toll-like receptor 8 agonist TL8-506 activate human tumor-derived dendritic cells.

BACKGROUND: Dendritic cells (DCs) are professional antigen presenting cells that initiate immune defense to pathogens and tumor cells. Human tumors contain only few DCs that mostly display a non-activated phenotype. Hence, activation of tumor-associated DCs may improve efficacy of cancer immunotherapies. Toll-like receptor (TLR) agonists and interferons are known to promote DC maturation. However, it is unclear if DCs in human tumors respond to activation signals and which stimuli induce the optimal activation of human tumor DCs. METHODS: We first screened combinations of TLR agonists, a STING agonist and interferons (IFNs) for their ability to activate human conventional DCs (cDCs). Two combinations: TL8-506 (a TLR8 agonist)+IFN-γ and TL8-506+Poly(I:C) (a TLR3 agonist) were studied in more detail. cDC1s and cDC2s derived from cord blood stem cells, blood or patient tumor samples were stimulated with either TL8-506+IFN-γ or TL8-506+Poly(I:C). Different activation markers were analyzed by ELISA, flow cytometry, NanoString nCounter Technology or single-cell RNA-sequencing. T cell activation and migration assays were performed to assess functional consequences of cDC activation. RESULTS: We show that TL8-506 synergized with IFN-γ or Poly(I:C) to induce high expression of different chemokines and cytokines including interleukin (IL)-12p70 in human cord blood and blood cDC subsets in a combination-specific manner. Importantly, both combinations induced the activation of cDC subsets in patient tumor samples ex vivo. The expression of immunostimulatory genes important for anticancer responses including CD40, IFNB1, IFNL1, IL12A and IL12B were upregulated on stimulation. Furthermore, chemokines associated with CD8+ T cell recruitment were induced in tumor-derived cDCs in response to TL8-506 combinations. In vitro activation and migration assays confirmed that stimulated cDCs induce T cell activation and migration. CONCLUSIONS: Our data suggest that cord blood-derived and blood-derived cDCs are a good surrogate to study treatment responses in human tumor cDCs. While most cDCs in human tumors display a non-activated phenotype, TL8-506 combinations drive human tumor cDCs towards an immunostimulatory phenotype associated with Th1 responses on stimulation. Hence, TL8-506-based combinations may be promising candidates to initiate or boost antitumor responses in patients with cancer.

Development and Validation of a Deep Neural Network for Accurate Identification of Endoscopic Images From Patients With Ulcerative Colitis and Crohn's Disease.

Background and Aim: The identification of ulcerative colitis (UC) and Crohn's disease (CD) is a key element interfering with therapeutic response, but it is often difficult for less experienced endoscopists to identify UC and CD. Therefore, we aimed to develop and validate a deep learning diagnostic system trained on a large number of colonoscopy images to distinguish UC and CD. Methods: This multicenter, diagnostic study was performed in 5 hospitals in China. Normal individuals and active patients with inflammatory bowel disease (IBD) were enrolled. A dataset of 1,772 participants with 49,154 colonoscopy images was obtained between January 2018 and November 2020. We developed a deep learning model based on a deep convolutional neural network (CNN) in the examination. To generalize the applicability of the deep learning model in clinical practice, we compared the deep model with 10 endoscopists and applied it in 3 hospitals across China. Results: The identification accuracy obtained by the deep model was superior to that of experienced endoscopists per patient (deep model vs. trainee endoscopist, 99.1% vs. 78.0%; deep model vs. competent endoscopist, 99.1% vs. 92.2%, P < 0.001) and per lesion (deep model vs. trainee endoscopist, 90.4% vs. 59.7%; deep model vs. competent endoscopist 90.4% vs. 69.9%, P < 0.001). In addition, the mean reading time was reduced by the deep model (deep model vs. endoscopists, 6.20 s vs. 2,425.00 s, P < 0.001). Conclusion: We developed a deep model to assist with the clinical diagnosis of IBD. This provides a diagnostic device for medical education and clinicians to improve the efficiency of diagnosis and treatment.

Comparative study of the photo­protective and anti­melanogenic properties of gomisin D, J and O.

Skin cancer is the most common human malignancy worldwide and solar ultraviolet (UV) radiation is known to serve an important role in its pathogenesis. Natural candidate compounds with antioxidant, photoprotective and anti­melanogenic effects were investigated against the background of skin photoprotective and anti­melanogenic properties. Gomisin D, J and O are dibenzocyclooctadiene lignans present in Kadsura medicinal plants and possess several pharmacological activities. In this study, the functions and mechanisms underlying the effects of gomisin D, J and O in UVA­and UVB­irradiated keratinocytes and α­melanocyte stimulating hormone (α­MSH)­stimulated melanocytes were explored. Following UVA and UVB irradiation, keratinocytes were treated with gomisin D, J and O, and keratinocyte viability, lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) production and apoptosis were examined. The results demonstrated that gomisin D and J improved keratinocyte viability and reduced LDH release under UVA and UVB irradiation. Intracellular ROS production induced by UVA and UVB irradiation was suppressed by gomisin D and J. In addition, Annexin V and TUNEL staining analysis indicated that gomisin D and J have significant anti­apoptotic effects on UVA­and UVB­irradiated keratinocytes. After α­MSH stimulation, melanocytes were treated with gomisin D, J and O, and the changes in melanocyte viability, intracellular melanin content, intracellular tyrosinase activity, and mechanisms underlying these changes were examined. Gomisin D markedly inhibited the α­MSH­induced increase in intracellular melanin content and tyrosinase activity. Mechanistically, gomisin D reduced the protein and mRNA expression levels of microphthalmia­associated transcription factor (MITF), tyrosinase, tyrosinase­related protein (TRP)­1 and TRP­2 in α­MSH­stimulated melanocytes. In addition, gomisin D markedly downregulated α­MSH­induced phosphorylation of protein kinase A and cAMP response element binding protein, which are known to be present upstream of the MITF, tyrosinase, TRP­1 and TRP­2 genes. Overall, gomisin D has photoprotective and anti­melanogenic effects; these findings provide a basis for the production of potential brightening and photoprotective agents using natural compounds such as gomisin D.

Dual modulation of the morphology and electric conductivity of NiCoP on nickel foam by Fe doping as a superior stability electrode for high energy supercapacitors.

Nickel-cobalt bimetallic phosphide (NiCoP) is a potential electrode material for supercapacitors on account of its high theoretical specific capacitance. However, its practical application is restricted because of its relatively poor cycling stability and rate performance. Herein, we constructed self-standing NiCoP nanowires and Fe doped NiCoP nanoarrays with different iron ion concentrations on nickel foam (Fe-NiCoP/NF-x%, x = 4, 6.25, 12.5, 25) as a positive electrode for asymmetric supercapacitors (ASCs). The morphological result reveals that the nanostructure of the material evolves from nanowires to nanosheets with the iron doping concentration, and the Fe-NiCoP/NF-12.5% nanosheets possess a more stable structure than NiCoP/NF nanowires. The density functional theory analysis implies that the conductivity of the material enhances after Fe doping because of the increased charge density and electron states. The combination of multicomponents and structural advantages endows the optimal Fe-NiCoP/NF-12.5% electrode with an ultrahigh areal capacitance of 9.93 F cm-2 (2758.34 F cm-3) under 1 mA cm-2, excellent rate capability (82.58% from 1 mA cm-2 to 50 mA cm-2) and superior cycling stability (95.72% retention over 5000 cycles under 20 mA cm-2), and the areal capacitance of Fe-NiCoP/NF-12.5% is 2.27 times higher than that of the pristine NiCoP/NF electrode at 1 mA cm-2. Moreover, the assembled Fe-NiCoP/NF-12.5%//activated carbon ASC device delivers a high energy density of 0.327 mW h cm-2 (60.43 mW h cm-3) at 1.10 mW cm-2 (202.54 mW cm-3). Therefore, this strategy may provide a novel route for the application of NiCoP with its intrinsic advantages in the energy storage field.

A Comparative Study on Photo-Protective and Anti-Melanogenic Properties of Different Kadsura coccinea Extracts.

Kadsura coccinea (KC), a beneficial plant for human health, has been used for centuries in China, Thailand, and Korea in folk medicine and food. There is evidence supporting the biological effects of highly bioactive ingredients in KC such as lignans, triterpenoids, flavonoids, phenolic acids, steroids, and amino acids. In this study, we aimed to explore the effects, functions, and mechanisms of the extracts from KC root (KCR), stem (KCS), leaf (KCL), and fruit (KCF) in UVA and UVB-irradiated keratinocytes and α-melanocyte stimulating hormone (α-MSH)-stimulated melanocytes. First, the total polyphenol and flavonoid contents of KCR, KCS, KCL, and KCF and their radical scavenging activities were investigated. These parameters were found to be in the following order: KCL > KCR > KCS > KCF. UVA and UVB-irradiated keratinocytes were treated with KCR, KCS, KCL, and KCF, and keratinocyte viability, LDH release, intracellular ROS production, and apoptosis were examined. Our results demonstrated that KC extracts improved keratinocyte viability and reduced LDH release, intracellular ROS production, and apoptosis in the presence UVA and UVB irradiation. The overall photoprotective activity of the KC extracts was confirmed in the following order: KCL > KCR > KCS > KCF. Moreover, KC extracts significantly decreased the intracellular melanin content and tyrosinase activity in α-MSH-stimulated melanocytes. Mechanistically, KC extracts reduced the protein and mRNA expression levels of tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2) in α-MSH-stimulated melanocytes. In addition, these extracts markedly downregulated myophthalmosis-related transcription factor expression and cAMP-related binding protein phosphorylation, which is upstream of the regulation of Tyrosinase, TRP-1, and TRP-2. The overall anti-melanogenic activity of the KC extracts was established in the following order. KCL > KCR > KCS > KCF. Overall, the KC extracts exert photoprotective and anti-melanogenic effects, providing a basis for developing potential skin-whitening and photoprotective agents.

SlTPL1 Silencing Induces Facultative Parthenocarpy in Tomato.

Facultative parthenocarpy is of great practical value. However, the molecular mechanism underlying facultative parthenocarpy remains elusive. Transcriptional co-repressors (TPL) act as a central regulatory hub controlling all nine phytohormone pathways. Previously, we proved that SlTPLs participate in the auxin signaling pathway by interacting with auxin/indole acetic acid (Aux/IAAs) in tomato; however, their function in fruit development has not been studied. In addition to their high expression levels during flower development, the interaction between SlTPL1 and SlIAA9 stimulated the investigation of its functional significance via RNA interference (RNAi) technology, whereby the translation of a protein is prevented by selective degradation of its encoded mRNA. Down-regulation of SlTPL1 resulted in facultative parthenocarpy. Plants of SlTPL1-RNAi transgenic lines produced similar fruits which did not show any pleiotropic effects under normal conditions. However, they produced seedless fruits upon emasculation and under heat stress conditions. Furthermore, SlTPL1-RNAi flower buds contained higher levels of cytokinins and lower levels of abscisic acid. To reveal how SlTPL1 regulates facultative parthenocarpy, RNA-seq was performed to identify genes regulated by SlTPL1 in ovaries before and after fruit set. The results showed that down-regulation of SlTPL1 resulted in reduced expression levels of cytokinin metabolism-related genes, and all transcription factors such as MYB, CDF, and ERFs. Conversely, down-regulation of SlTPL1 induced the expression of genes related to cell wall and cytoskeleton organization. These data provide novel insights into the molecular mechanism of facultative tomato parthenocarpy and identify SlTPL1 as a key factor regulating these processes.

Prediction of Multiple Organ Failure Complicated by Moderately Severe or Severe Acute Pancreatitis Based on Machine Learning: A Multicenter Cohort Study.

BACKGROUND: Multiple organ failure (MOF) may lead to an increased mortality rate of moderately severe (MSAP) or severe acute pancreatitis (SAP). This study is aimed to use machine learning to predict the risk of MOF in the course of disease. METHODS: Clinical and laboratory features with significant differences between patients with and without MOF were screened out by univariate analysis. Prediction models were developed for selected features through six machine learning methods. The models were internally validated with a five-fold cross-validation, and a series of optimal feature subsets were generated in corresponding models. A test set was used to evaluate the predictive performance of the six models. RESULTS: 305 (68%) of 455 patients with MSAP or SAP developed MOF. Eighteen features with significant differences between the group with MOF and without it in the training and validation set were used for modeling. Interleukin-6 levels, creatinine levels, and the kinetic time were the three most important features in the optimal feature subsets selected by K-fold cross-validation. The adaptive boosting algorithm (AdaBoost) showed the best predictive performance with the highest AUC value (0.826; 95% confidence interval: 0.740 to 0.888). The sensitivity of AdaBoost (80.49%) and specificity of logistic regression analysis (93.33%) were the best scores among the six models in the test set. CONCLUSIONS: A predictive model of MOF complicated by MSAP or SAP was successfully developed based on machine learning. The predictive performance was evaluated by a test set, for which AdaBoost showed a satisfactory predictive performance. The study is registered with the China Clinical Trial Registry (Identifier: ChiCTR1800016079).

Prediction of Disease Progression of COVID-19 Based upon Machine Learning.

BACKGROUND: Since December 2019, COVID-19 has spread throughout the world. Clinical outcomes of COVID-19 patients vary among infected individuals. Therefore, it is vital to identify patients at high risk of disease progression. METHODS: In this retrospective, multicenter cohort study, COVID-19 patients from Huoshenshan Hospital and Taikang Tongji Hospital (Wuhan, China) were included. Clinical features showing significant differences between the severe and nonsevere groups were screened out by univariate analysis. Then, these features were used to generate classifier models to predict whether a COVID-19 case would be severe or nonsevere based on machine learning. Two test sets of data from the two hospitals were gathered to evaluate the predictive performance of the models. RESULTS: A total of 455 patients were included, and 21 features showing significant differences between the severe and nonsevere groups were selected for the training and validation set. The optimal subset, with eleven features in the k-nearest neighbor model, obtained the highest area under the curve (AUC) value among the four models in the validation set. D-dimer, CRP, and age were the three most important features in the optimal-feature subsets. The highest AUC value was obtained using a support vector-machine model for a test set from Huoshenshan Hospital. Software for predicting disease progression based on machine learning was developed. CONCLUSION: The predictive models were successfully established based on machine learning, and achieved satisfactory predictive performance of disease progression with optimal-feature subsets.