Salivary Proteome and Intact N-Glycopeptides Analysis Reveal Specific Signatures in Periodontitis.

Periodontitis is a prevalent oral inflammatory disease that can result in tooth loss and is closely linked to type 2 diabetes (T2D). In this study, we analyzed the salivary proteome and intact N-glycopeptides (IGPs) of individuals with mild-moderate, severe, aggressive periodontitis, and periodontitis with T2D, including those treated with antidiabetic drugs, to identify specific signatures associated with the disease. Our results revealed that salivary proteins and glycoproteins were altered in all periodontitis groups (PRIDE ID: 1-20230612-72345), with fucose- and sialic acid-containing N-glycans showing the greatest increase. Additionally, differentially expressed proteins were classified into 9 clusters, including those that were increased in all periodontitis groups and those that were only altered in certain types of periodontitis. Interestingly, treatment with antidiabetic drugs reversed many of the changes observed in the salivary proteome and IGPs in T2D-related periodontitis, suggesting a potential therapeutic approach for managing periodontitis in patients with T2D. Consistent with MS/MS results, the expression of salivary IGHA2 and Fucα1-3/6GlcNAc (AAL) was significantly increased in MP. These findings provide new insights into the pathogenesis of periodontitis and highlight the potential of salivary biomarkers for diagnosis, prognosis, and monitoring of disease progression and treatment response.

Ubrogepant for the treatment of migraine attacks during the prodrome: a phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial in the USA.

BACKGROUND: Ubrogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist that is approved for acute treatment of migraine. The prodrome is the earliest phase of a migraine attack and is characterised by non-aura symptoms that precede headache onset. The aim of this trial was to evaluate the efficacy, safety, and tolerability of ubrogepant 100 mg compared with placebo for the acute treatment of migraine when administered during the prodrome. METHODS: This PRODROME trial was a phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial of ubrogepant 100 mg conducted at 75 research centres and headache clinics in the USA. Eligible participants were adults aged 18-75 years who had at least a 1-year history of migraine with or without aura and a history of two to eight migraine attacks per month with moderate to severe headache in each of the 3 months before screening. Eligible participants were randomly assigned (1:1) to either receive placebo to treat the first qualifying prodrome event and ubrogepant 100 mg to treat the second qualifying prodrome event or to receive ubrogepant 100 mg to treat the first qualifying prodrome event and placebo to treat the second qualifying prodrome event. An automated interactive web-response system used permuted blocks of four to manage randomisation. All people giving interventions and assessing outcomes were masked to group assignment during the study. People doing data analysis, which occurred after study completion, were not masked to group assignment. During the double-blind treatment period, each participant was instructed to orally take two tablets of the study drug at the onset of each qualifying prodrome event. The primary endpoint was absence of moderate or severe intensity headache within 24 h after study-drug dose; efficacy analyses were conducted with the modified intention-to-treat (mITT) population, defined as all randomly assigned participants with at least one headache assessment within 24 h after taking the study drug during the treatment period. The safety population included all treated participants who took at least one administration of study drug. The trial is registered with ClinicalTrials.gov (NCT04492020). FINDINGS: Between Aug 21, 2020, and April 19, 2022, 518 participants were randomly assigned to double-blind crossover treatment. The safety population included 480 participants and the mITT population included 477 participants; 421 (88%) of 480 participants were female and 59 (12%) were male. Absence of moderate or severe headache within 24 h after a dose occurred after 190 (46%) of 418 qualifying prodrome events that had been treated with ubrogepant and after 121 (29%) of 423 qualifying prodrome events that had been treated with placebo (odds ratio 2·09, 95% CI 1·63-2·69; p<0·0001). Adverse events that occurred within 48 h after study-drug administration were reported after 77 (17%) of 456 qualifying prodrome events that had been treated with ubrogepant and after 55 (12%) of 462 events that had been treated with placebo. INTERPRETATION: Ubrogepant was effective and well tolerated for the treatment of migraine attacks when taken during the prodrome. FUNDING: AbbVie.

Antimicrobial efficacy of aloe-emodin mediated photodynamic therapy against antibiotic-resistant Pseudomonas aeruginosa in vitro.

Multidrug-resistant Pseudomonas aeruginosa is a common pathogen that causes topical infections following burn injuries. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising approach for treating antibiotic-resistant bacterial infections. The objective of this study was to evaluate the aPDT efficacy of aloe-emodin (AE), which is a photosensitizer extracted from traditional Chinese herbs, on antibiotic-sensitive and antibiotic-resistant P. aeruginosa in vitro. In this study, we confirmed the effectiveness of AE-mediated aPDT against both standard and MDR P. aeruginosa, explored the effects of irradiation time and AE concentration on bacterial survival in AE-mediated aPDT, and observed the structural damage of P. aeruginosa by using transmission electron microscope. Our results showed that neither AE nor light irradiation alone caused cytotoxic effects on P. aeruginosa. However, AE-mediated aPDT effectively inactivated both antibiotic-sensitive and antibiotic-resistant P. aeruginosa. The transmission electron microscope investigation showed that aPDT mediated by AE primarily caused damage to the cytoplasm and cell membrane. Our findings suggest that AE is a photosensitizer in the aPDT of MDR P. aeruginosa-caused topical infections following burn injuries. Future investigations will concentrate on the safety and efficacy of AE-mediated aPDT in animal models and clinical trials.

Stretchable Ultrasound Metalens for Biomedical Zoom Imaging and Bone Quality Assessment with Subwavelength Resolution.

Ultrasound imaging is extensively used in biomedical science and clinical practice. Imaging resolution and tunability of imaging plane are key performance indicators, but both remain challenging to be improved due to the longer wavelength compared with light and the lack of zoom lens for ultrasound. Here, the ultrasound zoom imaging based on a stretchable planar metalens that simultaneously achieves the subwavelength imaging resolution and dynamic control of the imaging plane is reported. The proposed zoom imaging ultrasonography enables precise bone fracture diagnosis and comprehensive osteoporosis assessment. Millimeter-scale microarchitectures of the cortical bones at different depths can be selectively imaged with a 0.6-wavelength resolution. The morphological features of bone fractures, including the shape, size and position, are accurately detected. Based on the extracted ultrasound information of cancellous bones with healthy matrix, osteopenia and osteoporosis, a multi-index osteoporosis evaluation method is developed. Furthermore, it provides additional biological information in aspects of bone elasticity and attenuation to access the comprehensive osteoporosis assessment. The soft metalens also features flexibility and biocompatibility for preferable applications on wearable devices. This work provides a strategy for the development of high-resolution ultrasound biomedical zoom imaging and comprehensive bone quality diagnosis system.

MXene-Derived Na+ -Pillared Vanadate Cathodes for Dendrite-Free Potassium Metal Batteries.

Cation-intercalated vanadates, which have considerable promise as the cathode for high-performance potassium metal batteries (PMBs), suffer from structural collapse upon K+ insertion and desertion. Exotic cations in the vanadate cathode may ease the collapse, yet their effect on the intrinsic cation remains speculative. Herein, a stable and dendrite-free PMB, composed of a Na+ and K+ co-intercalated vanadate (NKVO) cathode and a liquid NaK alloy anode, is presented. A series of NKVO with tuneable Na/K ratios are facilely prepared using MXene precursors, in which Na+ is testified to be immobilized upon cycling, functioning as a structural pillar. Due to stronger ionic bonding and lower Fermi level of Na+ compared to K+ , moderate Na+ intercalation could reduce K+ binding to the solvation sheath and favor K+ diffusion kinetics. As a result, the MXene-derived Na+ -pillared NKVO exhibits markedly improved specific capacities, rate performance, and cycle stability than the Na+ -free counterpart. Moreover, thermally-treated carbon paper, which imitates the microscopic structure of Chinese Xuan paper, allows high surface tension liquid NaK alloy to adhere readily, enabling dendrite-free metal anodes. By clarifying the role of foreign intercalating cations, this study may lead to a more rational design of stable and high-performance electrode materials.

Fecal microbiota transplantation alleviates mild-moderate COVID-19 associated diarrhoea and depression symptoms: A prospective study of a randomized, double-blind clinical trial.

Currently, the emergence of the endemic Coronavirus disease (COVID-19) situation still poses a serious threat to public health. However, it remains elusive about the role of fecal microbiota transplantation in treating COVID-19. We performed a randomized, double-blind, placebo-controlled clinical trial enrolling a cohort of 40 COVID-19 patients with mild-moderate symptoms. Our results showed that fecal microbiota transplantation provided an amelioration in diarrhoea (p = 0.026) of digestive system and depression (p = 0.006) of neuropsychiatric-related symptom in COVID-19 patients, respectively. Meanwhile, we found that the number of patients with diarrhoea decreased from 19 to 0 on day 7 after fecal microbiota transplantation treatment, and it was statistically changed compared to the placebo group (p = 0.047). Of note, the serum concentration of aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT, fecal microbiota transplantation, pre vs. post: 0.966 vs. 0.817), a biomarker for predicting long COVID-19, was significantly reduced by fecal microbiota transplantation. In all, our study supports that fecal microbiota transplantation could be a novel therapeutic strategy for COVID-19 patients with diarrhoea and depressive symptoms, which is potentially valuable in ameliorating long COVID-19 symptoms.

Peripheral 5-HT Mediates Gonadotropin-Inhibitory Hormone-Induced Feeding Behavior and Energy Metabolism Disorder in Chickens via the 5-HT2C Receptor.

INTRODUCTION: Since the discovery of gonadotropin-inhibitory hormone (GnIH), it has been found to play a critical role in reproduction in vertebrates. Recently, a regulatory role of GnIH in appetite and energy metabolism has emerged, although its precise physiological mechanisms remain unknown. METHODS: Thus, the present study evaluated the effects of a single or long-term intraperitoneal GnIH treatment on the food intake, weight, and glucolipid metabolism of chickens, as well as investigating the possible neuroendocrinology factors and mechanisms involved in GnIH-induced obesity and glucolipid metabolism disorder. RESULTS: Our results show that the intraperitoneal administration of GnIH to chickens resulted in a marked body mass increase, hyperlipidemia, hyperglycemia, and glucose intolerance. Subsequently, the results of metabolomics studies and the pharmacological inhibition of the 5-HT2C receptor revealed that blocking the 5-HT2C receptor reinforced the effects of GnIH on food intake, body weight, and blood glucose and lipid levels, resulting in even worse cases of GnIH-induced hyperglycemia, hyperlipidemia, and hepatic lipid deposition. This suggests that, via the 5-HT2C receptor, peripheral 5-HT may act as a negative feedback regulator to interplay with GnIH and jointly control energy balance homeostasis in chickens. DISCUSSION: Our present study provides evidence of cross-talk between GnIH and 5-HT in food intake and energy metabolism at the in vivo pharmacological level, and it proposes a molecular basis for these interactions, suggesting that functional interactions between GnIH and 5-HT may open new avenues for understanding the mechanism of the neuroendocrine network involved in appetite and energy metabolism, as well as providing a new therapeutic strategy to prevent obesity, diabetes, and metabolic disorders.

Circadian light/dark cycle reversal exacerbates the progression of chronic kidney disease in mice.

Circadian disruption such as shift work, jet lag, has gradually become a global health issue and is closely associated with various metabolic disorders. The influence and mechanism of circadian disruption on renal injury in chronic kidney disease (CKD) remains inadequately understood. Here, we evaluated the impact of environmental light disruption on the progression of chronic renal injury in CKD mice. By using two abnormal light exposure models to induce circadian disruption, we found that circadian disruption induced by weekly light/dark cycle reversal (LDDL) significantly exacerbated renal dysfunction, accelerated renal injury, and promoted renal fibrosis in mice with 5/6 nephrectomy and unilateral ureteral obstruction (UUO). Mechanistically, RNA-seq analysis revealed significant immune and metabolic disorder in the LDDL-conditioned CKD kidneys. Consistently, renal content of ATP was decreased and ROS production was increased in the kidney tissues of the LDDL-challenged CKD mice. Untargeted metabolomics revealed a significant buildup of lipids in the kidney affected by LDDL. Notably, the level of ß-NMN, a crucial intermediate in the NAD+ pathway, was found to be particularly reduced. Moreover, we demonstrated that both ß-NMN and melatonin administration could significantly rescue the light-disruption associated kidney dysfunction. In conclusion, environmental circadian disruption may exacerbate chronic kidney injury by facilitating inflammatory responses and disturbing metabolic homeostasis. ß-NMN and melatonin treatments may hold potential as promising approaches for preventing and treating light-disruption associated CKD.

Prostate-specific antigen, androgen, progesterone and oestrogen receptors in Benign prostatic hyperplasia: human tissues and animal model study.

BACKGROUND: Direct evidence for the relationship between a large prostate (≥80 ml) and androgen receptor/PSA signal remains lacking in benign prostatic hyperplasia (BPH). Our aim is to identify whether the cause of a large prostate is related to progesterone receptor (PGR) androgen receptor (AR), oestrogen receptor α, ß (ERα,ß) and prostate-specific antigen (PSA). MATERIALS AND METHODS: Surgical specimens of BPH in plasmakinetic resection of the prostate (PKRP) with three groups of different prostate-sizes with mean volumes of 25.97 ml, 63.80 ml, and 122.37 ml were collected for immunohistochemical analysis of the tissue microarray with PGR, AR, PSA and ERs. Rats were castrated and treated with testosterone replacement to explore androgen and PGR, AR and ERs expression levels in the prostate. Quantitative real-time reverse transcription polymerase chain reaction (Rt-PCR) for mRNA detection of above genes was conducted. RESULTS: Immunoblotting, Rt-PCR and immunohistochemistry assays showed that PGR, PSA, AR, ERα expression levels were positively correlated with prostate size and that ERß expression levels were negatively correlated with prostate volume. Animal experiments have shown that prostate volume is decreased in castrated rats with decreased PGR, AR, ERα and increased ERß expression levels. CONCLUSION: PGR, AR, ERs signals can be regarded as important factors for large-sized prostates in BPH patients (≥100 ml).

GroEL triggers NLRP3 inflammasome activation through the TLR/NF-κB p-p65 axis in human periodontal ligament stem cells.

The interaction between bacteria and the host plays a vital role in the initiation and progression of systemic diseases, including gastrointestinal and oral diseases, due to the secretion of various virulence factors from these pathogens. GroEL, a potent virulence factor secreted by multiple oral pathogenic bacteria, is implicated in the damage of gingival epithelium, periodontal ligament, alveolar bone and other peripheral tissues. However, the underlying biomechanism is still largely unknown. In the present study, we verify that GroEL can trigger the activation of NLRP3 inflammasome and its downstream effector molecules, IL-1ß and IL-18, in human periodontal ligament stem cells (hPDLSCs) and resultantly induce high activation of gelatinases (MMP-2 and MMP-9) to promote the degradation of extracellular matrix (ECM). GroEL-mediated activation of the NLRP3 inflammasome requires the participation of Toll-like receptors (TLR2 and TLR4). High upregulation of TLR2 and TLR4 induces the enhancement of NF-κB (p-p65) signaling and promotes its nuclear accumulation, thus activating the NLRP3 inflammasome. These results are verified in a rat model with direct injection of GroEL. Collectively, this study provides insight into the role of virulence factors in bacteria-induced host immune response and may also provide a new clue for the prevention of periodontitis.

Sea spray aerosol concentration modulated by sea surface temperature.

Natural aerosols in pristine regions form the baseline used to evaluate the impact of anthropogenic aerosols on climate. Sea spray aerosol (SSA) is a major component of natural aerosols. Despite its importance, the abundance of SSA is poorly constrained. It is generally accepted that wind-driven wave breaking is the principle governing SSA production. This mechanism alone, however, is insufficient to explain the variability of SSA concentration at given wind speed. The role of other parameters, such as sea surface temperature (SST), remains controversial. Here, we show that higher SST promotes SSA mass generation at a wide range of wind speed levels over the remote Pacific and Atlantic Oceans, in addition to demonstrating the wind-driven SSA production mechanism. The results are from a global scale dataset of airborne SSA measurements at 150 to 200 m above the ocean surface during the NASA Atmospheric Tomography Mission. Statistical analysis suggests that accounting for SST greatly enhances the predictability of the observed SSA concentration compared to using wind speed alone. Our results support implementing SST into SSA source functions in global models to better understand the atmospheric burdens of SSA.

Backscatter measurement of cancellous bone using the ultrasound transit time spectroscopy.

Recently, ultrasound transit time spectroscopy (UTTS) was proposed as a promising method for bone quantitative ultrasound measurement. Studies have showed that UTTS could estimate the bone volume fraction and other trabecular bone structure in ultrasonic through-transmission measurements. The goal of this study was to explore the feasibility of UTTS to be adapted in ultrasonic backscatter measurement and further evaluate the performance of backscattered ultrasound transit time spectrum (BS-UTTS) in the measurement of cancellous bone density and structure. First, taking ultrasonic attenuation into account, the concept of BS-UTTS was verified on ultrasonic backscatter signals simulated from a set of scatterers with different positions and intensities. Then, in vitro backscatter measurements were performed on 26 bovine cancellous bone specimens. After a logarithmic compression of the BS-UTTS, a linear fitting of the log-compressed BS-UTTS versus ultrasonic propagated distance was performed and the slope and intercept of the fitted line for BS-UTTS were determined. The associations between BS-UTTS parameters and cancellous bone features were analyzed using simple linear regression. The results showed that the BS-UTTS could make an accurate deconvolution of the backscatter signal and predict the position and intensity of the simulated scatterers eliminating phase interference, even the simulated backscatter signal was with a relatively low signal-to-noise ratio. With varied positions and intensities of the scatterers, the slope of the fitted line for the log-compressed BS-UTTS versus ultrasonic propagated distance (i.e., slope of BS-UTTS for short) yield a high agreement (r2 = 99.84%-99.96%) with ultrasonic attenuation in simulated backscatter signal. Compared with the high-density cancellous bone, the low-density specimen showed more abundant backscatter impulse response in the BS-UTTS. The slope of BS-UTTS yield a significant correlation with bone mineral density (r = 0.87; p < 0.001), BV/TV (r = 0.87; p < 0.001), and cancellous bone microstructures (r up to 0.87; p < 0.05). The intercept of BS-UTTS was also significantly correlated with bone densities (r = -0.87; p < 0.001) and trabecular structures (|r|=0.43-0.80; p < 0.05). However, the slope of the BS-UTTS underestimated attenuation when measurements were performed experimentally. In addition, a significant non-linear relationship was observed between the measured attenuation and the attenuation estimated by the slope of the BS-UTTS. This study demonstrated that the UTTS method could be adapted to ultrasonic backscatter measurement of cancellous bone. The derived slope and intercept of BS-UTTS could be used in the measurement of bone density and microstructure. The backscattered ultrasound transit time spectroscopy might have potential in the diagnosis of osteoporosis in the clinic.

Ultrasonic Imaging of Deeper Bone Defect Using Virtual Source Synthetic Aperture with Phased Shift Migration: A Phantom Study.

Ultrasound imaging for bone is a difficult task in the field of medical ultrasound. Compared with other phase array techniques, the synthetic aperture (SA) has a better lateral resolution but a limited imaging depth due to the limited ultrasonic energy emitted by the single emitter in each transmission. In contrast, the virtual source (VS) synthetic aperture allows a simultaneous multi-element emission and could provide a higher ultrasonic incident energy in each transmission. Therefore, the VS might achieve a high imaging quality at a deeper depth for bone imaging than the traditional SA. In this study, we proposed the virtual source phase shift migration (VS-PSM) method to achieve ultrasonic imaging of the deeper bone defect featured in the multilayer structure. The proposed VS-PSM method was validated using standard soft tissue phantom and printed bone phantom with artificial defects. The image quality was evaluated in terms of contrast-to-noise ratios (CNR) and amplitudes of scatters and defects at different imaging depths. The results showed that the VS-PSM method could achieve a high imaging quality of the soft tissues with a significant improvement in the scattering amplitude and without a significant sacrifice of the lateral and axial resolution. The PSM was superior to the DAS in suppressing the background noise in the images. Compared with the traditional SA-PSM, the VS-PSM method could image deeper bone defects at different ultrasonic frequencies, with an average improvement of 50% in CNR. In conclusion, this study demonstrated that the proposed VS-PSM method could image deeper bone defects and might help the diagnosis of bone disease using ultrasonic imaging.

Prediction of martensite start temperature of steel combined with expert experience and machine learning.

The martensite start temperature (MS) plays a pivotal role in formulating heat treatment regimes for steel. This paper, through the compilation of experimental data from literature and the incorporation of expert knowledge to construct features, employs machine learning algorithms to predict the MS of steel. The study highlights that the ETR algorithm attains optimal prediction accuracy, and the inclusion of atomic features enhances the model's performance. Feature selection is accomplished by evaluating linear and nonlinear relationships between data using the Pearson correlation coefficient (PCC), variance inflation factor (VIF), and maximum information coefficient (MIC). Subsequently, the performance of machine learning models on unknown data is compared to validate the model's generalization ability. The introduction of SHAP values for model interpretability analysis unveils the influencing mechanisms between features and the target variable. Finally, utilizing a specific steel type as an illustration, the paper underscores the practical value of the model.

This study innovatively integrates experimental data, expert knowledge, and ETR algorithm for accurate MS prediction in steel, enhancing model performance with systematic feature selection and interpretability analysis, demonstrating practical utility.

Flavonoid Profiles in the Pulp of Different Lemon Cultivars and Their Antioxidant Activity Based on UPLC-Q-TOF-MS.

Previous studies have indicated that there may be differences among the varieties of lemon flavonoids, but the details have not yet been made clear, which limits the comprehensive use of different cultivated lemon varieties. In this study, ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) and ultraviolet-visible spectroscopy (UV-Vis) were used to investigate the types and contents of flavonoids in the flesh of the main cultivated variety (Eureka) and five common lemon varieties, as well as their in vitro antioxidant activity. A total of 21 compounds were identified, five of which were common compounds. Among them, Verna, Lisbon, and Bearss each have characteristic components that can serve as potential criteria for variety identification. Each of the six varieties of lemon has strong antioxidant activity. The antioxidant activity of different lemon varieties is related to flavonoids. Therefore, Eureka and the other five varieties of lemon are good natural antioxidants, and the cultivation and industrial production of lemons should consider the needs and selection of suitable varieties.

Characterization and application of in situ curcumin/ZNP hydrogels for periodontitis treatment.

BACKGROUND: Periodontitis is a chronic inflammatory disease that occurs in tooth-supporting tissues. Controlling inflammation and alleviating periodontal tissue destruction are key factors in periodontal therapy. This study aimed to develop an in situ curcumin/zinc oxide (Cur/ZNP) hydrogel and investigate its characteristics and effectiveness in the treatment of periodontitis. METHODS: Antibacterial activity and cytotoxicity assays were performed in vitro. To evaluate the effect of the in situ Cur/ZNP hydrogel on periodontitis in vivo, an experimental periodontitis model was established in Sprague‒Dawley rats via silk ligature and inoculation of the maxillary first molar with Porphyromonas gingivalis. After one month of in situ treatment with the hydrogel, we examined the transcriptional responses of the gingiva to the Cur/ZNP hydrogel treatment and detected the alveolar bone level as well as the expression of osteocalcin (OCN) and osteoprotegerin (OPG) in the periodontal tissues of the rats. RESULTS: Cur/ZNPs had synergistic inhibitory effects on P. gingivalis and good biocompatibility. RNA sequencing of the gingiva showed that immune effector process-related genes were significantly induced by experimental periodontitis. Carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1), which is involved in the negative regulation of bone resorption, was differentially regulated by the Cur/ZNP hydrogel but not by the Cur hydrogel or ZNP hydrogel. The Cur/ZNP hydrogel also had a stronger protective effect on alveolar bone resorption than both the Cur hydrogel and the ZNP hydrogel. CONCLUSION: The Cur/ZNP hydrogel effectively inhibited periodontal pathogenic bacteria and alleviated alveolar bone destruction while exhibiting favorable biocompatibility.

A cascading learning method with SegFormer for radiographic measurement of periodontal bone loss.

OBJECTIVE: Marginal alveolar bone loss is one of the key features of periodontitis and can be observed via panoramic radiographs. This study aimed to establish a cascading learning method with deep learning (DL) for precise radiographic bone loss (RBL) measurements at specific tooth positions. MATERIALS AND METHODS: Through the design of two tasks for tooth position recognition and tooth semantic segmentation using the SegFormer model, specific tooth's crown, intrabony portion, and suprabony portion of the roots were obtained. The RBL was subsequently measured by length through these three areas using the principal component analysis (PCA) principal axis. RESULTS: The average intersection over union (IoU) for the tooth position recognition task was 0.8906, with an F1-score of 0.9338. The average IoU for the tooth semantic segmentation task was 0.8465, with an F1-score of 0.9138. When the two tasks were combined, the average IoU was 0.7889, with an F1-score of 0.8674. The correlation coefficient between the RBL prediction results based on the PCA principal axis and the clinicians' measurements exceeded 0.85. Compared to those of the other two methods, the average precision of the predicted RBL was 0.7722, the average sensitivity was 0.7416, and the average F1-score was 0.7444. CONCLUSIONS: The method for predicting RBL using DL and PCA produced promising results, offering rapid and reliable auxiliary information for future periodontal disease diagnosis. CLINICAL RELEVANCE: Precise RBL measurements are important for periodontal diagnosis. The proposed RBL-SF can measure RBL at specific tooth positions and assign the bone loss stage. The ability of the RBL-SF to measure RBL at specific tooth positions can guide clinicians to a certain extent in the accurate diagnosis of periodontitis.

Hydrogen-Bond-Network Breakdown Boosts Selective CO2 Photoreduction by Suppressing H2 Evolution.

Conventional strategies for highly efficient and selective CO2 photoreduction focus on the design of catalysts and cocatalysts. In this study, we discover that hydrogen bond network breakdown in reaction system can suppress H2 evolution, thereby improving CO2 photoreduction performance. Photosensitive poly(ionic liquid)s are designed as photocatalysts owing to their strong hydrogen bonding with solvents. The hydrogen bond strength is tuned by solvent composition, thereby effectively regulating H2 evolution (from 0 to 12.6 mmol g-1 h-1). No H2 is detected after hydrogen bond network breakdown with trichloromethane or tetrachloromethane as additives. CO production rate and selectivity increase to 35.4 mmol g-1 h-1 and 98.9 % with trichloromethane, compared with 0.6 mmol g-1 h-1 and 26.2 %, respectively, without trichloromethane. Raman spectroscopy and theoretical calculations confirm that trichloromethane broke the systemic hydrogen bond network and subsequently suppressed H2 evolution. This hydrogen bond network breakdown strategy may be extended to other catalytic reactions involving H2 evolution.

Comparison of Colonoscopy, Fecal Immunochemical Test, and Risk-Adapted Approach in a Colorectal Cancer Screening Trial (TARGET-C).

BACKGROUND & AIMS: The screening yield and related cost of a risk-adapted screening approach compared with established screening strategies in population-based colorectal cancer (CRC) screening are not clear. METHODS: We randomly allocated 19,373 participants into 1 of the 3 screening arms in a 1:2:2 ratio: (1) one-time colonoscopy (n = 3883); (2) annual fecal immunochemical test (FIT) (n = 7793); (3) annual risk-adapted screening (n = 7697), in which, based on the risk-stratification score, high-risk participants were referred for colonoscopy and low-risk ones were referred for FIT. Three consecutive screening rounds were conducted for both the FIT and the risk-adapted screening arms. Follow-up to trace the health outcome for all the participants was conducted over the 3-year study period. The detection rate of advanced colorectal neoplasia (CRC and advanced precancerous lesions) was the main outcome. The trial was registered in the Chinese Clinical Trial Registry (number: ChiCTR1800015506). RESULTS: In the colonoscopy, FIT, and risk-adapted screening arms over 3 screening rounds, the participation rates were 42.4%, 99.3%, and 89.2%, respectively; the detection rates for advanced neoplasm (intention-to-treat analysis) were 2.76%, 2.17%, and 2.35%, respectively, with an odds ratio (OR)colonoscopy vs FIT of 1.27 (95% confidence interval [CI]: 0.99-1.63; P = .056), an ORcolonoscopy vsrisk-adapted screening of 1.17 (95% CI, 0.91-1.49; P = .218), and an ORrisk-adapted screeningvs FIT of 1.09 (95% CI, 0.88-1.35; P = .438); the numbers of colonoscopies needed to detect 1 advanced neoplasm were 15.4, 7.8, and 10.2, respectively; the costs for detecting 1 advanced neoplasm from a government perspective using package payment format were 6928 Chinese Yuan (CNY) ($1004), 5821 CNY ($844), and 6694 CNY ($970), respectively. CONCLUSIONS: The risk-adapted approach is a feasible and cost-favorable strategy for population-based CRC screening and therefore could complement the well-established one-time colonoscopy and annual repeated FIT screening strategies. (Chinese Clinical Trial Registry; ChiCTR1800015506).

A bacterial tyrosine phosphatase modulates cell proliferation through targeting RGCC.

Tyrosine phosphatases are often weaponized by bacteria colonizing mucosal barriers to manipulate host cell signal transduction pathways. Porphyromonas gingivalis is a periodontal pathogen and emerging oncopathogen which interferes with gingival epithelial cell proliferation and migration, and induces a partial epithelial mesenchymal transition. P. gingivalis produces two tyrosine phosphatases, and we show here that the low molecular weight tyrosine phosphatase, Ltp1, is secreted within gingival epithelial cells and translocates to the nucleus. An ltp1 mutant of P. gingivalis showed a diminished ability to induce epithelial cell migration and proliferation. Ltp1 was also required for the transcriptional upregulation of Regulator of Growth and Cell Cycle (RGCC), one of the most differentially expressed genes in epithelial cells resulting from P. gingivalis infection. A phosphoarray and siRNA showed that P. gingivalis controlled RGCC expression through Akt, which was activated by phosphorylation on S473. Akt activation is opposed by PTEN, and P. gingivalis decreased the amount of PTEN in epithelial cells. Ectopically expressed Ltp1 bound to PTEN, and reduced phosphorylation of PTEN at Y336 which controls proteasomal degradation. Ltp-1 induced loss of PTEN stability was prevented by chemical inhibition of the proteasome. Knockdown of RGCC suppressed upregulation of Zeb2 and mesenchymal markers by P. gingivalis. RGCC inhibition was also accompanied by a reduction in production of the proinflammatory cytokine IL-6 in response to P. gingivalis. Elevated IL-6 levels can contribute to periodontal destruction, and the ltp1 mutant of P. gingivalis incited less bone loss compared to the parental strain in a murine model of periodontal disease. These results show that P. gingivalis can deliver Ltp1 within gingival epithelial cells, and establish PTEN as the target for Ltp1 phosphatase activity. Disruption of the Akt1/RGCC signaling axis by Ltp1 facilitates P. gingivalis-induced increases in epithelial cell migration, proliferation, EMT and inflammatory cytokine production.