Diagnostic accuracy of artificial intelligence-assisted caries detection: a clinical evaluation.

OBJECTIVE: This clinical study aimed to evaluate the practical value of integrating an AI diagnostic model into clinical practice for caries detection using intraoral images. METHODS: In this prospective study, 4,361 teeth from 191 consecutive patients visiting an endodontics clinic were examined using an intraoral camera. The AI model, combining MobileNet-v3 and U-net architectures, was used for caries detection. The diagnostic performance of the AI model was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, with the clinical diagnosis by endodontic specialists as the reference standard. RESULTS: The overall accuracy of the AI-assisted caries detection was 93.40%. The sensitivity and specificity were 81.31% (95% CI 78.22%-84.06%) and 95.65% (95% CI 94.94%-96.26%), respectively. The NPV and PPV were 96.49% (95% CI 95.84%-97.04%) and 77.68% (95% CI 74.49%-80.58%), respectively. The diagnostic accuracy varied depending on tooth position and caries type, with the highest accuracy in anterior teeth (96.04%) and the lowest sensitivity for interproximal caries in anterior teeth and buccal caries in premolars (approximately 10%). CONCLUSION: The AI-assisted caries detection tool demonstrated potential for clinical application, with high overall accuracy and specificity. However, the sensitivity varied considerably depending on tooth position and caries type, suggesting the need for further improvement. Integration of multimodal data and development of more advanced AI models may enhance the performance of AI-assisted caries detection in clinical practice.

Global marine microbial diversity and its potential in bioprospecting.

The past two decades has witnessed a remarkable increase in the number of microbial genomes retrieved from marine systems1,2. However, it has remained challenging to translate this marine genomic diversity into biotechnological and biomedical applications3,4. Here we recovered 43,191 bacterial and archaeal genomes from publicly available marine metagenomes, encompassing a wide range of diversity with 138 distinct phyla, redefining the upper limit of marine bacterial genome size and revealing complex trade-offs between the occurrence of CRISPR-Cas systems and antibiotic resistance genes. In silico bioprospecting of these marine genomes led to the discovery of a novel CRISPR-Cas9 system, ten antimicrobial peptides, and three enzymes that degrade polyethylene terephthalate. In vitro experiments confirmed their effectiveness and efficacy. This work provides evidence that global-scale sequencing initiatives advance our understanding of how microbial diversity has evolved in the oceans and is maintained, and demonstrates how such initiatives can be sustainably exploited to advance biotechnology and biomedicine.

Taxonomic composition and functional potentials of gastrointestinal microbiota in 12 wild-stranded cetaceans.

Cetaceans play a crucial role in marine ecosystems; however, research on their gastrointestinal microbiota remains limited due to sampling constraints. In this study, we collected hindgut samples from 12 stranded cetaceans and performed 16S rRNA gene amplicon sequencing to investigate microbial composition and functional potentials. Analysis of ZOTUs profiles revealed that the phyla Firmicutes, Proteobacteria, and Bacteroidetes dominated all hindgut samples. However, unique microbial profiles were observed among different cetacean species, with significant separation of gut microbiota communities according to biological evolutionary lineages. Different genera that contain pathogens were observed distinguishing delphinids from physeteroids/ziphiids. Delphinid samples exhibited higher abundances of Vibrio, Escherichia, and Paeniclostridium, whereas physeteroid and ziphiid samples showed higher abundances of Pseudomonas, Enterococcus, and Intestinimonas. Functional analysis indicated convergence in the gut microbiota among all cetaceans, with shared bacterial infection pathways across hindgut samples. In addition, a comparison of the gastrointestinal microbial composition between a stranded short-finned pilot whale (Globicephala macrorhynchus) and a stranded rough-toothed dolphin (Steno bredanensis) using 16S rRNA gene sequencing revealed distinct microbial community structures and functional capacities. To the best of our knowledge, this study represents the first report on the gastrointestinal microbiota of the pantropical spotted dolphin (Stenella attenuata), Blainville's beaked whale (Mesoplodon densirostris), and rough-toothed dolphin, with various comparisons conducted among different cetacean species. Our findings enhance the understanding of microbial composition and diversity in cetacean gastrointestinal microbiota, providing new insights into co-evolution and complex interactions between cetacean microbes and hosts.

[Delineation of water ecological restoration zoning from a multi-dimensional perspective: A case study in Hechi, a typical karst region]. / 多维视角下水生态修复分区划定­­ä»¥å ¸åž‹å–€æ–¯ç‰¹åœ°åŒºæ²³æ± 市为例.

Water ecological restoration zoning, which involves articulating goals for restoring water ecosystems upwards and guiding the spatial layout of restoration projects downwards, is key to achieving systematic restoration of water resource elements. There are many challenges in water ecological restoration zoning, including disparate hierarchical systems, incomplete indicators, and vague boundaries. With Guangxi Hechi, a karst ecologically fragile region, as a case, we developed a multidimensional zoning system framework based on "watershed natural unit-dominant ecological function-ecological stress risk". The first-level zoning employed river systems and geomorphic types as indicators and delineated the sub-watershed unit as the boundary. The second-level zoning adopted a "top-down" division method to clarify the goal of water ecological restoration based on watershed natural geography and select three indicators (water conservation, biodiversity, and landscape cultural services) for evaluation. We used the K-means clustering method to identify dominant ecological functions in spatial units, with the sub-watershed unit demarcating second-level zoning boundaries. The third-level zoning was the specific implementation unit for ecological restoration projects. We used three indicators (soil erosion, flooding risk, and human interference) to characterize water ecosystem risk from external coercion, and defined the third-level zoning. We delineated 11 primary water ecological zones, four secondary zones, and three tertiary zones. Synthesizing tertiary zoning results accounted for spatial differentiation characteristics of watershed natural geography, dominant ecological functions, and ecological coercion risks, and combining sub-watershed and township administrative units determined zoning boundaries, water ecological restoration zoning was comprehensively classified into five categories and 32 sub-ecological zones. Corresponding ecological restoration strategies were proposed based on zoning and classification.

Synergistic Procoagulant Mechanism and Application of Kaolin-Zeolite Composite Hemostat for Effective Hemorrhage Control.

Achieving timely and effective hemorrhage control is imperative for the survival of individuals with severe bleeding. Hemostatic materials, by enhancing the natural cell-based coagulation response, are essential tools in modern and military medical practice for controlling bleeding, especially in emergency and surgical settings. Here, we report a new type of composite hemostatic material with two different aluminosilicate-based components, kaolin and zeolite, which synergistically work together in different stages of the coagulation cascade reactions. Kaolin can effectively activate the clotting factor FXII in the early stage, and zeolite can accumulate and assemble FXa and FVa on its surface and thereafter lead to the formation of highly active thrombin in the later stage. The synergistic action mechanism between kaolin and zeolite significantly boosts the levels of FXIIa and FXa, and it also greatly enhances plateau thrombin activity. For practical application, a kaolin-modified zeolite gauze is fabricated, and it demonstrates excellent hemostatic effectiveness. Compared to the combat gauze currently used in front-line treatment, it reduces blood loss by 75% and shortens hemostasis time by 33% in a rabbit femoral artery injury model. In addition, this kaolin-zeolite gauze has no heat release problem and a nearly zero particle shedding rate, which greatly decreases the safety risk compared to current commercial inorganic-based hemostatic gauzes.

Systematic detection and evaluation of cracking behavior of flawed brittle sandstones with AE and 3D-DIC techniques.

Determination of the cracking behavior during crack propagation helps to better understand damage and fracture processes in brittle rocks. The paper studies the cracking behavior of rocks on three scales: macro-deformation (or macro-cracking), internal micro-fracture, and surface crack coalescence. Under uniaxial compression, the cracking behavior of two types of sandstone specimens having single flaws was experimentally and systematically investigated. Acoustic emission (AE) and three-dimensional digital image correlation (3D-DIC) techniques were utilized to continuously monitor the acoustic shock signals generated by micro-fracture events inside the specimen and the specimen surface cracking process. The experimental results show that at the crack initiation stage, many micro-tensile fractures within the rock are initiated and coalesced, and small strain localized zones (SLZs) appear on the specimen surface. In the crack propagation stage, micro-fractures coalesce into macro-fractures that propagate in tensile mode to form surface cracks, which finally break in tension or slide against each other in shear mode. The formation of SLZs is related to the dip angle of pre-existing flaws, which determines the direction and mode of crack propagation. In conclusion, the strong acoustic-optical evidence accompanying different cracking behaviors is discussed in detail. From both acoustic and optical perspectives, it reveals and explains how flaws and material properties affect the strength and cracking mechanisms of brittle rocks. The study aids comprehension of the potential relation between internal micro-fracture and surface cracking in the process of engineering rock mass failure.

Nitrogen removal pathways in lake restoration using microalgal-bacterial granular sludge: Unraveling influence of organics and carbon to nitrogen ratio.

This study investigated the performance of microalgal-bacterial granular sludge (MBGS) in the restoration of Qingling Lake and Huangjia Lake, focusing on nitrogen removal under varying water quality conditions. Significant color changes in MBGS and differences in granule characteristics were observed, with Qingling Lake demonstrating superior removal efficiencies for ammonia nitrogen, nitrate nitrogen, and total nitrogen compared to Huangjia Lake. Stoichiometric analysis revealed that when the chemical oxygen demand (COD) and carbon-to-nitrogen (C/N) ratios were less than 20 mg/L and 20, respectively, assimilatory nitrate reduction was positively correlated with both, whereas denitrification was negatively correlated. Gene function analysis showed that Qingling Lake had a more active microbial community supporting efficient nitrogen metabolism. The findings highlighted the enormous potential of MBGS in lake restoration, demonstrating its ability to adapt to different COD concentrations and C/N ratios by altering its nitrogen removal pathways.

Ventricular activation pattern of left ventricular septal pacing in a canine model.

BACKGROUND: Left bundle branch pacing (LBBP) is a feasible and effective physiological pacing technique. The QRS morphology of left ventricular septal pacing (LVSP) is similar to that of LBBP. The ventricular activation pattern of LBBP is well-known, whereas the pattern of LVSP still needs further investigation. The present study aimed to determine ventricular activation pattern difference between LVSP and LBBP in a canine model. METHOD: All six canines underwent successful LBBP and LVSP through trans-ventricular septum using intracardiac echocardiography and intracardiac electrogram. Their hearts were isolated and stained with Lugol's iodine to determine the position of the pacing lead. The activation sequences of the left ventricular myocardium and His-Purkinje system were recorded by placing multiple electrode catheters. RESULTS: First, the left His-Purkinje system in LVSP was activated simultaneously from apical and basal regions to the left ventricular middle septal region, whereas the left ventricular septal myocardium was activated from the apical to basal region. The left His-Purkinje system activation in LBBP occurred in the direction of the apex from the pacing lead, but the left ventricular septal myocardium was activated in the apical to basal direction. Furthermore, the left intraventricular electrical synchrony was similar between LVSP and LBBP as determined by mapping the left ventricular septal to free wall activation time (46.7 ± 1.8 ms vs. 45.0 ± 1.4 ms, p = 0.11). CONCLUSION: The ventricular activation sequence of LVSP was similar to LBBP. LVSP can capture LBB due to the wide distribution of LBB. These findings suggest a rationale for clinical application of LVSP.

Spatial patterns and influencing factors of financial agglomeration in Guangdong-Hong Kong-Macao Greater Bay Area.

The Guangdong-Hong Kong-Macao Greater Bay Area (GBA) represents a significant economic zone with a diverse financial landscape. Understanding the spatial distribution of financial resources within this area is crucial for promoting balanced economic growth and financial development. This study investigates the spatial patterns of financial agglomeration in the GBA, identifying key influencing factors and assessing their impact on the region's financial landscape. We employ the entropy value method to evaluate financial agglomeration levels across the GBA's cities. Additionally, we use spatial econometric techniques to analyze the spatial correlations and the Geo-Detector model to determine the primary factors influencing financial agglomeration. The analysis reveals an overall increase in financial agglomeration, with significant disparities among cities. Key factors driving this agglomeration include transportation infrastructure, overseas trade, foreign direct investment (FDI), and technological advancements. Hong Kong and Shenzhen display notable unevenness in the distribution of financial industries. The interplay between finance, technology, and industrial sectors suggests considerable development potential. Understanding and optimizing the spatial distribution of financial resources is essential for fostering high-quality financial development and sustainable economic growth in the GBA. This study provides insights that can inform policy decisions aimed at enhancing financial integration and cooperation within the region.

Lack of ceramide synthase 5 protects retinal ganglion cells from ocular hypertensive injury.

Ceramides with varying acyl-chain lengths can have unique biological actions and hence, cellular responses to ceramides may depend not on their overall concentration but on that of individual ceramide species. The purpose of this study was to determine individual ceramide species impacting retinal ganglion cell (RGC) loss under the ocular hypertensive condition. Induced pluripotent stem cell (iPSC)-derived RGCs and primary cultures of human astrocytes were used to determine the effect of individual ceramide species on both RGC viability and astrocyte secretion of inflammatory cytokines in vitro. In in vivo experiments with wild-type (WT) and ceramide synthase 5 (CerS5) knockout mice, intraocular pressure was unilaterally elevated with microbead injection. Retinal function and morphology were evaluated using pattern electroretinography (pERG) and immunofluorescence, respectively. Ceramide levels were determined by LC-MS/MS analysis. Exposure to C16:0-, C18:0-, C18:1-, C20:0- and C24:0-ceramides significantly reduces RGC viability in vitro, with the very long chain C24:0-ceramide being the most neurotoxic; treatment with C18:0-, C18:1- and C24:0-ceramides stimulates an increase of TNF-α secretion by astrocytes. The retinas of CerS5 KO mice have significantly reduced levels of C16:0- and C18:1-ceramides compared to WT; ocular hypertensive eyes of these mice maintain higher pERG amplitudes and RGC numbers compared to WT. Individual ceramides with different chain lengths have different effects on RGCs and astrocytes. Our results demonstrate that suppressing C16:0- and C18:1-ceramide species effectively protects RGCs against ocular hypertensive injury. These results provide a basis for targeting specific ceramide species in the treatment of glaucoma.

Elevating Detection Performance in Optical Remote Sensing Image Object Detection: A Dual Strategy with Spatially Adaptive Angle-Aware Networks and Edge-Aware Skewed Bounding Box Loss Function.

In optical remote sensing image object detection, discontinuous boundaries often limit detection accuracy, particularly at high Intersection over Union (IoU) thresholds. This paper addresses this issue by proposing the Spatial Adaptive Angle-Aware (SA3) Network. The SA3 Network employs a hierarchical refinement approach, consisting of coarse regression, fine regression, and precise tuning, to optimize the angle parameters of rotated bounding boxes. It adapts to specific task scenarios using either class-aware or class-agnostic strategies. Experimental results demonstrate its effectiveness in significantly improving detection accuracy at high IoU thresholds. Additionally, we introduce a Gaussian transform-based IoU factor during angle regression loss calculation, leading to the development of Edge-aware Skewed Bounding Box Loss (EAS Loss). The EAS loss enhances the loss gradient at the final stage of angle regression for bounding boxes, addressing the challenge of further learning when the predicted box angle closely aligns with the real target box angle. This results in increased training efficiency and better alignment between training and evaluation metrics. Experimental results show that the proposed method substantially enhances the detection accuracy of ReDet and ReBiDet models. The SA3 Network and EAS loss not only elevate the mAP of the ReBiDet model on DOTA-v1.5 to 78.85% but also effectively improve the model's mAP under high IoU threshold conditions.

Topological Polymer Networks-Enabled Mechanically Strong Polyamide-Imide Aerogel Fibers for Thermal Insulation in Harsh Environments.

Aerogel fibers have sparked substantial interest as attractive candidates for thermal insulation materials. Developing aerogel fibers with the desired porous structure, good knittability, flame retardancy, and high- and low-temperature resistance is of great significance for practical applications; however, that is very challenging, especially by using an efficient method. Herein, mechanically strong and flexible aerogel fibers with remarkable thermal insulation performance are reported, which are achieved by constructing stiff-soft topological polymer networks and a multilevel hollow porous structure. The combination of polyamide-imide (PAI) with stiff chains and polyurethane (PU) with soft chains is first found to be able to form a topological entanglement architecture. More importantly, multilevel hollow pores can be constructed synchronously through just a one-step and green wet-spinning process. The resultant PAI/PU@340 aerogel fibers show an ultrahigh breaking strength of 94.5 MPa and superelastic property with a breaking strain of 20%. Furthermore, they can be knitted into fabrics with a low thermal conductivity of 25 mW/(m·K) and exhibit attractive thermal insulation property under extremely high (300 °C) and low temperatures (-191 °C), implying them as promising candidates for next-generation thermal insulation materials.

Atf3-mediated metabolic reprogramming in hepatic macrophage orchestrates metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is regulated by complex interplay between the macrophages and surrounding cells in the liver. Here, we show that Atf3 regulates glucose-fatty acid cycle in macrophages attenuates hepatocyte steatosis, and fibrogenesis in hepatic stellate cells (HSCs). Overexpression of Atf3 in macrophages protects against the development of MASH in Western diet-fed mice, whereas Atf3 ablation has the opposite effect. Mechanistically, Atf3 improves the reduction of fatty acid oxidation induced by glucose via forkhead box O1 (FoxO1) and Cd36. Atf3 inhibits FoxO1 activity via blocking Hdac1-mediated FoxO1 deacetylation at K242, K245, and K262 and increases Zdhhc4/5-mediated CD36 palmitoylation at C3, C7, C464, and C466; furthermore, macrophage Atf3 decreases hepatocytes lipogenesis and HSCs activation via retinol binding protein 4 (Rbp4). Anti-Rbp4 can prevent MASH progression that is induced by Atf3 deficiency in macrophages. This study identifies Atf3 as a regulator of glucose-fatty acid cycle. Targeting macrophage Atf3 or Rbp4 may be a plausible therapeutic strategy for MASH.

[Effects of inhibitors of DNA repair enzymes OGG1 and MTH1 on the replication of African swine fever virus].

African swine fever virus (ASFV), as a contagious viral pathogen, is responsible for the occurrence of African swine fever (ASF), a rapidly spreading and highly lethal disease. Since ASFV was introduced into China in 2018, it has been quickly spread to many provinces, which brought great challenges to the pig industry in China. Due to the limited knowledge about the pathogenesis of ASFV, neither vaccines nor antiviral drugs are available. We have found that ASFV infection can induce oxidative stress responses in cells, and DNA repair enzymes play a key role in this process. This study employed RNA interference, RT-qPCR, Western blotting, Hemadsorption (HAD), and flow cytometry to investigate the effects of the inhibitors of DNA repair enzymes OGG1 and MTH1 on ASFV replication and evaluated the anti-ASFV effects of the inhibitors. This study provides reference for the development of anti-viral drugs.

Therapeutic strategies targeting the epidermal growth factor receptor signaling pathway in metastatic colorectal cancer.

More than 1.9 million new colorectal cancer (CRC) cases and 935000 deaths were estimated to occur worldwide in 2020, representing about one in ten cancer cases and deaths. Overall, colorectal ranks third in incidence, but second in mortality. More than half of the patients are in advanced stages at diagnosis. Treatment options are complex because of the heterogeneity of the patient population, including different molecular subtypes. Treatments have included conventional fluorouracil-based chemotherapy, targeted therapy, immunotherapy, etc. In recent years, with the development of genetic testing technology, more and more targeted drugs have been applied to the treatment of CRC, which has further prolonged the survival of metastatic CRC patients.

Rare secondary hypertension caused by compound heterozygous CYP17A1 mutations: a case report.

Background: 17α-Hydroxylase deficiency, a rare form of congenital adrenal hyperplasia, presents diagnostic and treatment challenges because of the limited number of cases reported. Case summary: This report discusses the case of a 17-year-old Chinese girl who suffered from unexplained dizziness, headaches, and high blood pressure. She had amenorrhoea during puberty and had been diagnosed with ovarian delay. Initially, she was diagnosed with hypertension and received three antihypertensive medications. However, her blood pressure remained poorly controlled. Gene sequencing revealed 17α-hydroxylase deficiency caused by compound heterozygous mutations in CYP17A1. One of the mutation sites, potentially novel, has not been reported previously. Subsequently, dexamethasone therapy was initiated, her blood pressure was controlled, and the symptoms disappeared. During the 1-year follow-up, her blood pressure remained normal, and the symptoms did not recur. Discussion: 17α-Hydroxylase deficiency is a rare cause of secondary hypertension. Despite the low prevalence, it should not be overlooked in younger patients.

Elderly patients with advanced HER2-positive breast cancer with liver metastases benefit from low dose disitamab vedotin (RC48): case series and literature review.

Currently, although some antibody-drug conjugates have been shown to be safe and effective in the treatment of drug-resistant relapsed human epidermal growth factor receptor 2 (HER2)-positive (IHC 3+ or IHC 2+/fluorescence in situ hybridization+) breast cancer, they are already approved for clinical use in China. But the clinical needs of advanced HER2-positive patients cannot be met due to adverse reactions, drug resistance, drug accessibility and other problems, thus affecting the prognosis of patients. In particular, the representation of elderly and frail patients in randomized clinical trials is significantly under-represented. We report on two elderly women with breast cancer who developed recurrent metastatic lesions after breast cancer surgery and were again confirmed HER2-positive by histopathology and immunohistochemistry. They all developed multiple metastases in the liver after second- or third-line anti-HER2 therapy. Subsequent treatment with RC48 produced good responses and tolerable adverse reactions. One patient obtained progression-free survival for more than 7 months. Based on preliminary evidence, this study shows that RC48 in HER2-positive breast cancer with liver metastases can achieve rapid remission, thereby reducing tumor load and improving patients' quality of life. In particular, RC48 has low side effects and can be well tolerated by elderly patients after dose adjustment, providing them with treatment opportunities. It needs to be further discussed in the future research.

Sex-specific and cell-specific regulation of ER stress and neuroinflammation after traumatic brain injury in juvenile mice.

Endoplasmic reticulum (ER) stress and neuroinflammation play an important role in secondary brain damage after traumatic brain injury (TBI). Due to the complex brain cytoarchitecture, multiple cell types are affected by TBI. However, cell type-specific and sex-specific responses to ER stress and neuroinflammation remain unclear. Here we investigated differential regulation of ER stress and neuroinflammatory pathways in neurons and microglia during the acute phase post-injury in a mouse model of impact acceleration TBI in both males and females. We found that TBI resulted in significant weight loss only in males, and sensorimotor impairment and depressive-like behaviors in both males and females at the acute phase post-injury. By concurrently isolating neurons and microglia from the same brain sample of the same animal, we were able to evaluate the simultaneous responses in neurons and microglia towards ER stress and neuroinflammation in both males and females. We discovered that the ER stress and anti-inflammatory responses were significantly stronger in microglia, especially in female microglia, compared with the male and female neurons. Whereas the degree of phosphorylated-tau (pTau) accumulation was significantly higher in neurons, compared with the microglia. In conclusion, TBI resulted in behavioral deficits and cell type-specific and sex-specific responses to ER stress and neuroinflammation, and abnormal protein accumulation at the acute phase after TBI in immature mice.