The 1000 Mitoses Project: A Consensus-Based International Collaborative Study on Mitotic Figures Classification.

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.

Catalytic pyrolysis and in situ carbonization of walnut shells: poly-generation and enhanced electrochemical performance of carbons.

In this study, walnut shell (WS) was used as feedstock, incorporating lithium carbonate (LC), sodium carbonate (SC), potassium carbonate (PC), and potassium hydroxide (PH) as pyrolysis catalysts and carbonization activators. A one-step method that allows catalytic pyrolysis and carbonization to be carried out consecutively under their respective optimal conditions is employed, enabling the concurrent production of high-quality pyrolysis oil, pyrolysis gas, and carbon materials from biomass conversion. The effects of LC, SC, PC, and PH on the yield and properties of products derived from WS pyrolysis as well as on the properties and performance of the resulting carbon materials were examined. The results indicated that the addition of LC, SC, PC, and PH enhanced the secondary cracking of tar, leading to increased solid and gas yields from WS. Additionally, it increased the production of phenolic compounds in bio-oil and H2 in syngas, concurrently yielding a walnut shell-based carbon material exhibiting excellent electrochemical performance. Specifically, when PC was used as an additive, the phenolic content in the pyrolysis oil increased by 27.64% compared to that without PC, reaching 74.9%, but the content of ketones, acids, aldehydes, and amines decreased. The hydrogen content increased from 2.5% (without the addition of PC) to 12.75%. The resulting carbon (WSC-PC) displayed a specific surface area of 598.6 m2 g-1 and achieved a specific capacitance of 245.18 F g-1 at a current density of 0.5 A g-1. Even after 5000 charge and discharge cycles at a current density of 2 A g-1, the capacitance retention rate remained at 98.16%. This method effectively enhances the quality of the biomass pyrolysis oil, gas, and char, contributing to the efficient and clean utilization of biomass in industrial applications.

Distributed cyber attack detection and physical fault diagnosis for a class of interconnected large-scale systems.

In this paper we focus on the distributed cyber attack detection and physical fault diagnosis problem for a class of interconnected large-scale systems (ILSSs). In the proposed scheme, apart from node measurement, edge measurement is also used to construct distributed Kalman filter to estimate the state of each subsystem. The gain matrices of Kalman filter are determined by minimizing the covariance of estimation error in the attack-free and fault-free case, which reduces the false alarm rate of cyber attack detection and physical fault diagnosis. Based on this filter, a bank of adjacent residual generators is constructed to characterize the influence of cyber attack on the edge measurement, and the Chi-square test is used to detect whether the received edge measurements are attacked. At the same time, a local residual generator is constructed for each subsystem to characterize the influence of physical faults on it, and the residual signal is evaluated by variance and directional residual, so as to make distributed fault detection and isolation of each subsystem. It is worth noting that at each step, each subsystem first performs attack detection on the received edge measurements, and then estimates its own state using the attack-free edge measurements and node measurement, which further improves the accuracy of fault detection and isolation. In addition, a sufficient condition that ensuring the mean square exponential boundedness of the estimation error is given. Finally, the proposed scheme is verified by an illustrative example.

Bimetal doped Cu-Fe-ZIF-8/g-C3N4 nanocomposites for the adsorption of tetracycline hydrochloride from water.

Bimetal doped Cu-Fe-zeolitic imidazole framework-8 (ZIF-8)/graphitic carbon nitride (GCN) (Cu-Fe-ZIF-8/GCN) nanocomposites were prepared via one-pot and ion-exchange methods. The main influencing factors, such as adsorbent concentration, TC concentration, initial pH, and coexisting ions, were evaluated in detail. Due to the suitable pore structures and the presence of multiple interactions on the surface, the nanocomposite showed a high adsorption capacity up to 932 mg g-1 for tetracycline hydrochloride (TC), outperforming ZIF-8 by 4.8 times. The adsorption kinetics and adsorption isotherm were depicted in good detail using pseudo-second-order kinetic and Langmuir models, respectively. Thermodynamic calculation revealed that the adsorption of the nanocomposite under experimental conditions was a spontaneous heat absorption process, and was primarily driven by chemisorption. After four cycles of use, the nanocomposite retained 87.2% of its initial adsorption capacity, confirming its high reusability and broad application prospects in removing tetracycline-type pollutants from wastewater.

Melatonin inhibits the formation of intraplaque neovessels in ApoE-/- mice via PPARγ- RhoA-ROCK pathway.

BACKGROUND: According to former research, the atherosclerotic plaque is thought to be aggravated by intraplaque neovessels (IPN) and intraplaque hemorrhage (IPH). Intriguingly, a lower incidence of IPH was found in plaque treated with melatonin. In this study, we attempted to investigate the impact and underlying mechanism regarding the influences of melatonin upon IPN. METHODS: A mouse model was established by subjecting the high fat diet (HFD)-fed ApoE-/- mice to tandem stenosis (TS) surgery with melatonin and GW9662, a PPARγ antagonist, being given by gavage. In vitro experiment was conducted with HUVECs exposing to according treatments of VEGF, melatonin, GW9662, or Y27632. RESULTS: Plaque and IPN were attenuated by treatment with melatonin, which was then reversed by blocking PPARγ. Western blotting results showed that melatonin increased PPARγ and decreased RhoA/ROCK signaling in carotid artery. Elevated RhoA/ROCK signaling was observed in melatonin-treated mice when PPARγ was blocked. In accordance with it, experiments using protein and mRNA from HUVECs revealed that melatonin inhibited the RhoA/ROCK signaling by enhancing PPARγ. According to in vitro study, melatonin was able to inhibit cell migration and angiogenesis, which was aborted by GW9662. Blockage of ROCK using Y27632 was able to cease the effect of GW9662 and restored the suppression on cell migration and angiogenesis by melatonin. CONCLUSIONS: Our study demonstrates that melatonin is able to curb development of plaque and IPN formation by inhibiting the migration of endothelial cells via PPARγ- RhoA-ROCK pathway. That provides a therapeutic potential for both melatonin and PPARγ agonist targeting IPN, IPH, and atherosclerotic plaque.

RBM10 regulates the tumorigenic potential of human cancer cells by modulating PPM1B and YBX1 activities.

RNA binding protein RBM10 participates in various RNA metabolism, and its decreased expression or loss of function by mutation has been identified in many human cancers. However, how its dysregulation contributes to human cancer pathogenesis remains to be determined. Here, we found that RBM10 expression was decreased in breast tumors, and breast cancer patients with low RBM10 expression presented poorer survival rates. RBM10 depletion in breast cancer cells significantly promotes the cellular proliferation and migration. We further demonstrated that RBM10 forms a triple complex with YBX1 and phosphatase 1B (PPM1B), in which PPM1B serves as the phosphatase of YBX1. RBM10 knock-down markedly attenuated association between YBX1 and PPM1B, leading to elevated levels of YBX1 phosphorylation and its nuclear translocation. Furthermore, cancer cells with RBM10 depletion had a significantly accelerated tumor growth in nude mice. Importantly, these enhanced tumorigenic phenotypes can be reversed by overexpression of PPM1B. Our findings provide the mechanistic bases for functional loss of RBM10 in promoting tumorigenicity, and are potentially useful in the development of combined therapeutic strategies for cancer patients with defective RBM10.

Lactic acid promotes nucleus pulposus cell senescence and corresponding intervertebral disc degeneration via interacting with Akt.

The accumulation of metabolites in the intervertebral disc is considered an important cause of intervertebral disc degeneration (IVDD). Lactic acid, which is a metabolite that is produced by cellular anaerobic glycolysis, has been proven to be closely associated with IVDD. However, little is known about the role of lactic acid in nucleus pulposus cells (NPCs) senescence and oxidative stress. The aim of this study was to investigate the effect of lactic acid on NPCs senescence and oxidative stress as well as the underlying mechanism. A puncture-induced disc degeneration (PIDD) model was established in rats. Metabolomics analysis revealed that lactic acid levels were significantly increased in degenerated intervertebral discs. Elimination of excessive lactic acid using a lactate oxidase (LOx)-overexpressing lentivirus alleviated the progression of IVDD. In vitro experiments showed that high concentrations of lactic acid could induce senescence and oxidative stress in NPCs. High-throughput RNA sequencing results and bioinformatic analysis demonstrated that the induction of NPCs senescence and oxidative stress by lactic acid may be related to the PI3K/Akt signaling pathway. Further study verified that high concentrations of lactic acid could induce NPCs senescence and oxidative stress by interacting with Akt and regulating its downstream Akt/p21/p27/cyclin D1 and Akt/Nrf2/HO-1 pathways. Utilizing molecular docking, site-directed mutation and microscale thermophoresis assays, we found that lactic acid could regulate Akt kinase activity by binding to the Lys39 and Leu52 residues in the PH domain of Akt. These results highlight the involvement of lactic acid in NPCs senescence and oxidative stress, and lactic acid may become a novel potential therapeutic target for the treatment of IVDD.

The activation mechanism of peroxymonosulfate and peroxydisulfate by modified hydrochar: Based on the multiple active sites formed by N and Fe.

Modified hydrochar (NHC@Fe), with multiple functional groups and transition metal oxide-containing surface, was successfully synthesized by one-step hydrothermal method. The differences in its catalytic activity for peroxymonosulfate (PMS) and peroxydisulfate (PDS) activation were studied in detail. Experimental and DFT studies showed that abundant active sites, namely, transition metals and functional groups on NHC@Fe provided multiple effective pathways for the activation of persulfate (PS). The NHC@Fe/PMS and NHC@Fe/PDS systems could degrade about 80% of tetracycline hydrochloride (TC) in 120 min and were found to be better than those modified by iron or nitrogen alone. This emphasized the advantage of N-Fe co-modification in persulfate activation. Although the Fe2+/Fe3+ cycle accelerated the activation, the activation of PMS mainly relied on Fe3+, whereas that of PDS mainly relied on Fe2+. Moreover, Fe-N, pyrrolic N, pyridine N, C-O, and O-CO groups also played a key role in the activation process, but the dominant action sites were not the same. Multiple free radicals, such as SO4•-, •OH, O2•-, and 1O2 were generated in PMS and PDS activation systems. 1O2 induced non-free radical pathway was mainly involved in the degradation of TC in both activation systems, but the generation pathway of 1O2 was more direct and rapid in the PDS system. This study provides detailed DFT models of the active sites activated by PMS and PDS and discusses the activation pathways of PMS and PDS along with the similarities and differences in ROS reaction mechanisms.

Prediction of 19F NMR chemical shifts for organic compounds with ORCA.

Accurate assignment of 19F NMR has long been a challenge, and quantum chemical methods are possible solutions. Herein we reported a scaling method for the prediction of 19F NMR chemical shift with freely available ORCA program package. Performance of 31 DFT functionals coupled with 11 basis sets were evaluated and influence of geometry optimization was also studied with five functionals coupled with three basis sets. The significance of geometry was further examined through the execution of relaxed surface scans of seven flexible compounds, and averaged shieldings of obtained conformers yielded notable improvement of the correlation between calculated isotropic shielidings and experimental chemical shifts. Utilization of the best scaling factor obtained successfully assigned of fluorine atoms in multifluorinated molecules with different conformations. The method reported here was computationally inexpensive, easily available with acceptable accuracy.

Real-time 3D shape measurement of dynamic scenes using fringe projection profilometry: lightweight NAS-optimized dual frequency deep learning approach.

Achieving real-time and high-accuracy 3D reconstruction of dynamic scenes is a fundamental challenge in many fields, including online monitoring, augmented reality, and so on. On one hand, traditional methods, such as Fourier transform profilometry (FTP) and phase-shifting profilometry (PSP), are struggling to balance measuring efficiency and accuracy. On the other hand, deep learning-based approaches, which offer the potential for improved accuracy, are hindered by large parameter amounts and complex structures less amenable to real-time requirements. To solve this problem, we proposed a network architecture search (NAS)-based method for real-time processing and 3D measurement of dynamic scenes with rate equivalent to single-shot. A NAS-optimized lightweight neural network was designed for efficient phase demodulation, while an improved dual-frequency strategy was employed coordinately for flexible absolute phase unwrapping. The experiment results demonstrate that our method can effectively perform 3D reconstruction with a reconstruction speed of 58fps, and realize high-accuracy measurement of dynamic scenes based on deep learning for what we believe to be the first time with the average RMS error of about 0.08 mm.

Association Between Temperature During Intensive Care Unit and Mortality in Patients With Acute Respiratory Distress Syndrome.

The relationship between body temperature changes and prognosis in patients with acute respiratory distress syndrome (ARDS) remains inconclusive. Our study aimed to investigate the clinical value of body temperature in the management of ARDS. Data from the Medical Information Mart for Intensive Care III database were collected. Adult patients with ARDS were enrolled and further grouped based on their temperature values in the intensive care unit. Both the maximum (temperaturemax) and minimum (temperaturemin) temperatures were used. The primary outcome was 28-day mortality rate. Polynomial regression, subgroup analysis, and logistic regression analysis were performed in the final analysis. A total of 3922 patients with ARDS were enrolled. There was a U-shaped relationship between 28-day mortality and body temperature. For patients with infection, the elevated temperaturemax (≥37.0°C) was associated with decreased mortality, with an odds ratio ranging from 0.39 to 0.49, using temperaturemax from 36.5°C to 36.9°C as reference. For patients without infection, a similar tendency was observed, but the protective effect was lost at extremely high temperatures (≥38.0°C, p < 0.05). Elevated temperaturemin (≥37.0°C) and decreased temperaturemin (<35.0°C) were associated with increased mortality, using the temperaturemin from 36.0°C to 36.9°C as a reference. Hypothermia was associated with increased mortality in patients with ARDS, while the effect of hyperthermia (≥37.0°C) on the mortality of patients with ARDS was not fully consistent in the infection and noninfection subgroups. Short-term and transient temperatures above 37.0°C would be beneficial to patients with ARDS, but extreme hyperthermia and persistent temperatures above 37.0°C should be avoided.

Screening of Potential Probiotic Lactobacillaceae and Their Improvement of Type 2 Diabetes Mellitus by Promoting PI3K/AKT Signaling Pathway in db/db Mice.

The study aimed to isolate Lactobacillaceae strains with in vitro hypoglycemic activity and probiotic properties and to determine their antidiabetic abilities in vivo. Lactiplantibacillus plantarum 22, L. plantarum 25, Limosilactobacillus fermentum 11, and L. fermentum 305 with high in vitro hypoglycemic activity were screened from 23 strains of Lactobacillaceae isolated from human feces and identified by 16S rDNA sequencing. The fasting blood glucose (FBG) of the mice was recorded weekly. After 12 weeks, liver, kidney, and pancreas tissues were stained with hematoxylin and eosin (H&E) to observe histomorphology; the inflammatory factors were assayed by Quantitative Real-time PCR; PI3K and AKT were measured by Western blot; the short-chain fatty acids (SCFAs) were determined by LC-MS/MS. Inhibitory activities of L. plantarum 22, L. plantarum 25, L. fermentum 11, and L. fermentum 305 against α-amylase were 62.29 ± 0.44%, 51.81 ± 3.65%, 58.40 ± 1.68%, and 57.48 ± 5.04%, respectively. Their inhibitory activities to α-glucosidase were 14.89 ± 0.38%, 15.32 ± 0.89%, 52.63 ± 3.07%, and 51.79 ± 1.13%, respectively. Their survival rate after simulated gastrointestinal test were 12.42 ± 2.84%, 9.10 ± 1.12%, 5.86 ± 0.52%, and 8.82 ± 2.50% and their adhesion rates to Caco-2 cell were 6.09 ± 0.39%, 6.37 ± 0.28%, 6.94 ± 0.27%, and 6.91 ± 0.11%, respectively. The orthogonal tests of bacterial powders of the four strains showed that the maximum inhibitory activities to α-amylase and α-glucosidase were 93.18 ± 1.19% and 75.33 ± 2.89%, respectively. The results showed that the mixture of Lactobacillaceae could lower FBG, reduce inflammation, and liver, kidney, and pancreas damage, promote PI3K/AKT signaling pathway, and increase the content of SCFAs. The combination of L. plantarum 22, L. plantarum 25, L. fermentum 11, and L. fermentum 305 can potentially improve type 2 diabetes mellitus (T2DM).

Volatility Parametrization of Low-Volatile Components of Ambient Organic Aerosols Based on Molecular Formulas.

Evaluating the volatility of organic compounds based solely on their molecular formulas would avoid tough demands in deriving molecular structures. Here, we deployed an iodide-adduct Long Time-of-Flight Chemical Ionization Mass Spectrometry (LToF-CIMS) combined with a Filter Inlet for Gases and AEROsols (FIGAERO) to investigate molecular formulas and thermograms of organic compounds on ambient particulate samples collected in the summer of 2021 in a suburban site of Shanghai and to estimate saturation vapor pressures of low- and semivolatile components of ambient organic aerosols. Then, a hierarchical cluster analysis and a subsequent classification of obtained clusters by similarity calculation were applied to the measured data set of molecular formulas and saturation vapor pressures of organic aerosols with at least a 2/3 appearance frequency, together with a similar data set collected at a rural site in the Beijing-Tianjin-Hebei region during the winter of 2018 (Ren et al., 2018), to classify all compounds into multiple groups. For each group of compounds, parametrizations between volatility and elemental composition were derived, and then relationships between each group of parameters and the mean O:C were established to achieve a volatility-molecular formula parametrization with the O:C as a key input. Statistical comparison of estimated volatilities of low-volatile organic compounds shows a much better performance of our parametrization than previous molecular formula-based ones.

The Moderating Effects of Trust and Felt Trust on the Nonlinear Relationship Between Compulsory Citizenship Behavior and Counterproductive Work Behavior.

Purpose: This study explored the J-shaped effect of compulsory citizenship behavior on counterproductive work behavior of new generation employees, as well as the separate and joint moderating effects of trust and felt trust on the J-shaped relationship between compulsory citizenship behavior and counterproductive work behavior. Methods: Three waves of data were collected from 659 new generation employees in China. A self-report method was used to measure compulsory citizenship behavior, counterproductive work behavior, trust and felt trust. Then, based on the cognitive appraisal theory of stress and social information processing theory, a nonlinear model was constructed and tested. Results: (1) Compulsory citizenship behavior had a J-shaped effect on job performance. That is, when the compulsory citizenship behavior level was lower, the effect of compulsory citizenship behavior on counterproductive work behavior was not significant; but when it increased to medium and higher levels, the effect was significant and stronger. (2) The moderating effect of trust (employees' perceived trust in leader) or felt trust (employees' perception of being trusted by leader) was significant. That is, when trust or felt trust was lower, the J-shaped effect was stronger; conversely, the J-shaped effect was weak. (3) The joint moderating effect of trust and felt trust was significant. That is, when trust was high, the moderation effect of felt trust was significant; conversely, the moderation effect of felt trust was not significant. Conclusion: The results identify the nonlinear effect of compulsory citizenship behavior through exploring the J-shaped effect of compulsory citizenship behavior on counterproductive work behavior and the boundary conditions in the nonlinear relationship. Meanwhile, the study provide implications for organizations regarding how to manage employees' work behavior.

Embryonic 6:2 FTOH exposure causes reproductive toxicity by disrupting the formation of the blood-testis barrier in offspring mice.

Previous studies have revealed nephrotoxicity, hepatotoxicity, subchronic developmental and reproductive toxicity in rats exposed to fluorotelomer alcohol (FTOH). However, the effects of embryonic 6:2 FTOH exposure on the reproductive system of offspring mice remain unclear. The purpose of this study is to explore the reproductive toxic effects of embryonic 6:2 FTOH exposure on offspring male mice and the related molecular mechanisms. Therefore, the pregnant mice were given corn oil or 6:2 FTOH by gavage from gestational days 12.5-21.5. The results demonstrated that embryonic 6:2 FTOH exposure resulted in disrupted testicular structure, low expression of tight junction protein between Sertoli cells (SCs), impaired blood-testis barrier (BTB) formation and maturation, reduced sperm viability and increased malformation, and induced testicular inflammation in the offspring of mice. Further in vitro studies showed that 6:2 FTOH treatment upregulated MMP-8 expression by activating AKT/NF-κB signaling pathway, which in turn enhanced occludin cleavage leading to the disruption of SCs barrier integrity. In summary, this study demonstrated that 6:2 FTOH exposure caused reproductive dysfunction in male offspring through disruption of BTB, which provided new insights into the effects of 6:2 FTOH exposure on the offspring.

Local Axial Scale-Attention for Universal Lesion Detection.

Universal lesion detection (ULD) in computed tomography (CT) images is an important and challenging prerequisite for computer-aided diagnosis (CAD) to find abnormal tissue, such as tumors of lymph nodes, liver tumors, and lymphadenopathy. The key challenge is that lesions have a tiny size and high similarity with non-lesions, which can easily lead to high false positives. Specifically , non-lesions are nearby normal anatomy that include the bowel, vasculature, and mesentery, which decrease the conspicuity of small lesions since they are often hard to differentiate. In this study, we present a novel scale-attention module that enhances feature discrimination between lesion and non-lesion regions by utilizing the domain knowledge of radiologists to reduce false positives effectively. Inspired by the domain knowledge that radiologists tend to divide each CT image into multiple areas, then detect lesions in these smaller areas separately, a local axial scale-attention (LASA) module is proposed to re-weight each pixel in a feature map by aggregating local features from multiple scales adaptively. In addition, to keep the same weight, a combination of axial pixels in the height- and width-axes is designed, attached with position embedding. The model can be used in CNNs easily and flexibly. We test our method on the DeepLesion dataset. The sensitivities at 0.5, 1, 2, 4, 8, and 16 false positives (FPs) per image and average sensitivity at [0.5, 1, 2, 4] are calculated to evaluate the accuracy. The sensitivities are 78.30%, 84.96%, 89.86%, 93.14%, 95.36%, and 95.54% at 0.5, 1, 2, 4, 8, and 16 FPs per image; the average sensitivity is 86.56%, outperforming the former methods. The proposed method enhances feature discrimination between lesion and non-lesion regions by adding LASA modules. These encouraging results illustrate the potential advantage of exploiting the domain knowledge for lesion detection.

A Bibliometric Mapping Study of the Literature on Oral Health-related Quality of Life.

BACKGROUND: Oral health is an indispensable component of overall health, and oral health status significantly influences people's physical, mental, and social well-being. Oral health-related quality of life (OHRQoL), an important and widely used dental patient-reported outcome (dPRO), is attracting more and more researchers' attention and interest. This study aimed to analyze and map the existing scientific literature regarding OHRQoL through a bibliometric approach, including a summary of the characteristics of OHRQoL-related publications, the identification of prolific entities, high-frequency keywords analysis, and research trend analysis via periodic high-impact keywords. METHODS: A literature search was conducted in the Web of Science Core Collection to collect OHRQoL-related original research and review articles. After examination and deduplication, the following bibliometric information was extracted from each article: title, abstract, keywords, authors, affiliations, geographic origin (countries/regions), year of publication, journal name, and references. Various scientometric mapping tools including Microsoft Office spreadsheet, VOSviewer, Biblioshiny R-package software, and Scimago Graphica were used to analyze basic bibliometric parameters, leading producers, high-impact keywords, and research trends. RESULTS: A total of 3324 OHRQoL-related articles (3119 original research articles and 205 review papers) were collected, which received 65,704 citations. A total of 9950 authors from 2429 organizations contributed to this body of research. Prolific authors from Europe, USA, Brazil, New Zealand, China, and Canada were identified, and they also centered collaboration clusters in the co-author network. Community Dentistry and Oral Epidemiology was the most prolific journal. Twenty-one keywords with more than 200 occurrences, and 23 keywords with more than 150 occurrences, were identified for publications of 1994-2021 and 2012-2021, respectively. Keyword analysis revealed hot topics such as instrument development and validation, studies targeting children and adolescents, as well as clinical studies in operative dentistry, implantology, orthodontics, and community dentistry. Oral Health Impact Profile is the most commonly used instrument in OHRQoL-related research. CONCLUSIONS: OHRQoL is an impactful topic in dental health care as it is not only useful in dental research and patient-centered clinical outcome measures but also provides valuable guidance in dental public health administration and policy making. OHRQoL-related research presents a dynamic landscape and is expected to continue presenting high productivity and broad application in the future.

Knockdown of let-7b in leukemia associated macrophages inhibit acute myeloid leukemia progression.

Macrophages, critical components of bone marrow microenvironment, are reported to be remodeled into leukemia-associated macrophages (LAMs) in leukemic microenvironment where they contribute to leukemia development, characterized as M2 macrophages with pro-tumor effects. However, how leukemic microenvironment transforms macrophages into LAMs remains unknown. Here, we analyzed the clinical relevance of LAMs and profiled their RNA-Seq from acute myeloid leukemia (AML) patients with complete remission (CR) after induction treatment and refractory AML patients. Our results showed that the proportion and number of LAMs in refractory AML patients was higher than that in CR patients and LAM was a poor prognostic factor of AML patients. Furthermore, let-7b was a potentially aberrant gene in LAMs contributed to M2-subtype characteristics. Knockdown of let-7b in LAMs could inhibit the development of AML by repolarizing LAMs toward M1-subtype characteristics through the activation of Toll-like receptor and NF-κB pathway. Our study provides insight for future LAM-based immunotherapy strategies for AML.