Implementation factors of tuberculosis control program in primary healthcare settings in China: a mixed-methods using the Consolidated Framework for Implementation Research framework.

BACKGROUND: Tuberculosis (TB) is a major cause of death worldwide, and Chinese TB burden ranked the second globally. Chinese primary healthcare (PHC) sectors implement the TB Control Program (TCP) to improve active case finding, referral, treatment adherence, and health education. This study aimed to identify barriers and enablers of TCP implementation in high TB burden regions of West China. METHODS: We conducted a representative study using mixed-methods in 28 counties or districts in Chongqing Municipality and Guizhou Province of West China from October 2021 to May 2022. Questionnaire surveys and semi-structured in-depth interviews were conducted with 2720 TB healthcare workers (HCWs) and 20 interviewees in PHC sectors. Descriptive statistical analysis was used to investigate TB HCWs' characteristics, and path analysis model was utilized to analyze the impact of associated factors on TCP implementation. Thematic framework analysis was developed with the guide of the adapted Consolidated Framework for Implementation Research (CFIR) on factors of TCP implementation. RESULTS: This study found that 84.6% and 94.1% of community and village HCWs had low professional titles. Based on the results of multiple regression analysis and correlation analysis, lower TB core knowledge scores (-0.09) were identified as barriers for TCP implementation in community PHC sectors, and low working satisfaction (-0.17) and low working willingness (-0.10) are barriers for TPC implementation in village PHC sectors. The results of in-depth interviews reported barriers in all domains and enablers in four domains of CFIR. There were identified 19 CFIR constructs associated with TCP implementation, including 22 barriers such as HCWs' heavy workload, and 12 enablers such as HCWs' passion towards TCP planning. CONCLUSIONS: With the guide of the CFIR framework, complex factors (barriers and enablers) of TCP implementation in PHC sectors of West China were explored, which provided important evidences to promote TB program in high TB burden regions. Further implementation studies to translate those factors into implementation strategies are urgent needed.

Relationship between frailty and depressive symptoms in older adults: role of activities of daily living and sleep duration.

Introduction: Previous studies have demonstrated that frailty is associated with depressive symptoms among older people and significantly increase the risk of difficulty in activities of daily living (ADL). However, uncertainties remain regarding the mechanisms behind such relationship. The aim of this study was to investigate the mediating effect of ADL in the relationship between frailty and depressive symptoms among older adults in China, and to explore to what extend sleep duration moderated the association between ADL and depressive symptoms. Methods: In this study, we carried out cross-sectional descriptive analysis and 1,429 participants were included in the analysis. A survey was conducted using questionnaires and instruments measuring frailty, depressive symptoms, ADL and sleep duration. Bootstrap analyses served to explore the impact of ADL in mediating frailty and depressed symptoms, as well as the effect of sleep duration in moderating ADL and depressive symptoms. Results: Compared to the robust group, the mediating effects of ADL between frailty and depressive symptoms were significant in the prefrail group and the frail group. The interaction term between sleep duration and ADL was significantly presented in the regression on depressive symptoms. Specifically, the Johnson-Neyman technique determined a range from 8.31 to 10.19 h for sleep duration, within which the detrimental effect of frailty on depressive symptoms was offset. Conclusion: Sleep duration moderated the indirect effect of ADL on the association between frailty and depressive symptoms. This provides support for unraveling the underlying mechanism of the association between frailty and depressive symptoms. Encouraging older adults to enhance ADL and obtain appropriate sleep duration might improve depressive symptoms for older adults with frailty and prefrailty.

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Alpha-ketoglutarate (α-KG), an endogenous intermediate of the tricarboxylic acid cycle, is involved in a variety of cellular metabolic pathways. It serves as an energy donor, a precursor of amino acid biosynthesis, and an epigenetic regulator. α-KG plays physiological functions in immune regulation, oxidative stress, and anti-aging as well. In recent years, it has been reported that the level of α-KG in the body is closely associated with metabolic syndrome, including obesity, hyperglycemia, and other pathological factors. Exogenous supplementation of α-KG improves obesity, blood glucose levels, and cardiovascular disease risks associated with metabolic syndrome. Furthermore, α-KG regulates the common pathological mechanisms of metabolic syndrome, suggesting the potential application prospect of α-KG in metabolic syndrome. In order to provide a theoretical basis for further exploration of the application of α-KG in metabolic syndrome, we focused on α-KG and metabolic syndrome in this article and summarized the latest research progress in the role of α-KG in improving the pathological condition and disease progression of metabolic syndrome. For the next step, researchers may focus on the co-pathogenesis of metabolic syndrome and investigate whether α-KG can be used to achieve the therapeutic goal of "homotherapy for heteropathy" in the treatment of metabolic syndrome.

Bionic Potassium Ion Channel in Live Cells Repairs Cardiomyocyte Function.

The disturbance of potassium current in cardiac myocytes caused by potassium channel dysfunction can lead to cardiac electrophysiological disorders, resulting in associated cardiovascular diseases. The emergence of artificial potassium ion channels opens up a way to replace dysfunctional natural ion channels and cure related diseases. However, bionic potassium ion channels have not been introduced into living cells to regulate cell function. One of the biggest challenges is that when the bionic channel fuses with the cell, it is difficult to control the inserting angle of the bionic potassium channel to ensure its penetration of the entire cell membrane. In nature, the extracellular vesicles can fuse with living cells with a completely preserved structure of vesicle protein. Inspired by this, we developed a vesicle fusion-based bionic porin (VFBP), which integrates bionic potassium ion channels into cardiomyocytes to replace damaged potassium ion channels. Theoretical and experimental results show that the inserted bionic ion channels have a potassium ion transport rate comparable to that of natural ion channels, which can restore the potassium ion outflow in cardiomyocytes and repair the abnormal action potential and excitation-contraction coupling of cardiomyocytes. Therefore, the bionic potassium ion channel system based on membrane fusion is expected to become the research object in many fields such as ultrafast ion transport, transmembrane delivery, and channelopathies treatment.

Associations of Blood and Urinary Heavy Metals with Stress Urinary Incontinence Risk Among Adults in NHANES, 2003-2018.

People come into contact with heavy metals in various ways in their daily lives. Accumulating evidence shows that toxic metal exposure is hazardous to human health. However, limited information is available regarding the impact of metal mixtures on stress urinary incontinence (SUI). Therefore, we used data from 10,622 adults from the 2003-2018 National Health and Nutrition Examination Survey (NHANES) to investigate the independent and comprehensive association between heavy metal co-exposure and SUI. Among them, 2455 (23.1%) had been diagnosed with SUI, while the rest had no SUI. We evaluated the independent and combined associations of 3 blood metals and 10 urinary metals with SUI risk, along with subgroup analyses according to age and gender. In the single-exposure model, blood cadmium (Cd), lead (Pb), mercury (Hg), urinary Cd, Pb, and cesium (Cs) were found to be positively connected with SUI risk. Moreover, weighted quantile sum (WQS) regression, quantile-based g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) consistently demonstrated blood and urinary metal-mixed exposure were positively associated with the risk of SUI, and emphasized that blood Pb and Cd and urinary Cd and Cs were the main positive drivers, respectively. This association was more pronounced in the young and middle-aged group (20-59 years old) and the female group. Nevertheless, further research is necessary to validate these significant findings.

Effects of four types of natural bait on water quality, feeding, growth, and antioxidant enzyme activity of Monopterus albus in a recirculating aquaculture system.

Monopterus albus is one of China's renowned and superior aquaculture species, with its seedlings mainly sourced from wild capture. One of the bottlenecks in M. albus aquaculture is the high mortality rate and low feeding initiation rate from stocking wild fry to the initiation of feeding. In production, trash fish is commonly used to wean M. albus juveniles onto feeding. In this study, we introduced three other natural feeds, earthworms (EW), yellow mealworms (YMW), and fly maggots (FM), with frozen trash fish (TF) serving as the control group, to evaluate the effects of these four natural feeds on the survival rate, feeding initiation, antioxidant enzymes activity, and body composition of M. albus juveniles under recirculating water aquaculture conditions. The experiment comprised four treatments, each with three replicates. Each replicate consisted of stocking 150 M. albus juveniles weighing 10.02 ± 0.89 g in size, raised for 5 weeks. The survival rate of the YMW group was 73.33%-85.33%, which was significantly higher than that of the other three bait groups (p < 0.05). The four bait groups showed no significant differences in final body weight and specific growth rate (SGR) (p > 0.05). The EW group showed the highest final body weight, with an average SGR of 2.73, whereas the YMW group had an average SGR of 1.87. The average daily feeding amount was significantly higher in EW and YMW groups than in the other two groups (p < 0.05). The percentage of feeding amount to fish weight in the EW group reached 7.3% in the fifth week. After 5 weeks of cultivation, NO2 --N content was significantly higher in the waters of the TF and EW groups than in the waters of the FM and YMW groups (p < 0.05), there was no significant difference in TAN content among the treatment groups (p > 0.05). Liver malondialdehyde content was significantly higher in the TF group than in the other bait groups (p < 0.05). GSH-Px activity was significantly higher in the EW group than in the FM group and YMW group. No significant differences in SOD and CAT activity and T-AOC were observed among the bait groups (p > 0.05). The increase in crude protein content was significantly higher in the TF group than in the FM group, but the increase in crude ash content was significantly lower in the TFgroup. In conclusion, Tenebrio molitor could potentially serve as one of the alternative feeds during the initial stages of M. albus juveniles stocking.

An Integrated LSTM-Rule-Based Fusion Method for the Localization of Intelligent Vehicles in a Complex Environment.

To improve the accuracy and robustness of autonomous vehicle localization in a complex environment, this paper proposes a multi-source fusion localization method that integrates GPS, laser SLAM, and an odometer model. Firstly, fuzzy rules are constructed to accurately analyze the in-vehicle localization deviation and confidence factor to improve the initial fusion localization accuracy. Then, an odometer model for obtaining the projected localization trajectory is constructed. Considering the high accuracy of the odometer's projected trajectory within a short distance, we used the shape of the projected localization trajectory to inhibit the initial fusion localization noise and used trajectory matching to obtain an accurate localization. Finally, the Dual-LSTM network is constructed to predict the localization and build an electronic fence to guarantee the safety of the vehicle while also guaranteeing the updating of short-distance localization information of the vehicle when the above-mentioned fusion localization is unreliable. Under the limited arithmetic condition of the vehicle platform, accurate and reliable localization is realized in a complex environment. The proposed method was verified by long-time operation on the real vehicle platform, and compared with the EKF fusion localization method, the average root mean square error of localization was reduced by 66%, reaching centimeter-level localization accuracy.

Effects of dietary melatonin supplementation on growth performance and intestinal health of rice field eel (Monopterus albus).

The objective was to assess the impact of melatonin supplementation on the growth performance and intestinal health of rice field eel, Monopterus albus. Three hundred and sixty fish (28.46 ± 0.24 g) were fed five diets supplemented with melatonin of 0, 30, 60, 120, and 240 mg/kg for 70 days. The study found that the variables FBW, WGR, SGR, and FCR exhibited a statistically significant quadratic relationship (P < 0.05) with the dietary melatonin concentrations, and the highest FBW, WGR and SGR as well as lowest FCR were observed in the 120 mg/kg melatonin group, digestive enzymes activities (such as amylase, trypsin, and lipase) also had significant quadratic relationship (P < 0.05), and the highest intestinal villus height and goblet cells were found in the 120 mg/kg diet (P < 0.01), melatonin in diets significantly increased SOD and CAT activities in serum, up-regulated the expression of anti-inflammatory factors (IL-10) and tight junction protein (ZO-1), and down-regulated the expression of pro-inflammatory factors (IL-1ß, IL-8, IL-15, and TNF-α) in the gut, dietary melatonin improved the intestinal microflora compositions, in the group that supplementation a dosage of 120 mg/kg, there was a noticeable rise in the abundance of Firmicutes and the ratio of Firmicutes/Bacteroidota, compared with control group (P < 0.1). Conclusively, dietary supplementation of melatonin promoted growth performance, enhanced intestinal immune capacity and serum antioxidant level, and improved intestinal morphology properties and intestinal flora composition in M. albus. In conclusion, based on quadratic broken-line regression analysis of WGR and FCR, the optimal concentration of melatonin to be supplied is predicted to be 146-148 mg/kg.

Pseudo-Siamese network combined with label-free Raman spectroscopy for the quantification of mixed trace amounts of antibiotics in human milk: A feasibility study.

The utilization of antibiotics is prevalent among lactating mothers. Hence, the rapid determination of trace amounts of antibiotics in human milk is crucial for ensuring the healthy development of infants. In this study, we constructed a human milk system containing residual doxycycline (DXC) and/or tetracycline (TC). Machine learning models and clustering algorithms were applied to classify and predict deficient concentrations of single and mixed antibiotics via label-free SERS spectra. The experimental results demonstrate that the CNN model has a recognition accuracy of 98.85% across optimal hyperparameter combinations. Furthermore, we employed Independent Component Analysis (ICA) and the pseudo-Siamese Convolutional Neural Network (pSCNN) to quantify the ratios of individual antibiotics in mixed human milk samples. Integrating the SERS technique with machine learning algorithms shows significant potential for rapid discrimination and precise quantification of single and mixed antibiotics at deficient concentrations in human milk.

Defect Regulation Strategy of Porous Persistent Phosphors for Multiple and Dynamic Information Encryption.

Optical encryption technologies based on persistent luminescence material have currently drawn increasing attention due to the distinctive and long-lived optical properties, which enable multi-dimensional and dynamic optical information encryption to improve the security level. However, the controlled synthesis of persistent phosphors remains largely unexplored and it is still a great challenge to regulate the structure for optical properties optimization, which inevitably sets significant limitations on the practical application of persistent luminescent materials. Herein, a controlled synthesis method is proposed based on defect structure regulation and a series of porous persistent phosphors is obtained with different luminous intensities, lifetime, and wavelengths. By simply using diverse templates during the sol-gel process, the oxygen vacancy defects structures are successfully regulated to improve the optical properties. Additionally, the obtained series of porous Al2O3 are utilized for multi-color and dynamic optical information encryption to increase the security level. Overall, the proposed defect regulation strategy in this work is expected to provide a general and facile method for optimizing the optical properties of persistent luminescent materials, paving new ways for broadening their applications in multi-dimensional and dynamic information encryption.

Biochemical, Histological, and Transcriptomic Analyses Reveal Underlying Differences in Flesh Quality between Wild and Farmed Ricefield Eel (Monopterus albus).

The present study aimed to systematically investigate the underlying differences in flesh quality between wild and farmed Monopterus albus. Fifteen healthy M. albus per group with an average body weight of 45 g were sampled to analyze muscle parameters by biochemical indicators, histomorphology, and molecular biology. Compared with the wild fish, the farmed M. albus in flesh had lower crude protein, collagen, lysine, histidine, total amino acids, SFA, n-3 PUFA contents, and n-3/n-6 ratio (p < 0.05), and higher moisture, crude lipid, crude ash, MUFA, n-6PUFA, and total PUFA contents (p < 0.05). The thawing loss, drip loss, steaming loss, and boiling loss in the farmed group were significantly higher, and hardness, springiness, cohesiveness, gumminess, chewiness, and resilience were significantly lower than those in the wild group (p < 0.05). In addition, higher muscle fiber density and lower muscle fiber diameter were observed in wild M. albus (p < 0.05). In muscle transcriptome profiling, differentially expressed genes and enriched pathways are primarily associated with muscle development, protein synthesis, catabolism, lipid metabolism, and immunity. To the best of our knowledge, this is the first investigation that compares the flesh quality between wild and farmed M. albus in terms of biochemistry, histology, and molecular biology levels. Overall, wild M. albus had a higher nutritional value and texture quality than farmed M. albus.

Dendrobium officinale flos water extract ameliorates ethanol-induced acute gastric mucosal injury via inhibiting oxidative stress and inflammation.

BACKGROUND: Dendrobium officinale flos (DOF), a novel food raw material, is used in Chinese folk medicine to nourish the stomach. However, there is still no available study to evaluate the effects of DOF on animal models of acute gastric injury and its mechanism by modern pharmacological research. RESULTS: Herein, we characterized the major components of an aqueous extract of DOF and assessed its potential ameliorative effects in a rat model of acute gastric mucosal injury. The DOF water extract showed significant protective effects on the gastric mucosa and exhibited excellent antioxidant and anti-inflammatory activities. Acute gastric injury rat models induced by ethanol (6 mL kg-1) were pretreated with different doses of DOF water extract (50-100 mg kg-1 day-1), and the biological effects of DOF extract in gastric tissues were evaluated. DOF extract alleviated the symptoms of ethanol-stimulated acute gastric mucosal injury, as evidenced by a significant reduction in gastric injury index and the degree of gastric pathological changes. Additionally, treatment with DOF extract upregulated mucin expression in the gastric mucosa, attenuated oxidative stress, decreased the release of inflammatory mediators (TNF-α, IL-6), suppressed the expression of key proinflammatory enzymes (COX-2 and iNOS), reduced the phosphorylation of p38 MAPK and p65 NF-κB and increased the level of PGE2 in gastric tissues. CONCLUSION: DOF exerts protective effects against ethanol-induced acute gastric mucosal injury, mainly by inhibiting inflammation and oxidative stress. © 2024 Society of Chemical Industry.

Comparative studies on the intestinal health of wild and cultured ricefield eel (Monopterus albus).

Fish intestinal health under intensive aquaculture mode plays an important role in growth, development, and immune function. The present study was aimed to systematically investigate the differences of intestinal health between wild and cultured Monopterus albus by biochemical parameters, histomorphology, and molecular biology. A total of 15 healthy M. albus per group, with an average body weight of 45 g, were sampled to analyze intestinal health parameters. Compared with wild fish, the cultured M. albus in the foregut had lower trypsin, lipase, SOD, CAT, T-AOC, and GSH-Px activities (P < 0.05) and higher amylase activity and MDA content (P < 0.05). The villus circumference and goblet cells in the cultured group were significantly lower than those in the wild group (P < 0.05). In addition, the cultured fish showed lower relative expression levels of occludin, zo-1, zo-2, claudin-12, claudin-15, mucin5, mucin15, lysozyme, complement 3, il-10, tgf-ß1, tgf-ß2, and tgf-ß3 (P < 0.05) and higher il-1ß, il-6, il-8, tnf-a, and ifnγ mRNA expressions than those of wild fish (P < 0.05). In terms of gut microbiota, the cultured group at the phylum level displayed higher percentages of Chlamydiae and Spirochaetes and lower percentages of Firmicutes, Bacteroidetes, Actinobacteria, Cyanobacteria, and Verrucomicrobia compared to the wild group (P < 0.05). At the genus level, higher abundances of Pseudomonadaceae_Pseudomonas and Spironema and lower abundances of Lactococcus and Cetobacterium were observed in the cultured group than in the wild group (P < 0.05). To our knowledge, this is the first investigation of the intestinal health status between wild and cultured M. albus in terms of biochemistry, histology, and molecular biology levels. Overall, the present study showed significant differences in intestinal health between wild and cultured M. albus and the main manifestations that wild M. albus had higher intestinal digestion, antioxidant capacity, and intestinal barrier functions than cultured M. albus. These results would provide theoretical basis for the subsequent upgrading of healthy aquaculture technology and nutrient regulation of intestinal health of cultured M. albus.

Enhancing higher-order modal response in multifrequency atomic force microscopy with a coupled cantilever system.

Multifrequency atomic force microscopy (AFM) utilizes the multimode operation of cantilevers to achieve rapid high-resolution imaging and extract multiple properties. However, the higher-order modal response of traditional rectangular cantilever is weaker in air, which affects the sensitivity of multifrequency AFM detection. To address this issue, we previously proposed a bridge/cantilever coupled system model to enhance the higher-order modal response of the cantilever. This model is simpler and less costly than other enhancement methods, making it easier to be widely used. However, previous studies were limited to theoretical analysis and preliminary simulations regarding ideal conditions. In this paper, we undertake a more comprehensive investigation of the coupled system, taking into account the influence of probe and excitation surface sizes on the modal response. To facilitate the exploration of the effectiveness and optimal conditions for the coupled system in practical applications, a macroscale experimental platform is established. By conducting finite element analysis and experiments, we compare the performance of the coupled system with that of traditional cantilevers and quantify the enhancement in higher-order modal response. Also, the optimal conditions for the enhancement of macroscale cantilever modal response are explored. Additionally, we also supplement the characteristics of this model, including increasing the modal frequency of the original cantilever and generating additional resonance peaks, demonstrating the significant potential of the coupled system in various fields of AFM.

Identification of chronic non-atrophic gastritis and intestinal metaplasia stages in the Correa's cascade through machine learning analyses of SERS spectral signature of non-invasively-collected human gastric fluid samples.

The progression of gastric cancer involves a complex multi-stage process, with gastroscopy and biopsy being the standard procedures for diagnosing gastric diseases. This study introduces an innovative non-invasive approach to differentiate gastric disease stage using gastric fluid samples through machine-learning-assisted surface-enhanced Raman spectroscopy (SERS). This method effectively identifies different stages of gastric lesions. The XGBoost algorithm demonstrates the highest accuracy of 96.88% and 91.67%, respectively, in distinguishing chronic non-atrophic gastritis from intestinal metaplasia and different subtypes of gastritis (mild, moderate, and severe). Through blinded testing validation, the model can achieve more than 80% accuracy. These findings offer new possibilities for rapid, cost-effective, and minimally invasive diagnosis of gastric diseases.

Application value of MRI-guided wire localization to the non-palpable breast lesions only shown in Breast MRI.

Introduction: Magnetic resonance imaging (MRI)-guided wire localization can be applied to assist to remove suspected breast lesions accurately. This study aimed to evaluate the clinical application value of this technique in Chinese women. Methods: A total of 126 patients (131 lesions) who had underwent such technique in our hospital from April 2017 to June 2023 were enrolled. 1.5T MRI system and a wire localization device were used. Image characteristics, clinical features and postoperative pathology were collected and analyzed. Results: All of 126 patients (131 lesions) were successfully localized by MRI and excised for biopsy. There were 39 malignant lesions (29.77%) and 92 benign lesions (70.23%). There was no significant correlation between the morphology of DCE-MRI and the ratio of malignant lesions (P=0.763), while there was a statistical correlation between the BPE, TIC curve and the malignancy rate (P<0.05). All the lesions were assessed according to BI-RADS category of MRI (C4A=77, C4B=40, C4C=12, C5=2). The malignancy rates were as follows: 16.88% for 4A lesions (13/77), 37.50% for 4B lesions (15/40), 75.00% for 4C lesions (9/12) and 100% for 5 lesions (2/2). There was a significant correlation between the BI-RADS category and the incidence of benign-to-malignant lesions (P<0.001). Conclusion: MRI-guided wire localization can assist to remove suspected breast lesions early, safely and accurately. This technique makes up for the deficiency of X-ray and ultrasound, improves the accuracy of diagnosis and resection therapy in intraductal carcinoma and early invasive carcinoma, and helps to improve the the prognosis of breast cancer.

Laser-Induced Controllable Porosity in Additive Manufacturing Boosts Efficiency of Electrocatalytic Water Splitting.

In laser-based additive manufacturing (AM), porosity and unmelted metal powder are typically considered undesirable and harmful. Nevertheless in this work, precisely controlling laser parameters during printing can intentionally introduce controllable porosity, yielding a porous electrode with enhanced catalytic activity for the oxygen evolution reaction (OER). This study demonstrates that deliberate introduction of porosity, typically considered a defect, leads to improved gas molecule desorption, enhanced mass transfer, and increased catalytically active sites. The optimized P-93% electrode displays superior OER performance with an overpotential of 270 mV at 20 mA cm-2. Furthermore, it exhibits remarkable long-term stability, operating continuously for over 1000 h at 10 mA cm-2 and more than 500 h at 500 mA cm-2. This study not only provides a straightforward and mass-producible method for efficient, binder-free OER catalysts but also, if optimized, underscores the potential of laser-based AM driven defect engineering as a promising strategy for industrial water splitting.

NMR chemical shift assignment of Drosophila odorant binding protein 44a in complex with 8(Z)-eicosenoic acid.

The odorant binding protein, OBP44a is one of the most abundant proteins expressed in the brain of the developing fruit fly Drosophila melanogaster. Its cellular function has not yet been determined. The OBP family of proteins is well established to recognize hydrophobic molecules. In this study, NMR is employed to structurally characterize OBP44a. NMR chemical shift perturbation measurements confirm that OBP44a binds to fatty acids. Complete assignments of the backbone chemical shifts and secondary chemical shift analysis demonstrate that the apo state of OBP44a is comprised of six α-helices. Upon binding 8(Z)-eicosenoic acid (8(Z)-C20:1), the OBP44a C-terminal region undergoes a conformational change, from unstructured to α-helical. In addition to C-terminal restructuring upon ligand binding, some hydrophobic residues show dramatic chemical shift changes. Surprisingly, several charged residues are also strongly affected by lipid binding. Some of these residues could represent key structural features that OBP44a relies on to perform its cellular function. The NMR chemical shift assignment is the first step towards characterizing the structure of OBP44a and how specific residues might play a role in lipid binding and release. This information will be important in deciphering the biological function of OBP44a during fly brain development.

Inhibition of METTL3 Alleviates NLRP3 Inflammasome Activation via Increasing Ubiquitination of NEK7.

N6-methyladenosine (m6A) modification, installed by METTL3-METTL14 complex, is abundant and critical in eukaryotic mRNA. However, its role in oral mucosal immunity remains ambiguous. Periodontitis is a special but prevalent infectious disease characterized as hyperinflammation of oral mucosa and bone resorption. Here, it is reported that genetic deletion of Mettl3 alleviates periodontal destruction via suppressing NLRP3 inflammasome activation. Mechanistically, the stability of TNFAIP3 (also known as A20) transcript is significantly attenuated upon m6A modification. When silencing METTL3, accumulated TNFAIP3 functioning as a ubiquitin-editing enzyme facilitates the ubiquitination of NEK7 [NIMA (never in mitosis gene a)-related kinase 7], and subsequently impairs NLRP3 inflammasome assembly. Furtherly, Coptisine chloride, a natural small-molecule, is discovered as a novel METTL3 inhibitor and performs therapeutic effect on periodontitis. The study unveils a previously unknown pathogenic mechanism of METTL3-mediated m6A modifications in periodontitis and indicates METTL3 as a potential therapeutic target.

KAT7 serves as an oncogenic gene and regulates CCL3 expression via STAT1 signaling in osteosarcoma.

Osteosarcoma, considered as the primary cause of malignant bone tumors in children, necessitates novel therapeutic strategies to enhance overall survival rates. KAT7, a histone acetyltransferase, exerts pivotal functions in gene transcription and immune modulation. In light of this, our study identified a significant upregulation of KAT7 in the mRNA and protein levels in human osteosarcoma, boosting cell proliferation in vivo and in vitro. In addition, KAT7-mediated H3K14ac activation induced MMP14 transcription, leading to increased expression and facilitation of osteosarcoma cell metastasis. Subsequent bioinformatics analyses highlighted a correlation between KAT7 and adaptive immune responses, indicating CCL3 as a downstream target of KAT7. Mechanistically, STAT1 was found to transcriptionally upregulate CCL3 expression. Furthermore, overexpression of KAT7 suppressed CCL3 secretions, whereas knockdown of KAT7 enhanced its release. Overall, these findings underscore the oncogenic role of KAT7 in regulating immune responses for osteosarcoma treatment.