MPE-YOLO: enhanced small target detection in aerial imaging.

Aerial image target detection is essential for urban planning, traffic monitoring, and disaster assessment. However, existing detection algorithms struggle with small target recognition and accuracy in complex environments. To address this issue, this paper proposes an improved model based on YOLOv8, named MPE-YOLO. Initially, a multilevel feature integrator (MFI) module is employed to enhance the representation of small target features, which meticulously moderates information loss during the feature fusion process. For the backbone network of the model, a perception enhancement convolution (PEC) module is introduced to replace traditional convolutional layers, thereby expanding the network's fine-grained feature processing capability. Furthermore, an enhanced scope-C2f (ES-C2f) module is designed, utilizing channel expansion and stacking of multiscale convolutional kernels to enhance the network's ability to capture small target details. After a series of experiments on the VisDrone, RSOD, and AI-TOD datasets, the model has not only demonstrated superior performance in aerial image detection tasks compared to existing advanced algorithms but also achieved a lightweight model structure. The experimental results demonstrate the potential of MPE-YOLO in enhancing the accuracy and operational efficiency of aerial target detection. Code will be available online (https://github.com/zhanderen/MPE-YOLO).

The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt-Induced Hypertension.

The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure (BP). We administered hydroxylamine hydrochloride (HA), a cystathionine-ß-synthase (CBS) inhibitor, into the PVN to suppress endogenous hydrogen sulfide (H2S) and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the NS+PVN vehicle group, the NS+PVN HA group, the HS+PVN vehicle group, and the HS+PVN HA group, with 10 rats in each group. The rats in the NS (normal salt) groups were fed a normal-salt diet containing 0.3% NaCl, while the HS (high salt) groups were fed a high-salt diet containing 8% NaCl. The mean arterial pressure (MAP) was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini-pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H2S in the PVN and plasma norepinephrine (NE) using ELISA. Additionally, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time PCR. In the current study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of high salt-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.

The Mechanism of 540 nm Green Light in Promoting Salivary Secretion.

Background: Although low-level laser therapy (LLLT) is a widely used noninvasive treatment because of photobiomodulation effects, its application for xerostomia remained uncertain. Tight junctions (TJs), mainly composed of claudins, occludin, and ZO family members, are crucial structures that determine material transport through paracellular pathway in salivary gland epithelial cells. This work aimed to investigate whether LLLT affected salivary secretion through epithelial TJs. Methods: Transepithelial electrical resistance (TER) measurement and paracellular permeability assay were applied to evaluate paracellular permeability in submandibular gland (SMG)-C6 cells after irradiation with 540 nm green light. Immunofluorescence and western blot were used to detect the expression of TJ proteins. Quantitative phosphoproteomics were performed to explore possible intracellular signals. Results: We found that irradiation with 540 nm green light significantly decreased TER values while increased paracellular transport in SMG-C6 cells. 540 nm green light-induced redistribution of claudin-1, -3, and -4, but not occludin or ZO-1. Moreover, above phenomena were abolished by preincubation with capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. Notably, irradiation with 540 nm green light on the skin covering the whole submandibular gland regions promoted salivary secretion and attenuated lymphocytic infiltration in 21-week-old non-obese diabetic mice (n = 5 per group), a xerostomia animal model for Sjögren's syndrome. Through in-depth bioinformatics analysis and expression verification, ERK1/2 and EphA2 served as potential canonical and noncanonical signals underlying 540 nm green light. Conclusions: Our findings uncovered the novel therapeutic effects of 540 nm green light on xerostomia through regulation on the expression and distribution of TJs.

Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the primary form of lung cancer, and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease. However, the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies. Consequently, it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments. AIM: To identify the metabolic signatures associated with neutrophil extracellular traps (NETs) and chemoimmunotherapy efficacy in NSCLC patients. METHODS: In total, 159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled. We first investigated the characteristics influencing clinical efficacy. Circulating levels of NETs and cytokines were measured by commercial kits. Liquid chromatography tandem mass spectrometry quantified plasma metabolites, and differential metabolites were identified. Least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest algorithms were employed. By using plasma metabolic profiles and machine learning algorithms, predictive metabolic signatures were established. RESULTS: First, the levels of circulating interleukin-8, neutrophil-to-lymphocyte ratio, and NETs were closely related to poor efficacy of first-line chemoimmunotherapy. Patients were classed into a low NET group or a high NET group. A total of 54 differential plasma metabolites were identified. These metabolites were primarily involved in arachidonic acid and purine metabolism. Three key metabolites were identified as crucial variables, including 8,9-epoxyeicosatrienoic acid, L-malate, and bis(monoacylglycerol)phosphate (18:1/16:0). Using metabolomic sequencing data and machine learning methods, key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy. CONCLUSION: The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.

Myotis bat STING attenuates aging-related inflammation in female mice.

Bats, notable as the only flying mammals, serve as natural reservoir hosts for various highly pathogenic viruses in humans (e.g., SARS-CoV and Ebola virus). Furthermore, bats exhibit an unparalleled longevity among mammals relative to their size, particularly the Myotis bats, which can live up to 40 years. However, the mechanisms underlying these distinctive traits remain incompletely understood. In our prior research, we demonstrated that bats exhibit dampened STING-interferon activation, potentially conferring upon them the capacity to mitigate virus- or aging-induced inflammation. To substantiate this hypothesis, we established the first in vivo bat-mouse model for aging studies by integrating Myotis davidii bat STING ( MdSTING) into the mouse genome. We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on MdSTING and wild-type mice over a 3-year aging process. Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female MdSTING mice, as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines, immunopathology, and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice in vivo. These results indicated that MdSTING knock-in attenuates the aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner. Although the underlying mechanism awaits further study, this research has critical implications for bat longevity research, potentially contributing to our comprehension of healthy aging in humans.

A fatty acid elongase complex regulates cell membrane integrity and septin-dependent host infection by the rice blast fungus.

Very-long-chain fatty acids (VLCFAs) regulate biophysical properties of cell membranes to determine growth and development of eukaryotes, such as the pathogenesis of the rice blast fungus Magnaporthe oryzae. The fatty acid elongase Elo1 regulates pathogenesis of M. oryzae by modulating VLCFA biosynthesis. However, it remains unknown whether and how Elo1 associates with other factors to regulate VLCFA biosynthesis in fungal pathogens. Here, we identified Ifa38, Phs1 and Tsc13 as interacting proteins of Elo1 by proximity labelling in M. oryzae. Elo1 associated with Ifa38, Phs1 and Tsc13 on the endoplasmic reticulum (ER) membrane to control VLCFA biosynthesis. Targeted gene deletion mutants Δifa38, Δphs1 and Δtsc13 were all similarly impaired as Δelo1 in vegetative growth, conidial morphology, stress responses in ER, cell wall and membrane. These deletion mutants also displayed severe damage in cell membrane integrity and failed to organize the septin ring that is essential for penetration peg formation and pathogenicity. Our study demonstrates that M. oryzae employs a fatty acid elongase complex to regulate VLCFAs for maintaining or remodelling cell membrane structure, which is important for septin-mediated host penetration.

Individual virome analysis reveals the general co-infection of mammal-associated viruses with SARS-related coronaviruses in bats.

Bats are the natural reservoir hosts for SARS-related coronavirus (SARSr-CoV) and other highly pathogenic microorganisms. Therefore, it is conceivable that an individual bat may harbor multiple microbes. However, there is limited knowledge on the overall co-circulation of microorganisms in bats. Here, we conducted a 16-year monitoring of bat viruses in south and central China and identified 238 SARSr-CoV positive samples across nine bat species from ten provinces or administrative districts. Among these, 76 individual samples were selected for further metagenomics analysis. We found a complex microenvironment characterized by the general co-circulation of microbes from two different sources: mammal-associated viruses or environment-associated microbes. The later includes commensal bacteria, enterobacteria-related phages, and insect or fungal viruses of food origin. Results showed that 25% (19/76) of the samples contained at least one another mammal-associated virus, notably alphacoronaviruses (13/76) such as AlphaCoV/YN2012, HKU2-related CoV and AlphaCoV/Rf-HuB2013, along with viruses from other families. Notably, we observed three viruses co-circulating within a single bat, comprising two coronavirus species and one picornavirus. Our analysis also revealed the potential presence of pathogenic bacteria or fungi in bats. Furthermore, we obtained 25 viral genomes from the 76 bat SARSr-CoV positive samples, some of which formed new evolutionary lineages. Collectively, our study reveals the complex microenvironment of bat microbiome, facilitating deeper investigations into their pathogenic potential and the likelihood of cross-species transmission.

Bone-organ axes: bidirectional crosstalk.

In addition to its recognized role in providing structural support, bone plays a crucial role in maintaining the functionality and balance of various organs by secreting specific cytokines (also known as osteokines). This reciprocal influence extends to these organs modulating bone homeostasis and development, although this aspect has yet to be systematically reviewed. This review aims to elucidate this bidirectional crosstalk, with a particular focus on the role of osteokines. Additionally, it presents a unique compilation of evidence highlighting the critical function of extracellular vesicles (EVs) within bone-organ axes for the first time. Moreover, it explores the implications of this crosstalk for designing and implementing bone-on-chips and assembloids, underscoring the importance of comprehending these interactions for advancing physiologically relevant in vitro models. Consequently, this review establishes a robust theoretical foundation for preventing, diagnosing, and treating diseases related to the bone-organ axis from the perspective of cytokines, EVs, hormones, and metabolites.

Linking the relationship between dietary folic acid intake and risk of osteoporosis among middle-aged and older people: A nationwide population-based study.

Among middle-aged and older people, balanced and nutritious diets are the foundation for maintaining bone health and preventing osteoporosis. This study is aimed at investigating the link between dietary folic acid intake and the risk of osteoporosis among middle-aged and older people. A total of 20,686 people from the National Health and Nutritional Examination Survey (NHANES) 2007-2010 are screened and included, and 5312 people aged ≥45 years with integral data are ultimately enrolled in evaluation. Demographics and dietary intake-related data are gathered and analyzed, and the odds ratio (OR) and 95% confidence interval (CI) of each tertile category of dietary folic acid intake and each unit increase in folic acid are assessed via multivariate logistic regression models. On this basis, the receiver operating characteristic (ROC) curve is used to identify the optimal cutoff value of dietary folic acid intake for indicating the risk of osteoporosis. Of 5312 people with a mean age of 62.4 ± 11.0 years old, a total of 513 people with osteoporosis are screened, and the dietary folic acid intake amount of the osteoporosis group is significantly lower than that of the non-osteoporosis group (p < .001). The lowest tertile category is then used to act as a reference category, and a higher dietary folic acid intake amount is observed to be positively related to lower odds for risk of osteoporosis. This trend is also not changed in adjustments for combinations of different covariates (p all < .05). Based on this, a dietary folic acid intake of 475.5 µg/day is identified as an optimal cutoff value for revealing osteoporosis. Collectively, this nationwide population-based study reveals that a higher daily dietary folic acid intake has potential protective effects on osteoporosis in middle-aged and older people.

SpliceAPP: an interactive web server to predict splicing errors arising from human mutations.

BACKGROUND: Splicing variants are a major class of pathogenic mutations, with their severity equivalent to nonsense mutations. However, redundant and degenerate splicing signals hinder functional assessments of sequence variations within introns, particularly at branch sites. We have established a massively parallel splicing assay to assess the impact on splicing of 11,191 disease-relevant variants. Based on the experimental results, we then applied regression-based methods to identify factors determining splicing decisions and their respective weights. RESULTS: Our statistical modeling is highly sensitive, accurately annotating the splicing defects of near-exon intronic variants, outperforming state-of-the-art predictive tools. We have incorporated the algorithm and branchpoint information into a web-based tool, SpliceAPP, to provide an interactive application. This user-friendly website allows users to upload any genetic variants with genome coordinates (e.g., chr15 74,687,208 A G), and the tool will output predictions for splicing error scores and evaluate the impact on nearby splice sites. Additionally, users can query branch site information within the region of interest. CONCLUSIONS: In summary, SpliceAPP represents a pioneering approach to screening pathogenic intronic variants, contributing to the development of precision medicine. It also facilitates the annotation of splicing motifs. SpliceAPP is freely accessible using the link https://bc.imb.sinica.edu.tw/SpliceAPP . Source code can be downloaded at https://github.com/hsinnan75/SpliceAPP .

Pharmacology of Hydrogen Sulfide and Its Donors in Cardiometabolic Diseases.

Cardiometabolic diseases (CMDs) are major contributors to global mortality, emphasizing the critical need for novel therapeutic interventions. Hydrogen sulfide (H2S) has garnered enormous attention as a significant gasotransmitter with various physiological, pathophysiological, and pharmacological impacts within mammalian cardiometabolic systems. In addition to its roles in attenuating oxidative stress and inflammatory response, burgeoning research emphasizes the significance of H2S in regulating proteins via persulfidation, a well known modification intricately associated with the pathogenesis of CMDs. This review seeks to investigate recent updates on the physiological actions of endogenous H2S and the pharmacological roles of various H2S donors in addressing diverse aspects of CMDs across cellular, animal, and clinical studies. Of note, advanced methodologies, including multiomics, intestinal microflora analysis, organoid, and single-cell sequencing techniques, are gaining traction due to their ability to offer comprehensive insights into biomedical research. These emerging approaches hold promise in characterizing the pharmacological roles of H2S in health and diseases. We will critically assess the current literature to clarify the roles of H2S in diseases while also delineating the opportunities and challenges they present in H2S-based pharmacotherapy for CMDs. SIGNIFICANCE STATEMENT: This comprehensive review covers recent developments in H2S biology and pharmacology in cardiometabolic diseases CMDs. Endogenous H2S and its donors show great promise for the management of CMDs by regulating numerous proteins and signaling pathways. The emergence of new technologies will considerably advance the pharmacological research and clinical translation of H2S.

Prevalence of metabolic syndrome among patients with hepatocellular carcinoma of different etiologies: a retrospective study.

AIMS: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. CONCLUSION: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

Adjuvant Therapy for Hepatocellular Carcinoma After Curative Treatment: Several Unanswered Questions.

Most patients with hepatocellular carcinoma (HCC) have a poor prognosis. Hepatectomy and local ablation are the main curative treatments for HCC. Nevertheless, the recurrence rate after hepatectomy or ablation is up to 70%, which seriously affects patient prognosis. Several adjuvant therapies have been explored to reduce postoperative recurrence. However, although a variety of adjuvant therapies have been shown to reduce the recurrence rate and improve overall survival, a standard consensus of national HCC guidelines for adjuvant treatment is lacking. Therefore, there are significant differences in the recommendations for adjuvant therapy for HCC between the Eastern and Western guidelines. A variety of adjuvant treatment methods, such as antiviral therapy, transarterial chemoembolization or traditional Chinese medicine, are recommended by the Chinese HCC guidelines. However, Western guidelines make few recommendations other than antiviral therapy. Adjuvant immune checkpoint inhibitors are recommended only in the recently updated American Association for the Study of Liver Diseases guidelines. This review summarized the existing adjuvant therapy options after curative hepatectomy or ablation and discusses several important dilemmas of adjuvant treatments.

Cellular mechanism underlying leptin-induced anion secretion of rat epididymal epithelial cells.

BACKGROUND: A large number of studies have shown that leptin plays an important role in the regulation of fertility via the hypothalamus-pituitary-gonad axis. However, its peripheral function in epididymis was still elusive. OBJECTIVE: The purpose of this study was to determine the pro-secretion effect of leptin on the rat epididymal epithelium. MATERIALS AND METHODS: In the present study, real-time quantitative polymerase chain reaction, western blot, and immunohistochemical analysis were employed to detect the expression pattern of leptin receptors in rat epididymis. The pro-secretion effect of leptin on epididymal epithelial cells was measured by short-circuit current, and the prostaglandin E2 and cyclic adenosine monophosphate level was evaluated by enzyme-linked immunosorbent assay. RESULTS: We verified that the leptin receptor was located on the epididymal epithelium, with a relatively high expression level in corpus and cauda epididymis. Ussing chamber experiments showed that leptin stimulated a significant rise of the short-circuit current in rat epididymal epithelial cells, which could be abolished by the specific leptin receptor antagonist peptide Allo-aca, or by removing the ambient Cl- and HCO3 -. Furthermore, the leptin-stimulated short-circuit current response could be abrogated by blocking the apical cystic fibrosis transmembrane regulator or the basolateral Na+-K+-2Cl- cotransporter. Our pharmacological experiments manifested that interfering with the prostaglandin H synthase-2-prostaglandin E2-EP2/EP4-adenylate cyclase pathways could significantly blunt the cystic fibrosis transmembrane regulator-mediated anion secretion induced by leptin. The enzyme-linked immunosorbent assay demonstrated that leptin could induce a substantial increase in prostaglandin E2 release and cyclic adenosine monophosphate synthesis of primary cultured rat cauda epididymal epithelial cells. Our data also suggested that JAK2, ERK, and PI3K-dependent phosphorylation may be involved in the activation of prostaglandin H synthase-2 and the subsequent prostaglandin E2 production. CONCLUSIONS: The present study demonstrated the pro-secretion function of leptin in rat epididymal epithelium via the activation of cystic fibrosis transmembrane regulator and Na+-K+-2Cl- cotransporter, which was dependent on the paracrine/autocrine prostaglandin E2 stimulated EP2/EP4-adenylate cyclase pathways, and thus contributed to the formation of an appropriate microenvironment essential for sperm maturation.

Associations between blood manganese levels and sarcopenia in adults: insights from the National Health and Nutrition Examination Survey.

Background: While increasing concerns arise about the health effects of environmental pollutants, the relationship between blood manganese (Mn) and sarcopenia has yet to be fully explored in the general population. Objective: This study aims to investigate the association between blood manganese (Mn) levels and sarcopenia in adults. Methods: In our study, we evaluated 8,135 individuals aged 18-59 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2018. We employed generalized additive model (GAM) to discern potential non-linear relationships and utilized the two-piecewise linear regression model to probe the association between blood Mn levels and sarcopenia. Results: After adjusting for potential confounders, we identified non-linear association between blood Mn levels and sarcopenia, with an inflection point at 13.45 µg/L. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.006 (0.996 to 1.048) and 1.082 (1.043 to 1.122), respectively. Subgroup analysis showed that the effect sizes of blood Mn on sarcopenia have significant differences in gender and different BMI groups. Conclusion: Our results showed that a reverse U-shaped curve between blood Mn levels and sarcopenia, with an identified the inflection point at blood Mn level of 13.45 µg/L.

Potential clinical value of fibrinogen-like protein 1 as a serum biomarker for the identification of diabetic cardiomyopathy.

Diabetic individuals with diabetic cardiomyopathy (DbCM) present with abnormal myocardial structure and function. DbCM cannot be accurately diagnosed due to the lack of suitable diagnostic biomarkers. In this study, 171 eligible participants were divided into a healthy control (HC), type 2 diabetes mellitus (T2DM) patients without DbCM (T2DM), or DbCM group. Serum fibrinogen-like protein 1 (FGL-1) and other biochemical parameters were determined for all participants. Serum FGL-1 levels were significantly higher in patients with DbCM compared with those in the T2DM group and HCs. Serum FGL-1 levels were negatively correlated with left ventricular fractional shortening and left ventricular ejection fraction (LVEF) and positively correlated with left ventricular mass index in patients with DbCM after adjusting for age, sex and body mass index. Interaction of serum FGL-1 and triglyceride levels on LVEF was noted in patients with DbCM. A composite marker including serum FGL-1 and triglycerides could differentiate patients with DbCM from those with T2DM and HCs with an area under the curve of 0.773 and 0.789, respectively. Composite marker levels were negatively correlated with N-terminal B-type natriuretic peptide levels in patients with DbCM. Circulating FGL-1 may therefore be a valuable index reflecting cardiac functions in DbCM and to diagnose DbCM.

Comparison of epidermal growth factor expression and secretion in human salivary glands.

OBJECTIVE: To investigate the expression and secretion of epidermal growth factor (EGF) in major and minor salivary gland tissues of human subjects and to examine the potential influence of sex and age on EGF expression and secretion. DESIGN: Saliva samples from the oral cavity at rest and after citric acid stimulation, as well as serum samples, were collected from 150 healthy subjects, and the concentrations of EGF were measured with enzyme-linked immunosorbent assay (ELISA) and compared. The expression of EGF mRNA and protein in normal salivary gland tissues was measured by real-time polymerase chain reaction (RT-PCR), Western blot (WB), and immunohistochemistry (IHC). RESULTS: The EGF concentration in acid-stimulated saliva was significantly higher than that in resting saliva (P < 0.001), and significantly higher than that in serum (P < 0.001). No sex difference was observed in EGF levels of whole saliva and serum, whereas the EGF levels in saliva and serum were decreased with age (P < 0.001 and P < 0.001, respectively). The EGF concentration and compound secretion rate (CSR) in resting submandibular glands saliva were significantly higher than those in resting parotid glands saliva (P = 0.002 and P < 0.001, respectively). The EGF was expressed in all major and minor salivary glands and ranked in order of submandibular, parotid, sublingual, and labial glands. CONCLUSION: All salivary glands have the function of secreting EGF, and the submandibular gland is the main source of salivary EGF. Aging is a factor influencing the expression and secretion of EGF.

Cichoric acid ameliorates sepsis-induced acute kidney injury by inhibiting M1 macrophage polarization.

Cichoric acid (CA), a widely utilized polyphenolic compound in medicine, has garnered significant attention due to its potential health benefits. Sepsis-induced acute kidney disease (AKI) is related with an elevated risk of end-stage kidney disease (ESKD). However, it remains unclear whether CA provides protection against septic AKI. The aim of this study is to investigated the protective effect and possible mechanisms of CA against LPS-induced septic AKI. Sepsis-induced AKI was induced in mice through intraperitoneal injection of lipopolysaccharide (LPS), and RAW264.7 macrophages were incubated with LPS. LPS exposure significantly increased the levels of M1 macrophage biomarkers while reducing the levels of M2 macrophage indicators. This was accompanied by the release of inflammatory factors, superoxide anion production, mitochondrial dysfunction, activation of succinate dehydrogenase (SDH), and subsequent succinate formation. Conversely, pretreatment with CA mitigated these abnormalities. CA attenuated hypoxia-inducible factor-1α (HIF-1α)-induced glycolysis by lifting the NAD+/NADH ratio in macrophages. Additionally, CA disrupted the K (lysine) acetyltransferase 2A (KAT2A)/α-tubulin complex, thereby reducing α-tubulin acetylation and subsequently inactivating the NLRP3 inflammasome. Importantly, administration of CA ameliorated LPS-induced renal pathological damage, apoptosis, inflammation, oxidative stress, and disturbances in mitochondrial function in mice. Overall, CA restrained HIF-1α-mediated glycolysis via inactivation of SDH, leading to NLRP3 inflammasome inactivation and the amelioration of sepsis-induced AKI.

Histopathological changes in salivary glands after radioactive iodine treatment for thyroid diseases.

OBJECTIVES: We aimed to evaluate the histopathological alterations in human salivary glands after radioactive iodine (RAI) treatment for thyroid diseases. STUDY DESIGN: We retrospectively selected patients with a history of RAI treatment for thyroid diseases from a database of patients who underwent surgery for oral and maxillofacial diseases and had specimens of salivary glands at Peking University School of Stomatology between December 2012 and July 2023. The patients' clinical records and histopathological slides of the salivary glands were carefully reviewed. RESULTS: Sixteen patients were included. Three symptomatic patients showed duct cell cytoplasmic vacuolization and increased numbers of disordered duct cell layers (3/3), severe duct stenosis and dilation (2/3), and exfoliated epithelial cells in the duct lumen (1/3). The glandular parenchyma showed severe acinar atrophy (2/2), fat content enhancement (2/2), and severe periductal fibrosis (3/3). Thirteen asymptomatic patients showed duct cell cytoplasmic vacuolization (5/13), acinar atrophy and increased fat content in the parenchyma (5/13), and periductal fibrosis (5/13). CONCLUSION: Main histopathologic changes in the salivary glands after RAI treatment for thyroid diseases are cytoplasmic vacuolization of duct cells, acinar atrophy, fat content enhancement, and periductal fibrosis. These changes were evident in symptomatic cases, and were also seen in some asymptomatic patients.