Approximately 20% to 30% of the global workforce is engaged in shift work. As a significant cause of circadian disruption, shift work is closely associated with an increased risk for periodontitis. Nevertheless, how shift work-related circadian disruption functions in periodontitis remains unknown. Herein, we employed a simulated shift work model constructed by controlling the environmental light-dark cycles and revealed that shift work-related circadian disruption exacerbated the progression of experimental periodontitis. RNA sequencing and in vitro experiments indicated that downregulation of the core circadian protein brain and muscle ARNT-like protein 1 (BMAL1) and activation of the Gasdermin D (GSDMD)-mediated pyroptosis were involved in the pathogenesis of that. Mechanically, BMAL1 regulated GSDMD-mediated pyroptosis by suppressing NOD-like receptor protein 3 (NLRP3) inflammasome signaling through modulating nuclear receptor subfamily 1 group D member 1 (NR1D1), and inhibiting Gsdmd transcription via directly binding to the E-box elements in its promoter. GSDMD-mediated pyroptosis accelerated periodontitis progression, whereas downregulated BMAL1 under circadian disruption further aggravated periodontal destruction by increasing GSDMD activity. And restoring the level of BMAL1 by circadian recovery and SR8278 injection alleviated simulated shift work-exacerbated periodontitis via lessening GSDMD-mediated pyroptosis. These findings provide new evidence and potential interventional targets for circadian disruption-accelerated periodontitis.
Pyroptosis/physiology* ; ARNTL Transcription Factors/metabolism* ; Animals ; Periodontitis/etiology* ; Mice ; Phosphate-Binding Proteins/metabolism* ; Shift Work Schedule/adverse effects* ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Male ; Disease Models, Animal ; Gasdermins

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to numerous chronic conditions, including cardiovascular disease, atherosclerosis, chronic kidney disease, and type II diabetes. Previous research identified the natural flavonoid diosmin, derived from Chrysanthemum morifolium, as a regulator of glucose metabolism. However, its effects on lipid metabolism and underlying mechanisms remained unexplored. The AMP-activated protein kinase (AMPK) pathway serves a critical function in glucose and lipid metabolism. The relationship between diosmin and the AMPK pathway has not been previously documented. This investigation examined diosmin's capacity to reduce lipid content through AMPK pathway activation in hepatoblastoma cell line G2 (HepG2) and 3T3-L1 cells. The study revealed that diosmin inhibits lipogenesis, indicating its potential as an anti-obesity agent in obese mice. Moreover, diosmin demonstrated effective MASLD alleviation in vivo. These findings suggest that diosmin may represent a promising therapeutic candidate for treating obesity and MASLD.
Diosmin/administration & dosage* ; Animals ; AMP-Activated Protein Kinases/genetics* ; Humans ; Non-alcoholic Fatty Liver Disease/enzymology* ; Mice ; Obesity/enzymology* ; Hep G2 Cells ; Male ; 3T3-L1 Cells ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Lipid Metabolism/drug effects* ; Chrysanthemum/chemistry* ; Lipogenesis/drug effects*

Objective To compare the impact on ¹⁸F fluorodeoxyglucose （¹⁸F-FDG） positron emission tomography （PET） image quality when block sequential regularized expectation maximization （BSREM） algorithm and ordered subset expectation maximization （OSEM） algorithm were used at various acquisition times （ATs）, and to discuss the feasibility of AT optimization with BSREM algorithm. Methods In the phantom experiment, the NEMA/IEC PET phantom was adopted. In the clinical study, 66 pulmonary nodules with high uptake values from 61 patients who underwent a ¹⁸F-FDG PET-CT examination for pulmonary nodules from March to September 2020 were included. PET images were reconstructed according to BSREM algorithm and OSEM algorithm at various ATs in both the phantom experiment and the clinical study. Coefficient of variation, signal-to-noise ratio, contrast-to-noise ratio, and activity values （uptake value in the phantom experiment; standardized uptake value in the clinical study） were compared between the above sequence images for quality evaluation. Results The phantom experiment showed that the image quality of 120 s BSREM sequence was superior to that of 120 s OSEM sequence, and the image quality of 75 s BSREM sequence was similar to that of 120 s OSEM sequence. The clinical study showed that the image quality of 120 s BSREM sequence was superior to that of 120 s OSEM sequence, and the image quality of 75 s BSREM sequence was slightly better than that of 120 s OSEM sequence. Conclusion In the PET phantom experiment and the clinical study of pulmonary nodules with high uptake values, BSREM algorithm can significantly improve the image quality as compared to OSEM algorithm, and the image quality of 75 s BSREM sequence is slightly better than that of 120 s OSEM sequence.

Tumor-associated fibroblasts(TAFs),the most important stromal cells of the tumor microenvironment (TME),have been found to support tumorigenesis and tumor metastasis in a variety of ways,including paracrine, direct contact with cells,immune regulation and extracellular matrix remolding.Therefore,TAFs in the TME have been an optimal target for cancer therapy.In this review,the TAFs targeted therapies are summarized to provide the new strategy for tumor treatments based on the analysis of the location and specific biological phenotypes of TAFs in tumors.

Objective To evaluate the effect of desflurane on emergency in patients undergoing suspension microlaryngoscopy surgery.Methods Forty adult patients with ASA Ⅰ-Ⅱ who underwent elective microlaryngoscopy surgery were randomly divided into desflurane group (group D,n =20) and sevoflurane group (group S,n =20).Time from end of the surgery to resume of spontaneous breathing,extubation,and discharge from postanesthesia care unit (PACU) were recorded.The extent of cough reflex during extubation and cough episode after extubation were recorded.Perioperative mean arterial pressure (MAP) and heart rate (HR) were recorded before anesthesia induction (T0),on suspension laryngoscope instrument (Ttary),the gas concentration reached 1.3 MAC (T1.3mac),1 min after 1.3 MAC (T1.3 1),on arrival at PACU (Tpacu),on extubation (Textu),1 min after extubation (T 1),5 min after extubation (T 5),and on discharge from PACU (Tdis).Results Time from end of the surgery to resume of spontaneous breathing was not significantly different between the two groups.Time to extubation in group D was 4.6 min,which was shorter than it was in group S (P＜0.05).Time to discharge from PACU was 5.0 min in group D,which was shorter than it was in group S (P＜0.05).Incidence of cough was 100％ in group D and 55％ in group S during extubation (P＜0.05).The episode of coughing after extubation was not significantly different between the two groups.Perioperatively,changes of MAP and HR between the two groups were not significantly different (P ＞ 0.05).Conclusions Desflurane for adult patients undergoing suspension microlaryngoscopy surgery was associated with fast emergence.The incidence of cough was higher in group D than it was in group S during extubation,but it continued a short duration.

Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) are very two important pathogens that have coursed huge economic losses in swine production in worldwide. In this study,a vector pCMV-TJM containing the full-length cDNA clone of PRRSV attenuated strain TJM-F92 was firstly constructed by PCR method. Then a gene sequence containing Afl II/Mlu I e restriction enzyme sites and a transcription regulatory sequence for ORF6 (TRS6) was inserted be- tween ORF7 and 3'UTR, yielding a expression vector pCMV-TJM-TRS. Subsequently, a plasmid pCMV-TJM-Cap was constructed by cloning of PCV2 ORF2 gene into the unique sites Afl II /Mlu I of pCMV- TJM-TRS plasmid DNA. Then three recombinant PRRSV, rTJM, rTJM/TRS and rTJM/Cap, were rescued by transfection of pCMV-TJM, pCMV-TJM-TRS and pCMV-TJM-Cap into Marc-145 cells, respectively,and confirmed by the genome sequence, restriction enzyme digestion, Western Blot and IFA. They all had the molecular markers which was different from the parent virus. The growth characteristics of the rescued viruses were similar to that of parent virus. rTJM/Cap could also express efficiently PCV2 Cap protein in Marc-145 cells. At passage 8, it still had PCV2 ORF2 gene which examined by RT-PCR. It indicated that the full-length cDNA clone of PRRSV attenuated strain TJM-F92 and recombinant PRRSV rTJM/Cap expressing PCV2 Cap protein were successfully constructed. It made an important foundation for studying on the pathogenic mechanisms of PRRSV and PRRSV-PCV2 vaccine in the future.
Animals ; Capsid Proteins ; genetics ; immunology ; Cell Line ; Circoviridae Infections ; veterinary ; virology ; Circovirus ; classification ; genetics ; metabolism ; Gene Expression ; Open Reading Frames ; Porcine Reproductive and Respiratory Syndrome ; virology ; Porcine respiratory and reproductive syndrome virus ; genetics ; metabolism ; Recombination, Genetic ; Swine ; Swine Diseases ; virology ; Viral Vaccines ; genetics ; immunology

Objective To explore the epidemiological status of abnormal glucose metabolism and its influential factors among middle and aged population with hypertension in Chengdu area. Methods In 2008, after adopting the methods of stratified cluster sampling, the authors investigated 4685 subjects of the middle and aged population between the age of 40-79 in Chengdu urban and rural area by checking blood pressure and oral glucose tolerance test (OGTY). Patients with previously known diabetes mellitus (DM) were only asked to perform fasting glucose and to carry out a questionnaire. Comparison of the prevalence rates of abnormal glucose metabolism in hypertensive and non-hypertensive subjects was carried out. The prevalence rates of isolated impaired glucose tolerance (I-IGT) and isolated postprandial hyperglycemia (IPH) among middle and aged subjects with hypertension were acquired and the influential factors of abnormal glucose metabolism among middle and aged subjects with hypertension were analyzed. Results The prevalence rate of abnormal glucose metabolism in the hypertensive subjects was obviously higher than that in the non-hypertensive subjects; without using OGTT, 72.9% of the pre-diubetic and 54. 4% of the new diagnosed DM patients would remain undiagnosed if fasting plasma glucose detection was used alone. Age, diabetic history of first degree relatives ,overweight or obesity were the risk factors for the development of abnormal glucose metabolism among middle and aged male subjects with hypertension in Chengdu area. Exercise training and high education level were the protective factors. Age, diabetic history of first degree relatives,abdominal obesity and hypertriglyceridemia were the risk factors for the development of abnormal glucose metabolism among middle and aged female subjects with hypertension in Chengdu area. Conclusions More than 50% of middle and aged subjects with hypertension in Chengdu area has accompanying abnormal glucose metabolism. OGTT easily discloses the abnormal status and should be a routine procedure in the diagnosis of pre-diabetes or DM in such population. Appropriate exercise, learning diabetes-related knowledge to take reasonable lifestyle, and intervention of metabolic factors such as overweight or obesity are advised. Abdominal obesity and hypertriglyceridemia play important roles in leading to abnormal glucose metabolism among middle and aged population with hypertension.