Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

BackgroundModified electroconvulsive therapy （MECT） is a common front-line strategy widely used in psychiatric practice， and the optimal first stimulus dosage in MECT is usually estimated clinically based on the factors influencing the patient's initial seizure threshold （IST）. However， previous studies on the influencing factors of IST have mostly suffered from limitations such as small sample sizes and single-dimensional research perspectives. ObjectiveTo explore the factors influencing IST in MECT for patients with mental disorders， so as to provide references for stimulus dosing strategies in MECT for the patients. MethodsA retrospective study was used to include 1 446 inpatients fulfilling the diagnostic criteria for any specific mental disorder listed in the ICD-10 and receiving MECT at Shandong Daizhuang Hospital from January 1， 2021 to August 1， 2023. Their general and clinical data were collected， including IST， psychiatric diagnostic categories， gender， ethnicity， age， body weight， body mass index （BMI）， course of disease， family history of psychiatric disorders， first episode status， use of antiepileptic drugs the day before treatment， use of benzodiazepines the day before treatment， and previous MECT treatment history. Pearson correlation analysis was utilized to test the correlation of IST with age， height， body weight， BMI， and course of disease， and stepwise multivariate linear regression analysis was performed to identify the factors affecting IST. ResultsIST yielded statistical difference among patients in terms of gender， first episode status， use of antiepileptic drugs the day before treatment， and use of benzodiazepines the day before treatment （t=2.256， -3.059， -2.136， -3.006， P<0.05 or 0.01）. IST in patients of different ages and psychiatric diagnostic categories also demonstrated statistical difference （F=913.120， 6.212， P<0.01）. Within young population， IST varied significantly based on the psychiatric diagnostic categories （F=2.986， P<0.05）. Correlation analysis indicated that IST was positively correlated with age， body weight， BMI and course of disease （r=0.886， 0.055， 0.184， 0.456， P<0.05 or 0.01）， and negatively correlated with height （r=-0.183， P<0.01）. Stepwise multivariate linear regression analysis revealed that age， gender， and body weight were influencing factors of IST （β=0.888， -0.049， -0.035， P<0.01）. ConclusionsAge， gender and body weight may be factors influencing IST in MECT for patients with mental disorders. ［Funded by Key R&D Plan Projects of Jining City in 2024 (number, 2024YXNS202）］

Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

BACKGROUND:The lower cervical vertebral pedicle is the main stress site of the posterior column of the spine,which is of great significance for the maintenance of the stability of the human center of gravity and the reduction of shock.At present,there are few reports on the characteristics of the internal bone trabeculae,and the characteristics of the joint site of the vertebral pedicle with the articular process and the vertebral body.It is urgent to understand the fine anatomical structure of the vertebral pedicle and the relationship and function of each part. OBJECTIVE:To observe the microanatomical morphology of the vertebral pedicle by Micro-CT scanning of cervical vertebra specimens,and to measure and analyze the microstructure and morphometric parameters of the bone trabecula in the cervical pedicle under normal conditions to evaluate the safety performance of the cervical spine. METHODS:Micro-CT scanning was performed on 31 sets of cervical vertebrae C3-C7.By checking and reconstructing the areas of interest in the bone trabecular within the vertebral pedicle,the morphological characteristics and distribution direction of the bone trabecular within the cervical pedicle were observed,and the bone microstructure parameters were detected,and the differences in the bone microstructure of the C3-C7 vertebral pedicle were analyzed and compared. RESULTS AND CONCLUSION:(1)The Micro-CT images showed that the honeycomb bone trabeculae of the pedicle of the lower cervical spine presented a complex network of microstructures.The trabeculae near the cortical bone were lamellar and relatively compact,extending forward toward the vertebral body and backward toward the articular process lamina.Abatoid bone trabeculae extended into the medullary cavity and transformed into a network structure,and then into rod-shaped bone trabeculae.The rod-shaped bone trabeculae were sparsely distributed in the medullary cavity.(2)Statistical results of morphological parameters of bone trabeculae showed that bone volume fraction values in C4 and C5 were higher than that in C7(P＜0.05).The bone surface/bone volume value in C7 was higher than that in C3,C4 and C6(P＜0.05).The bone surface density of bone trabeculae in C7 was higher than that in C3,C4,C5 and C6(P＜0.05).Trabecular thickness in C7 was higher than that in C3,C4 and C5(P＜0.05).Bone surface/bone volume and bone surface density of the left pedicle bone trabecular were greater than those on the right side(P＜0.05).(3)The microstructural changes of C3-C7 were summarized,in which the load capacity and stress of the C7 pedicle were poor,and the risk of injury was high in this area.

BACKGROUND:As a unique structure of the cervical spine,the occurrence,development and progression of the uncovertebral joint directly affect the stability and range of motion of the cervical spine,and are also closely related to the pathogenesis of cervical spondylosis.A thorough understanding of the developmental characteristics of the uncovertebral joint is of great significance for the pathogenesis,diagnosis,and treatment of cervical spondylosis. OBJECTIVE:By using imaging and three-dimensional reconstruction technology to measure and observe the cervical uncinate process-related angle in a large sample of different age groups,the aim is to reveal the characteristics of its changes with age and vertebral growth,as well as its relationship with cervical spine stability. METHODS:Using a retrospective research design,we collected 1 447 cases of raw CT imaging data that meet the study requirements for complete cervical spine segments.The raw data were imported into Mimics 21.0 software in DICOM format for post-processing and measurement of angle of uncinate process and sagittal angle of uncinate process.The data were grouped based on gender,age,and side. RESULTS AND CONCLUSION:(1)With the increase of vertebral sequence,the angle of uncinate process increased in a V-shaped shape,and the lowest peak was at C5.The overall population showed a sharp peak with the increase of age,and the peak value mostly occurred in the age range of 30-39 years.(2)The sagittal angle of the uncinate process increased like a fishhook with the increase of the vertebral sequence,and the overall angle of the uncinate process increased with age,and the peak value mostly occurred in the age range of 20-29 years.The uncinate process angle and sagittal angle showed only partial significant differences between sides and genders(P<0.05).(3)It is concluded that the angle of the uncinate process increased with the increase of vertebral sequence in a V-shaped manner.The sagittal angle of the uncinate process increases like a fish hook with increasing vertebral order,while the two angles generally peak with increasing age.The angle of the uncinate process is about 131°,which may be closely related to the stability of the cervical spine,while the sagittal angle of the uncinate process is about 14°,and its function may play a certain role in limiting the excessive rotation of the cervical spine.

Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.

Objective To evaluate the characteristics of the mass balance and pharmacokinetics of[14 C]birociclib in Chinese male healthy volunteers after a single oral administration.Methods This study used a 14 C labeled method to investigate the mass balance and biological transformation of birociclib in human.Subjects were given a single oral dose of 360 mg/50 pCi of[14 C]birociclib suspension after meals.The blood,urine,and fecal samples were collected at specified time points/intervals after administration.The radiation levels of 14 C labeled birociclib-related compounds in the blood,plasma,urine,and feces were analyzed using liquid scintillation counting.In addition,a combination of high-performance liquid chromatography and on-line/off-line isotope detectors was used to obtain radioactive isotope metabolite spectra of plasma,urine,and fecal samples,and high-resolution mass spectrometry was used to identify the main metabolites.Results A total of 6 healthy male subjects were enrolled in this study.The median peak time of radioactive components in plasma was 5.00 h and the average terminal elimination half-life was 43.70 h after administration.The radioactive components were basically excreted and cleared from the body within 288.00 hours after administration,and average cumulative recovery rate of radioactive drugs was(94.10±8.19)％.The radioactive drugs were mainly excreted through feces,accounting for(84.60±7.10)％of the dose of radioactive drugs administered.Urine was the secondary excretory pathway,accounting for 9.41％of the dose of radioactive drugs administered.Metabolic analysis indicated that the prototype drug was the main radioactive components in plasma samples.The main metabolites in plasma were RM4(XZP-5286),RM6(XZP-3584),and RM7(XZP-5736).The drugs were mainly cleared from the body in the form of prototype drugs and metabolites.In addition to prototype drugs,a total of 9 metabolites were identified and analyzed in plasma,urine,and fecal samples,all of which were phase 1 metabolites.The main metabolic and clearance pathways of drugs in the body were deethylation,diisopropylat ion,oxidation,etc.Conclusion After a single oral administration of[14C]birociclib suspension to healthy subjects,it was mainly cleared from the body in the form of prototype drugs and metabolites,with feces as the main excretory pathway and urine as the secondary excretory pathway.Drugs mainly undergo metabolic reactions in the body,such as deethylation,diisopropylation,and oxidation.The subjects were well tolerance after administration.