The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

Sodium-glucose co-transporter protein 2 inhibitor(SGLT2i)has steadily demonstrated benefits in the treatment of type 2 diabetes complicated with cardiovascular diseases based on evidence-based medicine,but its precise mechanism is yet unknown.We identified type 2 diabetes patients with HFpEF by searching PubMed,Web of Science,China knowledge network(CNKI),and other databases.We then summarized the pathological mechanism of HFpEF caused by type 2 diabetes.At the same time,to link to evidence-based medical,we explored the future of SGLT2i in clinical application.

Purpose::To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis.Methods::A total of 282 healthy young male volunteers aged 18 -20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q 1, Q 3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. Results::Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass ( p = 0.001), total body water (TBW, p=0.006), extracellular water ( p=0.020) and intracellular water ( p=0.010) as well as a larger ratio of basal metabolic rate/total weight ( p=0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat ( p=0.001) and body fat mass index ( p=0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% ( p=0.050, odds ratio =3.114) and 3rd space water > 0.95% ( p=0.045, odds ratio =2.342) were independent risk factors for lower extremity muscle injuries. Conclusion::TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

ObjectiveTo prepare ⁶⁸Ga-labeled magnetic ferrite nanoparticles PET/MRI dual-modal imaging probe and evaluate the possibility of using it as a novel molecular probe for prostate cancer imaging. MethodsUsing superparamagnetic manganese iron oxide nanoparticles as the key component， fibroblast inhibitor and DOTA-NHS ester as the modification，along with chelating the positron radionuclide ⁶⁸Ga， we prepared the nanoprobe ⁶⁸Ga-DOTA-UMFNPs-FAPI-04. Characterization of nanoprobe and analysis of its cytotoxicity， radiochemical purity and stability were performed during the whole process. The observation of the distribution of nanoprobes in normal mice was performed. The effect of nanoprobes on MRI imaging on tumor-bearing mice was analyzed. ResultsAfter purification， the radiochemical purity of probe was 94%， also it had high stability. MRI T2 test showed that its T2 relaxation rate was about 39.02 mM^-1·s^-1. The bio-distribution in the normal mice showed that ⁶⁸Ga-DOTA-UMFNPs- FAPI-04 had a higher uptake in liver and spleen. MRI imaging demonstrated that tumor could be observed clearly after probe injection in 30 minutes. ConclusionsWe have successfully constructed the PET/MRI dual-modal imaging probe ⁶⁸Ga-DOTA-UMFNPs-FAPI-04. It has the characteristics of MRI T2 contrast agent and it also performs well in the MRI imaging of prostate tumors and has the potential of PET imaging. The study provides a new idea for constructing a multi-modal imaging probe for prostate cancer.

Objective: Constructing and validating a nomogram model for preoperative prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis to assist decision making during surgery. Methods: Retrospectively collecting the clinical and pathological data of 1 031 ICC patients who underwent partial hepatectomy at Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University,General Hospital of Eastern Theater Command,or Zhongda Hospital Southeast University from January 2003 to January 2014. There were 682 males and 349 females; mean age was 54.7 years(range:18 to 82 years). There were 562 patients who underwent lymph node dissection and 469 patients who did not. Among the patients in the dissection group,Lasso regression method was used to filtrate preoperative variables related to lymph node metastasis and establish a nomogram. Bootstrap method was used to internally validate the discrimination of the nomogram,and the accuracy of the nomogram was assessed by using calibration curves. Patients were divided into low-moderate and high-risk groups based on model prediction probability. Propensity score matching(PSM) was used to analyze the overall survival (OS) and recurrence-free survival (RFS) of patients with and without lymph node dissection in the two groups,and to judge the importance of lymph node dissection in the two groups. Results: Six factors related to ICC lymph node metastasis were determined by Lasso regression,including hepatitis B surface antigen,CA19-9,age,lymphadenopathy,carcinoembryo antigen and maximum tumor diameter. These factors were integrated into a nomogram to predict ICC lymph node metastasis. The aera under curve value was 0.764,and the C-index was 0.754. Stratified analysis showed that OS and RFS in the high-risk group of lymph node metastasis were significantly lower than those in the low-medium risk group(median OS:14.6 months vs. 27.0 months,P<0.01; median RFS:9.1 months vs. 15.5 months,P<0.01). In the high-risk group,the median OS was 16.7 months and 6.3 months(Log-rank test: P=0.187;Wilcoxon test:P=0.046),and the median RFS was 11.0 months and 4.8 months(P=0.403),respectively in the lymph node dissection group and undissected group after PSM. In the low-medium-risk group,the median OS was 22.7 months and 26.7 months(P=0.288),and the median RFS was 13.0 months and 14.5 months(P=0.306),respectively in the lymph node dissection group and undissected group after PSM. Conclusions: The nomogram could be used for preoperative prediction of lymph node metastasis and prognostic stratification in patients with ICC. For patients with high risk of lymph node metastasis predicted by the model,active dissection should be performed. For patients predicted to be at low-moderate risk,lymph node dissection might be optional in some specific cases.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; Cholangiocarcinoma/surgery* ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology* ; Lymphatic Metastasis ; Male ; Middle Aged ; Nomograms ; Prognosis ; Retrospective Studies

Objective:To observe the clinical effect of acupuncture for persistent allergic rhinitis (PAR).Methods:A total of 154 PAR patients were randomized into a treatment group and a control group,78 cases in the treatment group received acupuncture at meridian points,while 76 cases in the control group received acupuncture at non-meridian points.The treatment was done every other day,3 times a week for a total 4 weeks.The total nasal symptom score (TNSS),the total non-nasal symptom score (TNNSS) and the rhinoconjunctivitis quality of life questionnaire (RQLQ) were measured before the treatment and after 2 weeks and 4 weeks of treatment,as well as 1 month and 3 months after the treatment to compare the clinical effect between the two groups.Results:After 4 weeks of treatment,the total effective rate in the treatment group was 92.3％,versus 76.3％ in the control group,showing a statistically significant difference (P＜0.05).Intra-group comparisons of TNSS,TNNSS and RQLQ scores after 4 weeks of treatment showed statistically significant differences (all P＜0.05).Between-group comparisons of TNSS,TNNSS and RQLQ score after 4 weeks of treatment and in follow-up visits showed statistically significant differences (all P＜0.05).Conclusion:Acupuncture is effective for PAR,and acupuncture at meridian points can produce a better effect than acupuncture at non-meridian points.

OBJECTIVE: To analyze the sociodemographic and clinical factors related to anxiety in patients with major depressive disorder (MDD). METHODS: This study involved a secondary analysis of data obtained from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and conducted from September 1, 2010 to February 28, 2011. Based on the presence or absence of anxiety-related characteristics, 1,178 MDD patients were classified as suffering from anxious depression (n=915) or non-anxious depression (n=263), respectively. RESULTS: Compared with the non-anxious group, the anxious-depression group had an older age at onset (t=-4.39, p<0.001), were older (t=-4.69, p<0.001), reported more lifetime depressive episodes (z=-3.24, p=0.001), were more likely to experience seasonal depressive episodes (chi2=6.896, p=0.009) and depressive episodes following stressful life events (chi2=59.350, p<0.001), and were more likely to have a family history of psychiatric disorders (chi2=6.091, p=0.014). Their positive and total scores on the Mood Disorder Questionnaire (MDQ) and the 32-item Hypomania Checklist (HCL-32) (p<0.05) were also lower. The logistic regression analysis indicated that age (odds ratio [OR]=1.03, p<0.001), a lower total MDQ score (OR=0.94, p=0.011), depressive episodes following stressful life events (OR=3.04, p<0.001), and seasonal depressive episodes (OR=1.75, p=0.039) were significantly associated with anxious depression. CONCLUSION: These findings indicate that older age, fewer subclinical bipolar features, an increased number of depressive episodes following stressful life events, and seasonal depressive episodes may be risk factors for anxiety-related characteristics in patients with MDD.
Anxiety* ; Asian Continental Ancestry Group ; Bipolar Disorder ; Checklist ; China ; Depression ; Depressive Disorder ; Depressive Disorder, Major* ; Humans ; Logistic Models ; Mood Disorders ; Risk Factors* ; Seasons

This study is to explore new lead compounds by inhibition of Pin1 for anticancer therapy using temperature sensitive mutants. As Pin1 is conserved from yeast to human, we established a high-throughput screening method for Pin1 inhibitors, which employed yeast assay. This method led to the identification of one potent hits, 8-11. In vitro, 8-11 inhibited purified Pin1 enzyme activity with IC50 of (10.40 +/- 1.68) micromol x L(-1), induced G1 phase arrest and apoptosis, showed inhibitory effects on a series of cancer cell proliferation, reduced Cyclin D1 expression, was defined as reciprocally matched for protein-ligand complex in virtual docking analysis and reduced cell migration ability. In vivo, we could observe reduction of tumor volume after treatment with 8-11 in xenograft mice compared with vehicle DMSO treatment. Altogether, these results provide for the first time the involvement of 8-11 in the anticancer activity against Pin1.
Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cyclin D1 ; metabolism ; Drug Screening Assays, Antitumor ; methods ; G1 Phase ; High-Throughput Screening Assays ; methods ; Humans ; Mice ; NIMA-Interacting Peptidylprolyl Isomerase ; Neoplasms ; pathology ; Peptidylprolyl Isomerase ; antagonists & inhibitors ; Temperature ; Xenograft Model Antitumor Assays ; Yeasts

The objective was designed to assess the clinical efficiency of preventing febrile nonhemolytic transfusion reactions (FNHTR) with transfusion of leukocyte-depleted RBC and platelet concentrates. One hundred patients with cirrhosis of liver, gastric ulcer and cancer were selected to receive RBC concentrates with leukocyte filtration. Another group of 50 patients with liver necrosis, gastric ulcer and cancer were selected to receive non-filtered RBC concentrates. Two hundred and forty patients with acute or chronic leukemia, aplastic anemia, multiple myeloma, thrombocytopenia purpura, diabetes mellitus, cirrhosis of liver, upper gastrointestinal hemorrhage, severe hepatitis, burn and cancer post radioactive or chemical treatment were divided into two group with 120 patients in each one and selected randomly to receive platelet concentrates. The incidence rates of FNHTR in all patients were investigated. Results showed that there was no FNHTR in 100 transfusions with leukocyte-depleted RBC concentrates. Eight out of 50 patients with non-filtrated RBC concentrates showed FNHTR. The incidence of FNHTR was sixteen (16%) in non-filtrated transfusion. Twenty-five and 7 patients manifested FNHTR respectively in non-filtrated or filtrated platelets transfusions. The incidence of FNHTR was 20.83% and 5.83% respectively in non-filtrated or filtrated platelet transfusion. It is concluded that leukocyte-depleted RBC and platelet concentrates reduces FNH TR in blood transfusion.
Adult ; Blood Component Removal ; Female ; Fever ; prevention & control ; Filtration ; Humans ; Leukocytes ; Male ; Middle Aged ; Transfusion Reaction