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1.
CNS Neurosci Ther ; 30(6): e14782, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38828651

ABSTRACT

BACKGROUND: The thalamus system plays critical roles in the regulation of reversible unconsciousness induced by general anesthetics, especially the arousal stage of general anesthesia (GA). But the function of thalamus in GA-induced loss of consciousness (LOC) is little known. The thalamic reticular nucleus (TRN) is the only GABAergic neurons-composed nucleus in the thalamus, which is composed of parvalbumin (PV) and somatostatin (SST)-expressing GABAergic neurons. The anterior sector of TRN (aTRN) is indicated to participate in the induction of anesthesia, but the roles remain unclear. This study aimed to reveal the role of the aTRN in propofol and isoflurane anesthesia. METHODS: We first set up c-Fos straining to monitor the activity variation of aTRNPV and aTRNSST neurons during propofol and isoflurane anesthesia. Subsequently, optogenetic tools were utilized to activate aTRNPV and aTRNSST neurons to elucidate the roles of aTRNPV and aTRNSST neurons in propofol and isoflurane anesthesia. Electroencephalogram (EEG) recordings and behavioral tests were recorded and analyzed. Lastly, chemogenetic activation of the aTRNPV neurons was applied to confirm the function of the aTRN neurons in propofol and isoflurane anesthesia. RESULTS: c-Fos straining showed that both aTRNPV and aTRNSST neurons are activated during the LOC period of propofol and isoflurane anesthesia. Optogenetic activation of aTRNPV and aTRNSST neurons promoted isoflurane induction and delayed the recovery of consciousness (ROC) after propofol and isoflurane anesthesia, meanwhile chemogenetic activation of the aTRNPV neurons displayed the similar effects. Moreover, optogenetic and chemogenetic activation of the aTRN neurons resulted in the accumulated burst suppression ratio (BSR) during propofol and isoflurane GA, although they represented different effects on the power distribution of EEG frequency. CONCLUSION: Our findings reveal that the aTRN GABAergic neurons play a critical role in promoting the induction of propofol- and isoflurane-mediated GA.


Subject(s)
Anesthesia, General , Consciousness , GABAergic Neurons , Isoflurane , Propofol , Propofol/pharmacology , Isoflurane/pharmacology , Animals , GABAergic Neurons/drug effects , GABAergic Neurons/physiology , Mice , Consciousness/drug effects , Consciousness/physiology , Male , Electroencephalography , Anesthetics, Inhalation/pharmacology , Anterior Thalamic Nuclei/drug effects , Anterior Thalamic Nuclei/physiology , Mice, Inbred C57BL , Mice, Transgenic , Anesthetics, Intravenous/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , Optogenetics
2.
Oncol Lett ; 28(1): 337, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38846431

ABSTRACT

The present study aimed to investigate the anti-leukemic effects of dihydroartemisinin (DHA) on T-cell acute lymphoblastic leukemia (T-ALL) cell lines, Jurkat and Molt-4, and the underlying mechanisms. Cell Counting Kit-8 was performed to measure cell viability. Cell apoptosis and cell cycle distribution were assessed by flow cytometry. The expression levels of ATF4 and CHOP mRNA were assessed by reverse transcription-quantitative PCR, while the protein abundance of SLC7A11, GPX4, ATF4 and CHOP was determined by western blotting. Moreover, malondialdehyde, glutathione (GSH) and reactive oxygen species (ROS) assays were used to detect the levels of ferroptosis. The results showed that DHA suppressed T-ALL cell viability in vitro, and induced cell cycle arrest at S or G2/M phase. DHA also induced ROS burst, activated endoplasmic reticulum (ER) stress, disrupted the system Xc--GSH-GSH peroxidase 4 antioxidant system, and increased lipid peroxide accumulation, resulting in cell death. By contrast, the pharmacological inhibition of ferroptosis alleviated DHA-induced cell death, confirming that DHA induces T-ALL cell death via ferroptosis. Mechanistically, the effect of DHA on ferroptosis was partly mediated by downregulating SLC7A11 and upregulating the ATF4-CHOP signaling pathway, which is associated with ER stress. These results indicated that DHA may induce ferroptosis in T-ALL cell lines and could represent a promising therapeutic agent for treating T-ALL.

3.
Front Genet ; 15: 1366824, 2024.
Article in English | MEDLINE | ID: mdl-38846958

ABSTRACT

Background: An increasing amount of evidence suggests that gastrointestinal diseases are risk factors for herpes zoster (HZ) and postherpetic neuralgia (PHN). Among them, the gut microbiota may play a crucial role in this process. Therefore, this study aims to explore the potential causal association between the gut microbiota and HZ and PHN. Methods: Bidirectional two-sample Mendelian randomization (MR) analysis was used to detect the causal effect between HZ and PHN and the gut microbiota. Gut microbiota data were derived from the MiBioGen consortium, while HZ and PHN data were obtained from the FinnGen database. We selected single-nucleotide polymorphisms (SNPs) as instrumental variables with a threshold of p < 1 × 10⁻5 for the association with the gut microbiota in forward MR analysis and p < 5 × 10⁻8 for the association with HZ or PHN in reverse MR analysis and then removed SNPs in linkage disequilibrium (r 2 < 0.001) within a distance of 10,000 kb for both the gut microbiota and HZ and PHN. These SNPs were utilized to assess the causal effect between exposures and outcomes using inverse-variance weighting (IVW), MR-Egger, weighted mean, and weighted median tests. Results: The class Deltaproteobacteria, order Desulfovibrionales, family Desulfovibrionaceae, and genus Coprococcus 2 were found to reduce the risk of HZ, while the phylum Cyanobacteria, genus Eubacterium rectale group appeared to increase it. The class Coriobacteriia, order Coriobacteriales, family Coriobacteriaceae, genus Lachnospiraceae NK4A136 and genus Ruminococcaceae UCG011 were found to reduce the risk of PHN, while the genus Candidatus Soleaferrea, genus Eubacterium rectale group, and genus Methanobrevibacter appeared to increase it. Moreover, the onset of HZ was found to increase the level of the genus Eubacterium rectale group. These findings remained robust and unaffected by heterogeneity or horizontal pleiotropy among SNPs in both forward and reverse MR analysis. Conclusion: This MR study provided evidence supporting a potential causal relationship between the gut microbiota and HZ and PHN. Moreover, we found that the causal effect between the gut microbiota and HZ is bidirectional. Further studies are required to clarify the biological mechanisms linking the gut microbiota and these conditions.

4.
Adv Sci (Weinh) ; : e2401174, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38696650

ABSTRACT

Silver (Ag) is deemed a promising anode material for capacitive deionization (CDI) due to its high theoretical capacity and efficient selectivity to Cl-. However, the strong volume change during the conversion reaction significantly undermines the cycling performance of the Ag electrode. Additionally, achieving well-dispersed Ag in the active matrix is challenging, as Ag electrodes prepared by conventional thermal reduction tend to agglomerate. Herein, the organic linker confinement strategy is proposed, applying metal-organic framework (MOF) chemistry between Ag nodes and organic ligands to construct Ag-based MOF. The uniform dispersion of Ag at the molecular level, confined in the organic matrix, efficiently enhances the utilization of active sites, and strengthens the interfacial stability of Ag. Consequently, the Ag-MOF for the CDI anode exhibits an excellent Cl- removal capacity of 121.52 mg g-1 at 20 mA g-1 in 500 mg L-1 NaCl solution, and a high Ag utilization rate of 60.54%. After 100 cycles, a capacity retention of 96.93% is achieved. Furthermore, the Cl- capture mechanism of Ag-MOF is elucidated through density functional theory (DFT) calculations, ex situ XRD, ex situ Raman and XPS. This ingenious electrode design can offer valuable insights for the development of high-performance conversion electrodes for CDI applications.

5.
Mol Biol Rep ; 51(1): 697, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802698

ABSTRACT

Natural medicines are a valuable resource for the development of new drugs. However, factors such as low solubility and poor bioavailability of certain constituents have hindered their efficacy and potential as pharmaceuticals. Structural modification of natural products has emerged as an important research area for drug development. Phosphorylation groups, as crucial endogenous active groups, have been extensively utilized for structural modification and development of new drugs based on natural molecules. Incorporating phosphate groups into natural molecules not only enhances their stability, bioavailability, and pharmacological properties, but also improves their biological activity by altering their charge, hydrogen bonding, and spatial structure. This review summarizes the phosphorylation mechanism, modification approaches, and biological activity enhancement of natural medicines. Notably, compounds such as polysaccharides, flavonoids, terpenoids, anthraquinones, and coumarins exhibit increased antioxidation, anticancer, antiviral, immune regulatory, Antiaging, enzyme inhibition, bacteriostasis, liver protection, and lipid-lowering effects following phosphorylation modification.


Subject(s)
Biological Products , Biological Products/pharmacology , Biological Products/chemistry , Biological Products/metabolism , Phosphorylation , Humans , Animals , Flavonoids/chemistry , Flavonoids/metabolism , Flavonoids/pharmacology , Polysaccharides/chemistry , Polysaccharides/metabolism , Antioxidants/pharmacology , Antioxidants/chemistry , Anthraquinones/chemistry , Anthraquinones/pharmacology
6.
J Transl Med ; 22(1): 368, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637886

ABSTRACT

In this study, we investigated CD70 as a promising target for renal cell carcinoma (RCC) therapy and developed a potent chimeric antigen receptor T (CAR-T) cells for potential clinical testing. CD70, found to be highly expressed in RCC tumors, was associated with decreased survival. We generated CAR-T cells expressing VHH sequence of various novel nanobodies from immunized alpaca and a single-chain variable fragment (scFv) derived from human antibody (41D12). In our in vitro experiments, anti-CD70 CAR-T cells effectively eliminated CD70-positive tumor cells while sparing CD70-negative cells. The nanobody-based CAR-T cells demonstrated significantly higher production of cytokines such as IL-2, IFN-γ and TNF-ɑ during co-culture, indicating their potential for enhanced functionality. In xenograft mouse model, these CAR-T cells exhibited remarkable anti-tumor activity, leading to the eradication of RCC tumor cells. Importantly, human T cell expansion after infusion was significantly higher in the VHH groups compared to the scFv CAR-T group. Upon re-challenging mice with RCC tumor cells, the VHH CAR-T treated group remained tumor-free, suggesting a robust and long-lasting anti-tumor response. These findings provide strong support for the potential of nanobody-based CD70 CAR-T cells as a promising therapeutic option for RCC. This warrants further development and consideration for future clinical trials and applications.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Receptors, Chimeric Antigen , Humans , Animals , Mice , Carcinoma, Renal Cell/therapy , T-Lymphocytes , Cell Line, Tumor , Kidney Neoplasms/therapy , Immunotherapy, Adoptive , Xenograft Model Antitumor Assays , CD27 Ligand
7.
Sci Rep ; 14(1): 9203, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649403

ABSTRACT

Addressing the limitations of existing landslide displacement prediction models in capturing the dynamic characteristics of data changes, this study introduces a novel dynamic displacement prediction model for landslides. The proposed method combines Variational Mode Decomposition (VMD) with Sparrow Search Optimization (SSO) and Long Short-Term Memory (LSTM) techniques to formulate a comprehensive VMD-SSO-LSTM model. Through the application of VMD, the method dissects cumulative displacement and rainfall data, thereby extracting distinct components such as trend, periodicity, and fluctuation components for displacement, as well as low-frequency and high-frequency components for rainfall. Furthermore, leveraging Gray Correlational Analysis, the interrelationships between the periodic component of displacement and the low-frequency component of rainfall, as well as the fluctuation component of displacement and the high-frequency component of rainfall, are established. Building upon this foundation, the SSO-LSTM model dynamically predicts the interrelated displacement components, synthesizing the predicted values of each component to generate real-time dynamic forecasts. Simulation results underscore the effectiveness of the proposed VMD-SSO-LSTM model, indicating root-mean-square error (RMSE) and mean absolute percentage error (MAPE) values of 1.2329 mm and 0.1624%, respectively, along with a goodness of fit (R2) of 0.9969. In comparison to both back propagation (BP) prediction model and LSTM prediction model, the VMD-SSO-LSTM model exhibits heightened predictive accuracy.

8.
Sensors (Basel) ; 24(7)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38610296

ABSTRACT

The contact wire wear is an important parameter to ensure the safety operation of electric railways. The contact wire may break if the wear is serious, which leads to transportation interruptions. This study proposes an optical measurement method of contact wire wear, using stereovision technology. The matching method of stereovision based on line-scan cameras is proposed. A lookup-table method is developed to exactly determine the image resolution caused by the contact wire being in different spatial positions. The wear width of the contact wire is extracted from catenaries' images, and the residual thickness of the contact wire is calculated. The method was verified by field tests. The round-robin tests of the residual thickness at the same location present excellent measurement repetitiveness. The maximum difference value between dynamic test results and ground measurement results is 0.13 mm. This research represents a potential way to implement condition-based maintenance for contact wire wear in the future in order to improve the maintenance efficiency and ensure the safety of catenary infrastructure.

9.
Emerg Microbes Infect ; 13(1): 2348525, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38661428

ABSTRACT

To assess the clinical applicability of a semi-quantitative luciferase immunosorbent assay (LISA) for detecting antibodies against Treponema pallidum antigens TP0171 (TP15), TP0435 (TP17), and TP0574 (TP47) in diagnosing and monitoring syphilis. LISA for detection of anti-TP15, TP17, and TP47 antibodies were developed and evaluated for syphilis diagnosis using 261 serum samples (161 syphilis, 100 non-syphilis). Ninety serial serum samples from 6 syphilis rabbit models (3 treated, 3 untreated) and 110 paired serum samples from 55 syphilis patients were used to assess treatment effects by utilizing TRUST as a reference. Compared to TPPA, LISA-TP15, LISA-TP17, and LISA-TP47 showed a sensitivity of 91.9%, 96.9%, and 98.8%, specificity of 99%, 99%, and 98%, and AUC of 0.971, 0.992, and 0.995, respectively, in diagnosing syphilis. Strong correlations (rs = 0.89-0.93) with TPPA were observed. In serial serum samples from rabbit models, significant differences in the relative light unit (RLU) were observed between the treatment and control group for LISA-TP17 (days 31-51) and LISA-TP47 (day 41). In paired serum samples from syphilis patients, TRUST titres and the RLU of LISA-TP15, LISA-TP17, and LISA-TP47 decreased post-treatment (P < .001). When TRUST titres decreased by 0, 2, 4, or ≥8-folds, the RLU decreased by 17.53%, 31.34%, 48.62%, and 72.79% for LISA-TP15; 8.84%, 17.00%, 28.37%, and 50.57% for LISA-TP17; 22.25%, 29.79%, 51.75%, and 70.28% for LISA-TP47, respectively. Semi-quantitative LISA performs well for syphilis diagnosis while LISA-TP17 is more effective for monitoring syphilis treatment in rabbit models and clinical patients.


Subject(s)
Antibodies, Bacterial , Antigens, Bacterial , Sensitivity and Specificity , Syphilis , Treponema pallidum , Syphilis/diagnosis , Syphilis/microbiology , Syphilis/blood , Treponema pallidum/immunology , Animals , Humans , Rabbits , Antibodies, Bacterial/blood , Antigens, Bacterial/immunology , Male , Female , Adult , Luciferases/genetics , Syphilis Serodiagnosis/methods , Middle Aged , Disease Models, Animal , Young Adult
10.
Heliyon ; 10(5): e26170, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38439874

ABSTRACT

Objective: To analyse and summarise the regularity of acupoint selection in the treatment of opioid-induced constipation (OIC) in patients with cancer pain using a data mining technique and provide a reference for clinical practice and more valuable treatment options. Methods: The acupoint prescription database for the treatment of OIC-related cancer pain was established by searching the relevant literature on randomised controlled trials involving acupoint therapy for OIC-related cancer pain in seven major databases, including the China National Knowledge Infrastructure, Wanfang and VIP Chinese scientific journal databases, from database establishment to December 31, 2022. The main therapeutic measures of acupoint prescription, frequency of acupoint use and its subordinate meridians and subordinate sites were then analysed. Through systematic clustering and association rule analysis, the core acupoint prescriptions and most commonly used acupoint compatibility of acupoint therapy for OIC-related cancer pain were obtained. Results: A total of 649 articles were retrieved, with 72 articles included after screening. The treatment measures were found to be mainly acupoint applications involving 28 acupoints, with a total frequency of 234. The three most frequently used acupoints were Shenque, Tianshu and Zusanli. The number of points used in the Foot-Yangming stomach meridian was the highest. Commonly used acupoints were mainly distributed in the abdomen. The compatibility of two commonly used acupoints was obtained through systematic clustering. Through association rule analysis, it was found that in the compatibility of acupoints, the strongest correlation was between Tianshu and Zusanli, and their frequency of application was the highest. Conclusion: Tianshu and Zusanli are the core acupoints for acupoint therapy in the treatment of OIC-related cancer pain, and the Shangjuxu-Zhigou-Zusanli, Qihai-Guanyuan and Zhongwan-Tianshu acupoints exhibit the highest compatibility. This study provides a reference for the clinical acupoint selection programme of acupuncture and moxibustion in the treatment of OIC-related cancer pain.

11.
Behav Sci (Basel) ; 14(3)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38540498

ABSTRACT

Self-concept clarity is considered a crucial indicator of mental health. Although several studies have examined the correlation between self-concept clarity and loneliness, few studies have investigated the underlying mechanism. Based on the evolutionary theory of loneliness and social penetration theory, this cross-sectional study focused on cognitive and behavioral factors in interpersonal communication situations, aiming to explore the relationship between self-concept clarity and loneliness as well as its internal mechanism. An online questionnaire survey comprised 1145 college students in China to assess their self-concept clarity, fear of negative evaluation, self-disclosure, and loneliness. After controlling for demographic variables, the results showed that self-concept clarity was not only able to directly and negatively predict loneliness but also indirectly predict loneliness through the independent mediating effects of fear of negative evaluation and self-disclosure, as well as the chain-mediating effect of fear of negative evaluation to self-disclosure. This study provides important implications for cognitive and behavioral intervention strategies to alleviate people's loneliness and improve their mental health.

12.
Sex Health ; 212024 Mar.
Article in English | MEDLINE | ID: mdl-38538087

ABSTRACT

Coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an ongoing global public health challenge. This disease causes damage not only to the respiratory system, affecting the normal physiological function of the lungs, but also to other vital organs, such as the heart and testicles. Existing studies have shown that co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 is the main mechanism by which SARS-CoV-2 invades host cells. Angiotensin-converting enzyme 2-expressing cells are widespread in the corpus cavernosum, reproductive tract and testis of men, which has raised concerns. Furthermore, abnormal sex hormone levels and decreased semen parameters were observed in coronavirus disease 2019 patients. This study comprehensively assessed the effects of SARS-CoV-2 infection on the testis, semen parameters, sex hormone levels and erectile function, and discussed possible transmission routes during sexual intercourse and the effect of vaccination on male fertility.


Subject(s)
COVID-19 , Humans , Male , COVID-19/prevention & control , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Peptidyl-Dipeptidase A , Fertility , Gonadal Steroid Hormones , Vaccination
13.
J Clin Anesth ; 95: 111447, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38522144

ABSTRACT

STUDY OBJECTIVE: To investigate whether a single dosage of esketamine injection in the anesthesia period could improve postoperative negative emotions and early cognitive function in patients undergoing non-cardiac thoracic surgery. DESIGN: A prospective single center double blinded randomized placebo-controlled trial. SETTING: Perioperative period; operating room, post anesthesia care unit and hospital ward. PATIENTS: 129 adult patients that underwent elective non-cardiac thoracic surgery under general anesthesia. INTERVENTIONS: During the operation, pharmacologic prevention of postoperative negative emotion and early cognitive disorder with 0.2 mg/kg (Low esketamine group) and 0.5 mg/kg esketamine (High esketamine group) vs. placebo. MEASUREMENTS: Emotion and early cognitive performance were assessed on the day before surgery (POD-1), postoperative day 1 (POD1) and day 3 (POD3) using HADS-A, HADS-D, Pain Visual Analogue Scale (VAS), Confusion Assessment Method (CAM), Mini-Mental State Examination (MMSE), and serum biomarkers (S100ß, BDNF, IL-6, acetylcholine, and norepinephrine). MAIN RESULTS: The high esketamine group showed significantly lower HADS-A and HADS-D scores than control group on POD1 and POD3. No significant differences were observed between the low esketamine group and the control group. The esketamine-treated groups showed lower pain VAS scores than the control group at 2 h and on the first day after operation. There were no significant differences among the three groups in CAM and MMSE scores. However, the high esketamine group had lower S100ß and IL-6 levels, and higher BDNF levels postoperatively, while serum acetylcholine and norepinephrine were not significantly different. CONCLUSIONS: A single intraoperative injection of 0.5 mg/kg esketamine can alleviate postoperative anxiety, depression, and pain to some extent. Although cognitive function behavioral evaluation did not show obvious benefits, it can also reduce the production of pro-inflammatory and brain injury-related factors while promoting the generation of brain-derived neurotrophic factor. Registration Trial registry: http://www.chictr.org.cn/; Identifier: ChiCTR2100047067.


Subject(s)
Anesthesia, General , Ketamine , Thoracic Surgical Procedures , Humans , Ketamine/administration & dosage , Ketamine/adverse effects , Male , Female , Double-Blind Method , Middle Aged , Prospective Studies , Aged , Thoracic Surgical Procedures/adverse effects , Anesthesia, General/adverse effects , Postoperative Cognitive Complications/prevention & control , Postoperative Cognitive Complications/etiology , Cognition/drug effects , Emotions/drug effects , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Pain Measurement , Adult , Brain-Derived Neurotrophic Factor/blood
14.
Small Methods ; : e2301229, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38528393

ABSTRACT

The charge-transfer (CT) interactions between organic compounds are reflected in the (opto)electronic properties. Determining and visualizing crystal structures of CT complexes are essential for the design of functional materials with desirable properties. Complexes of pyranine (PYR), methyl viologen (MV), and their derivatives are the most studied water-based CT complexes. Nevertheless, very few crystal structures of CT complexes have been reported so far. In this study, the structures of two PYRs-MVs CT crystals and a map of the noncovalent interactions using 3D electron diffraction (3DED) are reported. Physical properties, e.g., band structure, conductivity, and electronic spectra of the CT complexes and their crystals are investigated and compared with a range of methods, including solid and liquid state spectroscopies and highly accurate quantum chemical calculations based on density functional theory (DFT). The combination of 3DED, spectroscopy, and DFT calculation can provide important insight into the structure-property relationship of crystalline CT materials, especially for submicrometer-sized crystals.

15.
Prev Med Rep ; 40: 102673, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38495769

ABSTRACT

Objectives: This research aimed to explore the prevalence and determinants of overweight, obesity, and central obesity in Shenmu City, Shaanxi Province, China and to offer guidance for preventative health measures. Methods: We conducted a multi-stage, stratified random sampling survey among 4,565 residents of Shenmu City. Data collection included questionnaires and anthropometric assessments to gather socio-demographic data and to identify cases of overweight, obesity, and central obesity. Multivariable logistic regression analysis was utilized to assess the association between various factors and these conditions. Results: The observed prevalence rates for overweight, obesity, central obesity, and the combination of overweight/obesity with central obesity were 39.9%, 18.2%, 48.0%, 32.8%, and 22.8%, respectively. Notably, the incidence of these conditions was significantly higher in men compared to women. The prevalence of overweight and obesity initially increased and then decreased with age, whereas the prevalence of central obesity consistently rose. Furthermore, a higher educational level correlated with lower prevalence rates. Additionally, our analysis indicated that hypertension, dyslipidemia, and hyperuricemia are risk factors for these conditions. Conclusions: The findings of this study offer crucial insights for formulating effective strategies to prevent and manage obesity in Shenmu City.

16.
J Biol Chem ; 300(4): 107150, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38462164

ABSTRACT

Histone 2A monoubiquitination (uH2A) underscores a key epigenetic regulation of gene expression. In this report, we show that the deubiquitinase for uH2A, ubiquitin-specific peptidase 16 (USP16), is modified by O-linked N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation involves the installation of the O-GlcNAc moiety to Ser/Thr residues. It crosstalks with Ser/Thr phosphorylation, affects protein-protein interaction, alters enzyme activity or protein folding, and changes protein subcellular localization. In our study, we first confirmed that USP16 is glycosylated on Thr203 and Ser214, as reported in a previous chemoenzymatic screen. We then discovered that mutation of the O-GlcNAcylation site Thr203, which is adjacent to deubiquitination-required Cys204, reduces the deubiquitination activity toward H2AK119ub in vitro and in cells, while mutation on Ser214 had the opposite effects. Using USP16 Ser552 phosphorylation-specific antibodies, we demonstrated that O-GlcNAcylation antagonizes cyclin-dependent kinase 1-mediated phosphorylation and promotes USP16 nuclear export. O-GlcNAcylation of USP16 is also required for deubiquitination of Polo-like kinase 1, a mitotic master kinase, and the subsequent chromosome segregation and cytokinesis. In summary, our study revealed that O-GlcNAcylation of USP16 at Thr203 and Ser214 coordinates deubiquitination of uH2A and Polo-like kinase 1, thus ensuring proper cell cycle progression.


Subject(s)
Acetylglucosamine , Ubiquitin Thiolesterase , Ubiquitination , Humans , Acetylglucosamine/metabolism , Active Transport, Cell Nucleus , Cell Cycle , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Glycosylation , HEK293 Cells , HeLa Cells , Histones/metabolism , Phosphorylation , Polo-Like Kinase 1 , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Ubiquitin Thiolesterase/metabolism , Ubiquitin Thiolesterase/genetics
17.
Microbiol Spectr ; 12(3): e0364523, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38319081

ABSTRACT

CRISPR-Cas technology has widely been applied to detect single-nucleotide mutation and is considered as the next generation of molecular diagnostics. We previously reported the combination of nucleic acid amplification (NAA) and CRISPR-Cas12a system to distinguish major severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. However, the mixture of NAA and CRISPR-Cas12a reagents in one tube could interfere with the efficiency of NAA and CRISPR-Cas12a cleavage, which in turn affects the detection sensitivity. In the current study, we employed a novel photoactivated CRISPR-Cas12a strategy integrated with recombinase polymerase amplification (RPA) to develop one-pot RPA/CRISPR-Cas12a genotyping assay for detecting SARS-CoV-2 Omicron sub-lineages. The new system overcomes the potential inhibition of RPA due to early CRISPR-Cas12a activation and cleavage of the target template in traditional one-pot assay using photocleavable p-RNA, a complementary single-stranded RNA to specifically bind crRNA and precisely block Cas12a activation. The detection can be finished in one tube at 39℃ within 1 h and exhibits a low limit of detection of 30 copies per reaction. Our results demonstrated that the photocontrolled one-pot RPA/CRISPR-Cas12a assay could effectively identify three signature mutations in the spike gene of SARS-CoV-2 Omicron variant, namely, R346T, F486V, and 49X, and distinguish Omicron BA.1, BA.5.2, and BF.7 sub-lineages. Furthermore, the assay achieved a sensitivity of 97.3% and a specificity of 100.0% and showed a concordance of 98.3% with Sanger sequencing results.IMPORTANCEWe successfully developed one-pot recombinase polymerase amplification/CRISPR-Cas12a genotyping assay by adapting photocontrolled CRISPR-Cas technology to optimize the conditions of nucleic acid amplification and CRISPR-Cas12a-mediated detection. This innovative approach was able to quickly distinguish severe acute respiratory syndrome coronavirus 2 Omicron variants and can be readily modified for detecting any nucleic acid mutations. The assay system demonstrates excellent clinical performance, including rapid detection, user-friendly operations, and minimized risk of contamination, which highlights its promising potential as a point-of-care testing for wide applications in resource-limiting settings.


Subject(s)
COVID-19 , Nucleic Acids , Humans , COVID-19/diagnosis , CRISPR-Cas Systems , SARS-CoV-2/genetics , Recombinases , RNA
18.
Entropy (Basel) ; 26(2)2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38392416

ABSTRACT

Correlations between exchange rates are valuable for illuminating the dynamics of international trade and the financial dynamics of countries. This paper explores the changing interactions of the US foreign exchange market based on detrended cross-correlation analysis. First, we propose an objective way to choose a time scale parameter appropriate for comparing different samples by maximizing the summed magnitude of all DCCA coefficients. We then build weighted signed networks under this optimized time scale, which can clearly display the complex relationships between different exchange rates. Our study shows negative cross-correlations have become pyramidally rare in the past three decades. Both the number and strength of positive cross-correlations have grown, paralleling the increase in global interconnectivity. The balanced strong triads are identified subsequently after the network centrality analysis. Generally, while the strong development links revealed by foreign exchange have begun to spread to Asia since 2010, Europe is still the center of world finance, with the euro and Danish krone consistently maintaining the closest balanced development relationship. Finally, we propose a fluctuation propagation algorithm to investigate the propagation pattern of fluctuations in the inferred exchange rate networks. The results show that, over time, fluctuation propagation patterns have become simpler and more predictable.

19.
Article in English | MEDLINE | ID: mdl-38416184

ABSTRACT

OBJECTIVE: To investigate the distribution characteristics of perioperative deep venous thrombosis (DVT) in patients with thoracolumbar fractures caused by high-energy injuries and analyze the risk factors of postoperative DVT exacerbation. METHODS: From October 2016 to July 2021, a total of 550 patients with thoracolumbar fractures due to high-energy injuries in our hospital were retrospectively analyzed. Both lower limbs were examined by ultrasound before and after operation. Depending on whether the postoperative DVT was exacerbating, the group was divided into a DVT exacerbation group and a non-DVT exacerbation group. Clinical data were used to study the characteristics of perioperative DVT. Logistic regression analysis and receiver operating characteristic (ROC) curve were used to explore the risk factors of postoperative DVT exacerbation. RESULTS: DVT was found in 97 patients before operation, including 78 cases of distal thrombus, 6 cases of proximal thrombus, and 13 cases of mixed thrombus. Postoperative DVT increased to 116, including 87 distal thrombus, 10 proximal thrombus, and 19 mixed thrombus. The intermuscular vein was the most easily involved vein. Compared with lumbar fractures, thoracic fractures were more likely to have postoperative proximal thrombus (P=0.014). There were 48 cases of thrombus exacerbation after operation. Logistic regression analysis revealed that age, lower extremity muscle strength, time from injury to operation, and blood loss were risk factors for postoperative DVT exacerbation. CONCLUSIONS: The intermuscular vein is the most easily involved vein. The anatomical distribution of DVT at different fracture sites is different, and patients with thoracic fractures are more likely to have proximal DVT after operation. Age, lower extremity muscle strength, time from injury to operation, and blood loss were risk factors for postoperative DVT exacerbation.

20.
Chem Commun (Camb) ; 60(17): 2369-2372, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38318781

ABSTRACT

Conventional methods for nitrile synthesis bring inherent environmental risks due to their reliance on oxidants and harsh reaction conditions. Meanwhile, direct electrooxidation of amines to nitriles suffers from low current density. In this study, we propose an innovative indirect electrooxidation strategy for nitrile formation, mediated by Br-/Br2, utilizing a highly efficient CoS2/CoS@Graphite Felt (GF) electrode. Notably, the anodic nitrile generation can be synergistically coupled with the cathodic hydrogen evolution reaction (HER). Through meticulous optimization of reaction parameters, we achieve an impressive 98% selectivity for octanenitrile at a current density of 60 mA cm-2 with a remarkable faradaic efficiency (FE) of 87%. Furthermore, our approach demonstrates excellent versatility, as we successfully evaluate both aliphatic and aromatic primary amines, highlighting its promising potential for practical applications in the field.

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