A sensitive fluorescence assay of serum dipeptidyl peptidase IV activity to predict the suitability of its inhibitors in patients with type 2 diabetes mellitus.

DPP-IV inhibitors, which are close to the natural hypoglycemic pathway of human physiology and have few side effects, have been extensively employed in the management of type 2 diabetes mellitus (T2DM). However, there are currently no specific blood indicators that can indicate or predict a patient's suitability for DPP-IV inhibitors. In this study, based on the self-developed high-specificity fluorescent substrate glycyl-prolyl-N-butyl-4-amino-1, 8-naphthimide (GP-BAN), a detection method of human serum DPP-IV activity was established and optimized. The method demonstrates a favorable lower limit of detection (LOD) at 0.32 ng/mL and a satisfactory lower limit of quantification (LOQ) of 1.12 ng/mL, and can be used for the detection of DPP-IV activity in trace serum (2 µL). In addition, Vitalliptin and Sitagliptin showed similar IC50 values when human recombinant DPP-IV and human serum were used as enzyme sources, and the intra-day and inter-day precision obtained by the microplate analyzer were less than 15 %. These results indicate that the microplate reader based detection technique has good accuracy, repeatability and reproducibility. A total of 700 volunteers were recruited, and 646 serum samples were tested for DPP-IV activity. The results showed that serum DPP-IV activity was higher in patients with T2DM than in controls (P < 0.01). However, the statistical data of family history of diabetes, gender and age of diabetic patients showed no statistical significance, and there was no contrast difference. The DPP-IV activity of serum in T2DM patients ranged from 2.4 µmol/min/L to 78.6 µmol/min/L, with a huge difference of up to 32-fold. These results suggest that it is necessary to test DPP-IV activity in patients with T2DM when taking DPP-IV inhibitors to determine the applicability of DPP-IV inhibitors in T2DM patients. These results suggest that it is necessary to detect the activity of DPP-IV in blood before taking DPP-IV inhibitors in patients with T2DM to judge the applicability of DPP-IV inhibitors in patients with T2DM.

Effects and neural mechanisms of different physical activity on major depressive disorder based on cerebral multimodality monitoring: a narrative review.

Major depressive disorder (MDD) is currently the most common psychiatric disorder in the world. It characterized by a high incidence of disease with the symptoms like depressed mood, slowed thinking, and reduced cognitive function. Without timely intervention, there is a 20-30% risk of conversion to treatment-resistant depression (TRD) and a high burden for the patient, family and society. Numerous studies have shown that physical activity (PA) is a non-pharmacological treatment that can significantly improve the mental status of patients with MDD and has positive effects on cognitive function, sleep status, and brain plasticity. However, the physiological and psychological effects of different types of PA on individuals vary, and the dosage profile of PA in improving symptoms in patients with MDD has not been elucidated. In most current studies of MDD, PA can be categorized as continuous endurance training (ECT), explosive interval training (EIT), resistance strength training (RST), and mind-body training (MBT), and the effects on patients' depressive symptoms, cognitive function, and sleep varied. Therefore, the present study was based on a narrative review and included a large number of existing studies to investigate the characteristics and differences in the effects of different PA interventions on MDD. The study also investigated the characteristics and differences of different PA interventions in MDD, and explained the neural mechanisms through the results of multimodal brain function monitoring, including the intracranial environment and brain structure. It aims to provide exercise prescription and theoretical reference for future research in neuroscience and clinical intervention in MDD.

Congenital Cutaneous Sinus at the Sternoclavicular Joint.

A 32-year-old female patient presented with chronic discharging sinus with recurrent infection at the left sternoclavicular joint. What is your diagnosis?

Janus kinase inhibitor tofacitinib successfully treated palmoplantar pustulosis after switching from secukinumab: A case report and review of the literature.

Palmoplantar pustulosis (PPP) is a chronic inflammatory recurrent disease characterized by sterile pustules involving palms and/or feet. Presently, there are no standard recommended treatment regimens. Tofacitinib is an oral Janus kinase (JAK) inhibitor, mainly acts on JAK 1 and 3 and has been approved for the treatment of rheumatoid arthritis in adults. Herein, we present a case of a patient with PPP who did not respond to IL-17A inhibitor secukinumab but was successfully treated by the JAK inhibitor tofacitinib.

Targeting pericentric non-consecutive motifs for heterochromatin initiation.

Pericentric heterochromatin is a critical component of chromosomes marked by histone H3 K9 (H3K9) methylation1-3. However, what recruits H3K9-specific histone methyltransferases to pericentric regions in vertebrates remains unclear4, as does why pericentric regions in different species share the same H3K9 methylation mark despite lacking highly conserved DNA sequences2,5. Here we show that zinc-finger proteins ZNF512 and ZNF512B specifically localize at pericentric regions through direct DNA binding. Notably, both ZNF512 and ZNF512B are sufficient to initiate de novo heterochromatin formation at ectopically targeted repetitive regions and pericentric regions, as they directly recruit SUV39H1 and SUV39H2 (SUV39H) to catalyse H3K9 methylation. SUV39H2 makes a greater contribution to H3K9 trimethylation, whereas SUV39H1 seems to contribute more to silencing, probably owing to its preferential association with HP1 proteins. ZNF512 and ZNF512B from different species can specifically target pericentric regions of other vertebrates, because the atypical long linker residues between the zinc-fingers of ZNF512 and ZNF512B offer flexibility in recognition of non-consecutively organized three-nucleotide triplets targeted by each zinc-finger. This study addresses two long-standing questions: how constitutive heterochromatin is initiated and how seemingly variable pericentric sequences are targeted by the same set of conserved machinery in vertebrates.

Elevating Discharge Voltage of Li2CO3-Routine Li-CO2 Battery over 2.9†V at an Ultra-Wide Temperature Window.

The Li-CO2 batteries utilizing greenhouse gas CO2 possess advantages of high energy density and environmental friendliness. However, these batteries following Li2CO3-product route typically exhibit low work voltage (<2.5 V) and energy efficiency. Herein, we have demonstrated for the first time that cobalt phthalocyanine (CoPc) as homogeneous catalyst can elevate the work plateau towards 2.98 V, which is higher than its theoretical discharge voltage without changing the Li2CO3-product route. This unprecedented discharge voltage is illustrated by mass spectrum and electrochemical analyses that CoPc has powerful adsorption capability with CO2 (-7.484 kJ mol-1) and forms discharge intermediate of C33H16CoN8O2. Besides high discharge capacity of 18724 mAh g-1 and robust cyclability over 1600 hours (1000 mAh g-1 cut-off) at a current density of 100 mA g-1, the batteries show high temperature adaptability (-30-80 °C). Our work is paving a promising avenue for the progress of high-efficiency Li-CO2 batteries.

Effect of acupuncture on tic disorder: a randomized controlled clinical trial based on energy metabolomics and infrared thermography.

BACKGROUND: Acupuncture is a method for treating tic disorder. However, there is a lack of sufficient clinical objective basis in regards of its treatment efficacy. Indeed, there are structural abnormalities present in energy metabolism and infrared thermography in children with tic disorder. Therefore, this study proposes a clinical trial scheme to explore the possible mechanism of acupuncture in treating tic disorder. METHODS: This randomized controlled trial will recruit a total of 90 children, in which they will be divided into non-intervention group and intervention group. The non-intervention group consists of 30 healthy children while the intervention group consists of 60 children with tic disorder. The intervention group will be randomly allocated into either the treatment group or the control group, with 30 children randomly assigned in each group. Children either received acupuncture treatment and behavioral therapy (treatment group) or sham acupuncture treatment and behavioral therapy (control group), 3 treatment sessions per week for a period of 12 weeks, with a total of 36 treatment sessions. Outcome measures include YGTSS, urinary and fecal metabolomics, infrared thermography of body surface including governor vessel. For the intervention group, these outcome measures will be collected at the baseline and 90th day prior to intervention. Whereas for the non-intervention group, outcome measures (excluding YGTSS) will be collected at the baseline. DISCUSSION: The main outcome will be to observe the changes of the severity of tic condition, the secondary outcome will be to observe the changes of structural characteristic of infrared thermography of body surface/acupoints along the governor vessel and to evaluate the changes of urinary and fecal metabolomics at the end of the treatment, so as to analyze the relationship between them and to provide further knowledge in understanding the possible mechanism of acupuncture in improving the clinical symptoms via regulating and restoring the body metabolomics network, which in future it can develop as a set of clinical guideline (diagnosis, treatment, assessment, prognosis) in treating tic disorder. ChiCTR2300075188(Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 29 August 2023).

LINE-1 transcription activates long-range gene expression.

Long interspersed nuclear element-1 (LINE-1 or L1) is a retrotransposon group that constitutes 17% of the human genome and shows variable expression across cell types. However, the control of L1 expression and its function in gene regulation are incompletely understood. Here we show that L1 transcription activates long-range gene expression. Genome-wide CRISPR-Cas9 screening using a reporter driven by the L1 5' UTR in human cells identifies functionally diverse genes affecting L1 expression. Unexpectedly, altering L1 expression by knockout of regulatory genes impacts distant gene expression. L1s can physically contact their distal target genes, with these interactions becoming stronger upon L1 activation and weaker when L1 is silenced. Remarkably, L1s contact and activate genes essential for zygotic genome activation (ZGA), and L1 knockdown impairs ZGA, leading to developmental arrest in mouse embryos. These results characterize the regulation and function of L1 in long-range gene activation and reveal its importance in mammalian ZGA.

Classification of peanut pod rot based on improved YOLOv5s.

Peanut pod rot is one of the major plant diseases affecting peanut production and quality over China, which causes large productivity losses and is challenging to control. To improve the disease resistance of peanuts, breeding is one significant strategy. Crucial preventative and management measures include grading peanut pod rot and screening high-contributed genes that are highly resistant to pod rot should be carried out. A machine vision-based grading approach for individual cases of peanut pod rot was proposed in this study, which avoids time-consuming, labor-intensive, and inaccurate manual categorization and provides dependable technical assistance for breeding studies and peanut pod rot resistance. The Shuffle Attention module has been added to the YOLOv5s (You Only Look Once version 5 small) feature extraction backbone network to overcome occlusion, overlap, and adhesions in complex backgrounds. Additionally, to reduce missing and false identification of peanut pods, the loss function CIoU (Complete Intersection over Union) was replaced with EIoU (Enhanced Intersection over Union). The recognition results can be further improved by introducing grade classification module, which can read the information from the identified RGB images and output data like numbers of non-rotted and rotten peanut pods, the rotten pod rate, and the pod rot grade. The Precision value of the improved YOLOv5s reached 93.8%, which was 7.8%, 8.4%, and 7.3% higher than YOLOv5s, YOLOv8n, and YOLOv8s, respectively; the mAP (mean Average Precision) value was 92.4%, which increased by 6.7%, 7.7%, and 6.5%, respectively. Improved YOLOv5s has an average improvement of 6.26% over YOLOv5s in terms of recognition accuracy: that was 95.7% for non-rotted peanut pods and 90.8% for rotten peanut pods. This article presented a machine vision- based grade classification method for peanut pod rot, which offered technological guidance for selecting high-quality cultivars with high resistance to pod rot in peanut.

Correlation between Disc Imaging Observations and Clinical Efficacy after Percutaneous Endoscopic Lumbar Discectomy: A 1-Year Follow-up Study.

OBJECTIVE: The connection between alterations in the disc structure following percutaneous endoscopic lumbar discectomy (PELD) and symptoms in patients postsurgery has not been reported yet. The purpose of the present study was to discuss the potential correlation between the changes in the morphological characteristics of various reference surfaces of the intervertebral disc after percutaneous endoscopic lumbar discectomy (PELD) and clinical outcomes, to identify the morphological parameters that affect efficacy and provide an evidence-based foundation for assessing postoperative efficacy. METHODS: From October 2019 to October 2021, after percutaneous endoscopic lumbar discectomy (PELD), 98 individuals were enrolled. MRI DICOM data of the lumbar spine were obtained before and after surgery, specifically around 3 months. The morphological parameters of the operated and adjacent segments of the discs were measured using T2-weighted images from three reference planes. Outcomes were assessed using the Oswestry disability index (ODI), visual analogue pain scores for the back and leg (VAS-back/VAS-leg), Japanese Orthopaedic Association (JOA) scores, and recovery rates. Postoperative changes in disc parameters and outcomes were compared between patients with different severity and types of LDH based on the MSU staging. Patients completed the questionnaire during outpatient follow-up appointments 3, 6, and 12 months after the surgery. The follow-up period was 14.69 ± 4.21 months, ranging from 12 to 24 months. RESULTS: Parameters such as area and circumference of intervertebral discs in the cross-section were not associated with the change in the efficacy index. Postoperatively, a negative correlation between the variation of the disc height, disc height index, and protrusion distance and the difference in VAS scores for low back pain at 3 and 6 months was observed among the two sagittal change parameters. Differences between changes in disc imaging parameters and postoperative efficacy were not statistically significant between various types of lumbar disc herniation. CONCLUSION: For the patients after percutaneous endoscopic lumbar discectomy, the changes in parameters such as disc area and circumference in the cross-sectional plane are not associated with efficacy, and the changes in disc height and herniation distance in the sagittal plane provide a morphologic basis for the assessment of short-term postoperative efficacy. In addition, the changes in disc morphologic parameters and postoperative efficacy do not differ between various types of lumbar disc herniation.

Comprehensive Evaluation of Tomato Growth Status under Aerated Drip Irrigation Based on Critical Nitrogen Concentration and Nitrogen Nutrient Diagnosis.

In order to provide a theoretical basis for the rational application of nitrogen fertilizer for tomatoes under aerated drip irrigation, a model of the critical nitrogen dilution curve was established in this study, and the feasibility of the nitrogen nutrition index (NNI) for the real-time diagnosis and evaluation of the nitrogen nutrient status was explored. The tomato variety "FENOUYA" was used as the test crop, and aerated drip irrigation was adopted by setting three levels of aeration rates, namely, A1 (dissolved oxygen concentration of irrigation water is 5 mg L-1), A2 (dissolved oxygen concentration of irrigation water is 15 mg L-1), and A3 (dissolved oxygen concentration of irrigation water is 40 mg L-1), and three levels of nitrogen rates, namely, N1 (120 kg ha-1), N2 (180 kg ha-1) and N3 (240 kg ha-1). The model of the critical nitrogen concentration dilution of tomatoes under different aerated treatments was established. The results showed that (1) the dry matter accumulation of tomatoes increased with the increase in the nitrogen application rate in a certain range and it showed a trend of first increase and then decrease with the increase in aeration rate. (2) As the reproductive period progressed, the nitrogen concentration in tomato plants showed a decreasing trend. (3) There was a power exponential relationship between the critical nitrogen concentration of tomato plant growth and above-ground biomass under different levels of aeration and nitrogen application rate, but the power exponential curves were characterized by A1 (Nc = 15.674DM-0.658), A2 (Nc = 101.116DM-0.455), A3 (Nc = 119.527DM-0.535), N1 (Nc = 33.819DM-0.153), N2 (Nc = 127.759DM-0.555) and N3 (Nc = 209.696DM-0.683). The standardized root mean square error (n-RMSE) values were 0.08%, 3.68%, 3.79% 0.50%, 1.08%, and 0.55%, which were less than 10%, and the model has good stability. (4) The effect of an increased nitrogen application rate on the critical nitrogen concentration dilution curve was more significant than that of the increase in aeration rate. (5) A nitrogen nutrition index model was built based on the critical nitrogen concentration model to evaluate the nitrogen nutritional status of tomatoes, whereby 180 kg ha-1 was the optimal nitrogen application rate, and 15 mg L-1 dissolved oxygen of irrigation water was the optimal aeration rate for tomatoes.

NLRP3 regulates CIITA/MHC II axis and interferon-γ-inducible chemokines in Malassezia globosa-infected keratinocytes.

CIITA, a member of NOD-like receptor (NLR) family, is the major MHC II trans-activator and mediator of Th1 immunity, but its function and interaction with NLRP3 have been little studied. We found activation of NLRP3 inflammasome, increased expression of CIITA, CBP, pSTAT1, STAT1, MHC II, IFN-γ and IFN-γ-inducible chemokines (CCL1 and CXCL8), and colocalisation of NLRP3 with CIITA in Malassezia folliculitis lesions, Malassezia globosa-infected HaCaT cells and mouse skin. CoIP with anti-CIITA or anti-NLRP3 antibody pulled down NLRP3 or both CIITA and ASC. NLRP3 silencing or knockout caused CIITA downexpression and their colocalisation disappearance in HaCaT cells and mouse skin of Nlrp3-/- mice, while CIITA knockdown had no effect on NLRP3, ASC, IL-1ß and IL-18 expression. NLRP3 inflammasome inhibitors and knockdown significantly suppressed IFN-γ, CCL1, CXCL8 and CXCL10 levels in M. globosa-infected HaCaT cells. CCL1 and CXCL8 expression was elevated in Malassezia folliculitis lesions and reduced in Nlrp3-/- mice. These results demonstrate that M. globosa can activate NLRP3 inflammasome, CIITA/MHC II signalling and IFN-γ-inducible chemokines in human keratinocytes and mouse skin. NLRP3 may regulate CIITA by their binding and trigger Th1 immunity by secreting CCL1 and CXCL8/IL-8, contributing to the pathogenesis of Malassezia-associated skin diseases.