Top 10 Signs and Symptoms of Psychotropic Adverse Drug Events to Monitor in Long-Term Care Residents.

OBJECTIVES: To produce a consensus list of the top 10 signs and symptoms suggestive of adverse drug events (ADEs) for monitoring in residents of long-term care facilities (LTCFs) who use antipsychotics, benzodiazepines, or antidepressants. DESIGN: A 3-round Delphi study. SETTING AND PARTICIPANTS: Geriatricians, psychiatrists, pharmacologists, general practitioners, pharmacists, nurses, and caregivers from 13 Asia Pacific, European, and North American countries. METHODS: Three survey rounds were completed between April and June 2023. In Round 1, participants indicated their level of agreement on a 9-point Likert scale on whether 41 signs or symptoms identified in a systematic review should be routinely monitored. Participants considered signs and symptoms that reduce quality of life or cause significant harm, are observable or measurable by nurses or care workers, and can be assessed at a single time point. Round 1 statements were included in a list for prioritization in Round 3 if ≥ 70% of participants responded ≥7 on the Likert scale. Statements were excluded if ≤ 30% of participants responded ≥7. In Round 2, participants indicated their level of agreement with statements that did not reach initial consensus, plus amended statements based on Round 1 participant feedback. Round 2 statements were included in Round 3 if ≥ 50% of the participants responded ≥7 on the Likert scale. In Round 3, participants prioritized the signs and symptoms. RESULTS: Forty-four participants (93.6%) completed all 3 rounds. Four of 41 signs and symptoms reached consensus for inclusion after Round 1, and 9 after Round 2. The top 10 signs and symptoms prioritized in Round 3 were recent falls, daytime drowsiness or sleepiness, abnormal movements (eg, shaking or stiffness), confusion or disorientation, balance problems, dizziness, postural hypotension, reduced self-care, restlessness, and dry mouth. CONCLUSIONS AND IMPLICATIONS: The top 10 signs and symptoms provide a basis for proactive monitoring for psychotropic ADEs.

Multiparametric mri-based radiomics nomogram for predicting lymph-vascular space invasion in cervical cancer.

PURPOSE: To develop and validate a multiparametric magnetic resonance imaging (mpMRI)-based radiomics model for predicting lymph-vascular space invasion (LVSI) of cervical cancer (CC). METHODS: The data of 177 CC patients were retrospectively collected and randomly divided into the training cohort (n=123) and testing cohort (n = 54). All patients received preoperative MRI. Feature selection and radiomics model construction were performed using max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) on the training cohort. The models were established based on the extracted features. The optimal model was selected and combined with clinical independent risk factors to establish the radiomics fusion model and the nomogram. The diagnostic performance of the model was assessed by the area under the curve. RESULTS: Feature selection extracted the thirteen most important features for model construction. These radiomics features and one clinical characteristic were selected showed favorable discrimination between LVSI and non-LVSI groups. The AUCs of the radiomics nomogram and the mpMRI radiomics model were 0.838 and 0.835 in the training cohort, and 0.837 and 0.817 in the testing cohort. CONCLUSION: The nomogram model based on mpMRI radiomics has high diagnostic performance for preoperative prediction of LVSI in patients with CC.

Age-standardized incidence, prevalence, and mortality rates of autoimmune diseases in adolescents and young adults (15-39 years): an analysis based on the global burden of disease study 2021.

BACKGROUND: Autoimmune diseases (ADs) present significant health challenges globally, especially among adolescents and young adults (AYAs) due to their unique developmental stages. Comprehensive analyses of their burden are limited. This study leverages the Global Burden of Disease (GBD) 2021 data to assess the global, regional, and national burden and trends of major ADs among AYAs from 1990 to 2021. METHODS: Utilizing data from the Global Burden of Disease (GBD) Study 2021 for individuals aged 15-39 years, we employed a direct method for age standardization to calculate estimates along with 95% uncertainty intervals (UIs) for assessing the age-standardized incidence rates (ASIR), prevalence rates (ASPR), and mortality rates (ASMR) of ADs. The diseases analyzed included rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), Asthma, and Psoriasis. Trends from 1990 to 2021 were analyzed using Joinpoint regression, providing average annual percentage changes (AAPC) and 95% confidence intervals (CIs). RESULT: In 2021, the global ASIR, ASPR, and ASMR of RA among AYAs (per 100,000 population) were 9.46 (95% UI: 5.92 to 13.54), 104.35 (77.44 to 137.84), and 0.016 (0.013 to 0.019), respectively. For IBD, the corresponding rates were 4.08 (3.07 to 5.37), 29.55 (23.00 to 37.83), and 0.10 (0.07 to 0.12). MS exhibited rates of 1.40 (0.93 to 1.93), 16.05 (12.73 to 19.75), and 0.05 (0.04 to 0.05), respectively. T1DM had rates of 6.63 (3.08 to 11.84), 245.51 (194.21 to 307.56), and 0.54 (0.47 to 0.60). Asthma demonstrated rates of 232.22 (132.11 to 361.24), 2245.51 (1671.05 to 2917.57), and 0.89 (0.77 to 1.08). Psoriasis showed rates of 55.08 (48.53 to 61.93) and 426.16 (394.12 to 460.18) for ASIR and ASPR, respectively. From 1990 to 2021, the global ASIR of RA (AAPC = 0.47, 95% CI: 0.46 to 0.49), IBD (0.22 [0.12 to 0.33]), MS (0.22 [0.19 to 0.26]), T1DM (0.83 [0.80 to 0.86]), and Psoriasis (0.33 [0.31 to 0.34]) showed increasing trends, whereas Asthma (-0.96 [-1.03 to -0.88]) showed a decreasing trend. The global ASPR of RA (0.70 [0.68 to 0.73]), MS (0.35 [0.32 to 0.37]), T1DM (0.68 [0.66 to 0.69]), and Psoriasis (0.29 [0.27 to 0.32]) also showed increasing trends, whereas IBD (-0.20 [-0.27 to -0.13]) and Asthma (-1.25 [-1.31 to -1.19]) showed decreasing trends. Notably, the estimated global ASMR of RA (-2.35 [-2.57 to -2.12]), MS (-0.63 [-0.86 to -0.41]), T1DM (-0.35 [-0.56 to -0.14]), and Asthma (-1.35 [-1.44 to -1.26]) in AYAs declined. Additionally, the burden of disease for ADs in AYAs varies considerably across continents and between 204 countries and territories. CONCLUSION: ADs among AYAs present a substantial public health burden with notable regional disparities in incidence, prevalence, and mortality rates. Understanding these patterns is essential for developing targeted public health interventions and policies to mitigate the impact of ADs in this population.

Genomic characteristics and evolution of Multicentric Esophageal and gastric Cardiac Cancer.

BACKGROUND: Esophageal carcinoma (EC) and gastric cardiac adenocarcinoma (GCA) have high incidence rates in the Chaoshan region of South China. Multifocal esophageal and cardiac cancer (MECC) is commonly observed in this region in clinical practice. However, the genomic characteristics of MECC remains unclear. MATERIALS AND METHODS: In this study, a total of 2123 clinical samples of EC and GCA were analyzed to determine the frequency of multifocal tumors, as well as their occurrence sites and pathological types. Cox proportional hazards regression was used to model the relationship between age, sex, and tumor state concerning survival in our analysis of the cohort of 541 patients with available follow-up data. We performed whole-genome sequencing on 20 tumor foci and 10 normal samples from 10 MECC patients to infer clonal structure on 6 MECC patients to explore genome characteristics. RESULT: The MECC rate of EC and GCA was 5.65% (121 of 2123). Age and sex were potential factors that may influence the risk of MECC (p < 0.001). Furthermore, MECC patients showed worse survival compared with single tumor patients. We found that 12 foci from 6 patients were multicentric origin model (MC), which exhibited significant heterogeneity of variations in paired foci and had an increased number of germline mutations in immune genes compared to metastatic model. In MC cases, different lesions in the same patient were driven by distinct mutation and copy number variation (CNV) events. Although TP53 and other driver mutation genes have a high frequency in the samples, their mutation sites show significant heterogeneity in paired tumor specimens. On the other hand, CNV genes exhibited higher concordance in paired samples, especially in the amplification of oncogenes and the deletion of tumor suppressor genes. CONCLUSIONS: The extent of inter-tumor heterogeneity suggests both monoclonal and polyclonal origins of MECC, which could provide insight into the genome diversity of MECC and guide clinical implementation.

Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions: an intravascular ultrasound study.

OBJECTIVES: To investigate whether negative remodeling (NR) detected by intravascular ultrasound (IVUS) of the side branch ostium (SBO) would affect in-stent neointimal hyperplasia (NIH) at the one-year follow-up and the clinical outcome of target lesion failure (TLF) at the long-term follow-up for patients with left main bifurcation (LMb) lesions treated with a two-stent strategy. METHODS: A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention (PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre- and post-PCI and at the 1-year follow-up were enrolled in phase I analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index (RI) for predicting NIH ≥ 50% was analyzed next. The phase II analysis focused on the incidence of TLF as the primary endpoint at the 1- to 5-year follow-up for all 328 patients by grouping based on the cutoff value of RI. RESULTS: In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic (ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893 (0.778, 1.000), P = 0.002. In phase II: the TLR rate (35.8% vs. 5.3%, P < 0.0001) was significantly higher in the several NR (sNR, defined as RI ≤ 0.85) group than in the non-sNR group. CONCLUSION: The NR of LCxO is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy, and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

Regulation of endocrine cell alternative splicing revealed by single-cell RNA sequencing in type 2 diabetes pathogenesis.

The prevalent RNA alternative splicing (AS) contributes to molecular diversity, which has been demonstrated in cellular function regulation and disease pathogenesis. However, the contribution of AS in pancreatic islets during diabetes progression remains unclear. Here, we reanalyze the full-length single-cell RNA sequencing data from the deposited database to investigate AS regulation across human pancreatic endocrine cell types in non-diabetic (ND) and type 2 diabetic (T2D) individuals. Our analysis demonstrates the significant association between transcriptomic AS profiles and cell-type-specificity, which could be applied to distinguish the clustering of major endocrine cell types. Moreover, AS profiles are enabled to clearly define the mature subset of ß-cells in healthy controls, which is completely lost in T2D. Further analysis reveals that RNA-binding proteins (RBPs), heterogeneous nuclear ribonucleoproteins (hnRNPs) and FXR1 family proteins are predicted to induce the functional impairment of ß-cells through regulating AS profiles. Finally, trajectory analysis of endocrine cells suggests the ß-cell identity shift through dedifferentiation and transdifferentiation of ß-cells during the progression of T2D. Together, our study provides a mechanism for regulating ß-cell functions and suggests the significant contribution of AS program during diabetes pathogenesis.

Real-world evidence of a novel tetravalent immunoglobulin Y effectiveness and safety in patients with the refractory Helicobacter pylori infection.

BACKGROUND: Refractory Helicobacter pylori (H. pylori) infection inevitably increase the difficulty of drug selection. Here, we described our experience with the use of a novel tetravalent IgY against H. pylori for the treatment of patients with refractory H. pylori infection. METHODS: Patients were randomly assigned to receive the standard quadruple therapy (amoxicillin, clarithromycin, omeprazole and bismuth potassium citrate ) for 2 weeks or 250 mg of avian polyclonal IgY orally twice a day for 4 weeks. The binding efficacy of IgY to H. pylori antigens was detected by western blotting13. C-urea breath test was performed to evaluate the eradication therap's efficacy. The side effects of IgY were evaluated via various routine tests. The questionnaire was used to gather clinical symptoms and adverse reactions. RESULTS: Western blot analysis showed that tetravalent IgY simultaneously bind to VacA, HpaA, CagA and UreB of H. pylori. Tetravalent IgY had an eradication rate of 50.74% in patients with refractory H. pylori and an inhibition rate of 50.04% against DOB (delta over baseline) of 13C-urea. The symptom relief rate was 61.76% in thirty-four patients with clinical symptoms, and no adverse reactions were observed during tetravalent IgY treatment period. CONCLUSIONS: Polyclonal avian tetravalent IgY reduced H. pylori infection, and showed good efficacy and safety in the treatment of refractory H. pylori infection patients, which represented an effective therapeutic option of choice for patients with refractory H. pylori infection.

HIF-2α inhibition disrupts leukemia stem cell metabolism and impairs vascular microenvironment to enhance chronic myeloid leukemia treatment.

Leukemic stem cells (LSCs) in chronic myeloid leukemia (CML) contribute to treatment resistance and disease recurrence. Metabolism regulates LSCs, but the mechanisms remain elusive. Here, we show that hypoxia-inducible factor 2α (HIF-2α) is highly expressed in LSCs in mouse and human CML and increases after tyrosine kinase inhibitor (TKI) treatment. Deletion of HIF-2α suppresses disease progression, reduces LSC numbers, and enhances the efficacy of TKI treatment in BCL-ABL-induced CML mice. Mechanistically, HIF-2α deletion reshapes the metabolic profile of LSCs, leading to increased production of reactive oxygen species (ROS) and apoptosis in CML. Moreover, HIF-2α deletion decreases vascular endothelial growth factor (VEGF) expression, thereby suppressing neovascularization in the bone marrow of CML mice. Furthermore, pharmaceutical inhibition of HIF-2α by PT2399 attenuates disease progression and improves the efficacy of TKI treatment in both mouse and human CML. Overall, our findings highlight the role of HIF-2α in controlling the metabolic state and vascular niche remodeling in CML, suggesting it is a potential therapeutic target to enhance TKI therapy.

Learning and depicting lobe-based radiomics feature for COPD Severity staging in low-dose CT images.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory condition that imposes a significant healthcare burden worldwide. Accurate staging of COPD severity is crucial for patient management and treatment planning. METHODS: The retrospective study included 530 hospital patients. A lobe-based radiomics method was proposed to classify COPD severity using computed tomography (CT) images. First, we segmented the lung lobes with a convolutional neural network model. Secondly, the radiomic features of each lung lobe are extracted from CT images, the features of the five lung lobes are merged, and the selection of features is accomplished through the utilization of a variance threshold, t-Test, least absolute shrinkage and selection operator (LASSO). Finally, the COPD severity was classified by a support vector machine (SVM) classifier. RESULTS: 104 features were selected for staging COPD according to the Global initiative for chronic Obstructive Lung Disease (GOLD). The SVM classifier showed remarkable performance with an accuracy of 0.63. Moreover, an additional set of 132 features were selected to distinguish between milder (GOLD I + GOLD II) and more severe instances (GOLD III + GOLD IV) of COPD. The accuracy for SVM stood at 0.87. CONCLUSIONS: The proposed method proved that the novel lobe-based radiomics method can significantly contribute to the refinement of COPD severity staging. By combining radiomic features from each lung lobe, it can obtain a more comprehensive and rich set of features and better capture the CT radiomic features of the lung than simply observing the lung as a whole.

Antibiotic-free production of sucrose isomerase in Bacillus subtilis by genome integration.

Sucrose isomerase (SIase) catalyzes the hydrolysis and isomerization of sucrose to form isomaltulose, a valuable functional sugar widely used in the food industry. However, the lack of safe and efficient heterologous expression systems hinders SIase production and application. In this study, we achieved antibiotic-free SIase expression in Bacillus subtilis through genome integration. Using CRISPR/Cas9 system, SIase expression cassettes were integrated into various genomic loci, including amyE and ctc, both individually and in combination, resulting in single-copy and muti-copy integration strains. Engineered strains with a maltose-inducible promoter effectively expressed and secreted SIase. Notably, multi-copy strain exhibited enhanced SIase production, achieving 4.4 U/mL extracellular activity in shake flask cultivations. Furthermore, crude enzyme solution from engineered strain transformed high concentrations sucrose into high yields of isomaltulose, reaching a maximum yield of 94.6%. These findings demonstrate antibiotic-free SIase production in B. subtilis via genome integration, laying the foundation for its industrial production and application.

Seizure, Motor, and Cognitive Outcomes After Epilepsy Surgery for Patients With Sturge-Weber Syndrome: Results From a Multicenter Study.

BACKGROUND AND OBJECTIVES: Surgery is widely performed for refractory epilepsy in patients with Sturge-Weber syndrome (SWS), but reports on its effectiveness are limited. This study aimed to analyze seizure, motor, and cognitive outcomes of surgery in these patients and to identify factors associated with the outcomes. METHODS: This was a multicenter retrospective observational study using data from patients with SWS and refractory epilepsy who underwent epilepsy surgery between 2000 and 2020 at 16 centers throughout China. Longitudinal postoperative seizures were classified by Engel class, and Engel class I was regarded as seizure-free outcome. Functional (motor and cognitive) outcomes were evaluated using the SWS neurologic score, and improved or unchanged scores between baseline and follow-up were considered to have stable outcomes. Outcomes were analyzed using Kaplan-Meier analyses. Multivariate Cox regression was used to identify factors associated with outcomes. RESULTS: A total of 214 patients with a median age of 2.0 (interquartile range 1.2-4.6) years underwent surgery (focal resection, FR [n = 87]; hemisphere surgery, HS [n = 127]) and completed a median of 3.5 (1.7-5.0) years of follow-up. The overall estimated probability for being seizure-free postoperatively at 1, 2, and 5 years was 86.9% (95% CI 82.5-91.6), 81.4% (95% CI 76.1-87.1), and 70.7% (95% CI 63.3-79.0), respectively. The overall estimated probability of being motor stable at the same time post operatively was 65.4% (95% CI 58.4-71.2), 80.2% (95% CI 73.8-85.0), and 85.7% (95% CI 79.5-90.1), respectively. The overall probability for being cognition stable at 1, 2, and 5 years was 80.8% (95% CI 74.8-85.5), 85.1% (95% CI 79.3-89.2), and 89.5% (95% CI 83.8-93.2), respectively. Both FR and HS were effective at ensuring seizure control. For different HS techniques, modified hemispherotomy had comparable outcomes but improved safety compared with anatomical hemispherectomy. Regarding FR, partial resection (adjusted hazard ratio [aHR] 11.50, 95% CI 4.44-29.76), acute postoperative seizure (APOS, within 30 days of surgery; aHR 10.33, 95% CI 3.94-27.12), and generalized seizure (aHR 3.09, 95% CI 1.37-6.94) were associated with seizure persistence. For HS, seizure persistence was associated with APOS (aHR 27.61, 9.92-76.89), generalized seizure (aHR 7.95, 2.74-23.05), seizure frequency ≥30 times/month (aHR 4.76, 1.27-17.87), and surgical age ≥2 years (aHR 3.78, 1.51-9.47); motor stability was associated with severe motor defects (aHR 5.23, 2.27-12.05) and postoperative seizure-free status (aHR 3.09, 1.49-6.45); and cognition stability was associated with postoperative seizure-free status (aHR 2.84, 1.39-5.78) and surgical age <2 years (aHR 1.76, 1.13-2.75). DISCUSSION: FR is a valid option for refractory epilepsy in patients with SWS and has similar outcomes to those of HS, with less morbidity associated with refractory epilepsy. Early surgical treatment (under the age of 2 years) leads to better outcomes after HS, but there is insufficient evidence that surgical age affects FR outcomes. These findings warrant future prospective multicenter cohorts with international cooperation and prolonged follow-up in better exploring more precise outcomes and developing prognostic predictive models. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in children with SWS and refractory seizures, surgical resection-focal, hemispherectomy, or modified hemispherotomy-leads to improved outcomes.

Research on the Asymmetric Phenomenon of Voltage Polarity Based on Dielectric Wetting.

The present research investigated the voltage polarity asymmetry phenomenon based on dielectric wetting. In an ITO-hydrophobic layer-droplet setup, three reagents with different pH values (3.96, 7.0, and 10.18), two types of hydrophobic materials (AF1601 and 6%T6), and two different thicknesses (340 nm and 2.5 µm) of each material were systematically investigated. The results show that the thickness of the hydrophobic dielectric layer and the pH of the droplets had a significant impact on the droplet contact angle variation with the voltage. The contact angle on the thick hydrophobic dielectric layer followed the Lippmann-Young equation as the voltage changed. The angle of the thin hydrophobic dielectric layer was affected by its own properties and the type of droplet, which led to the occurrence of voltage polarity asymmetry of the electrowetting phenomenon. After further investigation of this phenomenon, it was found that it mainly accounted for the decrease in electric field strength at both ends of the droplet, which was caused by electrochemical reactions and changes in circuit resistance. The leakage current is an important indicator, and this phenomenon can be prevented by increasing the thickness of the hydrophobic dielectric layer.

Di- and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair.

Histone H3 Lys36 (H3K36) methylation and its associated modifiers are crucial for DNA double-strand break (DSB) repair, but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is unclear. Here, we unveil the distinct roles of H3K36 dimethylation (H3K36me2) and H3K36 trimethylation (H3K36me3) in DSB repair via non-homologous end joining (NHEJ) or homologous recombination (HR). Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency. yKu70 and Rfa1 bind H3K36me2- or H3K36me3-modified peptides and chromatin, respectively. Disrupting these interactions impairs yKu70 and Rfa1 recruitment to damaged H3K36me2- or H3K36me3-rich loci, increasing DNA damage sensitivity and decreasing repair efficiency. Conversely, H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit yKu70 or Rfa1 under DSB stress. Importantly, human KU70 and RPA1, the homologs of yKu70 and Rfa1, exclusively associate with H3K36me2 and H3K36me3 in a conserved manner. These findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways, highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway.

Latest insights into the global epidemiological features, screening, early diagnosis and prognosis prediction of esophageal squamous cell carcinoma.

As a highly invasive carcinoma, esophageal cancer (EC) was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020. Esophageal squamous cell carcinoma (ESCC) is the major histological subtype of EC, and its incidence and mortality rates are decreasing globally. Due to the lack of specific early symptoms, ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis, and the incidence and mortality rates are still high in many countries, especially in China. Therefore, enormous challenges still exist in the management of ESCC, and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC. Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated, certain promising biomarkers are being investigated to facilitate clinical decision-making. With the advent and advancement of high-throughput technologies, such as genomics, proteomics and metabolomics, valuable biomarkers with high sensitivity, specificity and stability could be identified for ESCC. Herein, we aimed to determine the epidemiological features of ESCC in different regions of the world, especially in China, and focused on novel molecular biomarkers associated with ESCC screening, early diagnosis and prognosis prediction.

Delivery of nanosecond laser pulses by multi-mode anti-resonant hollow core fiber at 1†µm wavelength.

In this paper we explore the application of low-loss multimode anti-resonant hollow-core fiber (MM-AR-HCF) in the delivery of nanosecond laser pulses at 1 µm wavelength. MM-AR-HCF with large core offers a rich content of low-loss higher-order modes which plays a key role in the efficient coupling and transmission of high-power laser of low beam quality. In the experiment, laser pulses of an average pulse energy of 21.8 mJ with 14.6 ns pulse width (corresponding a peak power of 1.49 MW) are transmitted through MM-AR-HCF of 9.8 m length without damage. 85% transmission efficiency is achieved where the incident laser beam suffers a low beam quality with M2 x and M2 y of 2.18 and 1.99 respectively. Laser-induced damage threshold (LIDT) of MM-AR-HCF was measured to be 22.6 mJ for 85% transmission efficiency, which is 7 times higher than that for a multimode silica optical fiber with a large core of 200 µm.

Effect of progestin on thyroid function in female Wistar rats.

Introduction: To characterize the influence of female-specific hormones on women's thyroid function, the study investigated the influence of extra progestin from oral contraceptives on inducing thyroid dysfunction. Methods: Sixty female Wistar rats were divided into six groups based on levonorgestrel or desogestrel administration as the main active agents: control, low (0.0039 mg*20-fold), medium (0.0039 mg*100-fold), high (0.0318 mg*100-fold) levonorgestrel (pure product); and low (0.0083 mg*20-fold) and high (0.0083 mg*100-fold) desogestrel (pure product). Progestin was administered by gavage every 4 days for 1 month. Statistical analysis was performed using one-way analysis of variance and the Kruskal-Wallis test. Results: Following levonorgestrel gavage, serum free T4 and thyroidstimulating hormone levels were significantly lower in the experimental group than that in the control group (p=0.013 and 0.043). After desogestrel gavage, the serum free T4 and free T3 levels were lower in the experimental group than that in the control group (p=0.019 and 0.030). Thyroid hormone antibody concentrations were lower in rats administered levonorgestrel and desogestrel than that in control rats. Moreover, exposure to progestin upregulated the expression of the thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid. Discussion: Progestin stimulation enhanced the proliferation of follicular epithelial cells in rat thyroid tissues. Progestin exposure could cause thyroid dysfunction by upregulating the transcription of thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid, thus inducing pathomorphological changes in rats' thyroid.

Genetic mapping reveals a candidate gene CmoFL1 controlling fruit length in pumpkin.

Fruit length (FL) is an important economical trait that affects fruit yield and appearance. Pumpkin (Cucurbita moschata Duch) contains a wealth genetic variation in fruit length. However, the natural variation underlying differences in pumpkin fruit length remains unclear. In this study, we constructed a F2 segregate population using KG1 producing long fruit and MBF producing short fruit as parents to identify the candidate gene for fruit length. By bulked segregant analysis (BSA-seq) and Kompetitive Allele-Specific PCR (KASP) approach of fine mapping, we obtained a 50.77 kb candidate region on chromosome 14 associated with the fruit length. Then, based on sequence variation, gene expression and promoter activity analyses, we identified a candidate gene (CmoFL1) encoding E3 ubiquitin ligase in this region may account for the variation of fruit length. One SNP variation in promoter of CmoFL1 changed the GT1CONSENSUS, and DUAL-LUC assay revealed that this variation significantly affected the promoter activity of CmoFL1. RNA-seq analysis indicated that CmoFL1 might associated with the cell division process and negatively regulate fruit length. Collectively, our work identifies an important allelic affecting fruit length, and provides a target gene manipulating fruit length in future pumpkin breeding.

Earthworm gut digestion drives the transfer behavior of antibiotic resistance genes in layers of extracellular polymeric substances during vermicomposting of dewatered sludge.

Gut digestion by earthworms (GDE) is a crucial step in vermicomposting, affecting the fate of antibiotic resistance genes (ARGs) in vermicompost sludge. The extracellular polymeric substance (EPS) matrix of sludge is an important space for ARG transfer. However, the effect of GDE on EPS-associated ARGs remains unclear. Therefore, this study explored the role of GDE in driving the transfer of ARGs within different EPS layers in sludge. For this, the changes in intracellular ARGs and EPS-associated ARGs in sludge were analyzed after 5 days of the GDE process. The results showed that after the GDE process, both nitrate and dissolved organic carbon significantly increased in all EPS layers of sludge, while the proteins and polysaccharides only enhanced in soluble and loosely bound EPS of sludge. In addition, a 7.0% decrease in bacterial diversity was recorded after the GDE process, with a functional bacterial community structure emerging. Moreover, the absolute abundance of total ARGs and mobile genetic elements decreased by 90.71% and 61.83%, respectively, after the GDE process. Intracellular ARGs decreased by 92.1%, while EPS-associated ARGs increased by 4.9%, indicative of intracellular ARG translocation into the EPS during the GDE process. Notably, the ARGs exhibited significant enrichment in both the soluble and loosely bound EPS, whereas they were reduced in the tightly bound EPS. The structural equation modeling revealed that the GDE process effectively mitigated the ARG dissemination risk by modulating both the EPS structure and microenvironment, with the organic structure representing a primary factor influencing ARGs in the EPS.

Genome-wide analysis of the MADS-box gene family of sea buckthorn (Hippophae rhamnoides ssp. sinensis) and their potential role in floral organ development.

Sea buckthorn (Hippophae rhamnoides ssp. sinensis) is a deciduous shrub or small tree in the Elaeagnaceae family. It is dioecious, featuring distinct structures in female and male flowers. The MADS-box gene family plays a crucial role in flower development and differentiation of floral organs in plants. However, systematic information on the MADS-box family in sea buckthorn is currently lacking. This study presents a genome-wide survey and expression profile of the MADS-box family of sea buckthorn. We identified 92 MADS-box genes in the H. rhamnoides ssp. Sinensis genome. These genes are distributed across 12 chromosomes and classified into Type I (42 genes) and Type II (50 genes). Based on the FPKM values in the transcriptome data, the expression profiles of HrMADS genes in male and female flowers of sea buckthorn showed that most Type II genes had higher expression levels than Type I genes. This suggesting that Type II HrMADS may play a more significant role in sea buckthorn flower development. Using the phylogenetic relationship between sea buckthorn and Arabidopsis thaliana, the ABCDE model genes of sea buckthorn were identified and some ABCDE model-related genes were selected for qRT-PCR analysis in sea buckthorn flowers and floral organs. Four B-type genes may be involved in the identity determination of floral organs in male flowers, and D-type genes may be involved in pistil development. It is hypothesized that ABCDE model genes may play an important role in the identity of sea buckthorn floral organs. This study analyzed the role of MADS-box gene family in the development of flower organs in sea buckthorn, which provides an important theoretical basis for understanding the regulatory mechanism of sex differentiation in sea buckthorn.