Immunotoxicity and oxidative damage in Litopenaeus vannamei induced by polyethylene microplastics and copper co-exposure.

This study examines the combined effects of polyethylene microplastics (PE-MP) and copper (Cu2+) on the immune and oxidative response of Litopenaeus vannamei. PE-MP adsorbed with Cu2+ at 2.3, 6.8, and 16.8 ng (g shrimp)-1) were injected into L. vannamei. Over 14 days, survival rates were monitored, and immune and oxidative stress parameters were assessed. The results showed that combined exposure to PE-MP and Cu2+ significantly reduced the survival rate and decreased total haemocyte count. Immune-related parameters (phagocytic rate, phenoloxidase and superoxide dismutase (SOD)) and antioxidant-related parameters (SOD, catalase and glutathione peroxidase mRNA and enzyme) also decreased, while respiratory burst activity significantly increased, indicating immune and antioxidant system disruption. Additionally, there was a significant increase in oxidative stress, as measured by malondialdehyde levels. Histopathological analysis revealed severe muscle, hepatopancreas, and gill damage. These results suggest that simultaneous exposure to PE-MP and Cu2+ poses greater health risks to white shrimp.

Exoskeleton rehabilitation robot training for balance and lower limb function in sub-acute stroke patients: a pilot, randomized controlled trial.

PURPOSE: This pilot study aimed to investigate the effects of REX exoskeleton rehabilitation robot training on the balance and lower limb function in patients with sub-acute stroke. METHODS: This was a pilot, single-blind, randomized controlled trial. Twenty-four patients with sub-acute stroke (with the course of disease ranging from 3 weeks to 3 months) were randomized into two groups, including a robot group and a control group. Patients in control group received upright bed rehabilitation (n = 12) and those in robot group received exoskeleton rehabilitation robot training (n = 12). The frequency of training in both groups was once a day (60 min each) for 5 days a week for a total of 4 weeks. Besides, the two groups were evaluated before, 2 weeks after and 4 weeks after the intervention, respectively. The primary assessment index was the Berg Balance Scale (BBS), whereas the secondary assessment indexes included the Fugl-Meyer Lower Extremity Motor Function Scale (FMA-LE), the Posture Assessment Scale for Stroke Patients (PASS), the Activities of Daily Living Scale (Modified Barthel Index, MBI), the Tecnobody Balance Tester, and lower extremity muscle surface electromyography (sEMG). RESULTS: The robot group showed significant improvements (P < 0.05) in the primary efficacy index BBS, as well as the secondary efficacy indexes PASS, FMA-LE, MBI, Tecnobody Balance Tester, and sEMG of the lower limb muscles. Besides, there were a significant differences in BBS, PASS, static eye-opening area or dynamic stability limit evaluation indexes between the robotic and control groups (P < 0.05). CONCLUSIONS: This is the first study to investigate the effectiveness of the REX exoskeleton rehabilitation robot in the rehabilitation of patients with stroke. According to our results, the REX exoskeleton rehabilitation robot demonstrated superior potential efficacy in promoting the early recovery of balance and motor functions in patients with sub-acute stroke. Future large-scale randomized controlled studies and follow-up assessments are needed to validate the current findings. CLINICAL TRIALS REGISTRATION: URL: https://www.chictr.org.cn/index.html.Unique identifier: ChiCTR2300068398.

Human papillomavirus-driven head and neck cancers in Japan during 2008-2009 and 2018-2019: The BROADEN study.

There is limited understanding of epidemiology and time trends of human papilloma virus (HPV)-driven head and neck cancers (HNC) in Japan, especially outside of the oropharynx. To assess HPV-driven HNC, a non-interventional study (BROADEN) of HNC patients diagnosed in 2008-2009 and 2018-2019 was conducted in Japan. Adult patients with oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal or oral cavity cancers were included in this study. HPV was centrally tested using p16INK4a immunohistochemistry, HPV-DNA PCR and HPV E6*I mRNA. HPV attributability required positivity in at least two tests (p16INK4a immunohistochemistry, HPV-DNA PCR, HPV E6*I mRNA) in the oropharynx, and HPV-DNA and HPV E6*I mRNA positivity for non-oropharynx sites. Nineteen hospitals included a total of 1108 patients, of whom 981 had valid samples. Men accounted for 82% of HNC diagnoses. Patients in the earlier cohort were younger and included a higher percentage of smokers. There was an increasing trend of HPV-driven oropharyngeal cancer over the last decade, from 44.2% to 51.7%. HPV attribution in nasopharyngeal cancers was 3.2% in 2008-2009 and 7.5% in 2018-2019; and 4.4% and 0% for larynx respectively. In total, 95.2% of HPV-driven HNC were attributed to HPV genotypes included in the 9-valent HPV vaccine being HPV16 the most prominent genotype. These results suggest that an epidemiologic shift is happening in Japan, with a decrease in smoking and alcohol use and an increase in HPV-driven HNC. The increasing trend of HPV-driven HNC in Japan highlights the need for preventive strategies to mitigate the rise of HPV-driven HNC.

Bio-inspired foveal super-resolution method for multi-focal-length images based on local gradient constraints.

Most existing super-resolution (SR) imaging systems, inspired by the bionic compound eye, utilize image registration and reconstruction algorithms to overcome the angular resolution limitations of individual imaging systems. This article introduces a multi-aperture multi-focal-length imaging system and a multi-focal-length image super-resolution algorithm, mimicking the foveal imaging of the human eye. Experimental results demonstrate that with the proposed imaging system and an SR imaging algorithm inspired by the human visual system, the proposed method can enhance the spatial resolution of the foveal region by up to 4 × compared to the original acquired image. These findings validate the effectiveness of the proposed imaging system and computational imaging algorithm in enhancing image texture and spatial resolution.

Proteomic biomarkers for noninvasive left atrial appendage thrombus prediction in patients with atrial fibrillation.

INTRODUCTION AND OBJECTIVES: The CHA2DS2-VASc score, used to assess the risk of left atrial appendage thrombus (LAAT) formation in patients with atrial fibrillation (AF), has limited predictive value. Moreover, transesophageal echocardiography imaging, the gold standard diagnostic method to identify thrombi, is semi-invasive. Consequently, there is a need for alternative and noninvasive diagnostic methods for LAAT risk assessment. METHODS: Deep proteomic analysis was conducted in plasma samples from 8 patients with nonvalvular AF, divided into thrombus and control groups (4 patients in each group) based on the presence or absence of LAAT. Biomarkers associated with LAAT were validated using an enzyme-linked immunosorbent assay in a cohort of 179 patients with available clinical, transthoracic, and transesophageal echocardiography data. Predictive models were developed to assess the improvement in LAAT identification. RESULTS: The LAAT group had higher CHA2DS2-VASc scores, larger LA diameter, and lower LAA flow velocities. Deep proteomic analysis identified 30 differentially expressed proteins, including myosin light chain 4, prenylcysteine oxidase 1 (PCYOX1), and decorin as potential diagnostic biomarkers of LAAT. The model showed that PCYOX1 and decorin provided an area under the curve (AUC) of 0.970 for LAAT prediction compared with 0.672 in a model including the CHA2DS2-VASc score and LAA cauliflower morphology. The incremental value of proteomic biomarkers for LAAT in patients with nonvalvular AF was further confirmed with the net reclassification improvement and integrated discrimination improvement indices. CONCLUSIONS: Protein levels of PCYOX1 and decorin improve the predictive performance for LAAT in patients with nonvalvular AF.

Missense mutation of ISL1 (E283D) is associated with the development of type 2 diabetes.

AIMS/HYPOTHESIS: Mutations in Isl1, encoding the insulin enhancer-binding protein islet-1 (ISL1), may contribute to attenuated insulin secretion in type 2 diabetes mellitus. We made an Isl1E283D mouse model to investigate the disease-causing mechanism of diabetes mellitus. METHODS: The ISL1E283D mutation (c. 849A>T) was identified by whole exome sequencing on an early-onset type 2 diabetes family and then the Isl1E283D knockin (KI) mouse model was created and an IPGTT and IPITT were conducted. Glucose-stimulated insulin secretion (GSIS), expression of Ins2 and other ISL1 target genes and interacting proteins were evaluated in isolated pancreas islets. Transcriptional activity of Isl1E283D was evaluated by cell-based luciferase reporter assay and electrophoretic mobility shift assay, and the expression levels of Ins2 driven by Isl1 wild-type (Isl1WT) and Isl1E283D mutation in rat INS-1 cells were determined by RT-PCR and western blotting. RESULTS: Impaired GSIS and elevated glucose level were observed in Isl1E283D KI mice while expression of Ins2 and other ISL1 target genes Mafa, Pdx1, Slc2a2 and the interacting protein NeuroD1 were downregulated in isolated islets. Transcriptional activity of the Isl1E283D mutation for Ins2 was reduced by 59.3%, and resulted in a marked downregulation of Ins2 expression when it was overexpressed in INS-1 cells, while overexpression of Isl1WT led to an upregulation of Ins2 expression. CONCLUSIONS/INTERPRETATION: Isl1E283D mutation reduces insulin expression and secretion by regulating insulin and other target genes, as well as its interacting proteins such as NeuroD1, leading to the development of glucose intolerance in the KI mice, which recapitulated the human diabetic phenotype. This study identified and highlighted the Isl1E283D mutation as a novel causative factor for type 2 diabetes, and suggested that targeting transcription factor ISL1 could offer an innovative avenue for the precise treatment of human type 2 diabetes.

Elucidating the molecular mechanisms of pterostilbene against cervical cancer through an integrated bioinformatics and network pharmacology approach.

Pterostilbene (PTE), a natural phenolic compound, has exhibited promising anticancer properties in the preclinical treatment of cervical cancer (CC). This study aims to comprehensively investigate the potential targets and mechanisms underlying PTE's anticancer effects in CC, thereby providing a theoretical foundation for its future clinical application and development. To accomplish this, we employed a range of methodologies, including network pharmacology, bioinformatics, and computer simulation, with specific techniques such as WGCNA, PPI network construction, ROC curve analysis, KM survival analysis, GO functional enrichment, KEGG pathway enrichment, molecular docking, MDS, and single-gene GSEA. Utilizing eight drug target prediction databases, we have identified a total of 532 potential targets for PTE. By combining CC-related genes from the GeneCards disease database with significant genes derived from WGCNA analysis of the GSE63514 dataset, we obtained 7915 unique CC-related genes. By analyzing the intersection of the 7915 CC-related genes and the 2810 genes that impact overall survival time in CC, we identified 690 genes as crucial for CC. Through the use of a Venn diagram, we discovered 36 overlapping targets shared by PTE and CC. We have constructed a PPI network and identified 9 core candidate targets. ROC and KM curve analyses subsequently revealed IL1B, EGFR, IL1A, JUN, MYC, MMP1, MMP3, and ANXA5 as the key targets modulated by PTE in CC. GO and KEGG pathway enrichment analyses indicated significant enrichment of these key targets, primarily in the MAPK and IL-17 signaling pathways. Molecular docking analysis verified the effective binding of PTE to all nine key targets. MDS results showed that the protein-ligand complex between MMP1 and PTE was the most stable among the nine targets. Additionally, GSEA enrichment analysis suggested a potential link between elevated MMP1 expression and the activation of the IL-17 signaling pathway. In conclusion, our study has identified key targets and uncovered the molecular mechanism behind PTE's anticancer activity in CC, establishing a firm theoretical basis for further exploration of PTE's pharmacological effects in CC therapy.

Enhancing percutaneous kyphoplasty efficacy in elderly osteoporotic fractures through optimal cement filling ratio.

Objective: To explore the appropriate bone cement filling ratio in percutaneous kyphoplasty (PKP) for the treatment of osteoporotic vertebral compression fractures (OVCF). Methods: Clinical and radiological data from 150 OVCF patients treated with PKP were retrospectively analyzed. Patients were categorized into three groups based on bone cement filling ratio: low (<0.4), medium (0.4-0.6), and high (>0.6) filling ratio groups. The clinical characteristics (age, gender, BMI, etc.) and related study data (bone cement leakage and its location, pre/post-operative Visual Analogue Scale (VAS), pre/post-operative Oswestry Disability Index (ODI), vertebral height restoration, kyphotic Cobb angle, etc.) among the three groups were compared using statistical software to compare to identify the most appropriate cement filling ratio. Results: The 0.4-0.6 group presented a lower cement leakage rate compared to the >0.6 group, and there were no significant differences in pre-operative VAS, post-operative day 2 VAS, post-operative month 1 VAS, and pre-operative ODI (p>0.05). However, significant differences were observed in post-operative month 3 VAS (p=0.002), post-operative day 2 ODI (p=0.002), post-operative month 1 ODI (p<0.001), and post-operative month 3 ODI (p<0.001). The "0.4-0.6" group showed better pain improvement and functional recovery compared with the ">0.6" group at the 3-month follow-up. While presenting the best vertebral height restoration, the ">0.6" group also exhibited the greatest variability. Additionally, no significant difference in Cobb angle changes was observed among the groups. Conclusion: A bone cement filling ratio of 0.4-0.6 in PKP treatment for OVCF strikes a favorable balance between complication reduction and positive patient outcomes, warranting it as an optimal filling volume.

PARP14 is pro- and anti-viral host factor that promotes IFN production and affects the replication of multiple viruses.

PARP14 is a 203 kDa multi-domain protein that is primarily known as an ADP-ribosyltransferase, and is involved in a variety of cellular functions including DNA damage, microglial activation, inflammation, and cancer progression. In addition, PARP14 is upregulated by interferon (IFN), indicating a role in the antiviral response. Furthermore, PARP14 has evolved under positive selection, again indicating that it is involved in host-pathogen conflict. We found that PARP14 is required for increased IFN-I production in response to coronavirus infection lacking ADP-ribosylhydrolase (ARH) activity and poly(I:C), however, whether it has direct antiviral function remains unclear. Here we demonstrate that the catalytic activity of PARP14 enhances IFN-I and IFN-III responses and restricts ARH-deficient murine hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. To determine if PARP14's antiviral functions extended beyond CoVs, we tested the ability of herpes simplex virus 1 (HSV-1) and several negative-sense RNA viruses, including vesicular stomatitis virus (VSV), Ebola virus (EBOV), and Nipah virus (NiV), to infect A549 PARP14 knockout (KO) cells. HSV-1 had increased replication in PARP14 KO cells, indicating that PARP14 restricts HSV-1 replication. In contrast, PARP14 was critical for the efficient infection of VSV, EBOV, and NiV, with EBOV infectivity at less than 1% of WT cells. A PARP14 active site inhibitor had no impact on HSV-1 or EBOV infection, indicating that its effect on these viruses was independent of its catalytic activity. These data demonstrate that PARP14 promotes IFN production and has both pro- and anti-viral functions targeting multiple viruses.

Long-term follow-up of photodynamic therapy of cervical intraepithelial neoplasia grade 2 (CIN2).

BACKGROUND: To determine the long-term efficacy and safety of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) for treating cervical intraepithelial neoplasia grade 2 (CIN2) as well as the suitability of ALA-PDT in treating of cervical lesions divided into cervical transformation zone type 3. METHODS: We included 81 patients diagnosed with CIN2 at the Department of Gynecology of the Affiliated Hospital of Qingdao University with data collected between January 2019 and January 2021 following ALA-PDT. Furthermore, we analyzed the superiority of ALA-PDT in fertility preservation among women of childbearing age based on follow-up data from 11 patients with fertility requirements. RESULTS: Our findings confirmed the long-term efficacy of ALA-PDT for CIN2 treatment, with an overall efficacy of 95.83 % (23/24) at follow-up of 25-36 months. Moreover, the cervical transformation zone type 3 improvement and human papillomavirus (HPV)-negative efficacy were 69.2 % (18/26) and 82.4 % (14/17), respectively. ALA-PDT is recommended for consenting patients with cervical transformation zone type 3. Additionally, women without primary infertility could experience natural pregnancy and full-term birth of more than one baby following ALA-PDT for CIN2 treatment, with a satisfaction rate of ≈100 %. CONCLUSIONS: ALA-PDT is recommendable for treating high-grade squamous intraepithelial lesions, especially in patients with fertility requirements.

Development and validation of a prognostic prediction model for cervical cancer patients treated with radical radiotherapy: a study based on TCGA database.

Background: Radiotherapy or concurrent chemoradiotherapy is the standard treatment for patients with locally advanced or inoperable cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, treatment failure for CESC patients treated with radical radiotherapy still occurs due to local recurrence and distant metastasis. The previous prediction models were focused on all CESC patients, neglecting the prognostic differences under different treatment modalities. Therefore, there is a pressing demand to explore novel biomarkers for the prognosis and sensitivity of radiotherapy in CESC patients treated with radical radiotherapy. As a single biomarker has limited effect in stratifying these patients, our objective was to identify radioresponse-related mRNAs to ameliorate forecast of the prognosis for CESC patients treated with radical radiotherapy. Methods: Sample data on CESC patients treated with radical radiotherapy were obtained from The Cancer Genome Atlas (TCGA) database. We randomly separated these patients into a training and test cohorts using a 1:1 ratio. Differential expression analysis was carried out to identify radioresponse-related mRNA sets that were significantly dysregulated between complete response (CR) and radiographic progressive disease (RPD) groups, and univariate Cox regression analyses, least absolute shrinkage and selection operator (LASSO) method and multivariate Cox regression were performed to identify the radioresponse-related signature in the training cohort. we adopted survival analysis to measure the predictive value of the radioresponse-related signature both in the test and entire cohorts. Moreover, we developed a novel nomogram to predict the overall survival (OS) of CESC patients treated with radical radiotherapy. In addition, immune infiltration analysis and Gene Set Enrichment Analysis (GSEA) were conducted to preliminarily explore possible mechanisms. Results: This study included a total of 92 CESC patients subjected to radical radiotherapy. We developed and verified a risk score model based on radioresponse-related mRNA. The radioresponse-related mRNA signature and International Federation of Gynecology and Obstetrics (FIGO) stage were served as independent prognostic factors for CESC patients treated with radical radiotherapy. Moreover, a nomogram integrating radioresponse-related mRNA signature with FIGO stage was established to perform better for predicting 1-, 3-, and 5-year survival rates. Mechanically, the low-risk group under the risk score of this model had a better survival status, and the distribution of CD4 T cells was potentially involved in the regulation of radiotherapy response in CESC, leading to a better survival outcome in the low-risk group. Conclusions: This study presents a new radioresponse-related mRNA signature that shows promising clinical efficacy in predicting the prognosis of CESC patients treated with radical radiotherapy.

Psychache status and associated contributing factors among the Hakka elderly in Fujian, China.

BACKGROUND: Little is known about the state of psychological distress of the elderly in China, and research on specific subgroups such as Hakka older adults is almost lacking. This study investigates psychache and associated factors among Hakka elderly in Fujian, China. METHODS: The data analysed in this study were derived from China's Health-Related Quality of Life Survey for Older Adults 2018. The Chinese version of the Psychache Scale (PAS) was used to assess the frequency and intensity of psychache in Hakka older adults. Generalized linear regression analysis was conducted to identify the main socio-demographic factors associated with psychache overall and its frequency and intensity. RESULTS: A total of 1,262 older adults participated, with mean scores of 18.27 ± 6.88 for total PAS, 12.50 ± 4.79 for PAS-Frequency and 5.77 ± 2.34 for PAS-Intensity. On average, females scored higher than males on PAS-Frequency (ß = 0.84, 95% CI = 0.34, 1.35) and PAS-Intensity (ß = 0.48, 95% CI = 0.22, 0.73). Older adults currently living in towns (ß = -2.18, 95% CI = -2.81, -1.54), with their spouse only (ß = -3.71, 95% CI = -4.77, -2.65), or with children (ß = -3.24, 95% CI = -4.26, -2.22) were more likely to score lower on PAS-Frequency. Conversely, older adults who were regular sleepers (ß = -1.19, 95% CI =-1.49, -0.88) or lived with their spouse only (ß = -1.25, 95% CI = -1.78, -0.72) were more likely to score lower on PAS-Intensity. CONCLUSION: Among Hakka elderly, we found a higher frequency and greater intensity of psychache in females, those with poor health status, irregular sleepers, rural residents, solo dwellers, those with below CNY 10,000 in personal savings, and the medically uninsured. The study's findings indicate that policymakers should give more attention to the susceptible population and implement practical interventions to reduce their psychological burden.

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Metabolic reprogramming and interventions in angiogenesis.

BACKGROUND: Endothelial cell (EC) metabolism plays a crucial role in the process of angiogenesis. Intrinsic metabolic events such as glycolysis, fatty acid oxidation, and glutamine metabolism, support secure vascular migration and proliferation, energy and biomass production, as well as redox homeostasis maintenance during vessel formation. Nevertheless, perturbation of EC metabolism instigates vascular dysregulation-associated diseases, especially cancer. AIM OF REVIEW: In this review, we aim to discuss the metabolic regulation of angiogenesis by EC metabolites and metabolic enzymes, as well as prospect the possible therapeutic opportunities and strategies targeting EC metabolism. KEY SCIENTIFIC CONCEPTS OF REVIEW: In this work, we discuss various aspects of EC metabolism considering normal and diseased vasculature. Of relevance, we highlight that the implications of EC metabolism-targeted intervention (chiefly by metabolic enzymes or metabolites) could be harnessed in orchestrating a spectrum of pathological angiogenesis-associated diseases.

An Atlas of Dietary Intakes and Medication Uses on Risk of Bladder Cancer: A Wide-Angle Mendelian Randomization Analysis.

BACKGROUND: Observational studies suggests that diets and medications affect bladder cancer (BC) development, which are subject to confounding and difficult to make causal inference. Here we aimed to investigate whether those observational associations are causal and determining the potential directions and pathways. METHODS: We used 2-sample Mendelian randomization (MR) analysis to assess associations of dietary intakes, medication uses and molecules with BC risk. Genetic summary data were derived from participants of predominantly European ancestry with rigorous instruments selection, where univariable MR, mediation MR and multivariable MR were performed. RESULTS: The results of univariable MR showed 4 dietary intakes and 4 medication uses having a protective effect on BC, while 4 circulating metabolites, 440 circulating proteins and 2 gut microbes were observed to be causally associated with BC risk. Through mediation MR, we found 572 analytes showing consistent mediating effects between dietary intakes or medication uses and BC risk. Furthermore, 9 out of 16 diet-medication pairs showed significant interactions and alterations on BC when consumed jointly. CONCLUSION: In summary, the findings obtained from the current study have important implications for informing prevention strategies that point to potential lifestyle interventions or medication prescriptions to reduce the risk of developing BC.HighlightsThe current study extends observational literature in showing the importance of diets and medications on bladder cancer prevention.The associations of diets and medications on bladder cancer prevention might be through circulating metabolites, circulating proteins and gut microbiotaOur results provide a new understanding of interactions in certain diet-medication pairs which should be taken into account by both physicians and patients during the development of a treatment strategy.

Development and effectiveness of a BOPPPS teaching model-based workshop for community pharmacists training.

BACKGROUND/AIM: With the pharmaceutical innovation and clinical knowledge updating, the continuing education and on-the-job training are extremely important for improving community pharmacists' professional competence. Previous training often adopted traditional lecture-based teaching, and the efficacy was limited. The aim of this study is to develop a new strategy for community pharmacist training. METHODS: Based on the BOPPPS (Bridge-in, Objective, Pre-assessment, Participatory Learning, Post-assessment and Summary) teaching model and workshop method, a continuing on-the-job training program was constructed. Participates were randomly and evenly divided into two groups by random number table method. Twenty-four community pharmacists in total completed all training contents and evaluation components in this study. Twelve pharmacists in experimental group were trained via this new BOPPPS-based workshop, while others still adopted traditional didactic lecture-based approaches. RESULTS: After training, quantitative examination combined with clinical pharmacy practice tests were carried out to evaluate the effectiveness and outcomes of two training groups. For written exam, the total scores from the BOPPPS-based workshop group (82.67 ± 4.70) was higher than that of traditional lectured-base group (73.75 ± 6.15) (P < 0.001). Encouragingly, compared with the results of practical ability assessment from traditional training group (71.75 ± 4.75), the pharmacists receiving BOPPPS-based workshop training presented more excellent performance (78.25 ± 5.03), which displayed statistically significant differences (P < 0.01). In addition, an anonymous questionnaire was used to survey trainees' feelings after completing this continuing education program. The results revealed that the BOPPPS-based workshop can bring a better learning experience than traditional lecture-based training, and the percentages of positive response to each item were more than 91.7%. CONCLUSIONS: Through multi-dimensional evaluation, it was suggested that our BOPPPS-based workshop achieved desired training effects. Moreover, our research also demonstrated that this strategy had advantages of stimulating inspiration, autonomous learning, team-work spirit and pharmacy practice improvement. It may provide a reference of innovative training method for community pharmacists.

OsEIN2-OsEIL1/2 pathway negatively regulates chilling tolerance by attenuating OsICE1 function in rice.

Low temperature severely affects rice development and yield. Ethylene signal is essential for plant development and stress response. Here, we reported that the OsEIN2-OsEIL1/2 pathway reduced OsICE1-dependent chilling tolerance in rice. The overexpressing plants of OsEIN2, OsEIL1 and OsEIL2 exhibited severe stress symptoms with excessive reactive oxygen species (ROS) accumulation under chilling, while the mutants (osein2 and oseil1) and OsEIL2-RNA interference plants (OsEIL2-Ri) showed the enhanced chilling tolerance. We validated that OsEIL1 and OsEIL2 could form a heterxodimer and synergistically repressed OsICE1 expression by binding to its promoter. The expression of OsICE1 target genes, ROS scavenging- and photosynthesis-related genes were downregulated by OsEIN2 and OsEIL1/2, which were activated by OsICE1, suggesting that OsEIN2-OsEIL1/2 pathway might mediate ROS accumulation and photosynthetic capacity under chilling by attenuating OsICE1 function. Moreover, the association analysis of the seedling chilling tolerance with the haplotype showed that the lower expression of OsEIL1 and OsEIL2 caused by natural variation might confer chilling tolerance on rice seedlings. Finally, we generated OsEIL2-edited rice with an enhanced chilling tolerance. Taken together, our findings reveal a possible mechanism integrating OsEIN2-OsEIL1/2 pathway with OsICE1-dependent cascade in regulating chilling tolerance, providing a practical strategy for breeding chilling-tolerant rice.

Multi-omics association study of hexadecane degradation in haloarchaeal strain Halogranum rubrum RO2-11.

Haloarchaea with the capacity to degrade alkanes is promising to deal with petroleum pollution in hypersaline environments. However, only a limited number of haloarchaeal species are investigated, and their pathway and mechanism for alkane degradation remain unclear. In this study, Halogranum rubrum RO2-11, a haloarchaeal strain, verified the ability to degrade kerosene and hexadecane in 184 g/L NaCl, with 53% and 52% degradation rates after 9 and 4 days, respectively. Genome sequencing and gene annotation indicated that strain RO2-11 possesses a complete potential alkane-degrading pathway, of which alkane hydroxylases may include CYP450, AlmA, and LadA. Transcriptome and metabolome analyses revealed that the upregulation of related genes in TCA cycle, lysine biosynthesis, and acetylation may help improve hexadecane degradation. Additionally, an alternative degrading pathway of hexadecane based on dual-terminal ß-oxidation may occur in strain RO2-11. It is likely to be the first report of alkane degradation by the genus Halogranum, which may be helpful for applications of oil-pollution bioremediation under high-salt conditions.

The Mediating Role of Psychological Balance on the Effects of Dietary Behavior on Cognitive Impairment in Chinese Elderly.

BACKGROUND: Cognitive impairment, a significant problem in older adults, may be associated with diet. This study aims to examine the association between the dietary diversity score (DDS), dietary pattern (DP), and cognitive impairment in elderly Chinese. This research further explored the role of psychological balance (PB) as a mediator in the relationship between diet and cognitive impairment. METHODS: A total of 14,318 older adults from the Chinese Longitudinal Healthy Longevity Study (CLHLS) in 2018 were included. Latent class analysis (LCA) was used to identify patterns in seven food varieties. Binary logistic regression models were used to determine factors associated with the DDS, DP, and cognitive impairment. The multiple mediation effect model was evaluated using model 6 in the PROCESS version 3.5 program. RESULTS: Among the participants, 4294 (29.99%) developed cognitive impairment. Compared to people in food variety group two or lower, people with a high dietary diversity score (DDS) had lower odds of cognitive impairment. Compared to DP1, DP2 (OR = 1.24, 95%CI = 1.09 to 1.40) was associated with a higher risk of cognitive impairment, and DP4 (OR = 0.79, 95%CI = 0.69 to 0.89) was associated with a lower risk of cognitive impairment. PB mediated the relationship between DDS, DP, and cognitive impairment, with a mediating effect of 27.24% and 41.00%. CONCLUSIONS: A DP that is rich in fruits, vegetables, red meat, fish, eggs, beans, nuts, and milk was related to a lower risk of cognitive impairment. PB has an indirect impact on cognitive impairment. Our findings underscore the importance of promoting a diverse diet, which may contribute to a lower risk of cognitive impairment in older adults. The PB of the elderly should also be taken into consideration.

Ultrasound radiomics signature for predicting central lymph node metastasis in clinically node-negative papillary thyroid microcarcinoma.

BACKGROUND: Whether prophylactic central lymph node dissection is necessary for patients with clinically node-negative (cN0) papillary thyroid microcarcinoma (PTMC) remains controversial. Herein, we aimed to establish an ultrasound (US) radiomics (Rad) score for assessing the probability of central lymph node metastasis (CLNM) in such patients. METHODS: 480 patients (327 in the training cohort, 153 in the validation cohort) who underwent thyroid surgery for cN0 PTMC at two institutions between January 2018 and December 2020 were included. Radiomics features were extracted from the US images. Least absolute shrinkage and selection operator logistic regression were utilized to generate a Rad score. A nomogram consisting of the Rad score and clinical factors was then constructed for the training cohort. Both cohorts assessed model performance using discrimination, calibration, and clinical usefulness. RESULTS: Based on the six most valuable radiomics features, the Rad score was calculated for each patient. A multivariate analysis revealed that a higher Rad score (P < 0.001), younger age (P = 0.006), and presence of capsule invasion (P = 0.030) were independently associated with CLNM. A nomogram integrating these three factors demonstrated good calibration and promising clinical utility in the training and validation cohorts. The nomogram yielded areas under the curve of 0.795 (95% confidence interval [CI], 0.745-0.846) and 0.774 (95% CI, 0.696-0.852) in the training and validation cohorts, respectively. CONCLUSIONS: The radiomics nomogram may be a clinically useful tool for the individual prediction of CLNM in patients with cN0 PTMC.