Promotion Effect of Catalpol on Angiogenesis and Potential Mechanisms: A Research Based on Network Pharmacology.

Catalpol, a natural iridoid glycoside, has potential therapeutic benefits, including anti-inflammatory and neuroprotective effects. Investigating catalpol's role in angiogenesis is critical for understanding its potential therapeutic applications, particularly in diseases where modulating angiogenesis is beneficial. This study investigates catalpol's influence on angiogenesis and its mechanisms, combining network pharmacology and in vitro experiments. The target genes corresponding to the catalpol were analyzed by SwissTargetPrediction. Then angiogenesis-related targets were acquired from databases like GeneCards. Subsequently, the Database for Annotation, Visualization and Integrated Discovery was employed for Gene Ontology and pathway analysis, while Cytoscape visualized protein interactions. The effect of catalpol on viability and angiogenesis of HUVECs was further examined using Cell Counting Kit-8 and angiogenesis assays. RT-qPCR and western blot were applied to check the expression of angiogenesis-related proteins. Totally, 312 target genes of catalpol and 823 angiogenesis-related targets were obtained with 56 common targets leading to PPI network analysis, highlighting hub genes (AKT1, EGFR, STAT3, MAPK3, and CASP3). These hub genes were mainly enriched in lipid and atherosclerosis pathway and EGFR-related pathway. The in vitro experimental results showed that catalpol achieved a concentration-dependent increase in HUVECs viability. Catalpol also promoted the migration and angiogenesis of HUVECs and up-regulated the expression of EGFR. EGFR knockdown inhibited the effect of catalpol on HUVECs. Catalpol promotes angiogenesis in HUVECs by upregulating EGFR and angiogenesis-related proteins, indicating its potential therapeutic application in vascular-related diseases.

Rationale, Design, and Baseline Characteristics of Participants in the Health@NUS mHealth Augmented Cohort Study Examining Student-to-Work Life Transition: Protocol for a Prospective Cohort Study.

BACKGROUND: Integration of mobile health data collection methods into cohort studies enables the collection of intensive longitudinal information, which gives deeper insights into individuals' health and lifestyle behavioral patterns over time, as compared to traditional cohort methods with less frequent data collection. These findings can then fill the gaps that remain in understanding how various lifestyle behaviors interact as students graduate from university and seek employment (student-to-work life transition), where the inability to adapt quickly to a changing environment greatly affects the mental well-being of young adults. OBJECTIVE: This paper aims to provide an overview of the study methodology and baseline characteristics of participants in Health@NUS, a longitudinal study leveraging mobile health to examine the trajectories of health behaviors, physical health, and well-being, and their diverse determinants, for young adults during the student-to-work life transition. METHODS: University students were recruited between August 2020 and June 2022 in Singapore. Participants would complete biometric assessments and questionnaires at 3 time points (baseline, 12-, and 24-month follow-up visits) and use a Fitbit smartwatch and smartphone app to continuously collect physical activity, sedentary behavior, sleep, and dietary data over the 2 years. Additionally, up to 12 two-week-long bursts of app-based ecological momentary surveys capturing lifestyle behaviors and well-being would be sent out among the 3 time points. RESULTS: Interested participants (n=1556) were screened for eligibility, and 776 participants were enrolled in the study between August 2020 and June 2022. Participants were mostly female (441/776, 56.8%), of Chinese ethnicity (741/776, 92%), undergraduate students (759/776, 97.8%), and had a mean BMI of 21.9 (SD 3.3) kg/m2, and a mean age of 22.7 (SD 1.7) years. A substantial proportion were overweight (202/776, 26.1%) or obese (42/776, 5.4%), had indicated poor mental well-being (World Health Organization-5 Well-Being Index ≤50; 291/776, 37.7%), or were at higher risk for psychological distress (Kessler Psychological Distress Scale ≥13; 109/776, 14.1%). CONCLUSIONS: The findings from this study will provide detailed insights into the determinants and trajectories of health behaviors, health, and well-being during the student-to-work life transition experienced by young adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT05154227; https://clinicaltrials.gov/study/NCT05154227. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56749.

Microbiological characteristics of the lower airway in adults with bronchiectasis: a prospective cohort study.

BACKGROUND: Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis. METHODS: We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up. RESULTS: We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p < 0.001) with the time to the next exacerbation in bronchiectasis. CONCLUSION: We have revealed the pathogenic microbial spectrum in lower airways and the negative correlation of PPM colonization with the time to the next exacerbation in bronchiectasis. These results suggested that pathogens contribute to the progression of bronchiectasis.

Evaluating the carbon footprint of sedation practices in intensive care.

BACKGROUND: Healthcare's carbon footprint contributes to 4.4% of global net emissions and intensive care units (ICUs) are very resource intensive. Existing studies on environmental sustainability in ICUs focused on carbon footprint generated from energy and electricity consumption, use of medical consumables and equipment, but few studies quantified carbon footprint generated from pharmaceuticals used in ICUs. AIM: To evaluate carbon footprint arising from sedation practices in the ICUs. STUDY DESIGN: A pilot, prospective observational study was conducted in two ICUs from 1 August to 22 September 2022 in Singapore General Hospital. Adult patients who were consecutively sedated, intubated and expected to be mechanically ventilated for at least 24 h were included. Total amount of analgesia and sedatives used and wasted in eligible patients were collected. Carbon emission from ICU sedation practices were then quantified using available life cycle assessment data. RESULTS: A total of 31 patients were recruited. Top analgesia and sedative used in both ICUs were fentanyl and propofol, respectively. Carbon footprint from sedative usage and wastage across 7 weeks in both ICUs were 2.206 kg CO2-e and 0.286 g CO2-e, respectively. In total, this equates to driving 15.8 km by car. Proportion of drug wasted ranged from 5.1% to 25.0%, with the top reason for wastage being the drug was no longer clinically indicated. Recommendations to reduce carbon footprint include choosing sedatives with lower carbon emissions where possible and having effective communication among doctors and nurses regarding management plans to minimize unnecessary wastage. CONCLUSION: Our study quantified carbon footprint arising from sedation practices, mainly drug usage and wastage in two ICUs in Singpore General Hospital. RELEVANCE TO CLINICAL PRACTICE: Adopting a holistic approach to environmental sustainability in the ICU, sedation practices also contribute to generating greenhouse gases, albeit small, and can be targeted to reduce unnecessary carbon footprint.

Predictability of buprenorphine-naloxone treatment retention: A multi-site analysis combining electronic health records and machine learning.

BACKGROUND AND AIMS: Opioid use disorder (OUD) and opioid dependence lead to significant morbidity and mortality, yet treatment retention, crucial for the effectiveness of medications like buprenorphine-naloxone, remains unpredictable. Our objective was to determine the predictability of 6-month retention in buprenorphine-naloxone treatment using electronic health record (EHR) data from diverse clinical settings and to identify key predictors. DESIGN: This retrospective observational study developed and validated machine learning-based clinical risk prediction models using EHR data. SETTING AND CASES: Data were sourced from Stanford University's healthcare system and Holmusk's NeuroBlu database, reflecting a wide range of healthcare settings. The study analyzed 1800 Stanford and 7957 NeuroBlu treatment encounters from 2008 to 2023 and from 2003 to 2023, respectively. MEASUREMENTS: Predict continuous prescription of buprenorphine-naloxone for at least 6 months, without a gap of more than 30 days. The performance of machine learning prediction models was assessed by area under receiver operating characteristic (ROC-AUC) analysis as well as precision, recall and calibration. To further validate our approach's clinical applicability, we conducted two secondary analyses: a time-to-event analysis on a single site to estimate the duration of buprenorphine-naloxone treatment continuity evaluated by the C-index and a comparative evaluation against predictions made by three human clinical experts. FINDINGS: Attrition rates at 6 months were 58% (NeuroBlu) and 61% (Stanford). Prediction models trained and internally validated on NeuroBlu data achieved ROC-AUCs up to 75.8 (95% confidence interval [CI] = 73.6-78.0). Addiction medicine specialists' predictions show a ROC-AUC of 67.8 (95% CI = 50.4-85.2). Time-to-event analysis on Stanford data indicated a median treatment retention time of 65 days, with random survival forest model achieving an average C-index of 65.9. The top predictor of treatment retention identified included the diagnosis of opioid dependence. CONCLUSIONS: US patients with opioid use disorder or opioid dependence treated with buprenorphine-naloxone prescriptions appear to have a high (∼60%) treatment attrition by 6 months. Machine learning models trained on diverse electronic health record datasets appear to be able to predict treatment continuity with accuracy comparable to that of clinical experts.

The cross-sectional and prospective associations of parental practices and environmental factors with 24-hour movement behaviours among school-aged Asian children.

BACKGROUND: Parental practices and neighbourhood environmental factors may influence children's movement behaviours. We aimed to investigate the cross-sectional and prospective associations of parental practices and neighbourhood environmental factors with accelerometer-measured 24-hour movement behaviours (24 h-MBs) among school-aged children in Singapore. METHODS: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) study collected information on dimensions of parental practices and neighbourhood environment at age 5.5 years. Confirmatory factor analyses were performed to generate latent variables and used to compute overall parental practices [involvement in PA + support for PA + control of screen viewing context] and environmental scores [facilities for active play + active mobility facilitators + barriers*-1]. Children wore an accelerometer on their non-dominant wrist for seven consecutive days at ages 5.5 and 8 years. The R-package GGIR 2.6 was used to derive moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), inactivity, and total-sleep (napping+night sleep) minutes per day. Associations were determined using compositional data analysis with multivariate linear regression models, taking into account potential confounders. RESULTS: Among 425 children (48% girls, 59% Chinese), higher parental involvement in PA, parental support for PA and overall parental practices were associated with 24 h-MBs at ages 5.5 and 8 years, specifically with greater time spent in MVPA and less time being inactive relative to the remaining movement behaviours. The corresponding mean changes in the overall 24 h-MB for increasing parental practices from lowest to highest scores (- 2 to + 2 z-scores) indicated potential increases of up to 15-minutes in MVPA, 20-minutes in LPA, 5-minutes in sleep duration, and a reduction of 40-minutes in inactivity at age 5.5 years. At age 8 years, this could translate to approximately 15-minutes more of MVPA, 20-minutes more of LPA, a 20-minute reduction in sleep duration, and a 20-minute reduction in inactivity. Parental control of screen viewing contexts and neighbourhood environmental factors were not associated with 24 h-MBs. CONCLUSIONS: Parental practices but not environmental factors were associated with higher MVPA and lower inactivity among Singaporean children, even at a later age. Further research may provide insights that support development of targeted public health strategies to promote healthier movement behaviours among children. STUDY REGISTRATION: This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875.

Highly sensitive spatial transcriptomics using FISHnCHIPs of multiple co-expressed genes.

High-dimensional, spatially resolved analysis of intact tissue samples promises to transform biomedical research and diagnostics, but existing spatial omics technologies are costly and labor-intensive. We present Fluorescence In Situ Hybridization of Cellular HeterogeneIty and gene expression Programs (FISHnCHIPs) for highly sensitive in situ profiling of cell types and gene expression programs. FISHnCHIPs achieves this by simultaneously imaging ~2-35 co-expressed genes (clustered into modules) that are spatially co-localized in tissues, resulting in similar spatial information as single-gene Fluorescence In Situ Hybridization (FISH), but with ~2-20-fold higher sensitivity. Using FISHnCHIPs, we image up to 53 modules from the mouse kidney and mouse brain, and demonstrate high-speed, large field-of-view profiling of a whole tissue section. FISHnCHIPs also reveals spatially restricted localizations of cancer-associated fibroblasts in a human colorectal cancer biopsy. Overall, FISHnCHIPs enables fast, robust, and scalable cell typing of tissues with normal physiology or undergoing pathogenesis.

Role and Mechanism of Epigenetic Regulation in the Aging of Germ Cells: Prospects for Targeted Interventions.

In modern times, a notable trend toward delayed childbearing has been observed in most developed countries. As a result, sperm aging and quality loss, as well as premature ovarian failure (POF), have emerged as major causes of infertility. The pathogenesis of sperm aging and POF is complex and has not been clearly elucidated. However, evidence from some studies has linked germ cell aging to epigenetic modifications. Epigenetics refers to the heritable changes in gene expression that occur in the absence of any alterations to the gene's nucleotide sequence. This paper systematically reviewed and analyzed the relevant literature to describe the relationship of DNA methylation, non-coding RNA regulation, histone modifications, chromatin remodeling, and RNA modifications with sperm aging and POF. In addition, we analyzed how sperm aging and POF can be mitigated via epigenetic interventions. This review could provide new therapeutic insights and guide strategies for improving sperm quality and ovarian function.

Impact of therapeutic plasma exchange intervention timing and liver injury periodization on the prognosis of patients with exertional heat stroke / 中国输血杂志

【Objective】 To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE) intervention timing and liver injury periodization in patients with exertional heat stroke(EHS). 【Methods】 Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected, then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT, AST, TBIL and DBIL. According to propensity score matching analysis, 11 patients in the survival group and 12 patients in the death group were included in the statistical analysis, and 20 of them were treated with TPE. The changes in indicators and clinical outcomes before and after TPE were observed, in order to evaluate the impact of intervention timing on prognosis. 【Results】 Among the 23 patients, 14 had no liver injury or could progress to the repair phase, resulting in 3 deaths(with the mortality rate of 21.43%), while 9 patients failed to progress to the repair phase, resulting in 9 deaths(with the mortality rate of 100%), with significant differences(P<0.05). The mortality rate of the first TPE intervention before the third stage of liver injury was 23.08%(3/13), while that of intervention after reaching or exceeding the third stage was 85.71%(6/7), and the difference was statistically significant(P<0.05). 【Conclusion】 TPE should be executed actively in EHS patients combined with liver injury before the third phase to lock its pathological and physiological processes, thereby improving prognosis and reducing mortality.

Risk factors of allergic reactions caused by therapeutic plasma exchange: a single-center analysis / 中国输血杂志

【Objective】 To review the occurrence of allergic reactions during therapeutic plasma exchange (TPE) and to explore the risk factors of TPE allergic reactions. 【Methods】 The clinical data of 929 patients treated with TPE using plasma components by the Department of Transfusion Medicine in our medical center from 2018 to 2023 were collected. The influencing factors of allergic reactions were analyzed by univariate analysis, and the independent risk factors of allergic reactions were analyzed by logistic multivariate regression analysis. 【Results】 A total of 4 071 TPEs were performed in 929 patients.Among them, 198 patients (21.31%) experienced 349 times (8.57%) of allergic reactions, with the incidence of grade Ⅰ, Ⅱ and Ⅲ allergic reactions of 16.33%, 81.38% and 2.29%, respectively, and no deaths. The univariate analysis showed that the patient′s age, allergy history, diagnosis of immune-related diseases, ICU admission, plasma consumption, total blood volume, maximum blood flow rate and combined use of albumin were related to the occurrence of allergic reactions (P<0.05). Multivariate regression analysis showed that young patients, a history of allergy, immune-related diseases and non-ICU patients were prone to allergic reactions in TPE, but the treatment options of TPE such as substitute fluid category, plasma consumption and blood flow rate were not related to the occurrence of allergic reactions. 【Conclusion】 There are significant individual differences in the occurrence of allergic reactions for TPE, and young age, history of allergies, immune-related diseases and non-ICU patients are risk factors for allergic reactions in TPE. Identifying patients with risk factors before TPE treatment and giving corresponding preventive measures can reduce the incidence of allergic reactions.

A Case Report of Myotonic Dystrophy Type 1 Presenting as Acute Respiratory Failure / 罕见病研究

Myotonic dystrophy type 1 (DM1) is a multisystem trinucleotide repeat expansion disorder usually referred to the department of neurology with complaints of progressive muscle weakness and myotonia. This article reported a 33-year-old female patient with DM1 presenting with acute respiratory failure.Muscle biopsy in vastus lateralis showed significantly increased internal nuclei. Genetic test show CTG repeat expansions with the size of (847±76) in dystrophia myotonica protein kinase (DMPK) gene on chromosome 19. This case report broadens the clinician′s understanding of the atypical clinical manifestations of DM1, so as to avoid missed diagnosis and misdiagnosis.

Prospective clinical study of concurrent chemoradiotherapy combined with nituzumab for targeted treatment of locally advanced nasopharyngeal carci noma in Guangxi,Yunnan and Guizhou regions / 中国耳鼻咽喉头颈外科

OBJECTIVE To explore the clinical effect of concurrent chemoradiotherapy combined with nituzumab in the treatment of locally advanced nasopharyngeal carcinoma in Guangxi,Yunnan and Guizhou.METHODS A total of 80 patients with locally advanced nasopharyngeal carcinoma who were pathologically confirmed and admitted to Affiliated Hospital of Youjiang Ethnomedicine from July 2021 to July 2022 from ethnic minority areas near the border of Guangxi,Yunnan and Guizhou were selected as the subjects of this study.They were randomly divided into control group(standard concurrent chemoradiotherapy)and observation group(combined treatment with nituzumab on the basis of control group),with 40 cases in each group.The levels of tumor markers,oxidative stress indicators,adverse reactions,complications,and recent clinical efficacy of the two groups were compared.RESULTS After treatment,the levels of superoxide dismutase(SOD),cytokeratin 19 fragment antigen21-1(CYFRA21-1),squamous cell carcinoma associated antigen(SCCAg)and serum ferritin(SF)were significantly decreased in both groups,while nitric oxide(NO)and malondialdehyde(MDA)were significantly increased.The levels of SCCAg,SF,CYFRA21-1,NO and MDA in observation group were lower than those in control group,and the level of SOD was higher than those in control group(P<0.05).Compared with the control group,the objective response rate(ORR)in the observation group was increased(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).There was no significant difference in the incidence of complications between the two groups(P>0.05).CONCLUSION Concurrent chemoradiotherapy combined with nituzumab can effectively improve the short-term survival rate and clinical efficacy of patients with locally advanced nasopharyngeal carcinoma,regulate tumor markers and oxidative stress levels,and alleviate the disease.

Clinical Observation on the Modified Huangan Lipi Decoction Combined with Acupuncture at Sifeng Points in the Treatment of Children with Tic Disorders / 广州中医药大学学报

Objective To observe the clinical efficacy of the modified Huangan Lipi Decoction(mainly composed of Sclerotium Poriae Pararadicis,Paeoniae Radix Alba,Atractylodis Macrocephalae Rhizoma,Polygalae Radix,Acori Tatarinowii Rhizoma,and Curcumae Radix)combined with acupuncture at Sifeng(EX-UE10)points in the treatment of children with tic disorders(TD).Methods Seventy cases of TD children with spleen deficiency and liver hyperactivity syndrome were randomly divided into the treatment group and the control group,with 35 cases in each group.The control group was treated with conventional western medicine of Tiapride Hydrochloride Tablets,while the treatment group was treated with the combination of the modified Huangan Lipi Decoction and acupuncture at Sifeng points.Both groups were treated for 8 weeks.The changes of the Yale Global Tic Severity Scale(YGTSS)item scores of tic muscle group,tic frequency,tic intensity,complexity and interference degree as well as their total scores in the two groups were observed before and after treatment.Moreover,the clinical efficacy and safety in the two groups were evaluated.Results(1)After 8 weeks of treatment,the total effective rate of the treatment group was 88.57%(31/35),and that of the control group was 68.57%(24/35).The intergroup comparison showed that the total effective rate(tested by chi-square test)and the overall therapeutic efficacy(tested by rank-sum test)of the treatment group were significantly superior to those of the control group,and the differences were statistically significant(P＜0.05).(2)After treatment,the YGTSS item scores of tic muscle group,tic frequency,tic intensity,complexity and interference degree as well as their total scores in the two groups were significantly lower than those before treatment(P＜0.01),and the effect on lowering the above scores of the treatment group was significantly superior to that of the control group,the differences being all statistically significant(P＜0.01).(3)During the treatment,the incidence of adverse reactions in the treatment group was 2.86%(1/35)and that in the control group was 8.57%(3/35).The intergroup comparison showed that the incidence of adverse reactions in the treatment group tended to be lower than that of the control group,but the difference was not statistically significant(P＞0.05).Conclusion Modified Huangan Lipi Decoction combined with acupuncture at Sifeng points exert certain effect in the treatment of TD children with spleen deficiency and liver hyperactivity syndrome,and its efficacy is superior to that of the western medicine Tiapride Hydrochloride Tablets.

Strategies and methods for dynamic parking management under the conditions of ensuring both hospi-tal operation and campus expansions / 现代医院

In the aftermath of the pandemic,the government is accelerating the development of top-tier medical resources to broaden the supply and deliver superior healthcare services.However,during this transitional phase,hospitals are experiencing operational challenges due to concurrent construction activities.Notably,a shortage of parking facilities and increased traffic con-gestion continue to impactmedial consultation experience of patients.This paper tries to explore strategies and methods for dynam-ic parking management during hospital campus expansions,offering insights for other medical institutions into grappling with pa-tient parking issues.

Study on the toxicity characteristics of a clinical bloodstream isolate of Salmonella Telelkebir / 中国人兽共患病学报

The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.

[Distribution Characteristics and Environmental Driving Factors of Cyanobacteria Community in Impounded Lakes and Reservoirs in Shandong on the East Route of South-to-North Water Diversion Project].

To investigate the distribution characteristics of the cyanobacteria community and the driving factors in impounded lakes and reservoirs in Shandong on the east route of the South-to-North Water Diversion Project, monthly samples of phytoplankton and the aquatic environment from Nansi Lake, Dongping Lake, Datun Reservoir, Donghu Reservoir, and Shuangwangcheng Reservoir were collected from May to November during 2010 to 2019. A total of 44 planktonic cyanobacteria taxa were identified with 23 filamentous cyanobacteria taxa. Pseudanabaena limnetica, Cylindrospermopsis raciborskii, Microcystis aeruginosa, and Microcystis wesenbergii were the dominant harmful cyanobacteria species, with a high detection frequency and abundance in all lakes and reservoirs. By analyzing the distribution characteristics of the cyanobacteria community in impounded lakes and reservoirs, we found that filamentous cyanobacteria had growth advantages in the water with large hydraulic disturbances, which should be the key points of cyanobacteria prevention and control in the future. Pearson correlation analysis and generalized linear fitting curve results showed that total nitrogen, total phosphorus, water temperature, and water depth played a key role in affecting the growth of P. limnetica, C. raciborskii, M. aeruginosa, and M. wesenbergii. The nitrogen and phosphorus nutrients could promote the growth of harmful cyanobacteria. Due to the good temperature adaptability, P. limnetica could still become the dominant species in early summer and late autumn, and C. raciborskii, M. aeruginosa, and M. wesenbergii had growth advantages when the water temperature was higher than 25℃. In addition, shallow water was more conducive to the growth of C. raciborskii. It was suggested that based on strengthening of the control of nitrogen and phosphorus nutrient input in lakes and reservoirs, the key monitoring of P. limnetica in lakes should be conducted in early summer and late autumn, and the growth of C. raciborskii in shallow water areas should be paid close attention in the high temperature period to ensure the safety of water quality.

Pyroptosis and inflammasomes in cancer and inflammation.

Nonprogrammed cell death (NPCD) and programmed cell death (PCD) are two types of cell death. Cell death is significantly linked to tumor development, medication resistance, cancer recurrence, and metastatic dissemination. Therefore, a comprehensive understanding of cell death is essential for the treatment of cancer. Pyroptosis is a kind of PCD distinct from autophagy and apoptosis in terms of the structure and function of cells. The defining features of pyroptosis include the release of an inflammatory cascade reaction and the expulsion of lysosomes, inflammatory mediators, and other cellular substances from within the cell. Additionally, it displays variations in osmotic pressure both within and outside the cell. Pyroptosis, as evidenced by a growing body of research, is critical for controlling the development of inflammatory diseases and cancer. In this paper, we reviewed the current level of knowledge on the mechanism of pyroptosis and inflammasomes and their connection to cancer and inflammatory diseases. This article presents a theoretical framework for investigating the potential of therapeutic targets in cancer and inflammatory diseases, overcoming medication resistance, establishing nanomedicines associated with pyroptosis, and developing risk prediction models in refractory cancer. Given the link between pyroptosis and the emergence of cancer and inflammatory diseases, pyroptosis-targeted treatments may be a cutting-edge treatment strategy.

Biological roles of A-to-I editing: implications in innate immunity, cell death, and cancer immunotherapy.

Adenosine-to-inosine (A-to-I) editing, a key RNA modification widely found in eukaryotes, is catalyzed by adenosine deaminases acting on RNA (ADARs). Such RNA editing destabilizes endogenous dsRNAs, which are subsequently recognized by the sensors of innate immune and other proteins as autologous dsRNAs. This prevents the activation of innate immunity and type I interferon-mediated responses, thereby reducing the downstream cell death induced by the activation of the innate immune sensing system. ADARs-mediated editing can also occur in mRNAs and non-coding RNAs (ncRNAs) in different species. In mRNAs, A-to-I editing may lead to missense mutations and the selective splicing of coding regions. Meanwhile, in ncRNAs, A-to-I editing may affect targeting and disrupt ncRNAs maturation, leading to anomalous cell proliferation, invasion, and responses to immunotherapy. This review highlights the biological functions of A-to-I editing, its role in regulating innate immunity and cell death, and its potential molecular significance in tumorigenesis and cancer targeted therapy and immunotherapy.

Identifying Adult Stomach Tissue Stem/Progenitor Cells Using the Iqgap3-2A-CreERT2 Mouse.

Identification of unique gene markers of normal and cancer stem cells is an effective strategy to study cells of origin and understand tumor behavior. Lineage tracing experiments using the Cre recombinase driven by a stem cell-specific promoter in the CreERT2 reporter mouse model enables identification of adult stem cells and delineation of stem cell activities in vivo. In our recent research on the mouse stomach, Iqgap3 was identified as a homeostatic stem cell marker located in the isthmus of the stomach epithelium. Lineage tracing with the Iqgap3-2A-CreERT2;Rosa26-LSL-tdTomato mouse model demonstrated stem cell activity in Iqgap3-expressing cells. Using the Iqgap3-2A-CreERT2 mouse model to target oncogenic KrasG12D expression to Iqgap3-expressing cells, we observed the rapid development of precancerous metaplasia in the stomach and proposed that aberrant Iqgap3-expressing cells may be critical determinants of early carcinogenesis. In this chapter, we detail a lineage tracing protocol to assess stem cell activity in the murine stomach. We also describe the procedure of inducing KrasG12D expression in Iqgap3-expressing homeostatic stem cells to explore their role as cells of origin and to trace the early cellular changes that precede neoplastic transformation.

Prevalence estimation of ATTRv in China based on genetic databases.

Introduction: Amyloid transthyretin (ATTR) is divided into either hereditary (ATTRv) or sporadic (ATTRwt) and ATTRv is a rare hereditary disease transmitted as an autosomal dominant manner. Its global prevalence is traditionally estimated as 5,000 to 10,000 persons. However, it may be underestimated and the exact prevalence of ATTRv in China mainland remains unknown. Methods: The Genome Aggregation database (gnomAD) database (containing 125,748 exomes) and two genomic sequencing databases--China Metabolic Analytics Project (ChinaMAP) (containing 10588 individuals) and Amcarelab gene database (containing 45392 exomes), were integrated to estimate the prevalence of ATTRv in the world and mainland Chinese populations. Pathogenic variants allele frequency and the prevalence of ATTRv was calculated. Results: Six variants, counting 470 alleles, were defined as pathogenic variants in gnomAD. The prevalence of ATTRv in the world population was 57.4/100,000. Two variants (2 allele counts) and 15 variants (34 individuals) were defined as pathogenic variants in the ChinaMAP database and the Amcarelab exome database, respectively. Thus, the estimated prevalence interval of ATTRv in mainland China was 18.9/100,000-74,9/100,000. Conclusion: The present study demonstrated that the previous prevalence was greatly underestimated using traditional methods. Therefore, raising awareness of the disease is essential for recognizing ATTRv in its early stage.