Browse Articles

Study on the microstructural evolution mechanism of the angular contact ball bearing rings during the quenching and tempering process

A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia

ASXL transcriptional regulator 1 (ASXL1) is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside DNA methyltransferase 3 alpha (DNMT3A) and Tet methylcytosine dioxygenase 2 ( TET2) . CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML) and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways, respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing derepression of silenced elements in heterochromatin. In contrast, the mechanisms that connect mutant ASXL1 and CH are not yet fully understood. CH/CMML-associated ASXL1 mutations encode C-terminally truncated proteins that enhance the deubiquitinase activity of the ASXL-BAP1 “PR-DUB” deubiquitinase complex, which removes monoubiquitin from H2AK119Ub. Here, we show that ASXL1 mutant proteins interact with the euchromatic histone lysine methyltransferases 1 and 2 (EHMT1–EHMT2) complex, which generates H3K9me1 and me2, the latter a repressive modification in constitutive heterochromatin. Compared to cells from age-matched wild-type mice, we found that expanded myeloid cells from old (≥18-mo-old) Asxl1tm/+ mice, a heterozygous knock-in mouse model of CH, display genome-wide decreases of H3K9me2, H3K9me3, and H2AK119Ub as well as an associated increase in expression of transposable elements (TEs) and satellite repeats. Increased TE expression was also observed in monocytes from ASXL1 -mutant CMML patients compared to monocytes from healthy controls. Our data suggest that mutant ASXL1 proteins compromise the integrity of both constitutive and facultative heterochromatin in an age-dependent manner by reducing the levels of H3K9me2/3 and H2AK119Ub. This increase in TE expression correlated with increased expression of nearby genes, including many interferon-inducible (inflammation-associated) genes (ISGs).

Effects of different educational interventions on cervical cancer knowledge and human papillomavirus vaccination uptake among young women in Japan: Preliminary results of a cluster randomized controlled trial

The incidence and mortality rates of cervical cancer are increasing among young Japanese women. In November 2021, the Japanese Ministry of Health, Labour, and Welfare reinstated the active recommendation of the human papillomavirus (HPV) vaccine, after it had been suspended in June 2013 due to reports of adverse reactions. However, vaccine hesitancy is prevalent in the younger generation in Japan. To identify obstacles to vaccine uptake, we conducted a randomized study using different methods to provide educational content to improve health literacy regarding cervical cancer and HPV vaccination among Japanese female students. We surveyed 188 Japanese female students, divided into three groups according to the intervention: no intervention, print-based intervention, and social networking service-based intervention. Twenty questionnaires and the Communicative and Critical Health Literacy scales were used as health literacy scales. Participants’ knowledge and health literacy improved regardless of the method of education. In fact, participants acquired proper knowledge when given the opportunity to learn about the importance of the disease and its prevention. Therefore, medical professionals in Japan must provide accurate scientific knowledge regarding routine HPV vaccination and the risk of cervical cancer in young women to improve their health literacy and subsequently increase HPV vaccination rates in Japan, which may lead to cervical cancer elimination. Trial registration number: UMIN000036636.

Modelling hepatocellular carcinoma microenvironment phenotype to evaluate drug efficacy

Abstract Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Treating HCC is challenging because of the poor drug effectiveness and the lack of tools to predict patient responses. To resolve these issues, we established a patient-centric spheroid model using HepG2, TWNT-1, and THP-1 co-culture, that mimics HCC phenotype. We developed a target-independent cell killing (TICK) exclusion strategy to monitor the therapeutic response. We demonstrated that our model reproduced the Barcelona Clinic Liver Cancer (BCLC) molecular classification, displayed known alterations of epigenetic players, and responded to tyrosine kinase inhibitors (TKIs) such as sorafenib, cabozantinib, and lenvatinib in a patient-dependent manner. Importantly, we reported for the first time that our model correctly predicted 34 clinical outcomes to TKIs out of 37 case studies on 32 HCC patients confirming that patient-centric spheroids, combined with our TICK exclusion strategy, are valuable models for drug discovery and opening a near perspective to personalized care.

TRAMP assembly alters the conformation and RNA binding of Mtr4 and Trf4-Air2

The TRAMP complex contains two enzymatic activities essential for RNA processing upstream of the nuclear exosome. Within TRAMP, RNA is 3′ polyadenylated by a subcomplex of Trf4/5 and Air1/2 and unwound 3′ to 5′ by Mtr4, a DExH helicase. The molecular mechanisms of TRAMP assembly and RNA shuffling between the two TRAMP catalytic sites are poorly understood. Here, we report solution hydrogen–deuterium exchange data with thermodynamic and functional assays to uncover these mechanisms for yeast TRAMP with Trf4 and Air2 homologs. We show that TRAMP assembly constrains RNA-recognition motifs that are peripheral to catalytic sites. These include the Mtr4 Arch and Air2 zinc knuckles 1, 2, and 3. While the Air2 Arch-interacting motif likely constrains the Mtr4 Arch via transient interactions, these do not fully account for the importance of the Mtr4 Arch in TRAMP assembly. We further show that tRNA binding by single active-site subunits, Mtr4 and Trf4-Air2, differs from the double active-site TRAMP. TRAMP has reduced tRNA binding on the Mtr4 Fist and RecA2 domains, offset by increased tRNA binding on Air2 zinc knuckles 2 and 3. Competition between these RNA-binding sites may drive tRNA transfer between TRAMP subunits. We identify dynamic changes upon TRAMP assembly and RNA-recognition motifs that transfer RNA between TRAMP catalytic sites.

Gender difference in domain-specific quality of life measured by modified WHOQoL-BREF questionnaire and their associated factors among older adults in a rural district in Bangladesh

Background The global population of older adults has steadily increased in recent decades. Little is known about the gender difference in the quality of life (QoL) of older adults in the general population. This study aimed to identify factors associated with QoL among older adults by gender. Method Data on QoL using the World Health Organization Quality of Life (WHOQoL-BREF) questionnaire and socio-demographic characteristics, including living status and sources of income, were collected from 1147 older adults. The WHOQoL-BREF has four domains: physical, psychological, social and environmental. Rasch analysis was used to compute a combined score from Likert-type data to a continuous scale ranging from 0% satisfaction to 100% satisfaction in terms of QoL for each domain. We used a generalized linear model to compare the mean rate of QoL for different factors, and logistic regression analysis was used to quantify the associations of factors with below-average QoL measured as 50% or less in QoL. Results The domain-specific QoL mean (standard error), minimum-maximum values were physical 48.9 (0.41), 7–86, psychological 38.9 (0.51), 4–71, social 50.5 (0.49), 8–92, and environmental domains 47.8 (0.37), 6–91 in the total sample with significant gender difference in all but social domain. The proportion of below average QoL for females vs. males was physical 47.6% vs. 42.6%, psychological 74.4% vs.66.7%; social 34.8% vs. 30.1% and environmental domains 56.1% vs. 49.0%. In females, participants living alone were associated with a higher proportion of below average QoL in physical OR 30.2, 95% CI 2.47, 370, psychological OR 9.54, 95% CI1.09,83.27 and social domains OR 5.94, 95% CI 1.25,28.34. In males, participants’ sources of income from relatives were associated with a higher proportion of below average QoL in physical OR 3.6, 95% CI 2.01,6.44, psychological 30.2, 95% CI 2.47, 370, psychological OR 4.63 95% CI 2.56, 8.38, social domains OR 1.81, 95% CI 1.04, 3.16 and environmental domains OR 2.53 95% CI 1.44, 4.43 than those who had own income. Females engaged in income generation activities had better QoL in social and environmental domains than those with house duties, irrespective of their education or socioeconomic status. Males in retired life had the highest QoL in the social and environmental domains if they had better SES. Conclusions The study’s findings reveal that more than 50% of people had below-average QoL in each domain, which is significant. The study also highlighted that females living alone and males without their own income had the poorest QoL. On a positive note, it was found that females engaged in any income generation activities had better QoL in social and environmental domains. These results provide valuable insights for policymakers and healthcare professionals. They underscore the importance of implementing appropriate intervention programs to enhance the QoL of older adults, reiterating the urgency and necessity of their work to improve the health and well-being of older adults.

Ovario- protective effect of Moringa oleifera leaf extract against cyclophosphamide-induced oxidative ovarian damage and reproductive dysfunction in female rats

AbstractIt is crucial to develop new tactics to prevent ovarian tissue damage in women whose reproductive toxicity is caused by chemotherapy. The present investigation was performed to assess the protective effects of Moringa oleifera (M. oleifera) leaf extract on cyclophosphamide (CP)-induced ovarian damage and reproductive dysfunction. Thirty-two female, healthy Wistar albino rats were randomly assigned to four groups (8 rats/group). The first group was given saline intraperitoneally (i.p.). The second group was given a single dose of CP (200 mg/kg; i.p.). The third and fourth groups were given M. oleifera leaf extract (150 and 250 mg/kg; orally) for 20 days before receiving CP on the final day of the experiment. Hormonal assessments, including follicle stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (ES), were performed 24 h after CP administration. In addition, the antioxidant status and inflammatory response against CP were evaluated. Moreover, detailed histopathological and ultra- structural observations were conducted. For evaluation of statistical significance between different groups; One-way analysis of variance (ANOVA) with Tukey’s post hoc test was adopted. Our findings revealed that rats subjected to CP showed increased levels of FSH, LH, malondialdehyde (MDA), tumor necrosis factor-alpha, and interleukin-8 and decreased levels of ES and glutathione. Pre-treatment with M. oleifera leaf extract (250 mg/kg; orally) was statistically significant (p values < 0.05) as it could improve hormonal changes, oxidative stress indices, and pro- inflammatory mediator levels. Consequently, a marked improvement was observed in the ovarian and uterine architectures, with a normal ovarian reserve and a normal endothelium with normal tubular glands. In conclusion, M. oleifera leaf extract (250 mg/kg) could be used as a pharmaceutical supplement because it protects female rats against CP-induced ovarian damage and reproductive dysfunction.

An exchangeable SIM probe for monitoring organellar dynamics of necrosis cells and intracellular water heterogeneity in kidney repair

Monitoring subcellular organelle dynamics in real time and precisely assessing membrane heterogeneity in living cells are very important for studying fundamental biological mechanisms and gaining a comprehensive understanding of cellular processes. However, there remains a shortage of effective tools for these purposes. Herein, we propose a strategy to develop the exchangeable water-sensing probeAPBD for time-lapse imaging of dynamics in cellular membrane-bound organelle morphology with structured illumination microscopy at the nanoscale. In this work, our results reveal mitochondria as the first organelle to undergo morphological changes through swelling, fission, and fusion in cell necrosis, leading to the rupture of the endoplasmic reticulum (ER) sheet adhered to the mitochondria. Meanwhile, the ER tubules are then reconstructed by stretching and fusion of autophagosomes. Moreover, APBD allows us to directly visualize spatially resolved distribution of biomembranes vs. water inside single mammalian cells. Our findings show that the renal ischemia–reperfusion injury (IRI) model results in the increased biomembrane to cytoplasmic water ratio in the tissue. This reveals intracellular water heterogeneity between the nucleus and the cytoplasm during the IRI process. Overall, this study presents a strategy for development of the molecular tools for cellular water heterogeneity and organelle dynamics.

N-Acetyl cysteine exhibits antimicrobial and anti-virulence activity against Salmonella enterica

Salmonella enterica is a common foodborne pathogen that causes intestinal illness varying from mild gastroenteritis to life-threatening systemic infections. The frequency of outbreaks due to multidrug-resistant Salmonella has been increased in the past few years with increasing numbers of annual deaths. Therefore, new strategies to control the spread of antimicrobial resistance are required. In this work, we found that N-acetyl cysteine (NAC) inhibits S. enterica at MIC of 3 mg ml-1 and synergistically activates the bactericidal activities of common antibiotics from three-fold for ampicillin and apramycin up to1000-fold for gentamycin. In addition, NAC inhibits the expression of virulence genes at sub-inhibitory concentrations in a dose-dependent manner. The whole-genome sequencing revealed that continuous exposure of S. enterica to NAC leads to the development of resistance; these resistant strains are attenuated for virulence. These results suggest that NAC may be a promising adjuvant to antibiotics for treating S. enterica in combination with other antibiotics.

Long-term trends in water level fluctuations in lowland lakes in central Europe (Northern Poland)

Diverse plant RNAs coat <i>Arabidopsis</i> leaves and are distinct from apoplastic RNAs

Transgenic expression of a double-stranded RNA in plants can induce silencing of homologous mRNAs in fungal pathogens. Although such host-induced gene silencing is well documented, the molecular mechanisms by which RNAs can move from the cytoplasm of plant cells across the plasma membrane of both the host cell and fungal cell are poorly understood. Indirect evidence suggests that this RNA transfer may occur at a very early stage of the infection process, prior to breach of the host cell wall, suggesting that silencing RNAs might be secreted onto leaf surfaces. To assess whether Arabidopsis plants possess a mechanism for secreting RNA onto leaf surfaces, we developed a protocol for isolating leaf surface RNA separately from intercellular (apoplastic) RNA. This protocol yielded abundant leaf surface RNA that displayed an RNA banding pattern distinct from apoplastic RNA, suggesting that it may be secreted directly onto the leaf surface rather than exuded through stomata or hydathodes. Notably, this RNA was not associated with either extracellular vesicles or protein complexes; however, RNA species longer than 100 nucleotides could be pelleted by ultracentrifugation. Furthermore, pelleting was inhibited by the divalent cation chelator EGTA, suggesting that these RNAs may form condensates on the leaf surface. These leaf surface RNAs are derived almost exclusively from Arabidopsis, but come from diverse genomic sources, including rRNA, tRNA, mRNA, intergenic RNA, microRNAs, and small interfering RNAs, with tRNAs especially enriched. We speculate that endogenous leaf surface RNA plays an important role in the assembly of distinct microbial communities on leaf surfaces.

Neck circumference cutoff point as a predictor of metabolic syndrome in Brazilian rural workers

Neck circumference (NC) is a predictive measure for the diagnosis of Metabolic Syndrome (MS). The aim of the present study was to establish cutoff points for NC as a predictor of the presence of MS in Brazilian rural workers, based on the MS components according to the IDF and NCEP-ATP III criteria. This is a cross-sectional study carried out with rural workers in the municipality of Santa Maria de Jetibá, in the state of Espírito Santo, Brazil. The ROC curve was calculated and the cutoff points for predicting the risk of developing MS were stipulated from the NC, identified by the area under the curve, using different methods of criteria for determining MS. Sensitivity, specificity, positive and negative predictive values and Youden index were applied. The significance level adopted was 5%. The cutoff points were different for males, resulting in 39.550 cm (AUC 0.832) according to the NCEP-ATP III criterion and 39.125 cm (AUC 0.888) according to the IDF criterion. For women, the cutoffs were similar, resulting in a single cutoff of 34.725 cm (AUC 0.862 for NCEP-ATP III and 0.849 for IDF). The cutoff points defined for men and women for NC showed good sensitivity and specificity for predicting MS in the studied population. The NC measurement proved to be a simple, low-cost and accurate measure for assessing this morbidity in Brazilian rural workers.

Investigating the impact of age and sex on cataract surgery complications and outcomes

Spatio-temporal distribution and socioeconomic inequality of low birthweight rate in China from 1992 to 2021 and its predictions to 2030

This paper aims to investigate the trend, spatio-temporal distribution, and socioeconomic inequality of the low birthweight rate (LBWR) in China from 1992 to 2021 and to project the LBWR to 2030. We performed a secondary analysis of data from the China Health Statistics Yearbook. LBWR refers to the ratio of the number of infants born with a birth weight less than 2,500 grams to the number of live births in a given year. We used joinpoint regression models to estimate LBWR trends from 1992 to 2021 for the whole country and from 2002 to 2021 for the three regions (eastern, central, and western regions) and each province. The slope index of inequality (SII) and relative index of inequality (RII) were calculated for each year from 2002 to 2021 based on provincial data. LBWR increased from 2.52% (1992) to 3.70% (2021), and the average annual percentage change (AAPC) (95% confidence interval [CI]) was 1.35% (0.22%, 2.49%) in China. The overall LBWR from 2002 to 2021 was greatest in the Eastern region, but LBWR had the fastest increase in the Western region, with an AAPC (95% CI) of 3.15% (2.59%, 3.12%). There were spatio-temporal differences in the LBWR and trends between provinces. The SII and RII increased linearly from -0.15 and 0.94 to 0.53 (B = 0.035%, p &lt; 0.001) and 1.16 (B = 0.011, p &lt; 0.01), respectively, over the past 20 years. The results of the ARIAM model showed that the National LBWR will be increasedfrom 3.70% in 2021 to 5.28% in 2030. The LBWRs in the eastern, central and western regions in 2030 will be 4.93%, 6.02% and 5.82%, respectively. National and local governments must prioritize disadvantaged groups to mitigate the rapid prevalence of LBWR, reduce regional disparities, and improve perinatal and infant health and health equity in China.

Water and seawater splitting with MgB2 plasmonic metal-based photocatalyst

Abstract Plasmonic nanostructures can help to drive chemical photocatalytic reactions powered by sunlight. These reactions involve excitation of plasmon resonances and subsequent charge transfer to molecular orbitals under study. Here we engineered photoactive plasmonic nanostructures with enhanced photocatalytic performance using non-noble metallic MgB 2 high-temperature superconductor which represents a new family of photocatalysts. Ellipsometric study of fabricated MgB 2  nanostructures demonstrates that this covalent binary metal with layered graphite-like structure could effectively absorb visible and infrared light by excitation of multi-wavelengths surface plasmon resonances. We show that a MgB 2  plasmonic metal-based photocatalyst exhibit fundamentally different behaviour compared to that of a semiconductor photocatalyst and provides several advantages in photovoltaics applications. Excitation of localised surface plasmon resonances in MgB 2  nanostructures allows one to overcome the limiting factors of photocatalytic efficiency observed in semiconductors with a wide energy bandgap due to the usage of a broader spectrum range of solar radiation for water splitting catalytic reactions conditioned by enhanced local electromagnetic fields of localised plasmons. Excitation of localised surface plasmon resonances induced by absorption of light in MgB 2  nanosheets could help to achieve near full-solar spectrum harvesting in this photocatalytic system. We demonstrate a conversion efficiency of ~ 5% at bias voltage of V bias  = 0.3 V for magnesium diboride working as a catalyst for the case of plasmon-photoinduced seawater splitting. Our work could result in inexpensive and stable photocatalysts that can be produced in large quantities using a mechanical rolling mill procedure.

Incidence rate of total knee arthroplasties in eleven European countries: Do they reach a plateau?

Background From several decades, the evolutions of the Incidence Rate (IR) of Primary Knee Arthroplasties are continuously increasing worldwide and have been widely studied in several countries. Some recent works have highlighted the fact that the IR is following a sigmoid curve composed of an exponential growth followed by a linear phase and finished by a plateau. Our objective is to assess the IR evolution of eleven European countries, representing thus a large proportion of this continent, regarding this sigmoid. Methods IRs of primary knee arthroplasties for Austria, Denmark, Finland, France, Germany, Hungary, Italy, Poland, Spain, Sweden, and the United Kingdom between 2005 and 2019 were retrieved from the EUROSTAT database. Several regression models were fitted to each country’s IRs: Poisson, linear, asymptotic, logistic, and Gompertz regression. For each country and each model, the RMSE (Root Mean Square Error) and R2 were calculated and used to estimate their position with respect to this sigmoid curve. Results The best regression models for knee arthroplasties varied following countries. Logistic and Gompertz regressions had the lowest RMSE and R2 values for Austria, Denmark, Germany, Sweden, and the UK. Hungary, Italy, and Poland favored the Poisson regression model. Finland and Spain presented difficulties in determining the optimal model (linear or Poisson), while France faced challenges in choosing between logistic, Gompertz, and linear regression. Conclusion In conclusion, the growth dynamics of IR differ across European countries. Some countries seem to have already reached a plateau and will therefore experience slight growth in the future.

Click beetle larvae from Cretaceous Burmese amber represent an ancient Gondwanan lineage

Assessment tools for transition readiness in adolescents with inflammatory bowel disease: A scoping review

Background Assessing the level of transition readiness in adolescents with inflammatory bowel disease is crucial; however, standardized research tools are lacking. This study aimed to map transition readiness assessment tools for adolescents with inflammatory bowel disease and determine their suitability. Methods A literature review following the Arksey and O’Malley scoping review methodology was conducted. By using appropriate key terms, literature on transition readiness assessment tool searches were conducted in the CNKI, WanFang, SinoMed, Pubmed, Cochrane Library, Web of Science, and CINAHL databases, with a reference search. The retrieval period was from the establishment of the databases to January 2024. Results A total of 2561 studies were obtained through a preliminary search, and 5 references were obtained as retrospective references. Finally, 21 studies were selected for this review. In total, 20 transition readiness assessment tools were identified. Qualitative findings were grouped into five thematic areas: descriptive characteristics of reviewed articles, development procedures, design, psychometric properties, and cohort characteristics for validity testing of transition readiness assessment tools. Conclusions The most appropriate way to assess the transition readiness of adolescents with inflammatory bowel disease is to select an assessment tool that is most suitable for individual needs, accompanied by a comprehensive patient evaluation. Despite some flaws in the methodology, TRM is currently the most suitable assessment tool, and more population studies are needed to validate it.

Hydrocarbon potential in the Northern Egyptian Red Sea: insights from geophysical datasets and analysis of onshore marginal outcrop analogues and subsurface sequences

AbstractThe Red Sea remains a largely under-explored basin, with the Northern Egyptian Red Sea requiring further investigation due to limited borehole data, sparse case studies, and poor seismic quality. A petroleum system, regional structural cross-section, and geological block diagrams integrating onshore fieldwork from Gebel Duwi and offshore subsurface geology were utilized to assess the hydrocarbon potential of the Northern Egyptian Red Sea (NERS). The findings highlight that pre- and syn-rift organic-rich source units in the NERS could generate oil and gas, similar to the capped reservoirs of the Southern Gulf of Suez. The study also reveals that both regions (NERS and SGOS) were influenced by the Levant-Aqaba transform fault influenced both regions (NERS and SGOS), resulting in southwest-dipping strata, replicating the Northern Gulf of Suez structural style. Additionally, rifting extended the rotated basement faulted blocks from the shoreline to the axial trough, creating wedged Miocene sections. Most offshore boreholes in the Red Sea bottomed in Precambrian rock directly below the syn-rift Miocene sequence, suggesting these wells were off-structure, similar to sidetracked wells in the Gulf of Suez, which successfully captured thick pre- and syn-rift sediments. These insights can drive further advancements in hydrocarbon exploration in the Northern Egyptian Red Sea.

MYO7A is required for the functional integrity of the mechanoelectrical transduction complex in hair cells of the adult cochlea

Myosin-VIIA (MYO7A) is an unconventional myosin responsible for syndromic (Usher 1B) or nonsyndromic forms of deafness in humans when mutated. In the cochlea, MYO7A is expressed in hair cells, where it is believed to act as the motor protein tensioning the mechanoelectrical transducer (MET) channels, thus setting their resting open probability ( P o ). However, direct evidence for this unique role for an unconventional myosin in mature hair cells is lacking. Here, we show that MYO7A has a distinct role in hair cells, being crucial for the structural integrity of hair bundles. Postnatal deletion of Myo7a leads to 87 to 96% reduction in MYO7A from hair cells by postnatal day 20 (P20), without affecting hearing function. During the following week, mice showed progressive decline in both hearing function and MET current amplitude in hair cells without affecting the resting P o and calcium sensitivity of the MET channel. Hair-bundle stiffness was normal at P20 but halved at P30, despite it having a normal staircase morphology and tip links. The reduction of MYO7A in the stereocilia (&gt;87%) increased their vulnerability to sound-induced damage, with significantly more hearing loss and hair bundle deterioration than in control mice. RNA-sequencing identified a downregulation of several stereociliary genes in the Myo7a -deficient cochlea, indicating the presence of indirect compensatory mechanisms. This study reveals that mature hair cells seem to use a MYO7A-independent mechanism to maintain the resting P o of the MET channels. Instead, MYO7A is essential for maintaining the structural and functional integrity of the hair bundles.