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Current and emerging approaches to cochlear immunosuppression with translation to human inner ear stem cell therapy: A systematic review
Hearing loss is a significant health burden across all stages of life. One in 5 people suffer hearing loss, with 5% of the world’s population experiencing disabling hearing loss. A large proportion of this loss is the consequence of damage or loss of neurosensory structures, termed “sensorineural” hearing loss. A recent advance in the treatment of sensorineural hearing loss has occurred, with the advent of inner ear stem cell therapy. Focus has pivoted from augmenting existing neural structures to regenerating neural frameworks. To date, stem cell therapy is limited by the host immune system and rejection of donor cells. A better understanding of immunity in the inner is ear required to progress stem cell therapy for hearing loss. This review outlines a contemporary understanding of the inner ear immune system. We discuss concepts of immune dysregulation that may lead to common inner ear pathologies, and, in doing so, review the efficacy of current pharmacotherapies that mitigate end organ damage through a process of immunosuppression. Current literature is appraised through a systematic review exploring two areas of focus; immunosuppression therapies for the treatment of inner ear pathology associated immune dysregulation, and, subsequently, the efficacy of immunosuppressive agents in translational models of inner ear stem cell therapy. Through greater understanding of these concepts, and systematic appraisal of the literature, this review summarises the literature for contemporary immunosuppressive regimes that may facilitate stem cell accommodation in the cochlea and auditory nerve.
On people’s perceptions of climate change and its impacts in a hotspot of global warming
The Hindu Kush Himalayan region is a global hotspot for climate change and highly vulnerable to its direct and indirect impacts. Understanding people’s perception of climate change is crucial for effective adaptation strategies. We conducted a study by using quantitative (Household survey, n = 660) and qualitative data collection tools (Focus group discussion, n = 12; In-depth interviews, n = 27) in central Nepal encompassing three altitudinal regions: Lowland (<1000 m amsl; Terai region), Midland (1000–1500 m amsl; hilly region) and Highland (1500–2100 m amsl; mountainous region). We analyzed 37 years (1981–2017) of climatic data from respective districts (Lowland: Chitwan, Dhading; Midland: Kathmandu, Lalitpur; Highland: Nuwakot, Rasuwa). People’s perception was compared with climate extreme indices measured along these regions and evaluated if they accurately recognized the impacts on the environment and human health. Our findings show significant climate changes, including rising summer temperature, region-specific winter temperatures and extended monsoon seasons in Nepal. Participants in our study accurately perceived these trends but misperceived heavy precipitation patterns. Reported impacts are rise in crop diseases, human diseases, vector expansion and climate induced disasters like floods, landslides, and water resource depletion, with perception accuracy varying by region. These insights highlight the importance of understanding regional and cross-regional perceptions in relation to climate data in order to develop tailored climate adaptation strategies. Policymakers can use this information to establish region-specific educational and communication initiatives, addressing communities’ distinctive vulnerabilities and needs across diverse landscapes. Such approaches can enhance equitable and effective climate resilience in subtropical to alpine regions.
Editorial Expression of Concern: Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing
Zika virus modulates arthropod histone methylation for its survival in mosquito cells
Zika virus (ZIKV) is a mosquito-borne human pathogen that causes mild febrile illness in adults and severe neurological complications and microcephaly in newborns. Studies have reported that ZIKV modulates methylation of human and viral RNA critical for its replication in vertebrate cells. In this study, we show that ZIKV modulates mosquito S-adenosyl methionine (SAMe)-synthase, an enzyme involved in the production of SAMe (methyl donor), and histone methylation for its survival in mosquito cells. Reverse transcription quantitative PCR followed by immunoblotting analysis showed increased amounts of SAMe synthase at both RNA and protein levels, respectively, in C6/36 mosquito cells infected with ZIKV at day 1 post infection (p.i.). Increased levels of SAMe was noted upon ZIKV infection at day 1 p.i in mosquito cells. In addition, increased EZH2 histone methyl transferase-like gene transcripts and methylated histone (H3K27me3) levels were evident in mosquito cells upon ZIKV infection. Exogenous addition of SAMe to mosquito cells showed increased ZIKV loads and EZH2 histone methyl transferase-like gene transcript levels. Furthermore, treatment of mosquito cells with EZH2 inhibitor resulted in reduced histone methylation and ZIKV loads. Collectively, our study provides novel information in understanding the importance of SAMe and histone methylation in the survival of ZIKV in its arthropod vector.
The effect of acupuncture on quality of life in patients with irritable bowel syndrome: A systematic review and meta-analysis
Background Acupuncture has been used to improve the quality of life (QoL) of patients in clinical settings. However, the effect of acupuncture on QoL in patients with irritable bowel syndrome (IBS) remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of acupuncture on the QoL of patients with IBS. Method PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science were screened from inception to September 2023. RCTs published in English comparing acupuncture with sham acupuncture, usual care, pharmacological interventions, or other therapies were analyzed for QoL in patients with IBS. The primary outcome was QoL and secondary outcomes were the IBS-symptom severity scale (IBS-SSS) and abdominal pain. The Cochrane Collaboration recommendations were used to assess the risk of bias. Findings Fourteen articles with 2,038 participants were included. The pooled result showed acupuncture can significantly improve the QoL of patients with IBS compared to the conventional treatment (MD = 6.62, 95% CI, 2.30 to 10.94, P<0.001, I2 = 72.45%). Additionally, acupuncture was superior to other interventions in relieving the symptoms’ severity of IBS (MD = -46.58, 95% CI, -91.49 to -1.68, P<0.001, I2 = 90.76%). Nevertheless, acupuncture was not associated with abdominal pain reduction (MD = -0.35, 95% CI, -0.91 to 0.20, P = 0.21, I2 = 0.00%). Lower adverse events were observed in the acupuncture group. Thus, the quality of this study was relatively high. Conclusion The meta-analysis showed that acupuncture improves QoL and symptom severity in patients with IBS and that the optimal parameters for acupuncture to improve QoL in patients with IBS are 30 minutes of acupuncture per session, less than or equal to five sessions per week, and a 4-week course of treatment. However, more high-quality clinical trials are needed to provide stronger evidence.
Optimizing mechanical ventilation: Personalizing mechanical power to reduce ICU mortality ‐ a retrospective cohort study
Background Mechanical ventilation, a crucial intervention for acute respiratory distress syndrome (ARDS), can lead to ventilator-induced lung injury (VILI). This study focuses on individualizing mechanical power (MP) in mechanically ventilated patients to minimize VILI and reduce ICU mortality. Methods A retrospective analysis was conducted using the Amsterdam University Medical Centers Database (AmsterdamUMCdb) data. The study included patients aged 18 and older who needed at least 48 hours of pressure-controlled mechanical ventilation. Patients who died or were extubated within 48 hours and those with inadequate data were excluded. Patients were categorized into hypoxemia groups based on their PaO2/FiO2 ratio. MP was calculated using a surrogate formula and normalized to ideal body weight (IBW). Statistical analyses and machine learning models, including logistic regression and random forest, were used to predict ICU mortality and establish safe upper limits for IBW-adjusted MP. Results Out of 23,106 admissions, 2,338 met the criteria. Nonsurvivors had a significantly higher time-weighted average MP (TWA-MP) than survivors. Safe upper limits for IBW-adjusted MP varied across hypoxemia groups. The XGBoost model showed the highest predictive accuracy for ICU mortality. An individualization method for mechanical ventilation settings, based on real-time physiological variables, demonstrated reduced predicted mortality in a subset of patients. Discussion Elevated TWA-MP is associated with increased ICU mortality, underscoring the need for personalized mechanical ventilation strategies. The study highlights the complexity of VILI and the multifactorial nature of ICU mortality. Further studies to define a safe upper limit for IBW-adjusted MP may help clinicians optimize mechanical ventilation settings and decrease the risk of VILI and mortality. Conclusions Despite the fact that the study’s retrospective design and reliance on a single-center database may limit the generalizability of findings, this study offers valuable insights into the relationship between mechanical power and ICU mortality, emphasizing the need for individualized mechanical ventilation strategies. The findings suggest a potential for more personalized, data-driven approach in managing mechanically ventilated patients, which could improve patient outcomes in critical care settings.
Calculation of standard bodyweights for dogs, cats, rabbits, and guinea pigs
Standard bodyweights are an essential component of calculations that summarise many population-level measures in companion animals, including the defined daily doses for veterinary species (DDDVet) reporting antimicrobial usage. Standard species bodyweights may originate from data derived from clinical records, but current methods to obtain these values risk inaccuracy because they exclude measurements obtained from juvenile animals and consider only individuals that have achieved stable adult bodyweight. This study aimed to improve the accuracy of standard population level species bodyweights through the development of a prediction modelling approach to estimate point mean population bodyweight in dogs, cats, rabbits, and guinea pigs. Data were obtained from the VetCompass database and included bodyweight measurements from approximately three million dogs, two million cats, 220,000 rabbits and 62,000 guinea pigs across 1,800 veterinary practices in the United Kingdom. Initially, Loess models were used to identify the age at which juvenile animals transitioned from growth to stable adult bodyweight. Linear mixed effects models were developed to predict juvenile growth, calibrated such that predicted cessation of growth matched that observed in the Loess models. The prediction models were then used to adjust bodyweight measurements obtained from clinical records of juvenile patients, allowing historical measurements to be included for estimation of a point mean population bodyweight on a subsequent specified target date. Juvenile growth transitioned to stable adult bodyweight at approximately 14 months in dogs, and 13 months in cats, rabbits, and guinea pigs. Point mean whole-population bodyweights estimated on 31st December for each year 2014 – 2023 found that the mean bodyweight of cats, rabbits, and guinea pigs was approximately 4.2 kg, 2.3 kg, and 1.0 kg respectively and changed little over this time period. However, dogs showed a trend to lower mean bodyweight over time, with a mean value of 17.6 kg in 2014, reducing to 16.1 kg by 2023.
Untargeted lipidomics reveals unique lipid signatures of extracellular vesicles from porcine colostrum and milk
Extracellular vesicles (EV) are membranous vesicles considered as significant players in cell-to-cell communication. Milk provides adequate nutrition, transfers immunity, and promotes neonatal development, and milk EV are suggested to play a crucial role in these processes. Milk samples were obtained on days 0, 7, and 14 after parturition from sows receiving either a standard diet (ω-6:ω-3 = 13:1) or a test diet enriched in ω-3 (ω-6:ω-3 = 4:1). EV were isolated using ultracentrifugation coupled with size exclusion chromatography, and characterized by nanoparticle tracking analysis, transmission electron microscopy, and assessment of EV markers via Western blotting. The lipidome was determined following a liquid chromatography–quadrupole time-of-flight mass spectrometry approach. Here, we show that different stages of lactation (colostrum vs mature milk) have a distinct extracellular vesicle lipidomic profile. The distinct lipid content can be further explored to understand and regulate milk EV functionalities and primordial for enabling their diagnostic and therapeutic potential.
Correction: Correlation between cellular uptake and cytotoxicity of polystyrene micro/nanoplastics in HeLa cells: A size-dependent matter
Mixed fleet-based two-echelon vehicle routing optimization for cold chain logistics with diverse recharging strategies
The expansion of cold chain logistics necessitates a substantial fleet of fuel-refrigerated trucks, which presents environmental challenges. Electric vehicles (EVs) offer an environmentally friendly solution for low-carbon development despite the issue of range anxiety. Diverging from the conventional two-echelon distribution structure, this paper explores alternative recharging strategies and introduces an innovative scheme: employing fuel vehicles in suburban areas and EVs in urban central zones. The presented model optimizes economic and environmental considerations to mitigate air pollution and reduce dependence on non-renewable energy sources while providing feasible routes. This study proposes an allocation algorithm and an enhanced ant colony algorithm to address a single-objective two-echelon vehicle routing problem with the mixed fleet (2EVRPMF). The mixed fleet outperforms in terms of both cost and carbon emissions based on numerical experiments. Additionally, the study investigates the influence of battery capacity and recharging rate under various recharge strategies, including their correlation with costs. The findings can provide valuable insights for decision-making in implementing environmentally-friendly logistics within the cold chain industry.
Experimental study on the shear creep behavior of residual soil with varying rock content
Using residual soil from the Shanghecun landslide in the western Henan Province, shear creep tests of residual soil samples with different rock contents (RCs) were performed to explore the creep characteristics, creep rate, and long-term strength of the residual soil. The test results indicate that the residual soil samples with different RCs display typical creep characteristics. With increasing RC, both the instantaneous deformation and the total creep deformation of the residual soil gradually decrease. The shear strain of the residual soil increases gradually with increasing shear stress for the different RCs. With increasing time, the slope of the isochronous stress–strain curves of the residual soil samples with different RCs increases gradually. The Burgers model can simulate the rheological process of the residual soil samples with different RCs. The RC has a significant effect on the shear strength and the long-term strength of the residual soil. With increasing RC, the shear strength and the long-term strength of the residual soil gradually increase, with the long-term strength being approximately 39%–63% of the shear strength.
Research on quantitative assessment of translation quality from the perspective of phraseology
Supported by the relevant theories of phraseology, this study examined the translation quality of three genres of explanatory, argumentative, and narrative essays at the phrase level and aimed to construct a translation quality assessment model. In this study, a total of six variables were extracted from both linguistic form and linguistic meaning in strict accordance with the phrase screening criteria, among which the linguistic form features contained a 2-4 gram match degree and the linguistic meaning features contained a part-of-speech tagged 2-4 gram match degree. The results showed that, first, bigram-related variables were the strongest predictors of translation scores for the three genres. The trigram-related variables were slightly weaker, and the fourgram-related variables were the lowest. The bigram match degree had the highest correlation coefficient of .752** with explanatory text translation scores. Second, all translation quality assessment models of the three genres fit well, with the highest correlation coefficient for the explanatory text model, R = 0.820, R2 = 0.673, followed by argumentative text, and the lowest for narrative text. This study realized the automatic assessment of the meaning and form of translations of different genres, which had certain theoretical and practical significance.
Earliest short-tailed bird from the Late Jurassic of China
Relationship between chromatin configuration and maturation ability of rat oocytes in vitro and in vivo
Purpose Embryo engineering requires a large number of oocytes, which undergo in vitro maturation (IVM). Understanding how to select the best quality oocytes is key to improving IVM efficiency. Oocytes have different germinal vesicle (GV) chromatin configurations, which may explain the heterogeneity in oocyte quality during IVM. However, no reports have categorized, the chromatin configuration of rat GVs or evaluated, the association between the chromatin configuration and oocytes development. Methods The GV chromatin configuration of rat oocytes was divided into seven types according to the degree of chromatin compaction: non-surrounded nucleolus (NSN), prematurely condensed NSN, partly NSN, partly surrounded nucleolus (SN-1), SN-1, condensed SN-1, and aggregated (SN-2). The chromatin configuration distribution was compared during the different stages of oocyte growth and maturation. We also analyzed the changes in the chromatin configuration at different GV stages during IVM. Moreover, the factors affecting the chromatin configuration were analyzed. Results The SN-2 configuration increased with rat oocyte growth and maturation, suggesting that SN-2 facilitates oocyte development. RNA transcription activity in rat oocyte GVs was inversely correlated with oocyte IVM. Conclusions The SN-2 chromatin configuration was related to rat oocyte growth and maturation. RNA transcription activity in rat oocytes in the GV stage was inversely correlated with oocyte maturation.
Knowledge of behavioral risk factors for type 2 diabetes mellitus and its associated factors among women of reproductive age
Background Type 2 diabetes accounts for over 90% of all diabetes cases and is caused by a combination of behavioral risk factors. It is currently a serious health issue, particularly among women of reproductive age, as it is associated with reproductive disorders. Preventing it requires knowledge, but there is limited data on behavioral risk factors in Ethiopia. Objective To assess knowledge of the behavioral risks of type 2 diabetes mellitus and its associated factors among women of reproductive age. Methods A community-based cross-sectional study was conducted, with all women in the town serving as the source population. A multistage sampling method was utilized to recruit kebeles, and a systematic random technique was employed to select households at every 13th interval. We completed interview questionnaires for 623 samples. The crude odds ratio was calculated using a bivariate logistic model, and multivariate analysis was performed to control for confounding and identify associated factors among model-fitting variables using an adjusted odds ratio (AOR). Result The knowledge of behavioral risk factors (BRF) among women of reproductive age (WRA) is 47.0% [95% CI, 43.5–50.9], and significant associations were found with the following factors: average family income of between 3000 and 5000 Ethiopian Birr(ETH) 1.81 [95% CI, 1.03–3.18], > = 5001 ETH 1.93 [95% CI, 1.02–3.68], diabetes mellitus (DM) in the friend or relatives 4.03 [95% CI, 1.56–10.46], family history of DM 9.47 [95% CI, 4.74–18.90], source of information: health workers 1.87 [95% CI, 1.04–3.34] and friend or relatives 1.65 [95% CI, 1.04–2.62]. Conclusion Knowledge of behavioral risk factors for type 2 diabetes was poor among study participants. Factors such as family income, diabetes mellitus (DM) in friends or relatives, family history of DM, and sources of information were strongly associated with good knowledge. It is essential to emphasize health education about behavioral risk factors for women.
Observation of an ultra-high-energy cosmic neutrino with KM3NeT
The machine learning algorithm based on decision tree optimization for pattern recognition in track and field sports
This study aims to solve the problems of insufficient accuracy and low efficiency of the existing methods in sprint pattern recognition to optimize the training and competition strategies of athletes. Firstly, the data collected in this study come from high-precision sensors and computer simulation, involving key biomechanical parameters in sprint, such as step frequency, stride length and acceleration. The dataset covers multiple tests of multiple athletes, ensuring the diversity of samples. Secondly, an optimized machine learning algorithm based on decision tree is adopted. It combines the advantages of Random Forest (RF) and Gradient Boosting Tree (GBT), and improves the accuracy and efficiency of the model in sprint pattern recognition by adaptively adjusting the hyperparameter and tree structure. Specifically, by introducing adaptive feature selection and ensemble learning methods, the decision tree algorithm effectively improves the recognition ability of the model for different athletes and sports states, thus reducing the over-fitting phenomenon and improving the generalization ability. In the process of model training, cross-validation and grid search optimization methods are adopted to ensure the reasonable selection of super parameters. Moreover, the superiority of the model is verified by comparing with the commonly used algorithms such as Support Vector Machine (SVM) and Convolutional Neural Network (CNN). The accuracy rate on the test set is 94.9%, which is higher than that of SVM (87.0%) and CNN (92.0%). In addition, the optimized decision tree algorithm performs well in computational efficiency. However, the training data of this model comes from the simulation environment, which may deviate from the real game data. Future research can verify the generalization ability of the model through more actual data.
Research on energy optimization control strategy for parallel hybrid tractor based on AIPSO
In the research on energy optimization control for parallel hybrid tractors, torque has been identified as a crucial factor influencing the tractor’s fuel economy, operational efficiency, and agricultural development. This study focuses on the tractor’s overall demand torque as the primary research parameter and designs a comprehensive scheme for the parallel hybrid tractor. The study includes the design of power system parameters and the construction of a dynamic model for the entire machine. Based on this, an energy optimization control strategy, termed adaptive immune particle swarm optimization fuzzy control strategy (AIPSOFCS), is proposed. Simulation analysis is performed using representative plowing conditions, and AIPSOFCS is compared with the power follow control strategy (PFCS) and fuzzy control strategy (FCS). The results indicate that AIPSOFCS demonstrates higher fuel economy and operational efficiency compared to PFCS and FCS. In the plowing conditions, the fuel economy of AIPSOFCS is reduced by 8.45% and 2.93% compared to PFCS and FCS, respectively. In the rotary tillage conditions, the fuel economy of AIPSOFCS is reduced by 2.40% and 4.07% compared to PFCS and FCS, respectively. Finally, hardware-in-the-loop (HIL) testing of the controller confirms the effectiveness of AIPSOFCS. This research is of significant importance for enhancing the fuel economy and operational efficiency of parallel hybrid tractors and provides theoretical support and reference for the future.
Identifying iNOS and glycogen as biomarkers for degenerated cerebellar purkinje cells in autism spectrum disorder: Protective effects of erythropoietin and zinc sulfate
Autism spectrum disorder (ASD) is a collective neurodevelopmental disorder affecting young children and accounting for 1% of the world’s population. The cerebellum is the major part of the human brain affected by ASD and is associated with a substantial reduction in the number of Purkinje cells. An association between ASD and the expression of the nitrosative stress biomarker inducible nitric oxide synthase (iNOS), as well as glycogen deposition in damaged Purkinje cells, has not been previously reported in the medical literature. To explore this correlation, young rats were injected with propionic acid (PPA) (500 mg/kg) for 5 days (model group), while the protection groups were treated with either erythropoietin (EPO, 5,000 U/kg) or 2 mg/kg zinc sulfate immediately after the PPA injections. ASD-like features were developed in the model group, as evidenced by cerebellum damage (degeneration of Purkinje cells) and cerebellar dysfunction (behavioral impairment). This study documented the exclusive expression of iNOS in the degenerated Purkinje cells, along with glycogen deposition in these cells. Additionally, PPA significantly (p < 0.001) modulated cerebellar tissue levels of mammalian target of rapamycin (mTOR), gamma-aminobutyric acid (GABA), GABAA receptor, serotonin, the marker of neuronal loss (calbindin D28K), and social interaction deficit. Some of these parameters were differentially protected by EPO and zinc sulfate, with the former providing greater protection than zinc sulfate. Furthermore, a significant correlation between the iNOS score and these parameters associated with ASD was observed. These findings demonstrate the colocalization of iNOS and glycogen in the damaged Purkinje cells induced by ASD, along with the modulation of ASD parameters, which were protected by EPO and zinc sulfate treatments. Thus, these potential novel biomarkers may offer possible therapeutic targets for the treatment of ASD.