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Assessing climate sensitivity of the Upper Indus Basin using fully distributed, physically-based hydrologic modeling and multi-model climate ensemble approach
Skeletal muscle stem cells modulate niche function in Duchenne muscular dystrophy mouse through YY1-CCL5 axis
Abstract Adult skeletal muscle stem cells (MuSCs) are indispensable for muscle regeneration and tightly regulated by macrophages (MPs) and fibro-adipogenic progenitors (FAPs) in their niche. Deregulated MuSC/MP/FAP interactions and the ensuing inflammation and fibrosis are hallmarks of dystrophic muscle. Here we demonstrate intrinsic deletion of transcription factor Yin Yang 1 (YY1) in MuSCs exacerbates dystrophic pathologies by altering composition and heterogeneity of MPs and FAPs. Further analysis reveals YY1 loss induces expression of immune genes in MuSCs, including C-C motif chemokine ligand 5 ( Ccl5 ). Augmented CCL5 secretion promotes MP recruitment via CCL5/C-C chemokine receptor 5 (CCR5) crosstalk, which subsequently hinders FAP clearance through elevated Transforming growth factor-β1 (TGFβ1). Maraviroc-mediated pharmacological blockade of the CCL5/CCR5 axis effectively mitigates muscle dystrophy and improves muscle performance. Lastly, we demonstrate YY1 represses Ccl5 transcription by binding to its enhancer thus facilitating promoter-enhancer looping. Altogether, our study demonstrates the critical role of MuSCs in actively shaping their niche and provides novel insight into the therapeutic intervention of muscle dystrophy.
Polypharmacy and self-medication among older adults in Indian urban communities—a cross-sectional study
Abstract Older adults are vulnerable to unsafe medication practices. This cross-sectional study estimated the prevalence and factors of polypharmacy and self-medication among 600 older adults from six Indian cities. The updated Screening Tool of Older Persons’ Prescriptions and Screening Tool to Alert to Right Treatment criteria (version 3) were used. Knowledge, attitudes, and reported practices regarding self-medication were assessed. Descriptive statistics, binary logistic regression, and multivariable analysis were used. The prevalence of polypharmacy was 33.7% (95% CI 29.9–37.6%), with significant associations to multiple comorbidities [adjusted odds ratio (aOR) 2.5 (95% CI 1.1–4.1)], recent transition of care [aOR 3.3 (95% CI 1.4–5.7)], and recent hospitalization [aOR 4.6 (95% CI 2–7.7)]. The proportions of prescriptions with potentially inappropriate medications and potential prescribing omissions were 28.8% (95% CI 25.2–32.6%) and 20.3% (95% CI 17.2–23.8%), respectively. The prevalence of self-medication was 19.7% (95% CI 16.6–23.1%), associated with factors, such as staying alone [aOR 4.5 (95% CI 2.4–6.6)], multiple comorbidities [aOR 3 (95% CI 1.4–6.7)], and recent hospitalization [aOR 4.8 (95% CI 1.5–8)]. Among those who self-medicated, 65.3% lacked knowledge of self-medication, 50% did not comprehend the risks, and 40.7% reported unsafe self-medication practices. The findings emphasize interventions’ necessity for promoting safe medication use in older adults.
Duchenne muscular dystrophy: recent insights in brain related comorbidities
Potato starch quality in relation to the treatments and long-term storage of tubers
Abstract Starch is the most important component of potato tubers, the structure and composition of which play a key role in their utilization as well as processing and storage. Potato seed treatment may play the biggest role in ensuring proper plant growth and development. Isolated starch from tubers of different potato varieties for food processing was evaluated immediately after harvesting and after long-term storage with consideration of different products for potato seed treatment. The quality of starch was evaluated in terms of starch grain size, total starch content, pH, starch stability after freezing, gelatinization temperature as well as phosphorus and amylose content. The varieties differed significantly in starch content and quality. The Beo variety had the highest starch content in dry tuber weight (77.8%) and the best starch quality characteristics (the lowest starch stability after freezing − 18.0% and highest gelatinization temperature − 64.0 ℃ onset and 68.4 ℃ end). Simultaneous treatment of tubers with Supporter and Moncut 460 SC contributed to the highest starch content in tubers (77.6% d. m.) as well as increasing its stability after freezing (20.8%) and decreasing its gelatinization temperatures (61.7 ℃ onset and 66.0 ℃ end). This may be due to the increased proportion of large starch grains and higher amylose and phosphorus content. A slight decrease in starch quality traits was shown after long-term storage of tubers. Maintaining constant conditions during storage along with the applied treatments contributed to this. It is recommended to use products for potato seed treatment in the production technology of potato for consumption and for starch production.
In-situ electrochemical activation accelerates the magnesium-ion storage
A prospective cohort study of the association between mode of delivery and postpartum posttraumatic stress disorder
Recent centennial drought on the Tibetan Plateau is outstanding within the past 3500 years
Abstract Given growing concerns about global climate change, it is critical to understand both historical and current shifts in the hydroclimate, particularly in regions critically entwined with global circulation. The Tibetan Plateau, the Earth’s largest and highest plateau, is a nexus for global atmospheric processes, significantly influencing East Asian hydroclimate dynamics through the synergy of the Asian Monsoon and the Westerlies. Yet, understanding historical and recent hydroclimate fluctuations and their wide-ranging ecological and societal consequences remains challenging due to short instrumental observations and partly ambiguous proxy reconstructions. Here, we present a precisely-dated 3476-year precipitation reconstruction derived from tree-ring δ18O data on the Tibetan Plateau, representing one of the few multi-millennia-long annually-resolved terrestrial δ18O records to date. Our findings reveal that the 20th century drought extremes are severe within the past three millennia, and likely linked to the weakening of both the Asian Monsoon and Westerlies due to anthropogenic aerosol emissions. Additionally, our analyses identified three distinct stages (110 BC–AD 280, AD 330–770 and AD 950–1300) characterized by shifts toward arid hydroclimate conditions, corresponding to significant social unrest and dynasty collapses, which underscores the potential societal impacts of severe hydroclimatic shifts.
Corrosion and degradation behavior of MCSTE-Processed AZ31 magnesium alloy
Abstract This study aims to investigate the impact of multi-channel spiral twist extrusion (MCSTE) on the corrosion and degradation properties of biodegradable AZ31 (Mg-3Al-1Zn, wt.%) magnesium alloy. Square AZ31 billets were processed using route C-MCSTE (with a 180° rotation between passes) at 250°C and with a ram speed of 10 mm/min for up to 8 passes. The extrusion process was conducted via dies with twist angles of 30° and 40°. The microstructural changes and grain size distribution in the alloy were determined with a Scanning Electron Microscopy equipped with Electron Backscatter Diffraction. Electrochemical tests were conducted in a simulated body fluid to model the environment in which medical implants operate. The mechanical properties of the alloy were tested before and after processing using compression tests. The billets processed with a 30° twist angle demonstrated superior mechanical and corrosion resistance compared to those processed with a 40° die. A 66% reduction in grain size was found in billets processed for 4 passes using the 30°-die as compared to the as-annealed condition. Billets processed for 4 and 8 passes showed ultimate compressive strength improvements of 23% and 31%, respectively compared to the as-annealed condition. The 8-pass processed sample using the 30° twist ring die showed 76% improvement in the corrosion rate compared to the as-annealed state. Furthermore, billets processed for 4 passes showed corrosion resistance and ultimate compressive strength improvements of 108% and 23%; respectively compared to the as-annealed condition. These findings imply that the developed MCSTE process can be adopted for industrial use, especially in the manufacturing of biodegradable magnesium alloys for medical implants.
The role of climate and population change in global flood exposure and vulnerability
Phytoconstituent analysis, bioactivity, and safety evaluation of various colors of Chrysanthemum morifolium flower extracts for cosmetic application
An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice
Antihypertensive effect of sinapine extracted from rapeseed meal in 2K1C hypertensive rats
RECQ4-MUS81 interaction contributes to telomere maintenance with implications to Rothmund-Thomson syndrome
Abstract Replication stress, particularly in hard-to-replicate regions such as telomeres and centromeres, leads to the accumulation of replication intermediates that must be processed to ensure proper chromosome segregation. In this study, we identify a critical role for the interaction between RECQ4 and MUS81 in managing such stress. We show that RECQ4 physically interacts with MUS81, targeting it to specific DNA substrates and enhancing its endonuclease activity. Loss of this interaction, results in significant chromosomal segregation defects, including the accumulation of micronuclei, anaphase bridges, and ultrafine bridges (UFBs). Our data further demonstrate that the RECQ4-MUS81 interaction plays an important role in ALT-positive cells, where MUS81 foci primarily colocalise with telomeres, highlighting its role in telomere maintenance. We also observe that a mutation associated with Rothmund-Thomson syndrome, which produces a truncated RECQ4 unable to interact with MUS81, recapitulates these chromosome instability phenotypes. This underscores the importance of RECQ4-MUS81 in safeguarding genome integrity and suggests potential implications for human disease. Our findings demonstrate the RECQ4-MUS81 interaction as a key mechanism in alleviating replication stress at hard-to-replicate regions and highlight its relevance in pathological conditions such as RTS.
Schizophrenia recognition based on three-dimensional adaptive graph convolutional neural network
East Asian Gene flow bridged by northern coastal populations over past 6000 years
Non-linear effects of self-compassion and negative psychological states on nurses’ work engagement
Structural insights into dynamics of the BMV TLS aminoacylation
Extracorporeal hyperoxygenation therapy (EHT) for CO poisoning: in vitro and in vivo feasibility of a full-scale batch system
Abstract Carbon monoxide (CO) poisoning is one of the most common causes of injury and death from poisoning. The primary objective of therapy is to eliminate CO from the patient as quickly as possible to prevent acute and long-term effects. The ideal treatment is hyperbaric oxygen in a pressure chamber. However, pressure chambers are scarce, and therefore, the most common treatment is normobaric oxygen (NBO), which, however, has limited efficacy. Here, we present a full-scale batch system for extracorporeal hyperoxygenation therapy (EHT), which facilitates CO elimination extracorporeally by increasing the dissolved oxygen concentration in the blood. The EHT was characterized in vitro, resulting in a minimum carboxyhemoglobin half-life of 3.26 ± 0.11 min. In large animal trials the EHT reduced the median carboxyhemoglobin half-life by 42% (29.77 min EHT vs. 70.8 min control (NBO)). However, the EHT also induced oscillations in hemodynamic pressures due to changes in the animals’ circulatory volume during operation. After optimization, the EHT could be a promising option for treating CO poisoning.