Modified steady discrete unified gas kinetic scheme for multiscale radiative heat transfer

In this work, a steady discrete unified gas kinetic scheme (SDUGKS) is proposed to solve the steady radiative transfer equation (RTE), which is an improvement of the original SDUGKS [X. F. Zhou et al., J. Comput. Phys. 423, 109767 (2020)]. The trapezoidal rule other than the rectangular rule used in the original SDUGKS is adopted in the proposed method in the reconstruction of energy flux across cell interface, just as the unsteady DUGKS. By this way, the characteristic line length of the modified SDUGKS establishes a relationship with the Courant-Friedrichs-Lewy (CFL) number in the DUGKS, which guarantees the accuracy of the modified SDUGKS. Furthermore, the characteristic line length is no longer limited by the extinction coefficient like in original SDUGKS. As a result, the modified SDUGKS is more accurate and robust than original SDUGKS, and more efficient than the DUGKS for steady radiation problems. Furthermore, the smooth linear interpolation and the van Leer limiter are used for problems with smooth and discontinuous optical thicknesses, respectively. Several numerical tests with optical thickness varying from optical thin to thick are conducted to validate the present scheme. Numerical results demonstrate that the modified SDUGKS can serve as an effective tool in the study of multiscale steady radiative heat transfer in participating media.Comment: 23pages,16 figures,2 table

Wobble tRNA modification and hydrophilic amino acid patterns dictate protein fate.

peer reviewedRegulation of mRNA translation elongation impacts nascent protein synthesis and integrity and plays a critical role in disease establishment. Here, we investigate features linking regulation of codon-dependent translation elongation to protein expression and homeostasis. Using knockdown models of enzymes that catalyze the mcm(5)s(2) wobble uridine tRNA modification (U(34)-enzymes), we show that gene codon content is necessary but not sufficient to predict protein fate. While translation defects upon perturbation of U(34)-enzymes are strictly dependent on codon content, the consequences on protein output are determined by other features. Specific hydrophilic motifs cause protein aggregation and degradation upon codon-dependent translation elongation defects. Accordingly, the combination of codon content and the presence of hydrophilic motifs define the proteome whose maintenance relies on U(34)-tRNA modification. Together, these results uncover the mechanism linking wobble tRNA modification to mRNA translation and aggregation to maintain proteome homeostasis

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Adjustment Of Surface Chemical And Physical Properties With Functional Polymers To Control Cell Adhesion

Cell-surface interaction is crucial in many cellular functions such as movement, growth, differentiation, proliferation and survival. In the present work, we have developed several strategies to design and prepare synthetic polymeric materials with selected cues to control cell attachment. To promote neuronal cell adhesion on the surfaces, biocompatible, non-adhesive PEG-based materials were modified with neurotransmitter acetylcholine functionalities to produce hydrogels with a range of porous structures, swollen states, and mechanical strengths. Mice hippocampal cells cultured on the hydrogels showed differences in number, length of processes and exhibited different survival rates, thereby highlighting the importance of chemical composition and structure in biomaterials. Similar strategies were used to prepare polymer brushes to assess how topographical cues influence neuronal cell behaviors. The brushes were prepared using the "grown from" method through surface-initiated atom transfer radical polymerization (SI-ATRP) reactions and further patterned via UV photolithography. Protein absorption tests and hippocampal neuronal cell culture of the brush patterns showed that both protein and neuronal cells can adhere to the patterns and therefore can be guided by the patterns at certain length scales. We also prepared functional polymers to discourage attachment of undesirable cells on the surfaces. For example, we synthesized PEG-perfluorinated alkyl amphiphilic surfactants to modify polystyrene-block-poly(ethylene-ran-butylene)-block-polyisoprene (SEBI or K3) triblock copolymers for marine antifouling/fouling release surface coatings. Initial results showed that the polymer coated surfaces can facilitate removal of Ulva sporelings on the surfaces. In addition, we prepared both bioactive and dual functional biopassive/bioactive antimicrobial coatings based on SEBI polymers. Incubating the polymer coated surfaces with gram-positive bacteria (S. aureus), gram-negative bacteria (E. coli) and marine bacteria (C. marina) species demonstrated that, unlike biopassive surfaces, the dual functionality polymer coated surfaces can significantly reduce both live and dead cells, without killing the cells in the culture media. The knowledge gained from those studies offers opportunities for further modification and potential applications of those types of polymers in the future

tRNA modification: is cancer having a wobble?

peer reviewedTranslational control of protein synthesis supports tumor development and progression to metastasis. Wobble tRNA modifications are required during translation elongation and sustain proteome homeostasis. Recent work has highlighted the surprising upregulation of the wobble uridine 34 (U34) tRNA cascade in cancer, which underlies the specific requirement for this pathway in tumor development

Rapid qualitative and quantitative detection of formaldehyde in squids based on colorimetric sensor array

The colorimetric sensor array was used to detect the volatile organic compounds (VOCs) in squids with different formaldehyde content. In order to distinguish whether the formaldehyde is artificially added in the squids, the linear discriminant analysis (LDA) and K-nearest neighbor (KNN) based on principal component analysis (PCA) were used to make qualitative judgments, the result shows that the recognition rates of the training set and prediction set of the LDA model were 95% and 85% respectively, and the recognition rates of the training set and prediction set of the KNN model were both 90%. Moreover, error back propagation artificial neural network (BP-ANN) was used to quantitatively predict the concentration of formaldehyde in squids. The result indicates that the BP-ANN model acquired a good recognition rate with the correlation coefficient (Rp) for prediction was 0.9887 when the PCs was 10. To verify accuracy and applicability of the model, paired sample t-test was used to verify the difference between the predicted value of formaldehyde in the BP-ANN model and the actual addition amount. Therefore, this approach showed well potentiality to provide a fast, accuracy, no need for a pretreatment, and low-cost technique for detecting the formaldehyde in squids

The effect of doxorubicin curcumin co-loaded lipid nanoparticles and doxorubicin on osteosarcoma before surgery

Abstract Background The research aims to observe the difference in the effect of preoperative doxorubicin curcumin co-loaded lipid nanoparticles (DOX+CUR LPNs) and doxorubicin (VAD) in the treatment of osteosarcoma. Methods 68 patients with osteosarcoma who visited the hospital from January 2020 to December 2022 are chosen. They are separated into VAD group and DOX+CUR LPNs group, with 34 cases in each group. VAD and DOX+CUR LPNs groups VAD chemotherapy, and DOX+CUR LPNs treatment, respectively. All patients receive tumor resection. Comparison is made between the two groups before chemotherapy, at the end of chemotherapy and 1 week after surgery on the changes of vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), galectin-3 (Gal-3), renal function indicators cystatin-C (Cys-C), serum creatinine (Scr), blood urea nitrogen (BUN) in the peripheral blood. The clinical efficacy and adverse reactions are determined by observation and follow-up for 1 month. Results The VEGF, Ang-2, and Gal-3 in both groups were significantly lower at 1 week after chemotherapy and surgery compared to before chemotherapy (P < 0.05). The VEGF and Gal-3 in the DOX+CUR LPNs group were lower than those in the VAD group in the same period, with P < 0.05. The Cys-C, Scr, and BUN in both groups of patients after chemotherapy and surgery increased compared to before chemotherapy, with P < 0.05. The Cys-C, Scr, and BUN in the DOX+CUR LPNs group were lower than those in the VAD group during the same period, with P < 0.05. Following up for 1 month, the ORR of the DOX+CUR LPNs group was 94.12% (32/34) higher than that of the VAD group, with P < 0.05. The incidence of adverse reactions in the DOX+CUR LPNs group was 47.05% lower than that in the VAD group, with P < 0.05. Conclusion Preoperative application of DOX+CUR LPNs enables effective drug delivery to the tumor section by combining the antibacterial, antioxidant and anti-inflammatory effects of curcumin, which is co-wrapped in nanoparticles. It has the effect of promoting angiogenesis and damage repair, inhibiting inflammation-related factors, and protecting renal function, while adriamycin alone has drug resistance problems and toxic side effects, which can damage the patient's liver and kidney. Therefore, DOX+CUR LPNs are more effective than adriamycin alone, indicating that it can improve the therapeutic effect of the drug and reduce the side effects, which is of great significance for improving the survival rate and quality of life of patients