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Extensive early marine cementation at the seafloor has important environmental implications (e.g., ocean chemistry and atmosphere pCO2), but its driver remains controversial, because many factors have been proposed to affect early marine cementation. At the Abu Dhabi coastal area of the Persian Gulf, extensive early marine cementation at the seafloor provides a good modern study case for ancient analogs. Based on petrological (thin section, cathodoluminescence and scanning electron microscope) and geochemical (e.g., δ13CDIC, alkalinity, aragonite saturation) analyses, this study investigates integrated factors from seawater to sediment properties and tests previously proposed explanations about extensive early marine cementation at the seafloor. Results suggest multiple factors involved in the early marine cementation. CaCO3 saturation, small CaCO3 saturation gradient and higher sea level in the early Holocene are consistent with former explanations. A new finding is shallow redox boundary within the seafloor sediment promoting extensive early marine cementation. The formation of shallow redox boundary is unrelated to anoxic bottom water and/or enhanced organic influx, but rather is related to: (a) high salinity under hot and arid climate, and (b) low‐energy and restricted shallow marine settings., These conditions undoubtedly occurred in past shallow and warm epeiric marine seas. This provides new insights into formation mechanism and paleoenvironmental interpretation of ancient extensive early marine cementation at the seafloor on epeiric seas. Plain Language Summary Although nowadays (sub) tropical surface seawater is typically CaCO3 oversaturated, extensive early marine cementation is relatively uncommon at the seafloor. This is more complicated by the geological fact that early marine cementation at the seafloor is more common in Calcite seas with lower CaCO3 saturation than Aragonite seas. Understanding key factors controlling early marine cementation at the seafloor is important in many geological aspects, such as sequence stratigraphy, paleoenvironmental interpretation and hydrocarbon exploration. Based on research on a modern subtropical epeiric sea, this study suggests early marine cementation at the seafloor is controlled by both seawater properties and shallow redox boundary within seafloor sediment. The shallow redox boundary is linked to shallow, restricted marine settings and warm, arid climate. The findings herein shed new lights on ancient analogs and related environmental interpretation. Key Points Provide insitu seawater and sediment properties associated with extensive early marine seafloor cementation on a modern epeiric sea Both seawater properties and shallow redox boundary within the seafloor sediment are important for extensive early marine seafloor cementation The formation of shallow redox boundary is linked to climate and topography of the seafloor, and not necessarily related to ocean oxygen level and organic influx

Background: Over the past two decades, China has enjoyed impressive economic development, and her citizens have experienced many remarked changes in their lifestyle. These changes are often associated with an increase in obesity and chronic disease. Methods: In this meta-analysis, based on nationally representative data, we studied the current prevalence of obesity and the trends in obesity, mortality and morbidity in China. Results: Between 1992 and 2002, the prevalence of overweight and obesity increased in all gender and age groups and in all geographic areas. Using the World Health Organization body mass index cut points, the combined prevalence of overweight and obesity increased from 14.6 to 21.8%. The Chinese obesity standard shows an increase from 20.0 to 29.9%. The annual increase rate was highest in men aged 18-44 years and women aged 45-59 years (approximately 1.6 and 1.0% points, respectively). In general, male subjects, urban residents, and high-income groups had a greater increase. With the increase in overweight and obesity, obesity-, and diet-related chronic diseases (e.g., hypertension, cardiovascular disease (CVD), and type 2 diabetes) also increased over the past decade and became a more important preventable cause of death. Hypertension increased from 14.4% in 1991 to 18.8% in 2002 in adults; in older adults aged 35-74 years, it increased from 19.7 to 28.6%. Between 1993 and 2003, the prevalence of CVD increased from 31.4 to 50.0%; diabetes increased from 1.9 to 5.6%. During 1990-2003, although total mortality rate (per 100 000) decreased, overall the mortality rate and contribution (as percentages) to total death of obesity-related chronic disease increased, in particular, in rural areas. Mortality rate (per 100 000) of CVD increased from 128 to 145 and its contribution to total death, 27 to 32%, in rural areas; the figures decreased slightly in urban areas. The mortality rate of 'nutrition, endocrinology and metabolism-related disease' (NEMD) increased in both rural and urban areas between 1990 and 2000, 8.0 to 10.6 and 4.9 to 5.3, respectively. The current prevalence of hypertension, dyslipidaemia, metabolic syndrome, and diabetes among Chinese adults is approximately 20, 20, 15, and 3%, respectively. Conclusion: The prevalence of overweight and obesity and obesity-related chronic diseases have increased in China in the past decade. Our findings provide useful information for the projection of future trends and the formulation of national strategies and programmes that can address the challenges of the growing obesity and chronic disease epidemic.

How cellular and organismal complexity emerges from combinatorial expression of genes is a central question in biology. High-content phenotyping approaches such as Perturb-seq (single-cell RNA-sequencing pooled CRISPR screens) present an opportunity for exploring such genetic interactions (GIs) at scale. Here, we present an analytical framework for interpreting high-dimensional landscapes of cell states (manifolds) constructed from transcriptional phenotypes. We applied this approach to Perturb-seq profiling of strong GIs mined from a growth-based, gain-of-function GI map. Exploration of this manifold enabled ordering of regulatory pathways, principled classification of GIs (e.g., identifying suppressors), and mechanistic elucidation of synergistic interactions, including an unexpected synergy between CBL and CNN1 driving erythroid differentiation. Finally, we applied recommender system machine learning to predict interactions, facilitating exploration of vastly larger GI manifolds.

Theory and evidence converge to suggest perfectionism is a personality construct that matters a great deal and is linked with many consequential outcomes (e.g., depression, eating disorders, suicide, marital problems, and procrastination). With the multidimensional perfectionism construct turning 30 years of age, our review critically examines the past and the future of this construct with a focus on the six landmark dimensions of Hewitt and Flett's (1991) and Frost et al.'s (1990) seminal models: Self-oriented perfectionism, other-oriented perfectionism, socially prescribed perfectionism, personal standards, concerns over mistakes, and doubts about actions. Our review considers both what we understand about these dimensions given the extant empirical literature (i.e., known knowns) and areas where gaps exist in our understanding of multidimensional perfectionism and its consequences (i.e., known unknowns). Evidence suggests the core dimensions of Hewitt and Flett's (1991) and Frost et al.'s (1990) trait and attitudinal models of perfectionism, respectively, are neither captured by nor redundant with other well-established predictors. In fact, these perfectionism dimensions appear to represent core vulnerability factors that are tied intimately to the development and maintenance of a wide range of maladaptive outcomes. La théorie et la preuve convergent pour indiquer que le perfectionnisme est un aspect très important de la personnalité qui est lié à plusieurs conséquences (par ex., dépression, troubles alimentaires, suicide, problèmes conjugaux et procrastination). À l'occasion des 30 ans de la définition de la construction multidimensionnelle du perfectionnisme, notre revue jette un regard critique sur le passé et l'avenir de cette construction, en se concentrant sur les six dimensions repères des modèles précurseurs de Hewitt et Flett (1991) et de Frost et al. (1990) : le perfectionnisme orienté vers soi, le perfectionnisme orienté vers autrui, le perfectionnisme socialement prescrit, les normes personnelles, les préoccupations relatives à ses erreurs, les doutes relatifs à ses actions. Notre revue tient compte à la fois de ce que nous comprenons de ces dimensions, vu l'étendue de la littérature empirique (les connus connus) et des domaines où notre compréhension du perfectionnisme multidimensionnel et de ses conséquences (les connus inconnus) est lacunaire. Les données indiquent que les dimensions de base des traits et des modèles comportementaux du perfectionnisme établis par Hewitt et Flett (1991) et Frost et al. (1990), respectivement, ne sont jamais relevées ni reprises par d'autres indicateurs bien établis. En fait, ces dimensions du perfectionnisme semblent représenter les facteurs de vulnérabilité de base qui sont intimement reliés au développement et au maintien d'une vaste gamme de comportements inadaptés. Public Significance Statement Perfectionism is a personality style consisting of six major components: Self-oriented perfectionism (requiring perfection from the self), socially prescribed perfectionism (the belief that others require perfection from the self), other-oriented perfectionism (requiring perfection from others), personal standards (setting unattainable standards), concern over mistakes, and doubts about actions. This article reviews 30 years of research showing that these perfectionism components are related to various negative psychological, interpersonal, and physical health consequences in people of all ages. Therefore, further research must be conducted to improve the prevention and treatment of perfectionism.

Human colonization of the high-altitude Tibetan Plateau has generally been thought to have been confined to the past few thousand years of the Holocene. Zhang et al. report an investigation of the Nwya Devu archaeological site in central Tibet, 4600 meters above sea level, with Paleolithic occupation dates of ∼40 thousand to 30 thousand years ago (see the Perspective by Zhang and Dennell). The site has yielded a range of stone tools, indicating the adaptive ability of early modern humans to the harsh environment of the “roof of the world.” The findings also suggest that people from Tibet and Siberia may have interacted at this time. Science , this issue p. 1049 ; see also p. 992 The Nwya Devu Paleolithic site in Tibet, 4600 meters above sea level, preserves evidence of early human high-altitude adaptation. The Tibetan Plateau is the highest and one of the most demanding environments ever inhabited by humans. We investigated the timing and mechanisms of its initial colonization at the Nwya Devu site, located nearly 4600 meters above sea level. This site, dating from 40,000 to 30,000 years ago, is the highest Paleolithic archaeological site yet identified globally. Nwya Devu has yielded an abundant blade tool assemblage, indicating hitherto-unknown capacities for the survival of modern humans who camped in this environment. This site deepens the history of the peopling of the “roof of the world” and the antiquity of human high-altitude occupations more generally.

Programmed cell death (PCD) is used by plants for development and survival to biotic and abiotic stresses. The role of caspases in PCD is well established in animal cells. Over the past 15 years, the importance of caspase-3-like enzymatic activity for plant PCD completion has been widely documented despite the absence of caspase orthologues. In particular, caspase-3 inhibitors blocked nearly all plant PCD tested. Here, we affinity-purified a plant caspase-3-like activity using a biotin-labelled caspase-3 inhibitor and identified Arabidopsis thaliana cathepsin B3 (AtCathB3) by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Consistent with this, recombinant AtCathB3 was found to have caspase-3-like activity and to be inhibited by caspase-3 inhibitors. AtCathepsin B triple-mutant lines showed reduced caspase-3-like enzymatic activity and reduced labelling with activity-based caspase-3 probes. Importantly, AtCathepsin B triple mutants showed a strong reduction in the PCD induced by ultraviolet (UV), oxidative stress (H2O2, methyl viologen) or endoplasmic reticulum stress. Our observations contribute to explain why caspase-3 inhibitors inhibit plant PCD and provide new tools to further plant PCD research. The fact that cathepsin B does regulate PCD in both animal and plant cells suggests that this protease may be part of an ancestral PCD pathway pre-existing the plant/animal divergence that needs further characterisation.

The phase diagram of the cuprate superconductors continues to pose formidable scientific challenges. While these materials are typically viewed as doped Mott insulators, it is well known that they are Fermi liquids at high hole-dopant concentrations. It was recently demonstrated that at moderate doping, in the pseudogap (PG) region of the phase diagram, the charge carriers are also best described as a Fermi liquid. Nevertheless, the relationship between the two Fermi-liquid (FL) regions and the nature of the strange-metal (SM) state at intermediate doping have remained unsolved. Here we show for the case of the model cuprate superconductor HgBa2CuO4+δ that the normal-state transport scattering rate determined from the cotangent of the Hall angle remains quadratic in temperature across the PG temperature, upon entering the SM state, and that it is doping-independent below optimal doping. Analysis of prior transport results for other cuprates reveals that this behavior is universal throughout the entire phase diagram and points to a pervasive FL transport scattering rate. These observations can be reconciled with a variety of other experimental results for the cuprates upon considering the possibility that the PG phenomenon is associated with the gradual, non-uniform localization of one hole per planar CuO2 unit.

China's new \"Twelfth Five-Year Plan\" set a target for total NOx emission reduction of 10% for the period of 2011-2015. Heavy-duty diesel vehicles (HDDVs) have been considered a major contributor to NOx emissions in China. Beijing initiated a comprehensive vehicle test program in 2008. This program included a sub-task for measuring on-road emission profiles of hundreds of HDDVs using portable emission measurement systems (PEMS). The major finding is that neither the on-road distance-specific (g km-1 ) nor brake-specific (g kWh-1 ) NOx emission factors for diesel buses and heavy-duty diesel trucks improved in most cases as emission standards became more stringent. For example, the average NOx emission factors for Euro II, Euro III and Euro IV buses are 11.3 ± 3.3 g km-1 , 12.5 ± 1.3 g km-1 , and 11.8 ± 2.0 g km-1 , respectively. No statistically significant difference in NOx emission factors was observed between Euro II and III buses. Even for Euro IV buses equipped with SCR systems, the NOx emission factors are similar to Euro III buses. The data regarding real-time engine performance of Euro IV buses suggest the engine certification cycles did not reflect their real-world operating conditions. These new on-road test results indicate that previous estimates of total NOx emissions for HDDV fleet may be significantly underestimated. The new estimate in total NOx emissions for the Beijing HDDV fleet in 2009 is 37.0 Gg, an increase of 45% compared to the previous study. Further, we estimate that the total NOx emissions for the national HDDV fleet in 2009 are approximately 4.0 Tg, higher by 1.0 Tg (equivalent to 18% of total NOx emissions for vehicle fleet in 2009) than that estimated in the official report. This would also result in 4% increase in estimation of national anthropogenic NOx emissions. More effective control measures (such as promotion of CNG buses and a new in-use compliance testing program) are urged to secure the goal of total NOx mitigation for the HDDV fleet in the future.

Advanced paternal age (APA) has been shown to be a significant risk factor in the offspring for neurodevelopmental psychiatric disorders, such as schizophrenia and autism spectrum disorders. During aging, de novo mutations accumulate in the male germline and are frequently transmitted to the offspring with deleterious effects. In addition, DNA methylation during spermatogenesis is an active process, which is susceptible to errors that can be propagated to subsequent generations. Here we test the hypothesis that the integrity of germline DNA methylation is compromised during the aging process. A genome-wide DNA methylation screen comparing sperm from young and old mice revealed a significant loss of methylation in the older mice in regions associated with transcriptional regulation. The offspring of older fathers had reduced exploratory and startle behaviors and exhibited similar brain DNA methylation abnormalities as observed in the paternal sperm. Offspring from old fathers also had transcriptional dysregulation of developmental genes implicated in autism and schizophrenia. Our findings demonstrate that DNA methylation abnormalities arising in the sperm of old fathers are a plausible mechanism to explain some of the risks that APA poses to resulting offspring.

This study assessed the prognostic value of LCR in patients with cancer-associated malnutrition (CAM). Systemic inflammatory markers, particularly the lymphocyte-to-C-reactive protein ratio (LCR), are related to the survival of patients with CAM. The present retrospective analysis based on a prospective multicenter cohort study, which involved 1,437 hospitalized patients with CAM. The area under the receiver operating characteristic curve (AUC) of ten inflammatory indicators — LCR, advanced lung cancer inflammation index, neutrophil-to-lymphocyte ratio, prognostic nutritional index, modified Glasgow prognostic score, systemic immune-inflammation index, albumin-to-globulin ratio, LCR score, glucose-to-lymphocyte ratio, and platelet-to-lymphocyte ratio—were constructed. Nutritional status, blood markers, and quality of life (QoL) were evaluated within 48 h of admission. The overall survival (OS) was evaluated from September 1 to December 29, 2021. A total of 1,431 cancer patients diagnosed with malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria. Male patients were 62.8% of all, and the mean age was 60.66 years old. The AUC of LCR was higher than that of other inflammatory markers. The restricted cubic spline (RCS) of the Hazard ratios (HRs) showed an inverse L-shaped relationship with LCR. In addition, patients with low LCR had significantly poorer OS than those with high LCR. The addition of LCR to the model increased the predictive ability of 1-year mortality (AUC increase of 0.036), 3-year mortality (AUC increase of 0.038), and 5-year mortality (AUC increase of 0.031). Assessing the LCR can help the medical staff identify cancer patients with nutritional deficiency at high risk of oncological outcomes and develop individualized therapeutic strategies.