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Single‐cell technologies are revolutionizing biology but are today mainly limited to imaging and deep sequencing. However, proteins are the main drivers of cellular function and in‐depth characterization of individual cells by mass spectrometry (MS)‐based proteomics would thus be highly valuable and complementary. Here, we develop a robust workflow combining miniaturized sample preparation, very low flow‐rate chromatography, and a novel trapped ion mobility mass spectrometer, resulting in a more than 10‐fold improved sensitivity. We precisely and robustly quantify proteomes and their changes in single, FACS‐isolated cells. Arresting cells at defined stages of the cell cycle by drug treatment retrieves expected key regulators. Furthermore, it highlights potential novel ones and allows cell phase prediction. Comparing the variability in more than 430 single‐cell proteomes to transcriptome data revealed a stable‐core proteome despite perturbation, while the transcriptome appears stochastic. Our technology can readily be applied to ultra‐high sensitivity analyses of tissue material, posttranslational modifications, and small molecule studies from small cell counts to gain unprecedented insights into cellular heterogeneity in health and disease. Synopsis A new ultra‐high sensitivity LC‐MS workflow increases sensitivity by up to two orders of magnitude and enables true single‐cell proteome analysis. In‐depth comparison indicates that the single‐cell transcriptome is stochastic while the single‐cell proteome is complete and stable. A highly optimized data independent acquisition powered single‐cell proteomics workflow including sub‐µl sample preparation, very low flow chromatography and trapped ion mobility mass spectrometry (diaPASEF) is presented. Single‐cell proteome analysis is performed by injecting cells one‐by‐one across the cell cycle into the LC‐MS and correctly identifies cell states. Single‐cell proteome information is highly complementary to single‐cell transcriptome information. At the single‐cell level the proteome is quantitatively and qualitatively stable, while the transcriptome is stochastic. Graphical Abstract A new ultra‐high sensitivity LC‐MS workflow increases sensitivity by up to two orders of magnitude and enables true single‐cell proteome analysis. In‐depth comparison indicates that the single‐cell transcriptome is stochastic while the single‐cell proteome is complete and stable.

Transcatheter aortic valve replacement (TAVR) is a standard treatment for severe aortic stenosis (AS), but outcomes vary based on flow state. Low-flow, low-gradient aortic stenosis (LFLG AS) is a heterogenous condition and growing evidence suggests that response to TAVR differs by subtype. However, the generalizability of these studies to U.S. populations remains uncertain. This single-center, US-based retrospective study compared mortality outcomes from TAVR versus conservative management strategies in patients with classical (cLFLG) and paradoxical (pLFLG) LFLG AS. Adults with severe LFLG AS (valve area ≤1.0 cm2, stroke volume index ≤35 mL/m2, and mean pressure gradient <40 mmHg) evaluated for TAVR between 2019 and 2021 were included. Patients were stratified by subtype (cLFLG: left ventricular ejection fraction [LVEF] <50%; pLFLG: LVEF ≥50%) and treatment strategy (TAVR or conservative management). Of 490 patients included (207 cLFLG, 283 pLFLG), 67% underwent TAVR. Median follow-up was 19 months. TAVR was associated with lower mortality than conservative management (adjusted hazard ratio [HR] 0.47; 95% CI 0.33 to 0.69; p <0.001). In cLFLG AS, TAVR significantly reduced mortality (adjusted HR 0.37; 95% CI 0.23 to 0.60; p <0.001). In pLFLG AS, a nonsignificant trend towards benefit was observed (adjusted HR 0.62; 95% CI 0.33 to 1.15; p = 0.127). Among patients managed conservatively, those with pLFLG AS had lower mortality than cLFLG AS (adjusted HR 0.50; 95% CI 0.25 to 0.99; p = 0.046). In conclusion, TAVR is associated with improved survival in LFLG AS, particularly in patients with cLFLG AS. Comparable outcomes in conservatively managed pLFLG AS patients support a more individualized, phenotype-driven treatment approach.

Low-flow low-gradient (LF-LG) aortic stenosis (AS) may occur with preserved or depressed left ventricular ejection fraction (LVEF). Both situations represent the most challenging subset of patients to manage and generally have a poor prognosis. Few and controversial data exist on the outcomes of these patients compared with normal flow-high gradient (NF-HG) AS after transcatheter aortic valve replacement (TAVR). We sought to characterize different transvalvular flow-gradient patterns and to examine their prognostic value after TAVR. We enrolled 1,208 patients with severe AS and categorized as follow: 976 patients NF-HG (mean aortic pressure gradient [MPG] ≥40 mm Hg), 107 paradoxical LF-LG (pLF-LG, MPG <40 mm Hg, LVEF ≥50%, stroke volume index <35 ml/m2), and 125 classical LF-LG (cLF-LG) (MPG <40 mm Hg, LVEF <50%, stroke volume index <35 ml/m2). When compared with NF-HG and pLF-LG, cLF-LG had a worse symptomatic status (New York Heart Association III to IV 86% vs 62% and 67%, p <0.001), a higher prevalence of eccentric hypertrophy and a higher level of LV global afterload reflected by a higher valvuloarterial impedance. Valvular function after TAVR was excellent over time in all patients. While 30-day mortality (p = 0.911) did not differ significantly among groups, cLF-LG had a lower 5-year survival rate (LF-LG 50% vs pLF-LG 62% and NF-HG 68%, p <0.05). cLF-LG was associated with a hazard ratio for mortality of 2.41 (95% confidence interval 1.65 to 3.52, p <0.001). In conclusion, TAVR is an effective procedure regardless of transvalvular flow-gradient patterns. However, special care should be given to characterized hemodynamic of AS, as patients with pLF-LG had similar survival rates than patients with NF-HG, whereas cLF-LG is associated with a twofold increased risk of mortality at 5-year follow-up.

Axial flow pumps are widely used in water conservancy, petrochemical and agricultural industries. Efficient operation is crucial for energy conservation and emission reduction. Improving efficiency under severe conditions requires studying the internal flow of axial-flow pumps, particularly at low flow rates where backflow vortices form near the impeller inlet. This study investigates the unsteady flow characteristics of backflow vortices at different flow rates in an axial-flow pump. Results show that backflow vortices form when the flow rate decreases to 0.59 Q d . As the flow rate further declines, the backflow vortex progresses upstream, contracts, and rebounds. The flow rate range is divided into three stages: Stage I with no backflow vortex, stage II with initial vortex development extending upstream and relatively fragmented, and stage III with vortex contraction and rebound forming a more coherent structure. Besides, backflow vortices induce significant pressure fluctuations and velocity oscillations with the primary frequency being 0.5 f b . They exhibit a three-dimensional spiral motion involving changes in axial length, self-rotation, and revolution around the pump axis, with an angular velocity of approximately half the impeller’s rotational speed. This work enhances insights into backflow vortex behaviors, which is essential for optimizing pump design and improving operational stability in challenging environments.

There are different methods in hydrological approach for estimating the environmental flow and a comparative assessment is necessary. The low flow indexes (7Q2 and 7Q10), Smakhtin, Tennent and flow duration curve were used to estimate the environmental flow of Zohreh River in the southwest of Iran. The Smakhtin, 7Q2, 7Q10 and Tennant methods resulted in the estimation of constant values of 27.2, 12.7, 5.9 and (8 and 24) cms, so that, on average 52.8, 26.9 and 12.3, 36.7 percent of the monthly flow is allocated to the environmental flow. The monthly environmental flow pattern for these methods does not fit well with the monthly flow pattern, and thus it can be concluded that the Smakhtin, 7Q2, 7Q10 and Tennant methods cannot be used in the initial form. The application of the flow duration curve leads to an environmental flow assessment in the range of 6.8–38 cms in different months, whose time pattern completely matched with the monthly flow pattern. In this method, on average, 30.8% (range 18–48%) of the monthly flow allocated to the environmental flow, which is reasonable and acceptable amounts. Investigating the results of this study shows that the time pattern of the results should be analyzed in comparison with the observational flow pattern to estimate the environmental flow with a hydrological approach. The results also suggest that the methods that provide a constant amount of environmental flow in different months of the year should be interpreted cautiously along with other methods.

Extreme hydrological events, like floods and droughts, exert considerable effects on both human and natural systems. The frequency, intensity, and duration of these events are expected to change due to climate change, posing challenges for water resource management and adaptation. In this study, the Soil and Water Assessment Tool plus (SWAT +) model was calibrated and validated to simulate flow under future shared socioeconomic pathway (SSP2-4.5 and SSP5-8.5) scenarios in the Baro River Basin with R2 values of 0.88 and 0.83, NSE of 0.83 and 0.74, and PBIAS of 0.39 and 8.87 during calibration and validation. Six bias-corrected CMIP6 Global Climate Models (GCM) were selected and utilized to investigate the effects of climate change on the magnitude and timing of hydrological extremes. All climate model simulation results suggest a general increase in streamflow magnitude for both emission scenarios (SSP2-4.5 and SSP5-8.5). The multi-model ensemble projections show yearly flow increases of 4.8% and 12.4% during the mid-term (MT) (2041–2070) and long-term (LT) (2071–2100) periods under SSP2-4.5, and 15.7% and 35.6% under SSP5-8.5, respectively. Additionally, the analysis revealed significant shifts in the projected annual 1 day, 3 day, 7 day, and 30 day maximum flows, whereas the annual 3 day and 7 day minimum flow fluctuations do not present a distinct trend in the future scenario compared to the baseline (1985–2014). The study also evaluated the timing of hydrological extremes, focusing on low and peak flow events, utilizing the annual 7 day maximum and minimum flow for this analysis. An earlier occurrence was noted for both peak and low flow in the SSP2-4.5 scenario, while a later occurrence was observed in the SSP5-8.5 scenario compared to the baseline. In conclusion, this study showed the significant effect of climate change on river hydrology and extreme flow events, highlighting their importance for informed water management and sustainable planning.

•Classical low-flow low-gradient (C-LFLG) aortic stenosis (AS) was associated with worse outcomes after transcatheter aortic valve replacement (TAVR) compared with high-gradient AS.•Patients with normal-flow low-gradient AS had similar mortality at 1 year but higher mortality at 2 years after TAVR compared with those with high-gradient AS.•Multiple clinical characteristics, including tricuspid regurgitation and mitral regurgitation, correlated with C-LFLG AS.•Nontransfemoral access, anemia, and the degree of LV dysfunction, in addition to other clinical characteristics, correlated with higher mortality in patients with C-LFLG AS.•Ejection fraction and transvalvular flow improve after TAVR in patients with C-LFLG AS. This study sought to explore the clinical factors associated with classical low-flow low-gradient (C-LFLG) and normal-flow low-gradient (NFLG) aortic stenosis (AS) compared with high-gradient (HG) AS. We also compared clinical and echocardiographic outcomes after transcatheter aortic valve replacement (TAVR) across flow-gradient patterns. Patients with C-LFLG AS have a higher mortality rate after TAVR than those with HG AS. However, what leads to C-LFLG AS and the predictors of mortality in this population remain unclear. In this retrospective, single-center study involving 1,415 patients with severe AS, patients were classified as having (1) HG AS (aortic valve mean gradient [MG] >40 mm Hg), (2) C-LFLG AS (MG <40 mm Hg, stroke volume index <35 ml/m2, left ventricular ejection fraction <50%), and (3) NFLG AS (MG <40 mm Hg, stroke volume index ≥35 ml/m2, left ventricular ejection fraction ≥50%). Logistic regression was used for predictors of C-LFLG AS. Cox regression was used for predictors of mortality in the C-LFLG AS population. Male gender, multiple co-morbidities, and moderate to severe mitral and tricuspid regurgitation correlated with the C-LFLG AS group. Patients with C-LFLG AS had a higher mortality risk compared with patients with HG AS at 2 years after TAVR. Patients with NFLG AS had similar mortality at 1 year, but higher mortality at 2 years after TAVR compared with patients with HG AS. End-stage renal disease, atrial fibrillation, and other co-morbidities were predictors of 2-year mortality in patients with C-LFLG AS. In conclusion, the mortality rate after TAVR was higher among patients with C-LFLG AS than those with HG AS. Male gender and multiple co-morbidities were predictors of C-LFLG AS. Multiple co-morbidities were predictors of mortality among those patients.

Paired‐catchment studies are widely used to examine the effects of land management practices (“treatments”) on hydrologic processes. Catchments are matched and a pretreatment calibration regression is used to identify the hydrological relationship between the reference and treated catchments. This method assumes that the calibration regression represents the actual relationship between the catchments (assumption of representativeness) and that the relationship will remain stable over time (assumption of stability). Errors are assumed to be small and similar between reference and treated catchments. Thus, observed differences between the catchments following treatment are assumed to result from that treatment alone. However, calibration periods are often short and it is impossible to know if the calibration period is representative. Further, because the study is unreplicated, it is impossible to determine if stability is maintained. Consequently, it is difficult to determine a minimum detectable effect sizes (MDES) below which estimates of changes in streamflow are statistically uncertain. Here, we use bootstrapped sampling from reference‐by‐reference (RxR) comparisons in a paired‐catchment study design to evaluate the MDES. We generate frequency distributions of the potential changes in flow—changes that cannot be caused by treatment effects. From these, we estimate bootstrapped ±95% confidence intervals encompassing the non‐treatment effects which we use as the MDES. We apply this method to long‐term paired‐catchment studies and reexamine changes in both annual water yields and late summer low flows at the HJA Experimental Forest. This bootstrapping method is widely transferable to any long‐term paired catchment study sites where multiple reference catchments exist.

Prognostic implications of pulmonary hypertension (PH) in low-flow low-gradient (LG) aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR) remains unexplored. We aimed to investigate the impact of baseline and changes in PH after TAVR. In this single-center retrospective study, we included patients who underwent TAVR for low-flow LG AS. Patients were categorized into 2 groups: baseline pulmonary artery systolic pressure (PASP) <46 mm Hg (no-to-mild PH) and PASP ≥46 mm Hg (moderate-to-severe PH). On the basis of changes in PASP after TAVR, patients were stratified into increased (ΔPASP ≥ + 5 mm Hg), no change (−4 to +4 mm Hg), and decreased (≤ −5 mm Hg) groups. Primary end point was a composite of all-cause mortality and heart failure rehospitalization. In total, 210 patients were included, 148 in the no-to-mild PH group and 62 in the moderate-to-severe PH group. Median follow-up was 13.2 months. The moderate-to-severe PH group was at an increased risk of composite end point (adjusted hazard ratio [HR] 3.5, 95% confidence interval [CI] 1.8 to 6.9), all-cause mortality (HR 2.4, 95% CI 1.1 to 5.6), and heart failure rehospitalization (HR 8.3, 95% CI 2.9 to 23.7). There were no differences in clinical outcomes among those with increased (32%), no change (28%), and decreased (39%) PASP after TAVR. In conclusion, moderate-to-severe PH at baseline is an independent predictor of worse clinical outcomes in patients with low-flow LG AS who undergo TAVR, and this cohort of patients do not seem to derive the benefits of postoperative reduction of PASP.

Invasive non‐native species (INNS) threaten biodiversity and ecosystem functioning globally. However, there remains a pressing need to understand the environmental factors controlling the dispersal, successful establishment and subsequent ecological impacts of INNS for receiving ecosystems. Here, we examine how region‐wide flow regime magnitudes facilitate the successful establishment of an invasive crayfish species (Pacifastacus leniusculus, signal crayfish) in England (UK). We also consider the interactive effects of invasive crayfish with flow regime variations on the structural and functional diversity of macroinvertebrate communities. Low‐flow magnitudes increased the likelihood of P. leniusculus establishment, with 80% of recorded invasion dates falling in years with flow magnitudes below average (low‐ and low‐moderate flow classes), whilst only 1.6% occurred in high‐flow years. Temporal trajectories of structural and functional macroinvertebrate responses in invaded rivers demonstrated reduced diversity compared to control rivers. Lower taxonomic and functional richness measures typically coincided with periods of low discharge in invaded rivers and were greatest during regionally high‐flows. Macroinvertebrate communities displayed significant structural and functional responses to the interaction between invasive crayfish and flow regime variations. Specifically, a number of low‐ and high‐flow indices yielded significant associations, highlighting the role of extreme hydrological events in shaping INNS effects on receiving ecosystems. We also detected greater ecological effects of invasive crayfish under hydrologically stable conditions. Importantly, and for the first time, we observed that invasive crayfish reversed macroinvertebrate community responses to flow regime cues (e.g. discharge fall rate and minimum flows in the preceding 180 days). Synthesis and applications. Results from this study indicate that low‐flow events facilitate the spread/establishment of invasive crayfish and correspond with greater ecological effects for receiving ecosystems. Given that low‐flow events are predicted to increase in intensity, duration and frequency over the 21st century, our results highlight the potential threat that invasive crayfish may pose under future hydroclimatic changes. Managing river flow regimes effectively (including maintaining higher flow events and flow variability) is likely to be vital in conserving ecological diversity following crayfish invasion. Results from this study indicate that low‐flow events facilitate the spread/establishment of invasive crayfish and correspond with greater ecological effects for receiving ecosystems. Given that low‐flow events are predicted to increase in intensity, duration and frequency over the 21st century, our results highlight the potential threat that invasive crayfish may pose under future hydroclimatic changes. Managing river flow regimes effectively (including maintaining higher flow events and flow variability) is likely to be vital in conserving ecological diversity following crayfish invasion.