Ru-Mg promoted reductive cross-coupling of allyl bromides and alkenes to synthesize 1,7-octadienes with an all-carbon quaternary center.

A Ru-promoted reductive cross-coupling of allyl bromides and electron-deficient alkenes to provide terminal 1,7-octadienes with magnesium as a reductant is reported herein. This approach enables the facile construction of a series of complex terminal 1,7-octadienes with an all-carbon quaternary center under mild reaction conditions, and the synthetic utility of the current method has been demonstrated by a gram scale synthesis. Preliminary mechanism investigations suggested that a radical pathway might not be involved in this transformation.

The syndrome of inappropriate antidiuretic hormone associated with nasal and paranasal malignant tumors.

PURPOSE: To investigate the clinical characteristics of the syndrome of inappropriate antidiuretic hormone (SIADH) associated with nasal and paranasal malignant tumors. METHODS: Patients with locally advanced or recurrence/metastatic malignant tumors of the nasal and paranasal sinuses were included. The SIADH was diagnosed according to the diagnostic criteria. The clinical characteristics of SIADH patients were retrospectively analyzed. RESULTS: Six patients (6/188, 3.2%) met the diagnostic criteria of SIADH, including four olfactory neuroblastoma (4/26, 15.4%), one neuroendocrine carcinoma (1/9, 11.1%), and one squamous cell carcinoma (1/63, 1.6%). Five patients (83.3%) had severe hyponatremia; however, the hyponatremia could be improved by fluid restriction or tolvaptan. Three patients' SIADH were recovered during the chemotherapy and the other three were recovered after the surgery. CONCLUSION: The incidence of SIADH associated with nasal and paranasal malignant tumors is relatively more common in olfactory neuroblastoma and neuroendocrine carcinoma. The hyponatremia caused by SIADH may be corrected by fluid restriction or tolvaptan, and the SIADH may be recovered through anti-tumor therapy.

The Embodied Effect in the Comprehension of Chinese Action-Verb Metaphors.

Embodied cognition holds that one's body, actions, perceptions, and situations are integrated into the cognitive process and emphasizes the fact that sensorimotor systems play a role in language comprehension. Previous studies verified the embodied effect in literal language processing but few of them paid attention to metaphors in embodied cognition. The present study aims to explore the embodied effect in the comprehension of Chinese action-verb metaphor. Participants watched a video containing icons and corresponding actions to learn the relationship between them and how to perform these actions in the learning phase and in the test phase, a series of action-describing metaphor phrases were presented to participants with either the icons as primes or no prime at all. The results confirmed the embodied effect as the reaction times (RTs) were significantly shorter when action prime matched the action-verb in the following action-verb metaphor than that of no-prime condition, which are consistent with the facilitation observed in previous relevant studies in embodied cognition. In conclusion, this study verified the embodied effect in the comprehension of Chinese action-verb metaphor, offering further support to embodied cognition and providing a new interpretation for the metaphoric meaning construction of Chinese action-verbs.

Modifiable risk factors for ventilator associated diaphragmatic dysfunction: a multicenter observational study.

BACKGROUND: Diaphragmatic dysfunction is known to be associated with difficulties weaning from invasive mechanical ventilation and is related to worse patient outcomes yet our understanding of how to prevent diaphragmatic dysfunction remains incomplete. We examined potentially modifiable risk factors for diaphragmatic dysfunction and attempted to estimate benefits attributable to altering these modifiable risk factors. METHODS: This prospective multicenter observational study was undertaken in the general ICUs of two tertiary care teaching hospitals. Critically ill adults expected to receive invasive mechanical ventilation for at least 48 h were enrolled. Diaphragm function was assessed by ultrasound each study day, with dysfunction defined as thickening fraction less than 20%. RESULTS: From January to December 2019, 856 patients were screened and 126 patients were enrolled. Overall, 40.5% (51/126) of patients experienced diaphragmatic dysfunction during invasive mechanical ventilation. Patients with diaphragmatic dysfunction were more likely to develop ventilator associated pneumonia (risk difference [RD] + 12.9%, 95% Confidence Interval [CI] 1.4 to 24.4%, P = 0.028), were more likely to experience extubation failure (RD + 8.5%, 95% CI 0.4 to 16.6%, P = 0.039) and required a longer duration of invasive mechanical ventilation (RD + 1.3 days, 95% CI 0.1 to 2.5 days, P = 0.035). They also required a longer hospital stay (RD + 1.2 days, 95% CI 0.04 to 2.4 days, P = 0.041) and were more likely to die before hospital discharge (RD + 18.1%, 95% CI 3.7 to 32.5%, P = 0.014). Multivariable analysis considered the impact of age, sex, pre-existing nutritional status, caloric intake, amino acid intake, acute disease severity, modes of mechanical ventilation, measures of respiratory status, sedation, pain control and baseline diaphragm thickness. Only SOFA score (P = 0.008) and early amino acid intake (P = 0.001) remained significant independent risk factors for the onset of diaphragmatic dysfunction. Causal path modeling suggested early amino acid intake may significantly reduce diaphragmatic dysfunction (RRR 29%, 95% CI 10% to 48%, P = 0.003) and may also reduce mortality (RRR 49%, 95% CI 25% to 73%, P < 0.0001). CONCLUSIONS: Amino acid intake during the first 24 h of ICU stay may represent an important, modifiable risk factor for diaphragmatic dysfunction and may have a direct causal effect on mortality. We recommend additional research on this topic.

Anterior cruciate ligament femoral footprint is oblong-ovate, triangular, or two-tears shaped in healthy young adults: three-dimensional MRI analysis.

PURPOSE: This study aimed to evaluate the morphology of the anterior cruciate ligament (ACL) femoral footprint with three-dimensional magnetic resonance imaging (3D MRI) in healthy knees. METHODS: Fifty subjects with healthy knees were recruited, utilising 3D-SPACE sequences for ACL evaluation. The ACL was manually segmented, and the shape, size and location of the ACL femoral footprint were evaluated on a reformatted oblique-sagittal plane, which aligned closely with the ACL attachment. Statistical analysis included one-way ANOVA for continuous variables and Fisher's exact test for categorical variables, with a P value < 0.05 considered significant. RESULTS: Three types of ACL femoral footprint shape were identified, namely, oblong-ovate (OO) in 33 knees (66%), triangular (Tr) in 12 knees (24%) and two-tears (TT) in 5 knees (10%), with the mean areas being 58, 47 and 68 mm2, respectively. Within group TT, regions with similar sizes but different locations were identified: high tear (TT-H) and low tear (TT-L). Notably, group OO demonstrated a larger notch height index, whilst group TT was characterised by a larger α angle and lateral femoral condyle index. A noticeable variation was observed in the location of the femoral footprint centre across groups, with group TT-L and group Tr showing a more distal position relative to the apex of the deep cartilage. According to the Bernard and Hertel (BH) grid, the ACL femoral footprint centres in group TT-L exhibited a shallower and higher position than other groups. Furthermore, compared to group OO and TT-H, group Tr showed a significantly higher position according to the BH grid. CONCLUSION: In this study, the morphology of the ACL femoral footprint in healthy young adults was accurately evaluated using 3D MRI, revealing three distinct shapes: OO, Tr and TT. The different ACL femoral footprint types showed similar areas but markedly different locations. These findings emphasise the necessity of considering both the shape and precise location of the ACL femoral footprint during clinical assessments, which might help surgeons enhance patient-specific surgical plans before ACL reconstruction. LEVEL OF EVIDENCE: IV.

Characterizing the spatiotemporal distribution of dissolved organic matter (DOM) in the Yongding River Basin: Insights from flow regulation.

Artificial flow regulation is an important measure to alleviate water shortages and improve the ecological quality of river basins. Dissolved organic matter (DOM) plays a crucial role in the carbon cycle and regulates biogeochemical and ecological processes in aquatic systems. Among the numerous studies on the effects of anthropogenic activities on the quality and quantity of river DOM, few studies have focused on the influence of different artificially regulated flow on the composition, source, and fate of fluvial DOM. This study aims to elucidate the impact of different artificial regulation modes of river flows on the source, migration, and transformation of DOM. The optical properties of DOM were used to explore the temporal and spatial distribution characteristics of DOM in the Yongding River Basin, where artificial regulation of river flows by cross-basin and inner-basin water transfers were implemented. Excitation-emission matrix fluorescence spectroscopy coupled with parallel factor analysis revealed four fluorescent substances of DOM in the water: one microbial humic-like (C1), one terrestrial humic-like (C2), one non-point source pollution humic-like (C4), and one tryptophan-like (C3) substance. Due to cross-basin water transfer from the Yellow River, the flow is the highest (21.79 m3/s) during spring, which was the reason that the signal of C2 was stronger during spring (71.45 QSU) compared to summer (57.12 QSU) and autumn (51.78 QSU). Due to inner-basin water transfer from upstream reservoirs, C3 derived from autochthonous sources were higher during autumn (130.81 QSU) than during spring (77.17 QSU) and summer (93.16 QSU). With no water transfer, more C1 were present at higher temperatures during summer (141.51 QSU) than during spring (126.73 QSU) and autumn (128.8 QSU). Moreover, C4 originating from urban and/or agricultural non-point source runoff increased during summer (57.07 QSU) than during spring (33.29 QSU) and autumn (52.27 QSU) because of increased rainfall. The different modes of artificial regulation of river flows changed the hydrological characteristics of the basin, which in turn altered the temporal and spatial distribution characteristics of the quantity and quality of DOM. The finding of this study can help promote the development of appropriate management strategies for artificial regulation of river flows in the basin. Furthermore, this study provides a basis for investigating the effects of different artificial flow regulations on the carbon cycles and ecological risks of rivers in the basin.

Expression of TRIM44 and its correlation with TLR4 in laryngeal squamous cell carcinoma.

Some members of the tripartite motif-containing protein family have been reported as important regulators of carcinogenesis. In the present study, it was investigated whether tripartite motif-containing protein 44 (TRIM44) acts as a pro-oncogene through their over-expression in laryngeal squamous cell carcinoma. Its results showed that TRIM44 was up-regulated in tumor tissues and cell lines of laryngeal squamous cell carcinoma. In vitro, knockdown of TRIM44 significantly inhibited cell growth of laryngeal squamous cell carcinoma. Furthermore, TRIM44 knockdown inhibited tumor growth in nude mice in vivo, further suggesting the oncogenic activity of TRIM44 in laryngeal squamous cell carcinoma. Also, TRIM44 positively correlated with TLR4 at the mRNA and protein levels, and Si-RNA-NF-κB restrained laryngeal squamous cell carcinoma from proliferating. All indicated that TRIM44 might play a key role in tumor invasion through their over-expression and inhibition of TRIM44 is an effective strategy for the treatment of laryngeal squamous cell carcinoma.

Development and characterization of an amorphous curcumin-Eudragit®E100 solid dispersions with improved solubility, stability, and pharmacokinetic properties.

The development of amorphous solid dispersions (ASD) is one way to overcome the bioavailability challenges of poorly water-soluble drug. Herein, Curcumin (CUR) was dispersed in the polymeric matrix of Eudragit®E100 by solvent evaporation, giving ASD, donated as CUR@Eudragit®E100. Solubility and stability of CUR were greatly enhanced. DSC and XRD analysis confirmed that the incorporated CUR was present in an amorphous state. The interaction between CUR and Eudragit®E100 was investigated through FTIR and molecular modelling studies which implied that -OH groups in CUR, and carboxyl and amino groups in Eudragit®E100 involved in the hydrogen bond formation. High resolution atomic force microscopy was employed to directly visualize the molecular morphology of Eudragit®E100 and CUR in CUR@Eudragit®E100 and the interaction between CUR and the polymer. pH influenced CUR release profile in which the sustained release pattern was revealed vs the physical mixtures. From the plasma concentration vs time profile graph, oral bioavailability of Cur@Eudragit®E100 was approximately 5-fold higher than that of native CUR. These results confirmed the potential of designing ASD to enhance the solubility and bioavailability of CUR, simultaneously deliver CUR through this alternative administration route.

A Pyrene Fluorescent Probe for Rapid Detection of Ferric Ions.

The 1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt (PTSA) is a pyrene derivative with high fluorescence characteristics and is widely used in fluorescence tracer. This study aims at investigating a simple and fast fluorescence detection method for determining the concentration of ferric ion by using PTSA, which the principle is that the fluorescence quenching of PTSA by ferric ions. Theoretical and experimental methods were adopted to deeply analyze its detection performance and characteristics. The fluorescence quenching phenomena under different pH conditions and the effect of the different interfering metal ions on PTSA/Fe3+ system was studied. The results showed that the PTSA was quite promising for the fluorescence detection of trace ferric ions, and the limit of detection is 9 µg/L. This study is envisioned to provide inspirational insights on trace detection of iron ions, opening new routes for water monitoring use fluorescence properties.

Transmembrane transport mechanism of n-hexadecane by Candida tropicalis: Kinetic study and proteomic analysis.

Yeasts are the most predominant petroleum hydrocarbon-degrading fungi isolated from petroleum-contaminated soil. However, information of the transmembrane transport of petroleum hydrocarbon into yeast cells is limited. The present study was designed to explore the transmembrane transport mechanisms of the typical petroleum hydrocarbon n-hexadecane in Candida tropicalis cells with petroleum hydrocarbon biodegradation potential. Yeast cells were treated with n-hexadecane in different scenarios, and the percentage of intracellular n-hexadecane and transport dynamics were investigated accordingly. The intracellular concentration of n-hexadecane increased within 15 min, and transportation was inhibited by NaN3, an ATPase inhibitor. The uptake kinetics of n-hexadecane were well fitted by the Michaelis-Menten model, and Kt values ranged from 152.49 to 194.93 mg/L. All these findings indicated that n-hexadecane might cross the yeast cells in an energy-dependent manner and exhibit an affinity with the cell transport system. Moreover, the differentially expressed membrane proteins induced by n-hexadecane were identified and quantified by tandem mass tag labeling coupled with liquid chromatography tandem mass spectrometry analysis. The proteome analysis results demonstrated that energy production and conversion accounted for a large proportion of the functional classifications of the differentially expressed proteins, providing further evidence that sufficient energy supply is essential for transmembrane transport. Protein functional analysis also suggested that differentially expressed proteins associated with transmembrane transport processes are clearly enriched in endocytosis and phagosome pathways (p < 0.05), and the analysis supported the notion that the underlying transmembrane transport mechanism might be associated with endocytosis and phagosome pathways, revealing a new mechanism of n-hexadecane internalization by Candida tropicalis.

Prediction of harmful algal blooms in large water bodies using the combined EFDC and LSTM models.

Harmful algal blooms (HABs) is a worldwide water environmental problem. HABs usually happens in short time and is difficult to be controlled. Early warning of HABs using data-driven models is prospective in making time for taking precaution against HABs. High-frequency water quality monitoring data are necessary to improve the reliability of the model, but it is expensive. This research used environmental fluid dynamics code (EFDC) to extend one-point data obtained by only one instrument to the whole 249 ha water area instead of multi-instruments monitoring, followed by Long short-term memory (LSTM) to predict the HABs in the whole water body. Correlation analysis and principal component analysis were used to reduce the data dimension and improve model accuracy. Finally, the LSTM model was calibrated to predict chlorophyll-a (Chl-a) for the next 1 to 3 time steps. The Nash-Sutcliffe efficiency coefficient (NSE) and mean absolute percentage error (MAPE) of EFDC-LSTM were 0.797-0.991 and 2.74-13.16%, respectively, suggesting the promising utilization of this model in early warning systems for HABs. EFDC-LSTM achieves high-precision HABs forecasting in a cost-effective manner, providing a reliable way to detect HABs in advance.

Interannual variation in riparian vegetation cover and its relationship with river flow under a high level of human intervention: an example from the Yongding River Basin.

Riparian vegetation cover is significantly affected by a river's hydrological conditions. Especially in arid and semiarid areas, low flow will degrade riparian vegetation, and recent, intensive human activities in the Yongding River Basin have caused a sharp decrease in river flow. We analyzed interannual change in riparian vegetation, river flow effects, and land use on vegetation coverage using the 40 years (1977-2016) of remote sensing images and river flow, combined with 38 years (1980-2018) of land use data. The normalized difference vegetation index (NDVI) was used to determine vegetation cover in five different categories: extremely low, low, medium, high, and extremely high based on the pixel dichotomy model. The weighted average was calculated to obtain vegetation cover trends. We show that riparian vegetation cover from four rivers increased. Compared with 1977, in 2016, combined high and extremely high vegetation covers at the Dongyang, Yang, Sanggan, and Yongding Rivers increased by 20.3%, 26.7%, 50.0%, and 39.2%, respectively. High (R = -0.976, P < 0.01) and extremely high (R = -0.762, P < 0.05) vegetation covers are negatively correlated with flow in the Yongding River. The high vegetation cover of the Sanggan River riparian zone is negatively correlated with river flow (R = -0.683, P < 0.05). In the Dongyang and Sanggan Rivers, land use analysis in the riparian zone showed that change in cultivated land, grassland, and forest were significantly correlated with high and extremely high vegetation cover. The abundant cultivated land and restoration activities are likely responsible for the increase of riparian vegetation cover as river flows decline.

Thermostable arginase from Sulfobacillus acidophilus with neutral pH optimum applied for high-efficiency L-ornithine production.

This study aims to use neutral pH optimum arginase as the catalyst for high-efficiency L-ornithine production. Sulfobacillus acidophilus arginase was firstly cloned and overexpressed in Escherichia coli. The purified enzyme was obtained, and the molecular mass determination showed that this arginase was a hexamer. S. acidophilus arginase possessed similarities with the other arginases such as the conserved sequences, purification behavior, and the necessity for Mn2+ as a cofactor. The maximum enzyme activity was obtained at pH 7.5 and 70 °C. Thermostability and pH stability analysis showed that the arginase was stable at 30-60 °C and pH 7.0-8.5, respectively. The kinetic parameters suggested that S. acidophilus arginase could efficiently hydrolyze L-arginine. Bioconversion with this neutral pH optimum arginase had the advantages of avoiding producing by-product, high molar yield, and high-level production of L-ornithine. When the bioconversion was performed with a fed-batch strategy and a coupled-enzyme system involving S. acidophilus arginase and Jack bean urease, the final production of 2.87 mol/L was obtained with only 1.72 mmol/L L-arginine residue, and the molar yield was 99.9%. The highest production record suggests that S. acidophilus arginase has a great prospect in industrial L-ornithine production.

Next-Generation Sequencing of Plasma Cell-Free DNA for Treatment Monitoring in Advanced Head and Neck Cancer Patients.

BACKGROUND: Liquid biopsy, especially circulating tumor DNA (ctDNA), has been reported to provide information on tumor genetic features and possible disseminated disease in many kinds of solid tumors. In this pilot study, we investigated the utilization of ctDNA for monitoring treatment response and progression of the disease in patients with head and neck cancers (HNC) by next-generation sequencing (NGS). METHODS: We sequenced ctDNA from 24 plasma samples collected at different time points from 19 HNC patients undergoing surgery or chemotherapy using a targeted gene panel composed of 61 actionable genes recurrently mutated in human malignancies in Tongren Hospital from November 2016 to February 2018. Also, the presence or absence of the residual ctDNA after chemotherapy in 9 patients was associated with the treatment efficacy evaluated by computed tomography (CT). RESULTS: We found that TP53 (2/6) and PIK3CA (2/6) are the most commonly recurring mutated genes. Out of 7 patients with matched tissue and pre-treatment blood samples, we confirmed concordance of ctDNA mutation in 5 patients. In 4 post-surgery patients with undetectable ctDNA mutation, ctDNA did not reoccur during the follow-up period of over 20 months. CONCLUSIONS: These results suggested that NGS detection of ctDNA may contribute to minimal residual disease (MRD) detection and chemotherapy efficacy prediction in HNC.

Degradation of fluorescent dye-Solvent Green 7 (HPTS) in wastewater by advanced oxidation process.

Solvent Green 7 (HPTS) is a widely used fluorescent dye. As a kind of polycyclic aromatic hydrocarbon (PAHs) derivative, HPTS would cause pollution when it is discharged into the environment. This study adopted advanced oxidation processes (UV/H2O2) to degrade the HPTS in aqueous solution and investigated the effects of various factors on the degradation. The results showed that: the initial concentration and the fluorescence characteristics of HPTS reduced the degradation efficiency. When the oxidant concentration of H2O2 was 3 mg/L, the degradation efficiency and cost of HPTS (20 mg/L) were the most appropriate; when there were various inorganic anions in the solution, the degradations were not affected, but when the solution was strong acid and there existed a lot of chloride ions, the degradation of HPTS was inhibited. The degradation pathways indicated HPTS degraded into naphthalene derivatives, benzene derivatives through oxidation and decarboxylation reactions, finally into water and carbon dioxide. Further research for substances similar to HPTS structure will make progress in understanding the degradation process of PAHs.

Anterior cruciate ligament remnant tissue harvested within 3-months after injury predicts higher healing potential.

BACKGROUND: No study has examined the possible factors associated with different characteristics of stem-like cells derived from anterior cruciate ligament (ACL) remnants. And the purpose of the study is to elucidate whether demographic factors are associated with healing potential of stem-like cells derived from the ACL remnants tissue. METHODS: Thirty-six ACL remnants were harvested from patients who received primary arthroscopic ACL reconstruction. Interval from injury to surgery, age, sex, and combined meniscal or chondral injuries were analyzed. Cells were isolated from remnant tissues and their healing potential was evaluated by: 1) characterization of surface markers (CD34, CD44, CD45, CD146, CD29, and Stro-1), 2) cell expansion, 3) osteogenic differentiation, and 4) endothelial differentiation. Finally, using multivariable logistic regression to evaluate the relation between demographic factors and healing potential parameters. Adjusted odds ratios (OR) were calculated, and the significant difference was set at p < 0.05. RESULTS: ACL remnant tissue harvested less than 90 days after injury predicted higher fractions of stem-like cells [CD34+ (OR = 6.043, p = 0.025), CD44 + (OR = 8.440, p = 0.011), CD45+ (OR = 16.144, p = 0.015), and CD146+ (OR = 9.246, p = 0.015)] and higher expansion potential (passage 3: OR = 9.755, p = 0.034; passage 10: OR = 33.245, p = 0.003). Regarding osteogenic differentiation, higher gene expression of Osteocalcin (OR = 22.579, p = 0.009), Alkaline phosphatase (OR = 6.527, p = 0.022), and Runt-related transcription factor 2 (OR = 5.247, p = 0.047) can also be predicted. Younger age predicted higher CD34+ levels (20 ≤ age < 30 years, OR = 2.020, p = 0.027) and higher expansion potential at passage 10 (10 ≤ age < 20 years, OR = 25.141, p = 0.026). There was no significant relation found between meniscal or chondral injuries and ACL healing potential. CONCLUSION: Our results indicated that the ACL remnant tissue harvested within 3-months after injury yields higher healing potential, suggesting early surgical intervention may achieve better clinical results.

Feeding strategies for the enhanced production of α-arbutin in the fed-batch fermentation of Xanthomonas maltophilia BT-112.

To develop a cost-effective method for the enhanced production of α-arbutin using Xanthomonas maltophilia BT-112 as a biocatalyst, different fed-batch strategies such as constant feed rate fed-batch, constant hydroquinone (HQ) concentration fed-batch, exponential fed-batch and DO-control pulse fed-batch (DPFB) on α-arbutin production were investigated. The research results indicated that DPFB was an effective method for α-arbutin production. When fermentation with DO-control pulse feeding strategy to feed HQ and yeast extract was applied, the maximum concentrations of α-arbutin and cell dry weight were 61.7 and 4.21 g/L, respectively. The α-arbutin production was 394% higher than that of the control (batch culture) and the molar conversion yield of α-arbutin reached 94.5% based on the amount of HQ supplied (240 mM). Therefore, the results in this work provide an efficient and easily controlled method for industrial-scale production of α-arbutin.

Polymyxins: recent advances and challenges.

Antibiotic resistance is a pressing global health challenge, and polymyxins have emerged as the last line of defense against multidrug-resistant Gram-negative (MDR-GRN) bacterial infections. Despite the longstanding utility of colistin, the complexities surrounding polymyxins in terms of resistance mechanisms and pharmacological properties warrant critical attention. This review consolidates current literature, focusing on polymyxins antibacterial mechanisms, resistance pathways, and innovative strategies to mitigate resistance. We are also investigating the pharmacokinetics of polymyxins to elucidate factors that influence their in vivo behavior. A comprehensive understanding of these aspects is pivotal for developing next-generation antimicrobials and optimizing therapeutic regimens. We underscore the urgent need for advancing research on polymyxins to ensure their continued efficacy against formidable bacterial challenges.

Can restoring water and sediment fluxes across a mega-dam cascade alleviate a sinking river delta?

Hydropower, although an attractive renewable energy source, can alter the flux of water, sediments, and biota, producing detrimental impacts in downstream regions. The Mekong River illustrates the impacts of large dams and the limitations of conventional dam regulating strategies. Even under the most optimistic sluicing scenario, sediment load at the Mekong Delta could only recover to 62.3 ± 8.2 million tonnes (1 million tonnes = 109 kilograms), short of the (100 to 160)-million tonne historical level. Furthermore, unless retrofit to reroute sediments, the dams are doomed to continue trapping sediment for at least 170 years and thus starve downstream reaches of sediment, contributing to the impending disappearance of the Mekong Delta. Therefore, we explicitly challenge the widespread use of large dead storages-the portion of the reservoirs that cannot be emptied-in dam designs. Smaller dead storages can ease sediment starvation in downstream regions, thereby buffering against sinking deltas or relative sea level rises.