Both Resilience and Adhesivity Define Solid Electrolyte Interphases for a High Performance Anode.

Solid electrolyte interphases (SEIs) are sought to protect high-capacity anodes, which suffer from severe volume changes and fast degradations. The previously proposed effective SEIs were of high strength yet abhesive, inducing a yolk-shell structure to decouple the rigid SEI from the anode for accommodating the volume change. Ambivalently, the interfacial void-evolved electro-chemo-mechanical vulnerabilities become inherent defects. Here, we establish a new rationale for SEIs that resilience and adhesivity are both requirements and pioneer a design of a resilient yet adhesive SEI (re-ad-SEI), integrated into a conjugated surface bilayer structure. The re-ad-SEI and its protected particles exhibit excellent stability almost free from the thickening of SEI and the particle pulverization during cycling. More promisingly, the dynamically bonded intact SEI-anode interfaces enable a high-efficiency ion transport and provide a unique mechanical confinement effect for structural integrity of anodes. The high Coulombic efficiency (>99.8%), excellent cycling stability (500 cycles), and superior rate performance have been demonstrated in microsized Si-based anodes.

Weak-Interaction Environment in a Composite Electrolyte Enabling Ultralong-Cycling High-Voltage Solid-State Lithium Batteries.

Poly(vinylidene fluoride) (PVDF)-based solid electrolytes with a Li salt-polymer-little residual solvent configuration are promising candidates for solid-state batteries. Herein, we clarify the microstructure of PVDF-based composite electrolyte at the atomic level and demonstrate that the Li+-interaction environment determines both interfacial stability and ion-transport capability. The polymer works as a "solid diluent" and the filler realizes a uniform solvent distribution. We propose a universal strategy of constructing a weak-interaction environment by replacing the conventional N,N-dimethylformamide (DMF) solvent with the designed 2,2,2-trifluoroacetamide (TFA). The lower Li+ binding energy of TFA forms abundant aggregates to generate inorganic-rich interphases for interfacial compatibility. The weaker interactions of TFA with PVDF and filler achieve high ionic conductivity (7.0 × 10-4 S cm-1) of the electrolyte. The solid-state Li||LiNi0.8Co0.1Mn0.1O2 cells stably cycle 4900 and 3000 times with cutoff voltages of 4.3 and 4.5 V, respectively, as well as deliver superior stability at -20 to 45 °C and a high energy density of 300 Wh kg-1 in pouch cells.

Consummating ion desolvation in hard carbon anodes for reversible sodium storage.

Hard carbons are emerging as the most viable anodes to support the commercialization of sodium-ion (Na-ion) batteries due to their competitive performance. However, the hard carbon anode suffers from low initial Coulombic efficiency (ICE), and the ambiguous Na-ion (Na+) storage mechanism and interfacial chemistry fail to give a reasonable interpretation. Here, we have identified the time-dependent ion pre-desolvation on the nanopore of hard carbons, which significantly affects the Na+ storage efficiency by altering the solvation structure of electrolytes. Consummating the pre-desolvation by extending the aging time, generates a highly aggregated electrolyte configuration inside the nanopore, resulting in negligible reductive decomposition of electrolytes. When applying the above insights, the hard carbon anodes achieve a high average ICE of 98.21% in the absence of any Na supplementation techniques. Therefore, the negative-to-positive capacity ratio can be reduced to 1.02 for full cells, which enables an improved energy density. The insight into hard carbons and related interphases may be extended to other battery systems and support the continued development of battery technology.

Changes in physiology, antioxidant system, and gene expression in Microcystis aeruginosa under fenoxaprop-p-ethyl stress.

Fenoxaprop-p-ethyl (FE) is one of the typical aryloxyphenoxypropionate herbicides. FE has been widely applied in agriculture in recent years. Human health and aquatic ecosystems are threatened by the cyanobacteria blooms caused by Microcystis aeruginosa, which is one of the most common cyanobacteria responsible for freshwater blooming. Few studies have been reported on the physiological effects of FE on M. aeruginosa. This study analyzed the growth curves, the contents of chlorophyll a and protein, the oxidative stress, and the microcystin-LR (MC-LR) levels of M. aeruginosa exposed to various FE concentrations (i.e., 0, 0.5, 1, 2, and 5 mg/L). FE was observed to stimulate the cell density, chlorophyll a content, and protein content of M. aeruginosa at 0.5- and 1-mg/L FE concentrations but inhibit them at 2 and 5 mg/L FE concentrations. The superoxide dismutase and catalase activities were enhanced and the malondialdehyde concentration was increased by FE. The intracellular (intra-) and extracellular (extra-) MC-LR contents were also affected by FE. The expression levels of photosynthesis-related genes psbD1, psaB, and rbcL varied in response to FE exposure. Moreover, the expressions of microcystin synthase-related genes mcyA and mcyD and microcystin transportation-related gene mcyH were significantly inhibited by the treatment with 2 and 5 mg/L FE concentrations. These results might be helpful in evaluating the ecotoxicity of FE and guiding the rational application of herbicides in modern agriculture.

Enhanced SSD framework for detecting defects in cigarette appearance using variational Bayesian inference under limited sample conditions.

In high-speed cigarette manufacturing industries, occasional minor cosmetic cigarette defects and a scarcity of samples significantly hinder the rapid and accurate detection of defects. To tackle this challenge, we propose an enhanced single-shot multibox detector (SSD) model that uses variational Bayesian inference for improved detection of tiny defects given sporadic occurrences and limited samples. The enhanced SSD model incorporates a bounded intersection over union (BIoU) loss function to reduce sensitivity to minor deviations and uses exponential linear unit (ELU) and leaky rectified linear unit (ReLU) activation functions to mitigate vanishing gradients and neuron death in deep neural networks. Empirical results show that the enhanced SSD300 and SSD512 models increase the model's detection accuracy mean average precision (mAP) by up to 1.2% for small defects. Ablation studies further reveal that the model's mAP increases by 1.5%, which reduces the computational requirements by 5.92 GFLOPs. The model also shows improved inference in scenarios with limited samples, thus highlighting its effectiveness and applicability in high-speed, precision-oriented cigarette manufacturing industries.

SM22α deficiency: promoting vascular fibrosis via SRF-SMAD3-mediated activation of Col1a2 transcription following arterial injury.

Vascular fibrosis, characterized by increased Type I collagen expression, significantly contributes to vascular remodeling. Our previous studies show that disrupting the expression of SM22α (aka SM22, Tagln) induces extensive vascular remodeling following arterial injury, involving oxidative stress, inflammation, and chondrogenesis within the vessel wall. This study aims to investigate the molecular mechanisms underlying the transcription of Col1a2, a key fibrotic extracellular matrix marker. We observed upregulation of COL1A2 in the arterial wall of Sm22-/- mice following carotid injury. Bioinformatics and molecular analyses reveal that Col1a2 transcription depends on a CArG box in the promoter, activated synergistically by SRF and SMAD3. Notably, we detected enhanced nuclear translocation of both SRF and SMAD3 in the smooth muscle cells of the injured carotid artery in Sm22-/- mice. These findings demonstrate that SM22 deficiency regulates vascular fibrosis through the interaction of SRF and the SMAD3-mediated canonical TGF-ß1 signal pathway, suggesting SM22α as a potential therapeutic target for preventing vascular fibrosis.

Prognostic impact of age in advanced non-small cell lung cancer patients undergoing first-line checkpoint inhibitor immunotherapy and chemotherapy treatment.

BACKGROUND: Research on the association between age and clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy combined with chemotherapy as first-line setting is limited. The aim of study is to determine the influence of age on the progress-free survival (PFS) and overall survival (OS) in those patients after adjusting for potential confounders. METHODS: A total of 207 advanced NSCLC patients treated with immunotherapy combined with chemotherapy in the first-line treatment in Guangxi Medical University Cancer Hospital from March 10, 2019, to December 31, 2022, was retrospectively analyzed. χ2 (categorical variables) was used to analyze the differences among the different age groups. Cox regression and Kaplan-Meier analyses were used to assess the association between age and clinical outcomes. P values < 0.05 (two-sided) were considered statistically significant. RESULTS: The mean age of the cohort was 58.8 ± 10.3 years. The percentages of patients < 65, 65-69, 70-74, and ≥ 75 years were 66.7 %, 19.3 %, 9.2 % and 4.8 %, respectively. Compared to the aged < 65 years group, the HR for the risk of disease progression for each group are 0.67 (95 %CI = 0.40-1.12, P = 0.125), 0.66 (95 %CI = 0.31, 1.43, P = 0.298), and 2.27 (95 %CI = 0.80, 6.45, P = 0.124), respectively, with no significant differences in the results. And the HR for risk of death for the 65-69 years and 70-74 years groups was 1.16 (95 %CI = 0.64-2.08, P = 0.628) and 0.93 (95 %CI = 0.39-2.23, P = 0.879), respectively. The difference has no statistical significance. Whereas in patients aged ≥ 75, there is an increased risk of death after adjusted confounders with HR = 4.83 (95 %CI = 2.06-11.35). The difference was statistically significant (P < 0.001). Trend test indicates that with advancing age, the patient's risk of death increases (HR = 1.33, 95 % CI = 1.02-1.75, P = 0.034). CONCLUSION: Age may not be the primary factor influencing the efficacy of immunotherapy combined with chemotherapy, but particular attention should be given to the elderly population.

Ubiquitylation-independent cotranslational degradation of dihydrofolate reductase and ubiquitin.

Nascent proteins are degraded during or immediately after synthesis, a process called cotranslational protein degradation (CTPD). Although CTPD was observed decades ago, it has never been fully explored mechanistically and functionally. We show here that dihydrofolate reductase (DHFR) and ubiquitin (Ub), two stable proteins widely used in protein degradation studies, are actually subject to CTPD. Unlike canonical posttranslational protein degradation, CTPD of DHFR and Ub does not require prior ubiquitylation. Our data also suggest that protein expression level and N-terminal folding pattern may be two critical determinants for CTPD. Thus, this study reveals that CTPD plays a role in regulating the homeostasis of long-lived proteins and provides insights into the mechanism of CTPD.

Fluorinating All Interfaces Enables Super-Stable Solid-State Lithium Batteries by In Situ Conversion of Detrimental Surface Li2CO3.

Li-stuffed battery materials intrinsically have surface impurities, typically Li2CO3, which introduce severe kinetic barriers and electrochemical decay for a cycling battery. For energy-dense solid-state lithium batteries (SSLBs), mitigating detrimental Li2CO3 from both cathode and electrolyte materials is required, while the direct removal approaches hardly avoid Li2CO3 regeneration. Here, a decarbonization-fluorination strategy to construct ultrastable LiF-rich interphases throughout the SSLBs by in situ reacting Li2CO3 with LiPF6 at 60 °C is reported. The fluorination of all interfaces effectively suppresses parasitic reactions while substantially reducing the interface resistance, producing a dendrite-free Li anode with an impressive cycling stability of up to 7000 h. Particularly, transition metal dissolution associated with gas evolution in the cathodes is remarkably reduced, leading to notable improvements in battery rate capability and cyclability at a high voltage of 4.5 V. This all-in-one approach propels the development of SSLBs by overcoming the limitations associated with surface impurities and interfacial challenges.

Insights into elastic fiber fragmentation: Mechanisms and treatment of aortic aneurysm in Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in fibrillin 1 (FBN1) gene. These mutations result in defects in the skeletal, ocular, and cardiovascular systems. Aortic aneurysm is the leading cause of premature mortality in untreated MFS patients. Elastic fiber fragmentation in the aortic vessel wall is a hallmark of MFS-associated aortic aneurysms. FBN1 mutations result in FBN1 fragments that also contribute to elastic fiber fragmentation. Although recent research has advanced our understanding of MFS, the contribution of elastic fiber fragmentation to the pathogenesis of aneurysm formation remains poorly understood. This review provides a comprehensive overview of the molecular mechanisms of elastic fiber fragmentation and its role in the pathogenesis of aortic aneurysm progression. Increased comprehension of elastic fragmentation has significant clinical implications for developing targeted interventions to block aneurysm progression, which would benefit not only individuals with Marfan syndrome but also other patients with aneurysms. Moreover, this review highlights an overlooked connection between inhibiting aneurysm and the restoration of elastic fibers in the vessel wall with various aneurysm inhibitors, including drugs and chemicals. Investigating the underlying molecular mechanisms could uncover innovative therapeutic strategies to inhibit elastin fragmentation and prevent the progression of aneurysms.

OEA loaded liposomes with the neuroprotective effect for stroke therapy.

With high mortality, stroke has become a serious threat to human health. Nevertheless, the strategy for stroke therapy is quite limited in the clinic till now. In this research, we prepared a novel neuroprotective nanoformulation (OEA Liposomes) via encapsulating endogenous N-oleoylethanolamine (OEA) in liposomes for intravenous administration. The formulation largely increased the solubility and bioavailability of OEA. Then the following systematic experiments stated the excellent neuroprotective effect of OEA Liposomes in vivo. The survival rate of the nanodrug group was largely increased to 75%, while that of the Middle Cerebral Artery Occlusion (MCAO) group was only 41.7%. And the severe neurological functional deficit of the MCAO rats was also significantly improved. What's more, the OEA Liposomes could inhibit the apoptosis of neurons and the inflammation of reperfusion to a very slight level, indicating their outstanding neuroprotective effect. These results indicated that the OEA Liposomes have a great potential for clinic anti-stroke application.

Step-by-step desolvation enables high-rate and ultra-stable sodium storage in hard carbon anodes.

Hard carbon is regarded as the most promising anode material for sodium-ion (Na-ion) batteries, owing to its advantages of high abundance, low cost, and low operating potential. However, the rate capability and cycle life span of hard carbon anodes are far from satisfactory, severely hindering its industrial applications. Here, we demonstrate that the desolvation process defines the Na-ion diffusion kinetics and the formation of a solid electrolyte interface (SEI). The 3A zeolite molecular sieve film on the hard carbon is proposed to develop a step-by-step desolvation pathway that effectively reduces the high activation energy of the direct desolvation process. Moreover, step-by-step desolvation yields a thin and inorganic-dominated SEI with a lower activation energy for Na+ transport. As a result, it contributes to greatly improved power density and cycling stability for both ester and ether electrolytes. When the above insights are applied, the hard carbon anode achieves the longest life span and minimum capacity fading rate at all evaluated current densities. Moreover, with the increase in current densities, an improved plateau capacity ratio is observed. This step-by-step desolvation strategy comprehensively enhances various properties of hard carbon anodes, which provides the possibility of building practical Na-ion batteries with high power density, high energy density, and durability.

Hierarchical Context-Based Emotion Recognition With Scene Graphs.

For a better intention inference, we often try to figure out the emotional states of other people in social communications. Many studies on affective computing have been carried out to infer emotions through perceiving human states, i.e., facial expression and body posture. Such methods are skillful in a controlled environment. However, it often leads to misestimation due to the deficiency of effective inputs in unconstrained circumstances, that is, where context-aware emotion recognition appeared. We take inspiration from the advanced reasoning pattern of humans in perceived emotion recognition and propose the hierarchical context-based emotion recognition method with scene graphs. We propose to extract three contexts from the image, i.e., the entity context, the global context, and the scene context. The scene context contains abstract information about entity labels and their relationships. It is similar to the information processing of the human visual sensing mechanism. After that, these contexts are further fused to perform emotion recognition. We carried out a bunch of experiments on the widely used context-aware emotion datasets, i.e., CAER-S, EMOTIC, and BOdy Language Dataset (BoLD). We demonstrate that the hierarchical contexts can benefit emotion recognition by improving the accuracy of the SOTA score from 84.82% to 90.83% on CAER-S. The ablation experiments show that hierarchical contexts provide complementary information. Our method improves the F1 score of the SOTA result from 29.33% to 30.24% (C-F1) on EMOTIC. We also build the image-based emotion recognition task with BoLD-Img from BoLD and obtain a better emotion recognition score (ERS) score of 0.2153.

Dual Drug Loaded, pH-Sensitive Metal-Organic Particles for Synergistic Cancer Therapy.

The strategy for dual drug-loaded nanomedicine with targeting properties was always complex. Herein, a novel strategy for the preparation of metal-organic particle-based nanomedicine has been developed, and combretastatin A4 (CA4) and mitoxantrone (MIT) loaded MOPs (CMMOPs) have been obtained. In this system, using merely Cu(II) as a bridge to connect and coordinate with the dual drugs has resulted in the CMMOPs possessing a fairly high drug load of almost 90%. Moreover, the coordination between Cu(II) and the drugs was stable at physiological pH but easily cleavable in the tumor acidic microenvironment, which would provide a good targeting property for CMMOPs. The in vivo experiments indicated that CMMOPs possessed a significantly enhanced antitumor efficiency with negligible side effects. The results suggest that CMMOPs could be a potential anticancer formulation for tumor-targeted drug delivery.

Integrating SEI into Layered Conductive Polymer Coatings for Ultrastable Silicon Anodes.

Tackling the huge volume expansion of silicon (Si) anode desires a stable solid electrolyte interphase (SEI) to prohibit the interfacial side reactions. Here, a layered conductive polyaniline (LCP) coating is built on Si nanoparticles to achieve high areal capacity and long lifespan. The conformal LCP coating stores electrolyte in interlamination spaces and directs an in situ formation of LCP-integrated hybrid SEI skin with uniform distribution of organic and inorganic components, enhancing the flexibility of the SEI to buffer the volume changes and maintaining homogeneous ion transport during cycling. As a result, the Si anode shows a remarkable cycling stability under high areal capacity (≈3 mAh cm-2 ) after 150 cycles and good rate performance of 942 mAh g-1 at 5 A g-1 . This work demonstrates the great potential of regulating the SEI properties by a layered polymer-directing SEI formation for the mechanical and electrochemical stabilization of Si anodes.

Electrolyte Sieving Chemistry in Suppressing Gas Evolution of Sodium-Metal Batteries.

The sodium (Na)-metal batteries hold great promise as a sustainable technology owing to the high element abundance and low cost. However, the generally used carbonate electrolytes remain highly reactive towards Na metal, leading to flammable gas evolution. Here, we propose an electrolyte sieving strategy to separate anion-mediated ion-pairs from dilute electrolytes by introducing a 3A zeolite molecular sieve film. The anion-mediated ion-pair firstly weakens the electron-withdrawing property of the cation, which effectively suppresses the gassing. In addition, the sieved electrolyte promotes the formation of robust inorganic-dominated solid electrolyte interphases. Therefore, it contributes to stable Na plating/stripping in Na|Al half cells with Coulombic efficiency maintaining at 98.5 % and a long service life of 800 cycles in full cells. Moreover, the electrode stability is well preserved even under harsh conditions of high temperature and ester-based electrolytes with higher reactivity.

Formamidinium Perovskitizers and Aromatic Spacers Synergistically Building Bilayer Dion-Jacobson Perovskite Photoelectric Bulk Crystals.

Two-dimensional (2D) multilayer Dion-Jacobson (DJ) phase organic inorganic hybrid perovskites (OIHPs) have attracted extensive research attention due to the high stability and excellent charge-transport properties in the optoelectronic field. However, the synthesis of 2D multilayer DJ OIHPs is still very challenging. Until now, only few multilayer DJ perovskites have been reported and most of them are based on volatile methylamine (MA) cations. Compared with MA-based OIHPs, the OIHPs constructed with formamidinium (FA) as perovskitizers not only improve the stability but also extend the light absorption range. Meanwhile, the introducing aromatic diamines as spacers could promote the electron-hole separation in such DJ hybrids. However, the DJ OIHP bulk single crystal constructed by using the advantages of FA as perovskitizers and aromatic diamines as spacers is still blank. Herein, we integrate the properties of organic cations and inorganic skeletons at a molecular-scale to construct a broadband-responsive 2D bilayer DJ perovskite (3AMPY)(FA)Pb2I7 [3AMPY = 3-(aminomethyl)pyridinium], which shows a fascinating detectivity from X-ray (5.23 × 104 µC Gyair-1 cm-2 at 200 V bias) and visible light (6 × 1012 jones at 637 nm) to the near-infrared region (2.6 × 109 jones at 780 nm). After an in-depth analysis of structure and optical properties, we found that the distortion degree of Pb-I-Pb bond angles between adjacent PbI6 octahedra plays a crucial role on optical properties; on the other hand, the interlayer spacer cations (3AMPY) and intralayer perovskitizers (FA) mutual participate in the contribution of the conduction band, making (3AMPY)(FA)Pb2I7 have a narrow optical band gap of 1.54 eV. Such a 2D perovskite material with a wide spectra response will be the preferred choice for photodetection under complex conditions.

Hybrid Printing Method of Polymer and Continuous Fiber-Reinforced Thermoplastic Composites (CFRTPCs) for Pipes through Double-Nozzle Five-Axis Printer.

The most widely used 3D process, fused deposition modeling (FDM), has insufficient interlayer adhesion due to its layer-by-layer forming method. A support material is also essential for the hollow parts and cantilevers. Moreover, the polymer materials used have limited mechanical properties. These issues have restricted the application of FDM in high-performance fields. Continuous fiber-reinforced thermoplastic composites (CFRTPCs) have high mechanical properties and have recently become the focus of research in the field of 3D printing. This paper, using pipe parts as an example, proposes a hybrid of pure polymer (pure PLA used) and CFRTPC (flax fiber pre-impregnated filament) material to develop a printing method based on the outstanding mechanical properties of CFRTPC material. After studying the printing path planning algorithm, the CFRTPC filament is laid along the axial and radial directions on the surface of the polymer base to improve the printed parts' properties. The method feasibility and algorithm accuracy are verified through the development of five-axis printing equipment with a double nozzle. Through the printed sample's tensile, compression and bending tests, the results show that the tensile, compressive and bending properties of PLA pipe can be significantly enhanced by laying CFRTPC filament along the axial and radial directions of the pipe. To summarize, the introduction of CFRTPCs greatly improved the mechanical properties of the printed parts, and the implementation of our method provides an effective way to solve the defects of the FDM process.

Mutual impacts and interactions of antibiotic resistance genes, microcystin synthetase genes, graphene oxide, and Microcystis aeruginosa in synthetic wastewater.

The physiological impacts and interactions of antibiotic resistance gene (ARG) abundance, microcystin synthetase gene expression, graphene oxide (GO), and Microcystis aeruginosa in synthetic wastewater were investigated. The results demonstrated that the absolute abundance of sul1, sul2, tetW, and tetM in synthetic wastewater dramatically increased to 365.2%, 427.1%, 375.2%, and 231.7%, respectively, when the GO concentration was 0.01 mg/L. Even more interesting is that the sum gene copy numbers of mcyA-J also increased to 243.2%. The appearance of GO made the significant correlation exist between ARGs abundance and mcyA-J expression. Furthermore, M. aeruginosa displayed better photosynthetic performance and more MCs production at 0.01 mg/L GO. There were 65 pairs of positive correlations between the intracellular differential metabolites of M. aeruginosa and the abundance of sul1, sul2, tetM, and tetW with various GO concentrations. The GO will impact the metabolites and metabolic pathway in M. aeruginosa. The metabolic changes impacted the ARGs, microcystin synthetase genes, and physiological characters in algal cells. Furthermore, there were complex correlations among sul1, sul2, tetM, tetW, mcyA-J, MCs, photosynthetic performance parameters, and ROS. The different concentration of GO will aggravate the hazards of M. aeruginosa by promoting the expression of mcyA-J, producing more MCs; simultaneously, it may cause the spread of ARGs.

The effect of carbon-based copper nanocomposites on Microcystis aeruginosa and the movability of antibiotic resistance genes in urban water.

The presence of Microcystis aeruginosa (M. aeruginosa) can affect the transference of antibiotic resistance genes (ARGs), and the presence of carbon-based copper nanocomposites (CCN) can affect the growth of M. aeruginosa. However, the effect of CCN on M. aeruginosa and ARGs is not fully understood. In this study, metagenomic sequencing was employed to analyze the movability of ARGs, their potential transfer, and possible hosts in photobioreactor treating urban water. The results uggested that 20 mg/L of CCN changed the composition and abundance of microorganisms in urban water, significantly promoted the flocculation of M aeruginosa, and decreased the composing proportion of Cyanophyta sp. and M aeruginosa. The results indicated that 20 mg/L of CCN significantly decreased the absolute abundance and ARGs proportions which mediated by plasmids (32.7 %). Furthermore, the lower co-occurrence probability of ARGs and mobile genetic elements (MGEs) suggested that 20 mg/L of CCN weakened the movability potential of ARGs mediated by MGEs such as plasmids. Among the 452 metagenome-assembled genomes (MAGs), 95 MAGs belonging to 41 bacterial categories were identified as possible ARG hosts. These results will provide insights into the control of harmful cyanobacteria and the management of ARGs in urban water.