A Functionally Asymmetric Janus Hygro-Photothermal Hybrid for Atmospheric Water Harvesting in Arid Regions.

Metal-organic frameworks (MOFs) are high-performance adsorbents for atmospheric water harvesting but have poor water-desorption ability, requiring excess energy input to release the trapped water. Addressing this issue, a Janus-structured adsorbent with functional asymmetry is presented. The material exhibits contrasting functionalities on either face - a hygroscopic face interfaced with a photothermal face. Hygroscopic aluminum fumarate MOF and photothermal CuxS layers are in-situ grown on opposite sides of a Cu/Al bimetallic substrate, resulting in a CuxS-Cu/Al-MOF Janus hygro-photothermal hybrid. The two faces serve as independent "factories" for photothermal conversion and water adsorption-desorption respectively, while the interfacing bimetallic layer serves as a "heat conveyor belt" between them. Due to the high porosity and hydrophilicity of the MOF, the hybrid exhibits a water-adsorption capacity of 0.161 g g-1 and a fast adsorption rate (saturation within 52 min) at 30% relative humidity. Thanks to the photothermal CuxS, the hybrid can reach 71.5 °C under 1 Sun in 20 min and desorb 97% adsorbed water in 40 min, exhibiting a high photothermal conversion efficiency of over 90%. CuxS-Cu/Al-MOF exhibits minimal fluctuations after 200 cycles, and its water-generation capacity is 3.21 times that of powdery MOF in 3 h in a self-designed prototype in one cycle.

The cytoplasmic tail of rhodopsin triggers rapid rod degeneration in kinesin-2 mutants.

Photoreceptor degeneration can lead to blindness and represents the most common form of neural degenerative disease worldwide. Although many genes involved in photoreceptor degeneration have been identified, the underlying mechanisms remain to be elucidated. Here we examined photoreceptor development in zebrafish kif3a and kif3b mutants, which affect two subunits of the kinesin-2 complex. In both mutants, rods degenerated quickly, whereas cones underwent a slow degeneration process. Notably, the photoreceptor defects were considerably more severe in kif3a mutants than in kif3b mutants. In the cone photoreceptors of kif3a mutants, opsin proteins accumulated in the apical region and formed abnormal membrane structures. In contrast, rhodopsins were enriched in the rod cell body membrane and represented the primary reason for rapid rod degeneration in these mutants. Moreover, removal of the cytoplasmic tail of rhodopsin to reduce its function, but not decreasing rhodopsin expression levels, prevented rod degeneration in both kif3a and kif3b mutants. Of note, overexpression of full-length rhodopsin or its cytoplasmic tail domain, but not of rhodopsin lacking the cytoplasmic tail, exacerbated rod degeneration in kif3a mutants, implying an important role of the cytoplasmic tail in rod degeneration. Finally, we showed that the cytoplasmic tail of rhodopsin might trigger rod degeneration through activating the downstream calcium signaling pathway, as drug treatment with inhibitors of intracellular calcium release prevented rod degeneration in kif3a mutants. Our results demonstrate a previously unknown function of the rhodopsin cytoplasmic domain during opsin-triggered photoreceptor degeneration and may open up new avenues for managing this disease.

The effect of citral loading and fatty acid distribution on the oleogels: Physicochemical properties and in vitro digestion.

Oleogels containing bioactive substances such as citral (CT) are used as functional food ingredients. However, little information is available on the influence of different oleogel network structure caused by CT addition and fatty acid distribution on its digestion behavior. Coconut oil, palm oil, high oleic peanut oil, safflower seed oil, and perilla seed oil were used in this study. The results showed that perilla seed oil-CT-based oleogels had the highest oil-holding capacity (99.03 ± 0.3), whereas CT addition higher than 10 wt% could lead to the morphology collapse of oleogels. Physical and thermodynamic analyses revealed that CT could reduce oleogel hardness and higher unsaturated fatty acid content is more likely to form oleogel with stable and tight crystalline network. Moreover, the dense structure of oleogels hinders the contact between oleogels and lipase, thus weakening triglyceride digestion. These findings provide valuable insights into the design of oleogels loading with CT.

Interface chemistry affected the digestion fate of ketogenic diet based on medium- and long-chain triglycerides.

Ketogenic diet, characterized by high fat and low carbohydrate content, is gradually becoming a new perspective in the human diet; however, the mechanism of digestion of ketogenic diet remains unknown. In this study, we explored the oil-water interface to elucidate the digestion of a ketogenic diet based on typical representative medium- and long-chain triglycerides. The free fatty acids (FFAs) release indicated that glycerol trioctanoate with a shorter carbon chain (FFA = 920.55 ± 10.17 µmol) was significantly more digestible than glycerol tripalmitate (851.36 ± 9.48 µmol) and glycerol tristearate (805.81 ± 10.03 µmol). Particle size analysis revealed that the length of the carbon chain increased the size of triglycerides, resulting in a decreased contact area with lipase. The interfacial phenomenon indicated that the longer the carbon chain of triglycerides, the greater the reduction in binding capacity with salt ions in the digestive solution. Fluorescence spectroscopy analysis showed that the length of the carbon chain induced the displacement of the lipase peak, suggesting that the carbon chain length could alter the structure of lipase. Molecular dynamics simulation showed that the longer the carbon chain of triglycerides, the easier it was to loosen the structure of lipase. Bond energy analysis showed that the carbon chain length of triglycerides was positively correlated with the bond energy strength of the ester bonding. In conclusion, this study emphasizes that the ketogenic diet should primarily consist of shorter carbon chain triglycerides because carbon chain length can alter the digestion of triglycerides. This provides a new perspective on the quest for more effective ketogenic diet, in line with the current view of healthy diet.

Cobalt-Ion Superhygroscopic Hydrogels Serve as Chip Heat Sinks Achieving a 5 °C Temperature Reduction via Evaporative Cooling.

In the rapidly advancing semiconductor sector, thermal management of chips remains a pivotal concern. Inherent heat generation during their operation can lead to a range of issues such as potential thermal runaway, diminished lifespan, and current leakage. To mitigate these challenges, the study introduces a superhygroscopic hydrogel embedded with metal ions. Capitalizing on intrinsic coordination chemistry, the metallic ions in the hydrogel form robust coordination structures with non-metallic nitrogen and oxygen through empty electron orbitals and lone electron pairs. This unique structure serves as an active site for water adsorption, beginning with a primary layer of chemisorbed water molecules and subsequently facilitating multi-layer physisorption via Van der Waals forces. Remarkably, the cobalt-integrated hydrogel demonstrates the capability to harvest over 1 and 5 g g-1 atmospheric water at 60% RH and 95% RH, respectively. Furthermore, the hydrogel efficiently releases the entirety of its absorbed water at a modest 40°C, enabling its recyclability. Owing to its significant water absorption capacity and minimal dehydration temperature, the hydrogel can reduce chip temperatures by 5°C during the dehydration process, offering a sustainable solution to thermal management in electronics.

Alkylated chitosan-attapulgite composite sponge for rapid hemostasis.

This study reported the development of a composite sponge (ACATS) based on alkylated chitosan (AC) and attapulgite (AT) for rapid hemostasis. The well-designed ACATS, with an optimal AC N-alkylation of 5.9 % and an optimal AC/AT mass ratio of 3:1, exhibited a hierarchical porous structure with a favorable biocompatibility. The ACATS can effectively and rapidly stop the uncontrolled bleeding in 235 ± 64 s with a total blood loss of 8.4 ± 4.0 g in comparison with those of Celox as a positive control (602 ± 101 s and 22.3 ± 2.4 g, respectively) using rabbit carotid artery injury model in vivo. ACATS could rapidly interact with blood and its components, including platelets (PLs), red blood cells (RBCs), and coagulation factors, resulting in these blood components rapidly accumulation and the following thrombus formation and coagulation factors activation.

SEResUTer: a deep learning approach for accurate ECG signal delineation and atrial fibrillation detection.

Objective.Accurate detection of electrocardiogram (ECG) waveforms is crucial for computer-aided diagnosis of cardiac abnormalities. This study introduces SEResUTer, an enhanced deep learning model designed for ECG delineation and atrial fibrillation (AF) detection.Approach. Built upon a U-Net architecture, SEResUTer incorporates ResNet modules and Transformer encoders to replace convolution blocks, resulting in improved optimization and encoding capabilities. A novel masking strategy is proposed to handle incomplete expert annotations. The model is trained on the QT database (QTDB) and evaluated on the Lobachevsky University Electrocardiography Database (LUDB) to assess its generalization performance. Additionally, the model's scope is extended to AF detection using the the China Physiological Signal Challenge 2021 (CPSC2021) and the China Physiological Signal Challenge 2018 (CPSC2018) datasets.Main results.The proposed model surpasses existing traditional and deep learning approaches in ECG waveform delineation on the QTDB. It achieves remarkable average F1 scores of 99.14%, 98.48%, and 98.46% for P wave, QRS wave, and T wave delineation, respectively. Moreover, the model demonstrates exceptional generalization ability on the LUDB, achieving average SE, positive prediction rate, and F1 scores of 99.05%, 94.59%, and 94.62%, respectively. By analyzing RR interval differences and the existence of P waves, our method achieves AF identification with 99.20% accuracy on the CPSC2021 test set and demonstrates strong generalization on CPSC2018 dataset.Significance.The proposed approach enables highly accurate ECG waveform delineation and AF detection, facilitating automated analysis of large-scale ECG recordings and improving the diagnosis of cardiac abnormalities.

Manganese regulation of COPII condensation controls circulating lipid homeostasis.

Precise control of circulating lipids is instrumental in health and disease. Bulk lipids, carried by specialized lipoproteins, are secreted into the circulation, initially via the coat protein complex II (COPII). How the universal COPII machinery accommodates the abundant yet unconventional lipoproteins remains unclear, let alone its therapeutic translation. Here we report that COPII uses manganese-tuning, self-constrained condensation to selectively drive lipoprotein delivery and set lipid homeostasis in vivo. Serendipitously, adenovirus hijacks the condensation-based transport mechanism, thus enabling the identification of cytosolic manganese as an unexpected control signal. Manganese directly binds the inner COPII coat and enhances its condensation, thereby shifting the assembly-versus-dynamics balance of the transport machinery. Manganese can be mobilized from mitochondria stores to signal COPII, and selectively controls lipoprotein secretion with a distinctive, bell-shaped function. Consequently, dietary titration of manganese enables tailored lipid management that counters pathological dyslipidaemia and atherosclerosis, implicating a condensation-targeting strategy with broad therapeutic potential for cardio-metabolic health.

In vitro and in vivo assay of the ER lipid scramblase TMEM41B.

Amphipathic phospholipids translocated by scramblases play a central role in facilitating lipid movement across the membrane bilayer, especially at the endoplasmic reticulum (ER) membranes. Here, we present a protocol for assessing the activity of the ER-localized lipid scramblase TMEM41B. We detail an in vitro fluorescent liposome-based phospholipid scrambling assay and in vivo metabolic labeling in living cells using alkyne-choline. The scramblase activity of other VTT (VMP1, TMEM41, and Tvp38) domain-containing proteins, such as TMEM41A and VMP1, can be assayed. For complete details on the use and execution of this protocol, please refer to Huang et al. (2021).

Classification of multi-lead ECG with deep residual convolutional neural networks.

Objective. Automatic electrocardiogram (ECG) interpretation based on deep learning methods is attracting increasing attention. In this study, we propose a novel method to accurately classify multi-lead ECGs using deep residual neural networks.Approach. ECG recordings from seven different open databases were provided by PhysioNet/Computing in Cardiology Challenge 2021. All the ECGs were pre-processed to obtain the same sampling rate. The label inconsistency among the databases was corrected by adding or removing specific labels. A label mask was created to filter out potentially incorrectly labelled data. Five models based on deep residual convolutional neural networks were optimized using an asymmetric loss function to classify multi-lead ECGs.Main results. The proposed method achieved an official challenge score of 0.54, 0.52, 0.50, 0.51, and 0.50 on twelve-lead, six-lead, four-lead, three-lead, and two-lead ECG test sets, respectively. These scores were ranked 5th, 3rd, 7th, 5th and 7th, respectively, in the challenge.Significance. The proposed method can correct the differential labeling tendency of databases from different sources and exhibits good generalization for classifying multi-lead ECGs in the hidden test set. The proposed models have the potential for clinical applications.

Hepatic inactivation of murine Surf4 results in marked reduction in plasma cholesterol.

PCSK9 negatively regulates low-density lipoprotein receptor (LDLR) abundance on the cell surface, leading to decreased hepatic clearance of LDL particles and increased levels of plasma cholesterol. We previously identified SURF4 as a cargo receptor that facilitates PCSK9 secretion in HEK293T cells (Emmer et al., 2018). Here, we generated hepatic SURF4-deficient mice (Surf4fl/fl Alb-Cre+) to investigate the physiologic role of SURF4 in vivo. Surf4fl/fl Alb-Cre+ mice exhibited normal viability, gross development, and fertility. Plasma PCSK9 levels were reduced by ~60% in Surf4fl/fl Alb-Cre+ mice, with a corresponding ~50% increase in steady state LDLR protein abundance in the liver, consistent with SURF4 functioning as a cargo receptor for PCSK9. Surprisingly, these mice exhibited a marked reduction in plasma cholesterol and triglyceride levels out of proportion to the partial increase in hepatic LDLR abundance. Detailed characterization of lipoprotein metabolism in these mice instead revealed a severe defect in hepatic lipoprotein secretion, consistent with prior reports of SURF4 also promoting the secretion of apolipoprotein B (APOB). Despite a small increase in liver mass and lipid content, histologic evaluation revealed no evidence of steatohepatitis or fibrosis in Surf4fl/fl Alb-Cre+ mice. Acute depletion of hepatic SURF4 by CRISPR/Cas9 or liver-targeted siRNA in adult mice confirms these findings. Together, these data support the physiologic significance of SURF4 in the hepatic secretion of PCSK9 and APOB-containing lipoproteins and its potential as a therapeutic target in atherosclerotic cardiovascular diseases.

Deficiency of WTAP in hepatocytes induces lipoatrophy and non-alcoholic steatohepatitis (NASH).

Ectopic lipid accumulation and inflammation are the essential signs of NASH. However, the molecular mechanisms of ectopic lipid accumulation and inflammation during NASH progression are not fully understood. Here we reported that hepatic Wilms' tumor 1-associating protein (WTAP) is a key integrative regulator of ectopic lipid accumulation and inflammation during NASH progression. Hepatic deletion of Wtap leads to NASH due to the increased lipolysis in white adipose tissue, enhanced hepatic free fatty acids uptake and induced inflammation, all of which are mediated by IGFBP1, CD36 and cytochemokines such as CCL2, respectively. WTAP binds to specific DNA motifs which are enriched in the promoters and suppresses gene expression (e.g., Igfbp1, Cd36 and Ccl2) with the involvement of HDAC1. In NASH, WTAP is tranlocated from nucleus to cytosol, which is related to CDK9-mediated phosphorylation. These data uncover a mechanism by which hepatic WTAP regulates ectopic lipid accumulation and inflammation during NASH progression.

Acute gene inactivation in the adult mouse liver using the CRISPR-Cas9 technology.

Genetic manipulation in mice allows the discovery of gene function and biological mechanisms in vivo. The widely used Cre/LoxP system usually takes months to years especially when starting with the production of floxed alleles of a new gene of interest (GOI). Here, we describe a protocol using the CRISPR-Cas9 system to acutely inactivate the GOI in adult mice. This protocol enables hepatocyte-specific gene editing within 4 weeks in adult mice and avoids compensatory effects of traditional gene inactivation initiated during various developmental stages. For complete details on the use and execution of this protocol, please refer to Wang et al. (2020).

TMEM41B acts as an ER scramblase required for lipoprotein biogenesis and lipid homeostasis.

How amphipathic phospholipids are shuttled between the membrane bilayer remains an essential but elusive process, particularly at the endoplasmic reticulum (ER). One prominent phospholipid shuttling process concerns the biogenesis of APOB-containing lipoproteins within the ER lumen, which may require bulk trans-bilayer movement of phospholipids from the cytoplasmic leaflet of the ER bilayer. Here, we show that TMEM41B, present in the lipoprotein export machinery, encodes a previously conceptualized ER lipid scramblase mediating trans-bilayer shuttling of bulk phospholipids. Loss of hepatic TMEM41B eliminates plasma lipids, due to complete absence of mature lipoproteins within the ER, but paradoxically also activates lipid production. Mechanistically, scramblase deficiency triggers unique ER morphological changes and unsuppressed activation of SREBPs, which potently promotes lipid synthesis despite stalled secretion. Together, this response induces full-blown nonalcoholic hepatosteatosis in the TMEM41B-deficient mice within weeks. Collectively, our data uncovered a fundamental mechanism safe-guarding ER function and integrity, dysfunction of which disrupts lipid homeostasis.

Receptor-Mediated ER Export of Lipoproteins Controls Lipid Homeostasis in Mice and Humans.

Efficient delivery of specific cargos in vivo poses a major challenge to the secretory pathway, which shuttles products encoded by ∼30% of the genome. Newly synthesized protein and lipid cargos embark on the secretory pathway via COPII-coated vesicles, assembled by the GTPase SAR1 on the endoplasmic reticulum (ER), but how lipid-carrying lipoproteins are distinguished from the general protein cargos in the ER and selectively secreted has not been clear. Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. While both genes are implicated in lipid regulation in humans, hepatic inactivation of either mouse Sar1b or Surf4 selectively depletes plasma lipids to near-zero and protects the mice from atherosclerosis. These findings show that the pairing between SURF4 and SAR1B synergistically operates a specialized, dosage-sensitive transport program for circulating lipids, while further suggesting a potential translation to treat atherosclerosis and related cardio-metabolic diseases.

Stereological study on the numerical plasticity of myelinated fibers and oligodendrocytes in the rat spinal cord with painful diabetic neuropathy.

Painful diabetic neuropathy may associate with nerve morphological plasticity in both peripheral and central nervous system. The aim of this study was to determine numerical changes of myelinated fibers in the spinothalamic tract region and oligodendrocytes in the spinal dorsal horn of rats with painful diabetic neuropathy and the effects of metformin on the above changes. Male Sprague-Dawley rats were randomly allocated into the control group (n = 7), the painful diabetic neuropathy group (n = 6) and the painful diabetic neuropathy treated with metformin group (the PDN + M group, n = 7), respectively. Twenty-eight days after medication, numbers of myelinated fibers in the spinothalamic tract and oligodendrocytes in the spinal dorsal horn were estimated by the optical disector (a stereological technique). Compared to the control group, number of myelinated fibers in the spinothalamic tract increased significantly in the painful diabetic neuropathy and PDN + M group, compared to the painful diabetic neuropathy group, number of myelinated fibers decreased in the PDN + M group (P < 0.05). As the oligodendrocyte in the spinal dorsal horn was considered, its number increased significantly in the painful diabetic neuropathy group compared to the control and the PDN + M group (P < 0.05), there was no significant difference between the control and the PDN + M group (P > 0.05). Our results indicate that painful diabetic neuropathy is associated with a serial of morphometric plasticity in the rat spinal cord including the numerical increase of the myelinated fibers in the spinothalamic tract and the oligodendrocytes in the spinal dorsal horn. The analgesic effect of metformin against painful diabetic neuropathy might be related to its adverse effects on the above morphometric plasticity.

Removal of Cr (â ¢) from aqueous solution by using bauxite residue (red mud): Identification of active components and column tests.

Bauxite residue is the by-product of the aluminium industry with an annual output of more than 200 million metric tons in China. Its treatment is still a big problem because more than 96% of that is stockpiled on land causing environmental pollution and threatening the human health. This study used bauxite residue to remove Cr (Ⅲ) from aqueous solution and analyzed the removal mechanism. The removal time was dependent on the initial concentrations of Cr (Ⅲ) and different active components acted on different reaction period. Reaction time increased from <5 min to >2 h with an increase of Cr (Ⅲ) concentration from 5 to 100 and 170 mg/L. The existing forms of adsorbed-Cr were iron oxide-bound Cr (40.80%-87.85%), sulfide-bound Cr (4.04%-20.28%) and residue (6.60%-33.72%). All the components started to react as soon as bauxite residue was added. Cr did not precipitate in the presence of high alkalinity bauxite residue due to the slow release of alkalinity maintaining pH < 6, thus producing Cr(OH)2+, Cr2(OH)24+ and Cr3(OH)45+ by hydrolysis without precipitation. Fe2O3 and Al-containing components were the main active phases for Cr (Ⅲ) removal, with the reaction time lasting more than 2 h and producing Ca6Al4Cr2O15, AlCr2, (Si, Al)2O4, Fe(Cr, Al)2O4, FeCr2Si3O12, MgCr0·1Fe1·9O4 and MgCr0·4Fe1·6O4. Finally, bauxite residue was granulated and used for column tests. Cr (Ⅲ) wastewater (1 and 50 mg/L) was treated and the effluent can meet the first level of the Shanghai standard (0.1 mg/L) defined by Integrated Wastewater Discharge Standard (DB 31/199-2009).

Analysis of bauxite residue components responsible for copper removal and related reaction products.

Bauxite residue is a solid waste produced during alumina production process, and the storage of that in China reached 0.6 billion tons with an increase of more than 70 million annually. Bauxite residue can be used to remove heavy metals from water. This study analyzed components of bauxite residue responsible for copper removal, removal process and accompanying reaction products. Calcite (CaCO3), hematite (Fe2O3) and sulfur-Fe are main components contributing to copper removal. Sulfur in bauxite residue works with iron to remove copper. All these components reacted with copper immediately as bauxite residue was added. Reaction time of sulfur-Fe and carbonate was 5 min and 1 h, respectively. And hematite reacted until complete removal of copper (>2 h). Sulfur quickly reacted with coexisting iron to remove copper, producing chalcopyrite (CuFeS2), cubanite (CuFe2S3) and bornite (Cu5FeS4). Carbonate in bauxite residue reacted with copper, producing tenorite (CuO), copper hydroxide (Cu(OH)2), malachite (Cu2(OH)2CO3), carbonate cyanotrichite (Cu4Al2(CO3,SO4)(OH)12·2H2O), chalconatronite (Na2Cu(CO3)2·3H2O), nakauriite (Cu8(SO4)4(CO3)(OH)6·48H2O) and callaghanite (Cu2Mg2(CO3)(OH)6·2H2O). Copper precipitated through reaction with hematite to produce delafossite (CuFeO2). After removal reaction, the existing forms of copper in bauxite residue comprised carbonate-bound (73.6%-85.7%), iron oxide-bound (5.6%-23.8%), organic matter/sulfide-bound (0.5%-9.0%) and residual forms (0.9%-2.0%). In conclusion, removal of copper using bauxite residue features a more complex reaction than adsorption.

Effects of Arginine concentration on the in vitro expression of Casein and mTOR pathway related genes in mammary epithelial cells from dairy cattle.

Arginine (Arg) is a conditionally-essential amino acid that is taken up by bovine mammary gland in excess of its output in milk. In this study we evaluated the effects of Arg concentration on the expression of casein and signaling pathway-related genes in mammary epithelial cells. The treatments (applied for 24 h) were designed to be devoid of Arg 0X (control; 0.00 mg/L), resemble the profile of Arg in casein (Arg 1X; 278.00 mg/L), be deficient [Arg 0.25X (69.50 mg/L) and Arg 0.5X (139.00 mg/L)], or be in excess of the amount in casein [Arg 2X (556.00 mg/L), Arg 4X (1,112 mg/L), and Arg 8X (2,224 mg/L)]. The expression of CSN1S, CSN3 and mTOR in the experimental groups was higher than those of the control group (P<0.05). Except for Arg 0.25X and Arg 8X (P>0.05), the expression of CSN1S2, CSN2 and JAK2 in other experimental groups was higher (P<0.05) than those in the control group. Except for Arg 8X (P>0.05), the expression of STAT5 in the other experimental groups was higher than those of the control (P<0.05). It also was observed that except for Arg 0.5X, the S6K expression was higher in other experimental groups than the control (P<0.05). In contrast, except for Arg 0.25X the other experimental groups resulted in lower 4EBP1 expression than the control (P<0.05). Among groups, the expression of CSN1S1, CSN1S2, CSN2, CSN3, JAK2, STAT5, mTOR and S6K gene was highest with Arg 2X (P<0.05); the reverse was true for 4EBP1 gene, with the lowest expression in this group (P<0.05). Taken together, Arg appears to play an important role in the transcriptional regulation of casein genes and mTOR-related genes in bovine mammary epithelial cells.