Design, Synthesis, and Antimicrobial Activity of Amide Derivatives Containing Cyclopropane.

As an important small organic molecule, cyclopropane is widely used in drug design. In this paper, fifty-three amide derivatives containing cyclopropane were designed and synthesized by introducing amide groups and aryl groups into cyclopropane through the active splicing method, and their antibacterial and antifungal activities were evaluated in vitro. Among them, thirty-five compounds were new compounds, and eighteen compounds were known compounds (F14, F15, F18, F20-F26, F36, and F38-F44). Bioassay results disclosed that four, three, and nine of the compounds showed moderate activity against Staphylococcus aureus, Escherichia coli, and Candida albicans, respectively. Three compounds were sensitive to Candida albicans, with excellent antifungal activity (MIC80 = 16 µg/mL). The molecular docking results show that compounds F8, F24, and F42 have good affinity with the potential antifungal drug target CYP51 protein.

Hypoxia inducible factor (HIF) 3α prevents COPD by inhibiting alveolar epithelial cell ferroptosis via the HIF-3α-GPx4 axis.

Rationale: COPD patients are largely asymptomatic until the late stages when prognosis is generally poor. In this study, we shifted the focus to pre-COPD and smoking stages, and found enrichment of hypoxia inducible factor (HIF)-3α is in pre-COPD samples. Smoking induced regional tissue hypoxia and emphysema have been found in COPD patients. However, the mechanisms underlying hypoxia especially HIF-3α and COPD have not been investigated. Methods: We performed bulk-RNA sequencing on 36 peripheral lung tissue specimens from non-smokers, smokers, pre-COPD and COPD patients, and using "Mfuzz" algorithm to analysis the dataset dynamically. GSE171541 and EpCAM co-localization analyses were used to explore HIF-3α localization. Further, SftpcCreert2/+R26LSL-Hif3a knock-in mice and small molecular inhibitors in vitro were used to explore the involvement of HIF-3α in the pathophysiology of COPD. Results: Reactive oxygen species (ROS) and hypoxia were enriched in pre-COPD samples, and HIF-3α was downregulated in alveolar epithelial cells in COPD. In vitro experiments using lentivirus transfection, bulk-RNA seq, and RSL3 showed that the activation of the HIF-3α-GPx4 axis inhibited alveolar epithelial cell ferroptosis when treated with cigarettes smoking extracts (CSE). Further results from SftpcCreert2/+R26LSL-Hif3a knock-in mice demonstrated overexpression of HIF-3α inhibited alveolar epithelial cells ferroptosis and prevented the decline of lung function. Conclusion: Hypoxia and oxidation-related damage begins years before the onset of COPD symptoms, suggesting the imbalance and impairment of intracellular homeostatic system. The activation of the HIF-3α-GPx4 axis is a promising treatment target. By leveraging this comprehensive analysis method, more potential targets could be found and enhancing our understanding of the pathogenesis.

Colloidal Hydrogel with Staged Sequestration and Release of Molecules Undergoing Competitive Binding.

Competitive binding of distinct molecules in the hydrogel interior can facilitate dynamic exchange between the hydrogel and the surrounding environment. The ability to control the rates of sequestration and release of these molecules would enhance the hydrogel's functionality and enable targeting of a specific task. Here, we report the design of a colloidal hydrogel with two distinct pore dimensions to achieve staged, diffusion-controlled scavenging and release dynamics of molecules undergoing competitive binding. The staged scavenging and release strategy was shown for CpG oligodeoxynucleotide (ODN) and human epidermal growth factor (hEGF), two molecules exhibiting different affinities to the quaternary ammonium groups of the hydrogel. Fast ODN scavenging from the ambient environment occurred via diffusion through submicrometer-size hydrogel pores, while delayed hEGF release from the hydrogel was governed by its diffusion through nanometer-size pores. The results of the experiments were in agreement with simulation results. The significance of staged ODN-hEGF exchange was highlighted by the dual anti-inflammation and tissue proliferation hydrogel performance.

Oncogenic SLC2A11-MIF fusion protein interacts with polypyrimidine tract binding protein 1 to facilitate bladder cancer proliferation and metastasis by regulating mRNA stability.

Chimeric RNAs, distinct from DNA gene fusions, have emerged as promising therapeutic targets with diverse functions in cancer treatment. However, the functional significance and therapeutic potential of most chimeric RNAs remain unclear. Here we identify a novel fusion transcript of solute carrier family 2-member 11 (SLC2A11) and macrophage migration inhibitory factor (MIF). In this study, we investigated the upregulation of SLC2A11-MIF in The Cancer Genome Atlas cohort and a cohort of patients from Sun Yat-Sen Memorial Hospital. Subsequently, functional investigations demonstrated that SLC2A11-MIF enhanced the proliferation, antiapoptotic effects, and metastasis of bladder cancer cells in vitro and in vivo. Mechanistically, the fusion protein encoded by SLC2A11-MIF interacted with polypyrimidine tract binding protein 1 (PTBP1) and regulated the mRNA half-lives of Polo Like Kinase 1, Roundabout guidance receptor 1, and phosphoinositide-3-kinase regulatory subunit 3 in BCa cells. Moreover, PTBP1 knockdown abolished the enhanced impact of SLC2A11-MIF on biological function and mRNA stability. Furthermore, the expression of SLC2A11-MIF mRNA is regulated by CCCTC-binding factor and stabilized through RNA N4-acetylcytidine modification facilitated by N-acetyltransferase 10. Overall, our findings revealed a significant fusion protein orchestrated by the SLC2A11-MIF-PTBP1 axis that governs mRNA stability during the multistep progression of bladder cancer.

A human-specific cytotoxic neopeptide generated by the deafness gene Cingulin.

Accumulation of mutant proteins in cells can induce proteinopathies and cause functional damage to organs. Recently, the Cingulin (CGN) protein has been shown to maintain the morphology of cuticular plates of inner ear hair cells and a frameshift mutation in CGN causes autosomal dominant non-syndromic hearing loss. Here, we find that the mutant CGN proteins form insoluble aggregates which accumulate intracellularly and lead to cell death. Expression of the mutant CGN in the inner ear results in severe hair cell death and hearing loss in mice, resembling the auditory phenotype in human patients. Interestingly, a human-specific residue (V1112) in the neopeptide generated by the frameshift mutation is critical for the aggregation and cytotoxicity of the mutant human CGN. Moreover, the expression of heat shock factor 1 (HSF1) decreases the accumulation of insoluble mutant CGN aggregates and rescues cell death. In summary, these findings identify mutant-specific toxic polypeptides as a disease-causing mechanism of the deafness mutation in CGN, which can be targeted by the expression of the cell chaperone response regulator HSF1.

Ultralow-Energy-Consumption Photosynaptic Transistor Utilizing Conjugated Polymers/Perovskite Quantum Dots Nanocomposites With Ligand Density Optimization.

The photosynaptic transistor stands as a promising contender for overcoming the von Neumann bottleneck in the realm of photo-communication. In this context, photonic synaptic transistors is developed through a straightforward solution process, employing an organic semiconducting polymer with pendant-naphthalene-containing side chains (PDPPNA) in combination with ligand-density-engineered CsPbBr3 perovskite quantum dots (PQDs). This fabrication approach allows the devices to emulate fundamental synaptic behaviors, encompassing excitatory postsynaptic current, paired-pulse facilitation, the transition from short-to-long-term memory, and the concept of "learning experience." Notably, the phototransistor, incorporating the blend of the PDPPNA and CsPbBr3 PQDs washed with ethyl acetate, achieved an exceptional memory ratio of 104. Simultaneously, the same device exhibited an impressive paired-pulse facilitation ratio of 223% at a moderate operating voltage of -4 V and an extraordinarily low energy consumption of 0.215 aJ at an ultralow operating voltage of -0.1 mV. Consequently, these low-voltage synaptic devices, constructed with a pendant side-chain engineering of organic semiconductors and a ligand density engineering of PQDs through a simple fabrication process, exhibit substantial potential for replicating the visual memory capabilities of the human brain.

Ovarian cancer identification technology based on deep learning and second harmonic generation imaging.

Ovarian cancer is among the most common gynecological cancers and the eighth leading cause of cancer-related deaths among women worldwide. Surgery is among the most important options for cancer treatment. During surgery, a biopsy is generally required to screen for lesions; however, traditional case examinations are time consuming and laborious and require extensive experience and knowledge from pathologists. Therefore, this study proposes a simple, fast, and label-free ovarian cancer diagnosis method that combines second harmonic generation (SHG) imaging and deep learning. Unstained fresh human ovarian tissues were subjected to SHG imaging and accurately characterized using the Pyramid Vision Transformer V2 (PVTv2) model. The results showed that the SHG imaged collagen fibers could quantify ovarian cancer. In addition, the PVTv2 model could accurately differentiate the 3240 SHG images obtained from our imaging collection into benign, normal, and malignant images, with a final accuracy of 98.4%. These results demonstrate the great potential of SHG imaging techniques combined with deep learning models for diagnosing the diseased ovarian tissues.

Trehalose prevents the formation of aggregates of mutant ataxin-3 and reduces soluble ataxin-3 protein levels in an SCA3 cell model.

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by mutant ataxin-3 with an abnormally expanded polyQ tract and is the most common dominantly inherited ataxia worldwide. There are no suitable therapeutic options for this disease. Autophagy, a defense mechanism against the toxic effects of aggregation-prone misfolded proteins, has been shown to have beneficial effects on neurodegenerative diseases. Thus, trehalose, which is an autophagy inducer, may have beneficial effects on SCA3. In the present study, we examined the effects of trehalose on an SCA3 cell model. After trehalose treatment, aggregate formation, soluble ataxin-3 protein levels and cell viability were evaluated in HEK293T cells overexpressing ataxin-3-15Q or ataxin-3-77Q. We also explored the mechanism by which trehalose affects autophagy and stress pathways. A filter trap assay showed that trehalose decreased the number of aggregates formed by mutant ataxin-3 containing an expanded polyQ tract. Western blot and Cell Counting Kit-8 (CCK-8) results demonstrated that trehalose also reduced the ataxin-3 protein levels and was safe for ataxin-3-expressing cells, respectively. Western blot and total antioxidant capacity assays suggested that trehalose had great therapeutic potential for treating SCA3, likely through its antioxidant activity. Our data indicate that trehalose plays a neuroprotective role in SCA3 by inhibiting the aggregation and reducing the protein level of ataxin-3, which is also known to protect against oxidative stress. These findings provide a new insight into the possibility of treating SCA3 with trehalose and highlight the importance of inducing autophagy in SCA3.

Metabolic Profiling of Cochlear Organoids Identifies α-Ketoglutarate and NAD+ as Limiting Factors for Hair Cell Reprogramming.

Cochlear hair cells are the sensory cells responsible for transduction of acoustic signals. In mammals, damaged hair cells do not regenerate, resulting in permanent hearing loss. Reprogramming of the surrounding supporting cells to functional hair cells represent a novel strategy to hearing restoration. However, cellular processes governing the efficient and functional hair cell reprogramming are not completely understood. Employing the mouse cochlear organoid system, detailed metabolomic characterizations of the expanding and differentiating organoids are performed. It is found that hair cell differentiation is associated with increased mitochondrial electron transport chain (ETC) activity and reactive oxidative species generation. Transcriptome and metabolome analyses indicate reduced expression of oxidoreductases and tricyclic acid (TCA) cycle metabolites. The metabolic decoupling between ETC and TCA cycle limits the availability of the key metabolic cofactors, α-ketoglutarate (α-KG) and nicotinamide adenine dinucleotide (NAD+). Reduced expression of NAD+ in cochlear supporting cells by PGC1α deficiency further impairs hair cell reprogramming, while supplementation of α-KG and NAD+ promotes hair cell reprogramming both in vitro and in vivo. These findings reveal metabolic rewiring as a central cellular process during hair cell differentiation, and highlight the insufficiency of key metabolites as a metabolic barrier for efficient hair cell reprogramming.

Fine-regulation of gradient gate-opening in nanoporous crystals for sieving separation of ternary C3 hydrocarbons.

The adsorptive separation of ternary propyne (C3H4)/propylene (C3H6)/propane (C3H8) mixtures is of significant importance due to its energy efficiency. However, achieving this process using an adsorbent has not yet been accomplished. To tackle such a challenge, herein, we present a novel approach of fine-regulation of the gradient of gate-opening in soft nanoporous crystals. Through node substitution, an exclusive gate-opening to C3H4 (17.1 kPa) in NTU-65-FeZr has been tailored into a sequential response of C3H4 (1.6 kPa), C3H6 (19.4 kPa), and finally C3H8 (57.2 kPa) in NTU-65-CoTi, of which the gradient framework changes have been validated by in situ powder X-ray diffractions and modeling calculations. Such a significant breakthrough enables NTU-65-CoTi to sieve the ternary mixtures of C3H4/C3H6/C3H8 under ambient conditions, particularly, highly pure C3H8 (99.9%) and C3H6 (99.5%) can be obtained from the vacuum PSA scheme. In addition, the fully reversible structural change ensures no loss in performance during the cycling dynamic separations. Moving forward, regulating gradient gate-opening can be conveniently extended to other families of soft nanoporous crystals, making it a powerful tool to optimize these materials for more complex applications.

Electrocatalytic Glycerol Upgrading into Glyceric Acid on Ni3Sn Intermetallic Compound.

Electrochemical glycerol oxidation features an attractive approach of converting bulk chemicals into high-value products such as glyceric acid. Nonetheless, to date, the major product selectivity has mostly been limited as low-value C1 products such as formate, CO, and CO2, due to the fast cleavage of carbon-carbon (C-C) bonds during electro-oxidation. Herein, the study develops an atomically ordered Ni3Sn intermetallic compound catalyst, in which Sn atoms with low carbon-binding and high oxygen-binding capability allow to tune the adsorption of glycerol oxidation intermediates from multi-valent carbon binding to mono-valent carbon binding, as well as enhance *OH binding and subsequent nucleophilic attack. The Ni3Sn electrocatalyst exhibits one of the highest glycerol-to-glyceric acid performances, including a high glycerol conversion rate (1199 µmol h-1) and glyceric acid selectivity (62 ± 3%), a long electrochemical stability of > 150 h, and the capability of direct conversion of crude glycerol (85% purity) into glyceric acid. The work features the rational design of highly ordered catalytic sites for tailoring intermediate binding and reaction pathways, thereby facilitating the efficient production of high-value chemical products.

Immobilization of Amino-site into a Pore-Partitioned Metal-Organic Framework for Highly Efficient Separation of Propyne/Propylene.

Adsorptive separation of propyne/propylene (C3H4/C3H6) is a crucial yet complex process, however, it remains a great difficulty in developing porous materials that can meet the requirements for practical applications, particularly with an exceptional ability to bind and store trace amounts of C3H4. Functionalization of pore-partitioned metal-organic frameworks (ppMOFs) is methodically suited for this challenge owing to the possibility of dramatically increasing binding sites on highly porous and confined domains. We here immobilized Lewis-basic (-NH2) and Lewis-acidic (-NO2) sites on this platform. Along with an integrated nature of high uptake of C3H4 at 1 kPa, high uptake difference of C3H4-C3H6, moderated binding strength, promoted kinetic selectivity, trapping effect and high stability, the NH2-decorated ppMOF (NTU-100-NH2) can efficiently produce polymer-grade C3H6 (99.95 %, 8.3 mmol ⋅ g-1) at room temperature, which is six times more than the NO2-decorated crystal (NTU-100-NO2). The in situ infrared spectroscopy, crystallographic analysis, and sequential blowing tests showed that the densely packed amino group in this highly porous system has a unique ability to recognize and stabilize C3H4 molecules. Moving forward, the strategy of organic functionalization can be extended to other porous systems, making it a powerful tool to customize advanced materials for challenging tasks.

Interleukin-2/anti-interleukin-2 complex attenuates inflammation in a mouse COPD model by expanding CD4+ CD25+ Foxp3+ regulatory T cells.

BACKGROUND AND PURPOSE: Chronic, nonspecific inflammation of the alveoli and airways is an important pathological feature of chronic obstructive pulmonary disease (COPD), while sustained inflammatory reactions can cause alveolar damage. Regulatory T cells (Tregs) inhibit inflammation, whereas the interleukin-2/anti-interleukin-2 complex (IL-2C) increases the number of Tregs; however, whether the IL-2C has a therapeutic role in COPD remains unknown. Therefore, this study investigated whether IL-2C alleviates lung inflammation in COPD by increasing the number of Tregs. EXPERIMENTAL APPROACH: A mouse COPD model was created by exposing mice to lipopolysaccharides (LPS) and cigarette smoke (CS), and the effects of IL-2C treatment on COPD were evaluated. The number of Tregs in the spleen and lung, pulmonary pathological changes, and inflammatory damage were examined through flow cytometry, histopathology, and immunofluorescence, respectively. KEY RESULTS: IL-2C increased the number of Treg cells in the spleen and lungs after exposure to CS and LPS, reduced the number of T helper 17 (Th17) cells in lung tissue, and improved the Th17/Treg balance. IL-2C decreased the number of inflammatory cells and reduced the levels of pro-inflammatory cytokines IL-6, TNF-α, IL-1ß, CCL5, KC, and MCP-1 in bronchoalveolar lavage fluid and serum. IL-2C significantly reduced the pathological scores for lung inflammation, as well as decreased airway mucus secretion and infiltration of neutrophils and macrophages in the lungs. The depletion of Tregs using anti-CD25 antibodies eliminated the beneficial effects of IL-2C. CONCLUSIONS AND IMPLICATIONS: IL-2C is a potential therapeutic agent for alleviating excessive inflammation in the lungs of patients with COPD.

Recent progress in self-healable energy harvesting and storage devices - a future direction for reliable and safe electronics.

Electronic devices with multiple features bring in comfort to the way we live. However, repeated use causes physical as well as chemical degradation reducing their lifetime. The self-healing ability is the most crucial property of natural systems for survival in unexpected situations and variable environments. However, this self-repair property is not possessed by the conventional electronic devices designed today. To expand their lifetime and make them reliable by restoring their mechanical, functional, and electrical properties, self-healing materials are a great go-to option to create robust devices. In this review the intriguing self-healing polymers and fascinating mechanism of self-healable energy harvesting devices such as triboelectric nanogenerators (TENG) and storage devices like supercapacitors and batteries from the aspect of electrodes and electrolytes in the past five years are reviewed. The current challenges, strategies, and perspectives for a smart and sustainable future are also discussed.

Identification of Immune Infiltration and Iron Metabolism-Related Subgroups in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with a broad spectrum of symptoms and prognoses. Effective therapy requires understanding this variability. ASD children's cognitive and immunological development may depend on iron homoeostasis. This study employs a machine learning model that focuses on iron metabolism hub genes to identify ASD subgroups and describe immune infiltration patterns. A total of 97 control and 148 ASD samples were obtained from the GEO database. Differentially expressed genes (DEGs) and an iron metabolism gene collection achieved the intersection of 25 genes. Unsupervised cluster analysis determined molecular subgroups in individuals with ASD based on 25 genes related to iron metabolism. We assessed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, gene set variation analysis (GSVA), and immune infiltration analysis to compare iron metabolism subtype effects. We employed machine learning to identify subtype-predicting hub genes and utilized both training and validation sets to assess gene subtype prediction accuracy. ASD can be classified into two iron-metabolizing molecular clusters. Metabolic enrichment pathways differed between clusters. Immune infiltration showed that clusters differed immunologically. Cluster 2 had better immunological scores and more immune cells, indicating a stronger immune response. Machine learning screening identified SELENBP1 and CAND1 as important genes in ASD's iron metabolism signaling pathway. These genes express in the brain and have AUC values over 0.8, implying significant predictive power. The present study introduces iron metabolism signaling pathway indicators to predict ASD subtypes. ASD is linked to immune cell infiltration and iron metabolism disorders.

CDK12 regulates angiogenesis of advanced prostate cancer by IGFBP3.

Prostate cancer (PCa) is a prevalent malignancy among men, with a majority of patients presenting with distant metastases at the time of initial diagnosis. These patients are at a heightened risk of developing more aggressive castration­resistant PCa following androgen deprivation therapy, which poses a greater challenge for treatment. Notably, the inhibition of tumor angiogenesis should not be considered an ineffective treatment strategy. The regulatory role of CDK12 in transcriptional and post­transcriptional processes is essential for the proper functioning of various cellular processes. In the present study, the expression of CDK12 was first knocked down in cells using CRISPR or siRNA technology. Subsequently, RNA­seq analysis, co­immunoprecipitation, western blotting, reverse transcription­quantitative polymerase chain reaction and the LinkedOmics database were employed to reveal that CDK12 inhibits insulin like growth factor binding protein 3 (IGFBP3). Western blot analysis also demonstrated that CDK12 promoted VEGFA expression by inhibiting IGFBP3, which involves the Akt signaling pathway. Then, CDK12 was found to promote PCa cell proliferation, cell migration and angiogenesis by inhibiting IGFBP3 through cell proliferation assays, cell migration assays and tube formation assays, respectively. Finally, animal experiments were performed for in vivo validation. It was concluded that CDK12 promoted PCa and its angiogenesis by inhibiting IGFBP3.

Molecular Sieving of Propyne/Propylene by a Scalable Nanoporous Crystal with Confined Rotational Shutters.

Soft porous coordination polymers (PCPs) have the remarkable ability to recognize similar molecules as a result of their structural dynamics. However, their guest-induced gate-opening behaviors often lead to issues with selectivity and separation efficiency, as co-adsorption is nearly unavoidable. Herein, we report a strategy of a confined-rotational shutter, in which the rotation of pyridyl rings within the confined nanospace of a halogen-bonded coordination framework (NTU-88) creates a maximum aperture of 4.4 Å, which is very close to the molecular size of propyne (C3 H4 : 4.4 Å), but smaller than that of propylene (C3 H6 : 5.4 Å). This has been evidenced by crystallographic analyses and modelling calculations. The NTU-88o (open phase of activated NTU-88) demonstrates dedicated C3 H4 adsorption, and thereby leads to a sieving separation of C3 H4 /C3 H6 under ambient conditions. The integrated nature of high uptake ratio, considerable capacity, scalable synthesis, and good stability make NTU-88 a promising candidate for the feasible removal of C3 H4 from C3 H4 /C3 H6 mixtures. In principle, this strategy holds high potential for extension to soft families, making it a powerful tool for optimizing materials that can tackle challenging separations with no co-adsorption, while retaining the crucial aspect of high capacity.

Multiwavelength camouflage metamaterials with adjustable emissivity.

Metamaterials-based multispectral camouflage has attracted growing interest in most fields of military and aerospace due to its unprecedented emission adjustability covering an ultra-broadband spectral range. Conventional camouflage mainly concentrates on an individual spectral range, e. g. either of visible, mid-wavelength-infrared (MWIR) or long-wavelength-infrared (LWIR), which is especially incapable of self-adaptive thermal camouflage to the changing ambient environment. Here, we theoretically demonstrate a multispectral camouflage metamaterial consisting of a four-layer titanium/silicon/vanadium dioxide/ titanium (Ti/Si/VO2/Ti) nanostructure, where the background temperature-adaptive thermal camouflage is implemented by exploiting the switchable metal/dielectric state of the phase-changing material VO2 for regulating the infrared emissivity of the designed metamaterial, whilst visible color camouflage is also achieved by tuning thickness of middle Si layer to match the background's appearance. It has been shown that the designed metamaterial with the dielectric state of VO2 enables thermal camouflage of high background temperature by increasing the thermal emission (average emissivity of 0.69/0.83 for MWIR/LWIR range), meanwhile, the metamaterial of the metallic state of VO2 for low background temperature thermal camouflage stemming from low emission (average emissivity of 0.29 for both MWIR/LWIR range) due to high infrared reflection. Furthermore, the designed metamaterial structural color is robust for a phase change switching. This proposed adaptive camouflage provides a potential strategy to broaden dynamical camouflage technology for further practical application in the fields of military and civilian.

Delicate Softness in a Temperature-Responsive Porous Crystal for Accelerated Sieving of Propylene/Propane.

Soft nanoporous crystals with structural dynamics are among the most exciting recently discovered materials. However, designing or controlling a porous system with delicate softness that can recognize similar gas pairs, particularly for the promoted ability at increased temperature, remains a challenge. Here, we report a soft crystal (NTU-68) with a one-dimensional (1D) channel that expands and contracts delicately around 4 Å at elevated temperature. The completely different adsorption processes of propane (C3H8: kinetic dominance) and propylene (C3H6: thermodynamic preference) allow the crystal to show a sieving separation of this mixtures (9.9 min·g-1) at 273 K, and the performance increases more than 2-fold (20.4 min·g-1) at 298 K. This phenomenon is contrary to the general observation for adsorption separation: the higher the temperature, the lower the efficiency. Gas-loaded in situ powder X-ray analysis and modeling calculations reveal that slight pore expansion caused by the increased temperature provides plausible nanochannel for adsorption of the relatively smaller C3H6 while maintaining constriction on the larger C3H8. In addition, the separation process remains unaffected by the general impurities, demonstrating its true potential as an alternative sorbent for practical applications. Moving forward, the delicate crystal dynamics and promoted capability for molecular recognition provide a new route for the design of next-generation sieve materials.

Cingulin regulates hair cell cuticular plate morphology and is required for hearing in human and mouse.

Cingulin (CGN) is a cytoskeleton-associated protein localized at the apical junctions of epithelial cells. CGN interacts with major cytoskeletal filaments and regulates RhoA activity. However, physiological roles of CGN in development and human diseases are currently unknown. Here, we report a multi-generation family presenting with autosomal dominant non-syndromic hearing loss (ADNSHL) that co-segregates with a CGN heterozygous truncating variant, c.3330delG (p.Leu1110Leufs*17). CGN is normally expressed at the apical cell junctions of the organ of Corti, with enriched localization at hair cell cuticular plates and circumferential belts. In mice, the putative disease-causing mutation results in reduced expression and abnormal subcellular localization of the CGN protein, abolishes its actin polymerization activity, and impairs the normal morphology of hair cell cuticular plates and hair bundles. Hair cell-specific Cgn knockout leads to high-frequency hearing loss. Importantly, Cgn mutation knockin mice display noise-sensitive, progressive hearing loss and outer hair cell degeneration. In summary, we identify CGN c.3330delG as a pathogenic variant for ADNSHL and reveal essential roles of CGN in the maintenance of cochlear hair cell structures and auditory function.