ARF6 plays a general role in targeting palmitoylated proteins from the Golgi to the plasma membrane.

Protein palmitoylation is a post-translational lipid modification of proteins. Accumulating evidence reveals that palmitoylation functions as a sorting signal to direct proteins to destinations; however, the sorting mechanism remains largely unknown. Here, we show that ARF6 plays a general role in targeting palmitoylated proteins from the Golgi to the plasma membrane (PM). Through shRNA screening, we identified ARF6 as the key small GTPase in targeting CD36, a palmitoylated protein, from the Golgi to the PM. We found that the N-terminal myristoylation of ARF6 is required for its binding with palmitoylated CD36, and the GTP-bound form of ARF6 facilitates the delivery of CD36 to the PM. Analysis of stable isotope labeling by amino acids in cell culture revealed that ARF6 might facilitate the sorting of 359 of the 531 palmitoylated PM proteins, indicating a general role of ARF6. Our study has thus identified a sorting mechanism for targeting palmitoylated proteins from the Golgi to the PM.

The PRMT5/WDR77 complex restricts hepatitis E virus replication.

Hepatitis E virus (HEV) is one of the main pathogenic agents of acute hepatitis in the world. The mechanism of HEV replication, especially host factors governing HEV replication is still not clear. Here, using HEV ORF1 trans-complementation cell culture system and HEV replicon system, combining with stable isotope labelling with amino acids in cell culture (SILAC) and mass spectrometry (MS), we aimed to identify the host factors regulating HEV replication. We identified a diversity of host factors associated with HEV ORF1 protein, which were putatively responsible for viral genomic RNA replication, in these two cell culture models. Of note, the protein arginine methyltransferase 5 (PRMT5)/WDR77 complex was identified in both cell culture models as the top hit. Furthermore, we demonstrated that PRMT5 and WDR77 can specifically inhibit HEV replication, but not other viruses such as HCV or SARS-CoV-2, and this inhibition is conserved among different HEV strains and genotypes. Mechanistically, PRMT5/WDR77 can catalyse methylation of ORF1 on its R458, impairing its replicase activity, and virus bearing R458K mutation in ORF1 relieves the restriction of PRMT5/WDR77 accordingly. Taken together, our study promotes more comprehensive understanding of viral infections but also provides therapeutic targets for intervention.

KLF12 interacts with TRIM27 to affect cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma by regulating L1CAM expression.

Krüppel-like factor 12 (KLF12) has been characterized as a transcriptional repressor, and previous studies have unveiled its roles in angiogenesis, neural tube defect, and natural killer (NK) cell proliferation. However, the contribution of KLF12 to cancer treatment remains undefined. Here, we show that KLF12 is downregulated in various cancer types, and KLF12 downregulation promotes cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma (ESCC). Mechanistically, KLF12 binds to the promoters of L1 Cell Adhesion Molecule (L1CAM) and represses its expression. Depletion of L1CAM abrogates cisplatin resistance and cancer metastasis caused by KLF12 loss. Moreover, the E3 ubiquitin ligase tripartite motif-containing 27 (TRIM27) binds to the N-terminal region of KLF12 and ubiquitinates KLF12 at K326 via K33-linked polyubiquitination. Notably, TRIM27 depletion enhances the transcriptional activity of KLF12 and consequently inhibits L1CAM expression. Overall, our study elucidated a novel regulatory mechanism involving TRIM27, KLF12 and L1CAM, which plays a substantial role in cisplatin resistance and cancer metastasis in ESCC. Targeting these genes could be a promising approach for ESCC treatment.

Piezoelectric Hydrogels: Hybrid Material Design, Properties, and Biomedical Applications.

Hydrogels show great potential in biomedical applications due to their inherent biocompatibility, high water content, and resemblance to the extracellular matrix. However, they lack self-powering capabilities and often necessitate external stimulation to initiate cell regenerative processes. In contrast, piezoelectric materials offer self-powering potential but tend to compromise flexibility. To address this, creating a novel hybrid biomaterial of piezoelectric hydrogels (PHs), which combines the advantageous properties of both materials, offers a systematic solution to the challenges faced by these materials when employed separately. Such innovative material system is expected to broaden the horizons of biomedical applications, such as piezocatalytic medicinal and health monitoring applications, showcasing its adaptability by endowing hydrogels with piezoelectric properties. Unique functionalities, like enabling self-powered capabilities and inducing electrical stimulation that mimics endogenous bioelectricity, can be achieved while retaining hydrogel matrix advantages. Given the limited reported literature on PHs, here recent strategies concerning material design and fabrication, essential properties, and distinctive applications are systematically discussed. The review is concluded by providing perspectives on the remaining challenges and the future outlook for PHs in the biomedical field. As PHs emerge as a rising star, a comprehensive exploration of their potential offers insights into the new hybrid biomaterials.

Mechanoluminescent/Electric Dual-Mode Sensors Enabled by Trace Carbon Nanotubes.

Mechanoluminescence (ML)-based sensors are emerging as promising wearable devices, attracting attention for their self-powered visualization of mechanical stimuli. However, challenges such as weak brightness, high activation threshold, and intermittent signal output have hindered their development. Here, a mechanoluminescent/electric dual-mode strain sensor is presented that offers enhanced ML sensing and reliable electrical sensing simultaneously. The strain sensor is fabricated via an optimized dip-coating method, featuring a sandwich structure with a single-walled carbon nanotube (SWNT) interlayer and two polydimethylsiloxane (PDMS)/ZnS:Cu luminescence layers. The integral mechanical reinforcement framework provided by the SWNT interlayer improves the ML intensity of the SWNT/PDMS/ZnS:Cu composite film. Compared to conventional nanoparticle fillers, the ML intensity is enhanced nearly tenfold with a trace amount of SWNT (only 0.01 wt.%). In addition, the excellent electrical conductivity of SWNT forms a conductive network, ensuring continuous and stable electrical sensing. These strain sensors enable comprehensive and precise monitoring of human behavior through both electrical (relative resistance change) and optical (ML intensity) methods, paving the way for the development of advanced visual sensing and smart wearable electronics in the future.

Contributing to the Revolution of Electrolyte Systems via In Situ Polymerization at Different Scales: A Review.

Solid-state batteries have become the most anticipated option for compatibility with high-energy density and safety. In situ polymerization, a novel strategy for the construction of solid-state systems, has extended its application from solid polymer electrolyte systems to other solid-state systems. This review summarizes the application of in situ polymerization strategies in solid-state batteries, which covers the construction of polymer, the formation of the electrolyte system, and the design of the full cell. For the polymer skeleton, multiple components and structures are being chosen. In the construction of solid polymer electrolyte systems, the choice of initiator for in situ polymerization is the focus of this review. New initiators, represented by lithium salts and additives, are the preferred choice because of their ability to play more diverse roles, while the coordination with other components can also improve the electrical properties of the system and introduce functionalities. In the construction of entire solid-state battery systems, the application of in situ polymerization to structure construction, interface construction, and the use of separators with multiplex functions has brought more possibilities for the development of various solid-state systems and even the perpetuation of liquid electrolytes.

Regulate the Solvation Structure and Interface by Nitrate in Phosphate-Based Electrolytes for 4.5 V-Class Ni-Rich Batteries.

Phosphate-based electrolyte propels the advanced battery system with high safety. Unfortunately, restricted by poor electrochemical stability, it is difficult to be compatible with advanced lithium metal anodes and Ni-rich cathodes. To alleviate these issues, the study has developed a phosphate-based localized high-concentration electrolyte with a nitrate-driven solvation structure, and the nitrate-derived N-rich inorganic interface shows excellent performance in stabilizing the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode interface and modulating the lithium deposition morphology on the anode. The results show that the Li|| NCM811 cell has exceptional long-cycle stability of >80% capacity retention after 800 cycles at 4.3 V, 1 C. A more prominent capacity retention rate of 93.3% after 200 cycles can be reached with the high voltage of 4.5 V. While being compatible with the phosphate-based electrolyte with good flame retardancy and the good electrochemical stability of Ni-rich lithium metal battery (LMBs) systems, the present work expands the construction of anion-rich solvation structures, which is expected to promote the development of the high-performance LMBs with safety.

Construction of an Ohmic Contact Cathode by Two Metal Sulfides for efficient Capture and Catalysis of Polysulfide.

The slow reaction kinetics and severe shuttle effect of lithium polysulfide make Li-S battery electrochemical performance difficult to meet the demands of large electronic devices such as electric vehicles. Based on this, an electrocatalyst constructed by metal phase material (MoS2) and semiconductor phase material (SnS2) with ohmic contact is designed for inhibiting the dissolution of lithium polysulfide with improving the reaction kinetics. According to the density-functional theory calculations, it is found that the heterostructured samples with ohmic contacts can effectively reduce the reaction-free energy of lithium polysulfide to accelerate the sulfur redox reaction, in addition to the excellent electron conduction to reduce the overall activation energy. The metallic sulfide can add more sulfophilic sites to promote the capture of polysulfide. Thanks to the ohmic contact design, the carbon nanotube-MoS2-SnS2 achieved a specific capacity of 1437.2 mAh g-1 at 0.1 C current density and 805.5 mAh g-1 after 500 cycles at 1 C current density and is also tested as a pouch cell, which proves to be valuable for practical applications. This work provides a new idea for designing an advanced and efficient polysulfide catalyst based on ohmic contact.

Localized High-Concentration Sulfone Electrolytes with High-Voltage Stability and Flame Retardancy for Ni-Rich Lithium Metal Batteries.

The localized high-concentration electrolyte (LHCE) propels the advanced high-voltage battery system. Sulfone-based LHCE is a transformative direction compatible with high energy density and high safety. In this work, the application of lithium bis(trifluoromethanesulphonyl)imide and lithium bis(fluorosulfonyl)imide (LiFSI) in the LHCE system constructed from sulfolane and 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) is investigated. The addition of diluent causes an increase of contact ion pairs and ionic aggregates in the solvation cluster and an acceptable quantity of free solvent molecules. A small amount of LiFSI as an additive can synergistically decompose with TTE on the cathode and participate in the construction of both electrode interfaces. The designed electrolyte helps the Ni-rich system to cycle firmly at a high voltage of 4.5 V. Even with high mass load and lean electrolyte, it can keep a reversible specific capacity of 91.5% after 50 cycles. The constructed sulfone-based electrolyte system exhibits excellent thermal stability far beyond the commercial electrolytes. Further exploration of in-situ gelation has led to a quick conversion of the designed liquid electrolyte to the gel state, accompanied by preserved stability, which provides a direction for the synergistic development of LHCE with gel electrolytes.

Miniaturized leaky-wave antenna with backward-to-forward beam scanning and suppressed open stop-band based on substrate-integrated plasmonic waveguide.

This work presents a theoretical design and experimental demonstration of a novel miniaturized leaky-wave antenna (LWA) using composite waveguide based on substrate-integrated plasmonic waveguide (SIPW). The SIPW is designed by embedding hybrid dual spoof surface plasmon polariton (SSPP) structure into a three-layer substrate integrated waveguide (SIW). Due to the slow-wave effect of SIPW, the proposed miniaturized composite waveguide forms slowed phase velocity and decreased lower cutoff frequency. To excite backward-to-forward beam scanning mode and suppress the open stop-band, an asymmetric sinusoidal modulated structure is introduced to the surface of the composite waveguide. The experimental results indicate that the proposed SIPW-based LWA can achieve continuous beam scanning from the backward to the forward direction within the bandwidth of 10.6-13.7 GHz, passing through the broadside at 11.6 GHz.

Single-cell RNA sequencing reveals transcriptomic landscape and potential targets for human testicular ageing.

STUDY QUESTION: What is the molecular landscape underlying the functional decline of human testicular ageing? SUMMARY ANSWER: The present study provides a comprehensive single-cell transcriptomic atlas of testes from young and old humans and offers insights into the molecular mechanisms and potential targets for human testicular ageing. WHAT IS KNOWN ALREADY: Testicular ageing is known to cause male age-related fertility decline and hypogonadism. Dysfunction of testicular cells has been considered as a key factor for testicular ageing. STUDY DESIGN, SIZE, DURATION: Human testicular biopsies were collected from three young individuals and three old individuals to perform single-cell RNA sequencing (scRNA-seq). The key results were validated in a larger cohort containing human testicular samples from 10 young donors and 10 old donors. PARTICIPANTS/MATERIALS, SETTING, METHODS: scRNA-seq was used to identify gene expression signatures for human testicular cells during ageing. Ageing-associated changes of gene expression in spermatogonial stem cells (SSCs) and Leydig cells (LCs) were analysed by gene set enrichment analysis and validated by immunofluorescent and functional assays. Cell-cell communication analysis was performed using CellChat. MAIN RESULTS AND THE ROLE OF CHANCE: The single-cell transcriptomic landscape of testes from young and old men was surveyed, revealing age-related changes in germline and somatic niche cells. In-depth evaluation of the gene expression dynamics in germ cells revealed that the disruption of the base-excision repair pathway is a prominent characteristic of old SSCs, suggesting that defective DNA repair in SSCs may serve as a potential driver for increased de novo germline mutations with age. Further analysis of ageing-associated transcriptional changes demonstrated that stress-related changes and cytokine pathways accumulate in old somatic cells. Age-related impairment of redox homeostasis in old LCs was identified and pharmacological treatment with antioxidants alleviated this cellular dysfunction of LCs and promoted testosterone production. Lastly, our results revealed that decreased pleiotrophin signalling was a contributing factor for impaired spermatogenesis in testicular ageing. LARGE SCALE DATA: The scRNA-seq sequencing and processed data reported in this paper were deposited at the Genome Sequence Archive (https://ngdc.cncb.ac.cn/), under the accession number HRA002349. LIMITATIONS, REASONS FOR CAUTION: Owing to the difficulty in collecting human testis tissue, the sample size was limited. Further in-depth functional and mechanistic studies are warranted in future. WIDER IMPLICATIONS OF THE FINDINGS: These findings provide a comprehensive understanding of the cell type-specific mechanisms underlying human testicular ageing at a single-cell resolution, and suggest potential therapeutic targets that may be leveraged to address age-related male fertility decline and hypogonadism. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research and Development Program of China (2022YFA1104100), the National Natural Science Foundation of China (32130046, 82171564, 82101669, 82371611, 82371609, 82301796), the Natural Science Foundation of Guangdong Province, China (2022A1515010371), the Major Project of Medical Science and Technology Development Research Center of National Health Planning Commission, China (HDSL202001000), the Open Project of NHC Key Laboratory of Male Reproduction and Genetics (KF202001), the Guangdong Province Regional Joint Fund-Youth Fund Project (2021A1515110921, 2022A1515111201), and the China Postdoctoral Science Foundation (2021M703736). The authors declare no conflict of interest.

Using TiO2 to capture hot electrons for self-powered position-sensitive photodetection.

As environmental issues arise, the demand for self-powered position-sensitive detectors (PSDs) is increasing because of their advantages in miniaturization and low power consumption. Finding higher efficiency schemes for energy conversion is paramount for realizing high-performance self-powered PSDs. Here, a surface plasmon-based approach was used to improve the energy conversion efficiency, and a plasmon-enhanced lateral photovoltaic effect (LPE) was observed in PSD with TiO2/Au nanorods (NRs)/Si structure. The Au NRs convert absorbed light energy into electricity by generating hot electrons, which are efficiently captured by the TiO2 layer, and the PSD is capable of generating position sensitivity as high as 251.75 mV/mm when illuminated by a 780 nm laser without any external power supply, i.e. about five times higher than similar sensors in previous studies. In addition, the position sensitivity can be tailored by the thickness of TiO2 films. The enhancement mechanism is investigated by a localized surface plasmon (LSP)-driven carrier diffusion model. These findings reveal an important strategy for high sensitivity and low energy cost PSDs while opening up new avenues for energy harvesting self-powered position sensors.

Simultaneous Photocatalytic CO 2 Reduction and H 2 O Oxidation under Non-sacrificial Ambient Conditions.

The utilization of CO2, H2O, and solar energy is regarded as a sustainable route for converting CO2 into chemical feedstocks, paving the way for carbon neutrality and reclamation. However, the simultaneous photocatalytic CO2 reduction and H2O oxidation under non-sacrificial ambient conditions is still a significant challenge. Researchers have carried out extensive exploration and achieved dramatic developments in this area. In this review, we first primarily elucidate the principles of two half-reactions in the photocatalytic conversion of CO2 with H2O, i.e., CO2 reduction by the photo-generated electrons and protons, and H2O oxidation by the photo-generated holes without sacrificial agents. Subsequently, the strategies to promote two half-reactions are summarized, including the vacancy/facet/morphology design, adjacent redox site construction, and Z-scheme heterojunction development. Finally, we present the advanced in situ characterizations and future perspectives in this field. This review aims to provide fresh insights into effectively simultaneous photocatalytic CO2 reduction and H2O oxidation under non-sacrificial ambient conditions.

5-Methoxytryptophan enhances the sensitivity of sorafenib on the inhibition of proliferation and metastasis for lung cancer cells.

BACKGROUND: Lung cancer is a leading cause of cancer-related mortality worldwide, and effective therapies are limited. Lung cancer is a leading cause of cancer-related mortality worldwide with limited effective therapy. Sorafenib is a multi-tyrosine kinase inhibitor frequently used to treat numerous types of malignant tumors. However, it has been demonstrated that sorafenib showed moderate antitumor activity and is associated with several side effects in lung cancer, which restricted its clinical application. This study aimed to examine the antitumor effect of the combination treatment of sorafenib and 5-methoxytryptophan (5-MTP) on cell growth and metastasis of Lewis lung carcinoma (LLC) cells. METHOD: The anticancer effect of the combination treatment of sorafenib and 5-MTP was determined through cytotoxicity assay and colony forming assays. The mechanism was elucidated using flow cytometry and western blotting. Wound healing and Transwell assays were conducted to evaluate the impact of the combination treatment on migration and invasion abilities. An in vivo model was employed to analyze the effect of the combination treatment on the tumorigenic ability of LLC cells. RESULT: Our results demonstrated that the sorafenib and 5-MTP combination synergistically reduced viability and proliferation compared to sorafenib or 5-MTP treatment alone. Reduction of cyclin D1 expression was observed in the sorafenib alone or combination treatments, leading to cell cycle arrest. Furthermore, the sorafenib-5-MTP combination significantly increased the inhibitory effect on migration and invasion of LLC cells compared to the single treatments. The combination also significantly downregulated vimentin and MMP9 levels, contributing to the inhibition of metastasis. The reduction of phosphorylated Akt and STAT3 expression may further contribute to the inhibitory effect on proliferation and metastasis. In vivo, the sorafenib-5-MTP combination further reduced tumor growth and metastasis compared to the treatment of sorafenib alone. CONCLUSIONS: In conclusion, our data indicate that 5-MTP sensitizes the antitumor activity of sorafenib in LLC cells in vitro and in vivo, suggesting that sorafenib-5-MTP has the potential to serve as a therapeutic option for patients with lung cancer.

The Construction of Novel Spirocyclic Frameworks with Cyclobutane through Rh(III)-Catalyzed [3 + 2]-Annulation between Quinoxalines and Alkynylcyclobutanols.

An effective synthesis strategy for the preparation of 1'H-spiro[indene-1,2'-quinoxaline] has been developed. This involves a Rh(III)-catalyzed [3 + 2]-annulation of quinoxalines with alkynylcyclobutanols. The developed protocol offers a straightforward method for the preparation of versatile heterocyclic compounds with a four-membered ring and is compatible with a wide range of functional groups.

Rhodium(III)-Catalyzed Annulation Synthesis of Difluorinated Quinazolinone Derivatives Using an Amide Carbonyl as the Directing Group.

The use of amide carbonyl groups of substrates as weakly coordinating directing groups has received a significant amount of attention. Recently, difluoromethylene alkynes have been successfully used in fluorination reactions, resulting in the preparation of various fluorine-containing compounds. This work describes a [4+2] annulation method for creating a range of fluorinated quinolino[2,1-b]quinazolinone derivatives. The derivatives are formed through Rh(III)-catalyzed cascade cyclization of 3-phenylquinazolinones and gem-difluoromethylene alkynes.

Pd(II)-Catalyzed ß-C(sp3)-H Alkynylation of Alanine in Di- and Tripeptides with Asn as an Endogenous Directing Group.

The introduction of alkyne moieties into peptides remains in demand as it represents a promising approach for further structural diversification of peptides. Herein, we describe the Pd(II)-catalyzed C(sp3)-H alkynylation of Ala-Asn-embedded di- and tripeptides using Asn as the endogenous lead group. In addition, a key building block for the glycopeptide Tyc4PG-14 and Tyc4PG-15 was produced by our methodology.

Role of autophagy in myocardial remodeling after myocardial infarction.

Autophagy is the process of reusing the body's senescent and damaged cell components, which can be regarded as the cellular circulatory system. There are three distinct forms of autophagy: macro-autophagy, micro-autophagy, and chaperone-mediated autophagy. In the heart, autophagy is regulated mainly through mitophagy due to the metabolic changes of cardiomyocytes caused by ischemia and hypoxia. Myocardial remodeling is characterized by gradual heart enlargement, cardiac dysfunction, and extraordinary molecular changes. Cardiac remodeling after myocardial infarction is almost inevitable, which is the leading cause of heart failure. Autophagy has a protective effect on myocardial remodeling improvement. Autophagy can minimize cardiac remodeling by preventing misfolded protein accumulation and oxidative stress. This review summarizes the nestest molecular mechanisms of autophagy and myocardial remodeling, the protective effects, and the new target of autophagy medicine in cardiac remodeling. The future development and challenges of autophagy in heart disease are also summarized.

High-Performance Ir1/CeO2 Single-Atom Catalyst for the Oxidation of Toluene.

The elimination of toluene is an obligatory target with increasing VOC emission in recent years. This study successfully prepared a single-atom Ir catalyst (Ir1/CeO2) by a simple incipient wetness impregnation method, confirmed by in situ CO DRIFTS and AC-HAADF-STEM. Compared to the cluster Ir catalyst (Ir/CeO2-C), Ir1/CeO2 exhibited excellent catalytic performance, stability, and water resistance for the oxidation of toluene. By Raman, H2-TPR, O2-TPD, and XPS experiments, abundant oxygen defects and a unique Ir3+-Ov-Ce3+ structure were formed for the Ir1/CeO2 sample because it had a lower oxygen vacancy formation energy. Furthermore, the DFT results revealed that the Ir1/CeO2 sample had a lower ring-opening energy barrier and adsorption energy of the ring-opening products, which was the rate-determining step for the oxidation of toluene. This work provides instructive insights into the construction of Ir/CeO2 catalysts for the highly efficient removal of VOCs.

Copper-promoted ortho-directed C-H amination of 2-arylpyridines with NH-heterocycles.

Copper-mediated C-N coupling of azaheterocycles with aryl C-H bonds has been realized for the synthesis of N-(hetero)arylated heteroarenes. This method is characterized by high regioselectivity, atom economy and a wide substrate scope of 2-arylazines and azaheterocycles. The corresponding C-N coupling products were shown to undergo further transformation to synthesize more complex molecules.