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While the PROTAC approach to targeted protein degradation greatly benefits from rational design, the discovery of molecular glue degraders currently relies on screening strategies. Here, we describe screening of a library containing 3,630 cereblon binders against a panel of 9 patient-derived cancer cell lines. This led to the discovery of SJ7590, a potent degrader of CK1α, IKZF1 and IKZF3 proteins. Through a structure-guided optimization strategy we developed SJ3149, a uniquely potent and selective CK1α degrader. The crystal structure of the CK1α+CRBN+DDB1+SJ3149 quaternary complex provided a rationale for the improved degradation properties via direct contacts between SJ3149 and CK1α. In a panel of 115 human cancer cell lines SJ3149 displayed broad antiproliferative activity. This activity profile, which showed statistically significant correlation with MDM2 inhibitor Nutlin-3a, suggests potential for the development of treatments for hematological cancers, as well as solid tumors.

Since the end of 2019, a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has deprived numerous lives worldwide, called COVID-19. Up to date, omicron is the latest variant of concern, and BA.5 is replacing the BA.2 variant to become the main subtype rampaging worldwide. These subtypes harbor an L452R mutation, which increases their transmissibility among vaccinated people. Current methods for identifying SARS-CoV-2 variants are mainly based on polymerase chain reaction (PCR) followed by gene sequencing, making time-consuming processes and expensive instrumentation indispensable. In this study, we developed a rapid and ultrasensitive electrochemical biosensor to achieve the goals of high sensitivity, the ability of distinguishing the variants, and the direct detection of RNAs from viruses simultaneously. We used electrodes made of MXene-AuNP (gold nanoparticle) composites for improved sensitivity and the CRISPR/Cas13a system for high specificity in detecting the single-base L452R mutation in RNAs and clinical samples. Our biosensor will be an excellent supplement to the RT-qPCR method enabling the early diagnosis and quick distinguishment of SARS-CoV-2 Omicron BA.5 and BA.2 variants and more potential variants that might arise in the future.

LLC half-bridge converters have been extensively studied in low power industrial applications. However, the phase shift angle between the voltage and current of the LLC resonant network makes the converter have power circulation, that is, backflow power. The increase of the backflow power will increase the converter conduction loss, which restricts the improvement of the converter efficiency. The existing literature often improves the backflow power from the control aspect, which greatly increases the control complexity. To solve this problem, this paper proposes an LLC half-bridge resonant converter analysis method that takes the backflow power into account. Based on the analysis of operating mode and AC equivalent model of the converter, backflow power is indirectly characterized by the phase-shift angle of the resonant network voltage and current. Based on this, this paper analyzes the internal relationship between resonant parameters and backflow power to reduce backflow power by optimizing resonant parameters. Under the setting operating conditions, converter can achieve ZVS switching, voltage gain conditions and minimum backflow power. Compared with the existing methods, the proposed optimization method avoids additional auxiliary circuits and control complexity, improves the stability of the circuit. Experimental results verify the accuracy and feasibility of the theoretical analysis.

A mid-infrared laser based analytical approach is newly developed in this study for gas chromatography (GC) separation and carbon compound specific isotope analysis (CSIA) of aromatic organic pollutants in water.

The vinyltrimethoxysilane was utilized to modify the surface of α-AlH3 by a simple surface coating method. The α-AlH3@A171 composite obtained presents excellent stability, regarded as a potential fuel in the field of solid propellants.

The low-temperature CO + NH3 coupling denitration of the Mn/AC catalyst conforms to the L–H mechanism when the temperature is lower than 230 °C and the E–R mechanism when the temperature is higher than 230 °C.

Zn slats compete with CO and NO for the active sites. Cl− not only occupies oxygen vacancies but also inhibits the Oβ migration. SO42− increases the surface acidity and promotes the Oβ supplementation, which inhibits toxicity.

This study aims to explore the influence mechanism of ammonium nitrate produced by ozone denitrification on the crystallization of ammonium sulfate, a by-product of ammonia desulfurization. The laser method was used to study the influence of ammonium nitrate on the solubility and metastable zone width of ammonium sulfate. An experiment on the influence of ammonium nitrate on the particle size of ammonium sulfate was designed, and the influence mechanism was explored through scanning electron microscopy and X-ray diffraction. The findings showed that the addition of ammonium nitrate increased the size and aspect ratio of ammonium sulfate crystals. The addition of ammonium nitrate inhibited the dissolution of ammonium sulfate and widened its metastable zone. The addition of ammonium nitrate covered the active sites of crystal nucleus growth, which inhibited the formation of crystal nuclei to a certain extent, and crystal growth dominated the crystallization process. Moreover, the addition of ammonium nitrate induced the preferred orientation of the specific crystal plane of ammonium sulfate, and the addition of a small concentration of ammonium nitrate decreased the crystallinity of ammonium sulfate. The research results can provide a reference for crystallization optimization and quality improvement of ammonium sulfate in the ammonia desulfurization process.

Anaplastic thyroid carcinoma (ATC) is the most lethal thyroid carcinoma. Doxorubicin (DOX) is the only drug approved for anaplastic thyroid cancer treatment, but its clinical use is restricted due to irreversible tissue toxicity. Berberine (BER), an isoquinoline alkaloid extracted from Coptidis Rhizoma, has been proposed to have antitumor activity in many cancers. However, the underlying mechanisms by which BER regulates apoptosis and autophagy in ATC remain unclear. Thus, the present study aimed to assess the therapeutic effect of BER in CAL-62 and BHT-101 cells as well as the underlying mechanisms. In addition, we assessed the antitumor effects of a combination of BER and DOX in ATC cells. The present results showed that BER significantly inhibited cell growth and induced apoptosis in ATC cells. BER treatment also significantly upregulated the expression of LC3B-II and increased the number of GFP-LC3 puncta in ATC cells, suggesting that BER induced a high level of autophagy. Inhibition of autophagy by 3-methyladenine (3-MA) suppressed BER-induced autophagic cell death, which confirmed the anticancer role of autophagy induced by BER. Moreover, BER induced the generation of reactive oxygen species (ROS). N-acetylcysteine (NAC), a potential ROS scavenger, substantially suppressed the expression of autophagy-regulated proteins and apoptosis proteins induced by BER. Moreover, BER and DOX cooperated to promote apoptosis and autophagy in ATC cells. Mechanistically, we demonstrated that BER regulated the autophagy and apoptosis of human ATC cells through the PI3K/AKT/mTOR pathways. Taken together, the present findings indicated that BER induces apoptosis and autophagic cell death by activating ROS and regulating the PI3K/AKT/mTOR signaling pathway.

This paper presents a novel seamless switching technology between different operating conditions of the Unified Power Quality Conditioner (UPQC) with the energy storage system. Frequent start and stop of the series inverter will cause shock and loss under the conventional control method. Moreover, it is a key issue to achieve seamless switching when the UPQC operating condition changes. This paper proposes an improved power angle control (PAC) method to solve these problems. An agile power angle is calculated by this method under stable operating conditions. This feature enables the series inverter to share the load reactive power with the shunt inverter. On the other hand, both the series and shunt inverters are in an easy-to-switch operating state which can help achieve better seamless switching between different operating conditions. Simulation results show the shunt inverter capacity can be reduced up to 47% due to the reactive power sharing by both the inverters which means the reactive power burden of the shunt inverter is great lightened. It is also found that the switching time is about 300μs faster and the maximum voltage fluctuation amplitude is about 90V smaller under improved PAC than the conventional control method.

Liver fibrosis is the most common pathway in most types of chronic liver damage, characterized by an imbalance of ECM degradation and synthesis. Saikosaponin-d (SSd) possesses anti-inflammatory and anti-fibrotic effects. However, the underlying mechanism by which SSd represses hepatic stellate cell (HSC) activation remains unclear. Here, we found that SSd remarkably alleviated carbon tetrachloride (CCl4)-induced liver fibrosis, as evidenced by decreased collagen levels and profibrotic marker (COl1a1 and α-smooth muscle actin (SMA)) expression. SSd repressed CCl4-induced NOD-like receptor family pyrin-domain-containing-3 (NLRP3) activation in fibrotic livers, as suggested by decreased levels of NLRP3, IL-18, and IL-β. The primary HSCs of CCl4 mice exhibited a significant increase in profibrotic marker expression and NLRP3 activation, but SSd treatment reversed this effect. SSd also repressed TGF-β-induced profibrotic marker expression and NLRP3 activation in vitro. Mechanistically, TGF-β decreased the expression of estrogen receptor-β (ERβ) in HSCs, whereas SSd treatment reversed this effect. ERβ inhibition enhances NLRP3 activation in HSCs. More importantly, ERβ or NLRP3 inhibition partially destroyed the function of SSd in liver fibrosis. In summary, the current data suggest that SSd prevents hepatic fibrosis by regulating the ERβ/NLRP3 inflammasome pathway and suggests SSd as a potential agent for treating liver fibrosis.

We propose a feature color extraction method that improves the accuracy of water quality analysis using a digital image and eliminates the effect of interfering ions and chromogenic agents on the color after a color reaction. The proposed method is based on color deconvolution (CD) combined with machine learning for substance measurement in water. After an ordinary camera acquires the solution image after color reaction, the CD algorithm is applied to extract the feature image, calculate the first-order, second-order, and third-order color moments corresponding to RGB channels, and construct a gradient boosting regression tree prediction model based on color moment features to detect substances in water. In predicting ammonia, nitrite, and orthophosphate concentrations, the mean square error values were 0.01029, 0.00063, and 0.1361, and the mean absolute error values were 0.08103, 0.02231, and 0.32886, respectively. There was no significant difference in the results of the comparative spectrophotometric method on the actual water samples. The spiked recoveries of the samples ranged from 94% to 120%, confirming that the method can effectively measure the content of substances in water.

Numerical investigations were conducted of the plasmonically induced transparency (PIT) effect observed in a metal–insulator–metal waveguide coupled to asymmetric three-rectangle resonators, wherein, of the two PIT peaks that were generated, one PIT peak fell while the other PIT peak rose. PIT has been widely studied due to its sensing, slow light, and nonlinear effects, and it has a high potential for use in optical communication systems. To gain a better understanding of the PIT effect in multi-rectangle resonators, its corresponding properties, effects, and performance were numerically investigated based on PIT peak fluctuations. By modifying geometric parameters and filling dielectrics, we not only realized the off-to-on PIT optical response within single or double peaks but also obtained the peak fluctuation. Furthermore, our findings were found to be consistent with those of finite element simulations. These proposed structures have wide potential for use in sensing applications.

Background: Cerebrospinal fluid (CSF) shunt intervention is currently the standard and most effective treatment for idiopathic normal-pressure hydrocephalus (iNPH). However, many patients do not undergo surgery due to various reasons. The study aimed to assess the efficacy and safety of methazolamide (MTZ) in the treatment of iNPH. Methods: A 12-week randomized, double-blind, drug-placebo clinical studywas conducted at the Aviation General Hospital. Participants with a diagnosis of possible or probable iNPH according to Japanese second iNPH guidelines were consecutively recruited from September 2019 to May 2021. All patients were inoperable or had refused surgical treatment due to various reasons. The patients were assigned (2:1) to the MTZ or placebo group via a computer-generated randomization list. The gait and cognition function were assessed, and brain MRI scans were taken before and 12 weeks after drug administration. The primary endpoint was the difference change in the Boon gait sum score relative to baseline between the drug and placebo groups. Secondary endpoints were differences in MMSE and MOCA scores. In addition, the adverse reactions were also monitored. Results: Twenty participants were randomly included in the MTZ group and 12 in the placebo group. A total of 26 patients, 17 in the MTZ and 9 in the placebo group, were included in the final efficacy analysis. The difference in Boon sum score relative to baseline between the groups was -6.06 points (95% CI, -9.37 to -2.75; p =0.001) after 12 weeks of treatment. However, there was no significant difference in the MMSE and MoCA scores between the drug and placebo groups (MMSE 0.36, 95% CI, -2.36 to 3.09; p = 0.78; MoCA 0.001, 95% CI, -1.98 to 1.98; p = 1.00). No serious adverse reactions such as hypokalemia or acidosis occurred in any of the patients. Conclusions: MTZ significantly improved the gait of iNPH patients without any adverse effects. Large sample studies are needed for further confirmation of our results.

To explore the mechanism of low-temperature carbon monoxide and ammonia (CO + NH

With the rising need for energy resources, considerable work has done for building novel energy storage technologies. Supercapacitors (SCs) and batteries are a highly competitive choice for electrochemical energy storage devices (EESDs) due to their ultrahigh power density, improved rate capability, long-term cyclability, and remarkable safety. Because of their novel properties such as high mechanical flexibility, large specific surface area (SSA), chemical stability, and superior electric and thermal conductivities, graphene-based nanomaterials (NMs) have attracted considerable attention as alternative electrode materials for EESDs. Graphene is gaining a lot of interest since it has amazing qualities including 230 000 cm2 V-1 s-1 charge mobility, 3000 W m-1 K-1 thermal conductivity, 2.3% visible light absorption, 130 GPa mechanical strength, and 2600 m2 g-1 specific surface area (SSA). Mechanical exfoliation, reduction of graphene-oxide, chemical vapor deposition (CVD), and epitaxial growth of graphene-NMs are some of the synthetic procedures that can change these characteristics. Despite much effort, the detailed screening of high-performance electrode materials, such as graphene-based NMs, is still necessary. We covered the recent advancements in graphene-based NM research and development for high-performance batteries and SCs for specific applications in the next generation and smart electronics in this study. First, we discuss rechargeable batteries, a new-concept based on graphene with high energy density, longer life, improved safety, and shape-diversity capabilities in order to meet the needs of future electronics. Second, we discuss SCs for the present advanced nanotechnologies that outperform batteries with respect to power density, cyclability, quick charging/discharging rates capability, straightforward principles, high activity of the charge circulation, and low maintenance expenditure, including electrical double layer capacitors (EDLCs) and pseudocapacitors (PCs). Finally, graphene-based electrodes used in ESDs with their prospects and problems are briefly reviewed.

Background Depression is a recurrent and devastating mental disease that is highly prevalent worldwide. Prolonged exposure to stressful events or a stressful environment is detrimental to mental health. In recent years, an inflammatory hypothesis has been implicated in the pathogenesis of stress-induced depression. However, less attention has been given to the initial phases, when a series of stress reactions and immune responses are initiated. Peripheral CD4+ T cells have been reported as the major contributors to the occurrence of mental disorders. Chronic stress exposure-evoked release of cytokines can promote the differentiation of peripheral CD4+ cells into various phenotypes. Among them, Th17 cells have attracted much attention due to their high pathogenic potential in central nervous system (CNS) diseases. Thus, we intended to determine the crucial role of CD4+ Th17 cells in the development of specific subtypes of depression and unravel the underpinnings of their pathogenetic effect. Methods In the present research, a daily 6-h restraint stress paradigm was employed in rats for 28 successive days to mimic the repeated mild and predictable, but inevitable environmental stress in our daily lives. Then, depressive-like symptoms, brain–blood barrier (BBB) permeability, neuroinflammation, and the differentiation and functional changes of CD4+ cells were investigated. Results We noticed that restrained rats showed significant depressive-like symptoms, concomitant BBB disruption and neuroinflammation in the dorsal striatum (DS). We further observed a time-dependent increase in thymus- and spleen-derived naïve CD4+ T cells, as well as the aggregation of inflammatory Th17 cells in the DS during the period of chronic restraint stress (CRS) exposure. Moreover, increased Th17-derived cytokines in the brain can further impair the BBB integrity, thus allowing more immune cells and cytokines to gain easy access to the CNS. Our findings suggested that, through a complex cascade of events, peripheral immune responses were propagated to the CNS, and gradually exacerbated depressive-like symptoms. Furthermore, inhibiting the differentiation and function of CD4+ T cells with SR1001 in the early stages of CRS exposure ameliorated CRS-induced depressive-like behaviour and the inflammatory response. Conclusions Our data demonstrated that inflammatory Th17 cells were pivotal in accelerating the onset and exacerbation of depressive symptoms in CRS-exposed rats. This subtype of CD4+ T cells may be a promising therapeutic target for the early treatment of stress-induced depression.

The constitutive androstane receptor (CAR), a known xenobiotic sensor, plays an important role in drug metabolism by regulating numerous genes. The polycyclic aromatic hydrocarbon pyrene, an environmental pollutant, is a CAR activator and induces mouse hepatotoxicity via CAR. Here, we investigate the molecular mechanisms of the inflammatory response in pyrene-caused mice liver injury.Effects of pyrene on the liver were investigated in wild-type and CAR knockout (KO) mice. Levels of pyrene and its urinary metabolite were analysed by high performance liquid chromatography (HPLC). Inflammatory responses were measured by qRT-PCR, western blotting, and ELISA for cytokines.Serum amyloid A proteins (SAAs) were markedly increased in the liver and serum of pyrene-exposed wild-type mice. IL-17-producing helper T cells (Th17 cells) and IL-17 levels were increased in the liver of pyrene-exposed wild-type mice. Hepatic mRNA levels of inflammatory cytokines including IL-1β, IL-6 and TNFα, and serum IL-6 levels were significantly elevated in pyrene-treated wild-type mice. However, these changes were not observed in CAR KO mice.CAR plays a crucial role in pyrene-caused mice liver inflammatory response with increased SAAs and Th17 cells. Our results suggest that serum SAAs may be a convenient biomarker for early diagnosis of liver inflammatory response caused by polycyclic aromatic hydrocarbons, including pyrene. CAR and Th17 cells may be potential targets for novel therapeutic strategies for xenobiotic-induced liver inflammation.

Although cancer diagnosis research has continuously made breakthroughs in a single indicator, it is a challenging task to improve its multiple joint indicators. This study proposes a multi-category multi-state information ensemble-based classification method. We fuse protein-coding and non-coding genes to construct co-expression profiles, which ensemble the field information of classical genetics and epigenetics. A hierarchical feature selection algorithm based on control groups is put forward to quickly remove irrelevant and redundant features without the bias caused by unbalanced dataset. Multiple heterogeneous diagnosis models, which ensemble multiple diagnosis model structures and model states, are constructed and a competition mechanism is then introduced to automatically select the best model from multiple heterogeneous models without deeply grasping the positive and negative fusion effects between different algorithms and features. We apply the proposed method to classify three high-incidence cancers, in which the classification accuracy and sensitivity are over 99.23% and the classification specificity is over 97.37%. This illustrates that the proposed method has upgraded the three joint indicators of cancer diagnosis at the same time. Compared with the state-of-the-art classification methods, the classification accuracy has been improved by 2.23–9.23%, the sensitivity by 6.25–37.40%, and the specificity by 0–12.02%. In addition, feature analysis reveals three biological findings.

Two-dimensional (2D) selenium was synthesized successfully in 2017. Its advanced properties, including size-dependent bandgap, excellent environmental robustness, strong photoluminescence effect, anisotropic thermal conductivity, and high photoconductivity, render it and selenium-based composites a promising candidate for various device applications. These include batteries, modulators, photodetectors, and photothermal effects in medical applications. However, compared to other commonly used 2D materials, such as graphene, transition metal dichalcogenides, and black phosphorus, 2D Se is much less known. Motivated by the need to overcome this lack of knowledge, this article focuses on recent progress and elucidates the crystal structure, synthesis methods, physical properties, applications, challenges, and prospects of 2D Se nanoflakes.

The controlled introduction of elastic strains is an appealing strategy for modulating the physical properties of semiconductor materials. With the recent discovery of large elastic deformation in nanoscale specimens as diverse as silicon and diamond, employing this strategy to improve device performance necessitates first-principles computations of the fundamental electronic band structure and target figures-of-merit, through the design of an optimal straining pathway. Such simulations, however, call for approaches that combine deep learning algorithms and physics of deformation with band structure calculations to custom-design electronic and optical properties. Motivated by this challenge, we present here details of a machine learning framework involving convolutional neural networks to represent the topology and curvature of band structures in k-space. These calculations enable us to identify ways in which the physical properties can be altered through “deep” elastic strain engineering up to a large fraction of the ideal strain. Algorithms capable of active learning and informed by the underlying physics were presented here for predicting the bandgap and the band structure. By training a surrogate model with ab initio computational data, our method can identify the most efficient strain energy pathway to realize physical property changes. The power of this method is further demonstrated with results from the prediction of strain states that influence the effective electron mass. We illustrate the applications of the method with specific results for diamonds, although the general deep learning technique presented here is potentially useful for optimizing the physical properties of a wide variety of semiconductor materials. Nanyang Technological University Published version The computations involved in this work were conducted on the computer cluster at Skolkovo Institute of Science and Technology (Skoltech) CEST Multiscale Molecular Modelling group and Massachusetts Institute of Technology (MIT) Nuclear Science Engineering department. E.T., Z.S., A.S., and J.L. acknowledge support by the Skoltech-MIT Next Generation Program 2016-7/NGP. E.T. and A.S. acknowledge support by the Center for Integrated Nanotechnologies, an Office of Science User Facility operated for the U.S. Department of Energy Office of Science by Los Alamos National Laboratory (Contract 89233218CNA000001) and Sandia National Laboratories (Contract DE-NA-0003525). M.D. acknowledges support from MIT J-Clinic for Machine Learning and Health. S.S. acknowledges support from Nanyang Technological University through the Distinguished University Professorship.

Fe-loaded activated carbon (AC) has high surface acidity and more active sites, while manganese-loaded AC has high oxygen content. Coconut husk AC modified by Fe–Mn was studied with the aim of revealing the modification mechanism. First, HNO3/AC was prepared using the nitric acid immersion method. Second, Fe–Mn/AC was prepared using the Fe(NO3)3 and Mn(NO3)2 sequential immersion. The effects of HNO3, Fe(NO3)3, and Mn(NO3)2 on the pore texture and surface chemical characteristics of carbon materials were examined by scanning electron microscopy, Brunauer–Emmett–Teller (BET) analysis, X-ray diffraction and Fourier-transform infrared spectroscopy. The surface topography, pore structure, active material, and functional groups of AC, HNO3/AC, and Fe–Mn/AC were systematically studied. The following results were obtained. The surface of HNO3/AC has more ditches and air voids; the micropores of HNO3/AC are deformed and flattened compared to those of AC. The surface of Fe–Mn/AC exhibits an accumulation phenomenon. MnFe2O4 and FeMn2O4 formed more pore structures. AC and HNO3/AC have numerous micropores. The higher loading quantity of Fe–Mn results in bigger specific surface. The active components of Fe–Mn/AC-1, Fe–Mn/AC-2, Fe–Mn/AC-3, and Fe–Mn/AC-4 are MnFe2O4, Mn0.43Fe2.57O4, Mn3O4, and α-Fe2O3, respectively. The surface functional groups of AC and HNO3/AC are oxygen-containing functional groups. The effect of Fe–Mn modifying conditions on functional group species is rare; however, Fe/AC has more oxygen-containing functional groups. These research findings can aid in the desulfurization and denitrification of the Fe–Mn/AC catalyst.

Objective To analyze perioperative complications, resource consumption, and inpatient mortality of patients who receive total joint arthroplasty (TJA) with a concomitant diagnosis of a primary hypercoagulable state (PHS). The following questions were posed in the present paper. First, do patients undergoing TJA with PHS have increased risk of deep venous thrombosis (DVT), pulmonary embolism (PE), and periprosthetic joint infection (PJI)? Second, what other in‐hospital complications are more likely among PHS patients undergoing TJA? Third, do TJA patients with PHS usually consume greater in‐hospital resources? Fourth, do PHS patients suffer higher mortality rates compared to non‐PHS patients? Finally, have PHS patients received proper anticoagulant management in past arthroplasties? Methods The National Inpatient Sample (NIS) database for the years between 2003 and 2014 was searched to identify patients undergoing primary TJA. Patients with PHS were identified with the ICD‐9‐CM code 289.81. The χ2‐test, the Pearson test, and adjusted multivariate regression analysis were performed to evaluate the difference and odds ratios between the positive and negative diagnosis groups. Results From 2003 to 2014, a total of 2,044,356 patients were identified in the NIS as undergoing primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) in the United States. A total of 4664 patients (0.2%) were identified as having PHS. Compared with the non‐PHS group, TJA patients with PHS had a higher risk of DVT (THA: odds ratio [OR] = 8.343, 95% CI: 5.362–12.982, P, Analysis of the impacts of primary hypercoagulable states in total joint arthroplasty in clinical practice.

By increasing the charging voltage, a cell specific energy of >400 W h kg−1 is achievable with LiNi0.8Mn0.1Co0.1O2 in Li metal batteries. However, stable cycling of high-nickel cathodes at ultra-high voltages is extremely challenging. Here we report that a rationally designed sulfonamide-based electrolyte enables stable cycling of commercial LiNi0.8Co0.1Mn0.1O2 with a cut-off voltage up to 4.7 V in Li metal batteries. In contrast to commercial carbonate electrolytes, the electrolyte not only suppresses side reactions, stress-corrosion cracking, transition-metal dissolution and impedance growth on the cathode side, but also enables highly reversible Li metal stripping and plating leading to a compact morphology and low pulverization. Our lithium-metal battery delivers a specific capacity >230 mA h g−1 and an average Coulombic efficiency >99.65% over 100 cycles. Even under harsh testing conditions, the 4.7 V lithium-metal battery can retain >88% capacity for 90 cycles, advancing practical lithium-metal batteries. Charging at high voltages in principle makes batteries energy dense, but this is often achieved at the cost of the cycling stability. Here the authors design a sulfonamide-based electrolyte to enable a Li metal battery with a state-of-the-art cathode at an ultra-high voltage of 4.7 V while maintaining cyclability.