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Purpose: Mutant isocitrate dehydrogenase 1 (mIDH1) alters the epigenetic regulation of chromatin, leading to a hypermethylation phenotype in adult glioma. This work focuses on identifying gene targets epigenetically dysregulated by mIDH1 to confer therapeutic resistance to ionizing radiation (IR). Experimental Design: We evaluated changes in the transcriptome and epigenome in a radioresistant mIDH1 patient-derived glioma cell culture (GCC) following treatment with an mIDH1-specific inhibitor, AGI-5198. We identified Zinc Finger MYND-Type Containing 8 (ZMYND8) as a potential target of mIDH1 reprogramming. We suppressed ZMYND8 expression by shRNA knockdown and genetic knockout (KO) in mIDH1 glioma cells and then assessed cellular viability to IR. We assessed the sensitivity of mIDH1 GCCS to pharmacologic inhibition of ZMYND8-interacting partners: HDAC, BRD4, and PARP. Results: Inhibition of mIDH1 leads to an upregulation of gene networks involved in replication stress. We found that the expression of ZMYND8, a regulator of DNA damage response, was decreased in three patient-derived mIDH1 GCCs after treatment with AGI-5198. Knockdown of ZMYND8 expression sensitized mIDH1 GCCs to radiotherapy marked by decreased cellular viability. Following IR, mIDH1 glioma cells with ZMYND8 KO exhibit significant phosphorylation of ATM and sustained γH2AX activation. ZMYND8 KO mIDH1 GCCs were further responsive to IR when treated with either BRD4 or HDAC inhibitors. PARP inhibition further enhanced the efficacy of radiotherapy in ZMYND8 KO mIDH1 glioma cells. Conclusions: These findings indicate the impact of ZMYND8 in the maintenance of genomic integrity and repair of IR-induced DNA damage in mIDH1 glioma. See related commentary by Sachdev et al., p. 1648

Yunfei Wei,1,2,* Shiting Tang,1,* Zhouhua Xie,3 Yaoqin He,3 Yunli Zhang,4 Yiju Xie,5 Shijian Chen,1 Liuyu Liu,1 Yayuan Liu,1 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Tuberculosis, The Fourth People’s Hospital of Nanning City, Nanning, People’s Republic of China; 4Department of Neurology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 5Department of Neurology, Wuming hospital of Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China, Tel +86-771-5330705, Fax +86-771-5352627, Email liangzhijian@gxmu.edu.cnObjective: There have been only a few studies of ischemic stroke in patients with pulmonary tuberculosis (pTB). This study aimed to explore the clinical features and the underlying pathogenesis of pulmonary tuberculosis-related ischemic stroke (TBRIS).Methods: Active pulmonary tuberculosis patients with acute ischemic stroke (without conventional vascular risk factors) were recruited as the TBRIS group. Patients who solely had active pulmonary tuberculosis were recruited as the control group (pTB group). Clinical data were collected, and multiple logistic regression analysis was applied to analyze the independent risk factors for TBRIS.Results: A total of 179 TBRIS patients and 179 pTB patients were enrolled. Most (56.42%) of the TBRIS patients experienced the ischemic stroke events within 3 months after the diagnosis of tuberculosis. The multiple logistic regression analysis revealed that an increased mean platelet volume; elevated plasma D-dimer, C-reactive protein, and serum ferritin levels; and an increased monocyte percentage were independent risk factors for TBRIS. The AUC of the identification model was 0.778, with a sensitivity of 70.30% and a specificity of 78.90%.Conclusion: The findings in the present study suggested that most of the TBRIS patients experienced ischemic stroke within 3 months after the diagnosis of tuberculosis. And the more intensive immune response to the tuberculosis infection in the TBRIS group contributed to the initiation of platelet activation and to the development of a hypercoagulable state, which were attributed to the pathogenesis of TBRIS. Index of TBRIS equaling to 0.3234 facilitates clinicians to identify the pTB patients who were at higher risk for TBRIS, and allow physicians to take further effective measures to prevent ischemic stroke in patients with pTB. However, our findings will need to be confirmed by further studies.Keywords: pulmonary tuberculosis, ischemic stroke, tuberculosis-related ischemic stroke, independent risk factor, pathogenesis

Supplementary Figures and Figure Legends

Table S2. Liquid Chromatography and Mass Spectrometry Measurement of 2-hydroxyglutarate in the Conditioned Media of mIDH1 GCCs untreated, treated with vehicle (DMSO), or mIDH1 inhibitor (AGI-5198 or DS1001b)

Purpose:Mutant isocitrate dehydrogenase 1 (mIDH1) alters the epigenetic regulation of chromatin, leading to a hypermethylation phenotype in adult glioma. This work focuses on identifying gene targets epigenetically dysregulated by mIDH1 to confer therapeutic resistance to ionizing radiation (IR).Experimental Design:We evaluated changes in the transcriptome and epigenome in a radioresistant mIDH1 patient-derived glioma cell culture (GCC) following treatment with an mIDH1-specific inhibitor, AGI-5198. We identified Zinc Finger MYND-Type Containing 8 (ZMYND8) as a potential target of mIDH1 reprogramming. We suppressed ZMYND8 expression by shRNA knockdown and genetic knockout (KO) in mIDH1 glioma cells and then assessed cellular viability to IR. We assessed the sensitivity of mIDH1 GCCS to pharmacologic inhibition of ZMYND8-interacting partners: HDAC, BRD4, and PARP.Results:Inhibition of mIDH1 leads to an upregulation of gene networks involved in replication stress. We found that the expression of ZMYND8, a regulator of DNA damage response, was decreased in three patient-derived mIDH1 GCCs after treatment with AGI-5198. Knockdown of ZMYND8 expression sensitized mIDH1 GCCs to radiotherapy marked by decreased cellular viability. Following IR, mIDH1 glioma cells with ZMYND8 KO exhibit significant phosphorylation of ATM and sustained γH2AX activation. ZMYND8 KO mIDH1 GCCs were further responsive to IR when treated with either BRD4 or HDAC inhibitors. PARP inhibition further enhanced the efficacy of radiotherapy in ZMYND8 KO mIDH1 glioma cells.Conclusions:These findings indicate the impact of ZMYND8 in the maintenance of genomic integrity and repair of IR-induced DNA damage in mIDH1 glioma.See related commentary by Sachdev et al., p. 1648

Supplementary Methods

Silicon-vacancy (SiV) centers in diamond are emerging as promising quantum emitters in applications such as quantum communication and quantum information processing. Here, we demonstrate a sub-μs pulsed annealing treatment that dramatically increases the photoluminescence of SiV centers in diamond. Using a silane-functionalized adamantane precursor and a laser-heated diamond anvil cell, the temperature and energy conditions required to form SiV centers in diamond were mapped out via an optical thermometry system with an accuracy of ± 50 K and a 1 μs temporal resolution. Annealing scheme studies reveal that pulsed annealing can obviously minimize the migration of SiV centers out of the diamond lattice, and a 2.5-fold increase in the number of emitting centers was achieved using a series of 200-ns pulses at 50 kHz repetition rate via acousto-optic modulation. Our study provides a novel pulsed annealing treatment approach to improve the efficiency of the creation of SiV centers in diamond.

Background: Deep venous thrombosis (DVT) including limber and pulmonary embolism is a common complication of cancer. DVT and ischemic stroke may independently or jointly lead to poor prognosis in cancer patients. Case presentation: A 36-year-old female patient, received insertion of inferior vena cava filter and oral rivaroxaban for deep venous thrombosis in limbers and pulmonary artery, was suspected of cervical cancer for a three-month history of vaginal discharge and was transferred to our hospital for further treatment. After cervical tissue biopsy and pelvic cavity magnetic resonance imaging (MRI) examination, she was diagnosed with cervical adenocarcinoma (stage Ⅱ A). She discontinued taking oral rivaroxaban two days before surgery. Within 24 hours after ovariohysterectomy, she suffered from ischemic stroke following by pulmonary embolism，and was transferred to the intensive care unit（ICU）and received therapies including mechanical ventilation, mannitol and nadroparin calcium. Nevertheless, she worsened for cerebral hernia. Eventually, her family refused further treatment for her. Conclusions: It was still a challenge for clinicians to prevent arterial and venous thrombosis in cancer patients, especially in perioperative period with elevated risk for ischemic vascular events.

Skiing tourism is a kind of sports tourism product with high participation and high stimulation. With the construction of ski resorts, more and more people understand and participate in skiing tourism, and skiing tourism has gradually become one of the most popular leisure sports and tourism projects in winter. Most of the researches on skiing at home and abroad are based on experimental tests, and few of them involve theoretical modeling. At present, there is still a lack of a platform to comprehensively analyze and deal with skiing. To solve the above problems, this paper takes skiing as the research object. Starting with the related mechanical problems of skiing, the biomechanical model of skiing is established at the same time, to analyze the problems of various technical indexes in the process of skiing by mechanical calculation. The research involves the fields of multibody system dynamics, numerical optimization, mechanical modeling, skiing technical indexes, and so on. In the second part of this paper, based on the skiing motion mechanics model, physical mechanics formula, and load distribution function calculation of multirigid-body system, the sports problems in skiing process are studied.

Shiting Tang,1,* Liuyu Liu,1,* Zhouhua Xie,2 Yaoqin He,2 Yunli Zhang,3 Yiju Xie,4 Shijian Chen,1 Yayuan Liu,1 Yunfei Wei,1,5 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, People’s Republic of China; 2Department of Tuberculosis, The Fourth People’s Hospital of Nanning City, Nanning, People’s Republic of China; 3Department of Neurology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 4Department of Neurology, Wuming Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 5Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China, Email liangzhijian@gxmu.edu.cn Yunfei Wei, Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email danggege@163.comObjective: Ischemic stroke is a common complication in patients with tubercular meningitis (TBM). However, the risk factors for Ischemic stroke in TBM patients are not fully understood, especially in those patients without conventional vascular risk factors. The aim of the present study was to explore the clinical features and independent risk factors for tubercular meningitis-related Ischemic stroke (TBMRIS).Methods: Tubercular meningitis patients with acute Ischemic stroke without conventional vascular risk factors were recruited between July 2010 and July 2020 as the TBMRIS group. Patients who solely had tubercular meningitis were recruited as the control group (TMB group). Demographic characteristics, clinical presentations, and cerebrospinal fluid (CSF) examinations were collected, and multiple logistic regression analysis was applied to analyse the independent risk factors for TBMRIS.Results: A total of 70 TBMRIS patients and 70 TMB patients were enrolled. Most (82.86%) of the TBMRIS patients experienced Ischemic stroke events within 3 months after the diagnosis of tubercular meningitis. The multiple logistic regression analysis revealed that variation in red blood cell distribution width (RDW-CV), mean platelet volume (MVP), C-reactive protein (CRP), CSF glucose and Modified Research Council Grade II (MRC Grade II) were independent risk factors for TBRIS. The AUC of the identification model was 0.808, with a sensitivity of 68.60% and a specificity of 84.30%.Conclusion: This study revealed that RDW-CV, MVP, CRP, CSF glucose and MRC Grade II are potential independent risk factors for TBMRIS. The identification model established in this study may help monitor TBM patients who are at high risk of developing TBMRIS.Keywords: tubercular meningitis, Ischemic stroke, tubercular meningitis-related Ischemic stroke, independent risk factor

The buildup of carbon dioxide in the atmosphere is one of the grand challenges facing society. Addressing this challenge by removing carbon dioxide from the atmosphere or mitigating point source emissions through the separation and concentration of CO2 from these dilute sources requires reductions in energetic and monetary cost relative to traditional thermal and pressure-swing methods. Electrochemical methods of CO2 separation have drawn increasing attention in recent years as potentially cheap, low energy, scalable carbon capture technologies. In this Primer, we provide an overview of the experimentation and analysis needed for the study of electrochemical methods for CO2 separation, including a discussion of the considerations necessary for targeting the application of such techniques. This Primer focuses on ambient temperature techniques such as pH swing and direct redox processes, which utilize similar experimental setups. We include considerations on the choice of redox agent and an outlook on this growing body of research. Experimentation to address real-world conditions, particularly at practical oxygen concentrations and novel system designs that overcome transport limitations or potentially couple capture and CO2 utilization are emerging areas in the field.

Mutant isocitrate dehydrogenase 1 (mIDH1) alters the epigenetic regulation of chromatin, leading to a hypermethylation phenotype in adult glioma. Establishment of glioma-specific methylation patterns by mIDH1 reprogramming drives oncogenic features of cancer metabolism, stemness and therapeutic resistance. This work focuses on identifying gene targets epigenetically dysregulated by mIDH1. Treatment of glioma cells with mIDH1 specific inhibitor AGI-5198, upregulated gene networks involved in replication stress. Specifically, we found that the expression of ZMYND8, a regulator of DNA damage response was decreased in three patient-derived glioma cell cultures (GCC) after treatment with AGI-5198. ZMYND8 functions as a chromatin reader to modulate enhancer activity and recruit DNA repair machinery. Knockdown of ZMYND8 expression sensitized mIDH1 GCCs to radiotherapy marked by decreased cellular viability. Following IR, mIDH1 glioma cells with ZMYND8 knockout (KO) exhibit significant phosphorylation of ATM and sustained γH2AX activation. ZMYND8 KO mIDH1 GCCs were further responsive to IR when treated with either BRD4 or HDAC inhibitors. The accumulation of DNA damage in ZMYND8 KO mIDH1 GCCs promoted the phosphorylation of cell cycle checkpoint proteins Chk1 and Chk2. In addition, the recruitment of ZMYND8 to sites of DNA damage has been shown to be PARP- dependent. PARP inhibition further enhanced the efficacy of radiotherapy in ZMYND8 KO mIDH1 glioma cells. These findings indicate the impact of ZMYND8 in the maintenance of genomic integrity and repair of IR-induced DNA damage in mIDH1 glioma.Translational Relevance:Our understanding of radioresistance mechanisms in patient-derived glioma cell cultures (GCC) that endogenously express mIDH1-R132H are limited. We have uncovered a novel gene target Zinc Finger MYND-Type Containing 8 (ZMYND8) that is downregulated following treatment of human mIDH1 GCCs with mIDH1 specific inhibitors. We demonstrate that suppression of ZMYND8 expression by shRNA knockdown or genetic knockout reduces the cellular viability of mIDH1 GCCs to ionizing radiation (IR). Our findings reveal an epigenetic vulnerability of mIDH1 GCCs to ZMYND8 knockout (KO) which results in impaired resolution of IR-induced DNA damage and induction of cell cycle arrest. Additionally, ZMYND8 KO mIDH1 GCCs display increased radiosensitivity to inhibition of epigenetic regulators BRD4, HDAC, and PARP which could be mediated by enhanced replicative stress.

Phosphate solubilizing bacteria (PSB) induced phosphate precipitation is considered as an effective method for Pb(II) removal through the formation of stable Pb(II)-phosphate compound, but the location of end-products is still unclear. Herein, the PSB strain of Burkholderia cepacia (B. cepacia) coupled with the hydroxyapatite (HAP) was used in this study to investigate the Pb(II) removal mechanism and the biomineralization location. The dissolving phosphate of three particle sizes of HAP and Pb(II) resistant capabilities, and the effect factors such as HAP dosage, initial concentrations of Pb(II), pH, temperature, and different treatments were determined. The results indicated that the highest soluble phosphate could reach 224.85 mg/L in a 200 nm HAP medium and the highest removal efficiency of Pb(II) was about 96.32 %. Additionally, it was interesting that Pb(II) was mainly located in the periplasmic space through the cellular distribution experiment, which was further demonstrated by scanning electron microscope (SEM) and transmission electron microscopy (TEM). Besides, the characterization results showed that the functional groups such as amide, hydroxy, carboxy and phosphate played an important role in Pb(II) biomineralization, and the free Pb(II) in aqueous solution could be transformed into pyromorphite through phosphate dissolution, extracellular adsorption/complexation, and intracellular precipitation.

Basement membrane invasion defines malignant transformation of surface premalignancy. Treatment of oral squamous cell carcinoma (OSCC) cells with the synthetic vitamin A derivative, fenretinide (4HPR), induces numerous cancer-preventive effects including suppression of basement membrane invasion, elimination of anchorage-independent growth, disruption of actin cytoskeletal components and inhibition of the invasion-enabling focal adhesive kinase. The purpose of this study was to elucidate 4HPR’s effects on additional invasion-relevant mechanisms including matrix metalloproteinase (MMP) activation and function, cell–extracellular matrix (ECM) attachments and interaction with a kinase that is essential for the epithelial–myoepithelial transformation i.e. c-Jun NH2-terminal kinase (JNK). Our data revealed that 4HPR binds with high affinity to the ATP-binding site of all three JNK isoforms with concurrent suppression of kinase function. Additional studies showed 4HPR treatment inhibited both OSCC cell–ECM adhesion and MMP activation and function. JNK downregulation and induced expression studies confirmed that the JNK3 isoform conveyed that largest impact on OSCC migration and invasion. Biodegradable polymeric implants formulated to preserve 4HPR’s function and bioavailability were employed to assess 4HPR’s chemopreventive impact on an OSCC tumor induction model. These studies revealed 4HPR local delivery significantly inhibited OSCC tumor size, mitotic indices and expression of the endothelial marker, erythroblast transformation-specific-related gene with concurrent increases in tumor apoptosis (cleaved caspase-3). Collectively, these data show that 4HPR suppresses invasion at multiple sites including ‘outside-in’ signaling, cell–ECM interactions and suppression of MMPs. These functions are also essential for physiologic function. Regulation is therefore essential and reinforces the pharmacologic advantage of local delivery chemopreventive formulations. .

Yayuan Liu,1,&ast; Lizhi Lu,1,&ast; Xuemin Cheng,1 Qixiong Qin,1 Yunfei Wei,2 Dacheng Wang,3 Haihua Li,4 Guohui Li,5 Hongbin Liang,6 Shengyu Li,7 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi Province, People’s Republic of China; 3Department of Neurology, The Ninth Affiliated Hospital of Guangxi Medical University, Beihai, 536000, Guangxi Province, People’s Republic of China; 4Department of Neurology, Fusui County People’s Hospital, Chongzuo, 532100, Guangxi Province, People’s Republic of China; 5Department of Neurology, Wuzhou Red Cross Hospital, Wuzhou, 543002, Guangxi Province, People’s Republic of China; 6Department of Neurology, Cenxi People’s Hospital, Cenxi, 543200, Guangxi Province, People’s Republic of China; 7Department of Neurology, The Affiliated Wuming Hospital of Guangxi Medical University, Nanning, 530100, Guangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530000, People’s Republic of China, Tel +86-771-5330705, Fax +86-771-5352627, Email liangzhijian@gxmu.edu.cnPurpose: To investigate independent risk factors for esophageal cancer-related ischemic stroke (ECIS) and to use them to develop an index of ECIS to help clinicians identify patients at high risk for ECIS or to identify ECIS from other types of ischemic stroke.Methods: We retrospectively enrolled active esophageal cancer (EC) patients with acute ischemic stroke (ECIS group) and patients with active EC without ischemic stroke (EC group), age- and sex-matched with ECIS patients, at seven centers from January 2011 to December 2020. Clinical data and laboratory and imaging findings were collected. Univariate and multivariate analyses were performed to analyze the independent risk factors for ECIS. Optimal cutoffs for sensitivities and specificities were obtained by Youden’s J statistic following a receiver operator characteristic (ROC) analysis of each risk factor and the product of the risk factors.Results: A total of 91 ECIS patients and 91 EC patients were included. Elevated levels of carcinoembryonic antigen (CEA) [odds ratio (OR) = 0.105, 95% confidence interval (CI): 1.051– 1.174, P < 0.001], D-dimer (DD) (OR = 0.003, 95% CI: 1.002– 1.004, P < 0.001), and neutrophil count (OR = 0.857, 95% CI: 1.628– 3.407, P < 0.001) were independent risk factors for ECIS. The area under the curve (AUC) of each independent risk factor and the product of the three independent risk factors were calculated by a receiver operator characteristic (ROC) curve, and the cutoff value from the largest AUC was called the ECIS index.Conclusion: It was suggested that elevated plasma DD and CEA levels and increased neutrophils in EC patients may altogether contribute to the development of ECIS. The index of ECIS may facilitate clinicians to identify patients at high risk for ECIS or to identify ECIS from other etiologic types of ischemic stroke.Keywords: independent risk factors, carcinoembryonic antigen, D-dimer, neutrophil count

Liposomal Amphotericin B, known as AmBisome®, is a life-saving antifungal product that sold $407 million in 2019. AmBisome® has a rather complex physical structure in that Amphotericin B (AmpB) forms a stable ionic complex with the lipid bilayer to maintain AmBisome®'s low toxicity and high stability in systemic circulation. Failed attempts to reproduce AmBisome®'s precise structure has resulted in faster drug release and higher toxicity both in vitro and in vivo. In this study, we established several analytical methodologies to quantify liposomal AmpB components, characterize thermal properties of the liposome, and determine particle size distribution, AmpB aggregation state, and drug release kinetics. We applied these methodologies together with in vitro hemolytic potential and antifungal activity tests to characterize multiple lots of AmBisome® and two generic products approved in India, Phosome® and Amphonex®. We also used Fungizone®, a micellar AmpB formulation, and "leaky" AmpB liposomes as negative controls. Our results showed that Phosome® and Amphonex® were both similar to AmBisome®, while Fungizone® and 'leaky" liposomes exhibited differences in both thermal properties and AmpB aggregation state, leading to faster drug release and higher toxicity. Due to the increased interest of the pharmaceutical industry in making generic AmBisome® and the lack of standard analytical methods to characterize liposomal AmpB products, the methodologies described here are valuable for the development of generic liposomal AmpB products.

Significance Metallic lithium plating on the graphite anode is a predominant cause for capacity decays during the fast charging of lithium-ion batteries. This work studies the lithium-plating phenomenon in a previously neglected thermodynamic perspective, taking into account practical temperature distributions within batteries. We show that elevated temperatures could enhance the equilibrium potential of Li 0 /Li + , making local lithium plating more thermodynamically favorable. Furthermore, lithium-plating patterns are correlated with temperature heterogeneities, confirming the preferential lithium plating at high-temperature regions due to both kinetic and thermodynamic origins. These findings provide possible explanations of the heterogeneous lithium-plating morphology, deepen the understandings on the lithium plating phenomenon, and will guide future strategies to realize the extreme fast charging of lithium-ion batteries.

Inactive components and safety hazards are two critical challenges in realizing high-energy lithium-ion batteries. Metal foil current collectors with high density are typically an integrated part of lithium-ion batteries yet deliver no capacity. Meanwhile, high-energy batteries can entail increased fire safety issues. Here we report a composite current collector design that simultaneously minimizes the ‘dead weight’ within the cell and improves fire safety. An ultralight polyimide-based current collector (9 μm thick, specific mass 1.54 mg cm−2) is prepared by sandwiching a polyimide embedded with triphenyl phosphate flame retardant between two superthin Cu layers (~500 nm). Compared to lithium-ion batteries assembled with the thinnest commercial metal foil current collectors (~6 µm), batteries equipped with our composite current collectors can realize a 16–26% improvement in specific energy and rapidly self-extinguish fires under extreme conditions such as short circuits and thermal runaway. Batteries need to be energy-dense as well as safe. Yi Cui and team develop an ultralight polyimide-based current collector with embedded fire retardants that enables lithium-ion batteries with much-enhanced safety and energy density.

Tumor targeted drug delivery system with high efficiency of tumor accumulation, cell internalization and endosomal escape was considered ideal for cancer therapy. Herein, a cleavable polyethylene glycol (PEG) and octaarginines (R8) co-modified liposome (CL-R8-LP) was developed, in which the cholesterol was used as an alternative anchor to the commonest phospholipids for the diversified development of surface modification. The in vitro hemolysis assay and bio-distribution study demonstrated that CL-R8-LP improved biocompatibility and tumor accumulation compared with the single R8 modified liposomes (R8-LP), since the strong positive charges, toxicity and non-specificity of R8 were efficiently shielded by the outer cleavable PEG. And the cellular uptake, cytotoxicity and apoptosis of CL-R8-LP on C26 cells were much stronger than that of control liposomes in which R8 was not included or exposed. In addition, it was confirmed that CL-R8-LP entered cells via clathrin-mediated endocytosis and the macropinocytosis, and followed by a more efficient endosomal escape compared with R8-LP due to the topology change of R8. The enhanced in vivo delivery efficiency and anti-tumor efficacy were validated in C26 bearing mice. In conclusion, the results demonstrated that CL-R8-LP was a promising vehicle for enhancing the chemotherapy of solid cancers.

Abstract Li metal is the ultimate anode choice due to its highest theoretical capacity and lowest electrode potential, but it is far from practical applications with its poor cycle lifetime. Recent research progresses show that materials designs of interphase and host structures for Li metal are two effective ways addressing the key issues of Li metal anodes. Despite the exciting improvement on Li metal cycling capability, problems still exist with these methodologies, such as the deficient long-time cycling stability of interphase materials and the accelerated Li corrosion for high surface area three-dimensional composite Li anodes. As a result, Coulombic efficiency of Li metal is still not sufficient for full-cell cycling. In the near future, an interphase protected three-dimensional composite Li metal anode, combined with high performance novel electrolytes might be the ultimate solution. Besides, nanoscale characterization technologies are also vital for guiding future Li metal anode designs. Graphic Abstract

The complexation and decomplexation of CO2 with a series of quinones of different basicity during electrochemical cycling in dimethylformamide solutions were studied systematically by cyclic voltammetry. In the absence of CO2, all quinones exhibited two well-separated reduction waves. For weakly complexing quinones, a positive shift in the second reduction wave was observed in the presence of CO2, corresponding to the dianion quinone-CO2 complex formation. The peak position and peak height of the first re-duction wave were unchanged, indicating no formation of complexes between the semiquinones and CO2. The relative heights of both reduction waves remained constant. In the case of strongly complexing quinones, the second reduction wave disappeared while the peak height of the first reduction wave approximately doubled, indicating that the two electrons transferred simultaneously at this potential. The observed voltammograms were rationalized through several equilibrium arguments. Both weakly and strongly complexing quinones underwent either stepwise or concerted mechanisms of oxidation and CO2 dissociation depending on the sweep rate in the cyclic voltammetric experiments. Relative to stepwise oxidation, the concerted process requires a more positive electrode potential to remove the electron from the carbonate complexes to release CO2 and regenerate the quinone. For weakly complexing quinones, the stepwise process corresponds to oxidation of the uncomplexed dianion and accompanying equilibrium shift, while for strongly complexing quinones the stepwise process would correspond to the oxidation of mono(carbonate) dianion to the complexed semiquinone and accompanying equilibrium shift. This study provides a mechanistic interpretation of the interactions that lead to the formation of quinone-CO2 complexes required for the potential development of an energy efficient electrochemical separation process and discusses important considerations for practical implementation of CO2 capture in the presence of oxygen with lower vapor pressure solvents.

Synthetic high-density lipoprotein (sHDL) and rapamycin (Rap) have both been shown to be potential treatments for age-related macular degeneration (AMD). The low aqueous solubility of Rap, however, limits its therapeutic utility. Here we used an Apolipoprotein A-I mimetic peptide and phospholipid-based sHDL for the intravitreal delivery of Rap. By incorporation of Rap in sHDL nanoparticles (sHDL-Rap), we achieve 125-fold increase in drug aqueous concentration. When applied in vitro to retinal pigment epithelium cells, sHDL-Rap exhibited the abilities to efflux cholesterol, neutralize endotoxin, and suppress NF-κB activation. As an mTOR inhibitor, Rap induced autophagy and inhibited NF-κB-mediated pro-inflammatory signaling. Additionally, a greater reduction in lipofuscin accumulation and increased anti-inflammatory effects were achieved by sHDL-Rap relative to free drug or sHDL alone. In vivo studies demonstrated that sHDL reached the target retina pigment epithelium (RPE) layer following intravitreal administration in rats. These results suggest that sHDL-Rap holds potential as a treatment for AMD.

Within the field of carbon capture, electrochemically driven methods have drawn increasing attention due to their ability to operate at ambient temperature, their efficient scaling, and potentially low energetic cost. An important consideration in such systems is the method of gas contacting to enable efficient CO2 separation from the feed gas. Previous flow-based electrochemical processes that enable large-area gas contacting and desorption of concentrated CO2 at a point location all utilize water as the solvent and can require significant water feeds due to high evaporation rates. Here, we demonstrate the use of liquid, redox-active sorbents in a flow system that can decouple the electrode size from gas contacting area. The concept sorbent is a nonvolatile, liquid quinone species that can be reversibly reduced and oxidized to capture and release CO2, respectively. In this initial study, we employ the liquid quinone with sodium salts to achieve sorbent capacities near 2.5M CO2 and couple this sorbent to a ferrocene-derived counter electrolyte in a continuous capture – release process. Through this, we illustrate considerations in the salt choice, counter-electrolyte, and system design to best enable this concept sorbent, and discuss many opportunities for future optimizations.