Recovery of isolated lithium through discharged state calendar ageing.

Rechargeable Li-metal batteries have the potential to more than double the specific energy of the state-of-the-art rechargeable Li-ion batteries, making Li-metal batteries a prime candidate for next-generation high-energy battery technology1-3. However, current Li-metal batteries suffer from fast cycle degradation compared with their Li-ion battery counterparts2,3, preventing their practical adoption. A main contributor to capacity degradation is the disconnection of Li from the electrochemical circuit, forming isolated Li4-8. Calendar ageing studies have shown that resting in the charged state promotes further reaction of active Li with the surrounding electrolyte9-12. Here we discover that calendar ageing in the discharged state improves capacity retention through isolated Li recovery, which is in contrast with the well-known phenomenon of capacity degradation observed during the charged state calendar ageing. Inactive capacity recovery is verified through observation of Coulombic efficiency greater than 100% on both Li||Cu half-cells and anode-free cells using a hybrid continuous-resting cycling protocol and with titration gas chromatography. An operando optical setup further confirms excess isolated Li reactivation as the predominant contributor to the increased capacity recovery. These insights into a previously unknown pathway for capacity recovery through discharged state resting emphasize the marked impact of cycling strategies on Li-metal battery performance.

Dynamic spatial progression of isolated lithium during battery operations.

The increasing demand for next-generation energy storage systems necessitates the development of high-performance lithium batteries1-3. Unfortunately, current Li anodes exhibit rapid capacity decay and a short cycle life4-6, owing to the continuous generation of solid electrolyte interface7,8 and isolated Li (i-Li)9-11. The formation of i-Li during the nonuniform dissolution of Li dendrites12 leads to a substantial capacity loss in lithium batteries under most testing conditions13. Because i-Li loses electrical connection with the current collector, it has been considered electrochemically inactive or 'dead' in batteries14,15. Contradicting this commonly accepted presumption, here we show that i-Li is highly responsive to battery operations, owing to its dynamic polarization to the electric field in the electrolyte. Simultaneous Li deposition and dissolution occurs on two ends of the i-Li, leading to its spatial progression toward the cathode (anode) during charge (discharge). Revealed by our simulation results, the progression rate of i-Li is mainly affected by its length, orientation and the applied current density. Moreover, we successfully demonstrate the recovery of i-Li in Cu-Li cells with >100% Coulombic efficiency and realize LiNi0.5Mn0.3Co0.2O2 (NMC)-Li full cells with extended cycle life.

Interlayer engineering of Fe3GeTe2: From 3D superlattice to 2D monolayer.

The discoveries of ferromagnetism down to the atomically thin limit in van der Waals (vdW) crystals by mechanical exfoliation have enriched the family of magnetic thin films [C. Gong et al., Nature 546, 265-269 (2017) and B. Huang et al., Nature 546, 270-273 (2017)]. However, compared to the study of traditional magnetic thin films by physical deposition methods, the toolbox of the vdW crystals based on mechanical exfoliation and transfer suffers from low yield and ambient corrosion problem and now is facing new challenges to study magnetism. For example, the formation of magnetic superlattice is difficult in vdW crystals, which limits the study of the interlayer interaction in vdW crystals [M. Gibertini, M. Koperski, A. F. Morpurgo, K. S. Novoselov, Nat. Nanotechnol. 14, 408-419 (2019)]. Here, we report a strategy of interlayer engineering of the magnetic vdW crystal Fe3GeTe2 (FGT) by intercalating quaternary ammonium cations into the vdW spacing. Both three-dimensional (3D) vdW superlattice and two-dimensional (2D) vdW monolayer can be formed by using this method based on the amount of intercalant. On the one hand, the FGT superlattice shows a strong 3D critical behavior with a decreased coercivity and increased domain wall size, attributed to the co-engineering of the anisotropy, exchange interaction, and electron doping by intercalation. On the other hand, the 2D vdW few layers obtained by over-intercalation are capped with organic molecules from the bulk crystal, which not only enhances the ferromagnetic transition temperature (TC), but also substantially protects the thin samples from degradation, thus allowing the preparation of large-scale FGT ink in ambient environment.

Electrolytes with moderate lithium polysulfide solubility for high-performance long-calendar-life lithium-sulfur batteries.

Lithium-sulfur (Li-S) batteries with high energy density and low cost are promising for next-generation energy storage. However, their cycling stability is plagued by the high solubility of lithium polysulfide (LiPS) intermediates, causing fast capacity decay and severe self-discharge. Exploring electrolytes with low LiPS solubility has shown promising results toward addressing these challenges. However, here, we report that electrolytes with moderate LiPS solubility are more effective for simultaneously limiting the shuttling effect and achieving good Li-S reaction kinetics. We explored a range of solubility from 37 to 1,100 mM (based on S atom, [S]) and found that a moderate solubility from 50 to 200 mM [S] performed the best. Using a series of electrolyte solvents with various degrees of fluorination, we formulated the Single-Solvent, Single-Salt, Standard Salt concentration with Moderate LiPSs solubility Electrolytes (termed S6MILE) for Li-S batteries. Among the designed electrolytes, Li-S cells using fluorinated-1,2-diethoxyethane S6MILE (F4DEE-S6MILE) showed the highest capacity of 1,160 mAh g-1 at 0.05 C at room temperature. At 60 °C, fluorinated-1,4-dimethoxybutane S6MILE (F4DMB-S6MILE) gave the highest capacity of 1,526 mAh g-1 at 0.05 C and an average CE of 99.89% for 150 cycles at 0.2 C under lean electrolyte conditions. This is a fivefold increase in cycle life compared with other conventional ether-based electrolytes. Moreover, we observed a long calendar aging life, with a capacity increase/recovery of 4.3% after resting for 30 d using F4DMB-S6MILE. Furthermore, the correlation between LiPS solubility, degree of fluorination of the electrolyte solvent, and battery performance was systematically investigated.

Natural polymorphisms in ZMET2 encoding a DNA methyltransferase modulate the number of husk layers in maize.

DNA methylation affects agronomic traits and the environmental adaptability of crops, but the natural polymorphisms in DNA methylation-related genes and their contributions to phenotypic variation in maize (Zea mays) remain elusive. Here, we show that a polymorphic 10-bp insertion/deletion variant in the 3'UTR of Zea methyltransferase2 (ZMET2) alters its transcript level and accounts for variation in the number of maize husk layers. ZMET2 encodes a chromomethylase and is required for maintaining genome-wide DNA methylation in the CHG sequence context. Disruption of ZMET2 increased the number of husk layers and resulted in thousands of differentially methylated regions, a proportion of which were also distinguishable in natural ZMET2 alleles. Population genetic analyses indicated that ZMET2 was a target of selection and might play a role in the spread of maize from tropical to temperate regions. Our results provide important insights into the natural variation of ZMET2 that confers both global and locus-specific effects on DNA methylation, which contribute to phenotypic diversity in maize.

Dendrite-Free Lithium Batteries Enabled by an Artificial High-Dielectric Biopolymer Interface Layer.

Lithium (Li) metal batteries face challenges, such as dendrite growth and electrolyte interface instability. Artificial interface layers alleviate these issues. Here, cellulose nanocrystal (CNC) nanomembranes, with excellent mechanical properties and high specific surface areas, combine with polyvinylidene-hexafluoropropylene (PVDF-HFP) porous membranes to form an artificial solid electrolyte interphase (SEI) layer. The porous structure of PVDF-HFP equalizes the electric field near metallic lithium surfaces. The high mechanical modulus of CNC (6.2 GPa) effectively inhibits dendrite growth, ensures the uniform flow of lithium ions to the lithium metal electrode, and inhibits the growth of lithium dendrites during cycling. The synergy of high polarity ß-phase poly(vinylidene fluoride) (PVDF) and CNC provides over 1000 h of stability for Li//Li batteries. Moreover, Li//LiFePO4 (LFP) full cells with this artificial protective layer perform well at 5 C, showcasing the potential of this film in lithium metal batteries.

Lithiophilic Hydrogen-Substituted Graphdiyne Aerogels with Ionically Conductive Channels for High-Performance Lithium Metal Batteries.

Lithium (Li) metal stands as a promising anode in advancing high-energy-density batteries. However, intrinsic issues associated with metallic Li, especially the dendritic growth, have hindered its practical application. Herein, we focus on molecular combined structural design to develop dendrite-free anodes. Specifically, using hydrogen-substituted graphdiyne (HGDY) aerogel hosts, we successfully fabricated a promising Li composite anode (Li@HGDY). The HGDY aerogel's lithiophilic nature and hierarchical pores drive molten Li infusion and reduce local current density within the three-dimensional HGDY host. The unique molecular structure of HGDY provides favorable bulk pathways for lithium-ion transport. By simultaneous regulation of electron and ion transport within the HGDY host, uniform lithium stripping/platting is fulfilled. Li@HGDY symmetric cells exhibit a low overpotential and stable cycling. The Li@HGDY||lithium iron phosphate full cell retained 98.1% capacity after 170 cycles at 0.4 C. This study sheds new light on designing high-capacity and long-lasting lithium metal anodes.

Electrified Operando-Freezing of Electrocatalytic CO2 Reduction Cells for Cryogenic Electron Microscopy.

The ability to freeze and stabilize reaction intermediates in their metastable states and obtain their structural and chemical information with high spatial resolution is critical to advance materials technologies such as catalysis and batteries. Here, we develop an electrified operando-freezing methodology to preserve these metastable states under electrochemical reaction conditions for cryogenic electron microscopy (cryo-EM) imaging and spectroscopy. Using Cu catalysts for CO2 reduction as a model system, we observe restructuring of the Cu catalyst in a CO2 atmosphere while the same catalyst remains intact in air at the nanometer scale. Furthermore, we discover the existence of a single valence Cu (1+) state and C-O bonding at the electrified liquid-solid interface of the operando-frozen samples, which are key reaction intermediates that traditional ex situ measurements fail to detect. This work highlights our novel technique to study the local structure and chemistry of electrified liquid-solid interfaces, with broad impact beyond catalysis.

Spatially Confined LiF Nanoparticles in an Aligned Polymer Matrix as the Artificial SEI Layer for Lithium Metal Anodes.

The uncontrollable growth of lithium (Li) dendrites and the instability of the Li/electrolyte interface hinder the development of next-generation rechargeable lithium metal batteries. The combination of inorganic nanoparticles and polymers as the artificial SEI layer shows great potential in regulating lithium-ion flux. Here, we design spatially confined LiF nanoparticles in an aligned polymer matrix as the artificial SEI layer. A high dielectric polymer matrix homogenizes the electric field near the surface of lithium metal. Aligned pores with LiF nanoparticles promote the lithium-ion transport across the artificial SEI layer. The synergistic effect of the highly polar ß-phase PVDF and LiF nanoparticles provides high stability over 900 h for the Li//Li symmetrical cell. Besides, a Li//LFP full battery equipped with this artificial layer shows good performance in the commercial carbonate electrolyte, demonstrating the great potential of this protective film in lithium metal batteries.

Recent Advances and Opportunities in Reactivating Inactive Lithium in Batteries.

The loss of active materials is one of the main culprits of the battery failures. As a typical example, the presence of inactive lithium, also known as "dead lithium", contributes to the rapid capacity deterioration and reduces energy output in lithium batteries. This phenomenon has long been recognized as irreversible. In this Minireview, the first of this kind, we aim to summarize the formation of inactive lithium and reassess its impact on battery performance metrics. Additionally, we explore various strategies that have been devised to rejuvenate inactive lithium. This comprehensive overview of the latest advancements in reactivating inactive lithium not only offers insights into restoring capacity and enhancing battery performance metrics but also provides a foundation for future research in reviving other inactive materials found in next-generation batteries, such as lithium metal batteries, lithium-sulfur batteries, other alkali metal batteries, and liquid flow batteries.

Li2MoO4 tailored Anion-enhanced Solvation Sheath Layer Promotes Solution-phase Mediated Li-O2 Batteries.

The high overpotential of Li-O2 batteries (LOBs) is primarily triggered by sluggish charge transfer kinetics at the reaction interfaces. A typical LiBr redox mediator (RM) catalyst can effectively reduce the battery's overpotential. However, it is prone to shuttling and corroding the Li anode, leading to RM loss and reduced energy efficiency. To address these challenges, we introduced Li2MoO4 into the LiBr-containing electrolyte to promote the solution-phase mediated LOBs. This addition tailors the anion-enhanced Li+ solvation sheath layer and forms a robust anion-derived solid electrolyte interphases (SEI) on the Li anode. The robust SEI effectively mitigates the corrosion of soluble Br3-/Br2 and attacks by highly reactive oxygen species. Additionally, the dispersed and high-density Li2MoO4 exhibits strong adsorption capabilities for O2/LiO2 and Br-related species during the discharge/charge process, thereby promoting the growth and decomposition of Li2O2 in the solution phase and inhibiting the shuttle effect of Br-related species in LOBs. Consequently, the LOBs demonstrate exceptional cycling stability (415 cycles) and high energy efficiency (86.2%), paving the way for the sustainable development and practical application of these battery systems.

Underpotential lithium plating on graphite anodes caused by temperature heterogeneity.

Rechargeability and operational safety of commercial lithium (Li)-ion batteries demand further improvement. Plating of metallic Li on graphite anodes is a critical reason for Li-ion battery capacity decay and short circuit. It is generally believed that Li plating is caused by the slow kinetics of graphite intercalation, but in this paper, we demonstrate that thermodynamics also serves a crucial role. We show that a nonuniform temperature distribution within the battery can make local plating of Li above 0 V vs. Li0/Li+ (room temperature) thermodynamically favorable. This phenomenon is caused by temperature-dependent shifts of the equilibrium potential of Li0/Li+ Supported by simulation results, we confirm the likelihood of this failure mechanism during commercial Li-ion battery operation, including both slow and fast charging conditions. This work furthers the understanding of nonuniform Li plating and will inspire future studies to prolong the cycling lifetime of Li-ion batteries.

Heat Conductor-Insulator Transition in Electrochemically Controlled Hybrid Superlattices.

Designing materials with ultralow thermal conductivity has broad technological impact, from thermal protection to energy harvesting. Low thermal conductivity is commonly observed in anharmonic and strongly disordered materials, yet a microscopic understanding of the correlation to atomic motion is often lacking. Here we report that molecular insertion into an existing two-dimensional layered lattice structure creates a hybrid superlattice with extremely low thermal conductivity. Vibrational characterization and ab initio molecular dynamics simulations reveal strong damping of transverse acoustic waves and significant softening of longitudinal vibrations. Together with spectral correlation analysis, we demonstrate that the molecular insertion creates liquid-like atomic motion in the existing lattice framework, causing a large suppression of heat conduction. The hybrid materials can be transformed into solution-processable coatings and used for thermal protection in wearable electronics. Our work provides a generic mechanism for the design of heat insulators and may further facilitate the engineering of heat conduction based on understanding atomic correlations.

Stereotactic body radiotherapy plus pembrolizumab and trametinib versus stereotactic body radiotherapy plus gemcitabine for locally recurrent pancreatic cancer after surgical resection: an open-label, randomised, controlled, phase 2 trial.

BACKGROUND: There is paucity of investigations into immunotherapy or targeted therapy for postoperative locally recurrent pancreatic cancer. We aimed to assess the efficacy of stereotactic body radiotherapy (SBRT) plus pembrolizumab and trametinib in these patients. METHODS: In this open-label, randomised, controlled, phase 2 study, participants were recruited from Changhai Hospital affiliated to the Naval Medical University, Shanghai, China. Eligible patients were aged 18 years or older with histologically confirmed pancreatic ductal adenocarcinoma characterised by mutant KRAS and positive immunohistochemical staining of PD-L1, Eastern Cooperative Oncology Group performance status of 0 or 1, and documented local recurrence after surgery followed by chemotherapy (mFOLFIRINOX [ie, 5-fluorouracil, oxaliplatin, irinotecan, and folinic acid] or 5-fluorouracil). Eligible participants were randomly assigned (1:1) using an interactive voice or web response system, without stratification, to receive SBRT with doses ranging from 35-40 Gy in five fractions, intravenous pembrolizumab 200 mg once every 3 weeks, and oral trametinib 2 mg once daily or SBRT (same regimen) and intravenous gemcitabine (1000 mg/m2) on day 1 and 8 of a 21-day cycle for eight cycles until disease progression, death, unacceptable toxicity, or consent withdrawal. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the as-treated population in all participants who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02704156, and is now complete. FINDINGS: Between Oct 10, 2016, and Oct 28, 2017, 198 patients were screened, of whom 170 patients were enrolled and randomly assigned to receive SBRT plus pembrolizumab and trametinib (n=85) or SBRT plus gemcitabine (n=85). As of the clinical cutoff date (Nov 30, 2020), median follow-up was 13·1 months (IQR 10·2-17·1). Median overall survival was 14·9 months (12·7-17·1) with SBRT plus pembrolizumab and trametinib and 12·8 months (95% CI 11·2-14·4) with SBRT plus gemcitabine (hazard ratio [HR] 0·69 [95% CI 0·51-0·95]; p=0·021). The most common grade 3 or 4 adverse effects were increased alanine aminotransferase or aspartate aminotransferase (ten [12%] of 85 in SBRT plus pembrolizumab and trametinib group vs six [7%] of 85 in SBRT plus gemcitabine group), increased blood bilirubin (four [5%] vs none), neutropenia (one [1%] vs nine [11%]), and thrombocytopenia (one [1%] vs four [5%]). Serious adverse events were reported by 19 (22%) participants in the SBRT plus pembrolizumab and trametinib group and 12 (14%) in the SBRT plus gemcitabine group. No treatment-related deaths occurred. INTERPRETATION: The combination of SBRT plus pembrolizumab and trametinib could be a novel treatment option for patients with locally recurrent pancreatic cancer after surgery. Phase 3 trials are needed to confirm our findings. FUNDING: Shanghai Shenkang Center and Changhai Hospital. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

A Designed Lithiophilic Carbon Channel on Separator to Regulate Lithium Deposition Behavior.

Issues with unstable SEI formation and uncontrollable lithium dendrite growth impede the practical use of lithium anode in high-energy batteries. Herein, a lithiophilic carbon channel on separator is designed to regulate lithium deposition behavior. The designed channel is formed by carbon nanosheet with cubic cavity (CNCC) prepared by hard template method. The CNCC with a large specific surface area and good electrolyte wettability can effectively reduce the local current density. Besides, the CNCC coated separator with high Young's modulus can mechanically inhibit the growth of lithium dendrites. Notably, CNCC coating can become lithiophilic during lithium plating/striping process, which is beneficial for homogeneous lithium deposition and low lithium nucleation overpotential. As a result, based on the CNCC coated separator, the symmetric Li|Li cell cycle over 2600h at 6 mA cm-2 for 2 mAh cm-2 , while the Li|Cu cell reaches average Coulombic efficiency of 98.5% at 2 mA cm-2 for 2 mAh cm-2 .

Safety and Efficacy Study of Neoadjuvant Radiohormonal Therapy for Oligometastatic Prostate Cancer: Protocol of an Open-Label, Dose-Escalation, Single-Centre Phase I/II Clinical Trial.

BACKGROUND: The optimal treatment for oligometastatic prostate cancer (OMPC) is still on its way. Accumulating evidence has proven the safety and feasibility of radical prostatectomy and local or metastasis-directed radiotherapy for oligometastatic patients. The aim of this trial is to demonstrate the safety and feasibility outcomes of metastasis-directed neoadjuvant radiotherapy (naRT) and neoadjuvant androgen deprivation therapy (naADT) followed by robotic-assisted radical prostatectomy (RARP) for treating OMPC. METHODS: The present study will be conducted as a prospective, open-label, dose-escalation, phase I/II clinical trial. The patients with oligometastatic PCa will receive 1 month of naADT, followed by metastasis-directed radiation and abdominal or pelvic radiotherapy. Then, radical prostatectomy will be performed at intervals of 4-8 weeks after radiotherapy, and ADT will be continued for 2 years. The primary endpoints of the study are safety profiles, assessed by the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading scale, and perioperativemorbidities, assessed by the Clavien-Dindo classification system. The secondary endpoints include positive surgical margin (pSM), biochemical recurrence-free survival (bPFS), radiological progression-free survival (RPFS), postoperative continence, and quality of life (QoL) parameters. DISCUSSION: The optimal treatment for OMPC is still on its way, prompting investigation for novel multimodality treatment protocol for this patient population. Traditionally, radical prostatectomy has been recommended as one of the standard therapies for localized prostate cancer, but indications have expanded over the years as recommended by NCCN and EAU guidelines. RP has been carried out in some centres for OMPC patients, but its value has been inconclusive, showing elevated complication risks and limited survival benefit. Neoadjuvant radiotherapy has been proven safe and effective in colorectal cancer, breast cancer and other various types of malignant tumors, showing potential advantages in terms of reducing metastatic stem-cell activity, providing clinical downstaging, and reducing potential intraoperative risks. Existing trials have shown that naRT is well tolerated for high-risk and locally-advanced prostate cancer. In this study, we hope to further determine the optimal irradiation dose and patient tolerance for genitourinary, gastrointestinal and systemic toxicities with the design of 3+3 dose escalation; also, final pathology can be obtained following RP to further determine treatment response and follow-up treatment plans. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900025743. http://www.chictr.org.cn/showprojen.aspx?proj=43065.

Protocol of the integrated boost to the dominant intraprostatic nodule in stereotactic body radiation therapy for localized prostate cancer.

Aim: To explore the safety and efficacy of the integrated boost to the dominant intraprostatic nodule (DIN) based on 68Ga prostate-specific membrane antigen PET/MRI in stereotactic body radiation therapy (SBRT) for patients with localized prostate cancer. Methods: SBRT regimen is employed - namely, sequential integrated boost (SIB) to the DIN based on 68Ga prostate-specific membrane antigen PET/MRI. SIB prescription dose of 36.25 Gy in five fractions to fixed prophylactic tumoricidal region is delivered, followed by 7.25 Gy in one fraction added to the DIN every other day. The primary end point of the study will be toxicity assessed by the Common Terminology Criteria for Adverse Events 5.0 grading scale. Secondary end points include biochemical progression-free survival, local progression-free survival, distant metastasis-free survival and overall survival. Discussion: This trial is to prove the safety and efficacy of sequential integrated boost to the DIN in SBRT. Clinical Trial Registration: NCT04599699 (ClinicalTrials.gov).

Electrolyte-Resistant Dual Materials for the Synergistic Safety Enhancement of Lithium-Ion Batteries.

Safety issues associated with lithium-ion batteries are of major concern, especially with the ever-growing demand for higher-energy-density storage devices. Although flame retardants (FRs) added to electrolytes can reduce fire hazards, large amounts of FRs are required and they severely deteriorate battery performance. Here, we report a feasible method to balance flame retardancy and electrochemical performance by coating an electrolyte-insoluble FR on commercial battery separators. By integrating dual materials via a two-pronged mechanism, the quantity of FR required could be limited to an ultrathin coating layer (4 µm) that rarely influences electrochemical performance. The developed composite separator has a four-times better flame retardancy than conventional polyolefin separators in full pouch cells. Additionally, this separator can be fabricated easily on a large scale for industrial applications. High-energy-density batteries (2 Ah) were assembled to demonstrate the scaling of the composite separator and to confirm its enhanced safety through nail penetration tests.

Stereotactic body radiotherapy plus pembrolizumab and trametinib versus stereotactic body radiotherapy plus gemcitabine for locally recurrent pancreatic cancer after surgical resection: an open-label, randomised, controlled, phase 2 trial.

BACKGROUND: There is paucity of investigations into immunotherapy or targeted therapy for postoperative locally recurrent pancreatic cancer. We aimed to assess the efficacy of stereotactic body radiotherapy (SBRT) plus pembrolizumab and trametinib in these patients. METHODS: In this open-label, randomised, controlled, phase 2 study, participants were recruited from Changhai Hospital affiliated to Naval Medical University, Shanghai, China. Eligible patients were aged 18 years or older with histologically confirmed pancreatic ductal adenocarcinoma characterised by mutant KRAS and positive immunohistochemical staining of PD-L1, Eastern Cooperative Oncology Group performance status of 0 or 1, and documented local recurrence after surgery followed by chemotherapy (mFOLFIRINOX or 5-fluorouracil). Eligible participants were randomly assigned (1:1) using an interactive voice or web response system, without stratification, to receive SBRT with doses ranging from 35-40 Gy in five fractions, intravenous pembrolizumab 200 mg once every 3 weeks, and oral trametinib 2 mg once daily or SBRT (same regimen) and intravenous gemcitabine (1000 mg/m2) on day 1 and 8 of a 21-day cycle for eight cycles until disease progression, death, unacceptable toxicity, or consent withdrawal. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the as-treated population in all participants who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02704156, and is now complete. FINDINGS: Between Oct 10, 2016, and Oct 28, 2017, 198 patients were screen, of whom 170 patients were enrolled and randomly assigned to receive SBRT plus pembrolizumab and trametinib (n=85) or SBRT plus gemcitabine (n=85). As of the clinical cutoff date (Nov 30, 2020), median follow-up was 23·3 months (IQR 20·5-27·4). Median overall survival was 24·9 months (23·3-26·5) with SBRT plus pembrolizumab and trametinib and 22·4 months (95% CI 21·2-23·6) with SBRT plus gemcitabine (hazard ratio [HR] 0·60 [95% CI 0·44-0·82]; p=0·0012). The most common grade 3 or 4 adverse effects were increased alanine aminotransferase or aspartate aminotransferase (ten [12%] of 85 in SBRT plus pembrolizumab and trametinib group vs six [7%] of 85 in SBRT plus gemcitabine group), increased blood bilirubin (four [5%] vs none), neutropenia (one [1%] vs nine [11%]), and thrombocytopenia (one [1%] vs four [5%]). Serious adverse events were reported by 19 (22%) participants in the SBRT plus pembrolizumab and trametinib group and 12 (14%) in the SBRT plus gemcitabine group. No treatment-related deaths occurred. INTERPRETATION: The combination of SBRT plus pembrolizumab and trametinib could be a novel treatment option for patients with locally recurrent pancreatic cancer after surgery. Phase 3 trials are needed to confirm our findings. FUNDING: Shanghai Shenkang Center and Changhai Hospital. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

All-Solid-State Lithium-Sulfur Batteries Enhanced by Redox Mediators.

Redox mediators (RMs) play a vital role in some liquid electrolyte-based electrochemical energy storage systems. However, the concept of redox mediator in solid-state batteries remains unexplored. Here, we selected a group of RM candidates and investigated their behaviors and roles in all-solid-state lithium-sulfur batteries (ASSLSBs). The soluble-type quinone-based RM (AQT) shows the most favorable redox potential and the best redox reversibility that functions well for lithium sulfide (Li2S) oxidation in solid polymer electrolytes. Accordingly, Li2S cathodes with AQT RMs present a significantly reduced energy barrier (average oxidation potential of 2.4 V) during initial charging at 0.1 C at 60 °C and the following discharge capacity of 1133 mAh gs-1. Using operando sulfur K-edge X-ray absorption spectroscopy, we directly tracked the sulfur speciation in ASSLSBs and proved that the solid-polysulfide-solid reaction of Li2S cathodes with RMs facilitated Li2S oxidation. In contrast, for bare Li2S cathodes, the solid-solid Li2S-sulfur direct conversion in the first charge cycle results in a high energy barrier for activation (charge to ∼4 V) and low sulfur utilization. The Li2S@AQT cell demonstrates superior cycling stability (average Coulombic efficiency 98.9% for 150 cycles) and rate capability owing to the effective AQT-enhanced Li-S reaction kinetics. This work reveals the evolution of sulfur species in ASSLSBs and realizes the fast Li-S reaction kinetics by designing an effective sulfur speciation pathway.