Ether-based electrolytes hold promise for Li-ion batteries due to their inherently low viscosity and decent reduction stability, yet their poor oxidative stability limit practical deployment. Herein, we report a methoxyfunctionalized non-fluorinated ether, 2,5-dimethoxytetrahydrofuran (DOTHF). The molecular-design strategy incorporates two methoxys as electron donating groups to form a quasi-conjugation effect, which endows DOTHF with weak solvation ability and the anion-dominated solvation structure, thus improving oxidation and interface stability. Accordingly, a DOTHF-based electrolyte (DFD622) enables LiFePO4 (LFP) to retain 81.1 % capacity over 2200 cycles. The 1 Ah LFP||Graphite (Gr) commercial pouch cell keeps 80 % retention after 1000 cycles at 1C and delivers 71.6 % capacity retention at 6C, it also demonstrates exceptional low temperature performance at -20 degrees C with 99 % capacity retention after 100 cycles. Additionally, thanks to its good high-voltage stability, a 1 Ah NCM811||Gr commercial pouch cell with the 4.4 V cut-off voltage retains 90 % capacity after 200 cycles. This work demonstrates a molecular-design strategy for non-fluorinated ether solvents that cultivates highperformance LIBs.

The non-integer dimension and self-similarity characteristics of the electrodes of lithium-ion batteries (LIBs) in the microscopic form are the crucial characteristics of fractional-order theory. The non-classical energy dissipation mechanism of heat transfer mechanism in porous electrodes is the coupling of diffusion effect and heat wave effect. The inability of integer-order thermal models to precisely describe the transient thermal behavior of porous electrodes places constraints on the accuracy of electrochemical and structural models of the LIB. A fractional-order thermal-electrochemical-structural model (FOTESM) is established to analyze the stress evolution of the LIB under dynamic operating conditions. After introducing the historical weighting term, the fractional-order thermal model is applied to calculate the temperature state and adjust the temperature influencing factors of the electrochemical model. The correlation between the derivative order and the state of charge is studied. The results demonstrate that the stress simulation accuracy of FOTESM is improved by 14.05% at 0 degrees C and 10.92% at 40 degrees C versus the integer-order model. Due to the intervention of the derivative order, FOTESM can quickly track the true stress. FOTESM, as a high-order physical field form, is more suitable for analyzing the thermal and mechanical properties on porous electrodes.

Mutant Ras oncoproteins, particularly KRAS, are among the most prevalent drivers of cancer. Small-molecule inhibitors of KRAS have been developed, bearing high potential for cancer therapy but considerable risk of resistance development. To avoid cancer cell adaptation, effective combinatorial partners for increasing immediate efficacy remain to be explored. Here, we demonstrate that combining the KRAS inhibitor Sotorasib with the CDK4/6 inhibitor Palbociclib synergistically eliminates pancreatic ductal adenocarcinoma (PDAC) cells and organoids harboring KRAS G12C mutations. This synergy was particularly pronounced after drug washout, indicating a durable impact. Similar effects were observed in non-small-cell lung cancer (NSCLC) cells. Additionally, MRTX1133, a KRAS G12D inhibitor, synergized with Palbociclib to suppress KRAS G12D-mutant PDAC-derived cells. Mechanistically, these combinations induced sustained cell cycle arrest through reduced RB phosphorylation, decreased E2F1 levels, and increased CDKN1B/p27 expression. Deletion of CDKN1B largely rescued tumor cell proliferation, underscoring its critical role in mediating the observed synergy. These findings support the therapeutic potential of combining KRAS and CDK4/6 inhibitors for treating PDAC and other Ras-driven cancers. ### Competing Interest Statement The authors have declared no competing interest.

The electrodes of lithium-ion batteries exhibit non-integer dimensional and self-similar morphological characteristics, which are consistent with fractal theory. Heat transfer within porous electrodes does not follow a simple diffusion or thermal wave mode; instead, it represents a non-standard energy dissipation process. Conventional integer-order thermal models struggle to accurately capture the transient thermal behavior of electrodes, thereby limiting the precision of electrochemical and structural models of LIBs. To address this, a thermal-electrical model (TEM) with fractional order is developed to analyze the thermoelectric performance of batteries under low-temperature conditions. Historical weighting is applied to describe the heat transfer behavior in porous electrodes. Various charge-discharge scenarios are designed to validate the effectiveness of the model, and a finite difference scheme is established for the TEM with fractional order. The proposed model demonstrates improved performance in both tracking speed and temperature field simulation accuracy. Furthermore, the study explores the evolution of complex heat transfer mechanisms in electrodes across different states of charge (SOC). The intrinsic correlation among order terms, SOC, and temperature is also examined. Overall, this modeling approach provides effective guidance for investigating the thermal characteristics of batteries in low-temperature environments.

Glioma is characterized by strong immunosuppression and excessive angiogenesis. Based on existing reports, it can be speculated that the resistance to anti-angiogenic drug vascular endothelial growth factor A (VEGFA) antibody correlates to the induction of novel immune checkpoint indoleamine 2,3-dioxygenase 1 (IDO1), while IDO1 has also been suggested to be related to tumor angiogenesis. Herein, we aim to clarify the potential role of IDO1 in glioma angiogenesis and the mechanism behind it. Bioinformatic analyses showed that the expressions of IDO1 and angiogenesis markers VEGFA and CD34 were positively correlated and increased with pathological grade in glioma. IDO1-overexpression-derived-tryptophan depletion activated the general control nonderepressible 2 (GCN2) pathway and upregulated VEGFA in glioma cells. The tube formation ability of angiogenesis model cells could be inhibited by IDO1 inhibitors and influenced by the activity and expression of IDO1 in condition medium. A significant increase in serum VEGFA concentration and tumor CD34 expression was observed in IDO1-overexpressing GL261 subcutaneous glioma-bearing mice. IDO1 inhibitor RY103 showed positive anti-tumor efficacy, including the anti-angiogenesis effect and upregulation of natural killer cells in GL261 glioma-bearing mice. As expected, the combination of RY103 and anti-angiogenesis agent sunitinib was proved to be a better therapeutic strategy than either monotherapy.

Achieving health monitoring and chronic disease monitoring of the human body is a frontier topic in the world, including the scientific fields of materials science, information technology, electronics, and analytical chemistry. Wearable devices that continuously acquire physical signals such as temperature, pressure, and stress to achieve real-time monitoring of human activity have been commercialized. However, wearable sensors that continuously monitor various chemicals in human body fluids and exhaled breath still face many problems, such as the flexibility, sensitivity, accuracy and the fit of the sensor to human skin. This mini-review introduces the advantages of flexible wearable sensors applied to sweat monitoring, especially the research progress of flexible wearable sensors in monitoring glucose, lactate, pH value and various markers in sweat. At the same time, this review also analyzes the current shortcomings and limitations of flexible wearable sensors. We believe that future flexible wearable The future development of flexible wearable sweat sensors should be in the direction of low cost, easy manufacturing, high selectivity and sensitivity.

In Alzheimer's disease,the transporter P-glycoprotein is responsible for the clearance of amyloid-β in the brain.Amyloid-β correlates with the sphingomyelin metabolism,and sphingo myelin participates in the regulation of P-glycoprotein.The amyloid cascade hypothesis describes amyloid-β as the central cause of Alzheimer's disease neuropathology.Better understanding of the change of P-glycoprotein and sphingomyelin along with amyloid-β and their potential association in the pathological process of Alzheimer's disease is critical.Herein,we found that the expression of P-glycoprotein in APP/PS1 mice tended to increase with age and was significantly higher at 9 and 12 months of age than that in wild-type mice at comparable age.The functionality of P-glycoprotein of AP P/PS1 mice did not change with age but was significantly lower than that of wild-type mice at 12 months of age.Decreased sphingomyelin levels,increased ceramide levels,and the increased expression and activity of neutral sphingomyelinase 1 were observed in APP/PS1 mice at 9 and 12 months of age compared with the levels in wild-type mice.Similar results were observed in the Alzheimer's disease mouse model induced by intracerebroventricular injection of amyloid-β1-42 and human cerebral microvascular endothelial cells treated with amyloid-β1-42.In human cerebral microvascular endothelial cells,neutral sphingomyelinase 1 inhibitor interfered with the changes of sphingo myelin metabolism and P-glycoprotein expression and functionality caused by amyloid-β1-42 treatment.Neutral sphingo myelinase 1 regulated the expression and functionality of P-glycoprotein and the levels of sphingomyelin and ceramide.Togethe r,these findings indicate that neutral sphingomyelinase 1 regulates the expression and function of P-glycoprotein via the sphingomyelin/ceramide pathway.These studies may serve as new pursuits for the development of anti-Alzheimer's disease drugs.

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the rate-limiting step in tryptophan catabolism along the kynurenine (Kyn) pathway and exerts immunosuppressive properties mainly via activation of transcription factor aryl hydrocarbon receptor (AhR) pathway. IDO1 induces NK cells dysfunction via downregulation of the activating receptor NKG2D on NK cells, but whether and how it affects the expression of NKG2D Ligand (NKG2DL) on tumor cells remains unclear. Since a disintegrin and metalloprotease 10 (ADAM10) plays a potential role in the shedding of NKG2DL and the releasing of soluble NKG2DL (sNKG2DL), we investigated how IDO1 modulates the expression of NKG2DL via ADAM10 in non-small cell lung cancer (NSCLC). We found that IDO1 expression was negatively correlated with NKG2DL expression while positively correlated with ADAM10 expression with human lung cancer brain metastasis tissue, NSCLC cells and LLC tumor-bearing mice. IDO1 could regulate ADAM10 expression via IDO1-Kyn-AhR signaling pathway and subsequently regulate NKG2DL expression. IDO1 deficiency led to retarded tumor growth and improved NK cells function in NSCLC mice. IDO1 inhibitors improved NK cells function in vitro and in vivo. The combo of IDO1 inhibitor and NK cells exhibited more therapeutic efficacy than either of the single IDO1 inhibitor or NK cells treatment.

Indoleamine 2,3-dioxygenase 1 (IDO1), a monomeric heme-containing enzyme, catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan metabolism, which plays an important role in immunity and neuronal function. Its implication in different pathophysiologic processes including cancer and neurodegenerative diseases has inspired the development of IDO1 inhibitors in the past decades. However, the negative results of the phase III clinical trial of the would-be first-in-class IDO1 inhibitor (epacadostat) in combination with an anti-PD1 antibody (pembrolizumab) in patients with advanced malignant melanoma call for a better understanding of the role of IDO1 inhibition. In this review, the current status of the clinical development of IDO1 inhibitors will be introduced and the key pre-clinical and clinical data of epacadostat will be summarized. Moreover, based on the cautionary notes obtained from the clinical readout of epacadostat, strategies for the identification of reliable predictive biomarkers and pharmacodynamic markers as well as for the selection of the tumor types to be treated with IDO1inhibitors will be discussed.

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzing the conversion of tryptophan (Trp) to kynurenine (Kyn) in kynurenine pathway (KP) is involved in the immunosuppression in pancreatic cancer (PC), but the value of IDO1 as an independent prognostic marker for PC is uncertain. Moreover, the correlation between tryptophan 2,3-dioxygenase (TDO), an isozyme of IDO1, and PC is largely unknown. Using TCGA database, the correlation between IDO1 and/or TDO expression and PC patients' survival was analyzed. The expressions of IDO1 and TDO in PC cells and PC mice were examined. The effects of IDO1, TDO or dual inhibition on IDO1 and TDO effector pathway (Aryl hydrocarbon receptor, AhR) and on migration and invasion of PC cells were investigated. The block effect of IDO1/TDO dual inhibitor RY103 on KP was evaluated. The preclinical efficacy of RY103 and its immunomodulatory effect on KPIC orthotopic PC mice and Pan02 tumor-bearing mice were explored. Results showed that IDO1/TDO co-expression is an independent prognostic marker for PC. RY103 can significantly block KP and target Kyn-AhR pathway to blunt the migration and invasion of PC cells, exhibit preclinical efficacy and ameliorate IDO1/TDO-mediated immunosuppression in PC mice.

Dear Editor, Indoleamine 2,3-dioxygenase 1 (IDO1) inhibition has been developed as a potential new tool in cancer immunotherapy and some IDO1 inhibitors have been in clinical trials.1 However, the biomarker information of IDO1 inhibitors is very few. Here, we searched for potential IDO1 inhibitors biomarker by identifying molecular characteristic that can predict the effect of IDO1 on cancer prognosis. We evaluated the effect of IDO1 mRNA expression on prognosis in

This review presents a comprehensive summary of the recent development in semi-artificial photosynthesis, a biological-material hybrid approach to solar-to-chemical conversion that provides new concepts to shape a sustainable future fuelled by solar energy. We begin with a brief introduction to natural and artificial photosynthesis, followed by a discussion of the motivation and rationale behind semi-artificial photosynthesis. Then, we summarise how various enzymes can be combined with synthetic materials for light-driven water oxidation, H2 evolution, CO2 reduction, and chemical synthesis more broadly. In the following section, we discuss the strategies to incorporate microorganisms in photocatalytic and (photo)electrochemical systems to produce fuels and chemicals with renewable sources. Finally, we outline emerging analytical techniques to study the bio-material hybrid systems and propose unexplored research opportunities in the field of semi-artificial photosynthesis.

Extracellular electron transfer (EET) in microorganisms is prevalent in nature and has been utilized in functional bioelectrochemical systems. EET of Geobacter sulfurreducens has been extensively studied and has been revealed to be facilitated through c-type cytochromes, which mediate charge between the electrode and G. sulfurreducens in anodic mode. However, the EET pathway of cathodic conversion of fumarate to succinate is still under debate. Here, we apply a variety of analytical methods, including electrochemistry, UV-vis absorption and resonance Raman spectroscopy, quartz crystal microbalance with dissipation, and electron microscopy, to understand the involvement of cytochromes and other possible electron-mediating species in the switching between anodic and cathodic reaction modes. By switching the applied bias for a G. sulfurreducens biofilm coupled to investigating the quantity and function of cytochromes, as well as the emergence of Fe-containing particles on the cell membrane, we provide evidence of a diminished role of cytochromes in cathodic EET. This work sheds light on the mechanisms of G. sulfurreducens biofilm growth and suggests the possible existence of a nonheme, iron-involving EET process in cathodic mode.

Integration of electroactive bacteria into electrodes combines strengths of intracellular biochemistry with electrochemistry for energy conversion and chemical synthesis. However, such biohybrid systems are often plagued with suboptimal electrodes, which limits the incorporation and productivity of the bacterial colony. Here, we show that an inverse opal-indium tin oxide electrode hosts a large population of current-producing Geobacter and attains a current density of 3 mA cm-2 stemming from bacterial respiration. Differential gene expression analysis revealed Geobacter's transcriptional regulations to express more electron-relaying proteins when interfaced with electrodes. The electrode also allows coculturing with Shewanella for syntrophic electrogenesis, which grants the system additional flexibility in converting electron donors. The biohybrid electrode containing Geobacter can also catalyze the reduction of soluble fumarate and heterogenous graphene oxide, with electrons from an external power source or an irradiated photoanode. This biohybrid electrode represents a platform to employ live cells for sustainable power generation and biosynthesis.

Indoleamine 2,3-dioxygenase 1 (IDO1), which catalyzes the initial and rate-limiting step of the kynurenine pathway of tryptophan catabolism, has emerged as a key target in cancer immunotherapy because of its role in enabling cancers to evade the immune system. Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase 2 (IDO2) catalyze the same reaction and play a potential role in cancer immunotherapy. Starting from our previously discovered tryptanthrin IDO1 inhibitor scaffold, we synthesized novel N-benzyl/aryl substituted tryptanthrin derivatives and evaluated their inhibitory efficacy on IDO1, TDO, and IDO2. Most compounds showed similar high inhibitory activities on both IDO1 and TDO, which were significantly superior over that of IDO2 with magnitude difference. We showed that N-benzyl/aryl substituted tryptanthrin directly interacted with IDO1, TDO, and IDO2, significantly augmented the proliferation of T cells in vitro, blocked the kynurenine pathway, and suppressed tumor growth when administered to LLC and H22 tumor-bearing mice.

Semiartificial photosynthesis integrates photosynthetic enzymes with artificial electronics, which is an emerging approach to reroute the natural photoelectrogenetic pathways for sustainable fuel and chemical synthesis. However, the reduced catalytic activity of enzymes in bioelectrodes limits the overall performance and further applications in fuel production. Here, we show new insights into factors that affect the photoelectrogenesis in a model system consisting of photosystem II and three-dimensional indium tin oxide and graphene electrodes. Confocal fluorescence microscopy and in situ surface-sensitive infrared spectroscopy are employed to probe the enzyme distribution and penetration within electrode scaffolds of different structures, which is further correlated with protein film-photoelectrochemistry to establish relationships between the electrode architecture and enzyme activity. We find that the hierarchical structure of electrodes mainly influences the protein loading but not the enzyme activity. Photoactivity is more limited by light intensity and electronic communication at the biointerface. This study provides guidelines for maximizing the performance of semiartificial photosynthesis and also presents a set of methodologies to probe the photoactive biofilms in three-dimensional electrodes.

Metal anodes, such as zinc and bismuth have been regarded as ideal materials for aqueous batteries due to high gravimetrical capacity, high abundance, low toxicity, and intrinsic safety. However, their translation into practical applications are hindered by the low mass loading (≈1 mg cm-2 ) of active materials. Here, the multiscale integrated structural engineering of 3D scaffold and active material, i.e., bismuth is in situ intercalated in reduced graphene oxide (rGO) wall of network, are reported. Tailoring the rapid charge transport on rGO 3D network and facile access to nano- and microscale bismuth, the rGO/Bi hybrid anode shows high utilization efficiency of 91.4% at effective high load density of ≈40 mg cm-2 , high areal capacity of 3.51 mAh cm-2 at the current density of 2 mA cm-2 and high reversibility of >10 000 cycles. The resulting Ni-Bi full battery exhibits high areal capacity of 3.13 mAh cm-2 at the current density of 2 mA cm-2 , far outperforming the other counterpart batteries. It represents a general and efficient strategy in enhancing the battery performance by designing hierarchically networked structure.

Carbon nitrides (CNx) are a promising class of photocatalyst for fuel and chemical synthesis as they are nontoxic and readily synthesized at a low cost. This study reports the enhanced photocatalytic activity for simultaneous alcohol oxidation and proton reduction when graphene oxide (GO) or reduced graphene oxide (RGO) is employed as an interlayer between a cyanamide-functionalized melon-type carbon nitride ((CNx)-C-NCN) and a phosphonated Ni-bis(diphosphine) H-2-evolution catalyst (NiP). Introduction of the GO/RGO enhanced the activity three times, reaching a specific activity of 4655 +/- 448 mu mol H-2 (g (CNx)-C-NCN)-1 h(-1) with a NiP-based turnover frequency of 116 +/- 3 h(-1). Mechanistic studies into this closed photoredox system revealed that the rate of electron extraction from (CNx)-C-NCN is rate limiting. GO/RGO is commonly employed to improve the electron transfer dynamics on nanosecond time scales, but time-resolved photoluminescence and transient absorption spectroscopy reveal that these properties are not significantly affected in our (CNx)-C-NCN-GO hybrid on fast time scales (<0.1 s). However, long-lived trapped-electrons generated upon photoexcitation of (CNx)-C-NCN in the presence of organic substrates are shown by photoinduced absorption spectroscopy to be quenched faster with GO/RGO, supporting that GO/RGO improves electron transfer from (CNx)-C-NCN to NiP on time scales >0.1 s. The absorption profile of NiP in the presence of different GO loadings reveals that GO acts as a conductive interfacial binder between NiP and (CNx)-C-NCN. The enhancement in activity therefore does not primarily arise from changes in the photophysics of the (CNx)-C-NCN, but rather from GO/RGO enabling better electronic communication between (CNx)-C-NCN and NiP.

In the present work, we develop a scalable and inexpensive design for lithium-sulfur (Li-S) batteries by capping a flexible gel polymer/carbon nanofiber (CNF)composite membrane onto a free-standing and binder-free CNF + Li2S6 cathode, thus achieving a three-dimensional (3D) structural design. The CNF network is used as the current collector and S holder to overcome the insulating nature and volume expansion of S, while the composite membrane comprises a gel polymer poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP), and CNF additive is used as an interlayer to trap polysulfides and recycle the remaining S species, leading to a high specific capacity and long cycle life. This 3D structure enables excellent cyclability for 500 cycles at 0.5 °C with a small capacity decay of 0.092% per cycle. Furthermore, an outstanding cycle stability was also achieved at even higher current densities (1.0 to 2.0 °C), indicating its good potential for practical applications of Li-S batteries.

Lithium-ion batteries have been regarded as one of the most promising energy storage devices, and development of low-cost batteries with high energy density is highly desired so that the cost per watt-hour ($/Wh) can be minimized. In this work, we report using ball-milled low-cost silicon (Si) as the starting material and subsequent carbon coating to produce low-cost hierarchical carbon-coated (HCC) Si. The obtained particles prepared from different Si sources all show excellent cycling performance of over 1000 mAh/g after 1000 cycles. Interestingly, we observed in situ formation of porous Si, and it is well confined in the carbon shell based on postcycling characterization of the hierarchical carbon-coated metallurgical Si (HCC-M-Si) particles. In addition, lightweight and free-standing electrodes consisting of the HCC-M-Si particles and carbon nanofibers were fabricated, which achieved 1015 mAh/g after 100 cycles based on the total mass of the electrodes. Compared with conventional electrodes, the lightweight and free-standing electrodes significantly improve the energy density by 745%. Furthermore, LiCoO2 and LiNi0.5Mn1.5O4 cathodes were used to pair up with the HCC-M-Si anode to fabricate full cells. With LiNi0.5Mn1.5O4 as cathode, an energy density up to 547 Wh/kg was achieved by the high-voltage full cell. After 100 cycles, the full cell with a LiNi0.5Mn1.5O4 cathode delivers 46% more energy density than that of the full cell with a LiCoO2 cathode. The systematic investigation on low-cost Si anodes together with their applications in lightweight free-standing electrodes and high-voltage full cells will shed light on the development of high-energy Si-based lithium-ion batteries for real applications.