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Lattice oxygen (OL) redox chemistry is a key to alleviating the energy and environmental crisis, but it faces challenges in activating the OLwhile ensuring structural stability. We disclosed herein that engineering a heterogeneous interface between ultrathin oxide and amorphous carbon can attain the durable OLredox chemistry without introducing catalytically impure sites. To this end, we proposed a green strategy to grow ∼3.9 nm-thickness wrinkled δ-MnO2nanosheets that are rich in defects and are vertically aligned on amorphous carbon spheres. Experiments and calculations reveal that the electrons can easily migrate from the amorphous carbon to MnO2at the δ-MnO2@C heterointerface. The heterogeneous interfaces can not only regulate the Mn–O bond and create oxygen defects in δ-MnO2but also introduce lattice oxygen with varying reactivities. Specifically, the δ-MnO2@C structure carries more activated lattice oxygen that contributes to the enhanced activity on catalytic oxidation of bioderived 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA), with a high FDCA formation rate of 1759 μmol gcat–1h–1and a high selectivity of 95%. The heterogeneous interface of MnO2@C also brings inert lattice oxygen, so that it manifests high structural stability during the oxidation reactions. This work deepens the fundamental understandings in the engineering of lattice oxygen for durable lattice oxygen redox chemistry and showcases an effective interface technique in creating advanced catalysts for clean sustainable energy.

Graphene oxide (GO)-based fire alarm materials have garnered extensive attention because the thermal reduction of GO to reduced GO (RGO) enables rapid fire warning. However, they suffer from poor flame retardancy, irreversible fire warning, and dependence on an external power supply. Herein, a GO/MXene/chitosan aerogel with a low density of 0.018 g cm–3and good compressibility has been developed. The experimental results demonstrate that (i) MXene effectively reduces the peak and mean heat release rate of GO, while RGO nanosheets compensate for the structural instability of MXene in the flame due to thermal oxidation into TiO2; as such, long-lasting fire warning (>120 s) has been achieved; (ii) the reducibility and conductivity of MXene contribute to the ultrasensitive response of GO, with a fire response time of 1 s; and (iii) notably, the thermoelectric effect of MXene enables the reversible and self-powered fire warning of the GO/MXene/CS aerogel without an external power supply. Compared to pure MXene/CS aerogel, the presence of GO improves the sensitivity and stability of self-powered fire warning, owing to the formation of the highly conductive RGO nanosheets. The results of this work highlight the cooperation between GO and MXene in realizing ultrasensitive, long-lasting, reversible, and self-powered fire warning.

Background: The optimal anticoagulation regimen for continuous renal replacement therapy (CRRT) in liver failure (LF) patients without increased bleeding risk remains controversial. Therefore, we conducted a monocentric retrospective study to evaluate the efficacy and safety of the regional citrate anticoagulation (RCA) versus low molecular weight heparin (LMWH) anticoagulation for CRRT in LF without increased bleeding risk.Method: According to the anticoagulation strategy for CRRT, patients were divided into the RCA and LMWH-anticoagulation groups. The evaluated endpoints were patient survival, filter lifespan, bleeding, citrate accumulation, and totCa/ionCa ratio.Result: Totally 167 and 164 filters were used in the RCA and LMWH group, respectively. The median filter lifespan was significantly longer in the RCA group (34 h (IQR = 24–54) versus 24 h (IQR = 18–45.5) [95%CI, 24.5–33]; p< 0.001). The 4-week mortality rate was significantly higher in the LMWH-anticoagulation group (71 (57.72%) vs 53 (40.46%); p= 0.006). After adjusted the important parameters in the multivariate COX regression model, the mortality risk was significantly reduced in the RCA group (HR = 0.668 [95%CI, 0.468–0.955]; p= 0.027). In the LMWH group, 30 bleeding episodes (24,19%) were observed, whereas only 7 (5.34%) occurred in the RCA group (p< 0.001). Two patients (1.5%) in the RCA group occurred citrate accumulation.Conclusions: In LF patients without increased bleeding risk who underwent CRRT, RCA significantly extended the filter lifespan and improved patient survival rate. There was no significant difference in the rate of adverse events between the two groups.

Immunochemotherapy is the first-line standard for extensive-stage small-cell lung cancer (ES-SCLC). Combining the regimen with anti-angiogenesis may improve efficacy. ETER701 was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial that investigated the efficacy and safety of benmelstobart (a novel programmed death-ligand 1 (PD-L1) inhibitor) with anlotinib (a multi-target anti-angiogenic small molecule) and standard chemotherapy in treatment-naive ES-SCLC. The ETER701 trial assessed two primary endpoints: Independent Review Committee-assessed progression-free survival per RECIST 1.1 and overall survival (OS). Here the prespecified final progression-free survival and interim OS analysis is reported. Patients randomly received benmelstobart and anlotinib plus etoposide/carboplatin (EC; n= 246), placebo and anlotinib plus EC (n= 245) or double placebo plus EC (‘EC alone’; n= 247), followed by matching maintenance therapy. Compared with EC alone, median OS was prolonged with benmelstobart and anlotinib plus EC (19.3 versus 11.9 months; hazard ratio 0.61; P= 0.0002), while improvement of OS was not statistically significant with anlotinib plus EC (13.3 versus 11.9 months; hazard ratio 0.86; P= 0.1723). The incidence of grade 3 or higher treatment-related adverse events was 93.1%, 94.3% and 87.0% in the benmelstobart and anlotinib plus EC, anlotinib plus EC, and EC alone groups, respectively. This study of immunochemotherapy plus multi-target anti-angiogenesis as first-line treatment achieved a median OS greater than recorded in prior randomized studies in patients with ES-SCLC. The safety profile was assessed as tolerable and manageable. Our findings suggest that the addition of anti-angiogenesis therapy to immunochemotherapy may represent an efficacious and safe approach to the management of ES-SCLC. ClinicalTrials.gov identifier: NCT04234607.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor precursor homologous domain A (EGF-A) of low-density lipoprotein receptor (LDLR) in the liver and triggers the degradation of LDLR via the lysosomal pathway, consequently leading to an elevation in plasma LDL-C levels. Inhibiting PCSK9 prolongs the lifespan of LDLR and maintains cholesterol homeostasis in the body. Thus, PCSK9 is an innovative pharmacological target for treating hypercholesterolemia and atherosclerosis. In this study, we discovered that E28362 was a novel small-molecule PCSK9 inhibitor by conducting a virtual screening of a library containing 40,000 compounds. E28362 (5, 10, 20 μM) dose-dependently increased the protein levels of LDLR in both total protein and the membrane fraction in both HepG2 and AML12 cells, and enhanced the uptake of DiI-LDL in AML12 cells. MTT assay showed that E28362 up to 80 μM had no obvious toxicity in HepG2, AML12, and HEK293a cells. The effects of E28362 on hyperlipidemia and atherosclerosis were evaluated in three different animal models. In high-fat diet-fed golden hamsters, administration of E28362 (6.7, 20, 60 mg·kg−1·d−1, i.g.) for 4 weeks significantly reduced plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and PCSK9 levels, and reduced liver TC and TG contents. In Western diet-fed ApoE−/−mice (20, 60 mg·kg−1·d−1, i.g.) and human PCSK9 D374Y overexpression mice (60 mg·kg−1·d−1, i.g.), administration of E28362 for 12 weeks significantly decreased plasma LDL-C levels and the area of atherosclerotic lesions in en faceaortas and aortic roots. Moreover, E28362 significantly increased the protein expression level of LDLR in the liver. We revealed that E28362 selectively bound to PCSK9 in HepG2 and AML12 cells, blocked the interaction between LDLR and PCSK9, and induced the degradation of PCSK9 through the ubiquitin-proteasome pathway, which finally resulted in increased LDLR protein levels. In conclusion, E28362 can block the interaction between PCSK9 and LDLR, induce the degradation of PCSK9, increase LDLR protein levels, and alleviate hyperlipidemia and atherosclerosis in three distinct animal models, suggesting that E28362 is a promising lead compound for the treatment of hyperlipidemia and atherosclerosis.

A bis(imidazolidine)-derived NCN nickel-pincer complex (tBu-PhBidine-Ni-OTf: NCN-Ni-OTf) was synthesized by the oxidative addition of imidazolidine-containing aryl triflate to Ni(cod)2in MeCN. NCN-Ni-OTfexhibited asymmetric induction in three reactions. In the Friedel–Crafts reaction of indoles with N-Boc imines, 3-indolylmethanamine products were obtained in 79% yield with 99% ee. In a conjugate addition reaction of malononitrile to nitroalkenes, products were obtained in 95% yield with 75% ee. In iodolactonization, the pincer-Ni complex showed catalytic activity superior to that of tBu-PhBidine-Pd-OTf.

The abundance of uranium (U(VI)) reserves in seawater makes it crucial to develop economically efficient methods for uranium extraction from seawater. In this work, an enhanced polyamidoxime porous membrane (PAOM) was fabricated by pre-in situ amidoxime modification combined with nonsolvent-induced phase separation (NIPS). The strategy of in situ modification of the polyacrylonitrile (PAN) solution served to enhance the homogeneity of the reaction and avoid the destruction of the membrane matrix and pore structure. Compared with the control sample (AOPM), PAOM possessed better mechanical strength and hydrophilicity. The introduction of polyvinylpyrrolidone (PVP) formed a porous structure in PAOM, improving spatial accessibility and facilitating the diffusion transport and capture of UO22+inside the membrane. The more uniform and abundant distribution of amidoxime groups in PAOM gave it ultrahigh adsorption capacity and selectivity. The equilibrium adsorption capacity and Kdvalue of PAOM were 1.72 and 5.51 times higher than those of AOPM. Meanwhile, PAOM also demonstrated good recyclability, with only a 6.15% decrease in adsorption capacity after seven cycles. Additionally, PAOM exhibited excellent dynamic adsorption performance, and after 14 days of continuous filtration and adsorption, PAOM could extract 2.03 mg·g–1U(VI) from natural seawater.

Reckoning with the global environmental challenge of plastic pollution, particularly in terms of recycling and biodegradation of thermosetting plastics, sustainable alternatives are imperative. The rapidly growing and eco-friendly material bamboo has great potential as a sustainable resource; however, it lacks the inherent self-bonding and plasticity characteristics found in plastics. This study presents a feasible approach to enhance the plasticity of bamboo by selectively removing part of its lignin and disrupting the crystalline structure of cellulose. Concurrently, this process selectively transforms hydroxyl groups into highly reactive dialdehyde groups to increase the reactivity of bamboo. The resulting activated bamboo units undergo a hot-pressing process to transform them into a type of thermosetting plastic (ABTP). The ABTP is highly moldable, and its color can be precisely regulated by adjusting the lignin content. Additionally, it exhibits exceptional solvent and water resistance, along with notable mechanical properties, including a tensile strength of 50 MPa, flexural strength of 80 MPa, flexural modulus of 5 GPa, and Shore D hardness approaching 90. Furthermore, the bamboo-derived plastic exhibits exceptional reusability and biodegradability, presenting feasible and environmentally friendly alternatives to conventional plastics while harnessing the sustainable development potential of bamboo.

Layered oxide materials are widely used in the field of energy storage and conversion due to their high specific energy, high efficiency, long cycle life, and high safety. Herein, We summarize the latest research progress in the field of layered metal oxide cathode materials from three aspects: challenges faced, failure mechanisms, and modification methods. We also compare the characteristics of lithium-based layered oxides and sodium-based layered oxides, and predict future development directions. The layered oxide cathode materials for sodium-ion batteries and lithium-ion batteries exhibit overall structural and operational similarities. There are also some differences, such as lattice parameters and application extent. Sodium-ion battery cathode materials need to explore new materials and address structural instability issues, while lithium-ion batteries require finding alternative materials and improving production efficiency. Future challenges for both types of materials include enhancing capacity and cycle performance, elucidating deep mechanisms, reducing costs, and improving resource sustainability. Future development should focus on balancing cycle stability and charge cut-off voltage to meet the growing demand for battery applications. We comprehensively summarize and analyze the latest research results in the field of layered oxide cathode materials for lithium-ion and sodium-ion batteries, covering aspects such as failure mechanisms, modification methods, electrochemical performance, and comparisons of the characteristics of layered oxide cathode materials in lithium and sodium batteries.

Chronic hyperglycemia can result in damage to the hippocampus and dysfunction of the blood-brain barrier (BBB), potentially leading to neurological disorders. This study examined the histological structure of the hippocampus and the expression of critical genes associated with the BBB at 2 early stage time points in a streptozotocin-induced diabetes mellitus (DM) mouse model. Routine histology revealed vascular congestion and dilation of Virchow-Robin spaces in the hippocampal CA1 region of the DM group. Neuronal alterations included rounding and swelling and reduction in Nissl bodies and increased apoptosis. Compared to the control group, TJP1 mRNA expression in the DM group was significantly lower (P< .05 or P< .01), while mRNA levels of JAM3, TJP3, CLDN5, CLDN3, and OCLN initially increased and then decreased. At 7, 14, and 21 days, mRNA levels of the receptor for advanced glycation end products (AGER) were greater in the DM group than in the control group (P< .05 or P< .01). These findings indicate that early-stage diabetes may cause structural and functional impairments in hippocampal CA1 in mice. These abnormalities may parallel alterations in the expression of key BBB tight junction molecules and elevated AGER expression in early DM patients.

Large wood in rivers can lead to accumulations in the river channel, affecting local flow structures, aquatic habitats, and the river’s topography. This plays a crucial role in the ecological restoration of the river. This paper presents flow field measurements downstream of six types of logjams at different flow velocities using acoustic Doppler velocimetry (ADV) for artificially designed engineered logjams. The results indicate that the presence of logjams reduces the flow velocity and increases the turbulent kinetic energy in the wake region, and as the distance downstream increases, the flow velocity and turbulence intensity in the wake region gradually return to the upstream level. The minimum values of normalized flow velocity under different conditions are located in the region of the bottommost logs. The differences in normalized flow velocity at various flow rates are not significant. Jets are less likely to be generated in logjams with larger and more concentrated projection areas, but the strength of the jet is influenced by the physical structure of the logjam (projection area, gap ratio). The flow distribution behind the logjam is primarily influenced by the proportion of the projected area in different regions. Changes in the vertical physical structure of the logjam have minimal effect on the lateral flow distribution. Flow velocity in the gap area (b0) at the bottom of different logjams is influenced by their physical structure. The larger the overall blockage area of the logjams, the larger the flow velocity in the bottom gap area will be. The flow velocity in the bottom gap area of a densely placed logjam is mainly influenced by the gap ratio. The velocity of flow in the gap area can impact the initiation and deposition of sediment near the logjam. However, the internal structure complexity of the logjam does not significantly affect river energy dissipation and flow attenuation. This study broadens the applicability of certain theoretical models and explores the impact of logjams on river ecology and channel geomorphology. The findings can serve as a theoretical foundation for ecological restoration, timber management, and logjam construction in rivers.

Garsorasib (D-1553; InventisBio, Shangai, China), a potent KRASG12Cinhibitor, has shown promising antitumour activity in patients with KRASG12C-mutated (ie, Gly12Cys) non-small-cell lung cancer (NSCLC) in a phase 1 study. We report results from a phase 2 study conducted to evaluate the efficacy and safety of garsorasib in patients with locally advanced or metastatic KRASG12C-mutated NSCLC.

Hepatocellular carcinoma (HCC) is one of the most fatal malignancies. Early diagnosis of HCC is crucial in reducing the risk for mortality. This study analyzed a panel of nine fusion transcripts in serum samples from 61 patients with HCC and 75 patients with non-HCC conditions, using TaqMan real-time quantitative RT-PCR. Seven of the nine fusions frequently detected in patients with HCC included: MAN2A1–FER(100%), SLC45A2–AMACR(62.3%), ZMPSTE24–ZMYM4(62.3%), PTEN–NOLC1(57.4%), CCNH–C5orf30(55.7%), STAMBPL1–FAS(26.2%), and PCMTD1–SNTG1(16.4%). Machine-learning models were constructed based on serum fusion-gene levels to predict HCC in the training cohort, using the leave-one-out cross-validation approach. One machine-learning model, called the four fusion genes logistic regression model (MAN2A1–FER≤40, CCNH–C5orf30≤38, SLC45A2–AMACR≤41, and PTEN–NOLC1≤40), produced accuracies of 91.5% and 83.3% in the training and testing cohorts, respectively. When serum α-fetal protein level was incorporated into the machine-learning model, a two fusion gene (MAN2A1–FER≤40, CCNH–C5orf30≤38) + α-fetal protein logistic regression model was found to generate an accuracy of 94.8% in the training cohort. The same model resulted in 95% accuracy in both the testing and combined cohorts. Cancer treatment was associated with reduced levels of most of the serum fusion transcripts. Serum fusion-gene machine-learning models may serve as important tools in screening for HCC and in monitoring the impact of HCC treatment.

Saltmarshes are carbon-rich ecosystems that play a role in climate regulation by efficiently sequestrating atmospheric CO2. Climate change is a major threat to saltmarshes and will impact saltmarsh carbon sequestration. Notably, porewater-derived carbon outwelling emerges as a crucial pathway for carbon sequestration, but it has been largely overlooked in saltmarshes. Here, we assessed the drivers of dissolved carbon exports and greenhouse gas emissions in a saltmarsh and placed those observations into a global context. In our study site, porewater exchange (PEX) was the major process controlling dissolved carbon and greenhouse gas dynamics. Combining our results with 33 other studies in saltmarshes worldwide, porewater-derived carbon fluxes were equivalent to ∼48% of average global saltmarsh primary productivity and 2.2 times greater than global organic carbon burial. Hence, our local observations and global upscaling demonstrate the major role played by PEX in saltmarsh carbon budgets. While part of dissolved inorganic carbon returns to the atmosphere as CO2, the remaining bicarbonate fraction is stored in the ocean over long time scales. Our findings strengthen global blue carbon assessments and build arguments for the use of saltmarshes as nature-based solutions for global climate change.

Beyond traditional paper, multifunctional nanopaper has received much attention in recent years. Currently, many nanomaterials have been successfully used as building units of nanopaper. However, it remains a great challenge to prepare flexible and freestanding metal–organic framework (MOF) nanopaper owing to the low aspect ratio and brittleness of MOF nanocrystals. Herein, this work develops a flexible and free-standing MOF nanopaper with MOF nanowires as building units. The manganese-based MOF (Mn-MOF) nanowires with lengths up to 100 μm are synthesized by a facile solvothermal method. Through a paper-making technique, the Mn-MOF nanowires interweave with each other to form a three-dimensional architecture, thus creating a flexible and free-standing Mn-MOF nanowire paper. Furthermore, the surface properties can be engineered to obtain high hydrophobicity by modifying polydimethylsiloxane (PDMS) on the surfaces of the Mn-MOF nanowire paper. The water contact angle reaches 130°. As a proof of concept, this work presents two potential applications of the Mn-MOF/PDMS nanowire paper: (i) The as-prepared Mn-MOF/PDMS nanowire paper is compatible with a commercial printer. The as-printed colorful patterns are of high quality, and (ii) benefiting from the highly hydrophobic surfaces, the Mn-MOF/PDMS nanowire paper is able to efficiently separate oil from water.

Photocatalytic reduction of CO2with H2O is thought as an environment friendly approach for sustainable development. It is highly desirable but remains challenging to develop photocatalyst with metal-free site for CO2reduction. Here, we fabricated a heterostructure by integrating azine-based COF with ZnIn2S4, where the azine unit in COF acts as metal-free sites for CO2adsorption and reduction. The as-formed interfused heterointerface in the heterostructure ensures the effective electron transfer from ZnIn2S4across the interface to the COF, resulting in a spatial separation of redox sites for CO2reduction and water oxidation. The hybrid catalyst exhibits remarkably enhanced photocatalytic activity for CO2reduction to CO, which is 8 and 6 times than the COF and ZnIn2S4, respectively, and is even comparable with some metal-catalyzed CO2reduction systems. This study provides a new paradigm to mimic natural photosynthesis by using metal-free site for CO2reduction.

Ultrasensitive and reliable conductive hydrogels are significant in the construction of human–machine twinning systems. However, in extremely cold environments, freezing severely limits the application of hydrogel-based sensors. Herein, building on biomimetics, a zwitterionic hydrogel was elaborated for human–machine interaction employing multichemical bonding synergies and experimental signal analyses. The covalent bonds, hydrogen bonds, and electrostatic interactions construct a dense double network structure favorable for stress dispersion and hydrogen bond regeneration. In particular, zwitterions and ionic conductors maintained excellent strain response (99 ms) and electrical sensitivity (gauge factor = 14.52) in the dense hydrogel structure while immobilizing water molecules to enhance the weather resistance (-68 °C). Inspired by the high sensitivity, zwitterionic hydrogel-based strain sensors and remote-control gloves were designed by analyzing the experimental signals, demonstrating promising potential applications within specialized flexible materials and human–machine symbiotic systems.

Over the past decades, the role of rearranged during transfection (RET) alterations in tumorigenesis has been firmly established. RET kinase inhibition is an essential therapeutic target in patients with RET-altered cancers. In clinical practice, initial efficacy can be achieved in patients through the utilization of multikinase inhibitors (MKIs) with RET inhibitory activity. However, the effectiveness of these MKIs is impeded by the adverse events associated with off-target effects. Recently, many RET-selective inhibitors, characterized by heightened specificity and potency, have been developed, representing a substantial breakthrough in the field of RET precision oncology. This Perspective focuses on the contemporary understanding of RET mutations, recent advancements in next-generation RET inhibitors, and the challenges associated with resistance to RET inhibitors. It provides valuable insights for the development of next-generation MKIs and selective RET inhibitors.

Designing three-dimensional (3D) porous carbonaceous skeletons for K metal is one of the most promising strategies to inhibit dendrite growth and enhance the cycle life of potassium metal batteries. However, the nucleation and growth mechanism of K metal on 3D skeletons remains ambiguous, and the rational design of suitable K hosts still presents a significant challenge. In this study, the relationships between the binding energy of skeletons toward K and the nucleation and growth of K are systematically studied. It is found that a high binding energy can effectively decrease the nucleation barrier, reduce nucleation volume, and prevent dendrite growth, which is applied to guide the design of 3D current collectors. Density functional theory calculations show that P-doped carbon (P-carbon) exhibits the highest binding energy toward K compared to other elements (e.g., N, O). As a result, the K@P-PMCFs (P-binding porous multichannel carbon nanofibers) symmetric cell demonstrates an excellent cycle stability of 2100 h with an overpotential of 85 mV in carbonate electrolytes. Similarly, the perylene-3,4,9,10-tetracarboxylic dianhydride || K@P-PMCFs cell achieves ultralong cycle stability (85% capacity retention after 1000 cycles). This work provides a valuable reference for the rational design of 3D current collectors.

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871(1), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h, we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087are also presented. The encouraging outcomes indicate that probe 12hpossesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function.

Sunvozertinib is an oral, irreversible, and selective tyrosine kinase inhibitor that has a favourable safety profile and encouraging antitumour activity, as shown in phase 1 studies of patients with heavily pretreated non-small cell lung cancer (NSCLC) with EGFRexon 20 insertion mutation (exon20ins). We aimed to assess the antitumour efficacy of sunvozertinib in patients with platinum-pretreated locally advanced or metastatic NSCLC with EGFRexon20ins.