Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Stabilizing High-Voltage Performance of Nickel-Rich Cathodes via Facile Solvothermally Synthesized Niobium-Doped Strontium Titanate.

Ni-rich layered ternary cathodes are promising candidates thanks to their low toxic Co-content and high energy density (∼800 Wh/kg). However, a critical challenge in developing Ni-rich cathodes is to improve cyclic stability, especially under high voltage (>4.3 V), which directly affects the performance and lifespan of the battery. In this study, niobium-doped strontium titanate (Nb-STO) is successfully synthesized via a facile solvothermal method and used as a surface modification layer onto the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode. The results exhibited that the Nb-STO modification significantly improved the cycling stability of the cathode material even under high-voltage (4.5 V) operational conditions. In particular, the best sample in our work could provide a high discharge capacity of ∼190 mAh/g after 100 cycles under 1 C with capacity retention over 84% in the voltage range of 3.0-4.5 V, superior to the pristine NCM811 (∼61%) and pure STO modified STO-811-600 (∼76%) samples under the same conditions. The improved electrochemical performance and stability of NCM811 under high voltage should be attributed to not only preventing the dissolution of the transition metals, further reducing the electrolyte's degradation by the end of charge, but also alleviating the internal resistance growth from uncontrollable cathode-electrolyte interface (CEI) evolution. These findings suggest that the as-synthesized STO with an optimized Nb-doping ratio could be a promising candidate for stabilizing Ni-rich cathode materials to facilitate the widespread commercialization of Ni-rich cathodes in modern LIBs.

The rise of baobab trees in Madagascar.

The baobab trees (genus Adansonia) have attracted tremendous attention because of their striking shape and distinctive relationships with fauna1. These spectacular trees have also influenced human culture, inspiring innumerable arts, folklore and traditions. Here we sequenced genomes of all eight extant baobab species and argue that Madagascar should be considered the centre of origin for the extant lineages, a key issue in their evolutionary history2,3. Integrated genomic and ecological analyses revealed the reticulate evolution of baobabs, which eventually led to the species diversity seen today. Past population dynamics of Malagasy baobabs may have been influenced by both interspecific competition and the geological history of the island, especially changes in local sea levels. We propose that further attention should be paid to the conservation status of Malagasy baobabs, especially of Adansonia suarezensis and Adansonia grandidieri, and that intensive monitoring of populations of Adansonia za is required, given its propensity for negatively impacting the critically endangered Adansonia perrieri.

Enhanced Piezocatalytic Performance of Li-doped BaTiO3 Through a Facile Sonication-Assisted Precipitation Approach.

Piezocatalysis-induced dye degradation has garnered significant attention as an effective method for addressing wastewater treatment challenges. In our study, we employed a room-temperature sonochemical method to synthesize piezoelectric barium titanate nanoparticles (BaTiO3: BTO) with varying levels of Li doping. This approach not only streamlined the sample preparation process but also significantly reduced the overall time required for synthesis, making it a highly efficient and practical method. One of the key findings was the exceptional performance of the Li-doped BTO nanoparticles. With 20 mg of Li additive, we achieved 90 % removal of Rhodamine B (RhB) dye within a relatively short timeframe of 150 minutes, all while subjecting the sample to ultrasonic vibration. This rapid and efficient dye degradation was further evidenced by the calculated kinetic rate constant, which indicated seven times faster degradation rate compared to pure BTO. The enhanced piezoelectric performance observed in the Li-doped BTO nanoparticles can be attributed to the strategic substitution of Li atoms, which facilitated a more efficient transfer of charge charges at the interface. Overall, our study underscores the potential of piezocatalysis coupled with advanced materials like Li-doped BTO nanoparticles as a viable and promising solution for wastewater treatment, offering both efficiency and environmental sustainability.

Ultrastructure of the antennal sensilla of the praying mantis Creobroter nebulosa Zheng (Mantedea: Hymenopodidae).

The praying mantis Creobroter nebulosa Zheng (Mantedea: Hymenopodidae) is an insect that has medicinal and esthetical importance, and being a natural enemy for many insects, the species is used as a biological control agent. In this publication, we used scanning electron microscopy (SEM) to study the fine morphology of antennae of males and females of this species. The antennae of both sexes are filiform and consist of three parts: scape, pedicel, and flagellum (differing in the number of segments). Based on the external morphology and the sensilla distribution, the antennal flagellum is could be divided into five regions. Seven sensilla types and eleven subtypes of sensilla were observed: grooved peg sensillum (Sgp), Bohm bristles (Bb), basiconic sensillum (Sb), trichoid sensillum (StI, StII), campaniform sensillum (Sca), chaetic sensillum (ScI, ScII, ScIII), and coeloconic sensillum (ScoI, ScoII). In Mantodea, the ScoII is observed for the first time, and it is located on the tip of the flagellum. The external structure and distribution of these sensilla are compared to those of other insects and possible functions of the antennal sensilla are discussed. The males and females of the mantis could be distinguished by the length of antennae and number of Sgp. Males have antennae about 1.5 times longer and have significantly larger number of Sgp compared to females. The sexual difference in distribution of the Sgp suggests that this type of sensilla may play a role in sex-pheromones detection in mantis.

Multi-Interface Engineering of MXenes for Self-Powered Wearable Devices.

Self-powered wearable devices with integrated energy supply module and sensitive sensors have significantly blossomed for continuous monitoring of human activity and the surrounding environment in healthcare sectors. The emerging of MXene-based materials has brought research upsurge in the fields of energy and electronics, owing to their excellent electrochemical performance, large surface area, superior mechanical performance, and tunable interfacial properties, where their performance can be further boosted via multi-interface engineering. Herein, a comprehensive review of recent progress in MXenes for self-powered wearable devices is discussed from the aspects of multi-interface engineering. The fundamental properties of MXenes including electronic, mechanical, optical, and thermal characteristics are discussed in detail. Different from previous review works on MXenes, multi-interface engineering of MXenes from termination regulation to surface modification and their impact on the performance of materials and energy storage/conversion devices are summarized. Based on the interfacial manipulation strategies, potential applications of MXene-based self-powered wearable devices are outlined. Finally, proposals and perspectives are provided on the current challenges and future directions in MXene-based self-powered wearable devices.

Characteristics of spatial and temporal variability in the distribution of biological soil crusts on the Loess Plateau, China.

Biological soil crust (biocrust) is widely distributed on the Loess Plateau and plays multiple roles in regulating ecosystem stability and multifunctionality. Few reports are available on the distribution characteristics of biocrust in this region, which limits the assessment of its ecological functions. Based on 388 sampling points in different precipitation zones on the Loess Plateau from 2009 to 2020, we analyzed the coverage, composition, and influencing factors of biocrust across different durations since land abandonment, precipitation levels, topography (slope aspect and position), and utilization of abandoned slopelands (shrubland, forest, and grassland). On this base, with the assistance of machine learning and spatial modeling methods, we generated a distribution map of biocrust and its composition at a resolution of 250 m × 250 m, and analyzed the spatial distribution of biocrust on the Loess Plateau. The results showed that the average biocrust coverage in the woodlands and grasslands was 47.3%, of which cyanobacterial crust accounted for 25.5%, moss crust 19.7%, and lichen crust 2.1%. There were significant temporal and spatial variations. Temporally, the coverage of biocrust in specific regions fluctuated with the extension of the abandoned durations and coverage of cyanobacterial crust, while moss crust showed a reverse pattern. In addition, the coverage of biocrust in the wet season was slightly higher than that in the dry season within a year. Spatially, the coverage of biocrusts on the sandy lands area on the Loess Plateau was higher and dominated by cyanobacterial crusts, while the coverage was lower in the hilly and gully area. Precipitation and utilization of abandoned land were the major factors driving biocrust coverage and composition, while slope direction and position did not show obvious effect. In addition, soil organic carbon content, pH, and texture were related to the distribution of biocrust. This study uncovered the spatial and temporal variability of biocrust distribution, which might provide important data support for the research and management of biocrust in the Loess Plateau region.

Dual-responsive nanocarriers for efficient cytosolic protein delivery and CRISPR-Cas9 gene therapy of inflammatory skin disorders.

Developing protein drugs that can target intracellular sites remains a challenge due to their inadequate membrane permeability. Efficient carriers for cytosolic protein delivery are required for protein-based drugs, cancer vaccines, and CRISPR-Cas9 gene therapies. Here, we report a screening process to identify highly efficient materials for cytosolic protein delivery from a library of dual-functionalized polymers bearing both boronate and lipoic acid moieties. Both ligands were found to be crucial for protein binding, endosomal escape, and intracellular protein release. Polymers with higher grafting ratios exhibit remarkable efficacies in cytosolic protein delivery including enzymes, monoclonal antibodies, and Cas9 ribonucleoprotein while preserving their activity. Optimal polymer successfully delivered Cas9 ribonucleoprotein targeting NLRP3 to disrupt NLRP3 inflammasomes in vivo and ameliorate inflammation in a mouse model of psoriasis. Our study presents a promising option for the discovery of highly efficient materials tailored for cytosolic delivery of specific proteins and complexes such as Cas9 ribonucleoprotein.

The Cissus quadrangularis genome reveals its adaptive features in an arid habitat.

Cissus quadrangularis is a tetraploid species belonging to the Vitaceae family and is known for the Crassulacean acid metabolism (CAM) pathway in the succulent stem, while the leaves perform C3 photosynthesis. Here, we report a high-quality genome of C. quadrangularis comprising a total size of 679.2 Mb which was phased into two subgenomes. Genome annotation identified 51 857 protein-coding genes, while approximately 47.75% of the genome was composed of repetitive sequences. Gene expression ratios of two subgenomes demonstrated that the sub-A genome as the dominant subgenome played a vital role during the drought tolerance. Genome divergence analysis suggests that the tetraploidization event occurred around 8.9 million years ago. Transcriptome data revealed that pathways related to cutin, suberine, and wax metabolism were enriched in the stem during drought treatment, suggesting that these genes contributed to the drought adaption. Additionally, a subset of CAM-related genes displayed diurnal expression patterns in the succulent stems but not in leaves, indicating that stem-biased expression of existing genes contributed to the CAM evolution. Our findings provide insights into the mechanisms of drought adaptation and photosynthesis transition in plants.

Identification of core genes involved in the response of Apocynum venetum to salt stress based on transcriptome sequencing and WGCNA.

Apocynum venetum L. belongs to the Apocynaceae family and is a plant that is highly resistant to stress. It is important in the fields of ecology, feeding, industry and medicine. The molecular mechanism underlying salt tolerance has not been elucidated. In this study, RNA-seq based transcriptome sequencing of A. venetum leaves after 0, 2, 6, 12, 24 and 48 h of treatment with 300 mM NaCl was performed. We conducted a comprehensive analysis of the transcriptome expression profiles of A. venetum under salt stress using the WGCNA method and identified red, black, and brown as the core modules regulating the salt tolerance of A. venetum. A co-expression regulatory network was constructed to identify the core genes in the module according to the correlations between genes. The genes TRINITY_DN102_c0_g1 (serine carboxypeptidase), TRINITY_DN3073_c0_g1 (SOS signaling pathway) and TRINITY_DN6732_c0_g1 (heat shock transcription factor) in the red module were determined to be the core genes. Two core genes in the black module, TRINITY_DN9926_c0_g1 and TRINITY_DN7962_c0_g1, are pioneer candidate salt tolerance-associated genes in A. venetum. The genes in the brown module were mainly enriched in two pathways, namely photosynthesis and osmotic balance. Among them, the TRINITY_DN6321_c0_g2 and TRINITY_DN244_c0_g1 genes encode aquaporin, which is helpful for maintaining the cell water balance and plays a protective role in defending A. venetum under abiotic stress. Our findings contribute to the identification of core genes involved in the response of A. venetum to salt stress.

Nanocomposites of Conducting Polymers and 2D Materials for Flexible Supercapacitors.

Flexible supercapacitors (FSCs) with high electrochemical and mechanical performance are inevitably necessary for the fabrication of integrated wearable systems. Conducting polymers with intrinsic conductivity and flexibility are ideal active materials for FSCs. However, they suffer from poor cycling stability due to huge volume variations during operation cycles. Two-dimensional (2D) materials play a critical role in FSCs, but restacking and aggregation limit their practical application. Nanocomposites of conducting polymers and 2D materials can mitigate the above-mentioned drawbacks. This review presents the recent progress of those nanocomposites for FSCs. It aims to provide insights into the assembling strategies of the macroscopic structures of those nanocomposites, such as 1D fibers, 2D films, and 3D aerogels/hydrogels, as well as the fabrication methods to convert these macroscopic structures to FSCs with different device configurations. The practical applications of FSCs based on those nanocomposites in integrated self-powered sensing systems and future perspectives are also discussed.

Utility of Rapid On-Site Evaluation during Bronchoscopy in the Diagnosis of Pulmonary Tuberculosis.

INTRODUCTION: The diagnostic value of rapid on-site evaluation (ROSE) in bronchoscopy for lung tumors has been widely researched. However, the diagnostic efficacy of ROSE for pulmonary tuberculosis (TB) has not been extensively assessed yet. This study aimed to examine the value of ROSE in diagnosing pulmonary TB during bronchoscopy, and the relationship between ROSE cytology patterns and acid-fast bacilli (AFB) smears and mycobacterial cultures. METHODS: A retrospective study was conducted at a single respiratory endoscopy center, including 418 patients under clinical or radiological suspicion of having pulmonary TB who underwent bronchoscopy. In addition to the use of ROSE and definitive cytology, material obtained by aspiration/lavage or brushing was sent for AFB smear and mycobacterial culture. If histopathological examination was required, endobronchial biopsy, transbronchial lung biopsy, and transbronchial needle aspiration were performed at the discretion of the clinician. A composite reference standard (CRS) was used as the diagnostic gold standard for this study. The diagnosis obtained by ROSE was compared with the final diagnosis. RESULTS: Of the 418 patients studied, 282 (67.5%) were diagnosed on the basis of bronchoscopic findings, as follows: pulmonary TB, in 238 (84.4%); non-TB, in 44 (15.6%). In 238 pulmonary TB patients, ROSE cytology showed granulomas without necrosis were observed in 107 cases, granulomas and necrosis in 51 cases, caseous necrosis only in 25 cases, and nonspecific inflammation in 55 cases. For the diagnosis of TB according to CRS, ROSE showed the sensitivity, specificity, positive predictive value, and negative predictive value were 76.9%, 68.2%, 92.9%, and 35.3%, respectively. The positivity rate for bacterial detection through acid-fast staining and culture during bronchoscopy was 51.7%. The cytological pattern showed a higher detection rate for bacteria in cases of necrosis. DISCUSSION: The application of ROSE during bronchoscopy is a straightforward procedure that delivers an immediate and precise assessment regarding the adequacy of collected samples, enabling a preliminary diagnosis of pulmonary TB. ROSE has exhibited a higher sensitivity in detecting pulmonary TB compared to microbiological examinations. In addition, the cytological presentation of ROSE tends to show a higher positivity rate for microbiological testing in caseous necrosis. Therefore, samples with these characteristics should be prioritized for microbiological examination after on-site evaluation.

Graphene and MOF Assembly: Enhanced Fabrication and Functional Derivative via MOF Amorphization.

The integration of graphene and metal-organic frameworks (MOFs) has numerous implications across various domains, but fabricating such assemblies is often complicated and time-consuming. Herein, a one-step preparation of graphene-MOF assembly is presented by directly impregnating vertical graphene (VG) arrays into the zeolitic imidazolate framework (ZIF) precursors under ambient conditions. This approach can effectively assemble multiple ZIFs, including ZIF-7, ZIF-8, and ZIF-67, resulting in their uniform dispersion on the VG with adjustable sizes and shapes. Hydrogen defects on the VG surface are critical in inducing such high-efficiency ZIF assembly, acting as the reactive sites to interact with the ZIF precursors and facilitate their crystallisation. The versatility of VG-ZIF-67 assembly is further demonstrated by exploring the process of MOF amorphization. Surprisingly, this process leads to an amorphous thin-film coating formed on VG (named VG-IL-amZIF-67), which preserves the short-range molecular bonds of crystalline ZIF-67 while sacrificing the long-range order. Such a unique film-on-graphene architecture maintains the essential characteristics and functionalities of ZIF-67 within a disordered arrangement, making it well-suited for electrocatalysis. In electrochemical oxygen reduction, VG-IL-amZIF-67 exhibits exceptional activity, selectivity, and stability to produce H2O2 in acid media.

CCNI2 promotes pancreatic cancer through PI3K/AKT signaling pathway.

Globally, pancreatic cancer is recognized as one of the deadliest malignancies that lacks effective targeted therapies. This study aims to explore the role of cyclin I-like protein (CCNI2), a homolog of cyclin I (CCNI), in the progression of pancreatic cancer, thereby providing a theoretical basis for its treatment. Firstly, the expression of CCNI2 in pancreatic cancer tissues was determined through immunohistochemical staining. The biological role of CCNI2 in pancreatic cancer cells was further assessed using both in vitro and in vivo loss/gain-of-function assays. Our data revealed that CCNI2 expression was abnormally elevated in pancreatic cancer, and clinically, increased CCNI2 expression generally correlated with reduced overall survival. Functionally, CCNI2 contributed to the malignant progression of pancreatic cancer by promoting the proliferation and migration of tumor cells. Consistently, in vivo experiments verified that CCNI2 knockdown impaired the tumorigenic ability of pancreatic cancer cells. Moreover, the addition of phosphatidylinositol 3-kinase (PI3K) inhibitors could partially reverse the promoting effect of CCNI2 on the malignant phenotypes of pancreatic cancer cells. CCNI2 promoted pancreatic cancer through PI3K/protein kinase B (AKT) signaling pathway, indicating its potential as a prognostic marker and therapeutic target for pancreatic cancer.

Aluminium stress-induced modulation of root gravitropism in pea (Pisum sativum) via auxin signalling.

Aluminium (Al) toxicity stands out as a primary cause of crop failure in acidic soils. The root gravity setpoint angle (GSA), one of the important traits of the root system architecture (RSA), plays a pivotal role in enabling plants to adapt to abiotic stress. This study explored the correlation between GSA and Al stress using hydroponic culture with pea (Pisum sativum) plants. The findings revealed that under Al stress, GSA increased in newly developed lateral roots. Notably, this response remained consistent regardless of the treatment duration, extending for at least 3 days during the experiment. Furthermore, exposure to Al led to a reduction in both the size and quantity of starch granules, pivotal components linked to gravity perception. The accumulation of auxin in root transition zone increased. This variation was mirrored in the expression of genes linked to granule formation and auxin efflux, particularly those in the PIN-formed family. This developmental framework suggested a unique role for the root gravitropic response that hinges on starch granules and auxin transport, acting as mediators in the modulation of GSA under Al stress. Exogenous application of indole-3-acetic acid (IAA) and the auxin efflux inhibitor N-1-naphthylphthalamic acid (NPA) had an impact on the root gravitropic response to Al stress. The outcomes indicate that Al stress inhibited polar auxin transport and starch granule formation, the two processes crucial for gravitropism. This impairment led to an elevation in GSA and a reconfiguration of RSA. This study introduces a novel perspective on how plant roots react to Al toxicity, culminating in RSA modification in the context of acidic soil with elevated Al concentrations.

Long-term survival and portal vein patency with novel PVTT surgery approach in advanced HCC patients with Vp3/4 PVTT following combination therapy of TKIs and PD-1 inhibitors.

BACKGROUND: It is controversial whether patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) should undergo salvage surgery following the combination therapy of tyrosine kinase inhibitors (TKIs) and programmed cell death protein 1 (PD-1) inhibitors. This study aimed to elucidate the efficiency and safety of salvage surgery following combination therapy, while also summarizing a novel surgical approach for Vp3/4 PVTT. METHODS: Between April 2019 and December 2022, a consecutive series of unresectable HCC patients with PVTT who received salvage surgery following combination therapy were enrolled. Evaluation included perioperative and long-term follow-up outcomes. The complete removal of Vp3/4 PVTT was achieved using a novel surgical approach characterized by "longitudinal incision and transverse suturing" and "angle-to-straight conversion". RESULTS: Forty patients including 22 patients with Vp3 and 18 patients with Vp4 were included. Long-term follow-up showed similar rates of portal vein patency (Vp3: 95.5%, Vp4:94.4%, p = 0.900), and 3-year portal vein patency rates were 95.0%. There were no significant differences observed in combination therapy-related adverse events (p = 0.253) and perioperative complications (p = 0.613) between the Vp3 and Vp4 groups. The recurrence patterns were similar between the two groups (p = 0.131). There were no significant differences in overall survival (OS) and recurrence-free (RFS) survival between the Vp3 and Vp4 groups (OS p = 0.457, RFS p = 0.985). Patients who achieved a pathological complete response had significantly better RFS (p = 0.011). CONCLUSION: Salvage surgery after combination therapy demonstrated favorable efficacy and safety. The novel surgical approach for PVTT can effectively achieve complete removal of PVTT and ensured long-term portal vein patency.

Integrative analysis of microbiota and metabolomics in chromium-exposed silkworm (Bombyx mori) midguts based on 16S rDNA sequencing and LC/MS metabolomics.

The gut microbiota, a complex ecosystem integral to host wellbeing, is modulated by environmental triggers, including exposure to heavy metals such as chromium. This study aims to comprehensively explore chromium-induced gut microbiota and metabolomic shifts in the quintessential lepidopteran model organism, the silkworm (Bombyx mori). The research deployed 16S rDNA sequence analysis and LC/MS metabolomics in its experimental design, encompassing a control group alongside low (12 g/kg) and high (24 g/kg) feeding chromium dosing regimens. Considerable heterogeneity in microbial diversity resulted between groups. Weissella emerged as potentially resilient to chromium stress, while elevated Propionibacterium was noted in the high chromium treatment group. Differential analysis tools LEfSe and random forest estimation identified key species like like Cupriavidus and unspecified Myxococcales, offering potential avenues for bioremediation. An examination of gut functionality revealed alterations in the KEGG pathways correlated with biosynthesis and degradation, suggesting an adaptive metabolic response to chromium-mediated stress. Further results indicated consequential fallout in the context of metabolomic alterations. These included an uptick in histidine and dihydropyrimidine levels under moderate-dose exposure and a surge of gentisic acid with high-dose chromium exposure. These are critical players in diverse biological processes ranging from energy metabolism and stress response to immune regulation and antioxidative mechanisms. Correlative analyses between bacterial abundance and metabolites mapped noteworthy relationships between marker bacterial species, such as Weissella and Pelomonas, and specific metabolites, emphasizing their roles in enzyme regulation, synaptic processes, and lipid metabolism. Probiotic bacteria showed robust correlations with metabolites implicated in stress response, lipid metabolism, and antioxidant processes. Our study reaffirms the intricate ties between gut microbiota and metabolite profiles and decodes some systemic adaptations under heavy-metal stress. It provides valuable insights into ecological and toxicological aspects of chromium exposure that can potentially influence silkworm resilience.

Relieving Stress Concentration through Anion-Cation Codoping toward Highly Stable Nickel-Rich Cathode.

Nickel-rich LiNi0.8Co0.15Al0.015O2 (NCA) with excellent energy density is considered one of the most promising cathodes for lithium-ion batteries. Nevertheless, the stress concentration caused by Li+/Ni2+ mixing and oxygen vacancies leads to the structural collapse and obvious capacity degradation of NCA. Herein, a facile codoping of anion (F-)-cation (Mg2+) strategy is proposed to address these problems. Benefiting from the synergistic effect of F- and Mg2+, the codoped material exhibits alleviated Li+/Ni2+ mixing and demonstrates enhanced electrochemical performance at high voltage (≥4.5 V), outperformed the pristine and F-/Mg2+ single-doped counterparts. Combined experimental and theoretical studies reveal that Mg2+ and F- codoping decreases the Li+ diffusion energy barrier and enhances the Li+ transport kinetics. In particular, the codoping synergistically suppresses the Li+/Ni2+ mixing and lattice oxygen escape, and alleviates the stress-strain accumulation, thereby inhibiting crack propagation and improving the electrochemical performance of the NCA. As a consequence, the designed Li0.99Mg0.01Ni0.8Co0.15Al0.05O0.98F0.02 (Mg1+F2) demonstrates a much higher capacity retention of 82.65% than NCA (55.69%) even after 200 cycles at 2.8-4.5 V under 1 C. Furthermore, the capacity retention rate of the Mg1+F2||graphite pouch cell after 500 cycles is 89.6% compared to that of the NCA (only 79.4%).

Lenvatinib plus anti-PD-1 antibodies as conversion therapy for patients with unresectable intermediate-advanced hepatocellular carcinoma: a single-arm, phase II trial.

BACKGROUND: Over 70% of the patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage and lose the opportunity for radical surgery. Combination therapy of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death protein-1 (PD-1) antibodies has achieved a high tumor response rate in both the first-line and second-line treatment of advanced HCC. However, few studies have prospectively evaluated whether TKIs plus anti-PD-1 antibodies could convert unresectable intermediate-advanced HCC into resectable disease. METHODS: This single-arm, phase II study enrolled systemic therapy-naïve adult patients with unresectable Barcelona Clinic Liver Cancer stage B or C HCC. Patients received oral lenvatinib one time per day plus intravenous anti-PD-1 agents every 3 weeks (one cycle). Tumor response and resectability were evaluated before the fourth cycle, then every two cycles. The primary endpoint was conversion success rate by investigator assessment. Secondary endpoints included objective response rate (ORR) by independent imaging review (IIR) assessment per modified RECIST (mRECIST) and Response Evaluation Criteria in Solid Tumors, V.1.1 (RECIST 1.1), progression-free survival (PFS) and 12-month recurrence-free survival (RFS) rate by IIR per mRECIST, R0 resection rate, overall survival (OS), and safety. Biomarkers were assessed as exploratory objectives. RESULTS: Of the 56 eligible patients enrolled, 53 (94.6%) had macrovascular invasion, and 16 (28.6%) had extrahepatic metastasis. The median follow-up was 23.5 months. The primary endpoint showed a conversion success rate of 55.4% (31/56). ORR was 53.6% per mRECIST and 44.6% per RECIST 1.1. Median PFS was 8.9 months, and median OS was 23.9 months. Among the 31 successful conversion patients, 21 underwent surgery with an R0 resection rate of 85.7%, a pathological complete response rate of 38.1%, and a 12-month RFS rate of 47.6%. Grade ≥3 treatment-related adverse events were observed in 42.9% of patients. Tumor immune microenvironment analysis of pretreatment samples displayed significant enrichment of CD8+ T cells (p=0.03) in responders versus non-responders. CONCLUSION: Lenvatinib plus anti-PD-1 antibodies demonstrate promising efficacy and tolerable safety as conversion therapy in unresectable HCC. Pre-existing CD8+ cells are identified as a promising biomarker for response to this regimen. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR1900023914.

Dual-modification of Ni-rich cathode materials through strontium titanate coating and thermal treatment.

Ni-rich layered structure ternary oxides, such as LiNi0.8Co0.1Mn0.1O2 (NCM811), are promising cathode materials for high-energy lithium-ion batteries (LIBs). However, a trade-off between high capacity and long cycle life still obstructs the commercialization of Ni-rich cathodes in modern LIBs. Herein, a facile dual modification approach for improving the electrochemical performance of NCM811 was enabled by a typical perovskite oxide: strontium titanate (SrTiO3). With a suitable thermal treatment, the modified cathode exhibited an outstanding electrochemical performance that could deliver a high discharge capacity of 188.5 mAh/g after 200 cycles under 1C with a capacity retention of 90%. The SrTiO3 (STO) protective layer can effectively suppress the side reaction between the NCM811 and the electrolyte. In the meantime, the pillar effect provided by interfacial Ti doping could effectively reduce the Li+/Ni2+ mixing ratio on the NCM811 surface and offer more efficient Li+ migration between the cathode and the coating layer after post-thermal treatment (≥600 °C). This dual modification strategy not only significantly improves the structural stability of Ni-rich layered structure but also enhances the electrochemical kinetics via increasing diffusion rate of Li+. The electrochemical measurement results further disclosed that the 3 wt% STO coated NCM811 with 600 °C annealing exhibits the best performance compared with other control samples, suggesting an appropriate temperature range for STO coated NCM811 cathode is critical for maintaining a stable structure for the whole system. This work may offer an effective option to enhance the electrochemical performance of Ni-rich cathodes for high-performance LIBs.