Portal vein tumor thrombus (PVTT) is a frequent complication in hepatocellular carcinoma (HCC). HCC patients with PVTT have the characteristics of less treatment tolerance and poor prognosis. ...Immunotherapy, especially combined immunotherapy, has been successfully used in advanced HCC. However, there are no recognized universally indicators that can predict response or resistance to immunotherapy for HCC. Herein, we reported a 58-year-old HCC patient with PVTT, cirrhosis and chronic viral hepatitis, who achieved complete response (CR) after combined immunotherapy (camrelizumab combined with sorafenib or regorafenib), according to his high enrichment of tumor-infiltrating immune cells and tertiary lymphoid structure (TLS). In this case, we revealed the characteristics of the baseline tumor immune microenvironment (TIME) in a HCC patient who responded well to combined immunotherapy, suggesting that TIME can be used to assist in clinical decision making of immunotherapy for HCC.
Captivity is an important and efficient technique for rescuing endangered species. However, it induces infertility, and the underlying mechanism remains obscure. This study used the plateau pika (
) ...as a model to integrate physiological, metagenomic, metabolomic, and transcriptome analyses and explore whether dysbiosis of the gut microbiota induced by artificial food exacerbates infertility in captive wild animals. Results revealed that captivity significantly decreased testosterone levels and the testicle weight/body weight ratio. RNA sequencing revealed abnormal gene expression profiles in the testicles of captive animals. The microbial α-diversity and Firmicutes/Bacteroidetes ratio were drastically decreased in the captivity group.
and
abundance notably increased in captive pikas. Metagenomic analysis revealed that the alteration of flora increased the capacity for carbohydrate degradation in captivity. The levels of microbe metabolites' short-chain fatty acids (SCFAs) were significantly high in the captive group. Increasing SCFAs influenced the immune response of captivity plateau pikas; pro-inflammatory cytokines were upregulated in captivity. The inflammation ultimately contributed to male infertility. In addition, a positive correlation was observed between
family abundance and testosterone concentration. Our results provide evidence for the interactions between artificial food, the gut microbiota, and male infertility in pikas and benefit the application of gut microbiota interference in threatened and endangered species.
In this study, we investigate the dynamic magnetoelectric (ME) coupling behaviors of GdFeO3 under pulsed magnetic fields. When a magnetic field is applied along the c-axis, and the temperature is ...near the compensation temperature (T comp = 3.5 K), we observe a subtle transition involving the reversal of Fe3+ moments at approximately 0.8 T in magnetization (M) measurements. This transition induces a corresponding jump in electrical polarization (P), which is not present in the static field measurements. The dynamic intertwining between M and P signifies a competition between antiferromagnetic (AFM) coupling between Gd3+ and Fe3+ moments and their Zeeman energies. The robust AFM coupling leads to the reversal of Fe3+ moments near T comp, triggering the abrupt change in P. Based on the exchange striction mechanism in the ferrimagnetic GdFeO3, we propose the possibility of achieving highly magnetic field sensitive ME coupling near the compensation temperature in ferrimagnetic multiferroic orthoferrites.
Abstract The quest for smart electronics with higher energy densities has intensified the development of high‐voltage LiCoO 2 (LCO). Despite their potential, LCO materials operating at 4.7 V faces ...critical challenges, including interface degradation and structural collapse. Herein, we propose a collective surface architecture through precise nanofilm coating and doping that combines an ultra‐thin LiAlO 2 coating layer and gradient doping of Al. This architecture not only mitigates side reactions, but also improves the Li + migration kinetics on the LCO surface. Meanwhile, gradient doping of Al inhibited the severe lattice distortion caused by the irreversible phase transition of O3−H1−3−O1, thereby enhanced the electrochemical stability of LCO during 4.7 V cycling. DFT calculations further revealed that our approach significantly boosts the electronic conductivity. As a result, the modified LCO exhibited an outstanding reversible capacity of 230 mAh g −1 at 4.7 V, which is approximately 28 % higher than the conventional capacity at 4.5 V. To demonstrate their practical application, our cathode structure shows improved stability in full pouch cell configuration under high operating voltage. LCO exhibited an excellent cycling stability, retaining 82.33 % after 1000 cycles at 4.5 V. This multifunctional surface modification strategy offers a viable pathway for the practical application of LCO materials, setting a new standard for the development of high‐energy‐density and long‐lasting electrode materials.
The quest for smart electronics with higher energy densities has intensified the development of high-voltage LiCoO2 (LCO). Despite their potential, LCO materials operating at 4.7 V faces critical ...challenges, including interface degradation and structural collapse. Herein, we propose a collective surface architecture through precise nanofilm coating and doping that combines an ultra-thin LiAlO2 coating layer and gradient doping of Al. This architecture not only mitigates side reactions, but also improves the Li+ migration kinetics on the LCO surface. Meanwhile, gradient doping of Al inhibited the severe lattice distortion caused by the irreversible phase transition of O3-H1-3-O1, thereby enhanced the electrochemical stability of LCO during 4.7 V cycling. DFT calculations further revealed that our approach significantly boosts the electronic conductivity. As a result, the modified LCO exhibited an outstanding reversible capacity of 230 mAh g-1 at 4.7 V, which is approximately 28% higher than the conventional capacity at 4.5 V. To demonstrate their practical application, our cathode structure shows improved stability in full pouch cell configuration under high operating voltage. LCO exhibited an excellent cycling stability, retaining 82.33% after 1000 cycles at 4.5 V. This multifunctional surface modification strategy offers a viable pathway for the practical application of LCO materials.
Currently, the incidence of infertility has increased year by year. Assisted reproductive technology (ART) is one of the effective strategies to treat infertility. In the process of ART, commonly ...used methods for sperm separation have shortcomings and there is still room for improvement. In this study, a functional sperm selection strategy was established based on hyaluronic acid (HA) modified magnetic microbeads (MBs) and a supporting two-dimensional electromagnetic manipulation device system. Due to the modification of HA on the surface of MBs, HA-MBs has the ability to target and bind to specific receptors on the sperm membrane to form a sperm-MBs complex. A disulfide linker was introduced to connect HA and MBs. After modifying HA and connecting it with the disulfide linker, the sperm of sperm-MBs can be released under the combined effect of hyaluronidase and reduced GSH with the disulfide bond broken and HA degraded. A two-dimensional electromagnetic manipulation system was introduced to generate magnetic field and control the directional movement of the sperm-MBs complex under the guidance of an inverted microscope. The free MBs can also be removed after sperm gets released. Furthermore, the mice sperm selected through this strategy can achieve normal insemination via ICSI and the obtained blastocysts have normal morphology and developmental milestones. This strategy has potential to be developed into an automated screening solution for the screening of functional sperm for assisted reproductive technology.
Synergistic coupling among Mg2B2O5, polycarbonate, and N,N-dimethylformamide enhances the electrochemical performance of PVDF-HFP-based solid electrolyte.
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Polymer solid electrolytes ...(SPEs) based on the solvate-Li+ complex structure have promising prospects in lithium metal batteries (LMBs) due to their unique ion transport mechanism. However, the solvation structure may compromise the mechanical performance and safety, hindering practical application of SPEs. In this work, a composite solid electrolyte (CSE) is designed through the organic–inorganic synergistic interaction among N,N-dimethylformamide (DMF), polycarbonate (PC), and Mg2B2O5 in poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP). Flame-retardant Mg2B2O5 nanowires provide non-flammability to the prepared CSEs, and the addition of PC improves the dispersion of Mg2B2O5 nanowires. Simultaneously, the organic–inorganic synergistic action of PC plasticizer and Mg2B2O5 nanowires promotes the dissociation degree of LiTFSI and reduces the crystallinity of PVDF-HFP, enabling rapid Li ion transport. Additionally, Raman spectroscopy and DFT calculations confirm the coordination between Mg atoms in Mg2B2O5 and N atoms in DMF, which exhibits Lewis base-like behavior attacking adjacent C–F and C–H bonds in PVDF-HFP while inducing dehydrofluorination of PVDF-HFP. Based on the synergistic coupling of Mg2B2O5, PC, and DMF in the PVDF-HFP matrix, the prepared CSE exhibits superior ion conductivity (9.78 × 10−4 S cm−1). The assembled Li symmetric cells cycle stably for 3900 h at a current density of 0.1 mA cm−2 without short circuit. The LFP||Li cells assembled with PDL-Mg2B2O5/PC CSEs show excellent rate capability and cycling performance, with a capacity retention of 83.3% after 1000 cycles at 0.5 C. This work provides a novel approach for the practical application of organic–inorganic synergistic CSEs in LMBs.
The electric vehicle, if accessed in the distribution network disorderly and extensively, will influence the safe, stable, and economic operation of the network, due to the characteristics of its ...randomness, intermittency, and duality with source and load. Here, the power demand models of different electric vehicles were established by analysing the behaviour of electric vehicle loads attributed to different users, and the spatial-temporal distribution pattern of various electric vehicle loads in the distribution network was predicted with the Monte–Carlo method. Based on this regular pattern, an evaluation method for the adaptability of the distribution network to electric vehicles was proposed. Finally, the influence of electric vehicle loads under different access modes on the static voltage stability margin was tested with the IEEE33 node distribution network.
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Background: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with FOLFOX (5- fluorouracil, leucovorin, and oxaliplatin) in hepatocellular ...carcinoma (HCC) patients with microvascular invasion (MVI). Methods: In this randomized, open label, multicenter, phase 3 trial, histologically confirmed HCC patients with MVI were randomized (1:1) to receive either 1 to 2 cycles of adjuvant HAIC-FOLFOX (treatment group) or routine follow-up without any adjuvant treatment (control group). The primary endpoint was disease free survival (DFS), Secondary endpoints included overall survival (OS), recurrence rate and safety. Survival rates were calculated by the Kaplan-Meier plots. Adverse events (AE) were graded according to NCI-CTCAE version 5.0. Results: Between June, 2016 and August, 2021, a total of 315 patients in 5 centers were enrolled in to the study and eligible patients were randomly assigned to the treatment group (n = 157) or control group (n = 158) and were included in the intention-to-treat (ITT) population. Among these 14 patients from treatment group and 15 patients from control group were excluded from the per-protocol (PP) population. 148 patients in treatment group underwent at least 1 cycle of HAIC were included in safety analyses. The median DFS of treatment group and control group were 27.0 months (95% CI, 17.0-37.0) and 11.3 months (95% CI, 7.9-14.7), respectively in ITT population, while which was 20.4 months (95% CI, 9.5-31.3) and 9.7 months (95% CI, 6.9-12.4), respectively in PP population. The DFS were significantly better in the treatment group than in the control group in both ITT population and PP population (p = 0.001 and < 0.001, respectively). The DFS rates at 1, 2, and 3-years were 64.3%, 50.4%, and 44.3% in treatment group and 47.3%, 33.3%, and 24.2% in control group, respectively in ITT population, while which were 64.0%, 48.2%, and 42.2% in treatment group and 43.3%, 27.1%, and 18.4% in control group, respectively in PP population. The OS rates at 1, 2, and 3-year for the treatment group were 94.7%, 87.6%, and 80.5%, and were 91.9%, 85.9%, and 77.0% for the control group, respectively in ITT population, while which were 94.9%, 86.7%, and 80.9% in treatment group and 91.8%, 84.9%, and 75.3% in control group, respectively in PP population. Furthermore, in ITT population, there were 63 (40.1%) patients in the treatment group and 88 (55.7%) patients in the control group had recurrence. Majority of the AEs observed were grade 0-1 (n = 124 (83.8%)) and no treatment related death was observed during the study period. Conclusions: Postoperative adjuvant HAIC with FOLFOX significantly improved the survival benefits with acceptable toxicities in HCC patients with MVI. Clinical trial information: NCT03192618.
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