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Abstract The influences of thermal cycling ageing on structures and insulation performances of polypropylene (PP)/elastomer/boron nitride (BN) nanocomposites are investigated. The Melt blending method was used to prepare the nanocomposites, in which propylene‐based elastomer (PBE) or ethylene‐octene copolymer elastomer (EOC) was contained for comparison. Then, the samples were treated using a thermal cycling process with a temperature range from −30 to 150°C, and the number of thermal cycles was set from 0 to 15. Scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry and X‐ray diffraction measurements were taken to facilitate the comprehension of structural changes. Additionally, measurements were taken to assess the trap distribution and direct current (DC) breakdown strength of the samples. The obtained results revealed that following thermal cycling ageing, the morphology and crystallinity of PP/PBE/BN remained almost unchanged. In contrast, PP/EOC/BN exhibited substantial microstructural damage accompanied by a significant reduction in crystallinity. As the number of thermal cycles increased, the trap level and DC breakdown strength of PP/PBE/BN were maintained at high levels, while those of PP/EOC/BN initially remained stable but then experienced a sharp decline. It is suggested that the addition of BN nanoparticles enhances the thermal cycling ageing resistance of the PP/PBE blend, whereas it weakens this resistance of the PP/EOC blend.

Abstract Sonopiezocatalytic therapy is an emerging therapeutic strategy that utilizes ultrasound irradiation to activate piezoelectric materials, inducing polarization and energy band bending to facilitate the generation of reactive oxygen species (ROS). However, the efficient generation of ROS is hindered by the long distance of charge migration from the bulk to the material surface. Herein, atomically thin Bi2O2(OH)(NO3) (AT‐BON) nanosheets are rationally engineered through disrupting the weaker hydrogen bonds within the [OH] and [NO3] layer in the bulk material. The ultrathin structure of AT‐BON piezocatalytic nanosheets shortens the migration distance of carriers, expands the specific surface area, and accelerates the charge transfer efficiency, showcasing a natural advantage in ROS generation. Importantly, the non‐centrosymmetric polar crystal structure grants the nanosheets the ability to separate electron‐hole pairs. Under ultrasonic mechanical stress, Bi2O2(OH)(NO3) nanosheets with the remarkable piezoelectric feature exhibit the desirable in vivo antineoplastic outcomes in both breast cancer model and liver cancer model. Especially, the AT‐BON‐induced ROS bursts lead to the activation of the Caspase‐1‐driven pyroptosis pathway. This study highlights the beneficial impact of bulk material thinning on enhancing ROS generation efficiency and anti‐cancer effects.

Abstract The therapeutic efficacy of vaccines for treating cancers in clinics remains limited. Here, a rationally designed cancer vaccine by placing immunogenically differential and clinically approved aluminum (Al) or manganese (Mn) in a 2D nanosheet (NS) architecture together with antigens is reported. Structurally optimal NS with a high molar ratio of Mn to Al (MANS‐H) features distinctive immune modulation, markedly promoting the influx of heterogeneous innate immune cells at the injection site. Stimulation of multiple subsets of dendritic cells (DCs) significantly increases the levels, subtypes, and functionalities of antigen‐specific T cells. MANS‐H demonstrates even greater effectiveness in the production of antigen‐specific antibodies than the commercial adjuvant (Alhydrogel) by priming T helper (Th)2 cells rather than T follicular helper (Tfh) cells. Beyond humoral immunity, MANS‐H evokes high frequencies of antigen‐specific Th1 and CD8+ cell immunity, which are comparable with Quil‐A that is widely used in veterinary vaccines. Immunized mice with MANS‐H adjuvanted vaccines exert strong potency in tumor regression by promoting effector T cells infiltrating at tumor and overcoming tumor resistance in multiple highly aggressive tumor models. The engineered immunogen with an intriguing NS architecture and safe immunopotentiators offers the next clinical advance in cancer immunotherapy.

Abstract The recent discovery of nickelate superconductivity represents an important step toward understanding the four‐decade mastery of unconventional high‐temperature superconductivity. However, the synthesis of the infinite‐layer nickelate superconductors shows great challenges. Particularly, surface capping layers are usually unitized to facilitate the sample synthesis. This leads to an important question whether nickelate superconductors with d9 configuration and ultralow valence of Ni1+ are in metastable state and whether nickelate superconductivity can be robust? In this work, a series of redox cycling experiments are performed across the phase transition between perovskite Nd0.8Sr0.2NiO3 and infinite‐layer Nd0.8Sr0.2NiO2. The infinite‐layer Nd0.8Sr0.2NiO2 is quite robust in the redox environment and can survive the cycling experiments with unchanged crystallographic quality. However, as the cycling number goes on, the perovskite Nd0.8Sr0.2NiO3 shows structural degradation, suggesting stability of nickelate superconductivity is not restricted by the ultralow valence of Ni1+, but by the quality of its perovskite precursor. The observed robustness of infinite‐layer Nd0.8Sr0.2NiO2 up to ten redox cycles further indicates that if an ideal high‐quality perovskite precursor can be obtained, infinite‐layer nickelate superconductivity can be very stable and sustainable under environmental conditions. This work provides important implications for potential device applications for nickelate superconductors.

Abstract Background The blood–cerebrospinal fluid barrier (BCSFB) comprises the choroid plexus epithelia. It is important for brain development, maintenance, function, and especially for maintaining immune homeostasis in the cerebrospinal fluid (CSF). Although previous studies have shown that the peripheral immune function of the body is impaired upon exposure to microgravity, no studies have reported changes in immune cells and cytokines in the CSF that reflect neuroimmune status. The purpose of this study is to investigate the alterations in cerebrospinal fluid (CSF) immune homeostasis induced by microgravity and its mechanisms. This research is expected to provide basic data for brain protection of astronauts during spaceflight. Methods The proportions of immune cells in the CSF and peripheral blood (PB) of SMG rats were analyzed using flow cytometry. Immune function was evaluated by measuring cytokine concentrations using the Luminex method. The histomorphology and ultrastructure of the choroid plexus epithelia were determined. The concentrations of intercellular junction proteins in choroid plexus epithelial cells, including vascular endothelial‐cadherin (VE‐cadherin), zonula occludens 1 (ZO‐1), Claudin‐1 and occludin, were detected using western blotting and immunofluorescence staining to characterize BCSFB injury. Results We found that SMG caused significant changes in the proportion of CD4 and CD8 T cells in the CSF and a significant increase in the levels of cytokines (GRO/KC, IL‐18, MCP‐1, and RANTES). In the PB, there was a significant decrease in the proportion of T cells and NKT cells and a significant increase in cytokine levels (GRO/KC, IL‐18, MCP‐1, and TNF‐α). Additionally, we observed that the trends in immune markers in the PB and CSF were synchronized within specific SMG durations, suggesting that longer SMG periods (≥21 days) have a more pronounced impact on immune markers. Furthermore, 21d‐SMG resulted in ultrastructural disruption and downregulated expression of intercellular junction proteins in rat choroid plexus epithelial cells. Conclusions We found that SMG disrupts the BCSFB and affects the CSF immune homeostasis. This study provides new insights into the health protection of astronauts during spaceflight.

Abstract The treatment of colorectal cancer is always a major challenge in the field of cancer research. The number of estimated new cases of colorectal cancer worldwide in 2020 is 1 148 515, and the estimated number of deaths is 576 858, revealing that mortality accounted for approximately half of the disease incidence. The development of new drugs and strategies for colorectal cancer treatment is urgently needed. Thermosensitive injectable hydrogel PDLLA‐PEG‐PDLLA (PLEL) loaded with cabazitaxel (CTX) is used to explore its anti‐tumor effect on mice with orthotopic colorectal cancer. CTX/PLEL is characterized by a solution state at room temperature and a hydrogel state at physiologic temperature. The excipients MPEG‐PCL and PDLLA‐PEG‐PDLLA have good biocompatibility and biodegradability. The simple material synthesis and preparation process renders this system cost‐effective and more conducive to clinical transformation. An orthotopic colorectal cancer model is established by transplantation subcutaneous tumors onto the cecum of mice. According to the results of experiments in vivo, CTX/PLEL significantly inhibits orthotopic colorectal cancer and liver metastasis in mice. The results indicate that CTX/PLEL nanoparticle preparations have high security and excellent anti‐tumor effects, and have great application potential in colorectal cancer therapy.

Abstract Despite the proceeds in the management of acute myocardial infarction (AMI), the current therapeutic landscape still suffers from limited success in the clinic. Exaggerated inflammatory immune response and excessive oxidative stress are key pathological features aggravating myocardium damage. Herein, catalytic immunomodulatory nanocomplexes as anti‐AMI therapeutics to resolve reactive oxygen species (ROS)‐proinflammatory neutrophils‐specific‐inflammation is engineered. The nanocomplexes contain lyophilic S100A8/9 inhibitor ABR2575 in the core of nanoemulsions, which effectively disrupts the neutrophils‐S100A8/A9‐inflammation signaling pathway in the AMI microenvironment. Additionally, ROS scavenger ultrasmall CuxO nanoparticles are incorporated into the nanoemulsions via coordinating with SH groups of poly(ethylene glycol) (PEG)‐conjugated lipids, which mimic multiple enzymes, dramatically alleviating the oxidative stress damage to myocardial tissue. This combination strategy significantly suppresses the infiltration of pro‐inflammatory monocytes, macrophages, and neutrophils, as well as the secretion of inflammatory cytokines. Additionally, it potentially triggers cardiac Tert activation, which promotes myocardial function and decreases infarction size in preclinical murine AMI models. This approach offers a new nanomedicine for treating AMI, resulting in a dramatically enhanced therapeutic outcome.

Abstract In recent years, negative pressure wound dressings have garnered widespread attentions. However, it is challenging to drain the accumulated fluid under negative pressures for hydrogel dressings. To address this issue, this study prepared a chemical/physical duel‐network PEG‐CMCS/AG/MXene hydrogel composed by chemical disulfide crosslinked network of four‐arm polyethylene glycol/carboxymethyl chitosan (4‐Arm‐PEG‐SH/CMCS), and the physical network of hydrogen bond of agar (AG). Under near‐infrared light (NIR) irradiation, the PEG‐CMCS/AG/MXene hydrogel undergoes photothermal heating due to integrate of MXene, which destructs the hydrogen bond network and allows the removal of exudate through a mechanism mimicking the sweat gland‐like effect of skin pores. The photothermal heating effect also enables the antimicrobial activity to prevent wound infections. The excellent electrical conductivity of PEG‐CMCS/AG/MXene can promote cell proliferation under the external electrical stimulation (ES) in vitro. The animal experiments of full‐thickness skin defect model further demonstrate its ability to accelerate wound healing. The conversion between thioester and thiol achieved with L‐cysteine methyl ester hydrochloride (L‐CME) can provides the on‐demand dissolution of the dressing in situ. This study holds promises to provide a novel solution to the issue of fluid accumulations under hydrogel dressings and offers new approaches to alleviating or avoiding the significant secondary injuries caused by frequent dressing changes.

Abstract Collaboration between cancer treatment and inflammation management has emerged as an integral facet of comprehensive cancer care. Nevertheless, the development of interventions concurrently targeting both inflammation and cancer has encountered significant challenges stemming from various external factors. Herein, a bioactive agent synthesized by genetically engineering melanin‐producing Bacillus thuringiensis (B. thuringiensis) bacteria, simultaneously achieves eco‐friendly photothermal agent and efficient reactive oxygen/nitrogen species (RONS) scavenger benefits, perfectly tackling present toughies from inflammation to cancer therapies. The biologically derived melanin exhibits exceptional photothermal‐conversion performance, facilitating potent photonic hyperthermia that effectively eradicates tumor cells and tissues, thereby impeding tumor growth. Additionally, the RONS‐scavenging properties of melanin produced by B. thuringiensis bacteria contribute to inflammation reduction, augmenting the efficacy of photothermal tumor repression. This study presents a representative paradigm of genetic engineering in B. thuringiensis bacteria to produce functional agents tailored for diverse biomedical applications, encompassing inflammation and cancer therapy.

Key Clinical Message Adult‐onset immunodeficiency (AOID) is an emerging acquired immunodeficiency, characterized by multiple opportunistic infections including non‐tuberculous mycobacterium (NTM) due to the presence of anti‐IFN‐γ autoantibody (AIGA). This case highlights the challenges of accurate diagnosis of monoclonal gammaglobulinemia with NTM infection and favorable outcomes of anti‐plasma cell therapy in AOID. Abstract Adult‐onset immunodeficiency (AOID) is an emerging acquired immunodeficiency due to anti‐IFN‐γ autoantibody (AIGA) with low morbidity, frequent disseminated infections, a prolonged course, difficult diagnosis and treatment, and a poor prognosis. Here, we report a patient with positive AIGA and monoclonal gammaglobulinemia who was mimicking symptomatic multiple myeloma and resulting in a non‐tuberculous mycobacterial (NTM) infection. While he achieved an excellent therapeutic effect with anti‐plasma cell therapy, it also serves as a warning that monoclonal gammaglobulinemia with NTM infection is easily misdiagnosed as symptomatic multiple myeloma, and the screening for AIGA should not be ignored in patients with NTM infection.

Abstract Reliable and fast identification of high‐voltage direct current (HVDC) transmission line faults is important to the safety of power system. In traditional DC transmission line protection, differential protection is invulnerable to high fault resistance, but it needs long time delay for the influence of distributed capacitance current. In order to solve this problem, a novel pilot protection is proposed. The characteristics of the voltage and current processed by low‐pass filter under different fault conditions are analysed, and based on it the protection criteria is proposed. When external fault occurs, it reflects the line capacitance where the first forward fault traveling wave passes, which is increasing until equal to the whole line capacitance, then remains constant. However, when internal fault occurs, its value is negative in the initial stage, and after that its value is very different from the whole line capacitance. The analysis proves that this pilot protection method has fast operation speed, and can be applied for a relatively long period of time. What is more, the applicable time of superposition principle is considered in the analysis, which is not considered in many literatures. An UHVDC system is modelled for simulation in PSCAD/EMTDC, and the correctness and effectiveness of the proposed scheme is verified.

Abstract Mesenchymal stem cells (MSCs) are recruited by malignant tumor cells to the tumor microenvironment (TME) and play a crucial role in the initiation and progression of malignant tumors. This role encompasses immune evasion, promotion of angiogenesis, stimulation of cancer cell proliferation, correlation with cancer stem cells, multilineage differentiation within the TME, and development of treatment resistance. Simultaneously, extensive research is exploring the homing effect of MSCs and MSC‐derived extracellular vesicles (MSCs‐EVs) in tumors, aiming to design them as carriers for antitumor substances. These substances are targeted to deliver antitumor drugs to enhance drug efficacy while reducing drug toxicity. This paper provides a review of the supportive role of MSCs in tumor progression and the associated molecular mechanisms. Additionally, we summarize the latest therapeutic strategies involving engineered MSCs and MSCs‐EVs in cancer treatment, including their utilization as carriers for gene therapeutic agents, chemotherapeutics, and oncolytic viruses. We also discuss the distribution and clearance of MSCs and MSCs‐EVs upon entry into the body to elucidate the potential of targeted therapies based on MSCs and MSCs‐EVs in cancer treatment, along with the challenges they face.

Abstract Glioblastoma multiforme (GBM) is the most aggressive and lethal subtype of gliomas of the central nervous system. The efficacy of sonodynamic therapy (SDT) against GBM is significantly reduced by the expression of apoptosis‐inhibitory proteins in GBM cells. In this study, an intelligent nanoplatform (denoted as Aza‐BD@PC NPs) based on the aza‐boron‐dipyrromethene dye and phenyl chlorothionocarbonate‐modified DSPE‐PEG molecules is developed for synergistic ferroptosis‐enabled gas therapy (GT) and SDT of GBM. Once internalized by GBM cells, Aza‐BD@PC NPs showed effective cysteine (Cys) consumption and Cys‐triggered hydrogen sulfide (H2S) release for ferroptosis‐enabled GT, thereby disrupting homeostasis in the intracellular environment, affecting GBM cell metabolism, and inhibiting GBM cell proliferation. Additionally, the released Aza‐BD generated abundant singlet oxygen (1O2) under ultrasound irradiation for favorable SDT. In vivo and in vitro evaluations demonstrated that the combined functions of Cys consumption, H2S production, and 1O2 production induced significant death of GBM cells and markedly inhibited tumor growth, with an impressive inhibition rate of up to 97.5%. Collectively, this study constructed a cascade nanoreactor with satisfactory Cys depletion performance, excellent H2S release capability, and prominent reactive oxygen species production ability under ultrasound irradiation for the synergistic ferroptosis‐enabled GT and SDT of gliomas.

Abstract Photosynthesis, essential for life on earth, sustains diverse processes by providing nutrition in plants and microorganisms. Especially, photosynthesis is increasingly applied in disease treatments, but its efficacy is substantially limited by the well‐known low penetration depth of external light. Here, ultrasound‐mediated photosynthesis is reported for enhanced sonodynamic tumor therapy using organic sonoafterglow (ultrasound‐induced afterglow) nanoparticles combined with cyanobacteria, demonstrating the proof‐of‐concept sonosynthesis (sonoafterglow‐induced photosynthesis) in cancer therapy. Chlorin e6, a typical small‐molecule chlorine, is formulated into nanoparticles to stimulate cyanobacteria for sonosynthesis, which serves three roles, i.e., overcoming the tissue‐penetration limitations of external light sources, reducing hypoxia, and acting as a sonosensitizer for in vivo tumor suppression. Furthermore, sonosynthetic oxygenation suppresses the expression of hypoxia‐inducible factor 1α, leading to reduced stability of downstream SLC7A11 mRNA, which results in glutathione depletion and inactivation of glutathione peroxidase 4, thereby inducing ferroptosis of cancer cells. This study not only broadens the scope of microbial nanomedicine but also offers a distinct direction for sonosynthesis.

Abstract Photocatalytic carbon dioxide (CO2) reduction is an effective method for in vivo carbon monoxide (CO) generation for antibacterial use. However, the available strategies mainly focus on utilizing visible‐light‐responsive photocatalysts to achieve CO generation. The limited penetration capability of visible light hinders CO generation in deep‐seated tissues. Herein, a photothermal CO2 catalyst (abbreviated as NNBCs) to achieve an efficient hyperthermic effect and in situ CO generation is rationally developed, to simultaneously suppress bacterial proliferation and relieve inflammatory responses. The NNBCs are modified with a special polyethylene glycol and further embellished by bicarbonate (BC) decoration via ferric ion‐mediated coordination. Upon exposure to 1064 nm laser irradiation, the NNBCs facilitated efficient photothermal conversion and in situ CO generation through photothermal CO2 catalysis. Specifically, the photothermal effect accelerated the decomposition of BC to produce CO2 for photothermal catalytic CO production. Benefiting from the hyperthermic effect and in situ CO production, in vivo assessments using an osteomyelitis model confirmed that NNBCs can simultaneously inhibit bacterial proliferation and attenuate the photothermal effect‐associated pro‐inflammatory response. This study represents the first attempt to develop high‐performance photothermal CO2 nanocatalysts to achieve in situ CO generation for the concurrent inhibition of bacterial growth and attenuation of inflammatory responses.

Abstract Geologic storage of CO2 and H2 are climate‐positive techniques for meeting the energy transition. While similar formations could be considered for both gases, the flow dynamics could differ due to differences in their thermophysical properties. We conduct a rigorous pore‐scale study of water/CO2 and water/H2 systems at relevant reservoir conditions in a Bentheimer rock sample using the lattice Boltzmann method to quantify the effects of capillary, viscous, inertial, and wetting forces during gas invasion. At similar conditions, H2 invasion is weaker compared to CO2 due to unfavorable viscosity ratios. Increasing flow rate, however, increases the breakthrough saturation for both gas systems in the range of capillary numbers studied. At isolated conditions of flow rate, viscosity ratio, and wettability, local inertial effects are found to be critical and show consistent increase in the invaded gas saturation. The effect of inertial forces persits for both gases across all field conditions tested.

Abstract Background The liver is anatomically divided into eight segments based on the distribution of Glisson's triad. However, the molecular mechanisms underlying each segment and its association with hepatocellular carcinoma (HCC) heterogeneity are not well understood. In this study, our objective is to conduct a comprehensive multiomics profiling of the segmentation atlas in order to investigate potential subtypes and therapeutic approaches for HCC. Methods A high throughput liquid chromatography‐tandem mass spectrometer strategy was employed to comprehensively analyse proteome, lipidome and metabolome data, with a focus on segment‐resolved multiomics profiling. To classify HCC subtypes, the obtained data with normal reference profiling were integrated. Additionally, potential therapeutic targets for HCC were identified using immunohistochemistry assays. The effectiveness of these targets were further validated through patient‐derived organoid (PDO) assays. Results A multiomics profiling of 8536 high‐confidence proteins, 1029 polar metabolites and 3381 nonredundant lipids was performed to analyse the segmentation atlas of HCC. The analysis of the data revealed that in normal adjacent tissues, the left lobe was primarily involved in energy metabolism, while the right lobe was associated with small molecule metabolism. Based on the normal reference atlas, HCC patients with segment‐resolved classification were divided into three subtypes. The C1 subtype showed enrichment in ribosome biogenesis, the C2 subtype exhibited an intermediate phenotype, while the C3 subtype was closely associated with neutrophil degranulation. Furthermore, using the PDO assay, exportin 1 (XPO1) and 5‐lipoxygenase (ALOX5) were identified as potential targets for the C1 and C3 subtypes, respectively. Conclusion Our extensive analysis of the segmentation atlas in multiomics profiling defines molecular subtypes of HCC and uncovers potential therapeutic strategies that have the potential to enhance the prognosis of HCC.

Abstract Background Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood. Methods Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single‐cell RNA‐sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single‐cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations. Results There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone‐lysine N‐methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto‐oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues. Conclusions We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti‐inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications. Highlights Single‐cell RNA‐sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A‐mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.

Abstract Background Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. Methods A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow‐up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random‐effects meta‐analyses. Results Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06–1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07–1.60 vs 1.12, 1.01–1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02–1.28 vs 1.17, 0.77–1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02–1.46 vs 1.00, 0.62–1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77–5.86), and decreased with time (nonlinear p

Objectives Diabetes mellitus (DM) is correlated with poor clinical outcomes in spinal surgery. However, the effect of it on screw stabilization has not been investigated. The aim of this study was to evaluate the screw loosening rate and postoperative outcomes in diabetic patients and to identify potential risk factors associated with loosening. Methods This was a retrospective study. Two hundred and forty‐three patients who received cervical or lumbar internal fixation between 2015 and 2019 were enrolled. Screw loosening was assessed on radiography, and clinical outcomes were evaluated by the improvement of visual analogue scale (VAS), Oswestry disability index (ODI) or Japanese Orthopaedic Association (JOA) scores. The relationship of DM, screw loosening and clinical outcomes were analyzed with chi‐square tests and regression analyses. Results One hundred and twenty‐two patients (50.2%) with diabetes were included in this study. Diabetes led to the increase of the rate of screw loosening in the lumbar spine, while the loosening rate did not vary significantly in the cervical spine. The occurrence of screw loosening in the lumbar spine was more likely to be associated with clinical outcomes for motor performance including walking and sitting. However, no significant effect on JOA and VAS scores in the cervical spine of screw loosening was found. Moreover, the history of DM affected the outcomes of the patients who underwent spinal surgery. Conclusion DM had an adverse effect on screw stabilization. The impaired improvement of clinical outcomes in diabetics after spinal surgery was related to screw loosening. In addition to the direct effects on operative wounds and neural function, the impact on the screws due to DM was also worth noting.

Abstract Objective Our study aims to investigate the association between the Hounsfield unit (Hu) value of the insular cortex (IC) during emergency admission and the subsequent occurrence of post‐operative neurocardiogenic injury (NCI) among patients afflicted with aneurysmal subarachnoid hemorrhage (aSAH). Methods Patients baseline characteristics were juxtaposed between those with and without NCI. The significant variables were incorporated into a multivariable stepwise logistic regression model. Receiver operating characteristic (ROC) curves were drafted for each significant variable, yielding cutoff values and the area under the curve (AUC). Subgroup and sensitivity analyses were performed to assess the predictive performance across various cohorts and ascertain result stability. Propensity score matching (PSM) was ultimately employed to redress any baseline characteristic disparities. Results Patients displaying a right IC Hu value surpassing 28.65 exhibited an escalated risk of postoperative NCI upon confounder adjustment (p

Abstract The modification and recognition of 5‐methylcytosine (m5C) are involved in the initiation and progression of various tumor types. However, the precise role and potential mechanism of Y‐box‐binding protein 1 (YBX1) in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, it is found that YBX1 is frequently upregulated in ESCC compared with matched nontumor tissues. Gain‐ and loss‐of‐function assays show that YBX1 promoted the proliferation and metastasis of ESCC cells both in vitro and in vivo. Functional studies revealed that NOP2/Sun RNA methyltransferase family member 2 (NSUN2) is a critical RNA methyltransferase that facilitates YBX1‐mediated ESCC progression. Mechanistically, integrated analysis based on RNA immunoprecipitation sequencing (RIP‐seq) and m5C methylated RNA immunoprecipitation and sequencing (MeRIP‐seq) assays identified spermine oxidase (SMOX) as a target gene containing an m5C site in its coding sequence (CDS) region, which coincided well with the binding site of YBX1. Overexpression of SMOX‐WT but not SMOX‐Mut partially restored the proliferation and invasion ability of ESCC cells curbed by YBX1 knockdown. Moreover, YBX1 activated the mTORC1 signaling pathway by stabilizing SMOX mRNA. The study reveals that YBX1 promotes ESCC development by stabilizing SMOX mRNA in an m5C‐dependent manner, thus providing a valuable therapeutic target for ESCC.

Abstract Loss of refreshment in nucleus pulposus (NP) cellularity leads to intervertebral disc (IVD) degeneration. Nevertheless, the cellular sequence of NP cell differentiation remains unclear, although an increasing body of literature has identified markers of NP progenitor cells (NPPCs). Notably, due to their fragility, the physical enrichment of NP‐derived cells has limited conventional transcriptomic approaches in multiple studies. To overcome this limitation, a spatially resolved transcriptional atlas of the mouse IVD is generated via the 10x Genomics Visium platform dividing NP spots into two clusters. Based on this, most reported NPPC‐markers, including Cathepsin K (Ctsk), are rare and predominantly located within the NP‐outer subset. Cell lineage tracing further evidence that a small number of Ctsk‐expressing cells generate the entire adult NP tissue. In contrast, Tie2, which has long suggested labeling NPPCs, is actually neither expressed in NP subsets nor labels NPPCs and their descendants in mouse models; consistent with this, an in situ sequencing (ISS) analysis validated the absence of Tie2 in NP tissue. Similarly, no Tie2‐cre‐mediated labeling of NPPCs is observed in an IVD degenerative mouse model. Altogether, in this study, the first spatial transcriptomic map of the IVD is established, thereby providing a public resource for bone biology.

Abstract An innovative all‐metal self‐support microwave metamaterial absorber (MMA) based on a continuous complementary split ring resonator (CSRR) array frequency selective surface (FSS) is constructed. The CSRR‐based FSS has a selected frequency of 23 GHz and is proved to be polarization insensitive. And the all‐metal MMA has the same response frequency as the FSS, showing convenience in the geometrical scaling process. Additionally, in both transverse electric and transverse magnetic modes, the all‐metal MMA shows stable response at oblique incidences with an incident angle as large as 50°. Along with lightweight, easy fabrication and high cost‐performance ratio, the new proposed all‐metal FSS‐based MMA has good potential to serve in many practical applications.

Abstract Background Alzheimer's disease (AD) and related Tauopathies are characterised by the pathologically hyperphosphorylated and aggregated microtubule‐associated protein Tau, which is accompanied by neuroinflammation mediated by activated microglia. However, the role of Tau pathology in microglia activation or their causal relationship remains largely elusive. Methods The levels of nucleotide‐binding oligomerisation domain (NOD)‐like receptor pyrin domain containing 3 (NLRP3) acetylation and inflammasome activation in multiple cell models with Tau proteins treatment, transgenic mice with Tauopathy, and AD patients were measured by Western blotting and enzyme‐linked immunosorbent assay. In addition, the acetyltransferase activity of Tau and NLRP3 acetylation sites were confirmed using the test‐tube acetylation assay, co‐immunoprecipitation, immunofluorescence (IF) staining, mass spectrometry and molecular docking. The Tau‐overexpressing mouse model was established by overexpression of human Tau proteins in mouse hippocampal CA1 neurons through the adeno‐associated virus injection. The cognitive functions of Tau‐overexpressing mice were assessed in various behavioural tests, and microglia activation was analysed by Iba‐1 IF staining and [18F]‐DPA‐714 positron emission tomography/computed tomography imaging. A peptide that blocks the interaction between Tau and NLRP3 was synthesised to determine the in vitro and in vivo effects of Tau–NLRP3 interaction blockade on NLRP3 acetylation, inflammasome activation, microglia activation and cognitive function. Results Excessively elevated NLRP3 acetylation and inflammasome activation were observed in 3xTg‐AD mice, microtubule‐associated protein Tau P301S (PS19) mice and AD patients. It was further confirmed that mimics of ‘early’ phosphorylated‐Tau proteins which increase at the initial stage of diseases with Tauopathy, including TauT181E, TauS199E, TauT217E and TauS262E, significantly promoted Tau–K18 domain acetyltransferase activity‐dependent NLRP3 acetylation and inflammasome activation in HEK293T and BV‐2 microglial cells. In addition, Tau protein could directly acetylate NLRP3 at the K21, K22 and K24 sites at its PYD domain and thereby induce inflammasome activation in vitro. Overexpression of human Tau proteins in mouse hippocampal CA1 neurons resulted in impaired cognitive function, Tau transmission to microglia and microgliosis with NLRP3 acetylation and inflammasome activation. As a targeted intervention, competitive binding of a designed Tau–NLRP3‐binding blocking (TNB) peptide to block the interaction of Tau protein with NLRP3 inhibited the NLRP3 acetylation and downstream inflammasome activation in microglia, thereby alleviating microglia activation and cognitive impairment in mice. Conclusions In conclusion, our findings provide evidence for a novel role of Tau in the regulation of microglia activation through acetylating NLRP3, which has potential implications for early intervention and personalised treatment of AD and related Tauopathies.

Abstract High‐fat diet (HFD)‐induced obesity is a crucial risk factor for metabolic syndrome, mainly due to adipose tissue dysfunctions associated with it. However, the underlying mechanism remains unclear. This study has used genetic screening to identify an obesity‐associated human lncRNA LINK‐A as a critical molecule bridging the metabolic microenvironment and energy expenditure in vivo by establishing the HFD‐induced obesity knock‐in (KI) mouse model. Mechanistically, HFD LINK‐A KI mice induce the infiltration of inflammatory factors, including IL‐1β and CXCL16, through the LINK‐A/HB‐EGF/HIF1α feedback loop axis in a self‐amplified manner, thereby promoting the adipose tissue microenvironment remodeling and adaptive thermogenesis disorder, ultimately leading to obesity and insulin resistance. Notably, LINK‐A expression is positively correlated with inflammatory factor expression in individuals who are overweight. Of note, targeting LINK‐A via nucleic acid drug antisense oligonucleotides (ASO) attenuate HFD‐induced obesity and metabolic syndrome, pointing out LINK‐A as a valuable and effective therapeutic target for treating HFD‐induced obesity. Briefly, the results reveale the roles of lncRNAs (such as LINK‐A) in remodeling tissue inflammatory microenvironments to promote HFD‐induced obesity.

Objectives Anterior cervical decompression and fusion (ACF) has become a widely accepted surgical treatment for degenerative cervical diseases, but occasionally, significant intraoperative blood loss (SIBL), which is defined as IBL of 500 mL or more, will occur. We aimed to investigate the independent risk factors for SIBL during ACF for degenerative cervical diseases. Methods We enrolled 1150 patients who underwent ACF for degenerative cervical diseases at our hospital between 2013 and 2019. The patients were divided into two groups: the SIBL group (n = 38) and the non‐SIBL group (n = 1112). Demographic, surgical and radiographic data were recorded prospectively to investigate the independent risk factors for SIBL. For counting data, the chi‐square test or Fisher's exact probability test was used. Student's t‐test or the Mann–Whitney rank sum test was used for comparisons between groups of measurement data. Univariate analysis and multivariate logistic regression analysis were further used to analyze the significance of potential risk factors. Results The incidence of SIBL during ACF was 3.3% (38/1150). A multivariate analysis revealed that female sex (odds ratio [OR], 6.285; 95% confidence interval [CI], 2.707–14.595; p

Objective The application of three‐dimensional (3D) printing technology in the management of posterior wall acetabular fractures can greatly reduce surgical invasiveness and operative time and simplify the procedure of reconstruction plate contouring, but the cost and time of patient‐specific plate preparation on the basis of traditional 3D‐printed pelvis model should not be neglected. We described a new method for patient‐specific plate preparation by using 3D‐printed plate template. The study aimed to assess the effectiveness and feasibility of the 3D‐printed plate template in patient‐specific plate preparation for posterior wall acetabular fractures. Methods A total of 65 cases of posterior wall acetabular fractures with surgical treatment from December 2012 to December 2020 were chosen. According to the different plate contouring methods, the 65 cases were divided into three groups, which were group A (21 cases), group B (20 cases), and group C (24 cases). In group A, the 3D‐printed plate template was used to contour the patient‐specific reconstruction plate before surgery, whereas the 3D‐printed hemipelvis model was adopted for group B. In group C, the reconstruction plate was contoured intraoperatively. Among the three groups, the instrumentation time, surgical time, blood loss, patient‐specific plate preparation time, complications, reduction quality, and hip function were compared. The Kruskal–Wallis test was used to analyze the reduction quality and hip function among three groups. Results In comparison with group C, patients in groups A and B were featured by obviously shorter instrumentation time (−22, −23 min), shorter surgical time (−46, −44 min), and less intraoperative blood loss (−110, −122 mL). Compared to the hemipelvis model in group B (2.29 ± 0.56 vs. 12.70 ± 3.79 days), the 3D printing time for plate templates in group A was significantly shorter. The reduction quality and hip function had no obvious statistical difference among the three groups. The complication rate within group A (3/21) and group B (3/20) were both slightly lower than group C (5/24), with no obvious difference. Conclusions Both the patient‐specific pre‐contoured plate fixation methods based on the 3D‐printed hemipelvis model and plate template can achieve satisfactory clinical efficacy, with the advantage of shorter instrumentation and surgical time, and less intraoperative blood loss. However, 3D printing of plate template is easier and less time‐consuming, considering the shorter time and less cost for 3D printing of physical model.

Abstract The clinical significance of central beyond brachial blood pressure (BP) remains unclear. In patients who underwent coronary angiography, the authors explored whether elevated central BP would be associated with coronary arterial disease (CAD) irrespective of the status of brachial hypertension. From March 2021 to April 2022, 335 patients (mean age 64.9 years, 69.9% men) hospitalized for suspected CAD or unstable angina were screened in an ongoing trial. CAD was defined if a coronary stenosis of ≥50%. According to the presence of brachial (non‐invasive cuff systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) and central (invasive systolic BP ≥130 mmHg) hypertension, patients were cross‐classified as isolated brachial hypertension (n = 23), isolated central hypertension (n = 93), and concordant normotension (n = 100) or hypertension (n = 119). In continuous analyses, both brachial and central systolic BPs were significantly related to CAD with similar standardized odds ratios (OR, 1.47 and 1.45, p

Abstract Backgrounds Stress hyperglycemia ratio (SHR) reflects the acute blood glucose change in response to acute illnesses or injuries, including pneumonia. We aimed to investigate the associations of SHR with systemic inflammation and clinical outcomes in diabetic inpatients with pneumonia on admission. Methods A multicenter and retrospective study was conducted among diabetic inpatients with pneumonia on admission via electronic medical records from 2013 to 2019 in Ruijin Hospital, Shengjing Hospital, and China‐Japan Friendship Hospital. Results The study included 1631 diabetic inpatients with pneumonia on admission. Patients of the fourth quartile (Q4) of SHR on admission showed significantly elevated systemic inflammation compared with those of the first quartile (Q1), second quartile (Q2), or third quartile (Q3) of SHR, including more white blood cells (9.1 × 109/L in Q4 vs 7.6 × 109/L in Q1, 7.9 × 109/L in Q2, and 8.0 × 109/L in Q3, p

Abstract Background Mutations in one or more genes responsible for encoding subunits within the SWItch/Sucrose Non‐Fermentable (SWI/SNF) chromatin‐remodelling complexes are found in approximately 25% of cancer patients. Bromodomain containing 9 (BRD9) is a more recently identified protein coding gene, which can encode SWI/SNF chromatin‐remodelling complexes subunits. Although initial evaluations of the potential of BRD9‐based targeted therapy have been explored in the clinical application of a small number of cancer types, more detailed study of the diagnostic and prognostic potential, as well as the detailed biological mechanism of BRD9 remains unreported. Methods We used various bioinformatics tools to generate a comprehensive, pan‐cancer analyses of BRD9 expression in multiple disease types described in The Cancer Genome Atlas (TCGA). Experimental validation was conducted in tissue microarrays and cell lines derived from lung and colon cancers. Results Our study revealed that BRD9 exhibited elevated expression in a wide range of tumours. Analysis of survival data and DNA methylation for BRD9 indicated distinct conclusions for multiple tumours. mRNA splicing and molecular binding were involved in the functional mechanism of BRD9. BRD9 may affect cancer progression through different phosphorylation sites or N6‐methyladenosine site modifications. BRD9 could potentially serve as a novel biomarker for diagnosing different cancer types, especially could accurately forecast the prognosis of melanoma patients receiving anti‐programmed cell death 1 immunotherapy. BRD9 has the potential to serve as a therapeutic target, when pairing with etoposide in patients with melanoma. The BRD9/SMARCD1 axis exhibited promising discriminative performance in forecasting the prognosis of patients afflicted with liver hepatocellular carcinoma (LIHC) and mesothelioma. Additionally, this axis appears to potentially influence the immune response in LIHC by regulating the programmed death‐ligand 1 immune checkpoint. For experimental validation, high expression levels of BRD9 were observed in tumour tissue samples from both lung and colon cancer patients. Knocking down BRD9 led to the inhibition of lung and colon cancer development, likely via the Wnt/β‐catenin signalling pathway. Conclusions These pan‐cancer study revealed the diagnostic and prognostic potential, along with the biological mechanism of BRD9 as a novel therapeutic target in human tumours.

Abstract Metastasis is the leading cause of death in hepatocellular carcinoma (HCC) patients, and autophagy plays a crucial role in this process by orchestrating epithelial–mesenchymal transition (EMT). Stromal interaction molecule 1 (STIM1), a central regulator of store‐operated calcium entry (SOCE) in nonexcitable cells, is involved in the development and spread of HCC. However, the impact of STIM1 on autophagy regulation during HCC metastasis remains unclear. Here, we demonstrate that STIM1 is temporally regulated during autophagy‐induced EMT in HCC cells, and knocking out (KO) STIM1 significantly reduces both autophagy and EMT. Interestingly, STIM1 enhances autophagy through both SOCE‐dependent and independent pathways. Mechanistically, STIM1 directly interacts with microtubule‐associated protein 1A/1B‐light chain 3B (LC3B) to form a complex via the sterile‐α motif (SAM) domain, which promotes autophagosome formation. Furthermore, deletion of the SAM domain of STIM1 abolishes its binding with LC3B, leading to a decrease in autophagy and EMT in HCC cells. These findings unveil a novel mechanism by which the STIM1/LC3B complex mediates autophagy and EMT in HCC cells, highlighting a potential target for preventing HCC metastasis.

Abstract Objectives Primary pulmonary lymphoepithelioma‐like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein–Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation. Methods We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB‐treated PLELC. Viral EBNA‐1 and BamHI‐W DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction. Results Progression‐free survival (PFS) was significantly longer in EBNA‐1 high or BamHI‐W high groups. A longer PFS was also observed in patients with both high plasma EBNA‐1 or BamHI‐W and PD‐L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with EBNA‐1 and BamHI‐W. Plasma EBV load was negatively associated with intratumoral CD8+ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months. Conclusions Plasma EBV DNA could be a useful and easy‐to‐use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging.

Abstract Background T‐cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif domain (TIGIT) is an immune checkpoint molecule that suppresses CD8+ T‐cell function in cancer. However, the expression profile and functional significance of TIGIT in the immune microenvironment of lung adenocarcinoma (LUAD) remain elusive. Interleukin (IL)‐15 has emerged as a promising candidate for enhancing CD8+ T‐cell mediated tumour eradication. Exploring therapeutic strategies that combine IL‐15 with TIGIT blockade in LUAD is warranted. Methods We investigated the regulatory network involving coinhibitory TIGIT and CD96, as well as costimulatory CD226 in LUAD using clinical samples. The potential role of TIGIT in regulating the pathogenesis of LUAD was addressed through a murine model with transplanted tumours constructed in Tigit−/− mice. The therapeutic strategy that combines TIGIT blockade with IL‐15 stimulation was verified using a transplanted tumour murine model and a patient‐derived organoid (PDO) model. Results The frequency of TIGIT+CD8+ T cells was significantly increased in LUAD. Increased TIGIT expression indicated poorer prognosis in LUAD patients. Furthermore, the effector function of TIGIT+CD8+ tumour‐infiltrating lymphocytes (TILs) was impaired in LUAD patients and TIGIT inhibited antitumour immune response of CD8+ TILs in tumour‐bearing mice. Mechanistically, IL‐15 enhanced the effector function of CD8+ TILs but stimulated the expression of TIGIT on CD8+ TILs concomitantly. The application of IL‐15 combined with TIGIT blockade showed additive effects in enhancing the cytotoxicity of CD8+ TILs and thus further increased the antitumour immune response in LUAD. Conclusions Our findings identified TIGIT as a promising therapeutic target for LUAD. LUAD could benefit more from the combined therapy of IL‐15 stimulation and TIGIT blockade.

Abstract Due to the specific advantages of ultrasound (US) in therapeutic disease treatments, the unique therapeutic US technology has emerged. In addition to featuring a low‐invasive targeted cancer‐cell killing effect, the therapeutic US technology has been demonstrated to modulate the tumor immune landscape, amplify the therapeutic effect of other antitumor therapies, and induce immunosensitization of tumors to immunotherapy, shedding new light on the cancer treatment. Tremendous advances in nanotechnology are also expected to bring unprecedented benefits to enhancing the antitumor efficiency and immunological effects of therapeutic US, as well as therapeutic US‐derived bimodal and multimodal synergistic therapies. This comprehensive review summarizes the immunological effects induced by different therapeutic US technologies, including ultrasound‐mediated micro‐/nanobubble destruction (UTMD/UTND), sonodynamic therapy (SDT), and focused ultrasound (FUS), as well as the main underlying mechanisms involved. It is also discussed that the recent research progress of engineering intelligent nanoplatform in improving the antitumor efficiency of therapeutic US technologies. Finally, focusing on clinical translation, the key issues and challenges currently faced are summarized, and the prospects for promoting the clinical translation of these emerging nanomaterials and ultrasonic immunotherapy in the future are proposed.

Abstract Small‐molecule electrooxidation‐boosted water electrolysis (WE) is an energy‐saving method for hydrogen (H2) production. Herein, PdPt bimetallenes (PdPt BMLs) are obtained through the simple galvanic replacement reaction. PdPt BMLs reveal 2.93‐fold enhancement in intrinsic electroactivity and 4.53‐fold enhancement in mass electroactivity for the formate oxidation reaction (FOR) with respect to Pd metallenes (Pd MLs) at 0.50 V potential due to the synergistic effect. Meanwhile, the introduction of Pt atoms also considerably increases the electroactivity of PdPt BMLs for hydrogen evolution reaction (HER) with respect to Pd MLs in an alkaline medium, which even exceeds that with the use of commercial Pt nanocrystals. Inspired by the outstanding FOR and HER electroactivity of bifunctional PdPt BMLs, a two‐electrode FOR‐boosted WE system (FOR‐WE) is constructed by using PdPt BMLs as the cathode and the anode. The FOR‐WE system only requires an operational voltage of 0.31 V to achieve H2 production, which is 1.48 V lower than that (ca. 1.79 V) with the use of the traditional WE system.

Abstract With the changing disease spectrum, atherosclerosis has become increasingly prevalent worldwide and the associated diseases have emerged as the leading cause of death. Due to their fascinating physical, chemical, and biological characteristics, nanomaterials are regarded as a promising tool to tackle enormous challenges in medicine. The emerging discipline of nanomedicine has filled a huge application gap in the atherosclerotic field, ushering a new generation of diagnosis and treatment strategies. Herein, based on the essential pathogenic contributors of atherogenesis, as well as the distinct composition/structural characteristics, synthesis strategies, and surface design of nanoplatforms, the three major application branches (nanodiagnosis, nanotherapy, and nanotheranostic) of nanomedicine in atherosclerosis are elaborated. Then, state‐of‐art studies containing a sequence of representative and significant achievements are summarized in detail with an emphasis on the intrinsic interaction/relationship between nanomedicines and atherosclerosis. Particularly, attention is paid to the biosafety of nanomedicines, which aims to pave the way for future clinical translation of this burgeoning field. Finally, this comprehensive review is concluded by proposing unresolved key scientific issues and sharing the vision and expectation for the future, fully elucidating the closed loop from atherogenesis to the application paradigm of nanomedicines for advancing the early achievement of clinical applications.

Abstract Deformable superstructures are man‐made materials with large deformation properties that surpass those of natural materials. However, traditional deformable superstructures generally use conventional materials as substrates, limiting their applications in multi‐mode reconfigurable robots and space‐expandable morphing structures. In this work, amine‐acrylate‐based liquid crystal elastomers (LCEs) are used as deformable superstructures substrate to provide high driving stress and strain. By changing the molar ratio of amine to acrylate, the thermal and mechanical properties of the LCEs are modified. The LCE with a ratio of 0.9 exhibited improved polymerization degree, elongation at break, and toughness. Besides an anisotropic finite deformation model based on hyperelastic theory is developed for the LCEs to capture the configuration variation under temperature activation. Built upon these findings, an LCE‐based paper‐cutting structure with negative Poisson's ratio and a 2D lattice superstructure model are combined, processed, and molded by laser cutting. The developed superstructure is pre‐programmed to the configuration required for service conditions, and the deformation processes are analyzed using both experimental and finite element methods. This study is expected to advance the application of deformable superstructures and LCEs in the fields of defense and military, aerospace, and bionic robotics.

Abstract High‐performance artificial synapse with nonvolatile memory and low power consumption is a perfect candidate for brainoid intelligence. Unfortunately, due to the energy barrier paradox between ultra‐low power and nonvolatile modulation of device conductances, it is still a challenge at the moment to construct such ideal synapses. Herein, a proton‐reservoir type 4,4′,4″,4'''‐(Porphine‐5,10,15,20‐tetrayl) tetrakis (benzenesulfonic acid) (TPPS) molecule and fabricated organic protonic memristors with device width of 10 µm to 100 nm is synthesized. The occurrence of sequential proton migration and interfacial self‐coordinated doping will introduce new energy levels into the molecular bandgap, resulting in effective and nonvolatile modulation of device conductance over 64 continuous states with retention exceeding 30 min. The power consumptions of modulating and reading the device conductance approach the zero‐power operating limits, which range from 16.25 pW to 2.06 nW and 6.5 fW to 0.83 pW, respectively. Finally, a robust artificial synapse is successfully demonstrated, showing spiking‐rate‐dependent plasticity (SRDP) and spiking‐timing‐dependent plasticity (STDP) characteristics with ultra‐low power of 0.66 to 0.82 pW, as well as 100 long‐term depression (LTD)/potentiation (LTP) cycles with 0.14%/0.30% weight variations.

Abstract Controversy exists as toward the association of excessive fruits intake and certain disease risks. Longan is an edible fruit rich in high levels of fructose, glucose and sucrose. Herein, the effect of longan fruit on the development of nonalcoholic fatty liver disease (NAFLD) was investigated. Longan extracts at the doses of 4.0 g/kg, 8.0, and 16.0 g/kg were orally administered for 4 weeks to healthy C57BL/6J mice or to C57BL/6J mice fed with a HFD diet. In mice fed with a normal diet, repeated longan intake for 4 weeks at excess doses (8 or 16 g/kg), but not the normal dose (4 g/kg), promoted inflammation and gut dysbiosis‐like status and reduced short‐chain fatty acids (SCFAs) production. In high‐fat diet (HFD)‐fed mice, longan intake at 4 g/kg hardly influenced the NAFLD development. In contrast, excess longan intake (8 or 16 g/kg) promoted NAFLD pathogenesis, including increased abnormality in hepatic indices, elevated inflammation, and gut permeability associated with more severe liver steatosis and fibrosis. Moreover, the exacerbated pathogenic markers were positively correlated with increased blood sugar, aggravated HFD‐associated microbial dysbiosis. Effects mediated by excess longan intake resembled that of equivalent free sugars supplementation, suggesting that high level of free sugars in fruits contributed to the promotion of NAFLD development as demonstrated in case of excessive longan intake.

Abstract Current studies on actin function primarily rely on cytoplasmic actin due to the absence of cellular models specifically expressing nuclear actin. Here, cell models capable of expressing varying levels of nuclear F/G‐actin are generated and a significant role of nuclear actin in the regulation of epithelial‐mesenchymal transition (EMT) is uncovered. Through immunoprecipitation and mass spectrometry analyses, distinct binding partners for nuclear F‐actin (β‐catenin, SMAD2, and SMAD3) and nuclear G‐actin (MYBBP1A, NKRF, and MYPOP) are investigated, which respectively modulate EMT‐promoting and EMT‐repressing transcriptional events. While nuclear F‐actin promotes EMT with enhanced cell migration, survival, and elongated mesenchymal morphology, nuclear G‐actin represses EMT and related cell activities. Mechanistically, nuclear F‐actin enhances β‐catenin, SMAD2, and SMAD3 expression and stability in the nuclei, while nuclear G‐actin increases MYBBP1A, NKRF, and MYPOP expression and stability in the nuclei. The association between nuclear F/G‐actin and N‐cadherin/E‐cadherin in the cell lines (in vitro), and increased nuclear actin polymerization in the wound healing cells (in vivo) affirm a significant role of nuclear actin in EMT regulation. With evidence of nuclear actin polymerization and EMT during development, and irregularities in disease states such as cancer and fibrosis, targeting nuclear actin dynamics to trigger dysregulated EMT warrants ongoing study.

Abstract Artificial enzymes featuring the desirable catalytic activity built on nanomaterials are known as nanozymes. Compared with the natural counterparts, nanozymes have demonstrated distinct characteristics including cost‐effectiveness, ease of preparation, high stability, and excellent recycling efficiency. With the rapid innovation of nanoscience and technology, a growing number of nanozymes have been deeply applied in disease prevention, diagnosis, and treatment. In addition, a multimodal platform for effectively interacting with complicated biologic settings has also been achieved by the inherent nanomaterial and dynamic features of nanozymes, which goes beyond simply serving as an enzyme substitute. In this review, we systematically discuss and highlight the classification and catalytic mechanism of nanozymes, regulation of nanozyme activity as well as the research progresses of nanozyme‐enabled/augmented enzyodynamic therapy in treating cancer based on producing and eliminating reactive oxygen species, bacterial infection, inflammation, neurodegeneration, and radiation‐induced tissue damage. Furthermore, the current challenges and future development direction of nanozymes in enzyodynamic disease therapy have been outlined and outlooked. It is highly anticipated that this review will be of guiding significance for better understanding the physiochemical properties and biological effect of nanozymes and the corresponding emerging enzyodynamic disease therapeutics.

Abstract Retinal degeneration, characterized by the progressive loss of retinal neurons, is the leading cause of incurable visual impairment. Retinal progenitor cells (RPCs)‐based transplantation can facilitate sight restoration, but the clinical efficacy of this process is compromised by the imprecise neurogenic differentiation of RPCs and undermining function of transplanted cells surrounded by severely oxidative retinal lesions. Here, it is shown that ultrathin niobium carbide (Nb2C) MXene enables performance enhancement of RPCs for retinal regeneration. Nb2C MXene with moderate photothermal effect markedly improves retinal neuronal differentiation of RPCs by activating intracellular signaling, in addition to the highly effective RPC protection by scavenging free radicals concurrently, which has been solidly evidenced by the comprehensive biomedical assessments and theoretical calculations. A dramatically increased neuronal differentiation is observed upon subretinal transplantation of MXene‐assisted RPCs into the typical retinal degeneration 10 (rd10) mice, thereby contributing to the efficient restoration of retinal architecture and visual function. The dual‐intrinsic function of MXene synergistically aids RPC transplantation, which represents an intriguing paradigm in vision‐restoration research filed, and will broaden the multifunctionality horizon of nanomedicine.

Abstract Recent considerable technological advances in ultrasound‐based treatment modality provides a magnificent prospect for scientific communities to conquer the related diseases, which is featured with remarkable tissue penetration, non‐invasive and non‐thermal characteristics. As one of the critical elements that influences treatment outcomes, titanium (Ti)‐based sonosensitizers with distinct physicochemical properties and exceptional sonodynamic efficiency have been applied extensively in the field of nanomedical applications. To date, a myriad of methodologies has been designed to manipulate the sonodynamic performance of titanium‐involved nanomedicine and further enhance the productivity of reactive oxygen species for disease treatments. In this comprehensive review, the sonocatalytic optimization of diversified Ti‐based nanoplatforms, including defect engineering, plasmon resonance modulation, heterojunction, modulating tumor microenvironment, as well as the development of synergistic therapeutic modalities is mainly focused. The state‐of‐the‐art Ti‐based nanoplatforms ranging from preparation process to the extensive medical applications are summarized and highlighted, with the goal of elaborating on future research prospects and providing a perspective on the bench‐to‐beside translation of these sonocatalytic optimization tactics. Furthermore, to spur further technological advancements in nanomedicine, the difficulties currently faced and the direction of sonocatalytic optimization of Ti‐based therapeutic nanomedicine are proposed and outlooked.

Abstract While double perovskites of PrBaCo2O6 (PBC) have been extensively developed as the cathodes for proton‐conducting solid oxide fuel cells (H‐SOFCs), the effects of Sr‐ or Ca‐doping at the A site on the activity and stability of the oxygen reduction reaction are yet to be fully studied. Here, the effect of A‐site doping on the oxygen reduction reaction activity and stability has been studied by evaluating the performance of both symmetrical and single cells. It is shown that Ca‐doped PBC (PrBa0.8Ca0.2Co2O6, PBCC) shows a slightly smaller polarization resistance (0.076 Ω cm2) than that (0.085 Ω cm2) of Sr‐doped PBC (PrBa0.8Sr0.2Co2O6, PBSC) at 700°C in wet air. Moreover, the degradation rate of PBCC is 0.0003 Ω cm2 h−1 (0.3% h−1) in 100 h, about 1/10 of that of PBSC at 700°C in wet air. In addition, it is also confirmed that single cells with PBCC cathode show higher peak power density (1.22 W cm−2 vs. 1.08 W cm−2 at 650°C) and better durability (degradation rate of 0.1% h−1 vs. 0.13% h−1) than those with PBSC cathode. The distribution of relaxation time analyses suggests that the better stability of the PBCC electrode may come from the fast and stable surface oxygen exchange process in the medium frequency range of the electrochemical impedance spectrum.

Abstract The Belt and Road Initiative (BRI) initiated by China in 2013 is a new experiment in regional cooperation, which aims to improve infrastructure connectivity through investment. This paper investigates whether the BRI created exports for its member states (excluding China), based on a difference‐in‐differences model. We find a significant causal relationship between the signing of the initiative and the export growth of its member states. In addition to the large export creation between the BRI countries and China (considered as “give‐them‐a‐fish”), export creation also originated from the BRI countries excluding China (“teach‐them‐to‐fish”). Both the intensive and extensive margins are significantly important, indicating that export creation has not just come from expansion of the volume of existing products, but also from new products and new markets. The BRI achieved the goal of mutual benefit mainly through enlisting investment in both publicly funded infrastructure sectors and private sectors. Moreover, the initiative has enhanced the position and participation of its member states in the global value chain.

Abstract Immune checkpoint inhibitors (ICIs) have successfully treated a number of different types of cancer, which is of great significance for cancer treatment. With the widespread use of ICIs in clinical practice, the increasing checkpoint inhibitor pneumonia (CIP) will be a challenge to clinicians. To guide the diagnosis and treatment of CIP, we conducted in‐depth discussions based on the latest evidence, forming a consensus among Chinese experts on the multidisciplinary management of CIP.

Objective To evaluate the clinical efficacy and practicality of anterior trans‐intervertebral space decompression and fusion (ATIDF) by comparing radiological and clinical outcomes between ATIDF and traditional anterior cervical corpectomy and fusion (ACCF) in cervical spondylosis patients with severe disc space narrowing. Methods Seventy‐one cervical spondylosis patients with severe disc space narrowing underwent anterior cervical spine surgery were included in this retrospective study. Thirty‐seven patients underwent ATIDF and 34 patients underwent ACCF. The neck disability index (NDI), Japan Orthopaedic Association (JOA) score and the Hirabayashi improvement rate were used to evaluate patient neurological status. Cervical sagittal alignment (C2–C7 Cobb angle), surgical segment sagittal alignment (Cobb angle of surgical segment) and disc space height were also compared between the two groups. Results There were 39 males and 32 females; mean age was 63.72 ± 6.36 years (range, 39–81 years). Mean follow‐up was 22.4 months (range, 6–45 months). All patients achieved an adequate neurological improvement. There were no significant differences in NDI, JOA scores and Hirabayashi improvement rate between the two groups. The change of C2–7 Cobb angle and surgical segment Cobb angle were both greater in the ATIDF group. The average intervertebral height ratio of the patients in the ATIDF group increased significantly after surgery (0.38 ± 0.17 before surgery to 1.13 ± 0.32 after surgery, P

Abstract Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase (NTRK) gene fusions are among the first “tumor agnostic” drugs approved for pan‐cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second‐generation drugs designed to overcome first‐generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription‐polymerase chain reaction, and (DNA and/or RNA‐based) next‐generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first‐ and second‐generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.

Abstract Background The lack of standardized delineation of lymph node station in lung cancer radiotherapy leads to nonstandard clinical target volume (CTV) contouring, especially in patients with bulky lump gross target volume lymph nodes (GTVnd). This study defines lymph node region boundaries in radiotherapy for lung cancer and automatically contours lymph node stations based on the International Association for the Study of Lung Cancer (IASLC) lymph node map. Methods Computed tomography (CT) scans of 200 patients with small cell lung cancer were collected. The lymph node zone boundaries were defined based on the IASLC lymph node map, with adjustments to meet radiotherapy requirements. Contours of lymph node stations were confirmed by two experienced oncologists. A model (DiUNet) was constructed by incorporating the contours of GTVnd to precisely contour the boundaries. Quantitative evaluation metrics and clinical evaluations were conducted. Results The mean 3D Dice similarity coefficient (Dice similarity coefficient) values of DiUNet in most lymph node stations was greater than 0.7, 98.87% of the lymph node station slices are accepted. The mean DiUNet score was not significantly different from that of the man contoured in the evaluation of lymph node stations and CTV. Conclusion This is the first study to propose a method that automatically contours lymph node regions station by station based on the IASLC lymph node map with bulky lump GTVnd. Delineation of lymph node stations based on the DiUNet model is a promising strategy to obtain accuracy and efficiency for CTV delineation in lung cancer patients, especially for bulky lump GTVnd.