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Abstract Hepatocellular carcinoma (HCC) often occurs in the context of fibrosis or cirrhosis. Methylation of histone is an important epigenetic mechanism, but it is unclear whether histone methyltransferases are potent targets for fibrosis‐associated HCC therapy. ASH1L, an H3K4 methyltransferase, is found at higher levels in activated hepatic stellate cells (HSCs) and hepatoma cells. To determine the role of ASH1L in vivo, transgenic mice with conditional Ash1l depletion in the hepatocyte cell lineage (Ash1lflox/floxAlbcre) or HSCs (Ash1lflox/floxGFAPcreERT2) are generated, and these mice are challenged in a diethylnitrosamine (DEN)/carbon tetrachloride (CCl4)‐induced model of liver fibrosis and HCC. Depleting Ash1l in both hepatocytes and HSCs mitigates hepatic fibrosis and HCC development. Multicolor flow cytometry, bulk, and single‐cell transcriptomic sequencing reveal that ASH1L creates an immunosuppressive microenvironment. Mechanically, ASH1L‐mediated H3K4me3 modification increases the expression of CCL2 and CSF1, which recruites and polarizes M2‐like pro‐tumorigenic macrophages. The M2‐like macrophages further enhance tumor cell proliferation and suppress CD8+ T cell activation. AS‐99, a small molecule inhibitor of ASH1L, demonstrates similar anti‐fibrosis and tumor‐suppressive effects. Of pathophysiological significance, the increased expression levels of mesenchymal ASH1L and M2 marker CD68 are associated with poor prognosis of HCC. The findings reveal ASH1L as a potential small‐molecule therapeutic target against fibrosis‐related HCC.

Abstract Artificial skin with tactile perceptions is anticipated to play a pivotal role in next‐generation robotic and medical devices. The primary challenge lies in creating a biomimetic system that seamlessly integrates with the human body and biological systems. The authors have developed an electronic skin (e‐skin) that imitates the biological sensorimotor loop through medium‐scale circuit integration, boasting low power consumption and solid‐state synaptic transistors.

Abstract Background Cerebral ischemic disease is a common cerebrovascular disease, especially ischemic stroke. Exercise has protective functions on brain tissues following cerebral ischemia‐reperfusion injury (CIRI), but its preventive effects and mechanisms in CIRI remain unclear. We aimed to investigate the effects and mechanisms of exercise preconditioning on CIRI. Methods The middle cerebral artery occlusion (MCAO) operation was prepared to establish CIRI rats. All rats were randomized into the MCAO, exercise (exercise preconditioning plus MCAO operation), vector (exercise preconditioning, MCAO operation plus intraventricular injection of empty vector), and tissue inhibitor of metalloprotease 1 overexpression (OE‐TIMP1, exercise preconditioning, MCAO operation plus intraventricular injection of OE‐TIMP1) groups. Results The results indicated that exercise preconditioning suppressed approximately 66.67% of neurological deficit scores and 73.79% of TIMP1 mRNA expression in MCAO rats, which were partially offset by OE‐TIMP1. The protective effects of exercise against neuron death status and cerebral infarction size in MCAO rats were reversed by OE‐TIMP1. It also confirmed that exercise weakened apoptosis and oxidative stress damage, with notable increases of B‐cell lymphoma‐2, superoxide dismutase, and glutathione peroxidase production, and evident decreases of BCL2‐associated X, caspase 3, and malondialdehyde in MCAO rats, while these effects were partially reversed by OE‐TIMP1. Additionally, the inhibitory effects of exercise on the protein levels of TIMP1, hypoxia‐inducible factor‐alpha, vascular endothelial growth factor receptor 2, vascular endothelial growth factor, and neurogenic locus notch homolog protein 1 in MCAO rats were partially reversed by OE‐TIMP1. Conclusion Altogether, exercise preconditioning had protective effects on CIRI by restraining TIMP1, which provided new therapeutic strategies for preventing CIRI.

Abstract In this paper, the wake characteristics of Zell 2000 wind turbine under different tip velocity ratios are studied by using the lattice Boltzmann method and large eddy simulation. The adaptive mesh refinement method is performed to capture the fine flow structure and wake characteristics development. In this paper, we mainly focus on the effect of the tip speed ratio on the flow structure and unsteady characteristics of wind turbine wake. The three‐dimensional flow vorticity structures, the section vorticity diagram, the pressure fluctuation of wake and the lift coefficient of wind turbine wake are utilized to explore the effect of the tip speed ratio on the unsteady physics mechanism of wind turbine wake. With the increase of the tip speed ratio, the distance between two adjacent vortex rings along the axial direction gradually decreases, as the position of the broken vortex circles gradually approaches the center of the blade, separated vortexes are rapidly generated, and the coherent structure appears closer to the wind turbine. A relationship is established between the tip speed ratios and the positions of the broken vortex circles. It is further found that the dominant frequency amplitude gradually increases with the increase of tip speed ratio and the pressure amplitude spectra of vortex increases with the decrease of the distance between the wake and the center of the blade axis. The above series of studies can provide significant physical insight into deep understanding the influence of the tip speed ratio on the wake characteristics of wind turbines.

Abstract A novel quaternary copolymer of AA/AM/AOS/C16‐DMAAC was synthesized with acrylic acid (AA), acrylamide (AM), sodium α‐alkenyl‐sulfonate (AOS), and dimethyl‐hexadecyl‐allyl‐ammonium chloride (C16‐DMAAC), using ammonium persulfate and sodium bisulfate (NH4)2S2O8‐NaHSO3) as initiators. The structure of AA/AM/AOS/C16‐DMAAC was characterized using Fourier transform infrared spectroscopy and nuclear magnetic resonance hydrogen spectroscopy. It can be found that the thickening capacity, shearing resistance, temperature‐resistance, salt‐resistance, and emulsification properties of AA/AM/AOS/C16‐DMAAC were superior to those of most widely and cost‐effective partially hydrolyzed polyacrylamide (HPAM) solution at the same concentration. Specifically, the viscosity retention rate of AA/AM/AOS/C16‐DMAAC (3000 mg/L) solution was 86%, which was better than that of HPAM solution (52%) after 30 s of mechanical shearing at 28000 r/min. In addition, the enhanced oil recovery of AA/AM/AOS/C16‐DMAAC solution was 16% at 65 °C, which was about 1.5 times higher than that of HPAM solution (11%). Significantly, successful synthesis of zwitterionic quaternary copolymer emphasizes the importance of a systematic approach to designing appropriate copolymers for enhanced oil recovery. Highlights A novel zwitterionic quaternary copolymer of AA/AM/AOS/C16‐DMAAC was successfully synthesized. The performance on thickening capacity, shearing resistance, temperature‐resistance, salt‐resistance, and emulsification properties of AA/AM/AOS/C16‐DMAAC was superior to that of the most widely used partially hydrolyzed polyacrylamide (HPAM). The enhanced oil recovery of AA/AM/AOS/C16‐DMAAC (16%) was about 1.5 times higher than that of HPAM (11%).

Abstract Background Cetirizine and Loratadine are the two best‐selling second‐generation antihistamines for allergic diseases. This study aims to provide a comparative analysis of the differences in adverse drug events (ADEs) between these two medications, which can assist clinicians in making appropriate treatment decisions. Methods ADE reports related to Cetirizine and Loratadine obtained from the FDA adverse event reporting system (FAERS) database were analyzed using disproportionality analysis and Bayesian analysis to evaluate and compare the ADE signals of both drugs. Results A total of 28,051 and 28,073 ADE reports were retrieved from the FAERS database related to Cetirizine and Loratadine, respectively, with both drugs showing a predominance of middle‐aged females. Specifically, Loratadine was associated with respiratory symptoms, mainly nasal symptoms such as rhinorrhea (n = 326, ROR 6.75), sneezing (n = 251, ROR 15.24), and nasal congestion (n = 185, ROR 4.25), while Cetirizine did not show this association. Notably, both drugs exhibited strong signals for somnolence in the nervous and psychiatric systems, especially Cetirizine (Cetirizine, n = 2556, ROR 10.52 vs. Loratadine, n = 1200, ROR 7.76). Additionally, Cetirizine itself showed strong signals for attention disturbance (n = 233, ROR 3.3), while Loratadine was associated with nervousness (n = 145, ROR 3.3). Further exploration revealed more severe adverse reactions closely associated with Cetirizine, including hallucinations, aggression, and abnormal behavior. Importantly, Cetirizine was significantly associated with the occurrence of pericarditis (n = 138, ROR 8.13), potentially leading to serious adverse consequences. Conclusion Compared to Loratadine, Cetirizine poses a greater potential risk in the nervous and psychiatric systems. Additionally, this study reveals previously underestimated potential cardiac toxicity of Cetirizine; albeit at a relatively low incidence rate, the high signal intensity warrants further attention and exploration. These findings highlight the need for enhanced patient monitoring and therapy optimization when prescribing these medications, ensuring better management of allergic diseases while minimizing risks.

Abstract Background Depressive symptoms are frequently observed in patients with primary biliary cholangitis (PBC). The role of depressive symptoms on cirrhosis has not been fully noticed in PBC. We aimed to establish a risk model for cirrhosis that took depressive symptoms into account. Methods Depressive symptoms were assessed by the 17‐item Hamilton Depression Rating Scale (HAMD‐17). HAMD‐17 score was analyzed in relation to clinical parameters. Least absolute shrinkage and selection operator (Lasso)‐logistic regression and decision tree models were used to explore the effect of depressive symptoms on cirrhosis. Results The rate of depressive symptom in patients with PBC (n = 162) was higher than in healthy controls (n = 180) (52.5% vs. 16.1%; p

Abstract Medulloblastoma (MB) stands as one of the prevalent malignant brain tumors among pediatric patients. Despite its prevalence, the intricate interplay between the regulatory program driving malignancy in MB cells and their interactions with the microenvironment remains insufficiently understood. Leveraging the capabilities of single‐cell Assay for Transposase‐Accessible Chromatin sequencing (scATAC‐seq), the chromatin accessibility landscape is unveiled across 59,015 distinct MB cells. This expansive dataset encompasses cells belonging to discrete molecular subgroups, namely SHH, WNT, Group3, and Group4. Within these chromatin accessibility profiles, specific regulatory elements tied to individual subgroups are uncovered, shedding light on the distinct activities of transcription factors (TFs) that likely orchestrate the tumorigenesis process. Moreover, it is found that certain neurotransmitter receptors (NTRs) are subgroup‐specific and can predict MB subgroup classification when combined with their associated transcription factors. Notably, targeting essential NTRs within tumors influences both the in vitro sphere‐forming capability and the in vivo tumorigenic capacity of MB cells. These findings collectively provide fresh insights into comprehending the regulatory networks and cellular dynamics within MBs. Furthermore, the significance of the TF‐NTR regulatory circuits is underscored as prospective biomarkers and viable therapeutic targets.

Abstract Intrinsic plasticity, a fundamental process enabling neurons to modify their intrinsic properties, plays a crucial role in shaping neuronal input‐output function and is implicated in various neurological and psychiatric disorders. Despite its importance, the underlying molecular mechanisms of intrinsic plasticity remain poorly understood. In this study, a new ubiquitin ligase adaptor, protein tyrosine phosphatase receptor type N (PTPRN), is identified as a regulator of intrinsic neuronal excitability in the context of temporal lobe epilepsy. PTPRN recruits the NEDD4 Like E3 Ubiquitin Protein Ligase (NEDD4L) to NaV1.2 sodium channels, facilitating NEDD4L‐mediated ubiquitination, and endocytosis of NaV1.2. Knockout of PTPRN in hippocampal granule cells leads to augmented NaV1.2‐mediated sodium currents and higher intrinsic excitability, resulting in increased seizure susceptibility in transgenic mice. Conversely, adeno‐associated virus‐mediated delivery of PTPRN in the dentate gyrus region decreases intrinsic excitability and reduces seizure susceptibility. Moreover, the present findings indicate that PTPRN exerts a selective modulation effect on voltage‐gated sodium channels. Collectively, PTPRN plays a significant role in regulating intrinsic excitability and seizure susceptibility, suggesting a potential strategy for precise modulation of NaV1.2 channels' function.

Abstract Introduction Cerebral ischemia reperfusion injury (CIRI) often leads to deleterious complications after stroke patients receive reperfusion therapy. Exercise preconditioning (EP) has been reported to facilitate brain function recovery. We aim to explore the specific mechanism of EP in CIRI. Methods Sprague‐Dawley rats were randomized into Sham, middle cerebral artery occlusion (MCAO), and EP groups (n = 11). The rats in the EP group received adaptive training for 3 days (10 m/min, 20 min/day, with a 0° incline) and formal training for 3 weeks (6 days/week, 25 m/min, 30 min/day, with a 0° incline). Then, rats underwent MCAO surgery to establish CIRI models. After 48 h, neurological deficits and cerebral infarction of the rats were measured. Neuronal death and apoptosis in the cerebral cortices were detected. Furthermore, RNA sequencing was conducted to investigate the specific mechanism of EP on CIRI, and qPCR and Western blotting were further applied to confirm RNA sequencing results. Results EP improved neurological deficit scores and reduced cerebral infarction in MCAO rats. Additionally, pre‐ischemic exercise also alleviated neuronal death and apoptosis of the cerebral cortices in MCAO rats. Importantly, 17 differentially expressed genes (DEGs) were identified through RNA sequencing, and these DEGs were mainly enriched in the HIF‐1 pathway, cellular senescence, proteoglycans in cancer, and so on. qPCR and Western blotting further confirmed that EP could suppress TIMP1, SOCS3, ANGPTL4, CDO1, and SERPINE1 expressions in MCAO rats. Conclusion EP can improve CIRI in vivo, the mechanism may relate to TIMP1 expression and HIF‐1 pathway, which provided novel targets for CIRI treatment.

Abstract Background The meticulous selection of appropriate vaccine adjuvants is crucial for optimizing immune responses. Traditionally, pemphigus vulgaris (PV), an autoimmune disorder, has been modelled using complete Freund's adjuvant (CFA). In this study, we aimed to discern potential variations in immune responses elicited by Toll‐like receptor (TLR) ligands as compared to CFA. Methods A comprehensive investigation was conducted, comparing the effects of these adjuvants in conjunction with ovalbumin or desmoglein‐3. Flow cytometry was employed to analyse distinct cell subsets, while enzyme‐linked immunosorbent assay quantified antigen‐specific antibodies and cytokine levels. Histological examination of harvested skin tissues and transcriptome analysis of skin lesions were performed to identify differentially expressed genes. Results TLR ligands demonstrated efficacy in inducing PV‐like symptoms in wild‐type mice, in contrast to CFA. This underscored the substantial impact of the adjuvant on self‐antigen tolerance. Furthermore, we proposed an enhanced method for establishing a PV model through adoptive transfer, substituting CFA with TLR ligands. Our results revealed that in contrast to the perception that CFA being the most potent immunopotentiator reported, CFA promoted regulatory T cells (Treg), follicular regulatory T cells and IL‐10‐producing neutrophils, whereas TLR ligands downregulated CCL17 and IL‐10. This suggested potential implications for the recruitment and activation of Treg subsets. While B cell and CD8+ T cell responses exhibited similarity, CFA induced less activation in dendritic cell subsets. A novel mouse model of PV and systemic comparison of immunostimulatory effects of adjuvants were provided by this study. Conclusions The systematic comparison of CFA and TLR ligands shed light on the distinctive properties of these adjuvants, presenting innovative mouse models for the investigation of pemphigus. This study significantly contributes to adjuvant research and advances our understanding of PV pathogenesis. Key points/highlights Immunization with desmoglein 3 and Toll‐like receptor (TLR) ligands effectively induces pemphigus symptoms in wild‐type mice, whereas complete Freund's adjuvant (CFA) fails. TLR ligands heightened the autoreactivity of donor cells in the adoptive transfer pemphigus model. CFA promoted regulatory T cells and IL‐10‐producing neutrophils, whereas TLR ligands downregulated CCL17 and IL‐10, leading to more effective immune responses.

Abstract Malignant pleural mesothelioma (MPM) is a malignant tumor of the pulmonary pleural tissue for which there is a lack of effective targeted therapy. In this study, moderate to high V‐domain immunoglobulin T‐cell activation suppressor (VISTA) expression levels were observed in most MPM clinical tumor samples. We prepared two high‐affinity anti‐VISTA monoclonal antibodies (mAbs) and generated two novel VISTA‐targeted antibody‐drug conjugates (ADCs) by conjugating anti‐VISTA mAbs with the potent cytotoxic drug monomethyl auristatin E (MMAE). αV1‐MMAE and αV2‐MMAE showed potent killing effects to VISTA‐positive cell lines in vitro, with half‐maximal inhibitory concentration (IC50) of nanomolar levels. αV1‐MMAE and αV2‐MMAE were also able to significantly induce apoptosis and cause G2/M phase arrest in VISTA‐positive cells. In the VISTA‐positive human MPM xenograft model, both αV1‐MMAE and αV2‐MMAE showed significant antitumor activity, led to a significant survival advantage compared to mice in the control group, and effectively induced apoptosis in the tumor tissues of mice. In conclusion, we demonstrated that the novel VISTA‐targeted ADCs (αV1‐MMAE and αV2‐MMAE), especially αV1‐MMAE, had potent killing effects against VISTA‐positive MPM cells both in vitro and in vivo. Therefore, through further development, they may have the potential to become new drugs for the treatment of MPM.

Abstract To overcome the overheating phenomena of electronic devices and energy components, developing advanced energy‐free cooling coatings with promising radiative property seem an effective and energy‐saving way. However, the further application of these coatings is greatly limited by their sustainability because of their fragile and easy contamination. Herein, it is reported that a bioinspired radiative cooling coating (BRCC) displayed sustainably efficient heat dissipation by the combination of high emittance and robust self‐cleaning property. With the hierarchical porous structure constructed by multiwalled carbon nanotubes (MWCNTs), modified SiO2 and fluorosilicone (FSi) resin, the involvement of the BRCC improves the cooling performance by increasing ≈25% total heat transfer coefficient. During the abrasion and soiling tests, the BRCC‐coated Al alloy heat sink always displays stable radiative cooling performance. Moreover, the simulation and experimental results both revealed that reducing surface coverage of BRCC (≈80.9%) can still keep highly cooling efficiency, leading to a cost‐effective avenue. Therefore, this study may guide the design and fabrication of advanced radiative cooling coating.

Abstract Activated microglia in the retina are essential for the development of autoimmune uveitis. Yin‐Yang 1 (YY1) is an important transcription factor that participates in multiple inflammatory and immune‐mediated diseases. Here, an increased YY1 lactylation in retinal microglia within in the experimental autoimmune uveitis (EAU) group is observed. YY1 lactylation contributed to boosting microglial activation and promoting their proliferation and migration abilities. Inhibition of lactylation suppressed microglial activation and attenuated inflammation in EAU. Mechanistically, cleavage under targets & tagmentation （CUT&Tag） analysis revealed that YY1 lactylation promoted microglial activation by regulating the transcription of a set of inflammatory genes, including STAT3, CCL5, IRF1, IDO1, and SEMA4D. In addition, p300 is identified as the writer of YY1 lactylation. Inhibition of p300 decreased YY1 lactylation and suppressed microglial inflammation in vivo and in vitro. Collectively, the results showed that YY1 lactylation promoted microglial dysfunction in autoimmune uveitis by upregulating inflammatory cytokine secretion and boosting cell migration and proliferation. Therapeutic effects can be achieved by targeting the lactate/p300/YY1 lactylation/inflammatory genes axis.

Abstract Aim The aim of the study was to investigate the incidence of sleep disturbance and its relationship with anxiety and depression symptoms, social support and hope in breast cancer patients in China during chemotherapy. Design A single‐centre cross‐sectional study. Methods A total of 329 breast cancer patients were selected via convenience sampling method before they began chemotherapy (n = 115), before the 5th week of chemotherapy (n = 117) or 1 month after chemotherapy ended (n = 97) and administered paper‐and‐pencil questionnaires to evaluate sleep quality, depression and anxiety symptoms, social support and hope. Risk factors significantly associated with sleep disturbance during bivariate were incorporated in the multivariate analysis. Bivariate analyses showed that age, menopausal status, depression and anxiety symptoms, emotional/informational support, tangible support, affectionate support, positive social interaction and total support were predictors of sleep disturbance. Results Sleep disturbance was prevalent in breast cancer patients before (27.0%), during (32.5%) and after (39.2%) chemotherapy, with 37.4%, 41.9% and 52.6% of participants, respectively, reporting sleeping below the recommended 7 h. Only 8.6%–15.5% of patients reported taking sedative‐hypnotic drugs during the chemotherapy. Multivariate analyses found that participants reporting clinically significant anxiety (HADS > 8) were 3.5 times more likely to report sleep disturbance (PSQI > 8) than participants without clinically significant anxiety, and each increment in emotional/informational support was associated with a 9.04% reduced risk of sleep disturbance. Moreover, age was an independent predictor of sleep disturbance during multivariate modelling.

Abstract This study aimed to investigate the mechanism of FAK‐dependent hypoxia‐induced proliferation on human pulmonary artery smooth muscle cells (HPASMCs). Primary HPASMCs were isolated and cultured in vitro under normal and hypoxia conditions to assess cell proliferation with cell counting kit‐8. FAK and mitochondrial transcription termination factor 1 (mTERF1) were silenced with siRNA, mRNA, and protein levels of FAK, mTERF1, and cyclin D1 were determined. HPASMC proliferation increased under hypoxia compared to normal conditions. Knocking down FAK or mTERF1 with siRNA led to decreased cell proliferation under both normal and hypoxia conditions. FAK knockdown led to the reduction of both mTERF1 and cyclin D1 expressions under the hypoxia conditions, whereas mTERF1 knockdown led to the downregulation of cyclin D1 expression but not FAK expression under the same condition. However, under normal conditions, knocking down either FAK or mTERF1 had no impact on cyclin D1 expression. These results suggested that FAK may regulate the mTERF1/cyclin D1 signaling pathway to modulate cell proliferation in hypoxia.

Abstract Background The temporary pacing lead routinely is placed into right ventricular (RV), which pose a risk of dislocation and cardiac perforation. Objective We aim to evaluate the effectiveness and safety of temporary transvenous cardiac pacing (TTCP) leads placement into the coronary sinus vein (CSV) in patients with sick sinus syndrome (SSS). Methods We investigated patients with SSS who underwent TTCP lead placement into the CSV under the guidance of X‐ray between January 2013 and May 2023. Patients were randomly divided into two groups: RV group (n = 33) and CSV group (n = 22). The ordinary passive bipolar electrodes were applied in both groups. In RV groups, electrodes were placed into RV. In CSV group, electrodes were placed into CSV. We evaluated the operation duration, fluoroscopic exposure, first‐attempt success rate of leads placement, pacing threshold, success rate of leads placement, rate of leads displacement, and complications. Results Compared with that in RV group, the procedure time, fluoroscopic exposure was significantly prolonged, while the first‐attempt success rate of lead placement was obviously increased in CSV group (both p .05). Conclusion TTCP leads placement into the CSV is an effective and safe strategy in patients with SSS. It indicates a high rate of pacing effectiveness with low device replacement and complication rates.

Abstract Mitochondrial base editing with DddA‐derived cytosine base editor (DdCBE) is limited in the accessible target sequences and modest activity. Here, the optimized DdCBE tools is presented with improved editing activity and expanded C‐to‐T targeting scope by fusing DddA11 variant with different cytosine deaminases with single‐strand DNA activity. Compared to previous DdCBE based on DddA11 variant alone, fusion of the activation‐induced cytidine deaminase (AID) from Xenopus laevis not only permits cytosine editing of 5′‐GC‐3′ sequence, but also elevates editing efficiency at 5′‐TC‐3′, 5′‐CC‐3′, and 5′‐GC‐3′ targets by up to 25‐, 10‐, and 6‐fold, respectively. Furthermore, the A‐to‐G editing efficiency is significantly improved by fusing the evolved DddA6 variant with TALE‐linked deoxyadenosine deaminase (TALED). Notably, the authors introduce the reported high‐fidelity mutations in DddA and add nuclear export signal (NES) sequences in DdCBE and TALED to reduce off‐target editing in the nuclear and mitochondrial genome while improving on‐target editing efficiency in mitochondrial DNA (mtDNA). Finally, these engineered mitochondrial base editors are shown to be efficient in installing mtDNA mutations in human cells or mouse embryos for disease modeling. Collectively, the study shows broad implications for the basic study and therapeutic applications of optimized DdCBE and TALED.

Abstract Association between calcium intake and premature mortality in the general population has been well studied, but little is known about the association among specific populations. The authors aim to evaluate the association among people with hypertension and to provide a proper reference range of dietary calcium intake. This prospective cohort study included 8534 US adults with hypertension from National Health and Nutrition Examination Survey cycles 2003–2014. Dietary calcium intakes were self‐reported and mortality status was ascertained by National Death Index records. During a median follow‐up of 5.9 years, 1357 death occurred. Compared with participants of dietary calcium intake in quintile 1, participants in quintiles 2 and 4 had a 27% (HR: 0.73, 95% CI: 0.60–0.89) and a 29% lower risk (HR: 0.71, 95% CI: 0.57–0.88) of all‐cause mortality respectively. The authors also observed a 34% lower risk (HR: 0.66, 95% CI: 0.45–0.97) of CVD death among participants in quintile 3 and a 37% lower risk (HR: 0.63, 95% CI: 0.40–0.99) of cancer‐related death in participants in quintile 4 respectively. Restricted cubic spline (RCS) regression revealed a consistent protective effect of dietary calcium in participants with a daily intake of over 1000 mg, but a daily intake over 1200 mg fails to show further protective effect. Our findings suggest that elevated dietary calcium was associated with lower mortality risk from all‐causes, cardiovascular disease (CVD) and cancer, and supplying sufficient dietary calcium intake, between 1000 and 1200 mg per day, in people with hypertension may be considered cost‐effective to decrease risk of premature death.

Abstract The albumin‐bilirubin (ALBI) score was originally used to accurately assess liver dysfunction and predict the prognoses of patients with hepatocellular carcinoma. Following its more recent application to patients with gastrointestinal tumors, this study analyzed the prognostic value of the ALBI score in Chinese patients with advanced resectable (tumor‐node‐metastasis [TNM] stages I–III) gastric cancer (GC). This study investigated 1185 patients with advanced GC, including 429 with TNM stage I. The patients were divided into training and verifications groups (593 and 592 patients, respectively) in which these patients were classified as high risk (ALBI score ≥ −2.65) or low risk (ALBI score < −2.65). Univariate and multivariate Cox regression analyses were performed, and a visual survival prediction model (nomogram) was created. On Kaplan–Meier analysis, patients who were low‐risk and high‐risk according to their ALBI scores had significantly different survival rates in both the training and verification groups (p

Abstract Aim The aim of the study was to examine the relationships among nurses' shift work disorder, mental health and burnout to inform efforts to alleviate shift work disorder. Design This cross‐sectional study was conducted in China using a web‐based platform for questionnaire. Methods The study was comprised of a convenience sample of 1,268 Registered Nurses from 21 public hospitals in mainland China from June 2019–July 2019. Participants completed a web‐based survey designed to collect demographic and other self‐reported data. An independent sample t test and Pearson correlation were performed to analyse the relationship between shift work disorder, mental health and burnout. Results The vast majority (98.2%) of the participants were women between the ages of 20–59 years. The participants exhibited a higher incidence of mental health problems (58.1%) and burnout (65.5%) and those with shift work disorder exhibited a higher risk of mental health problems and burnout than those who did not have shift work disorder. Our research demonstrated that shift work disorder, combined with other variables, accounted for 40.5% of the variance in mental health (R2 = .405, adjusted R2 = .401, F = 107.214, p

Abstract Human gliomas are lethal brain cancers. Emerging evidence revealed the regulatory role of long noncoding RNAs (lncRNAs) in tumors. Here, we performed a comprehensive analysis of the expression profiles of RNAs in histologically lower‐grade glioma (LGG). Enrichment analysis revealed that glioma is influenced by immune‐related signatures. Survival analysis further established the close correlation between network features and glioma prognosis. Subsequent experiments showed lncRNA RP11‐770J1.4 regulates CTXN1 expression through hsa‐miR‐124‐3p. Correlation analysis identified lncRNA RP11‐770J1.4 was immune related, specifically involved in the cytosolic DNA sensing pathway. Downregulated lncRNA RP11‐770J1.4 resulted in increased spontaneous gene expression of the cGAS–STING pathway. Single‐cell RNA sequencing analysis, along with investigations in a glioblastoma stem cell model and patient sample analysis, demonstrated the predominant localization of CTXN1 within tumor cores rather than peripheral regions. Immunohistochemistry staining established a negative correlation between CTXN1 expression and infiltration of CD8+ T cells. In vivo, Ctxn1 knockdown in GL261 cells led to decreased tumor burden and improved survival while increasing infiltration of CD8+ T cells. These findings unveil novel insights into the lncRNA RP11‐770J1.4–CTXN1 as a potential immune regulatory axis, highlighting its therapeutic implications for histologically LGGs.

Abstract Background Inhibition of CDK7, a potent transcription regulator, may bring new hope for treating pancreatic ductal adenocarcinoma (PDAC), which is featured by large genetic heterogeneity and abundant KRAS mutations. This investigation aimed at exploring the discrepant efficacies of THZ1, a small‐molecule covalent CDK7 inhibitor, on PDACs with different KRAS mutations and the underlying mechanisms. Methods Associations of CDK7 expression with survival by KRAS mutations were first assessed. Effects of THZ1 on PDAC by different KRAS mutations were then investigated in vitro and in vivo. Moreover, the effects of THZ1 on gene transcription and phosphorylation of RNA polymerase II (RNAPOLII) in different KRAS mutant PDACs were assessed, and the effect of THZ1 on super‐enhancer activity was evaluated using chromatin immunoprecipitation sequencing. Lastly, the effects of THZ1 on the binding of H3K27ac to PIK3CA and on the PI3K/AKT/mTOR signalling were analysed. Results High CDK7 expression was significantly linked to worse survival within PDAC patients carrying KRAS‐G12V mutation but not in those with KRAS‐G12D mutation. The apoptosis‐inducing effect of THZ1 was markedly stronger in KRAS‐G12V PDAC than KRAS‐G12D cancer. THZ1 significantly inhibited the growth of xenograft tumour with KRAS‐G12V mutation, and the inhibition was markedly stronger than for KRAS‐G12D tumour. In mini‐cell‐derived xenograft (CDX) models, THZ1 significantly suppressed KRAS‐G12V PDAC but not KRAS‐G12D cancer. THZ1 significantly suppressed the phosphorylation of RNAPOLII, and this effect was stronger in KRAS‐G12V PDAC (especially at ser5). KRAS‐G12V PDAC had more H3K27ac‐binding super‐enhancers, and the inhibition of THZ1 on super‐enhancer activity was also stronger in KRAS‐G12V PDAC. Furthermore, THZ1 significantly weakened the binding of H3K27ac to PIK3CA in KRAS‐G12V PDAC. THZ1 significantly suppressed the PI3K/AKT/mTOR pathway and its downstream markers, and this effect was stronger in KRAS‐G12V cells. Conclusions In this hypothesis‐generating study, THZ1 might selectively inhibit certain PDACs with KRAS‐G12V mutation more potently compared with some other PDACs with KRAS‐G12D mutation, which might be associated with its effect on super‐enhancer activity and the PI3K/AKT/mTOR signalling. Our findings might offer novel key clues for the precise management of PDAC and important evidence for future targeted trial design. Highlights THZ1 had a stronger effect on PDAC‐bearing KRAS‐G12V mutation than G12D mutation. Suppressive effect of THZ1 on phosphorylation of RNAPOLII was stronger in KRAS‐G12V than KRAS‐G12D PDAC. Inhibition of THZ1 on super‐enhancer activity and H3K27ac binding to PIK3CA was stronger in KRAS‐G12V PDAC. Suppressive effect of THZ1 on PI3K/AKT/mTOR pathway was stronger in KRAS‐G12V PDAC.

Abstract Anthropogenic forcing caused the biodiversity loss and stability decline of communities. There is still controversy over whether the decline in biodiversity will lead to a decrease in community stability. The stability of biological communities is related to both biodiversity and structure, and this paper aims to reveal the human impacts on diatom communities' biodiversity and structure. We studied the richness, β‐diversity and network distance of diatom communities in Qinghai‐Xizang, Yunnan‐Sichuan and Lower Yangtze River Basin, China through empirical dataset and simulation method. The results showed that the diatoms richness in the Qinghai‐Xizang and the Yunnan‐Sichuan region was lower and the network distance was higher than that of the Lower Yangtze River Basin. β‐diversity in the Lower Yangtze River Basin was the lowest and the diatom network distance responds negatively to human population densities in China. The simulation showed that the network distance kept constant during random species loss, and declined while specialist species were lost or replaced by generalist species. The results suggested diatom communities' homogeneity and stability decline were associated with human activities. Human impacts may cause biodiversity loss targeted to specialist species or no biodiversity loss while generalist species replace those specialist species. This study showed that how diversity changes determined ecological stability depends on the type of species changes.

Abstract Background and Aims Nonsmall cell lung cancer accounts for over 85% of lung cancer incidences worldwide, and often has a poor prognosis. Proteasome inhibitors, such as bortezomib, have previously demonstrated evidence in preclinical and clinical models in the treatment of NSCLC both alone and as part of chemotherapeutic regimens. Methods Five databases were searched from inception to February 2023 to identify published clinical trial data and ongoing clinical trials on the use of proteasome inhibitors in treatment of NSCLC with a comprehensive search strategy. Results This review examines the clinical evidence from 21 completed and published phase I and II trials studying the use of bortezomib monotherapy and combination therapy in the treatment of NSCLC. Bortezomib/docetaxel combination resulted in longer median time‐to‐progression (TTP), median duration of response, median duration of disease control and median progression‐free survival (PFS) than bortezomib monotherapy, with concurrent administration having greater 6‐month PFS and median overall survival (OS) than sequential administration. Bortezomib/vorinostat with chemotherapy was well tolerated and effective. Bortezomib/gemcitabine/carboplatin, bortezomib/bevacizumab/carboplatin and bortezomib/paclitaxel/carboplatin combinations showed promising results and were of further investigational value. Conclusion Bortezomib showed some clinical promise in combination therapy but not monotherapy. It also demonstrated a manageable side effect profile. Combination regimens are of further investigation value in Phase II trials.

Abstract The effects of near surface or surface mechanisms on electrochemical performance (lower specific capacitance density) hinders the development of 3D printed micro supercapacitors (MSCs). The reasonable internal structural characteristics of printed electrodes and the appropriate intercalation material can effectively compensate for the effects of surface or near‐surface mechanisms. In this study, a layered structure is constructed inside an electrode using an ink with liquid‐crystal characteristics, and the pore structure and oxidation active sites of the layered electrode are optimized by controlling the amount of Co3O4‐quantum dots (Co3O4 QDs). The Co3O4 QDs are distributed in the pores of the electrode surface, and the insertion of Co3O4 QDs can effectively compensate for the limitations of surface or near‐surface mechanisms, thus effectively improving the pseudocapacitive characteristics of the 3D‐printed MSCs. The 3D printed MSC exhibits a high area capacitance (306.13 mF cm−2) and energy density (34.44 µWh cm−2 at a power density of 0.108 mW cm−2). Therefore, selecting the appropriate materials to construct printable electrode structures and effectively adjusting material ratios for efficient 3D printing are expected to provide feasible solutions for the construction of various high‐energy storage systems such as MSCs.

Abstract The selective removal of the β‐emitting pertechnetate ion (99TcO4−) from nuclear waste streams is technically challenging. Herein, a practical approach is proposed for the selective removal of 99TcO4− (or its surrogate ReO4−) under extreme conditions of high acidity, alkalinity, ionic strength, and radiation field. Hollow porous N‐doped carbon capsules loaded with ruthenium clusters (Ru@HNCC) are first prepared, then modified with a cationic polymeric network (R) containing imidazolium‐N+ units (Ru@HNCC‐R) for selective 99TcO4− and ReO4− binding. The Ru@HNCC‐R capsules offer high binding affinities for 99TcO4−/ReO4− under wide‐ranging conditions. An electrochemical redox process then transforms adsorbed ReO4− to bulk ReO3, delivering record‐high removal capacities, fast kinetics, and excellent long‐term durability for removing ReO4− (as a proxy for 99TcO4−) in a 3 m HNO3, simulated nuclear waste‐Hanford melter recycle stream and an alkaline high‐level waste stream (HLW) at the U.S. Savannah River Site (SRS). In situ Raman and X‐ray absorption spectroscopy (XAS) analyses showed that adsorbed Re(VII) is electrocatalytically reduced on Ru sites to a Re(IV)O2 intermediate, which can then be re‐oxidized to insoluble Re(VI)O3 for facile collection. This approach overcomes many of the challenges associated with the selective separation and removal of 99TcO4−/ReO4− under extreme conditions, offering new vistas for nuclear waste management and environmental remediation.

Background There are limited data on low‐density lipoprotein cholesterol (LDL‐C) goal achievement per the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidemia management guidelines and its impact on long‐term outcomes in patients undergoing coronary artery bypass grafting (CABG). We investigated the association between LDL‐C levels attained 1 year after CABG and the long‐term outcomes. Methods and Results A total of 2072 patients diagnosed with multivessel coronary artery disease and undergoing CABG between 2011 and 2020 were included. Patients were categorized by lipid levels at 1 year after CABG, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs) was evaluated. The goal of LDL‐C

Abstract Background Few studies have investigated the characteristics of non‐BRCA homologous recombination repair (HRR) pathway somatic mutations, and the impact of these mutations on efficacy of treatment in ovarian cancer patients is not clear. Therefore, we conducted this study to analyze the frequency and spectrum of somatic mutations in HRR pathway genes in patients with ovarian cancer and to examine the relationships between somatic mutations in HRR pathway genes and their effects on the efficacy of platinum‐based chemotherapy. Methods We performed targeted sequencing of 688 genes related to the occurrence, development, treatment, and prognosis of solid tumors. Somatic mutations were identified by paired analysis of tumor tissue and germline DNA in blood cells. Results A total of 38 patients with ovarian cancer were included in the study, and 35 (92.1%) patients were diagnosed with high‐grade serous carcinoma. All patients exhibited somatic mutations in the tumor tissue samples. The commonly mutated genes were TP53 (73.7%), BRCA2 (55.3%), NF1 (52.6%), BRCA1 (47.4%), and CDH1 (47.4%). Overall, 71.1% of the patients exhibited mutation in at least one HRR pathway gene. The most frequently altered HRR genes were BRCA2 (55.3%), followed by BRCA1 (47.4%), ATM (44.7%), BARD1 (42.1%), and CHEK1 (36.8%). The median progression‐free survival (PFS) in patients with HRR pathway mutation was 36.0 months compared with 13.6 months in patients with no HRR pathway mutation (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.08–0.77; p = 0.016). Patients harboring BRCA1/2 and/or CDK12 mutations displayed a longer PFS (median, 36.0 months) compared with patients with no BRCA1/2 or CDK12 mutation (median, 13.6 months; HR, 0.21; 95% CI, 0.07–0.61; p = 0.004). In multivariate analysis Cox proportional hazards models, after adjustment for tumor stage at diagnosis and histology of initial diagnosis, patients with HRR pathway mutation had a longer PFS than patients with HRR wild‐type genes (p = 0.006). Conclusions HRR pathway somatic mutations are common in Chinese patients with ovarian cancer. HRR pathway somatic mutations were associated with improved sensitivity to platinum‐based chemotherapy. Large‐scale prospective studies are needed to verify our findings.

Abstract Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by hemolytic anemia, bone marrow failure, thrombophilia. COVID‐19, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with many variants including Omicron. Methods This study collected demographic and clinical data of 20 PNH patients with SARS‐CoV‐2 Omicron infection. Results They all were with high disease activity, and LDH level exceeded any documented since the diagnosis of PNH, and those reported in the literature for previously stable treatment with complement inhibitors. D‐dimer level elevated in 10 patients. 2 patients developed mild pulmonary artery hypertension. Glomerular filtration rate declined in 5 patients. 1 patient developed acute renal failure and underwent hemodialysis. Anemia and hemolysis were improved in 5 patients treated with eculizumab. Conclusions Hemolytic exacerbation of PNH with COVID‐19 is severe and eculizumab may be an effective treatment.

Background Different T‐lymphocyte subsets, including CD1d‐dependent natural killer T (NKT) cells, play distinct roles in hypertension, highlighting the importance of identifying key immune cells for its treatment. This study aimed to determine the unknown effects of CD1d‐dependent NKT cells on hypertension and vascular injury. Methods and Results Hypertension models were induced in male CD1d knockout (CD1dko), wild‐type, and adoptive bone marrow transfer mice by angiotensin II (Ang II) or deoxycorticosterone acetate salt. Blood pressure was measured by the tail‐cuff system and radiotelemetry. Vascular injury was assessed by histologic studies or aortic ring assay. Inflammation was detected by flow cytometry, quantitative real‐time polymerase chain reaction, or ELISA. Results showed that Ang II infusion significantly reduced CD1d expression and NKT cell numbers in the aorta of mice. CD1dko mice exhibited worsened blood pressure elevation, vascular injury, and inflammatory response induced by Ang II or deoxycorticosterone acetate salt. However, these effects were markedly reversed in wild‐type mice treated with NKT cell–specific activator. Adoptive transfer of CD1dko bone marrow cells to wild‐type mice also significantly worsened Ang II–induced responses. Mechanistically, CD1dko increased Ang II–induced interleukin‐6 production and activated signal transducer and activator of transcription 3 and orphan nuclear receptor γ, subsequently inducing interleukin‐17A production. Neutralizing interleukin‐17A partially reversed Ang II–induced hypertension and vascular injury in CD1dko mice. In addition, levels of NKT cells were lower in the blood of patients with hypertension (n=57) compared with normotensive individuals (n=87). Conclusions These findings reveal a previously unknown role for CD1d‐dependent NKT cells in hypertension and vascular injury, indicating that NKT cell activation could be a promising therapeutic target for hypertension.

ABSTRACT Importance Bacteremia tuberculosis (TB) is a severe form of extrapulmonary TB. Studies assessing bacteremia TB in children are limited, especially for HIV‐negative children. Objective To explore the detailed clinical features of the bacteremia TB in children under 18 years of age. Methods We reviewed the clinical records of the patients retrospectively and collected the strains isolated from their blood cultures. We used mycobacterial interspersed repetitive‐unit‐variable‐number tandem‐repeat (MIRU‐VNTR) to characterize the bacterial genotypes and alamarBlue to determine their drug susceptibility profiles. Polymerase chain reactions and DNA sequencing were used to identify drug‐resistant mutations. Results There were 13 pediatric bacteremia TB patients, 10 of whom were diagnosed with Bacillus Calmette–Guérin (BCG) bacteremia TB. Thirteen patients aged from 0.30 to 11.58 years were enrolled, of whom 76.92% were boys. All had fevers before hospitalization, and 76.92% had respiratory symptoms. All had received BCG vaccinations, and 46.15% had adverse post‐vaccination reactions. Compared with Mycobacterium tuberculosis, BCG bacteremia was more likely to appear in younger children. Patients with BCG bacteremia had primary immunodeficiency diseases, and lower CD4, IgA, and IgE levels. Interpretation Bacteremia TB was rapidly fatal in a large proportion of the immunodeficient children. Because classic findings may not be diagnostically specific, a high level of clinical suspicion is required, especially for patients with certain types of immunosuppression. Studies are needed to develop rapid diagnostic tests and to determine the value of empirical therapy in childhood bacteremia TB.

Abstract Implantable electronic devices as a valuable biomedical tool are used to treat chronic diseases. However, traditional pacemakers exist a serious risk of complications. A biodegradable, closed‐loop sensor‐actuator system is developed for cardiac rhythm monitoring. This system could achieve autonomous electrotherapy.

Abstract Catalytically inactive CRISPR‐Cas13 (dCas13)‐based base editors can achieve the conversion of adenine‐to‐inosine (A‐to‐I) or cytidine‐to‐uridine (C‐to‐U) at the RNA level, however, the large size of dCas13 protein limits its in vivo applications. Here, a compact and efficient RNA base editor (ceRBE) is reported with high in vivo editing efficiency. The larger dCas13 protein is replaced with a 199‐amino acid EcCas6e protein, derived from the Class 1 CRISPR family involved in pre‐crRNA processing, and conducted optimization for toxicity and editing efficiency. The ceRBE efficiently achieves both A‐to‐I and C‐to‐U base editing with low transcriptome off‐target in HEK293T cells. The efficient repair of the DMD Q1392X mutation (68.3±10.1%) is also demonstrated in a humanized mouse model of Duchenne muscular dystrophy (DMD) after AAV delivery, achieving restoration of expression for gene products. The study supports that the compact and efficient ceRBE has great potential for treating genetic diseases.

Abstract Good safety, high interfacial compatibility, low cost, and facile processability make polymer‐based solid electrolytes promising materials for next‐generation batteries. Key issues related to polymer‐based solid electrolytes, such as synthesis methods, ionic conductivity, and battery architecture, are investigated in past decades. However, mechanistic understanding of the ionic conduction is still lacking, which impedes the design and optimization of polymer‐based solid electrolytes. In this review, the ionic conduction mechanisms and optimization strategies of polymer‐based solid electrolytes, including solvent‐free polymer electrolytes, composite polymer electrolytes, and quasi‐solid/gel polymer electrolytes, are summarized and evaluated. Challenges and strategies for enhancing the ionic conductivity are elaborated, while the ion‐pair dissociation, ion mobility, polymer relaxation, and interactions at polymer/filler interfaces are highlighted. This comprehensive review is especially pertinent for the targeted enhancement of the Li‐ion conductivity of polymer‐based solid electrolytes.

Abstract This review article deals with the ionic conductivity of solid‐state electrolytes for lithium batteries. It has discussed the mechanisms of ion conduction in ceramics, polymers, and ceramic‐polymer composite electrolytes. In ceramic electrolytes, ion transport is accomplished with mobile point defects in a crystal. Li+ ions migrate mainly via the vacancy mechanism, interstitial mechanism, or interstitial‐substitutional exchange mechanism. In solid polymer electrolytes, Li+ ions are transported mainly via the segment motion, ion hopping (Grotthuss mechanism), or vehicle mechanism (mass diffusion). This study has also introduced various electrolyte materials including perovskite oxides, garnet oxides, sodium superionic conductors, phosphates, sulfides, halides, cross‐linked polymers, block‐copolymers, metal‐organic frameworks, covalent organic frameworks, as well as ceramic‐polymer composites. In addition, it has highlighted some strategies to improve the ionic conductivity of solid‐state electrolytes, such as doping, defect engineering, microstructure tuning, and interface modification.

Abstract Aim To explore and describe nurses' self‐expression media image during COVID‐19 pandemic in China. Background Nurses play an important role in COVID‐19 pandemic. Although nurses were widely reported by the media, which included praise for nurses and nursing work, the researches on how nurses expressed their self‐images were limited. Design Qualitative media analysis. Methods Qualitative media analysis was conducted from January to April 2020, the researchers collected images and texts of 16 Chinese nurses who take care of COVID‐19 patients. These images and texts were published on WeChat Moments by themselves. After analysed each image and text, researchers identified the denotative and connotative elements in each image and summarized each image in narrative way. Findings This study analysed 219 pictures and 15 short videos of 16 nurses' self‐expression in WeChat moments. In this study, the media image self‐expression of nurses were mostly positive. The images expressed by nurses in this study included care image; hero image; soldier image; female image; hope image and team image. Nurses rarely showed negative images in the media; The negative nurses image were expressed in hidden way, which included exhausted nurses image and fragile nurses image. Moreover, the nurse self‐expression media image emphasized the nursing professionalism, but less showed the nursing connotation. Conclusions The positive media image self‐expression of nurses should be encouraged. Nurse Managers should pay attention to the deficiency of nursing image expression and guide nurses to show the essence and connotation of nursing.

Abstract Text detection methods based on grouping characters have emerged and have achieved promising performance. Nevertheless, previous methods that grouped characters by learning the relation of adjacent characters or used the heuristic clustering method with a handcrafted feature are unsuitable for dense, curved, or long texts. An effective manner of grouping characters is proposed by introducing K‐Means that is modified by the law of universal gravitation, an outlier detection mechanism and sufficient context information. Based on that, corresponding text detector is presented, named the Text Detector, based on modified K‐Means (KText), which can generate the bounding boundary of word‐level texts with an arbitrary shape. In the experimental stage, two novel stratagems are presented to replenish character‐level annotations to several datasets that provide only word‐level annotations. To evaluate the effectiveness of the method, experiments are carried out on three benchmarks, ICDAR2013, ICDAR2015 and Total‐Text, which contain horizontal, oriented and curved text. The results show that KText performs more competently than most state‐of‐the‐art text detectors when handling dense texts with an arbitrary shape.

Abstract Increasing the specific surface area of the anode foil of aluminum electrolytic capacitors is a research direction to improve the performance of capacitors. Industrial mass‐produced anode foil increases the specific surface area by electrochemical etching of the aluminum foil. However, the tunnels created by corrosion stop growing midway through this process. In this study, the effect of the solution flow rate on tunnel growth is investigated, and the growth of tunnels is analyzed using a new method of preparing oblique sections. Neater tunnels can be grown by increasing the solution flow rate to facilitate active tunnels.

Abstract Background Focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC) show persistent neuroinflammation, which promotes epileptogenesis and epilepsy progression, suggesting that endogenous resolution of inflammation is inadequate to relieve neuronal network hyperexcitability. To explore the potential roles of formyl peptide receptor 2 (FPR2), which is a key regulator of inflammation resolution, in epilepsy caused by FCDIIb and TSC, we examined the expression and cellular distribution of FPR2. Method The expression of FPR2 and nuclear factor‐κB (NF‐κB) signaling pathway was examined by real‐time PCR, western blots, and analyzed via one‐way analysis of variance. The distribution of FPR2 was detected using immunostaining. The expression of resolvin D1 (RvD1, the endogenous ligand of FPR2) was observed via enzyme‐linked immunosorbent assay. Pearson's correlation test was used to evaluate the correlation between the expression levels of FPR2 and RvD1 and the clinical variants. Results The expression of FPR2 was significantly lower in FCDIIb (p = .0146) and TSC (p = .0006) cortical lesions than in controls, as was the expression of RvD1 (FCDIIb: p = .00431; TSC: p = .0439). Weak FPR2 immunoreactivity was observed in dysmorphic neurons (DNs), balloon cells (BCs), and giant cells (GCs) in FCDIIb and TSC tissues. Moreover, FPR2 was mainly distributed in dysplastic neurons; it was sparse in microglia and nearly absent in astrocytes. The NF‐κB pathway was significantly activated in patients with FCDIIb and TSC, and the protein level of NF‐κB was negatively correlated with the protein level of FPR2 (FCDIIb: p = .00395; TSC: p = .0399). In addition, the protein level of FPR2 was negatively correlated with seizure frequency in FCDIIb (p = .0434) and TSC (p = .0351) patients. Conclusion In summary, these results showed that the expression and specific distribution of FPR2 may be involved in epilepsy caused by FCDIIb and TSC, indicating that downregulation of FPR2 mediated the dysfunction of neuroinflammation resolution in FCDIIb and TSC.

Abstract Background Apatinib is an oral anti‐angiogenic drug, its efficacy and prognosis in cervical carcinoma are unclear. This study evaluates the effectiveness and prognostic factors of apatinib in the treatment of recurrent or advanced cervical carcinoma. Methods Patients with recurrent or advanced cervical cancer, who agreed to take apatinib, were recruited into this single‐center and retrospective study, and administrated apatinib with or without combination of chemo‐ or radio‐therapy until progressive disease (PD) or unacceptable toxicity. Results From March 2017 to February 2019, 53 patients were reviewed. Among them, 2 (3.77%) patients occurred complete response, 16 (30.19%) patients showed partial response, 27 (50.95%) patients had stable disease, and 8 (15.09%) patients had PD. The objective response rate and disease control rate (DCR) of these patients were 33.96% and 84.91%, respectively. The DCR of patients younger than 50, nonsquamous carcinoma, first‐line apatinib therapy, combined radiotherapy, lesions within radiation field, surgical history, and Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 were significantly higher than other patients (p

Flexible artificial synapses, which use flexible electronic devices to simulate biological synapses, are the cornerstone of brain‐like computers and artificial intelligence systems. Devices based on field‐effect transistors (FETs) are suitable for emulating synaptic functions because of their diverse material selection, controllable parameters, and clear working mechanism. In addition, owing to their material fabrication and structural design, FETs can realize the special operation mechanisms of devices for constructing flexible artificial synapses with multiple functions. Herein, the essential principles of carrier transport in flexible artificial synapses based on FETs are focused. First, the selection of materials, carrier transfer mechanisms, and synaptic functions of flexible synaptic devices based on various transistors are summarized in detail. Subsequently, the applications of flexible synaptic devices in conformal artificial tactile and visual systems are introduced. Finally, future challenges and opportunities of flexible synaptic devices toward artificial neuromorphic electronics are discussed.

Abstract Seawater contains uranium at a concentration of ≈3.3 ppb, thus representing a rich and sustainable nuclear fuel source. Herein, an adsorption–electrocatalytic platform is developed for uranium extraction from seawater, comprising atomically dispersed indium anchored on hollow nitrogen‐doped carbon capsules functionalized with flexible amidoxime moieties (In–Nx–C–R, where R denotes amidoxime groups). In–Nx–C–R exhibits excellent uranyl capture properties, enabling a uranium removal rate of 6.35 mg g−1 in 24 h, representing one of the best uranium extractants reported to date. Importantly, In–Nx–C–R demonstrates exceptional selectivity for uranium extraction relative to vanadium in seawater (8.75 times more selective for the former). X‐ray absorption spectroscopy (XAS) reveals that the amidoxime groups serve as uranyl chelating sites, thus allowing selective adsorption over other ions. XAS and in situ Raman results directly indicate that the absorbed uranyl can be electrocatalytically reduced to an unstable U(V) intermediate, then re‐oxidizes to U(VI) in the form of insoluble Na2O(UO3·H2O)x for collection, through reversible single electron transfer processes involving InNx sites. These results provide detailed mechanistic understanding of the uranium extraction process at a molecular level. This work provides a roadmap for the adsorption–electrocatalytic extraction of uranium from seawater, adding to the growing suite of technologies for harvesting valuable metals from the earth's oceans.

Abstract This article proposes a novel flux‐adjustable permanent magnet eddy current coupling with multiple rotors. According to the different functions, the permanent magnet rotors are divided into fixed‐flux and flux‐adjustable rotors. By adjusting the relative position between two types of permanent magnet rotors, the magnetic field, torque, and output speed are controlled without changing the air‐gap length. To quickly and easily analyse the torque performance, an analytical model for the torque of such devices is developed based on the non‐linear magnetic equivalent circuit approach. In the modelling phase, a number of factors are considered, such as the skin effect, the inductance of eddy current field, the temperature effect, and so on. A three‐dimensional finite element method is employed to validate the model results, and the comparative analysis shows the advantages and potential of the proposed topology. The further sensitivity analysis of the key parameters is also made, which offers helpful information for the preliminary design of such devices.

Abstract A comparative investigation is made of stator consequent‐pole (SCP) machines with different permanent magnet (PM) arrangements. Compared with conventional surface‐mounted PM (SPM) configurations, SCP configurations produce more orders of air‐gap field harmonics. Due to asymmetrical PM magnetomotive force (MMF) distributions and the double‐side slotting effect, SCP machines exhibit multiple air‐gap field harmonics, especially relatively enhanced low‐order field harmonics, for torque production. As a consequence, improved torque capability can be obtained over that of conventional SPM counterparts. Machine topologies and operating principles are described. The design parameters of four SCP machines with different magnet arrangements are globally optimised. The key electromagnetic performances, including open‐circuit performance, torque quality, field‐weakening capability, and efficiency, are comprehensively investigated and compared by the finite element (FE) method. Finally, some experimental measurements on an optimally selected SCP machine prototype are carried out to validate the theoretical and FE analyses.