Search

Androgen‐regulated DNA damage response (DDR) is one of the essential mechanisms in prostate cancer (PCa), a hormone‐sensitive disease. The heterogeneous nuclear ribonucleoprotein K (hnRNPK)‐homology splicing regulatory protein known as far upstream element‐binding protein 2 (KHSRP) is an RNA‐binding protein that can attach to AU‐rich elements in the 3′ untranslated region (3′‐UTR) of messenger RNAs (mRNAs) to mediate mRNA decay and emerges as a critical regulator in the DDR to preserve genome integrity. Nevertheless, how KHSRP responds to androgen‐regulated DDR in PCa development remains unclear. This study found that androgen can significantly induce acetylation of KHSRP, which intrinsically drives tumor growth in xenografted mice. Moreover, enhanced KHSRP acetylation upon androgen stimuli impedes KHSRP‐regulated DDR gene expression, as seen by analyzing RNA sequencing (RNA‐seq) and Gene Set Enrichment Analysis (GSEA) datasets. Additionally, NAD‐dependent protein deacetylase sirtuin‐7 (SIRT7) is a promising deacetylase of KHSRP, and androgen stimuli impairs its interaction with KHSRP to sustain the increased KHSRP acetylation level in PCa. We first report the acetylation of KHSRP induced by androgen, which interrupts the KHSRP‐regulated mRNA decay of the DDR‐related genes to promote the tumorigenesis of PCa. This study provides insight into KHSRP biology and potential therapeutic strategies for PCa treatment, particularly that of castration‐resistant PCa.

Purpose Three‐level hybrid surgery (HS) consisting of cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) has been partly used for the treatment of multi‐level cervical degenerative disc disease (CDDD). The complications related to the implants and the collapse of the surgical vertebral bodies had been reported in multi‐level anterior cervical spine surgery. Thus, this study aimed to explore the biomechanical effects on the prostheses and vertebrae in three‐level HS. Methods A FE model of cervical spine (C0‐T1) was constructed. Five surgical models were developed. They were FAF model (ACDF‐CDA‐ACDF), AFA model (CDA‐ACDF‐CDA), FFF model (three‐level ACDF), SF model (single‐level ACDF), and SA model (single‐level CDA). A 75‐N follower load and 1.0‐N·m moment was applied to produce flexion, extension, lateral bending, and axial rotation. Results Compared with the intact model, the range of motion (ROM) of total cervical spine in FAF model decreased by 34.54%, 54.48%, 31.76%, and 27.14%, respectively, in flexion, extension, lateral bending, and axial rotation, which were lower than those in FFF model and higher than those in AFA model. The ROMs of CDA segments in FAF and AFA models were similar to the intact model and SA model. Compared with the intact model, the ROMs at C3/4 segment in FFF model increased from 5.71% to 7.85%, and increased from 5.31% to 6.81% at C7/T1 segment, following by FAF model, then the FAF model. The maximum interface pressures of the Prestige‐LP in FAF model were similar to SA model, however the corresponding values were increased in AFA model. The maximum interface pressures of the Zero‐P were increased in FAF and AFA model compared with those in SF and FFF models. The stress was mainly distributed on the screws. In AFA model, the maximum pressures of the ball and trough articulation in superior and inferior Prestige‐LP were all increased compared with those in SA and FAF model. In FFF model, the maximum pressures of the vertebrae were higher than those in other models. The stress was mainly distributed on the anterior area of the vertebral bodies. Conclusions HS seemed to be more suitable than ACDF for the surgical treatment of three‐level CDDD in consideration of the biomechanical effects, especially for the two‐level CDA and one‐level ACDF construct. But a more appropriate CDA prosthesis should be explored in the future.

Abstract Inflammatory responses play a central role in coordinating biomaterial‐mediated tissue regeneration. However, precise modulation of dynamic variations in microenvironmental inflammation post‐implantation remains challenging. In this study, the traditional β‐tricalcium phosphate‐based scaffold is remodeled via ultrathin MXene‐Ti3C2 decoration and Zn2+/Sr2+ ion‐substitution, endowing the scaffold with excellent reactive oxygen species‐scavenging ability, near‐infrared responsivity, and enhanced mechanical properties. The induction of mild hyperthermia around the implant via periodic near‐infrared irradiation facilitates spatiotemporal regulation of inflammatory cytokines secreted by a spectrum of macrophage phenotypes. The process initially amplifies the pro‐inflammatory response, then accelerates M1‐to‐M2 macrophage polarization transition, yielding a satisfactory pattern of osteo‐immunomodulation during the natural bone healing process. Later, sustained release of Zn2+/Sr2+ ions with gradual degradation of the 3D scaffold maintains the favorable reparative M2‐dominated immunological microenvironment that supports new bone mineralization. Precise temporal immunoregulation of the bone healing process by the intelligent 3D scaffold enhances bone regeneration in a rat cranial defect model. This strategy paves the way for the application of β‐tricalcium phosphate‐based materials to guide the dynamic inflammatory and bone tissue responses toward a favorable outcome, making clinical treatment more predictable and durable. The findings also demonstrate that near‐infrared irradiation‐derived mild hyperthermia is a promising method of immunomodulation.

Abstract For the need of direct contact with the skin, electronic skins (E‐skins) should not only fulfill electric functions, but also ensure comfort during wearing, including permeability, waterproofness, and easy removal. Herein, the study has developed a self‐adhesive, detach‐on‐demand, breathable, and waterproof E‐skin (PDSC) for motion sensing and wearable comfort by electrospinning styrene‐isoprene block copolymer rubber with carbon black nanosheets as the sensing layer and liner copolymers of N, N‐dimethylacrylamide, n‐octadecyl acrylate and lauryl methacrylate as the adhesive layer. The high elasticity and microfiber network structure endow the PDSC with good sensitivity and high linearity for strain sensing. The hydrophobic and crystallizable adhesive layer ensures robust, waterproof, and detaching‐on‐demand skin adhesion. Meanwhile, the fiber structure enables the PDSC good air and water permeability. The integration of electric and wearable functions endows the PDSC with great potential for motion sensing during human activities as both the sensing and wearable performances.

Abstract Material composition and structural design are important factors influencing the electromagnetic wave (EMW) absorption performance of materials. To alleviate the impedance mismatch attributed to the high dielectric constant of Ti3C2Tx MXene, we have successfully synthesized core‐shell structured SiO2@MXene@MoS2 nanospheres. This architecture, comprising SiO2 as the core, MXene as the intermediate layer, and MoS2 as the outer shell, is achieved through an electrostatic self‐assembly method combined with a hydrothermal process. This complex core‐shell structure not only provides a variety of loss mechanisms that effectively dissipate electromagnetic energy but also prevents self‐aggregation of MXene and MoS2 nanosheets. Notably, the synergistic combination of SiO2 and MoS2 with highly conductive MXene enables the suitable dielectric constant of the composites, ensuring optimal impedance matching. Therefore, the core‐shell structured SiO2@MXene@MoS2 nanospheres exhibit excellent EMW absorption performance, featuring a remarkable minimum reflection loss (RLmin) of −52.11 dB (2.4 mm). It is noteworthy that these nanospheres achieve an ultra‐wide effective absorption bandwidth (EAB) of 6.72 GHz. This work provides a novel approach for designing and synthesizing high‐performance EMW absorbers characterized by “wide bandwidth and strong reflection loss.”

Abstract Multi‐drug resistance (MDR) is a major cause of cancer therapy failure. Photodynamic therapy (PDT) is a promising modality that can circumvent MDR and synergize with chemotherapies, based on the generation of reactive oxygen species (ROS) by photosensitizers. However, overproduction of glutathione (GSH) by cancer cells scavenges ROS and restricts the efficacy of PDT. Additionally, side effects on normal tissues are unavoidable after PDT treatment. Here, to develop organic systems that deliver effective anticancer PDT and chemotherapy simultaneously with very little side effects, three GSH‐sensitive photosensitizer‐drug conjugates (CyR‐SS‐L) are designed and synthesized. CyR‐SS‐L localized in the mitochondria then is cleaved into CyR‐SG and SG‐L parts by reacting with and consuming high levels of intracellular GSH. Notably, CyR‐SG generates high levels of ROS in tumor cells instead of normal cells and be exploited for PDT and the SG‐L part is used for chemotherapy. CyR‐SS‐L inhibits better MDR cancer tumor inhibitory activity than indocyanine green, a photosensitizer (PS) used for PDT in clinical applications. The results appear to be the first to show that CyR‐SS‐L may be used as an alternative PDT agent to be more effective against MDR cancers without obvious damaging normal cells by the combination of PDT, GSH depletion, and chemotherapy.

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Abstract Automatic profiled fibre recognition and analysis can accelerate quality inspection and contributes to the upgrade of the textile industry. However, these tasks often require significant manual effort to generate instance‐level annotations for fully supervised training. In this paper, the authors propose a weakly supervised pipeline for profiled fibre inspection using electron‐microscopic (EM) images with only image‐level annotations. It automatically identifies fibre instances and estimates shape factors to facilitate fibre quality inspection. As the core of the pipeline, the weakly supervised network (WesNet) is designed to localize hundreds of crowded fibre samples by raw patch generation and fibre sample sifting. Particularly, the composite similarity measurement integrates different patch‐wise similarities, enabling the network to distinguish fibre from background robustly. For quality inspection, the pipeline further analyzes the fibre instances, utilizing several efficient techniques to estimate the shape factors. Experiments on the real fibre electron‐microscopic images demonstrate the efficacy and efficiency of the pipeline. Results show that WesNet outperforms several supervised and weakly supervised methods, including two state‐of‐the‐art weakly supervised networks.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Abstract Background Cell‐free long RNAs in human plasma and extracellular vesicles (EVs) have shown promise as biomarkers in liquid biopsy, despite their fragmented nature. Methods To investigate these fragmented cell‐free RNAs (cfRNAs), we developed a cost‐effective cfRNA sequencing method called DETECTOR‐seq (depletion‐assisted multiplexed cell‐free total RNA sequencing). DETECTOR‐seq utilised a meticulously tailored set of customised guide RNAs to remove large amounts of unwanted RNAs (i.e., fragmented ribosomal and mitochondrial RNAs) in human plasma. Early barcoding strategy was implemented to reduce costs and minimise plasma requirements. Results Using DETECTOR‐seq, we conducted a comprehensive analysis of cell‐free transcriptomes in both whole human plasma and EVs. Our analysis revealed discernible distributions of RNA types in plasma and EVs. Plasma exhibited pronounced enrichment in structured circular RNAs, tRNAs, Y RNAs and viral RNAs, while EVs showed enrichment in messenger RNAs (mRNAs) and signal recognition particle RNAs (srpRNAs). Functional pathway analysis highlighted RNA splicing‐related ribonucleoproteins (RNPs) and antimicrobial humoral response genes in plasma, while EVs demonstrated enrichment in transcriptional activity, cell migration and antigen receptor‐mediated immune signals. Our study indicates the comparable potential of cfRNAs from whole plasma and EVs in distinguishing cancer patients (i.e., colorectal and lung cancer) from healthy donors. And microbial cfRNAs in plasma showed potential in classifying specific cancer types. Conclusions Our comprehensive analysis of total and EV cfRNAs in paired plasma samples provides valuable insights for determining the need for EV purification in cfRNA‐based studies. We envision the cost effectiveness and efficiency of DETECTOR‐seq will empower transcriptome‐wide investigations in the fields of cfRNAs and liquid biopsy. Keypoints DETECTOR‐seq (depletion‐assisted multiplexed cell‐free total RNA sequencing) enabled efficient and specific depletion of sequences derived from fragmented ribosomal and mitochondrial RNAs in plasma. Distinct human and microbial cell‐free RNA (cfRNA) signatures in whole Plasma versus extracellular vesicles (EVs) were revealed. Both Plasma and EV cfRNAs were capable of distinguishing cancer patients from normal individuals, while microbial RNAs in Plasma cfRNAs enabled better classification of cancer types than EV cfRNAs.

Abstract N6‐methyladenosine (m6A) modification, installed by METTL3‐METTL14 complex, is abundant and critical in eukaryotic mRNA. However, its role in oral mucosal immunity remains ambiguous. Periodontitis is a special but prevalent infectious disease characterized as hyperinflammation of oral mucosa and bone resorption. Here, it is reported that genetic deletion of Mettl3 alleviates periodontal destruction via suppressing NLRP3 inflammasome activation. Mechanistically, the stability of TNFAIP3 (also known as A20) transcript is significantly attenuated upon m6A modification. When silencing METTL3, accumulated TNFAIP3 functioning as a ubiquitin‐editing enzyme facilitates the ubiquitination of NEK7 [NIMA (never in mitosis gene a)‐related kinase 7], and subsequently impairs NLRP3 inflammasome assembly. Furtherly, Coptisine chloride, a natural small‐molecule, is discovered as a novel METTL3 inhibitor and performs therapeutic effect on periodontitis. The study unveils a previously unknown pathogenic mechanism of METTL3‐mediated m6A modifications in periodontitis and indicates METTL3 as a potential therapeutic target.

Abstract Ulcerative colitis (UC) manifests clinically with chronic intestinal inflammation and microflora dysbiosis. Although biologics can effectively control inflammation, efficient delivery to the colon and colon epithelial cells remains challenging. Milk‐derived extracellular vesicles (EV) show promise as an oral delivery tool, however, the ability to load biologics into EV presents challenges to therapeutic applications. Here, we demonstrate that fusing cell‐penetrating peptide (TAT) to green fluorescent protein (GFP) enabled biologics loading into EV and protected against degradation in the gastrointestinal environment in vitro and in vivo after oral delivery. Oral administration of EV loaded with anti‐tumour necrosis factor‐α (TNF‐α) nanobody (VHHm3F) (EVVHH) via TAT significantly reduced tissue TNF‐α levels and alleviated pathologies in mice with acute UC, compared to VHH alone. In mice with chronic UC, simultaneously introducing VHH and an antimicrobial peptide LL37 into EV (EVLV), then administering orally improved intestinal barrier, inflammation and microbiota balance, resulted in relief of UC‐induced depression and anxiety. Collectively, we demonstrated that oral delivery of EVLV effectively alleviated UC in mice and TAT efficiently loaded biologics into EV to confer protection from degradation in the gastrointestinal tract. This therapeutic strategy is promising for UC and is a simple and generalizable approach towards drug‐loaded orally‐administrable EV treatment for other diseases.

Abstract Electrocatalytic water splitting seems to be an efficient strategy to deal with increasingly serious environmental problems and energy crises but still suffers from the lack of stable and efficient electrocatalysts. Designing practical electrocatalysts by introducing defect engineering, such as hybrid structure, surface vacancies, functional modification, and structural distortions, is proven to be a dependable solution for fabricating electrocatalysts with high catalytic activities, robust stability, and good practicability. This review is an overview of some relevant reports about the effects of defect engineering on the electrocatalytic water splitting performance of electrocatalysts. In detail, the types of defects, the preparation and characterization methods, and catalytic performances of electrocatalysts are presented, emphasizing the effects of the introduced defects on the electronic structures of electrocatalysts and the optimization of the intermediates' adsorption energy throughout the review. Finally, the existing challenges and personal perspectives of possible strategies for enhancing the catalytic performances of electrocatalysts are proposed. An in‐depth understanding of the effects of defect engineering on the catalytic performance of electrocatalysts will light the way to design high‐efficiency electrocatalysts for water splitting and other possible applications.

Abstract Despite recent advances in extrusion bioprinting of cell‐laden hydrogels, using naturally derived bioinks to biofabricate complex elastic tissues with both satisfying biological functionalities and superior mechanical properties is hitherto an unmet challenge. Here, we address this challenge with precisely designed biological tough hydrogel bioinks featuring a double‐network structure. The tough hydrogels consisted of energy‐dissipative dynamically crosslinked glycosaminoglycan hyaluronic acid (o‐nitrobenzyl‐grafted hyaluronic acid) and elastin through Schiff's base reaction, and free‐radically polymerized gelatin methacryloyl. The incorporation of elastin further improved the elasticity, stretchability (∼170% strain), and toughness (∼45 kJ m−3) of the hydrogels due to the random coiling structure. We used this novel class of hydrogel bioinks to bioprint several complex elastic tissues with good shape retention. Furthermore, in vitro and in vivo experiments also demonstrated that the existence of elastin in the biocompatible bioinks facilitated improved cell behaviors and biological functions of bioprinted tissues, such as cell spreading and phenotype maintenance as well as tissue regeneration. The results confirmed the potential of the elastin‐containing tough hydrogel bioinks for bioprinting of 3D complex elastic tissues with biological functionalities, which may find widespread applications in elastic tissue regeneration.

Abstract Exploring organic semiconductor gas sensors with high sensitivity and selectivity is crucial for the development of sensor technology. Herein, for the first time, a promising chemiresistive organic polymer P‐BNT based on a novel π‐conjugated triarylboron building block is reported, showcasing an excellent responsivity over 30 000 (Ra/Rg) against 40 ppm of NH3, which is ≈3300 times higher than that of its B‐N organic small molecule BN‐H. More importantly, a molecular induction strategy to weaken the bond dissociation energy between polymer and NH3 caused by strong acid‐base interaction is further executed to optimize the response and recovery time. As a result, the BN‐H/P‐BNT system with rapid response and recovery times can still exhibit a high responsivity of 718, which is among the highest reported NH3 chemiresistive sensors. Supported by in situ FTIR spectroscopy and theoretical calculations, it is revealed that the N‐H fractions in BN‐H small molecule promoted the charge distribution on phenyl groups, which increases charge delocalization and is more conducive to gas adsorption in such molecular systems. Notably, these distinctive small molecules also promoted charge transfer and enhanced electron concentration of the P‐BNT sensing polymer, thus achieving superior B‐N‐containing organic molecules with excellent sensing performance.

The use of collaborative robots (Cobots) for materials development in chemical laboratories is currently of high priority. Herein, the Cobot is used for autonomous continued analysis and synthesis of graphene oxide–polyethyleneimine‐based membrane to unify a method and prospects for big data collection are shown. Membranes have already demonstrated a selective affinity to potassium cations and promised to adjust permeability for other cations by changing pH. The Cobot allows a variation of membrane properties by its composition modification. The present strategy combines a novel perspective of material production by Cobots and the application of machine learning. Moreover, the current approach can be adapted for different modern chemical laboratories for various scientific research, and the proper workflow is provided.

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Objective Hip fractures are the most common fractures among older adults, with most patients undergoing surgery. The debate regarding the type of anesthetic technique for hip fracture surgery is still ongoing. This meta‐analysis aimed to compare the intraoperative and postoperative outcomes of spinal and general anesthesia in older patients undergoing hip fracture surgery. Methods Eligible studies that compared the effects of spinal and general anesthesia were systematically searched from PubMed, Embase, and the Cochrane Library until May 27, 2022. The intraoperative and postoperative outcomes of the two anesthesia techniques were compared. Quality assessment, heterogeneity analysis, and publication bias of the studies were also assessed. Results Nine articles of methodological quality were included in the meta‐analysis. The pooled results revealed that there were significant differences in hypotension (risk ratio [RR] (95% confidence interval [CI]) = 0.81 (0.68, 0.97), p = 0.02) and ephedrine dose (weighted mean difference [WMD] [95%CI] = −20.94 [−37.50, −4.37] mg, p = 0.01) between the spinal and general anesthesia groups. However, no significant differences were observed in the use of ephedrine (RR [95% CI] = 0.77 [0.19, 3.05]), blood loss (WMD [95%CI] = −34.38 [−89.56, 20.80) mL], myocardial infarction (RR [95% CI] = 0.78 [0.31, 1.94] mL), heart failure (RR [95% CI] = 0.87 [0.17, 4.36] mL), stroke (RR [95%CI) = 0.65 [0.22, 1.95] mL), postoperative nausea and vomiting (RR [95% CI] = 0.88 [0.17, 4.35] mL), delirium (RR [95% CI] = 1.08 [0.89, 1.31] mL), and mortality (RR [95% CI] = 1.10 [0.72, 1.68] mL) (all p

Abstract Background Chromosomal translocations involving core binding factor (CBF) genes account for 15% of adult acute myeloid leukemia (AML) cases in China. Despite being classified as favorable‐risk by European Leukemia Net (ELN), CBF‐AML patients have a 40% relapse rate. This study aims to analyze clinical characteristics and prognosis of CBF‐AML, compare its subtypes (inv(16) and t(8;21)), and validate prognostic factors. Methods Retrospective analysis of 149 AML patients (75 CBF‐AML, 74 non‐CBF) at Peking University First Hospital (March 2012–March 2022). Results CBF‐AML patients have significantly lower disease‐free survival (DFS) (p = 0.005) and higher non‐relapse mortality (NRM) (p = 0.028) compared to non‐CBF AML. inv (16) and t(8;21) show distinct co‐occurring gene mutation patterns, with inv(16) being prone to central nervous system (CNS) leukemia. Multivariate analysis identifies age as a risk factor for overall survival (OS) and disease free survival (DFS), kinase mutation as a risk factor for DFS and Recurrence, while WT1 mutation as a risk factor for OS and non relapse mortality (NRM) risk in t(8;21) AML. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) improves prognosis in low‐risk t(8;21). Conclusion Prognosis of CBF‐AML is poorer than ELN guidelines suggest. inv(16) and (8;21) are separate entities with relatively poor prognoses, requiring rational risk stratification strategies. Allo‐HSCT may benefit low‐risk t(8;21), but further research is needed for conclusive evidence.

Abstract The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.

Abstract INTRODUCTION Aging is often associated with cognitive decline. Understanding neural factors that distinguish adults in midlife with superior cognitive abilities (Positive‐Agers) may offer insight into how the aging brain achieves resilience. The goals of this study are to (1) introduce an optimal labeling mechanism to distinguish between Positive‐Agers and Cognitive Decliners, and (2) identify Positive‐Agers using neuronal functional connectivity networks data and demographics. METHODS In this study, principal component analysis initially created latent cognitive trajectories groups. A hybrid algorithm of machine learning and optimization was then designed to predict latent groups using neuronal functional connectivity networks derived from resting state functional magnetic resonance imaging. Specifically, the Optimal Labeling with Bayesian Optimization (OLBO) algorithm used an unsupervised approach, iterating a logistic regression function with Bayesian posterior updating. This study encompassed 6369 adults from the UK Biobank cohort. RESULTS OLBO outperformed baseline models, achieving an area under the curve of 88% when distinguishing between Positive‐Agers and cognitive decliners. DISCUSSION OLBO may be a novel algorithm that distinguishes cognitive trajectories with a high degree of accuracy in cognitively unimpaired adults. Highlights Design an algorithm to distinguish between a Positive‐Ager and a Cognitive‐Decliner. Introduce a mathematical definition for cognitive classes based on cognitive tests. Accurate Positive‐Ager identification using rsfMRI and demographic data (AUC = 0.88). Posterior default mode network has the highest impact on Positive‐Aging odds ratio.

Abstract In South and Southeast Asia, the habit of chewing betel nuts is prevalent, which leads to oral submucous fibrosis (OSF). OSF is a well‐established precancerous lesion, and a portion of OSF cases eventually progress to oral squamous cell carcinoma (OSCC). However, the specific molecular mechanisms underlying the malignant transformation of OSCC from OSF are poorly understood. In this study, the leading‐edge techniques of Spatial Transcriptomics (ST) and Spatial Metabolomics (SM) are integrated to obtain spatial location information of cancer cells, fibroblasts, and immune cells, as well as the transcriptomic and metabolomic landscapes in OSF‐derived OSCC tissues. This work reveals for the first time that some OSF‐derived OSCC cells undergo partial epithelial–mesenchymal transition (pEMT) within the in situ carcinoma (ISC) region, eventually acquiring fibroblast‐like phenotypes and participating in collagen deposition. Complex interactions among epithelial cells, fibroblasts, and immune cells in the tumor microenvironment are demonstrated. Most importantly, significant metabolic reprogramming in OSF‐derived OSCC, including abnormal polyamine metabolism, potentially playing a pivotal role in promoting tumorigenesis and immune evasion is discovered. The ST and SM data in this study shed new light on deciphering the mechanisms of OSF‐derived OSCC. The work also offers invaluable clues for the prevention and treatment of OSCC.

Abstract Evaluating and understanding the effect of manufacturing processes on the creep performance in superalloys poses a significant challenge due to the intricate composition involved. This study presents a machine‐learning strategy capable of evaluating the effect of the heat treatment process on the creep performance of superalloys and predicting creep rupture life with high accuracy. This approach integrates classification and regression models with domain‐specific knowledge. The physical constraints lead to significantly enhanced prediction accuracy of the classification and regression models. Moreover, the heat treatment process is evaluated as the most important descriptor by integrating machine learning with superalloy creep theory. The heat treatment design of Waspaloy alloy is used as the experimental validation. The improved heat treatment leads to a significant enhancement in creep performance (5.5 times higher than the previous study). The research provides novel insights for enhancing the precision of predicting creep rupture life in superalloys, with the potential to broaden its applicability to the study of the effects of heat treatment processes on other properties. Furthermore, it offers auxiliary support for the utilization of machine learning in the design of heat treatment processes of superalloys.

Abstract Stimuli‐responsive fluorescent hydrogels are three‐dimensional networked polymeric materials with tunable luminescence and dynamic properties, which play an important role as a water‐rich soft material in the fields of information encryption, bionic actuation, bioimaging, environmental monitoring, and luminescent materials. Compared with conventional hydrogels, their unique luminescent properties allow the visualization of microscopic dynamics within the polymer network. By rational inclusion of dynamic motifs, such as photoswitches, AIEgens, lanthanide complexes, and host–guest complexes, these materials are endowed with tunability of emission, shape, and phase in time and space in response to environmental effectors. In this review, we summarize the fabrication strategies that are mainly used by recently reported stimuli‐responsive fluorescent hydrogels and the applications of these materials.

Abstract Liquid permeation into silicone rubber (SR) may lead to the degradation or complete failure of the composite insulators. Aiming to inhibit liquid permeation, two kinds of superhydrophobic coatings are applied to the SR surface. The liquid permeation properties of SR with different types of liquids are investigated, and the Langmuir diffusion model is applied to analyse the experimental data. The results show that the composite superhydrophobic coating can effectively inhibit liquid permeation by reducing the contact area between the surface and liquid, and the stable structure of the composite coating can maintain the performance after the liquid permeation and effusion. However, the nano‐particle coating without the polymer binder experiences severe performance degradation during the immersion test, and it cannot restrain the liquid permeation anymore after it loses the superhydrophobicity. As a validation of the effective protection, the insulation resistivity change was measured. The resistivity decreases sharply for the pristine SR after water permeation; however, the decrease is much smaller for the coated SR. The current study not only provides new insight into the liquid permeation properties of SR with different surface wettability but also suggests an effective measure to prevent liquid permeation into SR.

Abstract Smart sensors with excellent performance are accelerating the development of biomedicine and the Internet of Energy. Nanodielectrics exhibit unique electrical and mechanical properties. As the predominant materials in optical magnetic field sensor (MFS), they can not only exert the anti‐interference of optical sensing, but improve the measuring characteristics of optical sensors. For instance, the optical fibre quantum probe for the magnetic field can obtain a higher sensitivity of 0.57 nT/Hz1/2, while the measurement range of the sensor that uses Co‐doped ZnO nanorods as cladding is 17–180 mT. Here, these exciting recent achievements in the realm of optical sensing methods for magnetic field detection are reviewed, with a focus on nanodielectrics, which provide an emerging opportunity to achieve higher sensitivity and a wider measurement range of MFS.

Abstract Flexible solar wings with high energy density, lightweight, small size and large deployment area are one of the first choices for next‐generation spacecraft. However, the flexible solar wings are subjected to irradiation in space and tensile mechanical stress, which produce the charge accumulation effect and result in electrostatic discharge. It is necessary to establish a test method for the conductivity and space charge behaviour of polyimide under tensile stress. The stress–strain characteristics of polyimide under different tensile stresses are studied by the authors. The longitudinal length‐strain characteristics and transverse thickness evolution characteristics under different stresses are also obtained. The results show that the variation of film thickness with tensile force is only about 1% before the yield point. The polyimide films from 50 to 200 μm thick have similar yield and tensile strengths. The ultimate stress of the specimen decreases from approximately 126 to 103 MPa with increasing thickness. The thickness model of polyimide under tensile stress were obtained, which could accurately calculate the voltage amplitude applied on the specimens for measuring the conductivity under different tensile stresses. A basis for investigating the stress–strain characteristics of polyimide films under different tensile stresses are provided, which will facilitate the formulation selection and performance improvement of polyimide for flexible solar wings of spacecraft.

Abstract Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high‐risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow‐up.

Abstract Composite polymer dielectrics have strong electrical, mechanical, thermal and environmental properties but experience both high electric fields and harsh environmental conditions as outdoor insulation. The present investigation of the stress‐strain characteristics and morphology of the fracture cross‐section reveal the risk of a weakly bonded interface between the aluminium hydroxide (ATH) filler and silicone rubber used for insulators in transmission lines and substations. Dielectric response measurements are proposed as a non‐destructive probe of the interface quality. An analysis, based on the Dissado–Hill model, indicated that the introduction of ATH interfaces gave rise to a quasi‐DC process, in which charge transport is in the form of hopping along the weakly bonded interfaces. A schematic plan is proposed that would allow such an analysis to be used to obtain quantitative information correlated to the status of the weakly bonded interface for the diagnosis of micro‐interface quality in ATH‐filled silicone rubber and dielectric composites in general.

Abstract Aim The aim of this study is to examine the incidence and risk factors for intimate partner violence (IPV) among patients with gynaecological cancer. Design A cross‐sectional study design was employed. Methods Patients with gynaecological cancer were recruited from a tertiary hospital in Shandong, China. Eligible patients completed a survey including questions regarding their demographic and cancer‐related characteristics, IPV experience and dyadic coping. Results A total of 429 patients were surveyed, 31% of them reported previous experiences with IPV, and negotiation was the most common type reported. The following variables were associated with IPV: a husband, wife and child/children family structure; a husband, wife, child/children and parent‐in‐law family structure; an annual household income ≥¥50,000 ($7207); and a similar or greater income earned by the patient than by her partner. Patient or Public Contribution IPV in patients with gynaecological cancer is investigated in this study.

Objective. This study aims to explore the relationships between serum indoxyl sulfate (IS) and Klotho protein levels with vascular calcification in patients with chronic kidney disease (CKD) stages 3–5. Methods. From December 2021 to January 2023, a total of 108 CKD patients in stages 3–5 were enrolled in this cross-sectional investigation. Demographic information and routine clinical biochemistry test results were gathered. Serum levels of IS and Klotho were quantified through enzyme-linked immunosorbent assays. Furthermore, multislice spiral computed tomography was employed to evaluate vascular calcification. The association between serum IS or Klotho levels and abdominal aorta calcification was assessed using univariate analysis and logistic regression analyses. Results. With the progression of CKD stages, serum creatinine, phosphorus, intact parathyroid hormone (iPTH), serum IS, and abdominal aortic calcification exhibited incremental trends, while serum calcium and Klotho protein levels showed a diminishing trend, with statistically significant differences (P

Abstract Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumour which rarely affects the chest cavity. We, for the first time, report a case of mediastinal EIMS with the EML4‐ALK fusion. A young woman presented to our hospital with cough, chest tightness and shortness of breath. Computed tomography (CT) showed a mixed attenuation soft‐tissue mass in the right middle and upper mediastinum. Negative results were obtained from bronchoscopy forceps biopsy and endobronchial ultrasound‐guided transbronchial fine needle aspiration. CT‐guided percutaneous biopsy was finally performed. However, due to the rapidly progressed EIMS that compressed the trachea and right main bronchus, the patient died of respiratory failure 1 day before diagnosis. EIMS progresses rapidly, and an early diagnosis is important. For mediastinal EIMS, CT‐guided percutaneous biopsy may be useful. Next‐generation sequencing of blood may be instructive to EIMS patients who are intolerant to invasive biopsy.

Abstract Bacterial extracellular vesicles (BEVs) are nano‐size particles secreted by bacteria that carry various bioactive components. These vesicles are thought to provide a new window into the mechanisms by which bacteria affect their hosts, but their fundamental proprieties within human remain poorly understood. Here, we developed a single‐vesicle analytical platform that enabled BEV detection in complex biological samples of host. Using this platform, we found the presence of BEVs in the host circulation and they were mainly derived from gut microbes. We showed that the levels of circulating BEVs in humans significantly increased with aging due to an age‐related increase in intestinal permeability. Significantly different levels of BEVs in blood were also found in patients with colorectal cancer and colitis. Together, our study provides new insights into circulating BEV biology and reveals their potential as a new class of biomarkers.

Abstract Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first‐ and second‐line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow‐up of TETs.

Abstract The DC link single sensor phase current reconstruction method has brought several challenges, which consist of the unobservable area and current zero drift error, where the duration of the effective vector is too short to measure, and current zero drift error leads to reconstruction error. An error self‐correction complementary non‐zero vector pulse width modulation (ESC2N‐PWM) method is proposed. Through the analysis of the DC link sampling principle, the minimum sample time is defined. Then applying complementary non‐zero vectors to replace zero voltage vector, the current sampling window is extended, and the sector boundary unobservable area is eliminated. At the same time, through the dynamic double sampling of the complementary effective voltage vectors, the zero drift of current is self‐detected and self‐corrected. The experimental results show that the reconstruction error of the proposed method is lower than 2.84%, and the current THD is lower than 6.20%.

Abstract Background Immunotherapy has exhibited efficacy in thymic carcinoma patients; however, there are insufficient data to confirm this efficacy in thymoma. The toxicity of immunotherapy also remains to be determined. Methods The efficacy and safety of immunotherapy were analyzed in 11 thymoma patients who received PD‐1 inhibitors according to a range of relevant indexes including the objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and immunotherapy‐related adverse events. Results The PFS and OS rates for all patients were 12.8 and 56.5 months, respectively. No difference in efficacy was detected between monotherapy and combination therapy (PFS: 12.8 vs 2.2 months, P = 0.787; OS: 73.8 vs 56.5 months, P = 0.367). The ORRs and DCRs for all patients were 27.3% and 90.9%, respectively. The incidence of adverse events was 45.5% among the 11 thymoma patients, including immune‐related myocarditis (36.4%), immune‐related liver damage (18.2%), and myasthenia gravis (18.2%). In the whole cohort of patients, the rate of adverse events of grade 3 or higher was 36.4%. The rates of adverse events of grade 3 or 4 in B3‐type and non‐B3‐type thymoma patients were 0% and 62.5%, respectively. Conclusions Immunotherapy elicited a response in thymoma patients; however, more attention should be paid to the immune‐related adverse events.

Abstract Glycolytic flux is a fundamental index in microbial cell factories. A glycolytic flux biosensor that can monitor glucose metabolism efficiency is a promising strategy in rewiring metabolic flux to balance growth and biosynthesis. A key design feature of the glycolytic flux biosensors is the interaction between the global transcriptional factor Cra and its regulated promoters. However, overexpression and mutation of Cra has unpredictable effects on global metabolism in Escherichia coli. Therefore, new orthogonal biosensor design strategies should be developed to circumvent metabolic issues. In this report, the promoters in glycolytic flux biosensor were replaced with synthetic promoters of varying strengths or phage‐derived promoters, and the Cra DNA‐binding sites were deployed into promoters at different positions and distances to yield biosensors. The de nova biosensors that depended on Cra could sense Fructose‐1,6‐diphosphate (FBP) with broad dynamic ranges and low basal leakage. Then the negative‐response biosensors were applied to fine‐tune the target ATP synthesis gene, leading to the desired increase in pyruvate production (the highest 9.66 g/L) and cell growth. Moreover, the membrane synthesis gene plsC was also dynamically activated by the positive‐response biosensor, leading to effective accumulation of lycopene in the cell membrane and a 50‐fold increase in lycopene titre (100.3 mg/L) when compared with the control strain, demonstrating the effective and broader usages of our biosensors.

Abstract Background The use of proteasome inhibitors (PIs), new immune modulators (IMiDs), and other new drugs, as well as high‐dose chemotherapy combined with autologous stem cell transplantation has considerably improved the survival of young patients with multiple myeloma (MM). However, the improvement in survival among elderly patients remains insufficient. Optimal treatment recommendation models for elderly patients with MM have not been developed especially there are quite few study in the real world. Methods We retrospectively analyzed the treatment patterns and outcomes of 328 Chinese patients (≥65 years) with MM in a real‐world setting. Patients were divided into three groups according to induction regimens. Results The median age of the cohort was 70 (65–86) years. The patients were divided into group 1 (PIs based regimens, n = 218), group 2 (IMiDs based regimens, n = 48) and group 3 (PIs + IMiDs, n = 62). Induction regimens in group 3 produced higher overall response rate than group 1 and 2 (85.42% vs. 71.08% vs. 66.67%, p = 0.016). The median follow‐up of the cohort was 30 (interquartile range [IQR] 18–36) months. For the entire cohort median progression‐free survival (PFS) was 26 (IQR 12.00–42.89) months and overall survival (OS) was 60 (IQR 40.00–67.20) months. The PFS were not significantly different among the three groups (28 months vs. 18 months vs. 26 months, p = 0.182). So were the OS (60 months vs. 59 months vs. not reached, p = 0.067). Multivariate analysis revealed that age >70 year, frailty status (Geriatric vulnerability score), induction efficacy

Abstract Single cell RNA sequencing (scRNA‐seq) provides a great convenience for studying tumor occurrence and development for its ability to study gene expression at the individual cell level. However, patient‐derived tumor tissues are composed of multiple types of cells including tumor cells and adjacent non‐malignant cells such as stromal cells and immune cells. The spatial locations of various cells in situ tissues plays a pivotal role in the occurrence and development of tumors, which cannot be elucidated by scRNA‐seq alone. Spatially resolved transcriptomics (SRT) technology emerges timely to explore the unrecognized relationship between the spatial background of a particular cell and its functions, and is increasingly used in cancer research. This review provides a systematic overview of the SRT technologies that are developed, in particular the more widely used cutting‐edge SRT technologies based on next‐generation sequencing (NGS). In addition, the main achievements by SRT technologies in precisely unveiling the underappreciated spatial locations on gene expression and cell function with unprecedented high‐resolution in cancer research are emphasized, with the aim of developing more effective clinical therapeutics oriented to a deeper understanding of the interaction between tumor cells and surrounding non‐malignant cells.

Abstract Periodontium supports teeth in a mechanically stimulated tissue environment, where heterogenous stem/progenitor populations contribute to periodontal homeostasis. In this study, Leptin receptor+ (Lepr+) cells are identified as a distinct periodontal ligament stem cell (PDLSC) population by single‐cell RNA sequencing and lineage tracing. These Lepr+ PDLSCs are located in the peri‐vascular niche, possessing multilineage potential and contributing to tissue repair in response to injury. Ablation of Lepr+ PDLSCs disrupts periodontal homeostasis. Hyper‐loading and unloading of occlusal forces modulate Lepr+ PDLSCs activation. Piezo1 is demonstrated that mediates the mechanosensing of Lepr+ PDLSCs by conditional Piezo1‐deficient mice. Meanwhile, Yoda1, a selective activator of Piezo1, significantly accelerates periodontal tissue growth via the induction of Lepr+ cells. In summary, Lepr marks a unique multipotent PDLSC population in vivo, to contribute toward periodontal homeostasis via Piezo1‐mediated mechanosensing.

Abstract Barrier membranes incorporated with anti‐adhesion drugs have been widely used for preventing postoperative adhesion. However, the bidirectional release of drugs may interfere with internal tissue healing. Herein, a unidirectional Janus membrane composed of two functional layers is prepared by sequential electrospinning. The outer layer is designed as random polycaprolactone fibers incorporated with tannic acid/Fe3+ particles to prevent tissue adhesion, while the inner layer is designed as oriented gelatin fibers to promote tissue repair. Hydrogen bonding was employed to act as a barrier for preventing the diffusion of the tannic acid to the inner side, and thus the release of tannic acid occurs in a unidirectional manner. As a result, asymmetric biological performances of the Janus membrane are achieved. The outer face can provide anti‐inflammatory capability to the membrane and inhibit the viability of fibroblasts, while the inner face can promote the proliferation and differentiation of tendon stem cells. Tendon injured model confirms the prominent inflammation modulation, adhesion prevention, and repair promotion capabilities of the Janus membrane in vivo. This study provides a new strategy to develop advanced functional barrier membranes for postoperative adhesion prevention and internal tissue repair promotion.

Abstract Human epidermal growth factor receptor 2 (HER2) possesses tyrosine kinase activity and participates in cell growth, differentiation and migration, and survival. Its alterations, mainly including mutations, amplifications, and overexpression are associated with poor prognosis and are one of the major drivers in non–small cell lung cancer (NSCLC). Several clinical trials had been investigating on the treatments of HER2‐altered NSCLC, including conventional chemotherapy, programmed death 1 (PD‐1) inhibitors, tyrosine kinase inhibitors (TKIs) and antibody‐drug conjugates (ADCs), however, the results were either disappointing or encouraging, but inconsistent. Trastuzumab deruxtecan (T‐DXd) was recently approved by the Food and Drug Administration as the first targeted agent for treating HER2‐mutant NSCLC. Effective screening of patients is the key to the clinical application of HER2‐targeted agents such as TKIs and ADCs. Various testing methods are nowadays available, including polymerase chain reaction (PCR), next‐generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), etc. Each method has its pros and cons and should be reasonably assigned to appropriate patients for diagnosis and guiding treatment decisions. To help standardize the clinical workflow, our expert group reached a consensus on the clinical management of HER2‐altered NSCLC, focusing on the diagnosis and treatment strategies.

Abstract Capacitors and sensors based on polymer dielectric materials are key components in electrical systems and electronic devices. Considering the temperature rise during operation, an effective evaluation method for the thermal ageing of polymer matrix is urgently needed. P(VDF‐HFP) film with a thickness of 20 μm is manufactured by solution casting and a thermal ageing experiment up to 1000 h is conducted. Dielectric responses of wide ranges of temperatures and frequencies are measured for samples with different ageing durations. The universal relaxation law and Dissado–Hill dielectric response model are applied to further investigate the results. The characteristics of individual processes are obtained, which demonstrate that the main chain relaxation following the Vogel−Fulcher−Tammann equation and side chain relaxation following the Arrhenius equation both remain unchanged after thermal ageing. However, the activation energies of those two processes change significantly during the process and show different variation trends. The activation energy of the side chain relaxation gets larger monotonically due to the influence of annealing and the breaking of crystalline region. As a result, a non‐destructive evaluation method for the thermal ageing of P(VDF‐HFP) is proposed accordingly.

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 This study aimed to compare the clinical effects of using pedicled double‐barrel fibular transplantation (PDBFT) and bone transport (BT) for the treatment of upper tibial osteomyelitis with bone defects. Methods A total of 83 patients with upper tibial osteomyelitis and bone defects were selected and retrospectively studied in Xi'an Hong Hui Hospital from January 2009 to January 2019. There were 52 males and 31 females, aged 19–72 years. The tibial defect range was 5–12 cm. Patients were divided into two groups, including the PDBFT (40 cases) and the BT group (43 cases). All patients were classified according to Cierny–Mader classification, including 48 cases of type III and 35 cases of type IV. Operation time, blood loss and cure time were compared. Ennecking score was used to evaluate limb functions, including pain, activity function, self‐perception, brace use, walking ability, and gait change, while self‐rating anxiety scale (SAS) was used for postoperative mental and psychological status. In addition, complications were recorded. All patients were followed for at least 2 years. SPSS 23.0 software was used to process data. Results There was no significant difference in demographic data between the two groups (p > 0.05). Operation time was 182.5 ± 22.7 min in PDBFT group vs, 124.2 ± 15.6 min in BT group, respectively (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 Aims/Introduction This study was carried out to assess the association of dehydroepiandrosterone (DHEA) with diabetic nephropathy (DN) in patients with type 2 diabetes mellitus to better predict the progression of diabetic nephropathy. Materials and Methods A total of 1,082 patients with type 2 diabetes mellitus in the Department of Endocrinology and Metabolism of Tianjin Medical University General Hospital were enrolled in this study, and grouped for comparison. The effect of serum DHEA on DN was evaluated by multivariate logistic regression analysis, and receiver operating characteristic curves were established to explore the optimal concentration of DHEA in patients with DN and non‐DN. Results DHEA was significantly decreased in patients with DN (P

Abstract Background The human immunodeficiency virus (HIV) continues to be one of the major public health challenges in the world. Despite the advancement in medication and changes in views towards HIV in Chinese society, little is known about the changes in the psychosocial and mental health of HIV‐positive women in recent years. Objectives The present study examined the change in depression, anxiety, stigma, relationship with the child, intimacy with a partner, and social support from family, friends, and health professionals, for HIV‐positive women in China from 2015 to 2020. Methods Two cross‐sectional surveys were conducted in 2015 and 2020, and 429 and 382 HIV‐positive women were recruited from the Women's Health Department in Yunnan and Guangxi, China between November 2015 to May 2016, and November 2019 to January 2020, respectively. Results After controlling for significant sociodemographic variables, participants recruited in 2019–2020 had significantly lower levels of depression and anxiety and higher scores on emotional and tangible support from friends. On the other hand, they had lower scores in intimacy with partners and emotional and tangible support from family. No significant changes were found in stigma, relationship with the child, and support from health professionals. Conclusion Results provide important information on the changes in psychosocial and mental health, which offer insights into the design of interventions to promote psychosocial and mental health among HIV‐positive women in China. Patient or Public Contribution HIV‐positive women contributed to the data of this study. Health care professionals were involved in the discussion of the methods and results.

Lung cancer is one of the most threatening malignant tumors to human health. Epidermal growth factor receptor (EGFR)‐targeted therapy is a common and essential means for the clinical treatment of lung cancer. However, drug resistance has always affected the therapeutic effect and survival rate in non‐small cell lung cancer (NSCLC). Tumor heterogeneity is a significant reason, yielding various drug resistance mechanisms, such as EGFR‐dependent or ‐independent extracellular signal‐regulated kinase 1 and/or 2 (ERK1/2) activation in NSCLC. To examine whether this aberrant activation of ERK1/2 is related to the loss of function of its specific phosphatase, a series of in vitro and in vivo assays were performed. We found that F‐box/SPRY domain‐containing protein 1 (Fbxo45) induces ubiquitination of NP‐STEP46, an active form of striatal‐enriched protein tyrosine phosphatase, with a K6‐linked poly‐ubiquitin chain. This ubiquitination led to proteasome degradation in the nucleus, which then sustains the aberrant level of phosphorylated‐ERK (pERK) and promotes tumor growth of NSCLC. Fbxo45 silencing can significantly inhibit cell proliferation and tumor growth. Moreover, NSCLC cells with silenced Fbxo45 showed great sensitivity to the EGFR tyrosine kinase inhibitor (TKI) afatinib. Here, we first report this critical pERK maintenance mechanism, which might be independent of the upstream kinase activity in NSCLC. We propose that inhibiting Fbxo45 may combat the issue of drug resistance in NSCLC patients, especially combining with EGFR‐TKI therapy.