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Abstract Background The initial randomized, double‐blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first‐line therapy in epidermal growth factor receptor (EGFR)‐mutated advanced non‐small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. Methods Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double‐blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow‐up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological‐BICR). The primary endpoint for this subgroup analysis was CNS progression‐free survival (PFS). Results Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological‐BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17‐0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11‐0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non‐CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. Conclusions These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR‐mutated advanced NSCLC with baseline CNS metastases. Trial registration ClinicalTrials.gov number, NCT03849768

Abstract Explicit signal coordination carries prior knowledge of traffic engineering and is widely accepted for global implementation. With the recent popularity of reinforcement learning, numerous researchers have turned to implicit signal coordination. However, these methods inevitably require learning coordination from scratch. To maximize the use of prior knowledge, this study proposes an explicit coordinated signal control (ECSC) method using a soft actor–critic for cycle length determination. This method can fundamentally solve the challenges encountered by traditional methods in determining the cycle length. Soft actor–critic was selected among various reinforcement learning methods. A single agent was administered to the arterials. An action is defined as the selection of a cycle length from among the candidates. The state is represented as a feature vector, including the cycle length and features of each leg at every intersection. The reward is defined as departures that indirectly minimize system vehicle delays. Simulation results indicate that ECSC significantly outperforms the baseline methods, as evident in system vehicle delay across nearly all demand scenarios and throughput in high demand scenarios. The ECSC revitalizes explicit signal coordination and introduces new perspectives on the application of reinforcement learning methods in signal coordination.

Abstract Aims Cardiac dysfunction is commonly observed in patients with subarachnoid haemorrhage (SAH). However, the specific timeline of cardiac remodelling and the underlying mechanisms responsible for this effect following SAH remain unknown. This study aims to explore the impact of SAH on cardiac dysfunction and its potential mechanisms over time. Methods and results In Protocol 1, we investigated cardiac function and potential mechanisms in a Sprague‐Dawley rat model of SAH at six time points (baseline and Days 1, 3, 7, 14, and 28) while exploring the underlying mechanisms. Our assessments included the haemodynamic profile, echocardiography, and the concentrations of plasma biomarkers at various time points post‐SAH. We determined neuropeptide Y (NPY) 1–5 receptor protein expression levels through western blotting. In Protocol 2, we administered an NPY1 receptor antagonist to evaluate the effects of cardiac dysfunction induced by SAH on Day 3. In Protocol 1, SAH gradually provoked cardiac systolic dysfunction during the acute phase, reaching its peak on Day 3 without concurrent alterations in wall thickness. However, no significant changes were observed from Days 14 to 28 compared with Day 0. The changes in cardiac dysfunction were consistent with myocardial injury, inflammatory biomarkers, and NPY levels. SAH resulted in a heightened heart rate and systolic blood pressure, correlating with elevated epinephrine and norepinephrine levels. In Protocol 2, the administration of the NPY1 receptor antagonist effectively ameliorated cardiac dysfunction. Conclusions SAH induces transient cardiac dysfunction in the acute phase, and the underlying mechanisms for this response involve the NPY–NPY1 receptor pathway, otherwise known as catecholamines.

Abstract There is an urgent need to fully understand the biology of third generation EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs), particularly osimertinib, and to develop mechanism‐driven strategies to manage their acquired resistance. Transient receptor potential melastatin‐2 (TRPM2) functions as an important regulator of Ca2+ influx, but its role in mediating therapeutic efficacies of EGFR‐TKIs and acquired resistance to EGFR‐TKIs has been rarely studied. This study has demonstrated a previously undiscovered role of suppression of TRPM2 and subsequent inhibition of Ca2+ influx and induction of ROS and DNA damage in mediating apoptosis induction and the therapeutic efficacy of osimertinib against EGFR mutant NSCLC. The rebound elevation represents a key mechanism accounting for the emergence of acquired resistance to osimertinib and other third generation EGFR‐TKIs. Accordingly, targeting TRPM2 is a potentially promising strategy for overcoming and preventing acquired resistance to osimertinib, warranting further study in this direction including the development of cancer therapy‐optimized TRPM2 inhibitors.

Abstract Neural ordinary differential equations (ODEs) (Neural ODEs) construct the continuous dynamics of hidden units using ODEs specified by a neural network, demonstrating promising results on many tasks. However, Neural ODEs still do not perform well on image recognition tasks. The possible reason is that the one‐hot encoding vector commonly used in Neural ODEs can not provide enough supervised information. A new training based on knowledge distillation is proposed to construct more powerful and robust Neural ODEs fitting image recognition tasks. Specially, the training of Neural ODEs is modelled into a teacher‐student learning process, in which ResNets are proposed as the teacher model to provide richer supervised information. The experimental results show that the new training manner can improve the classification accuracy of Neural ODEs by 5.17%, 24.75%, 7.20%, and 8.99%, on Street View House Numbers, CIFAR10, CIFAR100, and Food‐101, respectively. In addition, the effect of knowledge distillation is also evaluated in Neural ODEs on robustness against adversarial examples. The authors discover that incorporating knowledge distillation, coupled with the increase of the time horizon, can significantly enhance the robustness of Neural ODEs. The performance improvement is analysed from the perspective of the underlying dynamical system.

Abstract Extracellular vesicles (EVs) are emerging as promising carriers for the delivery of therapeutic biologics. Genetic engineering represents a robust strategy for loading proteins of interest into EVs. Identification of EV‐enriched proteins facilitates protein cargo loading efficiency. Many EV‐enriched proteins are sorted into EVs via an endosomal sorting complex required for transport (ESCRT)‐dependent pathway. In parallel, viruses hijack this EV biosynthesis machinery via conserved late domain motifs to promote egress from host cells. Inspired by the similarity of biogenesis between EVs and viruses, we developed a synthetic, Late domain‐based EV scaffold protein that enables the display of a set of single chain variable fragments (scFvs) on the EV surface. We named this scaffold the Late domain‐based exosomal antibody surface display platform (LEAP). We applied the LEAP scaffold to reprogramme HEK293T cell‐derived EVs to elicit T‐cell anti‐tumor immunity by simultaneously displaying αPD‐L1 and αCD3 scFvs on the EV surface (denoted as αPD‐L1×αCD3 bispecific T‐cell engaging exosomes, BiTExos). We demonstrated that αPD‐L1×αCD3 BiTExos actively redirected T cells to bind to PD‐L1+ tumor cells, promoting T‐cell activation, proliferation and tumoricidal cytokine production. Furthermore, the αPD‐L1×αCD3 BiTExos promoted T‐cell infiltration into the tumor microenvironment to mitigate the tumor burden in vivo. Our study suggested that the LEAP scaffold may serve as a platform for EV surface display and could be applied for a broad range of EV‐based biomedical applications.

Abstract The inflammatory response is a key factor affecting tissue regeneration. Inspired by the immunomodulatory role of spermidine, an injectable double network hydrogel functionalized with spermidine (DN‐SPD) is developed, where the first and second networks are formed by dynamic imine bonds and non‐dynamic photo‐crosslinked bonds respectively. The single network hydrogel before photo‐crosslinking exhibits excellent injectability and thus can be printed and photo‐crosslinked in situ to form double network hydrogels. DN‐SPD hydrogel has demonstrated desirable mechanical properties and tissue adhesion. More importantly, an “operando” comparison of hydrogels loaded with spermidine or diethylenetriamine (DETA), a sham molecule resembling spermidine, has shown similar physical properties, but quite different biological functions. Specifically, the outcomes of 3 sets of in vivo animal experiments demonstrate that DN‐SPD hydrogel can not only reduce inflammation caused by implanted exogenous biomaterials and reactive oxygen species but also promote the polarization of macrophages toward regenerative M2 phenotype, in comparison with DN‐DETA hydrogel. Moreover, the immunoregulation by spermidine can also translate into faster and more natural healing of both acute wounds and diabetic wounds. Hence, the local administration of spermidine affords a simple but elegant approach to attenuate foreign body reactions induced by exogenous biomaterials to treat chronic refractory wounds.

Abstract Cardiac contractility modulation (CCM) offers a novel therapeutic avenue for heart failure patients, particularly those unresponsive to cardiac resynchronization therapy within specific QRS duration ranges. This review elucidates CCM's mechanistic underpinnings, its impact on myocardial function, and utility across patient demographics. However, CCM is limited by insufficient data on mortality and hospitalization rate reductions, as well as the need for specialized device implantation skills. While prevailing research has concentrated on left ventricular effects, a knowledge gap persists for other patient subsets. Future inquiries should address combinatory treatment strategies, extended usage and the impact of atrial fibrillation on device implantation. Such expanded studies could refine therapeutic outcomes and widen the scope of beneficiaries.

Abstract With the continuously increasing penetration of electric vehicles (EVs), the mutual match between the distribution of charging resources and the spatial–temporal distribution of EV charging demands is becoming increasingly important. To address this, this paper proposes a novel two‐stage customized EV charging–navigation strategy. Building on previous research on the real‐time information from dynamic traffic networks, a personalized dynamic road impedance (PDRI) model is built to transform three main criteria (distance, time, and finance) affecting charging–navigation into comprehensive road impedance. In the first navigation stage, fast‐charging stations (FCSs) with the lowest overall objective are selected. In the second navigation stage, an improved Floyd–Warshall algorithm is utilized to identify the routes with the lowest personalized weight to the selected FCS in the PDRI model. Notably, the personalized preferences of EV drivers for the three primary criteria are considered in both stages of the navigation process. Finally, simulation results demonstrate a significant improvement in the degree of matching between charging navigation plans and drivers' personalized requirements, and a more balanced spatial–temporal distribution of EV charging demands among FCSs, which verifies the effectiveness of the proposed strategy.

Abstract Background Combination of chidamide and anti‐PD‐L1 inhibitor produce synergistic anti‐tumor effect in advanced NSCLC patients resistant to anti‐PD‐1 treatment. However, the effect of chidamide plus envafolimab has not been reported. Aims This study aimed to evaluate the efficacy of chidamide plus envafolimab in advanced NSCLC patients resistant toanti‐PD‐1 treatment. Materials and Methods Eligible advanced NSCLC patients after resistant to anti‐PD‐1 therapy received chidamide and envafolimab. The primary endpoint was objective response rate (ORR). The secondary end points included disease control rate (DCR), progression‐free survival (PFS), and safety. The expression of histone deacetylase 2 (HDAC2), PD‐L1, and blood TMB (bTMB) was also analyzed. Results After a median follow‐up of 8.1 (range: 7.6–9.2) months, only two patients achieved partial response. The ORR was 6.7% (2/30), DCR was 50% (15/30), and median PFS (mPFS) was 3.5 (95% confidence interval: 1.9–5.5) months. Biomarker analysis revealed that patients with high‐level HDAC2 expression had numerically superior ORR (4.3% vs. 0), DCR (52.2% vs. 0) and mPFS (3.7 vs. 1.4m). Patients with negative PD‐L1 had numerically superior DCR (52.2% vs. 33.3%) and mPFS (3.7m vs. 1.8m), so were those with low‐level bTMB (DCR: 59.1% vs. 16.7%, mPFS: 3.8 vs.1.9m). Overall safety was controllable. Discussion High HDAC2patients showed better ORR, DCR, and PFS. In addition, patient with negative PD‐L1 and low‐level bTMB had better DCR and PFS. This may be related to the epigenetic function of chidamide. However, the sample size was not big enough, so it is necessary to increase sample size to confirm the conclusion. Conclusion Combination of chidamide and envafolimab showed efficacy signals in certain NSCLC patients. But further identification of beneficial population is necessary for precision treatment.

Abstract Fluorescent poly(N‐isopropylacrylamide‐co‐Nile blue) (pNIPAm‐co‐NB) microgels were synthesized that exhibited fluorescence intensity changes in a water temperature‐dependent fashion. NB is well known to exhibit fluorescence intensity that depends on the hydrophobicity of the environment, while pNIPAm‐based microgels are well known to transition from swollen (hydrophilic) to collapsed (relatively hydrophobic) at temperatures greater than 32 °C; hence, we attribute the above behavior to the hydrophobicity changes of the microgels with increasing temperature. This phenomenon is ultimately due to NB dimers (relatively quenched fluorescence) being broken in the hydrophobic environment of the microgels leading to relatively enhanced fluorescence. We went on to show that the introduction of cucurbit[7]uril (CB[7]) into the pNIPAm‐co‐NB microgels enhanced their fluorescence allowing them to be used for polyamine (e.g., spermine [SPM]) detection. Specifically, CB[7] forms a host–guest interaction with NB in the microgels, which prevents NB dimerization and enhances their fluorescence. When SPM is present, it forms a host–guest complex that is favored over the CB[7]‐NB host–guest interaction, which frees the NB for dimerization and leads to fluorescence quenching. As a result, we could generate an SPM sensor capable of SPM detection down to ~0.5 µmol/L in complicated matrixes such as serum and urine.

Abstract Background Retinoblastoma (Rb) is the most common intraocular malignancy in childhood, originating from primitive retinal stem cells or cone precursor cells. It can be triggered by mutations of the RB1 gene or amplification of the MYCN gene. Rb may rarely present with polydactyly. Methods We conducted karyotype analysis, copy number variation sequencing, and whole‐genome sequencing on the infant proband and his family. The clinical course and laboratory results of the proband's infant were documented and collected. We also reviewed the relevant literature. Results A 68‐day‐old boy presented with preaxial polydactyly and corneal edema. His intraocular pressure (IOP) was 40/19 mmHg, and color Doppler imaging revealed vitreous solid mass‐occupying lesions with calcification in the right eye. Ocular CT showed flaky high‐density and calcification in the right eye. This was classified as an International Retinoblastoma Staging System group E retinoblastoma with an indication for enucleation. Enucleation and orbital implantation were performed on the child's right eye. Karyotype analysis revealed an abnormal 46, XY, 15pstk+ karyotype, and the mother exhibited diploidy of the short arm of chromosome 15. The Alx‐4 development factor, 13q deletion syndrome, and the PAPA2 gene have been reported as potential mechanisms for Rb combined with polydactyly. Conclusion We report the case of a baby boy with Rb and polydactyly exhibiting a 46, XY, 15pstk+ Karyotype. We discuss potential genetic factors related to both Rb and polydactyly. Furthermore, there is a need for further exploration into the impact of chromosomal polymorphisms in Rb with polydactyly.

Abstract Aims Previous studies have shown a significant reduction in skeletal muscle content in patients with chronic heart failure (CHF). The present study focused on the erector spinae muscle (ESM) to determine whether ESM content is associated with the development and severity of CHF. Methods and results A total of 652 patients were included in this trial for the study. According to the diagnostic criteria of CHF, 652 patients were divided into two groups, namely, the control group (268 patients) and the CHF group (384 patients). Meanwhile, to assess whether the ESM is associated with the severity of CHF, patients in the CHF group were divided into two groups according to left ventricular ejection fraction (LVEF) values: heart failure with preserved ejection fraction (HFpEF, LVEF ≥50%, 256 patients) and heart failure with reduced ejection fraction (HFrEF, LVEF ≤40%, 68 patients). Receiver operating curve analysis was performed to assess whether ESM content could predict CHF and determine its severity. Compared with the control group, the patients in the CHF group were older, the prevalence of coronary heart disease (CHD) and atrial fibrillation was higher, the colour ultrasound results showed that LVEF decreased significantly, and the left ventricular end‐diastolic internal diameter and left ventricular end‐systolic internal diameter increased significantly. Besides, patients in the CHF group had significantly lower ESM content, and ESM is an independent predictor of heart failure, with an odds ratio of 0.713 (CHF group vs. control group, 95% confidence interval 0.626–0.811, P

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 By adopting agile and lean practices, DevOps aims to achieve rapid value delivery by speeding up development and deployment cycles, which however lead to more security concerns that cannot be fully addressed by an isolated security role only in the final stage of development. DevSecOps promotes security as a shared responsibility integrated into the DevOps process that seamlessly intertwines development, operations, and security from the start throughout to the end of cycles. While some companies have already begun to embrace this new strategy, both industry and academia are still seeking a common understanding of the DevSecOps movement. The goal of this study is to report the state‐of‐the‐practice of DevSecOps, including the impact of DevOps on security, practitioners' understanding of DevSecOps, and the practices associated with DevSecOps as well as the challenges of implementing DevSecOps. The authors used a mixed‐methods approach for this research. The authors carried out a grey literature review on DevSecOps, and surveyed the practitioners of DevSecOps in industry of China. The status quo of DevSecOps in industry is summarized. Three major software security risks are identified with DevOps, where the establishment of DevOps pipeline provides opportunities for security‐related activities. The authors classify the interpretations of DevSecOps into three core aspects of DevSecOps capabilities, cultural enablers, and technological enablers. To materialise the interpretations into daily software production activities, the recommended DevSecOps practices from three perspectives—people, process, and technology. Although a preliminary consensus is that DevSecOps is regarded as an extension of DevOps, there is a debate on whether DevSecOps is a superfluous term. While DevSecOps is attracting an increasing attention by industry, it is still in its infancy and more effort needs to be invested to promote it in both research and industry communities.

Abstract Background The prognosis of patients with small cell lung cancer (SCLC) and brain metastases (BM) was poor. This study aimed to explore the efficacy and safety of anlotinib as third‐line or above treatment in SCLC with BM. Methods This was a subgroup analysis of the ALTER1202 trial, which was a randomized, placebo‐controlled trial aimed to evaluate the role of anlotinib as third‐line treatment or above in patients with SCLC. This study included patients with BM at baseline. The efficacy and safety outcomes included progression‐free survival (PFS), overall survival (OS), central nervous system (CNS), objective response rate (ORR), CNS disease control rate (DCR), time to CNS progression, and adverse events (AEs). Results Twenty‐one and nine patients with BM were included in the anlotinib and placebo groups, respectively. The median PFS and OS were 3.8 months (95% confidence interval [CI]: 1.8–6.1) and 6.1 months (95% CI: 4.1–8.0) in the anlotinib group. Anlotinib was associated with a significant improvement in PFS (hazard ratio [HR] = 0.15, 95% CI: 0.04–0.51, p = 0.0005) and OS (HR = 0.26, 95% CI: 0.09–0.73, p = 0.0061) than placebo. Anlotinib significantly prolonged the time to CNS progression (p

Abstract Background Posteroseptal accessory pathways (APs) associated with coronary sinus (CS) diverticulum present a rare and challenge for ablation. This study aimed to compare the safety and efficacy of conventional approach and three‐dimensional (3D) mapping system in the catheter ablation. Methods and Results This was a retrospective study of all patients (from January 2013 to July 2022) who underwent catheter ablation of posteroseptal AP associated with CS diverticula in our center. Patients who underwent catheter ablation using the traditional fluoroscopy method were included in the conventional method group (n = 13). Patients who underwent catheter ablation using the 3D mapping method were included in the 3D mapping group (n = 11). Clinical characteristics, ablation procedure, and outcomes were recorded and analyzed between the two groups. Out of 669 patients with posteroseptal APs, 24 of them (3.6%) were associated with CS diverticula. All patients in both groups successfully completed the electrophysiological study. In the conventional method group, two patients experienced complications (one patient with pericardial effusion and the other patient with femoral arterial hematoma), and two patients had recurrence. However, no patients suffered from complications or recurrence during follow‐up. The procedure time and fluoroscopy time in the conventional method group were significantly longer than those in the 3D mapping method group. Conclusions The utilization of 3D mapping led to reduced fluoroscopy time, shorter procedure duration, enhanced acute success rates, and decreased incidence of complications.

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 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 transformation from non‐small‐cell lung cancer (NSCLC) to small‐cell lung cancer (SCLC) is one of the mechanisms of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) resistance. Previous studies exhibited that the median transformation time was 17.8 months for NSCLC to SCLC. Here we introduced a case of lung adenocarcinoma (LADC) with EGFR19 exon deletion mutation in which the pathological transformation emerged only 1 month after lung cancer surgery and receiving EGFR‐TKI inhibitor. Eventually, the pathological examination confirmed the patient experienced a transformation from LADC to SCLC with EGFR, tumor protein p53 (TP53), RB transcriptional corepressor 1 (RB1), and SRY‐box transcription factor 2 (SOX2) mutation. Although the transformation of LADC with EGFR‐mutant into SCLC after targeted therapy was frequent, the pathological results of most patients were only biopsy specimens, which cannot rule out the existence of mixed pathological components of the primary tumor. In this case, the patient's postoperative pathology was sufficient to exclude the probability of mixed tumor components, confirming that the patient's pathological change was indeed transformation from LADC to SCLC. In addition, primary drug resistance in such a short time after surgery and osimertinib‐targeted therapy has not been reported before. We detected the molecular state of this patient before and after SCLC transformation through targeted gene capture and high‐throughput sequencing, and also found for the first time that the mutations of EGFR, TP53, RB1, and SOX2 continue to exist before and after transformation, but the mutation abundance is different. In our paper, the occurrence of small‐cell transformation is affected largely by these gene mutations.

Abstract Myocardial infarction (MI) remains the leading cause of death worldwide. Cardiac fibroblasts (CFs) are abundant in the heart and are responsible for cardiac repair post‐MI. NF‐κB‐repressing factor (NKRF) plays a significant role in the transcriptional inhibition of various specific genes. However, the NKRF action mechanism in CFs remains unclear in cardiac repair post‐MI. This study investigates the NKRF mechanism in cardiac remodeling and dysfunction post‐MI by establishing a CF‐specific NKRF‐knockout (NKRF‐CKO) mouse model. NKRF expression is downregulated in CFs in response to pathological cardiac remodeling in vivo and TNF‐α in vitro. NKRF‐CKO mice demonstrate worse cardiac function and survival and increased infarct size, heart weight, and MMP2 and MMP9 expression post‐MI compared with littermates. NKRF inhibits CF migration and invasion in vitro by downregulating MMP2 and MMP9 expression. Mechanistically, NKRF inhibits human antigen R (HuR) transcription by binding to the classical negative regulatory element within the HuR promoter via an NF‐κB‐dependent mechanism. This decreases HuR‐targeted Mmp2 and Mmp9 mRNA stability. This study suggests that NKRF is a therapeutic target for pathological cardiac remodeling.

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 Background Although programmed cell death 1 (PD‐1) blockade plus chemotherapy can significantly prolong the progression‐free survival (PFS) and overall survival (OS) in first‐line settings in patients with driver‐negative advanced non‐small‐cell lung cancer (NSCLC), the predictive biomarkers remain undetermined. Here, we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD‐1 blockade plus chemotherapy. Methods Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone. Tumor immune microenvironmental markers, including PD‐1 ligand (PD‐L1), CD8, CD68, CD4 and forkhead box P3, were assessed using multiplex immunofluorescence (mIF) assays. Kaplan‐Meier curves were used to determine treatment outcome differences according to their expression status. Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations. Results Responders had significantly higher CD8/PD‐L1 (P = 0.015) or CD68/PD‐L1 co‐expression levels (P = 0.021) than non‐responders in the camrelizumab plus chemotherapy group, while no difference was observed in the chemotherapy group. Patients with high CD8/PD‐L1 or CD68/PD‐L1 co‐expression level was associated with significantly longer PFS (P = 0.002, P = 0.024; respectively) and OS (P = 0.006, P = 0.026; respectively) than those with low co‐expression in camrelizumab plus chemotherapy group. When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD‐L1 co‐expression stratification, significantly better PFS (P = 0.003) and OS (P = 0.032) were observed in high co‐expression subgroups. The predictive value of CD8/PD‐L1 and CD68/PD‐L1 co‐expression remained statistically significant for PFS and OS when adjusting clinicopathological features. Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD‐L1 or CD68/PD‐L1 co‐expression, the positive groups had a significantly higher proportion of TP53/KRAS co‐mutations than the negative groups (both 13.0% vs. 0.0%, P = 0.023). Notably, enriched PI3K (P = 0.012) and cell cycle pathway (P = 0.021) were found in the CD8/PD‐L1 co‐expression group. Conclusion Tumor immune microenvironmental marker expression, especially CD8/PD‐L1 or CD68/PD‐L1 co‐expression, was associated with the efficacy of PD‐1 blockade plus chemotherapy as first‐line treatment in patients with advanced NSCLC.

Abstract Chemiluminescence (CL) imaging, as an excitation‐free technique, exhibits a markedly improved signal‐to‐noise ratio (SNR) owing to the absence of an excitation light source and autofluorescence interference. However, conventional chemiluminescence imaging generally focuses on the visible and first near‐infrared (NIR‐I) regions, which hinders high‐performance biological imaging due to strong tissue scattering and absorption. To address the issue, self‐luminescent NIR‐II CL nanoprobes with a second near‐infrared (NIR‐II) luminescence in the presence of hydrogen peroxide are rationally designed. A cascade energy transfer, including chemiluminescence resonance energy transfer (CRET) from the chemiluminescent substrate to NIR‐I organic molecules and Förster resonance energy transfer (FRET) from NIR‐I organic molecules to NIR‐II organic molecules, occurs in the nanoprobes, contributing to NIR‐II light with great efficiency and good tissue penetration depth. Based on excellent selectivity, high sensitivity to hydrogen peroxide, and long‐lasting luminescence performance, the NIR‐II CL nanoprobes are applied to detect inflammation in mice, showing a 7.4‐fold enhancement in SNR compared with that of fluorescence.

Abstract Meat is among the most consumed foods worldwide and has a unique flavor and high nutrient density in the human diet. However, the genetic and biochemical bases of meat nutrition and flavor are poorly understood. Here, 3431 metabolites and 702 volatiles in 423 skeletal muscle samples are profiled from a gradient consanguinity segregating population generated by Pekin duck × Liancheng duck crosses using metabolomic approaches. The authors identified 2862 metabolome‐based genome‐wide association studies (mGWAS) signals and 48 candidate genes potentially modulating metabolite and volatile levels, 79.2% of which are regulated by cis‐regulatory elements. The level of plasmalogen is significantly associated with TMEM189 encoding plasmanylethanolamine desaturase 1. The levels of 2‐pyrrolidone and glycerophospholipids are regulated by the gene expression of AOX1 and ACBD5, which further affects the levels of volatiles, 2‐pyrrolidone and decanal, respectively. Genetic variations in GADL1 and CARNMT2 determine the levels of 49 metabolites including L‐carnosine and anserine. This study provides novel insights into the genetic and biochemical basis of skeletal muscle metabolism and constitutes a valuable resource for the precise improvement of meat nutrition and flavor.

Abstract Nucleic acid biosensors, integrated with functional nucleic acids, have drawn extensive attention for diverse biomedical applications. In particular, many nucleic acid probes have been developed for biosensing and imaging of tumor‐associated species, including pH, small molecules, RNAs, metal ions, proteins, and cells. Despite the progress made, these sensors are mainly performed at the level of test tube assays or live cells for disease diagnosis and pathological studies. In recent years, increasing research works are pushing the limit of nucleic acid sensors in preclinical applications and imaging‐guided therapy. However, the applicability of current nucleic acid sensors in vivo is largely hindered by the complexity of living animals. Herein, we review recent advances in the design and applications of nucleic acid biosensors in vivo, in which the key factors for the fabrication of eligible sensors are highlighted. Additionally, given the inherent shortcomings of nucleic acid, we will also describe the challenges of the current in vivo nucleic acid biosensors and some new strategies that may significantly accelerate the development of biosensors.

Abstract Ruthenium has been hailed as a competitive alternative for platinum toward hydrogen evolution reaction (HER), a critical process in electrochemical water splitting. In this study, we successfully prepare metallic Ru nanoparticles supported on carbon paper by utilizing a novel magnetic induction heating (MIH) method. The samples are obtained within seconds, featuring a Cl‐enriched surface that is unattainable via conventional thermal annealing. The best sample within the series shows a remarkable HER activity in both acidic and alkaline media with an overpotential of only ‐23 and ‐12 mV to reach the current density of 10 mA/cm2, highly comparable to that of the Pt/C benchmark. Theoretical studies based on density functional theory show that the excellent electrocatalytic activity is accounted by the surface metal‐Cl species that facilitate charge transfer and downshift the d‐band center. Results from this study highlight the unique advantages of MIH in rapid sample preparation, where residual anion ligands play a critical role in manipulating the electronic properties of the metal surfaces and the eventual electrocatalytic activity.

Abstract Cell membrane encapsulation is a growing concept in nanomedicine, for it achieves the purpose of camouflage nanoparticles, realizing the convenience for drug delivery, bio‐imaging, and detoxification. Cell membranes are constructed by bilayer lipid phospholipid layers, which have unique properties in cellular uptake mechanism, targeting ability, immunomodulation, and regeneration. Current medical applications of cell membranes include cancers, inflammations, regenerations, and so on. In this article, a general bibliometric overview is conducted of cell membrane‐coated nanoparticles covering 11 years of evolution in order to provide researchers in the field with a comprehensive view of the relevant achievements and trends. The authors analyze the data from Web of Science Core Collection database, and extract the annual publications and citations, most productive countries/regions, most influential scholars, the collaborations of journals and institutions. The authors also divided cell membranes into several subgroups to further understand the application of different cell membranes in medical scenarios. This study summarizes the current research overview in cell membrane‐coated nanoparticles and intuitively provides a direction for future research.

Objectives To analyze the causes of misdiagnosis and missed diagnosis in spinal osteoid osteoma, and to put forward solutions to improve diagnosis accuracy and treatment efficacy in patients. Methods We performed a retrospective cohort study on patients with spinal osteoid osteoma in Beijing Jishuitan Hospital from January 1983 to September 2019. All patients underwent surgery. The outcome measures were the extent of local pain, nocturnal pain, radicular symptoms of extremities after surgery, and reduction or disappearance of lesions on CT after surgery. Results Thirty‐seven patients with spinal osteoid osteoma were recruited in the study. A total of 27% were female, and the mean (SD) age at diagnosis was 21.3 (8.7) years. A total of 87.0% of patients presented with nocturnal pain, and 94.7% of patients were responsive to NSAIDS treatment. The mean (SD) time from the initial onset of symptoms to the final diagnosis was 14.7 (12.5) months. Only four of 37 (10.8%) patients were correctly diagnosed with spinal osteoid osteoma on the first visit to the local hospital. CT is associated with a higher diagnosis rate than X‐ray or MRI on the first visit. Surgical navigation was used in 88.9% of patients who underwent curettage resection, and in 10% of patients who underwent en bloc resection. A total of 37 of 37 patients (100%) reported relief of local pain and radicular symptoms of extremities after surgery, and no recurrence of tumors was found during follow‐ups. Conclusions Spinal CTs are recommended to be performed if osteoid osteoma is suspected based on clinical manifestation, including nocturnal pain and responsiveness to NSAIDS treatment, to avoid misdiagnosis and missed diagnosis of spinal osteoid osteoma.

Abstract Liver metastasis is common in advanced small cell lung cancer (SCLC). There is no evidence‐proven treatment beyond the second line in patients with SCLC and liver metastasis. This study aimed to investigate survival in patients with SCLC and liver metastasis treated with anlotinib compared with placebo. This study was a post hoc analysis of the phase II ALTER 1202 trial, including patients who had liver metastasis at baseline. The participants were randomized 2:1 to receive either 12 mg/day anlotinib (anlotinib group) or placebo (placebo group). Tumor response, progression‐free survival (PFS), and overall survival (OS) were compared. In the original trial, there were 39 participants with liver metastasis at baseline, including 27 and 12 in the anlotinib and placebo groups, respectively. The objective response rate was 3.7% and 0% in the anlotinib and placebo groups, respectively (p = 0.9999). An elevated disease control rate was found in the anlotinib group (44.4%) compared with the placebo group (8.3%, p = 0.0173). The median PFS was 1.51 vs. 0.71 months in favor of anlotinib (hazard ratio [HR] = 0.365, 95% confidence interval [CI]: 0.17–0.78; p = 0.0064), with no marked difference in median OS (3.29 vs. 1.91 months; HR = 0.51, 95% CI: 0.22–1.16; p = 0.0996). The most common AEs in the anlotinib group were hypertension (40.7%), fatigue (29.6%), loss of appetite (22.2%), and weight loss (22.2%). There were no grade 5 AE. In conclusion, anlotinib increased PFS compared with placebo in patients with SCLC and liver metastasis.

Abstract Background Circular RNAs (circRNAs) have been reported to play a significant role in tumorigenesis. However, the detailed function of circRNA in prostate cancer (PCa) is still largely unknown. Methods We quantified circTFDP2 expression in PCa tissues and adjacent normal tissues using quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). Colony formation, Cell Counting Kit‐8 (CCK‐8), flow cytometry, transwell, and in vivo progression and metastasis assays were applied to reveal the proliferation and metastatic abilities of circTFDP2 in PCa cells. Mass spectrometry, RNA pulldown, RNA‐immunoprecipitation (RIP), western blotting and immunofluorescence were used for the mechanistic studies. qRT‐PCR and RIP assays were used to explore the regulatory role of eIF4A3 in the biogenesis of circTFDP2. Finally, functional assays showed the effect of circTFDP2‐containing exosomes on PCa cell progression. Results circTFDP2 was upregulated in PCa tissues compared with adjacent normal tissues. Furthermore, high circTFDP2 expression was positively correlated with the Gleason score. Functionally, circTFDP2 promoted PCa cell proliferation and metastasis both in vivo and in vitro. Mechanistically, circTFDP2 interacted with poly(ADP‐ribose) polymerase 1 (PARP1) protein in its DNA‐binding domain to prevent it from active caspase‐3‐dependent cleavage, and finally relieved PCa cells from DNA damage. In addition, RNA‐binding protein eIF4A3 can interact with the flanking region of circTFDP2 and promote the biogenesis of circTFDP2. Moreover, exosome‐derived circTFDP2 promoted PCa cell progression. Conclusions In general, our study demonstrated that circTFDP2 promoted PCa cell progression through the PARP1/DNA damage axis, which may be a promising therapeutic target for PCa.

Abstract The power conversion efficiencies (PCEs) of organic solar cells (OSCs) have improved considerably in recent years with the development of fused‐ring electron acceptors (FREAs). Currently, FREAs‐based OSCs have achieved high PCEs of over 19% in single‐junction OSCs. Whereas the relatively high synthetic complexity and the low yield of FREAs typically result in high production costs, hindering the commercial application of OSCs. In contrast, noncovalently fused‐ring electron acceptors (NFREAs) can compensate for the shortcomings of FREAs and facilitate large‐scale industrial production by virtue of the simple structure, facile synthesis, high yield, low cost, and reasonable efficiency. At present, OSCs based on NFREAs have exceeded the PCEs of 15% and are expected to reach comparable efficiency as FREAs‐based OSCs. Here, recent advances in NFREAs in this review provide insight into improving the performance of OSCs. In particular, this paper focuses on the effect of the chemical structures of NFREAs on the molecule conformation, aggregation, and packing mode. Various molecular design strategies, such as core, side‐chain, and terminal group engineering, are presented. In addition, some novel polymer acceptors based on NFREAs for all‐polymer OSCs are also introduced. In the end, the paper provides an outlook on developing efficient, stable, and low‐cost NFREAs for achieving commercial applications.

Abstract Liver metastasis is associated with immunotherapy resistance, although the underlying mechanisms remain incompletely understood. By applying single cell RNA‐sequencing to a concurrent subcutaneous and liver tumor murine model to recapitulate liver metastases, it is identified that subsets within tumor‐infiltrating exhausted CD8+ T (Tex) cells and immunosuppressive tumor‐associated macrophages (TAMs) display opposite responses to concurrent liver tumors and anti‐PD‐1 treatment, suggesting a complex immune regulating network. Both angiogenic and interferon‐reactive TAMs show increased frequencies in implanted liver tumors, and anti‐PD‐1 treatment further elevates the frequencies of angiogenic TAMs. Such TAMs frequencies negatively correlate with the proportions of cytotoxic T cell subsets. Further, expression of interferon‐stimulated genes in TAMs is dramatically reduced under effective anti‐PD‐1 treatment, while such tendencies are diminished in mice with implanted liver tumors. Therefore, the study indicates that liver metastases could increase immunosuppressive TAMs frequencies and inhibit Tex responses to PD‐1 blockade, resulting in compromised systemic antitumor immunity and limited immunotherapy efficacy.

Abstract Background The presence of pleural effusion is an independent predictor for poor survival in patients with small‐cell lung cancer (SCLC). The aim of this study was to assess the efficacy and safety of anlotinib in patients with SCLC and pleural effusion. Methods This was a randomized, double‐blind, multicenter, phase II trial. Patients histologically diagnosed with SCLC and pleural effusion and had received at least two lines of chemotherapy were enrolled into the study. The patients received anlotinib 12 mg/day or a placebo. Results The overall response rate (ORR) was 3.7% for anlotinib (n = 27) and 0% in the placebo group (n = 15) (p = 1.000). The disease control rate (DCR) of the anlotinib group (63.0%) was higher than that of the placebo group (0%, p

Rhus chinensis Mill. (RCM) is the host plant of Galla chinensis, which is valued in traditional medicine. Environmental temperature directly determines the probability of gallnut formation and RCM growth. At present, there is no experiment to systematically analyse the stability of internal reference gene (RG) expression in RCM. In this experiment, leaves that did not form gallnuts were used as the control group, while leaves that formed gallnuts were used as the experimental group. First, we conducted transcriptome experiments on RCM leaves to obtain 45 103 differential genes and functional enrichment annotations between the two groups. On this basis, this experiment established a transcriptional gene change model of leaves in the process of gallnut formation after being bitten by aphids, and RCM reference candidate genes were screened from RNA sequencing (RNA‐seq) data. This study is based on RCM transcriptome data and evaluates the stability of 11 potential reference genes under cold stress (4 °C) and heat stress (34 °C), using three statistical algorithms (geNorm, NormFinder, and BestKeeper). The results show that GAPDH1 + PP2A2/UBQ are stable reference genes under heat stress, while GAPDH1 + ACT are the most stable under cold stress. This study is the first to screen candidate reference genes in RCM and could help guide future molecular studies in this genus.

Abstract Background There is a lack of targeted therapeutic options for squamous cell lung cancer (SCC). Accelerated hypertension is an issue with many targeted therapies for lung cancer. This study aimed to analyze the efficacy of anlotinib, based on progression‐free survival (PFS) and overall survival (OS) in patients with SCC, stratified by hypertension and Eastern Cooperative Oncology Group (ECOG) score. Methods This was a post hoc analysis of a multicenter, double‐blind, phase III ALTER0303 randomized controlled trial. Only patients with SCC were included. The occurrence of hypertension during the study period was defined according to CTCAE 4.03. OS and PFS were the primary and secondary endpoints, respectively. The patients were stratified according to hypertension and ECOG score, respectively. Results The median PFS in the patients who developed hypertension was longer than in those who did not (7.2 (95% CI: 3.5–11.0) versus 3.2 (95% CI: 1.2–5.3) months, p = 0.001; HR (95% CI), 0.4 (0.2–0.8)). In the ECOG 0 patients, the median PFS in the patients who developed hypertension versus those who did not was 5.6 vs. 1.8 months, respectively (Figure 2(d)). In the ECOG 1 patients, the median PFS in the patients who developed hypertension versus those who did not was 7.0 (95% CI: 3.0–11.0) vs. 4.8 (95% CI: 1.2–8.5) months (p = 0.043). No statistically significant differences were found in OS in the stratified analyses. Conclusions The occurrence of hypertension might be a clinical indicator predicting the efficacy of third‐line anlotinib treatment in patients with SCC.

Abstract A 37‐year‐old man was admitted to our hospital with paroxysmal palpitation for half year. A previous electrogram showed a narrow complex tachycardia. Electrophysiologic study (EPS) found a concealed left‐sided free wall pathway accessory. In addition, a transseptal approach was used for radiofrequency ablation. After successful ablation, EPS induced a wide complex tachycardia and a narrow complex tachycardia. The wide complex tachycardia was diagnosed as a right‐sided Mahaim fiber atriofascicular accessory pathway, and the narrow complex tachycardia was diagnosed as atypical atrioventricular nodal reentrant tachycardia (AVNRT). Then, the right‐sided Mahaim fiber atriofascicular accessory pathway and atypical AVNRT were successfully ablated. Herein, we report a rare case of a concealed left‐sided accessory pathway combined with a right atriofascicular Mahaim fiber and atypical AVNRT.

Abstract Background It is difficult to insert cardiac pacing leads in patient with tricuspid valve surgery (TVS). The aim of this study was to evaluate safety and effectiveness of a novel technique applied for bedside temporary pacemaker placement (TPP) in patients with TVS. Methods We investigated patients with TVS who required bedside TPP without X‐ray guidance in cardiac intensive care unit between January 2019 and March 2022. They were divided into Novel pre‐shaped group (N = 21) and Control group (routine pre‐shaped group, N = 26). The ordinary bipolar electrodes were applied in both groups. In Novel pre‐shaped group, electrodes were reshaped by a novel technique with three‐curve with anterior tip method, while electrodes were shaped by traditional strategy in Control group. We evaluated the operation duration, first‐attempt success rate of the lead placement, pacing threshold, success rate of lead placement, the rate of leads displacement, and complications. Results Compared with that in Control group, the procedure time was significantly shortened and the first‐attempt success rate of lead placement was obviously increased in Novel pre‐shaped group (both p