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Abstract Purpose Higher medical education has always been a major project in the fields of education and health, and therefore, the quality of education has received much attention. Learning engagement has emerged as a significant indicator of teaching quality, attracting considerable research attention. This study aims to explore the relationship between medical students’ learning engagement and their sense of school belonging, professional identity, and academic self-efficacy. Methods We conducted an online survey using convenience sampling method with 311 medical students. We employed Revised version of the Utrech Work Engagement Scale-Student (UWES-S), Chinese version of the Psychological Sense of School Membership (PSSM) scale, Academic Self-Efficacy Scale, and the questionnaire of college students’ speciality identity for evaluation. Network analysis was used to analyze the relationships among these factors. Results Medical students’ overall performance in school showed a positive trend. However, there is still room for improvement. In the network structure of learning engagement and its influencing factors, the “emotional” aspect of professional identity (EI = 1.11) was considered to be an important node with strong centrality. And “academic competence self-efficacy” aspect of academic self-efficacy (BEI = 0.72) was considered an important node with strong transitivity. Conclusion Deepening medical students’ emotional identification with their profession and enhancing their confidence in their academic abilities may improve their learning engagement and educational quality.

Abstract This single-arm, multicenter, phase 2 trial (NCT04106180) investigated the triple combination of sintilimab (anti-PD1 antibody), stereotactic body radiotherapy (SBRT) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in metastatic non-small cell lung cancer (NSCLC). With a median follow-up of 32.1 months, 18 (36.7%, 90% CI 25.3%–49.5%) of the 49 evaluable patients had an objective response, meeting the primary endpoint. Secondary endpoints included out-of-field (abscopal) response rate (ASR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). The ASR was 30.6% (95% CI 18.3%–45.4%). The median PFS and OS were 5.9 (95% CI 2.5–9.3) and 18.4 (95% CI 9.7–27.1) months, respectively. Any grade and grade 3 TRAEs occurred in 44 (86.3%) and 6 (11.8%) patients, without grade 4–5 TRAEs. Moreover, in pre-specified biomarker analyses, SBRT-induced increase of follicular helper T cells (Tfh) in unirradiated tumor lesions and patient’s blood, as well as of circulating IL-21 levels, was found associated with improved prognosis. Taken together, the triple combination therapy was well tolerated with promising efficacy and Tfh may play a critical role in SBRT-triggered anti-tumor immunity in metastatic NSCLC.

Abstract Background Preventive treatment of tuberculosis infection (TBI) is considered a crucial strategy to prevent and control tuberculosis (TB). However, the acceptance and completion rates of preventive therapy for TBI are still far from optimistic. Evidence is mounting that TB knowledge and stigma may have a substantial effect on acceptance of TBI treatment. This study aimed to explore the effect of stigma on the relationship between the level of TB knowledge and acceptance of TBI treatment. Methods 7017 general population were included in the study. We adjusted for the covariates at the individual. Stepwise logistic regression was used to examine the moderating role of TB stigma and also explore the association between TB knowledge and acceptance of TBI treatment. Results The acceptance rate of TBI treatment among the respondents was 84.38% (n = 5921). Among respondents, a significant positive correlation between acceptance of TBI treatment and TB knowledge (OR = 1.096,95%CI = 1.073,1.118). Additionally, the association between TB knowledge and acceptance of TBI treatment was found to be moderated by TB stigma. In other words, TB stigma was found to weaken the impact of TB knowledge on acceptance of TBI treatment (OR = 0.994,95%CI = 0.991,0.996). Conclusion The findings of the study indicated that having a high level of awareness about TB can enhance the general population’s acceptability of TBI treatment. TB stigma moderated this association; it weakened the relationship between TB knowledge and individuals’ willingness to accept TBI treatment. To mitigate TB stigma and enhance the intention of individuals with TBI to accept preventive therapy, it is imperative to enhance TB-related health education.

Abstract Suitable and effective matching area selection is crucial for gravity matching‐aided navigation. In this paper, an all‐field extended extremum algorithm based on an adaptive threshold (AT‐AEE) is proposed for matching area selection in the Arctic Sea. The gradient data is obtained by using the convolution of gravity reference graph data and all‐field extended extremum parameters. Then, the adaptive threshold method was employed to determine the optimal gradient threshold based on gravity anomaly data across various test areas. Data points with gradients exceeding the specified threshold are identified as local candidate points for matching areas. The test areas containing a certain proportion of local candidate points are designated as the suitable matching areas. Nine test areas in the Arctic Sea with different gravity change characteristics were chosen for simulation experiments to verify the performance of the proposed algorithm. Simulation experiments showed that superior navigation positioning results could be obtained in the matching areas selected by the AT‐AEE algorithm. Compared to traditional algorithm, the matching areas derived from the AT‐AEE algorithm performed with a better consistency in the gravity matching navigation results. In suitable matching areas with the proportion of local candidate points reaching 70%, the average positioning errors could be reduced to less than 1.5 n miles.

This study investigated the characteristics of dissolved organic matter (DOM) in two distinct water bodies, through the utilization of three-dimensional fluorescence spectroscopy coupled with self-organizing map (SOM) methodology. Specifically, this analysis concentrated on neurons 3, 14, and 17 within the SOM model, identifying notable differences in the DOM compositions of a coal subsidence water body (TX) and the MaChang Reservoir (MC). The humic substance content of DOM TX exceeded that of MC. The origin of DOM in TX was primarily linked to agricultural inputs and rainfall runoff, whereas the DOM in MC was associated with human activities, displaying distinctive autochthonous features and heightened biological activity. Principal component analysis revealed that humic substances dominated the DOM in TX, while the natural DOM in MC was primarily autochthonous. Furthermore, a multiple linear regression model (MLR) determined that external pollution was responsible for 99.11% of variation in the humification index (HIX) of water bodies. HIGHLIGHTS Study of the variation in DOM spectral characteristics of different waterbodies.; Neural networks were applied to spectral resolution.; Source analysis was performed to identify the origin of water pollution.;

Abstract Background The increasing use of intracardiac echocardiography (ICE) in the ablation of premature ventricular complexes (PVCs) has raised questions about its true efficacy and safety. Methods This retrospective study collected the periprocedural complications and PVC burden post ablation. The risk factors of PVC recurrence was further explored. Results The study included patients treated without ICE (control group, n = 451) and with ICE (ICE group, n = 155) from May 2019 to July 2022. The ICE group demonstrated significantly lower fluoroscopy times and X-ray doses. There were no major complications in the ICE group, and the difference in the occurrence of periprocedural complications between the groups was not statistically significant (p = 0.072). The long-term success rates were similar for the control and ICE groups (89.6% and 87.1%, respectively). The origin of PVCs was identified as the independent factor for ablation success. Conclusions The use of ICE did not confer an advantage with regard to long-term success in PVCs ablation. To thoroughly evaluate the safety and effectiveness of ICE in PVCs ablation, a prospective, multicenter, randomized study is warranted.

Immunotherapy has changed the treatment landscape of advanced non-small cell lung cancer (NSCLC), showing great potential in the treatment of untreated and relapsed or refractory (R/R) patients. However, numerous issues that need further exploration remain with the wide application of immunotherapy. They include the exploration of biomarkers for efficacy prediction, the optimization of immunotherapy modalities, immune-related adverse effects, and the management of special populations. This review summarizes the progress of the research on immunotherapy for advanced NSCLC and discusses its challenges and future directions.

Abstract Background China experienced an overwhelming COVID-19 pandemic from middle December 2022 to middle January 2023 after lifting the zero-COVID-19 policy on December 7, 2022. However, the infection rate was less studied. We aimed to investigate the SARS-CoV-2 infection rate in children shortly after discontinuation of the zero-COVID-19 policy. Methods From February 20 to April 10, 2023, we included 393 children aged 8 months to less than 3 years who did not receive COVID-19 vaccination and 114 children aged 3 to 6 years who received inactivated COVID-19 vaccines based on the convenience sampling in this cross-sectional study. IgG and IgM antibodies against nucleocapsid (N) and subunit 1 of spike (S1) of SARS-CoV-2 (anti-N/S1) were measured with commercial kits (Shenzhen YHLO Biotech, China). Results Of the 393 unvaccinated children (1.5 ± 0.6 years; 52.2% boys), 369 (93.9%) were anti-N/S1 IgG positive. Of the 114 vaccinated children (5.3 ± 0.9 years; 48.2% boys), 112 (98.2%) were anti-N/S1 IgG positive. None of the unvaccinated or vaccinated children was anti-N/S1 IgM positive. The median IgG antibody titers in vaccinated children (344.91 AU/mL) were significantly higher than that in unvaccinated children (42.80 AU/mL) (P

Abstract Brain metastases (BM) are common in patients with epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC) and confer poor prognoses. Zorifertinib (AZD3759), an EGFR‐tyrosine kinase inhibitor (TKI) with high blood‐brain barrier penetration, has previously demonstrated promising systemic and intracranial antitumor activity in phase 1–3 studies. This is the first report of a patient with EGFR‐mutant (exon 21 L858R) NSCLC and symptomatic untreated multiple BM who achieved a long overall survival (OS) of more than 65 months after sequential treatment with zorifertinib and a third‐generation EGFR‐TKI. This new treatment paradigm offers a new treatment option and deserves further clinical exploration to prolong OS of patients with EGFR‐mutant NSCLC and untreated multiple BM.

Abstract Experimental realization of strong coupling between a single exciton and plasmons remains challenging as it requires deterministic positioning of the single exciton and alignment of its dipole moment with the plasmonic fields. This study aims to combine the host–guest chemistry approach with the cucurbit[7]uril-mediated active self-assembly to precisely integrate a single methylene blue molecule in an Au nanodimer at the deterministic position (gap center of the nanodimer) with the maximum electric field (EFmax) and perfectly align its transition dipole moment with the EFmax, yielding a large spectral Rabi splitting of 116 meV for a single-molecule exciton—matching the analytical model and numerical simulations. Statistical analysis of vibrational spectroscopy and dark-field scattering spectra confirm the realization of the single exciton strong coupling at room temperature. Our work may suggest an approach for achieving the strong coupling between a deterministic single exciton and plasmons, contributing to the development of room-temperature single-qubit quantum devices.

Abstract Background Haemophagocytic lymphohistiocytosis (HLH) is a syndrome that occurs in patients with severe systemic hyperinflammation. GATA binding protein 2 (GATA2) is a transcription factor and key component in haematopoiesis and stem cell biology. Case presentation Three patients with HLH, one with Mycobacterium avium infection, one with Epstein–Barr virus (EBV) infection, and one with Mycobacterium kansasii infection, were all subsequently found to have a defect in the GATA2 gene through genetic testing. Conclusions GATA2 deficiency syndrome should be considered in patients with myelodysplastic syndrome, nontuberculous mycobacterium infection and HLH. In addition, the GATA2 gene variant may be a genetic defect that could be the cause of the primary HLH. However, further studies are needed to confirm the role of GATA2 pathogenic variants in the pathogenesis of HLH.

Abstract Background To establish a method to induce Campylobacter jejuni colonization in the intestines of C57BL/6 mice through antibiotic-induced microbiome depletion. Results Fifty-four female C57BL/6 mice were divided into the normal, control, and experimental groups. The experimental group was administered intragastric cefoperazone sodium and sulbactam sodium (50 mg/mL) for 2 days; then, the experimental and control mice were intragastrically administered 200 µL C. jejuni, which was repeated once more after 2 days. Animal feces were collected, and the HipO gene of C. jejuni was detected using TaqMan qPCR from day 1 to day 14 after modeling completion. Immunofluorescence was used to detect intestinal C. jejuni colonization on day 14, and pathological changes were observed using hematoxylin and eosin staining. Additionally, 16S rDNA analyses of the intestinal contents were conducted on day 14. In the experimental group, C. jejuni was detected in the feces from days 1 to 14 on TaqMan qPCR, and immunofluorescence-labeled C. jejuni were visibly discernable in the intestinal lumen. The intestinal mucosa was generally intact and showed no significant inflammatory-cell infiltration. Diversity analysis of the colonic microbiota showed significant inter-group differences. In the experimental group, the composition of the colonic microbiota differed from that in the other 2 groups at the phylum level, and was characterized by a higher proportion of Bacteroidetes and a lower proportion of Firmicutes. Conclusions Microbiome depletion induced by cefoperazone sodium and sulbactam sodium could promote long-term colonization of C. jejuni in the intestines of mice.

Abstract Background Poor nurse-patient relationship poses an obstacle to care delivery, jeopardizing patient experience and patient care outcomes. Measuring nurse-patient relationship is challenging given its multi-dimensional nature and a lack of well-established scales. Purpose This study aimed to develop a multi-dimensional scale measuring nurse-patient relationship in China. Methods A preliminary scale was constructed based on the existing literature and Delphi consultations with 12 nursing experts. The face validity of the scale was tested through a survey of 45 clinical nurses. This was followed by a validation study on 620 clinical nurses. Cronbach’s α, content validity and known-group validity of the scale were assessed. The study sample was further divided into two for Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA), respectively, to assess the construct validity of the scale. Results The Nurse-Patient Relationship Scale (NPRS) containing 23 items was developed and validated, measuring five dimensions: nursing behavior, nurse understanding and respect for patient, patient misunderstanding and mistrust in nurse, communication with patient, and interaction with patient. The Cronbach’s α of the NPRS ranged from 0.725 to 0.932, indicating high internal consistency. The CFA showed excellent fitness of data into the five-factor structure: χ2/df = 2.431, GFI = 0.933, TLI = 0.923, CFI = 0.939, IFI = 0.923, RMSEA = 0.070. Good content and construct validity are demonstrated through expert consensus and psychometric tests. Conclusion The NPRS is a valid tool measuring nurse-patient relationship in China.

Abstract The dynamic control of electromagnetic waves is a persistent pursuit in modern industrial development. The state-of-the-art dynamic devices suffer from limitations such as narrow bandwidth, limited modulation range, and expensive features. To address these issues, we fuse origami techniques with metamaterial design to achieve ultra-wideband and large-depth reflection modulation. Through a folding process, our proposed metamaterial achieves over 10-dB modulation depth over 4.96 – 38.8 GHz, with a fractional bandwidth of 155% and tolerance to incident angles and polarizations. Its ultra-wideband and large-depth reflection modulation performance is verified through experiments and analyzed through multipole decomposition theory. To enhance its practical applicability, transparent conductive films are introduced to the metamaterial, achieving high optical transparency (>87%) from visible to near-infrared light while maintaining cost-effectiveness. Benefiting from lightweight, foldability, and low-cost properties, our design shows promise for extensive satellite communication and optical window mobile communication management.

Abstract Icosahedral carboranes, C2B10H12, have long been considered to be aromatic but the extent of conjugation between these clusters and their substituents is still being debated. m- and p-Carboranes are compared with m- and p-phenylenes as conjugated bridges in optical functional chromophores with a donor and an acceptor as substituents here. The absorption and fluorescence data for both carboranes from experimental techniques (including femtosecond transient absorption, time-resolved fluorescence and broadband fluorescence upconversion) show that the absorption and emission processes involve strong intramolecular charge transfer between the donor and acceptor substituents via the carborane cluster. From quantum chemical calculations on these carborane systems, the charge transfer process depends on the relative torsional angles of the donor and acceptor groups where an overlap between the two frontier orbitals exists in the bridging carborane cluster.

Abstract Background A temporal network of generalized anxiety disorder (GAD) symptoms could provide valuable understanding of the occurrence and maintenance of GAD. We aim to obtain an exploratory conceptualization of temporal GAD network and identify the central symptom. Methods A sample of participants (n = 115) with elevated GAD-7 scores (Generalized Anxiety Disorder 7-Item Questionnaire [GAD-7] ≥ 10) participated in an online daily diary study in which they reported their GAD symptoms based on DSM-5 diagnostic criteria (eight symptoms in total) for 50 consecutive days. We used a multilevel VAR model to obtain the temporal network. Results In temporal network, a lot of lagged relationships exist among GAD symptoms and these lagged relationships are all positive. All symptoms have autocorrelations and there are also some interesting feedback loops in temporal network. Sleep disturbance has the highest Out-strength centrality. Conclusions This study indicates how GAD symptoms interact with each other and strengthen themselves over time, and particularly highlights the relationships between sleep disturbance and other GAD symptoms. Sleep disturbance may play an important role in the dynamic development and maintenance process of GAD. The present study may develop the knowledge of the theoretical model, diagnosis, prevention and intervention of GAD from a temporal symptoms network perspective.

Abstract Large‐scale underground hydrogen storage (UHS) provides a promising method for increasing the role of hydrogen in the process of carbon neutrality and energy transition. Of all the existing storage deposits, salt caverns are recognized as ideal sites for pure hydrogen storage. Evaluation and optimization of site selection for hydrogen storage facilities in salt caverns have become significant issues. In this article, the software CiteSpace is used to analyze and filter hot topics in published research. Based on a detailed classification and analysis, a “four‐factor” model for the site selection of salt cavern hydrogen storage is proposed, encompassing the dynamic demands of hydrogen energy, geological, hydrological, and ground factors of salt mines. Subsequently, 20 basic indicators for comprehensive suitability grading of the target site were screened using the analytic hierarchy process and expert survey methods were adopted, which provided a preliminary site selection system for salt cavern hydrogen storage. Ultimately, the developed system was applied for the evaluation of salt cavern hydrogen storage sites in the salt mines of Pingdingshan City, Henan Province, thereby confirming its rationality and effectiveness. This research provides a feasible method and theoretical basis for the site selection of UHS in salt caverns in China.

Abstract The blue and white porcelain produced in Jingdezhen during China’s Yuan Dynasty is an outstanding cultural heritage of ceramic art that has attracted wide attention for its identification. However, the traditional visual identification method is susceptible to misjudgment, thermoluminescence dating damages the samples, and the methods based on chemical analysis are limited by the accuracy and specificity of the elemental features. In this paper, we address the identification challenge by using machine learning techniques combined with portable X-ray Fluorescence Spectrometer (pXRF) analysis. We collect a large dataset of chemical compositions of Yuan blue and white porcelain from Jingdezhen using pXRF, and propose a graph anomaly detection method based on gradient attention map (GRAM) to identify the porcelain from different dynasties. We treat the porcelain produced in the Yuan dynasty as normal samples and those from other dynasties as abnormal samples. For GRAM, we merely train the variational graph autoencoder (VGAE) model with normal graphs and then use its encoder to extract graph features and compute the anomaly scores by utilizing the GRAM of the graph representations with respect to the node feature embeddings. Finally, we compare GRAM with state-of-the-art graph anomaly detection techniques and show that it achieves superior performance.

Abstract Potassium Channel Tetramerization Domain Containing 15 (KCTD15) participates in the carcinogenesis of several solid malignancies; however, its role in colorectal cancer (CRC) remains unclear. Here we find that KCTD15 exhibits lower expression in CRC tissues as compared to para-carcinoma tissues. Tetracycline (tet)-induced overexpression and knockdown of KCTD15 confirms KCTD15 as an anti-proliferative and pro-apoptotic factor in CRC both in vitro and in xenografted tumors. N6-methyladenosine (m6A) is known to affect the expression, stabilization, and degradation of RNAs with this modification. We demonstrate that upregulation of fat mass and obesity-associated protein (FTO), a classical m6A eraser, prevents KCTD15 mRNA degradation in CRC cells. Less KCTD15 RNA is recognized by m6A ‘reader’ YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) in FTO-overexpressed cells. Moreover, KCTD15 overexpression decreases protein expression of histone deacetylase 1 (HDAC1) but increases acetylation of critical tumor suppressor p53 at Lys373 and Lys382. Degradation of p53 is delayed in CRC cells post-KCTD15 overexpression. We further show that the regulatory effects of KCTD15 on p53 are HDAC1-dependent. Collectively, we conclude that KCTD15 functions as an anti-growth factor in CRC cells, and its expression is orchestrated by the FTO-YTHDF2 axis. Enhanced p53 protein stabilization may contribute to KCTD15’s actions in CRC cells.

ObjectivesEvidence on the relationship between self-rated health status and incident type 2 diabetes (T2DM) in China is scarce. This study aims to examine the prospective association of self-rated health status with the subsequent risk of T2DM among middle-aged and older Chinese subjects.MethodsData were obtained from the China Health and Retirement Longitudinal Study of 9844 Chinese individuals aged 45 years or older. Cox proportional hazards models were used to yield hazard ratios (HRs) relating self-rated health status to the 7-year incidence of T2DM, adjusting for conventional risk factors.ResultsCompared to those with very good or good self-rated health, individuals with poor health had a significantly higher risk of developing T2DM in the multivariable-adjusted model [HR = 1.36 (1.07, 1.73)]. Subgroup analysis by sex showed stronger associations in women [HR = 1.53 (1.11, 2.12)]. Interaction analyses indicated that factors such as age, sex, obesity, smoking status, drinking status, history of hypertension and history of dyslipidemia did not modify the association (all P-interaction >0.05).ConclusionPoor self-rated health status is associated with a higher risk of developing T2DM in middle-aged and older Chinese people.

Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002–1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056–2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.

Background: MET overexpression represents the most MET aberration in advanced non-small-cell lung cancer (NSCLC). However, except MET exon 14 ( MET ex14) skipping mutation was recognized as a clinical biomarker, the role of MET overexpression as a predictive factor to MET inhibitor is not clear. Objectives: The purpose of the pooled analysis is to explore the safety and efficiency of gumarontinib, a highly selective oral MET inhibitor, in drive-gene negative NSCLC patients with MET overexpression. Design and methods: NSCLC patients with MET overexpression [immunohistochemistry (IHC) ⩾3+ as determined by central laboratory] not carrying epidermal growth factor receptor mutation, MET ex14 skipping mutation or other known drive gene alternations who received Gumarontinib 300 mg QD from two single arm studies were selected and pooled for the analysis. The efficacy [objective response rate (ORR), disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival (OS)] and safety [treatment emergent adverse event (TEAE), treatment related AE (TRAE) and serious AE (SAE) were assessed. Results: A total of 32 patients with MET overexpression were included in the analysis, including 12 treatment naïve patients who refused or were unsuitable for chemotherapy, and 20 pre-treated patients who received ⩾1 lines of prior systemic anti-tumour therapies. Overall, the ORR was 37.5% [95% confidence interval (CI): 21.1–56.3%], the DCR was 81.3% (95% CI: 63.6–92.8%), median PFS (mPFS) and median OS (mOS) were 6.9 month (95% CI: 3.6–9.7) and 17.0 month (95% CI: 10.3–not evaluable), respectively. The most common AEs were oedema (59.4%), hypoalbuminaemia (40.6%), alanine aminotransferase increased (31.3%). Conclusion: Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT03457532; NCT04270591.

Background: Mitochondrial dysfunction is one of the important patho-mechanisms in the development of atrial fibrillation (AF) with underidentified genetic pathophysiology.Methods: Summarized data of methylation, expression and protein abundance levels of mitochondria-related genes were obtained from corresponding studies, respectively. Genes related to mitochondria dysfunction in associations with AF were obtained from the UK Biobank (discovery), and the FinnGen study (replication). Summary-data-based Mendelian randomization analysis (SMR) was performed to assess potential causal relationships between mitochondria-related genes related to the molecular features of AF. Colocalization analysis was further conducted to assess whether the identified signal pairs shared causal genetic variants.Results: Five mitochondria-related genes were found to have causal effects with AF in the sensitivity and the colocalization analyses. Strong associations with increased risk of AF were identified with increased expression level of 4 mitochondria-related genes, including PCCB (OR 1.09, 95% CI 1.05–1.12; PPH4 = 0.95), COX18 (OR 1.83, 95% CI 1.29–2.60; PPH4 = 0.83), SLC25A15 (OR 1.34, 95% CI 1.14-1.58; PPH4 = 0.85), and STX17 (OR 1.16, 95% CI 1.08–1.24; PPH4 = 0.76). Conversely, genetically predicted higher levels expression of UQCC1 (OR 0.94, 95% CI 0.91–0.97) were associated with decreased risk of AF. After further tissue-specific validation, genetically predicted expression levels of PCCB (OR 1.12, 95%, CI 1.01-1.24, p = 0.025) and STX17 (OR 1.13, 95%, CI 1.04-1.23, p = 0.006) in atrial appendage were strongly associated with the increased risk of AF.Conclusion: Mitochondria-related genes are involved either positively (PCCB, COX18, SLC25A15 and STX17) or negatively (UQCCI) in the pathogenesis and the development of AF. These candidate genes may serve as targets for potential development of agents in the prevention and treatment of AF.

BackgroundThe digital finance era has reshaped young people’s lifestyles, risk perceptions and insurance participation decisions. Modern youth have to constantly seek for rational social security support and construct individual protection barriers to adapt to new lifestyles and social structures. China’s multi-tiered, universal health insurance system is urgently needed to satisfy young people’s flexible needs and rational decision-making.MethodsBased on the micro data from 2011 ~ 2021 Chinese General Social Survey (CGSS), this paper uses macro data from Digital Inclusive Finance Index (DIFI) matching to construct probit and m-logit model to assess the impact of the development of digital finance on Chinese youth whether or not to participate in health insurance, and how they choose the concrete type of health insurance.Results(1) Baseline regression results shows that digital finance has a significant positive effect on Chinese youth’s health insurance participation decisions, and has different effects on choices within health insurance types. Strong support for the conclusions is provided by endogeneity and robustness tests. (2) The results of the heterogeneity analysis reveal that the marginal effect of digital finance on young people’s health insurance decisions shows urban–rural differences, divergence in levels of self-rated health. (3) The mechanism analysis results suggest that there are two mechanism paths of digital finance on youth health insurance decisions: the household income effect and the subjective well-being effect, and two moderating effects: employment type and family structure.ConclusionHighlighting the positive value that digital finance brings to the perception of youth insurance participation and the construction of social security systems, it needs to pay close attention to the dynamic changes in employment security and family structure through data, and explore the socio-psychological fluctuation and demand for social security among modern youth. To provide a way forward to achieve the integration of the health insurance system in China and solve the current problem of health insurance equity.

Summary: Background: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in the FURLONG study. Here we present prespecified secondary endpoints of patient-reported outcomes (PRO). Methods: In this multicentre, double-blind, double-dummy, randomised phase 3 study, patients were 1:1 randomly assigned to receive furmonertinib 80 mg once daily or gefitinib 250 mg once daily. PROs assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and Quality-of-Life Questionnaire Lung Cancer 13 were analysed using a mixed model for repeated measures and time-to-event analyses. A difference in score of 10 points or more was deemed clinically relevant. Findings: Three hundred and fifty-seven patients (furmonertinib group, n = 178; gefitinib group, n = 179) received at least one dose of the study drug, all of whom completed at least one PRO assessment. Statistically significant difference of overall score changes from baseline favoured furmonertinib in physical functioning (between-group difference 2.14 [95% CI 0.25–4.04], p = 0.027), nausea/vomiting (−1.56 [95% CI −2.62 to −0.49], p = 0.004), appetite loss (−2.24 [95% CI −4.26 to −0.23], p = 0.029), diarrhoea (−3.36 [95% CI −5.19 to −1.54], p < 0.001), alopecia (−2.62 [95% CI −4.54 to −0.71], p = 0.007), and pain in other parts (−4.55 [95% CI −7.37 to −1.74], p = 0.002), but not reached clinical relevance. Time to deterioration in physical functioning (hazard ratio 0.63 [95% CI 0.42–0.94], p = 0.021), cognitive functioning (0.73 [95% CI 0.54–0.98], p = 0.034), nausea/vomiting (0.64 [95% CI 0.41–0.99], p = 0.042), appetite loss (0.63 [95% CI 0.43–0.92], p = 0.016), diarrhoea (0.63 [95% CI 0.46–0.85], p = 0.002), dyspnoea (0.72 [95% CI 0.53–0.98], p = 0.034), cough (0.67 [95% CI 0.44–1.00], p = 0.049), dysphagia (0.54 [95% CI 0.35–0.83], p = 0.004), and alopecia (0.62 [95% CI 0.42–0.90], p = 0.012) was longer with furmonertinib versus gefitinib. Interpretation: In patients with locally advanced or metastatic EGFR mutation-positive NSCLC, furmonertinib showed improved scores and delayed deterioration in several functioning and symptoms compared to gefitinib. Funding: Shanghai Allist Pharmaceutical Technology Co., Ltd and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by infiltration of inflammatory cells, hyperplasia of synovium, and destruction of the joint cartilage. Owing to the low drug delivery efficiency and limited immunosuppression effect, complete cure for RA remains a formidable challenge. Here, we show that live macrophages (Mφs) carrying protoporphyrin-loaded Fe3O4 nanoparticles can migrate to the RA tissues and inhibit the inflammation by sonodynamic therapy. The inflammation of RA leads to the release of cytokines, which guides the migration of the Mφs into the RA tissues, realizing precise delivery of therapeutics. The following sonodynamic therapy induced by ultrasound and protoporphyrin destructs the proliferating synovial cells and also infiltrated inflammatory cells, demonstrating significant therapeutic effect for RA. Meanwhile, the cytokines and relapse of RA can be remarkably suppressed because of the efficient damage to the resident inflammatory cells.

Herba Epimedii’s leaves are highly valued in traditional Chinese medicine for their substantial concentration of flavonoids, which play a crucial role in manifesting the plant’s therapeutic properties. This study investigated the metabolomic, transcriptomic and proteomic profiles of leaves from two Herba Epimedii cultivars, Epipremnum sagittatum (J) and Epipremnum pubescens (R), at three different developmental stages. Metabolite identification and analysis revealed a total of 1,412 and 1,421 metabolites with known structures were found. Flavonoids made up of 33%, including 10 significant accumulated icariin analogues. Transcriptomic analysis unveiled totally 41,644 differentially expressed genes (DEGs) containing five encoded genes participated in icariin biosynthesis pathways. Totally, 9,745 differentially expressed proteins (DEPs) were found, including Cluster-47248.2.p1 (UDP-glucuronosy/UDP-glucosyltransferase), Cluster-30441.2.p1 (O-glucosyltransferase), and Cluster-28344.9.p1 (anthocyanidin 3-O-glucoside 2 “-O-glucosyltransferase-like) through proteomics analysis which are involved to icariin biosynthesis. Protein-protein interaction (PPI) assay exhibited, totally 12 proteins showing a strong relationship of false discovery rate (FDR)

A brake dynamometer has been modified to accurately study the concentration and size distribution of wear particles in different testing conditions. The test equipment was a charged low-pressure impactor ELPI+ from Dekati, Finland. 29 test conditions were defined based on speed, acceleration and initial brake temperature. Additionally, five different types of brake pads were selected for testing to provide a more comprehensive understanding of the particle size distribution characteristics of brake wear particles. The results showed that the mass of BWPs was unimodal in the range of 0.01–8.11 μm, with peak sizes at 2–5 μm or >8.11 μm, and particles of 0.5–3.0 μm accounted for an average of 49.09% of the total particulate mass, while particles with sizes of 3.0–8.11 μm accounted for an average of 49.72% of the total particulate mass. The number of particles emitted by abrasion had a bimodal distribution, with one in the nucleation mode and the other in the accumulation mode, with peak sizes of

Background: Doxorubicin (DOX) is a chemotherapeutic drug, while its clinical use is greatly limited by the life-threatening cardiotoxicity. N6-methyladenosine (m6A) RNA modification participates in varieties of cellular processes. Nonetheless, it remains elusive whether m6A modification and its methyltransferase METTL3 are involved in the progression of DOX-induced cardiotoxicity (DIC). Methods: Mice were administrated with DOX (accumulative dosage of 20 mg/kg) repeatedly to establish a chronic DIC model. Cardiomyocyte-specific conditional METTL3 knockout mice were employed to evaluate the effects of altered m6A RNA modification on DIC. The effects of METTL3 on cardiomyocyte ferroptosis were also examined in response to DOX stimulation. Results: DOX led to increased levels in m6A modification and METTL3 expression in cardiomyocytes in a c-Jun-dependent manner. METTL3-knockout mice exhibited improved cardiac function, remodeling and injury following DOX insult. Besides, inhibition of METTL3 alleviated DOX-induced iron accumulation and ferroptosis in cardiomyocytes, whereas METTL3 overexpression exerted the opposite effects. Mechanistically, METTL3 promoted m6A modification of TFRC mRNA, a critical gene governing iron uptake, and enhanced its stability through recognition of the m6A reader protein, IGF2BP2. Moreover, pharmacological administration of a highly selective METTL3 inhibitor STM2457 effectively ameliorated DIC in mice. Conclusion: METTL3 plays a cardinal role in the etiology of DIC by regulating cardiac iron metabolism and ferroptosis through TFRC m6A modification. Inhibition of METTL3 might be a potential therapeutic avenue for DIC.

Abstract Background Advanced lung adenocarcinoma patients often develop resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), leaving uncertainties regarding subsequent treatment strategies. Although personalized therapy targeting individual acquired resistances (ARs) shows promise, its efficacy has not been systematically compared with platinum-containing doublet chemotherapy, a widely accepted treatment after EGFR-TKIs failure. Methods A retrospective dual-center study was conducted involving patients with advanced lung adenocarcinoma and EGFR mutations who developed resistance to EGFR-TKIs between January 2017 and December 2022. Eligible patients were adults aged 18 years or older with an Eastern Cooperative Oncology Group score of 0–1, normal organ function, and no prior chemotherapy. Patients were divided into the chemotherapy group (CG) or personalized therapy group (PG) based on the treatment received after disease progression. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). Results Of the 144 patients enrolled, there were 53 patients in the PG and 91 patients in the CG. The PG acquired resistance to EGFR-TKIs through the MET amplification (27, 50%) and small cell lung cancer transformation (16, 30%) and 18% of them reported multiple resistance mechanisms. The ORR of the PG was similar to that of the CG (34% vs. 33%, P = 1.0) and the PFS of the PG patients was not statistically different from that of their CG counterparts [4.2 months (95% CI: 3.6–4.8 months) vs. 5.3 months (95% CI: 4.6–6.0 months), P = 0.77]. Conclusions These findings suggest that the therapeutic efficacy of chemotherapy approximates to that of personalized therapy, which signifies that chemotherapy is still a reliable choice for patients who develop resistance to EGFR-TKIs and that further research is awaited to explore the benefit of personalized treatment.

Abstract Background Burnout is a common issue among medical professionals, and one of the well-studied predisposing factors is the Big Five personality traits. However, no studies have explored the relationships between these traits and burnout from a trait-to-component perspective. To understand the specific connections between each Big Five trait and burnout components, as well as the bridging effects of each trait on burnout, we employed network analysis. Methods A cluster sampling method was used to select a total of 420 Chinese medical personnel. The 15-item Chinese Big Five Personality Inventory-15 (CBF-PI-15) assessed the Big Five personality traits, while the 15-item Maslach Burnout Inventory-General Survey (MBI-GS) assessed burnout components. Network analysis was used to estimate network structure of Big Five personality traits and burnout components and calculate the bridge expected influence. Results The study revealed distinct and clear relationships between the Big Five personality traits and burnout components. For instance, Neuroticism was positively related to Doubt significance and Worthwhile, while Conscientiousness was negatively related to Accomplish all tasks. Among the Big Five traits, Neuroticism displayed the highest positive bridge expected influence, while Conscientiousness displayed the highest negative bridge expected influence. Conclusions The network model provides a means to investigate the connections between the Big Five personality traits and burnout components among medical professionals. This study offers new avenues for thought and potential targets for burnout prevention and treatment in medical personnel, which can be further explored and tested in clinical settings.

Abstract This single-arm, multi-center clinical trial aimed to evaluate the safety, tolerability, DLT, recommended dose (RD), preliminary efficacy, and pharmacokinetics (PK) characteristics of lurbinectedin, a selective inhibitor of oncogenic transcription, in Chinese patients with advanced solid tumors, including relapsed SCLC. Patients with advanced solid tumors were recruited in the dose-escalation stage and received lurbinectedin in a 3 + 3 design (two cohorts: 2.5 mg/m2 and 3.2 mg/m2, IV, q3wk). The RD was expanded in the following dose-expansion stage, including relapsed SCLC patients after first-line platinum-based chemotherapy. The primary endpoints included safety profile, tolerability, DLT, RD, and preliminary efficacy profile, while the secondary endpoints included PK characteristics. In the dose-escalation stage, ten patients were included, while one patient had DLT in the 3.2 mg/m2 cohort, which was also the RD for the dose-expansion stage. At cutoff (May 31, 2022), 22 SCLC patients were treated in the ongoing dose-expansion stage, and the median follow-up was 8.1 months (range 3.0–11.7). The most common grade ≥ 3 treatment-related adverse events (TRAEs) included neutropenia (77.3%), leukopenia (63.6%), thrombocytopenia (40.9%), anemia (18.2%), and ALT increased (18.2%). The most common severe adverse events (SAEs) included neutropenia (27.3%), leukopenia (22.7%), thrombocytopenia (18.2%), and vomiting (9.1%). No treatment-related deaths occurred. The Independent Review Committee (IRC)-assessed ORR was 45.5% (95% CI 26.9–65.3). Lurbinectedin at the RD (3.2 mg/m2) showed manageable safety and acceptable tolerability in Chinese patients with advanced solid tumors, and demonstrates promising efficacy in Chinese patients with SCLC as second-line therapy. Trial registration: This study was registered with ClinicalTrials.gov NCT04638491, 20/11/2020.

Abstract Approximately 36% of patients with neuromyelitis optica spectrum disorders (NMOSD) suffer from severe visual and motor disability (blindness or light perception or unable to walk) with abnormalities of whole-brain functional networks. However, it remains unclear how whole-brain functional networks and their dynamic properties are related to clinical disability in patients with NMOSD. Our study recruited 30 NMOSD patients (37.70 ± 11.99 years) and 45 healthy controls (HC, 41.84 ± 11.23 years). The independent component analysis, sliding-window approach and graph theory analysis were used to explore the static strength, time-varying and topological properties of large-scale functional networks and their associations with disability in NMOSD. Compared to HC, NMOSD patients showed significant alterations in dynamic networks rather than static networks. Specifically, NMOSD patients showed increased occurrence (fractional occupancy; P

Abstract Objective There is currently no widely accepted multidimensional health assessment questionnaire for individuals in the Chinese People Liberation Army (PLA). This study developed a multidimensional health survey questionnaire (Comprehensive Health Self-Assessment Questionnaire, CHSAQ) suitable for personnel in the PLA and conducted a preliminary examination of its reliability, validity, and discriminative ability. Methods After 183 items from 32 dimensions were selected to form the initial version of the CHSAQ, three groups of soldiers were selected from May 2022 to April 2023 and completed three survey rounds (with 183, 131, and 55 valid items). The items were screened based on classic test theory. After screening, the final questionnaire entries were formed, the structure of the questionnaire was explored through exploratory factor analysis and confirmatory factor analysis, and its reliability, structural validity, and discriminative ability were evaluated. Results The final questionnaire consisted of 8 dimensions and 55 items on job satisfaction, anxiety and depression, daily activities, physical function, the otolaryngology system, the integumentary system, sleep disorders, and the visual system. The total cumulative variance contribution rate was 64.648% according to exploratory factor analysis. According to the confirmatory factor analysis, the normed fit index (NFI) was 0.880, and the comparison fit index (CFI) was 0.893 (close to 0.90). The Cronbach’s α coefficient of the total questionnaire was 0.970, the split half reliability coefficient was 0.937, and the retest reliability coefficient was 0.902. The results are presented as different pairwise comparisons. Conclusion Our study developed a self-report questionnaire for evaluating the comprehensive health status of personnel in the PLA in accordance with the standard procedure for questionnaire development. Our findings also showed that the CHSAQ for individuals in the PLA has good reliability and structural validity.

Abstract. Background:. Artificial intelligence (AI) technology represented by deep learning has made remarkable achievements in digital pathology, enhancing the accuracy and reliability of diagnosis and prognosis evaluation. The spatial distribution of CD3+ and CD8+ T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer (CRC). This study aimed to investigate CD3CT (CD3+ T cells density in the core of the tumor [CT]) prognostic ability in patients with CRC by using AI technology. Methods:. The study involved the enrollment of 492 patients from two distinct medical centers, with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation cohort. To facilitate tissue segmentation and T-cells quantification in whole-slide images (WSIs), a fully automated workflow based on deep learning was devised. Upon the completion of tissue segmentation and subsequent cell segmentation, a comprehensive analysis was conducted. Results:. The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3CT and CD3-CD8 (the combination of CD3+ and CD8+ T cells density within the CT and invasive margin) in predicting mortality (C-index in training cohort: 0.65 vs. 0.64; validation cohort: 0.69 vs. 0.69). The CD3CT was confirmed as an independent prognostic factor, with high CD3CT density associated with increased overall survival (OS) in the training cohort (hazard ratio [HR] = 0.22, 95% confidence interval [CI]: 0.12–0.38, P

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 To investigate the instent restenosis rate of sirolimus-coated stents in percutaneous coronary intervention (PCI) and risk factors for in-stent restenosis, patients with unstable angina (UA) caused by coronary artery stenosis were enrolled, and all clinical and imaging data were analyzed. Among 143 enrolled patients with UA aged 35–83 (mean 60.9 ± 10.0) years enrolled, there were 114 (79.7%) male and 29 (20.3%) female patients. Arterial stenosis was present in one coronary artery in 6 (4.2%) patients, in two coronary arteries in 20 (14.0%) patients, in three arteries in 116 (81.1%), and in four coronary arteries in 1 (0.7%) patient. Stenting was successfully performed in all (100%) patients, and 181 stents were deployed. The quantitative flow ratio (QFR) was 0.92 ± 0.03 (range 0.84–0.96) immediately after stenting, and the TIMI was grade 3 in all patients. The diameter of the stents deployed ranged 2.25–4 mm (mean 3.04 ± 0.44) with a length ranging 10 mm to 104 mm (mean 32.73 ± 15.5). Follow-up angiography was performed in all patients with a duration of 1–92 (mean 15.0 ± 18.8) months. Instent restenosis ≥ 50% occurred in 25 (17.5%) patients. In univariate logistic regression analysis, significant (P

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Water-body type problems classification plays a vital role in ecological conservation, water resource management, and urban planning. Accurate classification can aid decision-makers in understanding the functions of different water-body types, providing key information for urban planning and promoting harmony between human activities and the natural environment. Despite extensive research in the field of water-body segmentation, exploration in the water-body type classification community is not as widespread. Therefore, this article proposes a novel water-body type classification method based on a two-step deep-learning model, decomposing water-body type classification into water-body segmentation and water-body type identification. Especially, this method constructs a unique data strategy by organically integrating backscatter features, polarimetric features, and DEM features, providing the model with rich and comprehensive information. In the first step, the segmentation network uses the fused feature to extract all water-body from synthetic aperture radar images. Subsequently, the extracted water-body are combined with the input data, forming a multifeature input for the identification network to distinguish between natural and artificial water-body. During this process, a swarm intelligence optimization algorithm is employed to explore the optimal hyperparameters of the network, including those of the segmentation and identification networks. Finally, the proposed method is assessed using extensive experiments on water-body segmentation tasks, water-body type identification tasks, and joint water-body type classification tasks. This article not only provides a new perspective in the field of water-body type classification but also demonstrates the immense potential of deep-learning network hyperparameter optimization and feature fusion in solving such.

Abstract Coupling high-capacity cathode and Li-anode with solid-state electrolyte has been demonstrated as an effective strategy for increasing the energy densities and safety of rechargeable batteries. However, the limited ion conductivity, the large interfacial resistance, and unconstrained Li-dendrite growth hinder the application of solid-state Li-metal batteries. Here, a poly(ether-urethane)-based solid-state polymer electrolyte with self-healing capability is designed to reduce the interfacial resistance and provides a high-performance solid-state Li-metal battery. With its dynamic covalent disulfide bonds and hydrogen bonds, the proposed solid-state polymer electrolyte exhibits excellent interfacial self-healing ability and maintains good interfacial contact. Full cells are assembled with the two integrated electrodes/electrolytes. As a result, the Li||Li symmetric cells exhibit stable long-term cycling for more than 6000 h, and the solid-state Li-S battery shows a prolonged cycling life of 700 cycles at 0.3 C. The use of ultrasound imaging technology shows that the interfacial contact of the integrated structure is much better than those of traditional laminated structure. This work provides an interesting interfacial dual-integrated strategy for designing high-performance solid-state Li-metal batteries.

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.

Abstract Background Sex hormones play important roles in the estrus return of post-weaning sows. Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota. However, the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown. Results In this study, we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows. Using metagenomic sequencing data from 85 fecal samples, we identified 37 bacterial species that were significantly associated with estrus return. Normally returning sows were characterized by increased abundances of L. reuteri and P. copri and decreased abundances of B. fragilis, S. suis, and B. pseudolongum. The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome. The results were confirmed in a validation cohort. Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis. An integrated analysis of differential bacterial species, metagenome, and fecal metabolome provided evidence that normal return-associated bacterial species L. reuteri and Prevotella spp. participated in the degradation of pregnenolone, progesterone, and testosterone, thereby promoting estrogen biosynthesis. Furthermore, the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return. Conclusions An integrated analysis of differentially abundant bacterial species, metagenome, and fecal metabolome revealed the involvement of L. reuteri and Prevotella spp. in sow estrus return. These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones, suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.

Abstract The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.

Abstract Aims To investigate the predictive value of baseline C-reactive protein (CRP) levels on the efficacy of chemotherapy plus immune checkpoint inhibitors (ICI) in patients with advanced lung squamous cell carcinoma (LSCC). Materials and methods In this retrospective multicenter study spanning from January 2016 to December 2020, advanced LSCC patients initially treated with chemotherapy or a combination of chemotherapy and ICI were categorized into normal and elevated CRP subgroups. The relationship between CRP levels and treatment outcomes was analyzed using multivariate Cox proportional hazards models and multivariate logistic regression, focusing primarily on the progression-free survival (PFS) endpoint, and secondarily on overall survival (OS) and objective response rate (ORR) endpoints. Survival curves were generated using the Kaplan-Meier method, with the log-rank test used for comparison between groups. Results Of the 245 patients evaluated, the 105 who received a combination of chemotherapy and ICI with elevated baseline CRP levels exhibited a significant reduction in PFS (median 6.5 months vs. 11.8 months, HR, 1.78; 95% CI: 1.12–2.81; p = 0.013) compared to those with normal CRP levels. Elevated CRP was identified as an independent risk factor for poor PFS through multivariate-adjusted analysis. However, among the 140 patients receiving chemotherapy alone, baseline CRP levels did not significantly influence PFS. Furthermore, within the combination therapy group, there was a notable decrease in the ORR (51% vs. 71%, p = 0.035), coupled with a significantly shorter OS (median 20.9 months vs. 31.5 months, HR, 2.24; 95% CI: 1.13–4.44; p = 0.033). Conclusion In patients with advanced LSCC, elevated baseline CRP levels were identified as an independent predictive factor for the efficacy of combination therapy with chemotherapy and ICI, but not in chemotherapy alone. This suggests that CRP may be a valuable biomarker for guiding treatment strategies.

Working memory (WM) is an essential cognitive function that underpins various higher-order cognitive processes. Improving WM capacity through targeted training interventions has emergered as a potential approach for enhancing cognitive abilities. The present study employed an 8-week regimen of computerized WM training (WMT) to investigate its effect on neuroplasticity in healthy individuals, utilizing neuroimaging data gathered both before and after the training. The key metrics assessed included the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and the spatial distribution correlations of neurotransmitter. The results indicated that post-training, compared to baseline, there was a reduction in ALFF in the medial superior frontal gyrus and an elevation in ALFF in the left middle occipital gyrus within the training group. In comparison to the control group, the training group also exhibited decreased ALFF in the anterior cingulate cortex, angular gyrus, and superior parietal lobule, along with increased ALFF in the postcentral gyrus post-training. VBM analysis revealed a significant increase in gray matter volume (GMV) in the right dorsal superior frontal gyrus after the training period, compared to the initial baseline measurement. Furthermore, the training group showed GMV increases in the dorsal superior frontal gyrus, Rolandic operculum, precentral gyrus, and postcentral gyrus when compared to the control group. In addition, significant associations were identifed between neuroimaging measurements (AFLL and VBM) and the spatial patterns of neurotransmitters such as serotonin (5-HT), dopamine (DA), and N-methyl-D-aspartate (NMDA), providing insights into the underlying neurochemical processes. These findings clarify the neuroplastic changes caused by WMT, offering a deeper understanding of brain plasticity and highlighting the potential advantages of cognitive training interventions.

IntroductionAs an important coniferous tree in northeast China, Pinus koraiensis not only maintains the stability of the forest ecosystem at high latitudes but also plays a crucial role in regional socioeconomic development. With the intensification of climate change in recent years, the stability of P. koraiensis habitats is constantly disturbed by external uncertain environmental factors, which greatly affects the geographical distribution of P. koraiensis. However, its geographical distribution is still unclear, which greatly hinders further understanding of the ecological process of P. koraiensis. Consequently, it is particularly important to explore the potential distribution and migration of P. koraiensis during several critical periods.MethodsRandom forest (RF) was used to establish the redistribution of P. koraiensis.ResultsThe results showed that temperature seasonality and precipitation in the coldest quarter were the key factors limiting the current distribution of P. koraiensis. Currently, P. koraiensis is mainly distributed in the Lesser Khingan Mountains and Changbai Mountains, with a total suitable area of ~4.59 × 105 km2. In the past, the historical distribution of P. koraiensis during the LIG period was basically consistent with the current distribution range, but its distribution range was more complete. In the LGM period, the suitable distribution of P. koraiensis became fragmented, especially at the connection between the Lesser Khingan Mountains and the Changbai Mountains. Under future climate scenarios, the suitable distribution of P. koraiensis is projected to increase, while the highly suitable distribution will be reduced. The dramatically worrying change is that the suitable habitats of P. koraiensis are gradually breaking and separating in the junction zone between the Lesser Khingan Mountains and Changbai Mountains, which will cause the ecological corridor to break. The shifts in the distribution centroid indicated that the P. koraiensis population will migrate northward.DiscussionHowever, it remains to be verified whether long-distance migration can be achieved without human assistance. Our results can provide some solutions for protection and management strategies for P. koraiensis populations and the impact of climate change, shedding light on the effectiveness of management responses.

AF is a prevalent condition that is associated with various modifiable and unmodifiable risk factors. Drug-induced AF, despite being commonly under-recognised, can be relatively easy to manage. Numerous cardiovascular and non-cardiovascular agents, including catecholaminergic agents, adenosine, anti-tumour agents and others, have been reported to induce AF. However, the mechanisms underlying drug-induced AF are diverse and not fully understood. The complexity of clinical scenarios and insufficient knowledge regarding drug-induced AF have rendered the management of this condition complicated, and current treatment guidelines follow those for other types of AF. Here, we present a review of the epidemiology of drug-induced AF and highlight a range of drugs that can induce or exacerbate AF, along with their molecular and electrophysiological mechanisms. Given the inadequate evidence and lack of attention, further research is crucial to underscore the clinical significance of drug-induced AF, clarify the underlying mechanisms and develop effective treatment strategies for the condition.

Airborne LiDAR bathymetry (ALB) system is an attractive and efficient method for nearshore bathymetry and underwater topography mapping. To ensure and improve the measurement accuracy and reliability in various water environments, different receivers using a segmented field of view (FOV) have been designed and are implemented in ALB. These are used to obtain various echo data of multiple channels and perform bathymetry at various water depths. However, in echo waveform processing, detailed information about the water body described by the different echo waveforms is lacking, making it difficult to overcome severe waveform superposition in extremely shallow areas or to separate the weak echo of the water bottom from the noise in extremely deep areas. Therefore, we employed a novel method of multi-channel waveform fusion bathymetry (MWFB) to achieve information complementarity, gain multi-channel waveforms, and detect the robustness of water and bottom echo signals. This method uses an adaptive signal waveform extraction of a multichannel fusion mechanism to eliminate systematic and random noise, and the waveform curvature is used to reconstruct the energy–waveform curves. Iterative decomposition based on waveform curvature and energy curves was conducted to improve the correctness of waveform decomposition and the reliability of waveform components. Furthermore, the water surface and bottom peaks were detected based on the multichannel waveform curvature, which enabled acquisition of the accurate temporal positions of the peaks and achieve high-accuracy bathymetry. According to the experimental results and a comparison with reference datasets, the highest bathymetric accuracy of the MWFB method reached an RMSE of 0.22. For the different study areas, the bathymetric accuracy of the slope reached 95%, 92%, and 97% at Ganquan Island, Lingyang Reef, and Bei Island, respectively. Furthermore, the bathymetric point numbers were effectively increased and bathymetric accuracy was also improved in shallow and deep water, which illustrates the superior bathymetric performance of the MWFB method and its ability to provide a high-efficiency waveform dataset through multi-channel data fusion. The novel LiDAR bathymetric method proposed in this study can effectively achieve high-accuracy nearshore bathymetry and seafloor topographical mapping.