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Objective N6-methyladenosine (m6A) is the most prevalent methylation of mRNA and plays crucial roles in various physiological processes, including pigmentation. Yet, the regulatory mechanisms, including long noncoding RNAs (lncRNAs) m6A methylation contributing to pigmentation in sheep skin remains unclear. The purpose of this study was to identify potential lncRNAs and the m6A methylation of lncRNAs associated with pigmentation. Methods RNA-seq and MeRIP-seq were performed to study the expression of lncRNAs and the m6A methylation of lncRNAs in black and white sheep skin. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency with the RNA-seq and MeRIP-seq data. Results We identified 168 differentially expressed lncRNAs between the two sheep skin colors. The differentially expressed lncRNAs enriched in the pathway of ECM-receptor interaction, Rap1 signaling pathway, and Non-homologous end-joining may play essential roles in pigmentation. We identified 577 m6A peaks and 617 m6A peaks in black and white sheep skin, respectively, among which 20 m6A peaks showed significant differences. The enriched motif in sheep skin was “GGACU”, which aligned with the consensus motif “RRACH” (R = A or G, H = A, C or U). Differently methylated lncRNAs enriched in PI3K-Akt signaling pathway and Wnt signaling pathway might participate in skin pigmentation. ENSOARG00020015168 was the unique lncRNA with high expression and methylation (Hyper-Up) in black sheep shin. A lncRNA-mRNA network was constructed, with pigmentation-related genes, such as PSEN2, CCND3, COL2A1, and ERCC3. Conclusion The m6A modifications of lncRNAs in black and white colored sheep skin were analyzed comprehensively, providing new candidates for the regulation of pigmentation.

Abstract Inhaled delivery of messenger RNA (mRNA) using lipid nanoparticle (LNP) holds immense promise for treating pulmonary diseases or serving as a mucosal vaccine. However, the unsatisfactory delivery efficacy caused by the disintegration and aggregation of LNP during nebulization represents a major obstacle. To address this, we develop a charge-assisted stabilization (CAS) strategy aimed at inducing electrostatic repulsions among LNPs to enhance their colloidal stability. By optimizing the surface charges using a peptide-lipid conjugate, the leading CAS-LNP demonstrates exceptional stability during nebulization, resulting in efficient pulmonary mRNA delivery in mouse, dog, and pig. Inhaled CAS-LNP primarily transfect dendritic cells, triggering robust mucosal and systemic immune responses. We demonstrate the efficacy of inhaled CAS-LNP as a vaccine for SARS-CoV-2 Omicron variant and as a cancer vaccine to inhibit lung metastasis. Our findings illustrate the design principles of nebulized LNPs, paving the way of developing inhaled mRNA vaccines and therapeutics.

Cross-Regional Model Transfer (CRMT) provides a solution to crop classification challenges in target regions with limited labeled samples. However, when the source region (source domain) and the target region (target domain) are spatially distant, a shift in crop Satellite Image Time Series (SITS) occurs, resulting in suboptimal performance of SITS-based classification models in the target domain. To address this issue, we propose a novel domain adaptation method, named SITS Correction. This method mitigates the SITS shift by introducing correction factors to improve the classification performance of CRMT. The correction factors consist of source domain correction units and target domain correction units, which are from variables associated with the SITS shift. In cases where labeled samples are available in the target domain, the SITS have calculated Barycenter (i.e. SitsB) as the correction units, which then combine the source domain and the target domain’s SitsB to form a SITS-based correction factor. When no labeled samples are available, the correction units are substituted by Barycenter of the temperature variables time series (i.e. temperature indicator) influencing crop growth, and the correction factors are composed of temperature indicators from both the source and target domains. We validate SITS Correction through transfer experiments conducted in four regions, encompassing various years, crops, and classification methods. Experimental results demonstrate a significant improvement in crop classification performance with SITS Correction in both scenarios – target domain with labeled samples (accuracy increased by 39.1%) and target domain without labeled samples (accuracy increased by 14.8%). This research provides a practical option for crop classification in target regions with either limited or no labeled samples.

Abstract Intrahepatic circulation is essential for the repair of acute liver injury (ALI); however, very limited information is available concerning changes in the circulatory pathways during ALI. Therefore, multi-scale X-ray phase-contrast CT combined with three-dimensional (3D) visualization is used to quantitatively analyze the intrahepatic circulation pathway (including the hepatic vein, portal vein and hepatic sinusoid) in the mouse model via the intraperitoneal injection of carbon tetrachloride (CCl4) from acute injury to recovery. The results demonstrate that the liver still preserves some vessel-like channels accessed to the central vein when the injury causes the severe collapse of the hepatic sinusoids that cannot be observed in two-dimensional pathologic slices. Moreover, angiogenesis is observed in the terminal branches of the hepatic vein and portal vein. Additionally, we extend the two-dimensional primary lobule to a 3D model and find that the sinusoids in zone III have the most severe injury. The sinusoids in different zones also show changes in parameters such as density and mean diameter during the ALI. In conclusion, phase-contrast CT can reveal the intact vascular system within the liver lobes, thus providing critical information for studying the mechanisms involved in the evolution of circulatory structures from damage to repair.

Abstract Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and metabolic abnormality disease that mainly affects women of reproductive age. LINC00173, a novel long noncoding RNA (lncRNA), has emerged as an important factor in the development of PCOS. However, the role of LINC00173 in PCOS development and its specific upstream and downstream mechanisms remain to be further clarified. Here, we found that LINC00173 was significantly upregulated in granulosa cells (GCs) of PCOS patients, and played a crucial role in promoting apoptosis of GCs. Mechanistically, we observed the activation of endoplasmic reticulum (ER) stress in the GCs of PCOS patients, and the ER stress sensor ATF4 could directly induce LINC00173 expression by binding to its promoter. LINC00173 further upregulated the expression of Harakiri (HRK) and subsequently inhibited downstream PI3K/AKT pathway. In conclusions, our study uncovered that ER stress-induced upregulation of LINC00173 leads to increased HRK expression and inhibition of the PI3K/AKT pathway, thereby promoting the progression of PCOS. These findings provide a new therapeutic strategy for the treatment of PCOS.

Abstract Weeds are undesired plants competing with crops for light, nutrients, and water, negatively impacting crop growth. Identifying weeds in wheat fields accurately is important for precise pesticide spraying and targeted weed control. Grass weeds in their early growth stages look very similar to wheat seedlings, making them difficult to identify. In this study, we focused on wheat fields with varying levels of grass weed infestation and used unmanned aerial vehicles (UAVs) to obtain images. By utilizing deep learning algorithms and spectral analysis technology, the weeds were identified and extracted accurately from wheat fields. Our results showed that the precision of weed detection in scattered wheat fields was 91.27% and 87.51% in drilled wheat fields. Compared to areas without weeds, the increase in weed density led to a decrease in wheat biomass, with the maximum biomass decreasing by 71%. The effect of weed density on yield was similar, with the maximum yield decreasing by 4320 kg·ha− 1, a drop of 60%. In this study, a method for monitoring weed occurrence in wheat fields was established, and the effects of weeds on wheat growth in different growth periods and weed densities were studied by accurately extracting weeds from wheat fields. The results can provide a reference for weed control and hazard assessment research.

Abstract There is still room for improvement in first-line treatment of advanced small cell lung cancer (SCLC). This trial firstly investigated efficacy and safety of antiangiogenic therapy (surufatinib) (200 mg, qd, po) plus anti-PD-1 treatment (toripalimab) (240 mg, d1, ivdrip) combined with etoposide (100 mg/m², d1-d3, iv, drip) and cisplatin (25 mg/m², d1-d3, ivdrip) for advanced SCLC as first-line treatment, which has been registered on ClinicalTrials.gov under the identifier NCT04996771. The four-drug regimen was conducted q3w for 4 cycles with maintenance therapy of surufatinib and toripalimab. The primary endpoint was progression-free survival (PFS). The secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. All of the 38 patients were enrolled for safety analysis, while only 35 patients were enrolled for efficacy analysis since loss of efficacy evaluation in 3 cases after treatment. After a median follow-up of 21.3 months, the ORR was 97.1% (34/35), and the DCR and the tumor shrinkage rate were both 100% (35/35). The median PFS was 6.9 months (95% CI: 4.6 m–9.2 m) and the median OS was 21.1 months (95% CI: 12.1 m–30.1 m). The 12-month, 18-month, and 24-month OS rates were 66.94%, 51.39% and 38.54%. The occurrence rate of grade ≥3 treatment-emergent adverse events (TEAEs) was 63.2% (24/38), including neutrophil count decreased (31.6%, 12/38), white blood cell count decreased (23.7%, 9/38) and platelet count decreased (10.5%, 4/38). No unexpected adverse events occurred. This novel four-drug regimen (surufatinib, toripalimab, etoposide plus cisplatin) revealed impressive therapeutic efficacy and tolerable toxicities.

Objective Coat color is an important characteristic and economic trait in domestic sheep. In this study, we explored the potential mechanisms and the signaling pathways involved in coat color regulation for sheep. Methods Isobaric tags for relative and absolute quantification (iTRAQ) technology was used to catalog global protein expression profiles in skin of sheep with black versus white coat color. Immunofluorescence was used to observe the expression localization of differential protein. Western blot and quantitative real time polymerase chain reaction (qRT-PCR) were used to evaluate their role in the coat color formation of sheep. Results A total of 136 differential proteins were obtained in different coat colors, including 101 up-regulated and 35 down-regulated. Pigmentation function entries were enriched through gene ontology annotation. Tyrosine metabolism and platelet activation signaling pathway were extracted by Kyoto encyclopedia of genes and genomes analysis. Apolipoprotein A-1 (APOA1) and fibrinogen alpha chain (FGA) were found to be critical differential proteins by the interaction of differential proteins in the direct-interaction network diagram. Strikingly, twenty candidate differential proteins were screened, from which beta-actin (ACTB) protein showed higher expression in white sheep skin, while albumin (ALB), APOA1, MAOA (amine oxidase) and FGA proteins showed higher expression in black sheep skin, which was validated by immunofluorescence, western blot, and qRT-PCR. Conclusion This study identified several novel proteins that may be involved in the coat color formation of sheep. The white and black sheep skin proteome profiles obtained provide a valuable resource for future research to understand the network of protein expression controlling skin physiology and melanogenesis in sheep.

Fly ash exhibits volcanic ash activity and can be utilized as a cementitious material to reduce filling costs. The limited flow characteristics of mine solid waste filling slurry can impact backfill efficiency. Instead of using a large amount of cement, we employ fly ash as a cementing material to prepare filling slurries with varying air-entraining agent dosages. The results indicate that as the air-entraining agent dosage increases from 0 to 8%, the fluidity of the filling slurry improves, and the strength increases within the first 5 days of curing. The strength of the filling increases initially from 5 to 28 days of curing with the increase in air-entraining agent dosage, reaching a peak at 4% dosage, with an 11.35% higher strength compared to the filling body without the air-entraining agent. The microscopic pore structure and hydration product analysis reveal that introducing an appropriate amount of bubbles results in an even distribution of cementitious material and aggregates, improving fluidity and strength. However, excessive addition of air-entraining agents inhibits the growth of C–S–H and the filling ability of AFt for primary pores, ultimately impacting the long-term strength growth of the filling body.

In recent years, as the infectious diseases caused by pathogens such as novel coronavirus and mpox (formerly called monkeypox) spread globally, the significance of identification, preservation, and sharing of pathogenic resources become prominent. Along with the rapid development of biorepositories, it is imperative to evaluate their operation in a scientific manner. By using the literature review and modified Delphi method, this study develops a benchmarking tool for the comprehensive evaluation of the operation of biorepositories for pathogenic resources. The effective response rates of both rounds of expert surveys were 100 %. The authority coefficients (Cr) were 0.82 and 0.85, respectively, manifesting the reliability of consultation results. In the second-round survey, the Kendall’s coefficient of concordance (Kendall’s W) of all indicators ranged from 0.09 to 0.31 (P

Abstract The ability to manipulate the flux of ions across membranes is a key aspect of diverse sectors including water desalination, blood ion monitoring, purification, electrochemical energy conversion and storage. Here we illustrate the potential of using daily changes in environmental humidity as a continuous driving force for generating selective ion flux. Specifically, self-assembled membranes featuring channels composed of polycation clusters are sandwiched between two layers of ionic liquids. One ionic liquid layer is kept isolated from the ambient air, whereas the other is exposed directly to the environment. When in contact with ambient air, the device showcases its capacity to spontaneously produce ion current, with promising power density. This result stems from the moisture content difference of ionic liquid layers across the membrane caused by the ongoing process of moisture absorption/desorption, which instigates selective transmembrane ion flux. Cation flux across the polycation clusters is greatly inhibited because of intensified charge repulsion. However, anions transport across polycation clusters is amplified. Our research underscores the potential of daily cycling humidity as a reliable energy source to trigger ion current and convert it into electrical current.

Abstract Aging is associated with an increased risk of myocardial ischemia/reperfusion injury (IRI). With an increasing prevalence of cardiovascular diseases such as coronary arteriosclerosis in older people, there has been increasing interest in understanding the mechanisms of myocardial IRI to develop therapeutics that can attenuate its damaging effects. Previous studies identified that abnormal mitochondria, involved in cellar senescence and oxidative stress, are the master subcellular organelle that induces IRI. In addition, endoplasmic reticulum (ER) stress is also associated with IRI. Cellular adaptation to ER stress is achieved by the activation of ER molecular chaperones and folding enzymes, which provide an important link between ER stress and oxidative stress gene programs. In this review, we outline how these ER stress-related molecules affect myocardial IRI via the crosstalk of ER stress and mitochondrial homeostasis and discuss how these may offer promising novel therapeutic targets and strategies against age-related cardiovascular diseases.

Abstract Purpose Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials. Methods Patients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined “EBV response” as 3 consecutive timepoints of load below 50% of baseline, and “EBV progression” as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples. Results We found that the baseline EBV DNA load was positively correlated with tumor size (spearman p

PurposeCurrently, chemoimmunotherapy is effective only in a subset of patients with advanced non-squamous non-small cell lung cancer. Robust biomarkers for predicting the efficacy of chemoimmunotherapy would be useful to identify patients who would benefit from chemoimmunotherapy. The primary objective of our study was to develop an artificial intelligence-based immunoscore and to evaluate the value of patho-immunoscore in predicting clinical outcomes in patients with advanced non-squamous non-small cell lung cancer (NSCLC).MethodsWe have developed an artificial intelligence–powered immunoscore analyzer based on 1,333 whole-slide images from TCGA-LUAD. The predictive efficacy of the model was further validated in the CPTAC-LUAD cohort and the biomarker cohort of the ORIENT-11 study, a randomized, double-blind, phase 3 study. Finally, the clinical significance of the patho-immunoscore was evaluated using the ORIENT-11 study cohort.ResultsOur immunoscore analyzer achieved good accuracy in all the three cohort mentioned above (TCGA-LUAD, mean AUC: 0.783; ORIENT-11 cohort, AUC: 0.741; CPTAC-LUAD cohort, AUC: 0.769). In the 259 patients treated with chemoimmunotherapy, those with high patho-immunoscore (n = 146) showed significantly longer median progression-free survival than those with low patho-immunoscore (n = 113) (13.8 months vs 7.13 months, hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.38 – 0.73; p < 0.001). In contrast, no significant difference was observed in patients who were treated with chemotherapy only (5.07 months vs 5.07 months, HR: 1.04, 95% CI: 0.71 – 1.54; p = 0.83). Similar trends were observed in overall survival.ConclusionOur study indicates that AI-powered immunoscore applied on LUAD digital slides can serve as a biomarker for survival outcomes in patients with advanced non-squamous NSCLC who received chemoimmunotherapy. This methodology could be applied to other cancers and facilitate cancer immunotherapy.

Abstract Burley tobacco, a chlorophyll‐deficient mutant with impaired nitrogen use efficiency (NUE), generally requires three to five times more nitrogen fertilization than flue‐cured tobacco to achieve a comparable yield, which generates serious environmental pollution and negatively affects human health. Therefore, exploring the mechanisms underlying NUE is an effective measure to reduce environmental pollution and an essential direction for burley tobacco plant improvement. Physiological and genetic factors affecting tobacco NUE were identified using two tobacco genotypes with contrasting NUE in hydroponic experiments. Nitrogen use inefficient genotype (TN90) had lower nitrogen uptake and transport efficiencies, reduced leaf and root biomass, lower nitrogen assimilation and photosynthesis capacity, and lower nitrogen remobilization ability than the nitrogen use efficient genotype (K326). Transcriptomic analysis revealed that genes associated with photosynthesis, carbon fixation, and nitrogen metabolism are implicated in NUE. Three nitrate transporter genes in the leaves (NPF2.11, NPF2.13, and NPF3.1) and three nitrate transporter genes (NPF6.3, NRT2.1, and NRT2.4) in roots were down‐regulated by nitrogen starvation, all of which showed lower expression in TN90 than in K326. In addition, the protein–protein interaction (PPI) network diagram identified eight key genes (TPIP1, GAPB, HEMB, PGK3, PSBO, PSBP2, PSAG, and GLN2) that may affect NUE. Less advantageous changes in nitrogen uptake, nitrogen assimilation in combination with nitrogen remobilization, and maintenance of photosynthesis in response to nitrogen deficiency led to a lower NUE in TN90. The key genes (TPIP1, GAPB, PGK3, PSBO, PSBP2, PSAG, and GLN2) were associated with improving photosynthesis and nitrogen metabolism in tobacco plants grown under N‐deficient conditions.

Abstract The buried interface in the perovskite solar cell (PSC) has been regarded as a breakthrough to boost the power conversion efficiency and stability. However, a comprehensive manipulation of the buried interface in terms of the transport layer, buried interlayer, and perovskite layer has been largely overlooked. Herein, we propose the use of a volatile heterocyclic compound called 2‐thiopheneacetic acid (TPA) as a pre‐buried additive in the buried interface to achieve cross‐layer all‐interface defect passivation through an in situ bottom‐up infiltration diffusion strategy. TPA not only suppresses the serious interfacial nonradiative recombination losses by precisely healing the interfacial and underlying defects but also effectively enhances the quality of perovskite film and releases the residual strain of perovskite film. Owing to this versatility, TPA‐tailored CsPbBr3 PSCs deliver a record efficiency of 11.23% with enhanced long‐term stability. This breakthrough in manipulating the buried interface using TPA opens new avenues for further improving the performance and reliability of PSC.

Abstract Bile infarct is a pivotal characteristic of obstructive biliary disease, but its evolution during the disease progression remains unclear. Our objective, therefore, is to explore morphological alterations of the bile infarct in the disease course by means of multiscale X-ray phase-contrast CT. Bile duct ligation is performed in mice to mimic the obstructive biliary disease. Intact liver lobes of the mice are scanned by phase-contrast CT at various resolution scales. Phase-contrast CT clearly presents three-dimensional (3D) images of the bile infarcts down to the submicron level with good correlation with histological images. The CT data illustrates that the infarct first appears on day 1 post-BDL, while a microchannel between the infarct and hepatic sinusoids is identified, the number of which increases with the disease progression. A 3D model of hepatic acinus is proposed, in which the infarct starts around the portal veins (zone I) and gradually progresses towards the central veins (zone III) during the disease process. Multiscale phase-contrast CT offers the comprehensive analysis of the evolutionary features of the bile infarct in obstructive biliary disease. During the course of the disease, the bile infarcts develop infarct-sinusoidal microchannels and gradually occupy the whole liver, promoting the disease progression.

Abstract Background Healthy lifestyle behaviors (LBs) have been widely recommended for the prevention and management of cardiovascular disease (CVD). Despite a large number of studies exploring the association between combined LBs and CVD, a notable gap exists in integration of relevant literatures. We conducted a systematic review and meta-analysis of prospective cohort studies to analyze the correlation between combined LBs and the occurrence of CVD, as well as to estimate the risk of various health complications in individuals already diagnosed with CVD. Methods Articles published up to February 10, 2023 were sourced through PubMed, EMBASE and Web of Science. Eligible prospective cohort studies that reported the relations of combined LBs with pre-determined outcomes were included. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using either a fixed or random-effects model. Subgroup analysis, meta-regression, publication bias, and sensitivity analysis were as well performed. Results In the general population, individuals with the healthiest combination of LBs exhibited a significant risk reduction of 58% for CVD and 55% for CVD mortality. For individuals diagnosed with CVD, adherence to the healthiest combination of LBs corresponded to a significant risk reduction of 62% for CVD recurrence and 67% for all-cause mortality, when compared to those with the least-healthy combination of LBs. In the analysis of dose-response relationship, for each increment of 1 healthy LB, there was a corresponding decrease in risk of 17% for CVD and 19% for CVD mortality within the general population. Similarly, among individuals diagnosed with CVD, each additional healthy LB was associated with a risk reduction of 27% for CVD recurrence and 27% for all-cause mortality. Conclusions Adopting healthy LBs is associated with substantial risk reduction in CVD, CVD mortality, and adverse outcomes among individuals diagnosed with CVD. Rather than focusing solely on individual healthy LB, it is advisable to advocate for the adoption of multiple LBs for the prevention and management of CVD. Trial registration PROSPERO: CRD42023431731.

Abstract Background Cancer‐related pain is one of the common priority symptoms in advanced lung cancer patients at the end‐of‐life (EOL). Alleviating pain is undoubtedly a critical component of palliative care in lung cancer. Our study was initiated to examined trends in opioid prescription‐level outcomes as potential indicators of undertreated pain in China. Methods This study used data on 1330 patients diagnosed with lung cancer of urban city medical insurance in China who died between 2014 and 2017. Opioid prescription‐level outcomes were determined by annual trends of the proportion of patients filling an opioid prescription, the total dose of opioids filled by decedents, and morphine milligram equivalents per day (MMED) at the EOL (defined as the 60 days before death). We further analyzed monthly changes in the number of opioid prescriptions filled, MMED, and mean daily dose of opioids per prescription (MDDP) of the last 60 days of life by year at death and age, respectively. Results A total of 959 patients with exact dates of death were included, with 432 cases (45.06%; 95% CI: 44.36%–45.77%) receiving at least one opioid prescription at the EOL. The declining trends were shown in the proportion of patients filling any opioid prescription, the total dose of opioids filled by decedents and MMED, with an annual decrease of 0.341% (p = 0.01), 104.23 mg (p = 0.011) and 2.84 mg (p = 0.014), respectively. Within the 31–60 days to the 0–30 days of life, the MMED declined 6.08 mg (95% CI: −7.14 to −5.03; p = 0.000351), while the number of opioid prescriptions rose 0.66 (95% CI: 0.160–1.16; p = 0.025). Like the MMED, the MDDP fell 4.11 mg (95% CI: −5.86 to −2.37; p = 0.005) within the last month before death compared to the previous month. Conclusion Terminal lung cancer populations in urban China have experienced reduced access to opioids at the EOL. The clinicians did not prescribe a satisfactory dose of opioids per prescription, while the patients suffered increasing pain in the last 30 days of life. Sufficient opioid analgesic administration should be advocated for lung cancer patients during the EOL period.

Abstract Sequential immunotherapy has shown certain advantages in malignancy. Here, we aim to evaluate the efficacy of sequential anti-CTLA-4 and anti-PD-1 treatment for recurrent or metastatic nasopharyngeal carcinoma patients (R/M NPC). We retrospectively analysis 2 phase I trial of ipilimumab and camrelizumab in Chinese R/M NPC patients. These patients were initially treated with ipilimumab, a CTLA4 blockade, followed by anti-PD-1 treatment. We observed a durable tumor remission in these patients (mPFS: 12.3 months; mDoR: 20.9 months). Multimodal investigations of biopsy samples disclosed remodeling of tumor-immune microenvironment triggered by ipilimumab. In responders, we found increased tumoral PD-L1/PD-L2 expression and T-cell infiltration after ipilimumab treatment, accompanied by reduced stroma and malignant cell components. In contrast, non-responders exhibited increased B-cell infiltration and increased peripheral CD19 + B cells, suggesting a defective transition from memory B cells to plasma cells. This study proposes that sequential therapy can potentially enhance treatment efficacy in chemotherapy-resistant NPC patients and provides insights into how preexisting anti-CTLA4 blockade can influence subsequent anti-PD-1 efficacy by remodeling the TME. Additionally, our results highlight the need for therapeutic strategies targeting naïve/memory B cells.

Pullulan (PUL) is a widely used agent for electrospinning. However, nanofibers electrospun solely from PUL exhibit a highly hydrophilic nature and a bead-like structure. In this study, 1–5 wt% citrus pectin (CP) was introduced to construct a hybrid electrospinning system to investigate the effects of CP concentration on the properties of the electrospun nanofibers. The results reveal that the bead-like structure, rigidity, and hydrophobicity of the nanofibers underwent significant improvements following the introduction of CP. Furthermore, to demonstrate the protective effect of the nanofiber on astaxanthin, 0.1 wt% astaxanthin was encapsulated in the hybrid electrospinning system containing 5 wt% CP. The results show that after encapsulating astaxanthin, the rigidity of the nanofiber further increased, with a tensile strength of 12.5 MPa and a break elongation of 2.9 %. Additionally, the nanofiber system demonstrates excellent protection of the antioxidant activity of astaxanthin under UV exposure compared to free astaxanthin.

Regulated cell death (RCD) has been documented to have great potentials for discovering novel biomarkers and therapeutic targets in malignancies. But its role and clinical value in HR+/HER2- breast cancer, the most common subtype of breast cancer, are obscure. In this study, we comprehensively explored 12 types of RCD patterns and found extensive mutations and dysregulations of RCD genes in HR+/HER2- breast cancer. A prognostic RCD scoring system (CDScore) based on six critical genes (LEF1, SLC7A11, SFRP1, IGFBP6, CXCL2, STXBP1) was constructed, in which a high CDScore predicts poor prognosis. The expressions and prognostic value of LEF1 and SFRP1were also validated in our tissue microarrays. The nomogram established basing on CDScore, age and TNM stage performed satisfactory in predicting overall survival, with an area under the ROC curve of 0.89, 0.82 and 0.8 in predicting 1-year, 3-year and 5-year overall survival rates, respectively. Furthermore, CDScore was identified to be correlated with tumor microenvironments and immune checkpoints by excavation of bulk and single-cell sequencing data. Patients in CDScore high group might be resistant to standard chemotherapy and target therapy. Our results underlined the potential effects and importance of RCD in HR+/HER2- breast cancer and provided novel biomarkers and therapeutic targets for HR+/HER2- breast cancer patients.

Reliable classification results are crucial for guiding agricultural production, forecasting crop yield, and ensuring food security. Generating reliable classification results is relatively simple in regions with sufficient labeled samples, but regions with limited labeled samples remain a significant challenge. In this study, we propose two new solutions that leverage the feature representation capabilities of deep learning and the sample reuse potential of transfer learning to solve the limited label problem. Specifically, we develop a Variable-dimensional Symmetric Network with Position Encoding (VPSNet) to improve the efficiency of labeled sample utilization. Additionally, we introduce a transfer strategy based on the Inter-Regional Discrepancies in Crop Time Series (IRDCTS) to expand the labeled sample reuse region. We evaluated the proposed model in three regions with limited labels between 2017 and 2018. Experimental results show that our model has superior discriminative feature extraction capabilities compared to other existing models. The feasibility of the proposed transfer strategy is tested in three pair regions, showing that IRDCTS can enhance the model adaptability by reducing inter-domain discrepancies. This study provides a comprehensive solution to the classification problem of the limited labeled samples, involving both the development of classification models and the implementation of transfer strategies.

ABSTRACTHigh-quality samples for training and validation are crucial for land cover classification, especially in some complex scenarios. The reliability, representativeness, and generalizability of the sample set are important for further researches. However, manual interpretation is subjective and prone to errors. Therefore, this study investigated the following questions: (1) How much difference is there in the interpreters’ performance across educational levels? (2) Do the accuracies of human and AI (Artificial Intelligence) improve with increased training and supporting material? (3) How sensitive are the accuracies of land cover types to different supporting material? (4) Does interpretation accuracy change with interpreters’ consistency? The experiment involved 50 interpreters completing five cycles of manual image interpretation. Higher educational background interpreters showed better performance: accuracies pre-training at 52.22% and 58.61%, post-training at 61.13% and 70.21%. Accuracy generally increased with more supporting material. Ultra-high-resolution images and background knowledge contributed the most to accuracy improvement, while the time series of normalized difference vegetation index (NDVI) contributed the least. Group consistency was a reliable indicator of volunteer sample reliability. In the case of limited samples, AI was not as good as manual interpretation. To ensure quality in samples through manual interpretation, we recommend inviting educated volunteers, providing training, preparing effective support material, and filtering based on group consistency.

ABSTRACTContinuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enhanced transmissibility, significant immune escape, and waning immunity call for booster vaccination. We evaluated the safety, immunogenicity, and efficacy of heterologous booster with a SARS-CoV-2 mRNA vaccine SYS6006 versus an active control vaccine in a randomized, open-label, active-controlled phase 3 trial in healthy adults aged 18 years or more who had received two or three doses of SARS-CoV-2 inactivated vaccine in China. The trial started in December 2022 and lasted for 6 months. The participants were randomized (overall ratio: 3:1) to receive one dose of SYS6006 (N = 2999) or an ancestral receptor binding region-based, alum-adjuvanted recombinant protein SARS-CoV-2 vaccine (N = 1000), including 520 participants in an immunogenicity subgroup. SYS6006 boosting showed good safety profiles with most AEs being grade 1 or 2, and induced robust wild-type and Omicron BA.5 neutralizing antibody response on Days 14 and 28, demonstrating immunogenicity superiority versus the control vaccine and meeting the primary objective. The relative vaccine efficacy against COVID-19 of any severity was 51.6% (95% CI, 35.5–63.7) for any variant, 66.8% (48.6–78.5) for BA.5, and 37.7% (2.4–60.3) for XBB, from Day 7 through Month 6. In the vaccinated and infected hybrid immune participants, the relative vaccine efficacy was 68.4% (31.1–85.5) against COVID-19 of any severity caused by a second infection. All COVID-19 cases were mild. SYS6006 heterologous boosting demonstrated good safety, superior immunogenicity and high efficacy against BA.5-associated COVID-19, and protected against XBB-associated COVID-19, particularly in the hybrid immune population.Trial registration: Chinese Clinical Trial Registry: ChiCTR2200066941

Abstract Active oxygen highly affects the efficiency and stability of perovskite solar cells (PSCs) owing to the capacity to either passivate defects or decompose perovskite lattice. To better understand the in‐depth interaction, we demonstrate for the first time that photooxidation mechanism in all‐inorganic perovskite film dominates the phase deterioration kinetics by forming superoxide species in the presence of light and oxygen, which is significantly different from that in organic‒inorganic hybrid and even tin‐based perovskites. In all‐inorganic perovskites, the superoxide species prefer to oxidize longer and weaker Pb‒I bond to PbO and I2, leaving the much stable CsPbBr3 phase. From this chemical proof‐of‐concept, we employ an organic bioactive factor, Tanshinone IIA, as a superoxide sweeper to enhance the environmental tolerance of inorganic perovskite, serving as a “skincare” agent for anti‐aging organisms. Combined with another key point on healing defective lattice, the best carbon‐based all‐inorganic CsPbI2Br solar cell delivers an efficiency as high as 15.12% and superior stability against oxygen, light, humidity, and heat attacks. This method is also applicable to enhance the efficiency of p‒i‒n inverted (Cs0.05MA0.05FA0.9)Pb(I0.93Br0.07)3 cell to 23.46%. These findings not only help us understand the perovskite decomposition mechanisms in depth but also provide a potential strategy for advanced PSC platforms.

Background and aims: Tumor recurrence significantly affects the prognostic outcomes for liver cancer patients following liver transplantation. However, existing predictive models often neglect the inclusion of body composition indicators. Hence, this research aimed to investigate the significance of the psoas muscle index (PMI) in evaluating the post-transplant prognosis of liver cancer. Methods: A retrospective analysis was conducted on liver cancer patients who underwent liver transplantation surgery. Imaging analysis was performed using CT data to calculate PMI based on the left and right psoas muscle areas. Subsequently, the patients were categorized into PMI-Low and PMI-High groups using the established cut-off values. Univariate and multivariate analyses were performed using Cox proportional hazards regression to assess the correlation between PMI and clinical outcomes, and a nomogram was constructed accordingly. Results: Among the 225 patients included in the analysis, the PMI-High group exhibited significantly improved overall survival (P

IntroductionSleep loss and sleep deprivation (SD) cause deleterious influences on health, cognition, mood and behaviour. Nevertheless, insufficient sleep and SD are prevalent across many industries and occur in various emergencies. The deleterious consequences of SD have yet to be fully elucidated. This study aimed to assess the extensive influences of SD on physiology, vigilance, and plasma biochemical variables.MethodsSeventeen volunteers were recruited to participate in a 32.5-h SD experiment. Multiple physiological and cognitive variables, including tympanic temperature, blood oxygen saturation (SaO2), and vigilance were recorded. Urinal/salivary samples were collected and subjected to cortisol or cortisone analysis, and plasma samples were subjected to transcriptomic analysis of circular RNA (circRNA) expression using microarray. Plasma neurotransmitters were measured by targeted metabolic analysis, and the levels of inflammatory factors were assessed by antibody microarray.ResultsThe volunteers showed significantly increased sleepiness and decreased vigilance during SD, and the changes in circadian rhythm and plasma biochemistry were observed. The plasma calcium (p = 0.0007) was induced by SD, while ischaemia-modified albumin (IMA, p = 0.0030) and total bile acid (TBA, p = 0.0157) decreased. Differentially expressed circRNAs in plasma were identified, which are involved in multiple signaling pathways including neuronal regulation and immunity. Accordingly, SD induced a decrease in 3-hydroxybutyric acid (3OBH, p = 0.0002) and an increase in thyroxine (T4, p

Clusters, an aggregation of several to thousands of atoms, molecules, or ions, are the building blocks of novel functional materials by atomic manufacturing and exhibit excellent applications in catalysis, quantum information, and nanomedicine. The evolution of cluster structures has been studied for many years. Many effective structural search methods, such as genetic algorithm, basin‐hopping, and so on, have been developed. However, the efficient execution of these methods relies on precise energy calculators, such as density functional theory (DFT) calculations. Up to now, limited by computational methods and capabilities, the researches mainly focus on free‐standing clusters, which are different from clusters in practical applications. Recently, the rapid development of big data‐driven machine learning is expected to replace DFT for high‐precision large‐scale computing. In this review, the present cluster search methods and challenges currently faced have been summarized. It is proposed that the development of artificial intelligence has the potential to solve some practical problems including the structural and properties evolution of clusters in complex environment, causing revolutionary developments in the fields of catalysis, quantum information, and nanomedicine based on clusters.

Abstract Suppressing nonradiative recombination and releasing residual strain are prerequisites to improving the efficiency and stability of perovskite solar cells (PSCs). Here, long‐chain polyacrylic acid (PAA) is used to reinforce SnO2 film and passivate SnO2 defects, forming a structure similar to “reinforced concrete” with high tensile strength and fewer microcracks. Simultaneously, PAA is also introduced to the SnO2/perovskite interface as a “buffer spring” to release residual strain, which also acts as a “dual‐side passivation interlayer” to passivate the oxygen vacancies of SnO2 and Pb dangling bonds in halide perovskites. As a result, the best inorganic CsPbBr3 PSC achieves a champion power conversion efficiency of 10.83% with an ultrahigh open‐circuit voltage of 1.674 V. The unencapsulated PSC shows excellent stability under 80% relative humidity and 80°C over 120 days.

Abstract Messenger RNA (mRNA) cancer vaccines are a new class of immunotherapies that can activate the immune system to recognize and destroy cancer cells. However, their effectiveness in treating colorectal cancer located on the mucosal surface of the gut is limited due to the insufficient activation of mucosal immune response and inadequate infiltration of cytotoxic T cells into tumors. To address this issue, a new mRNA cancer vaccine is developed that can stimulate mucosal immune responses in the gut by co‐delivering all‐trans‐retinoic acid (ATRA) and mRNA using lipid nanoparticle (LNP). The incorporation of ATRA has not only improved the mRNA transfection efficiency of LNP but also induced high expression of gut‐homing receptors on vaccine‐activated T cells. Additionally, the use of LNP improves the aqueous solubility of ATRA, eliminating the need for toxic solvents to administer ATRA. Upon intramuscular injections, ATRA‐adjuvanted mRNA‐LNP significantly increase the infiltration of antigen‐specific, cytotoxic T cells in the lamina propria of the intestine, mesenteric lymph nodes, and orthotopic colorectal tumors, resulting in significantly improved tumor inhibition and prolonged animal survival compared to conventional mRNA‐LNP without ATRA. Overall, this study provides a promising approach for improving the therapeutic efficacy of mRNA cancer vaccines against colorectal cancer.

Radish (Raphanus sativus L.) undergoes texture changes in their phy-chemical properties during the long-term dry-salting process. In our study, we found that during the 60-day salting period, the hardness and crispness of radish decreased significantly. In further investigation, we observed that the collaborative action of pectin methylesterase (PME) and polygalacturonase (PG) significantly decreased the total pectin, alkali-soluble pectin (ASP), and chelator-soluble pectin (CSP) content, while increasing the water-soluble pectin (WSP) content. Furthermore, the elevated activities of cellulase and hemicellulase directly led to the notable fragmentation of cellulose and hemicellulose. The above reactions jointly induced the depolymerization and degradation of cell wall polysaccharides, resulting in an enlargement of intercellular spaces and shrinkage of the cell wall, which ultimately led to a reduction in the hardness and crispness of the salted radish. This study provided key insights and guidance for better maintaining textural properties during the dry-salting process of radish.

As global economic growth increases, the demand for energy sources boosts. While fossil fuels have traditionally satisfied this demand, their environmental influence and limited reserves require alternatives. Fossil fuel combustion contributes substantially to greenhouse gas emissions, with a pressing need to halve these emissions by 2030 and target net-zero by 2050. Renewable energy sources, contributing currently to 29% of global electricity, are viewed as promising substitutes. With wind energy's potential, Zheng's team developed a novel method to harness even low wind speeds using well-aligned nanofibers and an innovative “drop wind generator”. This system, combining moisture-saturated ionic liquid 3-Methyl-1-octylimidazolium chloride with specific nanofiber arrays, exploits wind-induced flows for energy conversion. This study highlights the vast untapped potential of low-speed wind as a sustainable energy source potentially for electronics.

In response to the problems of high nonlinearity and dimensionality of existing underwater glider models, as well as difficulty in designing effective engineering controllers, the composition and working principle of the motion mechanism of underwater gliders were first studied. By neglecting secondary influencing factors in the modeling process, lightweight modeling of underwater gliders was conducted to reduce model nonlinearity and complexity. The effectiveness of the lightweight model was demonstrated through comparative verification. Subsequently, according to the motion in the vertical plane, the dynamic equation was further simplified, and the advantages of low dimension and small calculation amount of the model were brought into play. The actual constraints of state and control variables were introduced, and a realistic predictive attitude control algorithm for a real-time linearized model was designed. The numerical simulation results show that under the two common working conditions of ±17.4° and ±22.5° for underwater gliders, the control algorithm based on the lightweight model proposed in this paper can quickly track the desired attitude, and the rise time and steady-state settling time are improved by more than 70% compared with traditional controllers.

In order to improve the ability of bad data identification and fault location accuracy in power system risk control, a new risk control method for power systems using embedded technology was designed.S3C2440 chip was used as the central processing unit, the phasor measurement unit (PMU) technology was used to identify bad data in the power system, improving the efficiency of identification.Improved on the basis of traditional multiverse algorithms, fault localization was based on data collected by PMU, effectively improving the accuracy of fault localization.In the simulation experiment, the efficiency of identifying bad data by the proposed method has been improved by at least 33.76%, the accuracy of fault localization has been improved by 26.33%, and the efficiency has been improved by at least 43.4%.The proposed method has good risk control capabilities in the power system.

Abstract Covalent probes coupled with chemical proteomics represent a powerful method for investigating small molecule and protein interactions. However, the creation of a reactive warhead within various ligands to form covalent probes has been a major obstacle. Herein, we report a convenient and robust process to assemble a unique electrophile, an α-acyloxyenamide, through a one-step late-stage coupling reaction. This procedure demonstrates remarkable tolerance towards other functional groups and facilitates ligand-directed labeling in proteins of interest. The reactive group has been successfully incorporated into a clinical drug targeting the EGFR L858R mutant, erlotinib, and a pan-kinase inhibitor. The resulting probes have been shown to be able to covalently engage a lysine residue proximal to the ATP-binding pocket of the EGFR L858R mutant. A series of active sites, and Mg2+, ATP-binding sites of kinases, such as K33 of CDK1, CDK2, CDK5 were detected. This is the first report of engaging these conserved catalytic lysine residues in kinases with covalent inhibition. Further application of this methodology to natural products has demonstrated its success in profiling ligandable conserved lysine residues in whole proteome. These findings offer insights for the development of new targeted covalent inhibitors (TCIs).

With the rapid advancement of electrified high-speed railways, electromagnetic exposure within train carriages has become a subject of growing concern. To evaluate the electromagnetic safety of passengers during bow network arcing events, this study utilizes numerical simulation tools to model the train’s traction power supply system and simulate the voltage fluctuations in the contact network during arcing events. The simulations reveal a maximum voltage fluctuation of 30 kV. Subsequently, a three-dimensional electromagnetic environment model of passengers in the CR400AF-type train compartments is constructed using specialized simulation software. The study focuses on analyzing the magnetic field strength, electric field strength, and current density distribution, specifically in the brain region of passengers. The results indicate that the maximum values of magnetic induction, induced electric field strength, and induced current density in the passengers’ brains are $7.55~\mu $ T, 0.90 mV/m, and $831.2~\mu $ A/m2, respectively—values that are well below the exposure limits set by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) for industrial-frequency electromagnetic fields. Additionally, the study demonstrates that the intermediate-frequency magnetic field generated by the contact network fluctuations due to bow network arcing is effectively shielded by the aluminum alloy body of the train, further mitigating the risk of electromagnetic exposure. These findings suggest that electromagnetic field (EMF) exposure in CR400AF rolling stock caused by contact network fluctuations during bow network arcing does not pose a significant health risk to passengers, providing valuable insights for the assessment of EMF safety in high-speed rail systems.

Abstract First-line chemoimmunotherapy (with or without bevacizumab) has improved outcomes in advanced non-small cell lung cancer (NSCLC). Here, this open-label, multi-cohort phase II study (NCT05329025) was done to investigate the safety and efficacy of QL1706 (a single bifunctional MabPair product against PD-1 and CTLA-4) and chemotherapy with or without bevacizumab in this population. Patients were enrolled into five different cohorts based on genotype (cohorts 1-4, epidermal growth factor receptor [EGFR] wild-type; cohort 5, EGFR-mutant and progressed on EGFR-tyrosine kinase inhibitors [TKIs]). Between June 11, 2021 and December 29, 2021, 91 patients were enrolled. Most frequent treatment-related adverse events (TRAEs) included decreased appetite (60 [65.9%]), anemia (60 [65.9%]), infusion-related reactions (48 [52.7%]), and pruritus (44 [48.4%]). Grade ≥ 3 TRAEs occurred in 30 (33.0%) patients. Twenty-seven (45%) patients with wild-type EGFR achieved partial response (PR) (objective response rate [ORR] = 45%) and had a median progression-free survival (mPFS) of 6.8 months (95% CI: 5.2-9.7). For 31 patients harboring mutated EGFR, 17 (54.8%) achieved PR (ORR = 54.8%), with an mPFS of 8.5 months (95% CI: 5.72-not evaluable). Overall, QL1706 plus chemotherapy, regardless of having bevacizumab, was generally tolerable and had promising antitumor activity for EGFR wild-type advanced NSCLC in first-line setting. Moreover, QL1706 plus chemotherapy and bevacizumab showed favorable antitumor activity for patients who had EGFR mutated NSCLC but failed in TKI therapy, demonstrating a potential for treating this population.

Abstract Background Smart nursing homes (SNHs) integrate advanced technologies, including IoT, digital health, big data, AI, and cloud computing to optimise remote clinical services, monitor abnormal events, enhance decision-making, and support daily activities for older residents, ensuring overall well-being in a safe and cost-effective environment. This study developed and validated a 24-item Expectation and Acceptability of Smart Nursing Homes Questionnaire (EASNH-Q), and examined the levels of expectations and acceptability of SNHs and associated factors among older adults in China. Methods This was an exploratory sequential mixed methods study, where the qualitative case study was conducted in Hainan and Dalian, while the survey was conducted in Xi’an, Nanjing, Shenyang, and Xiamen. The validation of EASNH-Q also included exploratory and confirmatory factor analyses. Multinomial logistic regression analysis was used to estimate the determinants of expectations and acceptability of SNHs. Results The newly developed EASNH-Q uses a Likert Scale ranging from 1 (strongly disagree) to 5 (strongly agree), and underwent validation and refinement from 49 items to the final 24 items. The content validity indices for relevance, comprehensibility, and comprehensiveness were all above 0.95. The expectations and acceptability of SNHs exhibited a strong correlation (r = 0.85, p

Protein‐based therapeutics and vaccines play a pivotal role in the realm of biomedical science. Pulmonary administration offers several advantages including rapid adsorption, non‐invasive, increased local drug concentration, and bypassed first‐pass metabolism, thus holding great potential to address multiple unmet medical needs in lung‐related diseases and vaccination. However, the limited success of inhaled proteins in clinical settings highlights the challenges associated with protein stability and the physiological barriers within the respiratory system. To overcome these hurdles, a variety of delivery systems including polymers, liposomes, cell‐derived membranes, and inorganic materials are developed to improve the stability, mucus penetration, retention time, and bioavailability of proteins. With the outbreak of COVID‐19, the pulmonary administration of proteins has drawn great attention. In this review, the design principle, preparation, biomedical application, progress in clinical translation, advantages, and disadvantages of each kind of delivery system are summarized, with an emphasis on carrier materials.

In order to investigate the effects of different drying methods on the properties of porous starch. The present study used four drying methods, namely hot air drying (HD), spray drying (SPD), vacuum freeze drying (FD) and supercritical carbon dioxide drying (SCD) to prepare maize and kudzu porous starch. Findings indicated that the physicochemical properties (e.g., morphology, crystallinity, enthalpy value, porosity, surface area and water absorption capacity as well as dye absorption capacity, particle size) of porous starch were significantly affected by the drying method. Compared with other samples, SCD-treated porous starch exhibited the highest surface areas of the starch (2.943 and 3.139 m2/g corresponding to kudzu and maize, respectively), amylose content (22.02 % and 16.85 % corresponding to kudzu and maize, respectively), MB and NR absorption capacity (90.63 %, 100.26 % and 90.63 %, 100.26 %, corresponding to kudzu ad maize, respectively), and thermal stability, whereas HD-treated porous starch showed the highest water-absorption capacity (123.8 % and 131.31 % corresponding to kudzu and maize, respectively). The dye absorption of the maize and kudzu porous starch was positively correlated with surface area, according to Pearson's correlation analysis. Therefore, in this study, our aim was to explore the effects of different drying methods on the Structure and properties of porous starch, and provide reference for selecting the best drying method for its application in different fields.

Abstract There remains an unmet need for targeted therapies against advanced non‐small‐cell lung cancer (NSCLC) with HER2 mutations. To improve the antitumor activity of single anti‐HER2 agent, this prospective, single‐arm clinical trial (NCT05016544) examined the safety profile and efficacy of anti‐HER2 antibody inetetamab and pan‐HER TKI pyrotinib in HER2‐posivite advanced NSCLC patients. Enrolled patients received inetetamab every 3 weeks and pyrotinib once per day (pyrotinib, dose‐escalation part, 240 mg, 320 mg; dose‐expansion part, 320 mg). Primary endpoints were dose‐limiting toxicity (DLT) dosage and safety. Secondary endpoints included progression‐free survival (PFS), objective response rate (ORR), and disease control rate (DCR). A total of 48 patients were enrolled. During the dose‐escalation period, no DLT occurred. Diarrhea was the most commonly reported treatment‐related adverse event (TRAE). Grade 3 TRAEs occurred in seven patients. The median PFS (mPFS) was 5.5 months [95% confidence interval (CI): 4.4–8.6 months]. The confirmed ORR and DCR reached 25% (11/44) and 84.1% (37/44), respectively. Responses were shown in patients with distinct HER2 aberrations. In summary, inetetamab in combination with pyrotinib demonstrated acceptable safety and antitumor activity among patients with advanced HER2‐mutant NSCLC.

Background: Intestinal metaplasia (IM) of gastric epithelium has traditionally been regarded as an irreversible stage in the process of the Correa cascade. Exploring the potential molecular mechanism of IM is significant for effective gastric cancer prevention. Methods: The GSE78523 dataset, obtained from the Gene Expression Omnibus (GEO) database, was analyzed using RStudio software to identify the differently expressed genes (DEGs) between IM tissues and normal gastric epithelial tissues. Subsequently, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GESA), and protein-protein interaction (PPI) analysis were used to find potential genes. Additionally, the screened genes were analyzed for clinical, immunological, and genetic correlation aspects using single gene clinical correlation analysis (UALCAN), Tumor–Immune System Interactions Database (TISIDB), and validated through western blot experiments. Results: Enrichment analysis showed that the lipid metabolic pathway was significantly associated with IM tissues and the apolipoprotein B ( APOB ) gene was identified in the subsequent analysis. Experiment results and correlation analysis showed that the expression of APOB was higher in IM tissues than in normal tissues. This elevated expression of APOB was also found to be associated with the expression levels of hepatocyte nuclear factor 4A ( HNF4A ) gene. HNF4A was also found to be associated with immune cell infiltration to gastric cancer and was linked to the prognosis of gastric cancer patients. Moreover, HNF4A was also highly expressed in both IM tissues and gastric cancer cells. Conclusion: Our findings indicate that HNF4A regulates the microenvironment of lipid metabolism in IM tissues by targeting APOB . Higher expression of HNF4A tends to lead to a worse prognosis in gastric cancer patients implying it may serve as a predictive indicator for the progression from IM to gastric cancer.

Gastric-type endocervical adenocarcinoma (G-EAC) represents a rare variant of cervical mucinous adenocarcinoma that is typically unrelated to human papillomavirus (HPV) infection. G-EAC exhibits highly atypical clinical presentations and characteristics, and aggressive biological behavior often leads to challenges in timely diagnosis. Here, we present a case study involving a 74-year-old Chinese woman who experienced urinary incontinence for one month. Biopsy pathology confirmed the diagnosis of G-EAC, revealing stage IVa by imaging examinations. The patient subsequently underwent three cycles of chemotherapy, followed by adjuvant radiotherapy and surgical excision of residual tumor foci. This comprehensive treatment approach yielded a favorable survival outcome. For patients with advanced G-EAC, a multimodal therapeutic approach holds promise and warrants further exploration.

PurposesDomestic and international research has found that patients with advanced cancer prioritize increasing their quality of life above extending their lives with simple or intensive treatments. The current study investigates the pathways to improve patients’ sense of well-being from the family, social, and individual levels, that is to say, it investigates the mediating roles of comprehending social support as well as psychological resilience in the relationship between family resilience and subjective well-being, and it also provides references for future intervention.MethodThe Family Resilience Questionnaire (FRQ), General Well-being Schedule (GWB), Perceived Social Support Scale (PSSS), and the Chinese version of the Cornor-Davidson Resilience Scale 10-item (CD-RISC) were all completed by 338 patients with advanced cancer who took part in the study.ResultsThe study’s findings demonstrated a significant and positive correlation between family resilience, subjective well-being, perceived social support, and psychological resilience. Additionally, there was a significant direct effect of family resilience on subjective well-being as well as a mediating and chain mediating effect between perceived social support and psychological resilience. The findings of this study will be very helpful in the future when it comes to enhancing the quality of life for patients with advanced cancer through intervention.ConclusionSubjective well-being can be influenced directly by the family resilience of advanced cancer patients, or indirectly through the psychological resilience and perceived social support.

IntroductionSalmonella is a major foodborne pathogen worldwide that causes severe morbidity and mortality. It is mainly caused by consuming contaminated food, with retail food considered the primary source.MethodsIn Guizhou, China, 102 Salmonella strains isolated from 2016 to 2021 underwent phenotypic antimicrobial resistance testing and whole-genome sequencing (WGS) to understand Salmonella diversity, including serotypes, sequencing types (STs), antimicrobial genes, virulence genes, plasmid types, multi-locus sequence types (MLST), and core genome MLST (cgMLST).Results and discussionS.Typhimurium was the dominant serotype, and O:4(B) was the leading serogroup. The most prevalent genotype was ST40. Phenotypic antimicrobial resistance identified 66.7% of the sampled isolates as multi-drug resistant (MDR). S.Enteritidis (n = 7), S.Typhimurium (n = 1), S.Indiana (n = 1), S.Kentucky (n = 1), S.Uganda (n = 1), all of which were MDR, were resistant to Colistin. Resistance rates varied significantly across different strains and food types, particularly meat products exhibiting higher resistance. Notably, significant increases in resistance were observed from 2016 to 2021 for the following: ≥ 1 resistant (P = 0.001), MDR (P = 0.001), ampicillin (P = 0.001), tetracycline (P

Summary: Purpose: This study aims to explore the expectations and acceptability of a smart nursing home model among Chinese older adults and their family members based on a scoping review that defines the concept of smart nursing homes. Methods: A qualitative case study was employed for this research. Semi-structured, in-depth interviews and focus group discussions were conducted on WeChat. Participants were purposively sampled through snowball sampling in Hainan and Dalian, China. A total of 28 older adults aged 60–75 and six adult children were interviewed until data saturation was achieved, followed by a thematic analysis. Results: The expectations of smart nursing homes include: 1) quality of care supported by governments and societies; 2) smart technology applications; 3) the presence of a skilled healthcare professional team; 4) access to and scope of basic medical services; and 5) integration of medical services. The acceptability of smart nursing homes included factors such as stakeholders’ perceived efficaciousness, usability, and collateral damages of using smart technologies, and the coping process of adoption was influenced by factors such as age, economic status, health status, education, and openness to smart technologies among older adults. Conclusions: Chinese older adults and their family members have a positive perception of the smart nursing home model. The qualitative evidence regarding their expectations and acceptability of smart nursing homes contributes valuable insights for a wide range of stakeholders involved in the planning and implementation of smart nursing homes.

The study of estimating rapeseed above-ground biomass (AGB) is of significant importance, as it can reflect the growth status of crops, enhance the commercial value of crops, promote the development of modern agriculture, and predict yield. Previous studies have mostly estimated crop AGB by extracting spectral indices from spectral images. This study aims to construct a model for estimating rapeseed AGB by combining spectral and LiDAR data. This study incorporates LiDAR data into the spectral data to construct a regression model. Models are separately constructed for the overall rapeseed varieties, nitrogen application, and planting density to find the optimal method for estimating rapeseed AGB. The results show that the R² for all samples in the study reached above 0.56, with the highest overall R² being 0.69. The highest R² for QY01 and ZY03 varieties was 0.56 and 0.78, respectively. Under high- and low-nitrogen conditions, the highest R² was 0.64 and 0.67, respectively. At a planting density of 36,000 plants per mu, the highest R² was 0.81. This study has improved the accuracy of estimating rapeseed AGB.

Objective(s): Hyperandrogenism is a key pathological characteristic of polycystic ovary syndrome (PCOS). Tumor necrosis factor α (TNF-α) is both an adipokine and a chronic inflammatory factor, which has been proven to be involved in the pathologic process of PCOS. This study aimed to determine how TNF-α affects glucose uptake in human granulosa cells in the presence of high testosterone concentration. Materials and Methods: KGN cell line was treated with testosterone and TNF-α alone or co-culture combination for 24 hr, or starved for 24 hr. Quantitative real-time polymerase chain reaction (qPCR) and western blot were performed to measure glucose transporter type 4 (GLUT4) message RNA (mRNA) and protein expression in treated KGN cells. Glucose uptake and GLUT4 expression were detected by immunofluorescence (IF). Furthermore, western blot was performed to measure the contents in the nuclear factor kappa-B (NF-κB) pathway. Meantime, upon addition of TNF-α receptor II (TNFRII) inhibitor or Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) antagonist to block the TNFRII-IKKβ-NF-κB signaling pathway, the glucose uptake in KGN cells and GLUT4 translocation to cytomembrane were detected by IF, and related proteins in TNFRII-IKKβ-NF-κB were detected by western blot.Results: The glucose uptake in Testosterone + TNF-α group was lowered significantly, and Total GLUT4 mRNA and proteins were reduced significantly. GLUT4 translocation to cytomembrane was tarnished visibly; concurrently, the phosphorylated proteins in the TNFRII-IKKβ-NF-κB signaling pathway were enhanced significantly. Furthermore, upon addition of TNFRII inhibitor or IKKβ inhibitor to block the TNFRII-IKKβ-NF-κB signaling pathway, the glucose uptake of treated granulosa cells was improved. Conclusion: TNFRII and IKKβ antagonists may improve glucose uptake in granulosa cells induced by TNF-α by blocking the TNFRII-IKKβ-NF-κB signaling pathway under high androgen conditions.