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Objective: CDK4/6 inhibitors (CDK4/6is) in combination with endocrine therapy have secured a central role in the treatment of hormone receptor (HR)-positive advanced breast cancer (ABC) and have transformed the therapeutic landscape. Cross-line CDK4/6i therapy in which another CDK4/6i is continued after progression on a prior CDK4/6i may still offer advantageous therapeutic effects. Cross-line CDK4/6i therapy is an area of active investigation in the ongoing pursuit to improve outcomes for patients with HR+/human epidermal growth factor receptor 2 (HER2)– ABC. Methods: This retrospective study enrolled 82 patients with HR+/HER2– ABC who were treated with cross-line CDK4/6is (abemaciclib, palbociclib, ribociclib, and dalpiciclib) after progression with another CDK4/6i. The primary endpoint was progression-free survival (PFS) according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included toxicity, objective response rate, disease control rate, and overall survival. Adverse events (AEs) were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events, as promulgated by the U.S. Department of Health and Human Services. Results: Eighty-two HR+/HER2– ABC patients who received cross-line CDK4/6i therapy from January 2022 to February 2024 were enrolled. The median age of the patients was 60 years. The median PFS of all patients was 7.6 months (95% CI, 5.9-9.2). Cox regression analysis identified lung metastasis and a switch to endocrine therapy following prior CDK4/6i therapy as independent predictive factors for PFS. Notably, patients who previously received abemaciclib and switched to palbociclib upon disease progression had a median PFS of 10.7 months. The strategy of transitioning to chemotherapy after progression on a prior CDK4/6i, then to a subsequent CDK4/6i merits further investigation. Hematologic toxicity was the most common grade ≥ 3 AEs. No instances of fatal safety events were observed. Conclusions: Cross-line CDK4/6i therapy is associated with significant clinical benefits and manageable safety profiles in patients with HR+/HER2– ABC, which underscores cross-line CDK4/6i therapy potential as an effective treatment strategy.

Abstract This study aimed to analyze the molecular characteristics of insulin-like growth factor 1 (IGF1) gene in the testes of Tibetan sheep and its role in the testosterone synthesis and cell development. First, we cloned IGF1 gene for bioinformatics analysis, and the primary Leydig cells (LCs) of Tibetan sheep were isolated to explore its effect on the proliferation, apoptosis and function of LCs. Finally, the specific regulatory mechanism of IGF1 on LCs was analyzed by transcriptome sequencing. Results showed that overexpression of IGF1 increased the proliferation rate and decreased apoptosis of LCs. In addition, overexpression of IGF1 altered expression of genes related to testosterone synthesis and transformation and significantly increased amount of the final product testosterone. Mechanistically, IGF1 stimulated the expression of the proliferating cell nuclear antigen and IGF1R and promoted the proliferation of LCs via the PI3K/Akt signaling pathway. Collectively, what should be clear from the results reported here is that IGF1 might play roles in the proliferation or differentiation and testosterone synthesis of LCs. These findings add to our understanding on the regulation of testosterone synthesis in sheep and other mammals.

Abstract Background Although de novo metastatic breast cancer (dnMBC) is acknowledged as a heterogeneous disease, the current staging systems do not distinguish between patients within the M1 or stage IV category. This study aimed to refine the M1 category and prognostic staging for dnMBC to enhance prognosis prediction and guide the choice of locoregional treatment. Methods We selected patients with dnMBC from the SEER database (2010–2019), grouping them into training (N = 8048) and internal validation (N = 3450) cohorts randomly at a 7:3 ratio. An independent external validation cohort (N = 660) was enrolled from dnMBC patients (2010–2023) treated in three hospitals. Nomogram‐based risk stratification was employed to refine the M1 category and prognostic stage, incorporating T/N stage, histologic grade, subtypes, and the location and number of metastatic sites. Both internal and external validation sets were used for validation analyses. Results Brain, liver, or lung involvement and multiple metastases were independent prognostic factors for overall survival (OS). The nomogram‐based stratification effectively divided M1 stage into three groups: M1a (bone‐only involvement), M1b (liver or lung involvement only, with or without bone metastases), and M1c (brain metastasis or involvement of both liver and lung, regardless of other metastatic sites). Only subtype and M1 stage were included to define the final prognostic stage. Significant differences in OS were observed across M1 and prognostic subgroups. Patients with the M1c stage benefited less from primary tumor surgery in comparison with M1a stage. Conclusion Subdivision of the M1 and prognostic stage could serve as a supplement to the current staging guidelines for dnMBC and guide locoregional treatment.

Abstract Background Exploration of novel combination mode of pyrotinib and chemotherapy for heavily pretreated HER2-positive metastatic breast cancer (MBC) and how to balance survival benefits and compliance are still urgent problems in clinical practice. The current single-arm prospective phase II study aimed to evaluate the efficacy and safety of pyrotinib in combination with metronomic oral etoposide in heavily pretreated HER2-positive MBC. Methods HER2-positive MBC patients previously treated with trastuzumab were enrolled to receive oral pyrotinib 400 mg per day and metronomic oral etoposide 50 mg per day d1-21 every 28 days, until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), and safety. Results 22 patients were enrolled with a median of 4 prior treatment regimens for MBC. During the follow-up of 20 evaluable patients, the median PFS was 9.0 months (95% CI, 7.6–10.4 months), and the median OS was 27.0 months (95%CI, 20.9–33.1 months). The ORR was 30% (6/20), the DCR was 80% (16/20), and the CBR was 65% (13/20). The most common grade 3 adverse events (AEs) included nausea (15%), vomiting (15%), diarrhea (5%), anemia (5%), and peripheral neuropathy (5%). No grade 4 or lethal AEs were observed. Conclusion The combination of pyrotinib with metronomic oral etoposide has achieved promising clinical benefits in heavily pretreated HER2-positive MBC, with acceptable and manageable toxicity. Trial registration Registry number: NCT03923179. Registered April 18, 2019.

This study synthesized hawthorn polyphenol microparticles (HPM) based on the polyelectrolyte self-assembly technology. Plackett-burman combined with Box-Behnken design was used to study the factors affecting the preparation of HPM in response to the encapsulation efficiency and drug loading of hawthorn polyphenols. The Plackett-Burman design was used to screen for factors that significantly affect the outcomes, such as preparation time, sulfuric acid concentration, and the ratio of encapsulating materials, which were optimized through Box-Behnken response surface methodology. The morphology of HPM was examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and their gastrointestinal release kinetics were assessed using simulated gastric and intestinal fluids. The results indicated that the preparation time, sulfuric acid concentration, and the ratio of encapsulating materials significantly effect the fabrication of HPM. An encapsulation efficiency of 96.27%±1.37% was achieved with a preparation time of 3 h, a sulfuric acid concentration of 0.0254%, and a 4:1 ratio of chitosan to sodium alginate. Morphological analysis of HPM revealed irregularly shaped, well-dispersed spherical particles. The release rate of HPM in simulated intestinal fluid was higher than in gastric fluid, with the release kinetics corresponding to zero-order in gastric fluid and first-order in intestinal fluid. In summary, this study successfully produced HPM with a high encapsulation efficiency, substantial drug loading, and good dispersion. The HPM formulated could reduce the degradation of hawthorn polyphenols in the gastrointestinal tract, offering a novel approach for incorporating hawthorn polyphenols into food products.

Abstract Background Polystyrene nanoplastics (PS-NPs) are becoming increasingly prevalent in the environment with great advancements in plastic products, and their potential health hazard to animals has received much attention. Several studies have reported the toxicity of PS-NPs to various tissues and cells; however, there is a paucity of information about whether PS-NPs exposure can have toxic effects on mammalian oocytes, especially livestock. Herein, porcine oocytes were used as the model to investigate the potential effects of PS-NPs on mammalian oocytes. Results The findings showed that different concentrations of PS-NPs (0, 25, 50 and 100 μg/mL) entering into porcine oocytes could induce mitochondrial stress, including a significant decrease in mitochondrial membrane potential (MMP), and the destruction of the balance of mitochondrial dynamic and micromorphology. Furthermore, there was a marked increase in reactive oxygen species (ROS), which led to oocyte lipid peroxidation (LPO). PS-NPs exposure induced abnormal intracellular iron overload, and subsequently increased the expression of transferrin receptor (TfRC), solute carrier family 7 member 11 (SLC7a11), and acyl-CoA synthetase long-chain family member 4 (ACSL4), which resulted in ferroptosis in oocytes. PS-NPs also induced oocyte maturation failure, cytoskeletal dysfunction and DNA damage. Cotreatment with 5 μmol/L ferrostatin-1 (Fer-1, an inhibitor of ferroptosis) alleviated the cellular toxicity associated with PS-NPs exposure during porcine oocyte maturation. Conclusions In conclusion, PS-NPs caused ferroptosis in porcine oocytes by increasing oxidative stress and altering lipid metabolism, leading to the failure of oocyte maturation. Graphical Abstract PS-NPs could enter oocytes, caused mitochondrial dysfunction and oxidative stress, induced lipid peroxidation and ferroptosis, which eventually resulted in failure of oocyte maturation.

Normally, in the downlink Network-Coded Multiple Access (NCMA) system, the same power is allocated to different users. However, equal power allocation is unsuitable for some scenarios, such as when user devices have different Quality of Service (QoS) requirements. Hence, we study the power allocation in the downlink NCMA system in this paper, and propose a downlink Network-Coded Multiple Access with Diverse Power (NCMA-DP), wherein different amounts of power are allocated to different users. In terms of the Bit Error Rate (BER) of the multi-user decoder, and the number of packets required to correctly decode the message, the performance of the user with more allocated power is greatly improved compared to the Conventional NCMA (NCMA-C). Meanwhile, the performance of the user with less allocated power is still much better than NCMA-C. Furthermore, the overall throughput of NCMA-DP is greatly improved compared to that of NCMA-C. The simulation results demonstrate the remarkable performance of the proposed NCMA-DP.

To promote adsorption capacity of biochar as engineering material, pinewood biochar (PC) and bamboo biochar (BC) were prepared by slow pyrolysis (700 °C) and then directly irradiated with UV light at room temperature. The elemental analysis, SEM, FTIR, XPS, and Boehm titration measurements showed that UV irradiation significantly increased the BET surface area, porosity, and surface oxygen functional groups of the biochar. After UV treatment, the BET surface areas of PC and BC were increased by 63.0% and 217%, while the amount of total (acidic) groups increased by 62.0% (155%) and 24.9% (28.2%), respectively. FTIR and XPS measurements suggested that photochemical reactions, including photodegradation and photooxidation processes, may play primary roles in altering biochar the pore structure and surface functional groups of biochar. The Langmuir model capacities (qmax) of modified PC and BC were increased by 94.5% and 50.5% for Pb (II), 18.5% and 13.7% for Cd (II), respectively, compared to their unmodified counterparts. This study examined the effects of UV irradiation on the surface properties of biochar and demonstrate its potential as an effective, simple, and green method for functionalizing biomass material.

Abstract Background Inetetamab is the first domestically developed innovative anti-HER2 monoclonal antibody in China, proven effective and safe in HER2-positive advanced breast cancer. However, its efficacy and safety in neoadjuvant treatment of HER2-positive locally advanced breast cancer (LABC) remain to be validated. Methods This prospective cohort study aimed to evaluate the efficacy and safety of inetetamab combined with pertuzumab, taxanes, and carboplatin (TCbIP) in neoadjuvant therapy for HER2-positive LABC, comparing it to data from patients treated with the TCbHP regimen (trastuzumab combined with pertuzumab, taxanes, and carboplatin) using propensity score matching (PSM). The primary endpoint was total pathological complete response (tpCR). Adverse events (AEs), objective response rate (ORR), and near-pCR were key secondary endpoints. Results Forty-four patients with clinical stage IIA-IIIC HER2-positive LABC were prospectively enrolled and treated with the TCbIP regimen. The tpCR rate among 28 patients who completed surgery was 60.7%, comparable to and slightly higher than the TCbHP group in PSM (60.7% vs. 53.6%, P = 0.510). The ORR was 96.4%, and the DCR reached 100.0%. The most common ≥ grade 3 AE was neutropenia (21.4% vs. 11.9%, P = 0.350). No significant reduction in left ventricular ejection fraction was observed, and no patient withdrew from treatment due to AEs. Conclusion Neoadjuvant therapy with TCbIP showed good efficacy and safety in patients with HER2-positive LABC and might be another promising option for neoadjuvant treatment. Trial registration NCT05749016 (registration date: Nov 01, 2021).

Background: The lack of reference genes makes it difficult to conduct molecular biology research on the plant genus, Clematis L. Clematis lanuginosa belongs to Sect. Viticella DC of Clematis L. It is also an important ornamental cultivated variety parent of the early and late large-flowered groups. Studying the reference genes of C. lanuginosa in different tissues will provide a theoretical basis for the reference selection of early and late large-flowered groups of Clematis, which could promote research progress on molecular biology of ornamental Clematis. Results: The roots, stems, leaves, sepals, stamens, and carpels of C. lanuginosa were used as research materials, and seven candidate reference genes were used for quantitative real-time PCR analysis. Comprehensive stability analysis using geNorm, NormFinder, BestKeeper, and RefFinder software showed that suitable reference genes in C. lanuginosa root, stem, and leaf were PP2A-2 and UBC34; and in floral tissue were UBC34, PP2A-2, and ARP7. These reference genes can be used as internal reference either alone or in combination. The pairwise variation value evaluated with geNorm software showed that two internal reference genes were needed for gene expression correction in the tissues. In the floral organs, three reference genes were required for gene expression correction. Conclusions: Our results provide a foundation for future gene expression analysis of C. lanuginosa and guidance for the screening of reference genes in Clematis.How to cite: Li Q, Wang S, Lv F, et al. Selection and validation of reference genes for quantitative real-time PCR in different tissues of Clematis lanuginosa. Electron J Biotechnol 2024;70. https://doi.org/10.1016/j.ejbt.2024.04.005.

Abstract Functional traits reveal the adaptive strategies of species to their environment, and are relevant to the formation of communities, the function of ecosystems, and the mechanisms underlying biodiversity. However, trait databases have not been established for most biological taxa, especially for insects, which encompass a vast number of species. This study measured the morphological traits of 307 species of Heteroptera insects collected in 2019 from the “Xishuangbanna Priority Conservation Area” in Southwest China using sweep netting and light trapping methods. This study provides a dataset for 307 Heteroptera species, comprising 34 morphometric measurements and 17 morphological traits. The dataset contains information on species sex, abundance, and the average, maximum, and minimum values of traits. This dataset facilitates an enhanced understanding of the functional traits and ecological associations of Heteroptera insects and offers opportunities for exploring a more diverse range of research topics.

In order to build a very-low-level γ ray radiation field and its magnitude transfer system，the scattering contribution caused by different mechanical device structure is researched based on the experimental conditions of the Jinping underground laboratory in China. In this research，the Monte Carlo model of the irradiation device，the magnitude transfer detector，and the internal transmission structure of the shielding box were built in the MCNP5 software. After that，the scattering contribution caused by three spatial variables: the emission angle of the irradiation device，the distance between the detector and the edge of the shielding box，and the distance between the source and the detector，was simulated，and the appropriate device design and layout scheme were obtained. The emission angle of 20°，30° and 40° were used in this research. The energy deposition in sensitive area (with/without the shielding box) was recorded under three different distances between the source and the detector. Three locations of the irradiation device were designed to analyze the change of energy deposition caused by the change of locations. The energy deposition in sensitive area was simulated under more distances between the source and the detector. According to the data，the increase in energy deposition with the emission angle of 20° is less than that caused by the emission angle of 30° and 40°，and the increase in energy deposition is less when the irradiation device is far from the edge of the shielding box. In this research，energy deposition caused by scattering radiation under various irradiation conditions were obtained and analyzed，the device design and layout in the radiation field were optimized，and the idea for establishing an extremely-low-background radiation field was provided.

Abstract Currently approved HER2-targeting antibody-drug conjugates (ADCs) for HER2-positive breast cancer (BC) are associated with safety concerns. In this multicenter, single-arm, dose-escalation (phase 1a) and dose-expansion (phase 1b) phase 1 trial (NCT03944499), patients with HER2-expressing advanced solid tumors received FS-1502 (an anti-HER2 ADC) with a 3 + 3 design in phase 1a; patients with metastatic HER2-positive BC received FS-1502 at the recommended phase 2 dose (RP2D) in phase 1b. The primary end points were dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and RP2D for phase 1a and objective response rate (ORR) for phase 1b. A total of 150 patients with HER2-expressing solid tumors (n = 5) and BC (n = 145) were enrolled (female, n = 146, 97.3%). One DLT each was reported at 3.0 and 3.5 mg/kg; the MTD was not reached. The RP2D was 2.3 mg/kg once every 3 weeks. Five (3.3%) patients experienced pneumonitis; four (2.7%) had grade 3 reversible ocular events. Of 67 HER2-positive BC patients receiving the RP2D, the best ORR was 53.7% (95% CI, 41.1-66.0%), including PRs confirmed (confirmed ORR, 37.5%) and pending for confirmation. FS-1502 was well tolerated with limited ocular and pulmonary findings and demonstrated promising antitumor activity in HER2-positive BC patients.

BackgroundInjuries constitute a significant global public health concern, particularly among individuals aged 0–34. These injuries are affected by various social, psychological, and physiological factors and are no longer viewed merely as accidental occurrences. Existing research has identified multiple risk factors for injuries; however, they often focus on the cases of children or the older adult, neglecting the university students. Machine learning (ML) can provide advanced analytics and is better suited to complex, nonlinear data compared to traditional methods. That said, ML has been underutilized in injury research despite its great potential. To fill this gap, this study applies ML to analyze injury data among university students in Hainan Province. The purpose is to provide insights into developing effective prevention strategies. To explore the relationship between scores on the self-rating anxiety scale and self-rating depression scale and the risk of non-fatal injuries within 1 year, we categorized these scores into two groups using restricted cubic splines.MethodsChi-square tests and LASSO regression analysis were employed to filter factors potentially associated with non-fatal injuries. The Synthetic Minority Over-Sampling Technique (SMOTE) was applied to balance the dataset. Subsequent analyses were conducted using random forest, logistic regression, decision tree, and XGBoost models. Each model underwent 10-fold cross-validation to mitigate overfitting, with hyperparameters being optimized to improve performance. SHAP was utilized to identify the primary factors influencing non-fatal injuries.ResultsThe Random Forest model has proved effective in this study. It identified three primary risk factors for predicting non-fatal injuries: being male, favorable household financial situation, and stable relationship. Protective factors include reduced internet time and being an only child in the family.ConclusionThe study highlighted five key factors influencing non-fatal injuries: sex, household financial situation, relationship stability, internet time, and sibling status. In identifying these factors, the Random Forest, Logistic Regression, Decision Tree, and XGBoost models demonstrated varying effectiveness, with the Random Forest model exhibiting superior performance.

BackgroundThe Polymorphic Low-Grade Neuroepithelial Tumor of the Young (PLNTY) is a rare, epilepsy-associated brain tumor that has been increasingly recognized but is not well understood due to the scarcity of clinical reports. Our study reviews the clinical characteristics and treatment outcomes of 14 patients with PLNTY to enhance the understanding of this condition from an epilepsy surgery perspective.MethodsWe performed a retrospective analysis of 14 PLNTY cases at our hospital. A literature review on prior studies was also conducted.ResultsOur study included 8 males and 6 females, all presenting with epilepsy. Despite anti-seizure medication, 92.3% of patients continued to have seizures, with 58.3% diagnosed as having drug-resistant epilepsy. Neuroimaging revealed that 64.3% of the lesions were in the temporal lobe, with 75.0% showing calcification on CT, 71.4% exhibiting mixed signals on T2-weighted images, and 92.7% showing tumor enhancement. The transmantle sign was noted in 57.1% of T2 FLAIR sequences. EEGs indicated abnormal activity in 69.2% of patients, with 30.7% showing bilateral discharges. SEEG in two patients confirmed the tumor’s epileptogenicity. A 78.6% total resection rate was achieved, with a 90.0% postoperative seizure-free rate and an 85.7% excellent Engel grade 1 rate. No instances co-occurring with focal cortical dysplasia (FCD) were observed.ConclusionPLNTY is characterized by unique neuroimaging features and a strong association with epilepsy. SEEG is pivotal for cases with unclear lateralization, aiding in identifying the link between the tumor and seizures. Following established epilepsy surgery protocols for brain tumor management, early intervention and extended resection can improve the rate of postoperative seizure freedom.

The gut-liver axis in ruminants can explain nutrient regulation, the gut-liver cycle, and immune function in ruminant biology through the gut microbe-gut metabolite-liver metabolite relationship. to investigate the effects of herbal feed additives on the gut-liver axis of Hu sheep. In this study, a broadly targeted UPLC-MS/MS metabolomics approach and 16s sequencing of gut microorganisms were used to detect, identify and quantify changes in ileal microorganisms, liver metabolites and ileal metabolites following the addition of Chinese herbal preparations. The addition of a 0.5% herbal feed additive increased ileal IgA, IgG and complement C3 levels. The addition of Chinese herbal preparations can increase the abundance of Firmicutes, Actinobacteriota, Bacteroidota, at the portal level of the ileum, increase the metabolism of organic matter and its derivatives, bile acids, amino acids and their metabolites, coenzymes, and vitamins in the liver and ileum, enhance nutrient absorption and waste metabolism, accelerate liver metabolism, promote gut-liver circulation, and improve ileal and liver immunity. This study provides a theoretical basis for understanding the effects of herbal feed additives on the gut-liver axis in ruminants.

Changes in the ecological environment quality (EEQ) in the main inland Tarim River Basin in China substantially impact the regional development. Indeed, comprehensive ecological environment measures have been implemented in the Tarim River Basin since 2000. In this context, the main objective of the present study was to investigate the spatiotemporal evolution of the EEQ and monitor the effectiveness of ecological restoration measures in the Tarim River Basin over the 2000–2020 period using remote sensing data. First, a Remote Sensing Ecological Index (RSEI) was constructed based on the Moderate Resolution Imaging Spectroradiometer remote sensing data. Second, the spatial distributions and factors of the RSEI were analyzed by using Moran’s Index and Geodetector. The results indicated that the overall RSEI values for the Tarim River Basin increased from 0.22 in 2000 to 0.25 in 2020. Moreover, the values for areas with poor EEQ decreased from 50.7% to 44.73%, while those with moderate EEQ increased from 11.45% to 16.91%. Therefore, the results demonstrated a slight overall improvement in the EEQ of the study area over the 2000–2020 period. On the other hand, the EEQ in the Tarim River Basin exhibited a significant spatial autocorrelation in the 2000–2020 period, with a relatively stable overall spatial distribution. Areas with high–high aggregation were distributed in the high-elevation mountainous areas in the western, northern, and southern parts of the study area. In contrast, areas with low–low aggregation were observed in the central and eastern low-elevation desert areas. The EEQ in the Tarim River Basin was driven by the interactions of several factors, including the normalized difference vegetation index, land surface moisture, land surface temperature, normalized differential build-up and bare soil index, and elevation. In particular, heat was the main driving factor that severely impacted the EEQ in the study area. Indeed, increase in the heat values could directly enhance meltwater runoff from glaciers in the basin, thereby resulting in short-term improvement in the basin EEQ. Furthermore, rapid urbanization from 2015 to 2020 resulted in a decrease in the average RSEI value of the Tarim River Basin by 0.1 over this period, consequently, the EEQ level decreased slightly. Briefly, the EEQ in the Tarim River Basin showed an overall increasing trend from 2000 to 2020, further demonstrating the effectiveness of a series of implemented ecological restoration measures in the Tarim River Basin over this period.

Abstract Background We explored the efficacy and safety of inetetamab combined with sirolimus and chemotherapy for the treatment of human epidermal factor receptor 2 (HER2)‐positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR (PAM) pathway after trastuzumab treatment. Methods For this prospective multicenter clinical study, HER2‐positive metastatic breast cancer patients with PAM pathway mutations confirmed by histology or peripheral blood genetic testing were enrolled from July 2021 to September 2022. Patients were randomly assigned to a trial or control group. The patients in the trial group received inetetamab combined with sirolimus and chemotherapy, while the control group patients received pyrotinib and chemotherapy. The RECIST v1.1 standard was used to evaluate efficacy. Descriptive statistics were used to summarize the clinicopathological features, and the Kaplan–Meier method was used to generate survival curves. The log‐rank test was used to compare progression‐free survival (PFS) between the two groups. Results A total of 59 HER2‐positive metastatic breast cancer patients with abnormal activation of the PAM pathway were included, of which 37 received inetetamab combined with sirolimus and chemotherapy treatment and 22 received pyrotinib and chemotherapy treatment. The median PFS was 4.64 months in the inetetamab group and 5.69 months in the pyrotinib group, with no statistically significant difference (p = 0.507). The objective response rates were 27.3% for the inetetamab group and 29.4% for the pyrotinib group. The safety assessment indicated that the adverse event (AE) incidences were 86.1% (31/36) in the inetetamab group and 78.9 (15/19) in the pyrotinib group, with 9 (25%) and four (21.1%) Grade 3/4 AEs in the inetetamab and pyrotinib groups, respectively. Conclusions For metastatic HER2‐positive breast cancer patients with abnormal PAM pathway activation and previous trastuzumab treatment, the combination of inetetamab with sirolimus and chemotherapy is equivalent to the combination of pyrotinib and chemotherapy. Therefore, this regimen could be a treatment option for PAM pathway‐activated metastatic HER2‐positive breast cancer patients.

Apoptosis-inducing factor mitochondrion-associated 2 (AIFM2) has been identified as a gene with anti-ferroptosis properties. To explore whether AIFM2 exerts anti-ferroptosis role in yaks (Bos grunniens), we cloned yak AIFM2 gene and analyzed its biological characteristics. The coding region of AIFM2 had 1122 bp and encoded 373 amino acids, which was conserved in mammals. Next, RT-qPCR results showed an extensive expression of AIMF2 in yak tissues. Furthermore, we isolated yak skin fibroblasts (YSFs) and established a bisphenol A (BPA)-induced ferroptosis model to further investigate the role of AIFM2. BPA elevated oxidative stress (reactive oxygen species, ROS) and lipid peroxidation (malondialdehyde, MDA and BODIPY), and reduced cell viability and antioxidant capacity (glutathione, GSH), with the severity depending on the dosage. Of note, a supplement of Ferrostatin-1 (Fer), an inhibitor of ferroptosis, restored the previously mentioned indicators. Subsequently, we constructed an AIFM2 overexpression vector and designed AIFM2 specific interfering siRNAs, which were transfected into YSFs. The results showed that overexpressing AIFM2 alleviated ferroptosis, characterizing by significant changes of cell viability, ROS, BODIPY, MDA and GSH. Meanwhile, interfering AIFM2 aggravated ferroptosis, demonstrating the critical anti-ferroptosis role of the yak AIFM2 gene. This study shed light on further exploring the molecular mechanism of AIFM2 in plateau adaptability.

It's crucial to understand the biomechanical properties of brain tissue to comprehend the potential mechanisms of traumatic brain injury. This study, distinct from homogeneous models, integrates axonal coupling in both axial and transverse compressive experiments within a continuum mechanics framework to capture its intricate mechanical behaviors. Fresh porcine brains underwent unconfined compression at strain rates of 0.001/s and 0.1/s to 0.3 strain, allowing for a comprehensive statistical analysis of the directional, regional, and strain-rate-dependent mechanical properties of brain tissue. The established constitutive model, fitted to experimental data, delineates material parameters providing intuitive insights into the stiffness of gray/white matter isotropic matrices and neural fibers. Additionally, it predicts the mechanical performance of white matter matrix and axonal fibers under compressive loading. Results reveal that gray matter is insensitive to loading direction, exhibiting insignificant stiffness variations within regions. White matter, however, displays no significant differences in mechanical properties under axial and transverse loading, with an overall higher average stress than gray matter and a more pronounced strain-rate effect. Stress-strain curves indicate that, under axial compression, white matter axons primarily resist the load before transitioning to a matrix-dominated response. Under transverse loading, axonal fibers exhibit weaker resistance to lateral pressure. The mechanical behavior of brain tissue is highly dependent on loading rate, region, direction, and peak strain. This study, by combining experimentation with phenomenological modeling, elucidates certain phenomena, contributing valuable insights for the development of precise computational models.

There are few reports about primary intracranial granulomas without an identifiable infectious history. A 25-year-old male with intracranial granuloma. The patient presented with a history of tinnitus with intermittent headache for 1 week. Consequently, MRI showed pronounced and extensive enhancement lesions in the left frontal lobe involved in the cerebral longitudinal fissure cistern and the inside of the right frontal lobe, accompanied by a moderate degree of oedema; The lesion was a pilomyxoid astrocytoma preoperatively. Following a systemic examination, gross total resection of the lesion was performed, and postoperative pathological examination revealed the presence of inflammatory lesions. The patient exhibited notable symptom amelioration post-surgery, leading to discharge after the treatment. Subsequently, a sequential treatment involving steroid therapy was administered, resulting in successful patient recovery.

Background: Inetetamab is a novel antibody targeting human epidermal growth factor receptor 2 (HER2) developed in China. Due to its optimized antibody-dependent cell-mediated cytotoxicity effect compared with trastuzumab, it has shown good efficacy and safety in the treatment of HER2-positive advanced breast cancer (ABC). Objectives: This study aimed to investigate the efficacy and safety of inetetamab combination therapy in the treatment of HER2-positive ABC in real-world clinical practice. Design: Retrospective study. Methods: A total of 133 patients with HER2-positive ABC who were treated with inetetamab-based regimens between March 2020 and January 2024 were retrospectively included in this study. The main endpoint was median progression-free survival (mPFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Results: The study included 133 HER2-positive ABC patients, and the median age was 55 years. The mPFS was 8.0 (6.7–9.3) months. The ORR was 50.4%, while the DCR was 88.7%. The mPFS for patients receiving inetetamab-based therapy as first to second, third to fourth, and later lines of metastatic treatment were 14.0, 7.0, and 6.0 months, respectively. Patients treated with inetetamab plus pyrotinib plus chemotherapy, especially with capecitabine, had the best outcomes (mPFS = 14.0 months). Multivariate analysis revealed that prior HER2-TKI treatment was significantly associated with worse PFS (hazard ratios 2.829, 95% confidence interval 1.265–6.328, p = 0.011). Subgroup analysis indicated that patients without visceral metastases had significantly better PFS (14.0 months vs 8.0 months, p = 0.003). The overall incidence of any grade adverse events (AEs) was 100%, with most being grades 1–2. Severe complications included neutropenia (37.6%) and leukopenia (33.1%). Conclusions: Inetetamab-based combination therapy shows promising efficacy and good safety in patients with HER2-positive ABC. It is one of the late-line treatment options for Chinese patients with HER2-positive ABC.

Osteoblasts are mechanosensitive cells. Tensile stress with different conditions, including loading time, frequency, magnitude, etc. would cause varied responses in osteoblasts. However, it was not clarified that the effect of the loading types on the osteoblasts. In this study, we focused on the effect of varied tensile stress types on osteoblasts, including isotropic stretch, biaxial stretch, and uniaxial stretch with the negative ratio of transverse strain to axial strain (NR) −1, 0, and 0.2 respectively. Cell proliferation was determined to be most efficient when stimulated by 6% strain at a frequency of 1 Hz and a negative value of 0 for 1 h/day. The varied strain resulted in a thickening of the F-actin cytoskeleton and a thinning of the nucleus. Nuclear flattening caused Yes-associated protein (YAP) to be transported to the nucleus. It was suggested that the influence of loading types on the mechanobiology responses must be noticed. The mechanism of cell mechanical sensitivity under varied loading types was explored, which would provide good suggestions for designing microstructures to control deformation patterns in bone tissue engineering.

Abstract Saliva, an oral secretion primarily originating from salivary glands (SGs), exert critical roles in the ongoing evolutionary interaction between insects and plants. However, identifying insect salivary components poses challenges due to the tiny size of insects, low secretion amounts, and the propensity for degradation after secretion. In this study, we developed a transcriptome-based approach to comprehensively analyze the salivary proteins of the short-headed planthopper, Epeurysa nawaii, a species with unique feeding habits on bamboo. A total of 165 salivary proteins were identified, with 114 secretory genes highly and specifically expressed in SGs. Consistent with most phloem-feeding insects, digestive enzymes, calcium-binding proteins, oxidoreductases, and a few previously reported salivary effectors were ubiquitously distributed in E. nawaii saliva. However, we also identified a substantial portion of salivary proteins exhibiting taxonomy specificity, including 60 E. nawaii-specific and 62 Delphacidae-specific proteins. These taxonomy-restricted proteins potentially play a role in insect adaptation to specific host plants. Our study provides an efficient pipeline for salivary protein identification and serves as a valuable resource for the functional characterization of effectors.

Background: The majority of HR+/HER2-breast cancer patients can also achieve long-term survival despite not attaining pCR, indicating limited prognostic value of pCR in this population. This study aimed to identify novel pathologic end points for predicting long-term outcomes in HR+/HER2-breast cancer after neoadjuvant chemotherapy. Methods: We analyzed HR+/HER2-breast cancer patients with stage II-III tumors who underwent curative surgery after neoadjuvant chemotherapy from three hospitals. Major pathologic response (MPR), defined as the presence of Miller-Payne grades 3–5 and positive lymph node ratio of ≤10 %, was used as a pathological evaluation indicator. We assessed the association between MPR and event-free survival (EFS) and performed Multivariable Cox regression to identify independent factors associated with EFS. Results: From January 2010 to December 2020, 386 patients were included in the final analysis. 28 patients (7.3 %) achieved pCR and 118 patients (30.6 %) achieved MPR. The median duration of follow-up was 54.4 months,5-year EFS was 87 % in the MPR group vs. 68 % in the non-MPR group. Multivariate analysis showed that low PR expression, high clinical stage, lower Miller–Payne grades and Positive lymph node ratio were independent poor prognostic factors for EFS (all P values

Detection of flow fields constitutes a critical role in the advancement and innovation of hypersonic aircraft. Under hypersonic conditions, aircraft aerodynamics manifest a multitude of complex phenomena, including intense turbulence and fluctuations, transitions within the boundary layer, interactions between shock waves and boundary layers, as well as the effects of high-temperature gas. Thus, the surveillance of hypersonic aircraft flow fields is imperative not only for flight safety but also for the progression of hypersonic technologies. Given the practical limitations that restrict sensors installed to only key areas for detection, we propose a GNN-based method for hypersonic aircraft flow field reconstruction from limited sensors. Moreover, we have introduced a novel graph modeling technique for enhancing the reconstruction motivated by that solely the most significant edges within the graph are efficacious for field reconstruction. The methodology encompasses the following steps, modeling graphs from diverse perspectives, and transforming them into minimum spanning trees. These sparse graphs are then integrated with learnable weights optimized by automatic differentiation. Our method has been tested on an open-source turbulence dataset, the two components of graph pruning and weight optimization bring about 34% and 10% improvements on average. Furthermore, our approach has been validated in the reconstruction of hypersonic aircraft flow fields for at least 10% error reduction among all the situations.

We aimed to explore the effect of salidroside (SAL) on meat quality, antioxidant capacity, and lipid metabolism in broilers. The results demonstrated that SAL significantly reduced the yellowness (b*), shear force, cooking loss, drip loss, MDA, TBARS, and carbonyl content in breast (P

Background: Mg alloys have attractive properties, including biocompatibility, biodegradability, and ideal mechanical properties. Moreover, Mg alloys are regarded as one of the promising candidates for manufacturing ureteral stents. This study proposed a multi-objective optimization method based on the Kriging surrogate model, NSGA-Ⅲ, and finite element analysis to improve the degradation performance of Mg alloy ureteral stents. Methods: The finite element model for the degradation of Mg alloy ureteral stents has been established to compare the degradation performance of the stents under different parameters. Latin hypercube sampling was adopted to generate train sample points in the design space. Meanwhile, the Kriging surrogate model was constructed between strut parameters and stent degradation behavior. The NSGA-Ⅲ was utilized to determine the optimal solution in the global design space. Results: The optimized stent achieved 5.52 ​× ​degradation uniformity (M), 10 ​× ​degradation time (DT), and 4 ​× ​work time (FT). The errors between the Kriging surrogate model and the finite element calculation results were less than 6%. Conclusion: The optimized stent achieved better degradation performance. The degradation behavior of stents was dependent on the design parameters. The multi-objective optimization method based on the Kriging surrogate model and finite element analysis was effective in stent design optimization problems.

Abstract This multicenter, phase II study (NCT03872791) aims to evaluate the efficacy and safety of the anti-PD-L1/CTLA-4 bispecific antibody KN046 combined with nab-paclitaxel in the first-line treatment of patients with metastatic triple-negative breast cancer (TNBC). The primary endpoints included objective response rate (ORR) and duration of response (DoR), and secondary endpoints included progression-free survival (PFS), overall survival (OS) rate, safety, and the correlation of PD-L1 status with clinical efficacy. This trial met pre-specified endpoints. 27 female patients were enrolled sequentially to receive KN046 in two dose levels (3 mg/kg or 5 mg/kg). Among the 25 evaluable patients, the ORR achieved 44.0% (95% CI, 24.4% − 65.1%), and the median DoR was not mature. The median PFS reached 7.33 months (95%CI, 3.68 − 11.07 months), and the median OS was 30.92 months (95%CI, 14.75 - NE months). In PD-L1 positive patients, PFS was 8.61 months (versus 4.73 months) and the 2-year OS rate was 62.5% (versus 57.1%) compared to PD-L1 negative patients. Patients tolerated well the combination therapy. In general, KN046 combined with nab-paclitaxel showed favorable efficacy and survival benefits with tolerable toxicity in the first-line treatment of metastatic TNBC, especially PD-L1 positive, which is worth further investigation.

Clinical studies have proved significant improvements in hand motor function in stroke patients when assisted by robotic devices. However, there were few studies on neural activity changes in the brain during execution. This study aimed to investigate the brain activation pattern caused by soft rehabilitation glove and virtual reality scenes. Twenty healthy subjects and twenty stroke patients were recruited to complete three controlled trials: grasping passively with robotic glove assistance (RA), watching grasping movement video in virtual reality (VR), and the joint use of robotic glove and virtual reality (VRA). Neural activity in the prefrontal cortex, motor cortex and occipital lobe was synchronously collected by the functional near-infrared spectroscopy (fNIRS) device. Activation level and functional connectivity of these brain regions were subsequently calculated and statistically analyzed. For both groups, the VR and VRA tasks induced activation of larger cortical areas. Stroke group had higher average cortical activation in all three tasks compared to healthy group, especially in the prefrontal cortex ( ${P} \lt 0.05$ ). Functional connectivity was weaker in the stroke group than in the healthy group across most regions, but was significantly stronger across some regions of the right hemisphere. These findings suggest significant differences in activation patterns across three tasks. In addition, multi-sensory stimulation can promote functional communication between more brain regions in patients. It has potential for neuromodulation in rehabilitation training by setting up different sensory stimulation modalities.

Objective To investigate the frequency of platelet antibodies in voluntary blood donors and patients in Zhongshan, Guangdong Province, and to study the specificity and cross-matching of platelet antibodies. Methods Platelet antibodies of blood donors and patients were screened by solid-phase immunoadsorption (SPIA), rechecked by flow cytometry (FCM), and antibody specificity was identified by PakPlus enzyme immunoassay, and platelet cross-matching was simulated by SPIA. Results A total of 1 049 blood donor samples and 598 patient samples were tested, with 6 (0.57%) and 49 (8.19%) samples positive for SPIA,respectively(P

Abstract Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by the infiltration of inflammatory cells and demyelination of nerves. Mitochondrial dysfunction has been implicated in the pathogenesis of MS, as studies have shown abnormalities in mitochondrial activities, metabolism, mitochondrial DNA (mtDNA) levels, and mitochondrial morphology in immune cells of individuals with MS. The presence of mitochondrial dysfunctions in immune cells contributes to immunological dysregulation and neurodegeneration in MS. This review provided a comprehensive overview of mitochondrial dysfunction in immune cells associated with MS, focusing on the potential consequences of mitochondrial metabolic reprogramming on immune function. Current challenges and future directions in the field of immune-metabolic MS and its potential as a therapeutic target were also discussed.

Bidens pilosa is recognized as one of the major invasive plants in China. Its invasion has been associated with significant losses in agriculture, forestry, husbandry, and biodiversity. Soil ecosystems play an important role in alien plant invasion. Microorganisms within the soil act as intermediaries between plants and soil ecological functions, playing a role in regulating soil enzyme activities and nutrient dynamics. Understanding the interactions between invasive plants, soil microorganisms, and soil ecological processes is vital for managing and mitigating the impacts of invasive species on the environment. In this study, we conducted a systematic analysis focusing on B. pilosa and Setaria viridis, a common native companion plant in the invaded area. To simulate the invasion process of B. pilosa, we constructed homogeneous plots consisting of B. pilosa and S. viridis grown separately as monocultures, as well as in mixtures. The rhizosphere and bulk soils were collected from the alien plant B. pilosa and the native plant S. viridis. In order to focus on the soil ecological functional mechanisms that contribute to the successful invasion of B. pilosa, we analyzed the effects of B. pilosa on the composition of soil microbial communities and soil ecological functions. The results showed that the biomass of B. pilosa increased by 27.51% and that of S. viridis was significantly reduced by 66.56%. The organic matter contents in the bulk and rhizosphere soils of B. pilosa were approximately 1.30 times those in the native plant soils. The TN and NO3– contents in the rhizosphere soil of B. pilosa were 1.30 to 2.71 times those in the native plant soils. The activities of acid phosphatase, alkaline phosphatase, and urease in the rhizosphere soil of B. pilosa were 1.98–2.25 times higher than in the native plant soils. Using high-throughput sequencing of the 16S rRNA gene, we found that B. pilosa altered the composition of the soil microbial community. Specifically, many genera in Actinobacteria and Proteobacteria were enriched in B. pilosa soils. Further correlation analyses verified that these genera had significantly positive relationships with soil nutrients and enzyme activities. Plant biomass, soil pH, and the contents of organic matter, TN, NO3–, TP, AP, TK, and AK were the main factors affecting soil microbial communities. This study showed that the invasion of B. pilosa led to significant alterations in the composition of the soil microbial communities. These changes were closely linked to modifications in plant traits as well as soil physical and chemical properties. Some microbial species related to C, N and P cycling were enriched in the soil invaded by B. pilosa. These findings provide additional support for the hypothesis of soil-microbe feedback in the successful invasion of alien plants. They also offer insights into the ecological mechanism by which soil microbes contribute to the successful invasion of B. pilosa. Overall, our research contributes to a better understanding of the complex interactions between invasive plants, soil microbial communities, and ecosystem dynamics.

Abstract Adaptation studies in media have been carried out for decades since the 1950s. When media is adapted between different forms, the narrative inherently changes; even more so when they cross a cultural divide between Japan and the United States. That is precisely the topic of discussion between the anime Ghost in the Shell (1995) and its live action film adaptation Ghost in the Shell (2017). With narrative being a key focus for comparison in this article, Joseph Campbell’s Hero’s Journey is applied. Taken from his seminal work Hero with a Thousand Faces, the theory of the Hero’s Journey has been the go-to reference for monomyth studies for decades which identifies the parallelism and common themes in diverse stories, from classic myths embedded in ancient cultures to film and other contemporary media based on popular culture. Yet, most studies stop there, and do not consider bringing in Campbell’s other works—namely his follow-up collection of books The Masks of God which delves deeper into the mythologies of various regions. His books, Oriental Mythology and Occidental Mythology, zeroes in on the myths in the East and West, which would aid in conducting comparisons between materials originating from the two opposite regions, further supplementing its usefulness in adaptation studies concerning Japanese anime and their corresponding Hollywood adaptations. This article covers the changes in narrative themes corresponding to Campbell’s Oriental and Occidental mythology between the anime Ghost in the Shell (1995) and its live action film adaptation Ghost in the Shell (2017).

Pericarp browning and fruit decay severely reduce the postharvest quality of litchi. Improving the antioxidant capacity of the fruit is an effective way to solve these problems. In our study, the appropriate zinc oxide nanoparticles (ZnO NPs) treatment and its mechanism of action on the storability of litchi was investigated. Litchi fruit was soaked in a 100 mg·L−1 ZnO NPs suspension, water, and 500 mg·L−1 prochloraz for 2 min, respectively. The results showed that the ZnO NPs treatment delayed pericarp browning and decay in litchi fruit and was more effective than prochloraz treatment. The ZnO NPs-treated fruit showed significantly increased contents of total anthocyanin, total phenols, and activities of DPPH scavenging, superoxide dismutase, and glutathione peroxidase, as well as the lowest activities of polyphenol oxidase and laccase. ZnO NPs generated hydrogen peroxide and superoxide anion radicals, which were beneficial in slowing down the decay and inducing antioxidant capacity. However, these reactive oxygen species also consumed catalase, peroxidase, glutathione, and glutathione peroxidase. This means that litchi should be treated with an appropriate concentration of ZnO NPs. We concluded that treatment with a 100 mg·L−1 ZnO NPs suspension could induce antioxidant capacity, which is a promising and effective method to maintain the postharvest quality of litchi.

In China, the processing of prickly ash (PA) produces a large number of by-products, including prickly ash seeds (PASs), which are rich in bioactive components such as flavonoids and phenolic compounds, and which may have an important influence on meat quality and muscle metabolites. Therefore, this study aimed to assess the impact of dietary PAS supplementation on the meat quality, antioxidant activity, and metabolite characteristics of lambs. Eighteen 3-month-old Hu lambs (25.66 ± 3.03 kg body weight) were randomly allotted to three different dietary treatment groups. In the three dietary treatments, 0% (basal diet, CON), 3% (CON with 3% PAS, low-dose PAS, and LPS), and 6% (CON with 6% PAS, high-dose PAS, and HPS) PASs were used. Results indicated significant improvements in the HPS group, including reduced cooking loss and increased fat content. The L* and b* 45 min values were significantly lower in the PAS groups than those in the CON group (p < 0.05). Additionally, dietary PAS supplementation increased in MUFA, PUFA, n-3 PUFA, PUFA/MUFA ratio, NEAA, and FFA compared to the CON group. Furthermore, PAS supplementation significantly improved serum and muscle antioxidant capacity. Metabolomic analyses revealed that increased metabolites, such as tryptophan, leucine, citric acid, adenosine 5′-triphosphate, creatine phosphate, inosine, and α-ketoglutaric acid, were primarily enriched in the biosynthesis of cofactors and nucleotide and purine metabolism pathways. Notably, supplementation with 6% of PASs exhibited the most prominent effect on lamb meat quality in this study. Therefore, the application of PASs as a feed component in lamb production can not only improve meat quality and muscle antioxidant capacity but also save feed costs.

The survival of relict Taxus wallichiana var. wallichiana (Yunnan yew) is threatened by overexploitation for its quality wood and medicinal properties, particularly for taxol extraction. Understanding the current status of its communities and populations is crucial for protecting existing natural forest resources. We established 53 vegetation plots in Yunnan, southwestern China, where T. wallichiana var. wallichiana is the primary dominant species. These plots were classified into four forest types. The forests were multi-stratified, with T. wallichiana var. wallichiana frequently dominating the subcanopy and shrub layer. Species diversity indices did not significantly differ among the four forest types. The age structure of T. wallichiana var. wallichiana exhibited a multi-modal pattern, with a maximum age of 1165 years. Growth was slow, with an average radial growth rate of 0.78 mm/year. Despite its strong sprouting ability, the species had a poor seedling/sapling bank and suffered from inadequate regeneration. Its seedlings/saplings are shade-intolerant. This study provides a scientific basis for effective conservation strategies, emphasizing the need for in situ regeneration to ensure the survival of T. wallichiana var. wallichiana and its contributions to biodiversity and ecosystem services.

Accurate monitoring of irrigation areas is of great significance to ensure national food security and rational utilization of water resources. The low resolution of the Moderate Resolution Imaging Spectroradiometer and Landsat data makes the monitoring accuracy insufficient for actual demand. Thus, this paper proposes a method of extracting the irrigated area in arid regions based on Sentinel-2 long time-series imagery to realize the accurate monitoring of irrigation areas. In this paper, a typical irrigation area in the arid region of Northwest China–Xinjiang Santun River is selected as the study area. The long time series Sentinel-2 remote sensing data are used to classify the land use of the irrigation area. The random forest, CART decision tree, and support vector machine algorithms are used to combine the field collection of the typical irrigation point and non-irrigated sample points. The irrigation area is extracted by calculating the Normalized Vegetation Index (NDVI), Soil-Adjusted Vegetation Index (SAVI), and Optimized Soil-Adjusted Vegetation Index (OSAVI) time series data as the classification parameters. The results show that (1) the irrigated area of the dryland irrigation region can be effectively extracted using the SAVI time-series data through an object-oriented approach combined with the random forest algorithm. (2) The extracted irrigated areas were 44,417, 42,915, 43,411, 48,908, and 47,900 hm2 from 2019 to 2023, and the overall accuracies of the confusion matrix validation were 94.34%, 90.22%, 92.03%, 93.23%, and 94.63%, with kappa coefficients of 0.9011, 0.8887, 0.8967, 0.9009, and 0.9265, respectively. The errors of the irrigated area compared with the statistical data were all within 5%, which demonstrated the effectiveness of the method in extracting the irrigated area. This method provides a reference for extracting irrigated areas in arid zones.

Background: Atrial fibrillation (AFib) detection via mobile ECG devices is promising, but algorithms often struggle to generalize across diverse datasets and platforms, limiting their real-world applicability. Objective: This study aims to develop a robust, generalizable AFib detection approach for mobile ECG devices using crowdsourced algorithms. Methods: We developed a voting algorithm using random forest, integrating six open-source AFib detection algorithms from the PhysioNet Challenge. The algorithm was trained on an AliveCor dataset and tested on two disjoint AliveCor datasets and one Apple Watch dataset. Results: The voting algorithm outperformed the base algorithms across all metrics: the average of sensitivity (0.884), specificity (0.988), PPV (0.917), NPV (0.985), and F1-score (0.943) on all datasets. It also demonstrated the least variability among datasets, signifying its highest robustness and effectiveness in diverse data environments. Moreover, it surpassed Apple’s algorithm on all metrics and showed higher specificity but lower sensitivity than AliveCor’s Kardia algorithm. Conclusions: This study demonstrates the potential of crowdsourced, multi-algorithmic strategies in enhancing AFib detection. Our approach shows robust cross-platform performance, addressing key generalization challenges in AI-enabled cardiac monitoring and underlining the potential for collaborative algorithms in wearable monitoring devices.

Background Drought is a critical limiting factor affecting the growth and development of spring maize (Zea mays L.) seedlings in northeastern China. Sodium 5-nitroguaiacol (5-NGS) has been found to enhance plant cell metabolism and promote seedling growth, which may increase drought tolerance. Methods In the present study, we investigated the response of maize seedlings to foliar application of a 5-NGS solution under osmotic stress induced by polyethylene glycol (PEG-6000). Four treatment groups were established: foliar application of distilled water (CK), foliar application of 5-NGS (NS), osmotic stress + foliar application of distilled water (D), and osmotic stress + foliar application of 5-NGS (DN). Plant characteristics including growth and photosynthetic and antioxidant capacities under the four treatments were evaluated. Results The results showed that under osmotic stress, the growth of maize seedlings was inhibited, and both the photosynthetic and antioxidant capacities were weakened. Additionally, there were significant increases in the proline and soluble sugar contents and a decrease in seedling relative water content (RWC). However, applying 5-NGS alleviated the impact of osmotic stress on maize seedling growth parameters, particularly the belowground biomass, with a dry mass change of less than 5% and increased relative water content (RWC). Moreover, treatment with 5-NGS mitigated the inhibition of photosynthesis caused by osmotic stress by restoring the net photosynthetic rate (Pn) through an increase in chlorophyll content, photosynthetic electron transport, and intercellular CO2 concentration (Ci). Furthermore, the activity of antioxidant enzymes in the aboveground parts recovered, resulting in an approximately 25% decrease in both malondialdehyde (MDA) and H2O2. Remarkably, the activity of enzymes in the underground parts exhibited more significant changes, with the contents of MDA and H2O2 decreasing by more than 50%. Finally, 5-NGS stimulated the dual roles of soluble sugars as osmoprotectants and energy sources for metabolism under osmotic stress, and the proline content increased by more than 30%. We found that 5-NGS played a role in the accumulation of photosynthates and the effective distribution of resources in maize seedlings. Conclusions Based on these results, we determined that foliar application of 5-NGS may improve osmotic stress tolerance in maize seedlings. This study serves as a valuable reference for increasing maize yield under drought conditions.

HDAC11 is an epigenetic repressor of gene transcription, acting through its deacetylase activity to remove functional acetyl groups from the lysine residues of histones at genomic loci. It has been implicated in the regulation of different immune responses, metabolic activities, as well as cell cycle progression. Recent studies have also shed lights on the impact of HDAC11 on myogenic differentiation and muscle development, indicating that HDAC11 is important for histone deacetylation at the promoters to inhibit transcription of cell cycle related genes, thereby permitting myogenic activation at the onset of myoblast differentiation. Interestingly, the upstream networks of HDAC11 target genes are mainly associated with cell cycle regulators and the acetylation of histones at the HDAC11 target promoters appears to be residue specific. As such, selective inhibition, or activation of HDAC11 presents a potential therapeutic approach for targeting distinct epigenetic pathways in clinical applications.

Neuropathic pain (NP) is a common debilitating chronic pain condition with limited effective therapeutics. Further investigating mechanisms underlying NP is therefore of great importance for discovering more promising therapeutic targets. In the current study, we employed high-throughput RNA sequencing to explore transcriptome profiles of mRNAs and microRNAs in the dorsal root ganglia (DRG) following chronic constriction injury (CCI) and also integrated published datasets for comprehensive analysis. First, we established CCI rat model confirmed by behavioral testings, and excavated 467 differentially expressed mRNAs (DEGs) and 16 differentially expressed microRNAs (DEmiRNAs) in the ipsilateral lumbar 4–6 DRG of CCI rats 11 days after surgery. Functional enrichment analysis of 337 upregulated DEGs showed that most of the DEGs were enriched in inflammation- and immune-associated biological processes and signaling pathways. The protein-protein interaction networks were constructed and hub DEGs were screened. Besides hub DEGs, we also identified 113 overlapped DEGs by intersecting our dataset with dataset GSE100122. Subsequently, we predicted potential miRNA-mRNA regulatory pairs using DEmiRNAs and a given set of key DEGs (including hub and overlapped DEGs). By integrative analysis, we found commonly differentially expressed mRNAs and miRNAs following CCI of different time points and different nerve injury types. Highlighted mRNAs include Atf3, Vip, Gal, Npy, Adcyap1, Reg3b, Jun, Cd74, Gadd45a, Tgm1, Csrp3, Sprr1a, Serpina3n, Gap43, Serpinb2 and Vtcn1, while miRNAs include miR-21-5p, miR-34a-5p, miR-200a-3p, miR-130a-5p, miR-216b-5p, miR-217-5p, and miR-541-5p. Additionally, 15 DEGs, including macrophages-specific (Cx3cr1, Arg1, Cd68, Csf1r) and the ones related to macrophages’ involvement in NP (Ccl2, Fcgr3a, Bdnf, Ctss, Tyrobp) were verified by qRT-PCR. By functional experiments in future studies, promising therapeutic targets for NP treatment may be identified among these mRNAs and miRNAs.

This study aimed to investigate the effect of prickly ash seeds (PAS) on the microbial community found in rumen microbes of Hu sheep by adding different percentages of prickly ash seeds and to carry out research on the relation between rumen flora and production performance. Twenty-seven male lambs of Hu sheep were classified into three groups based on the content of prickly ash seeds (PAS) fed for 90 days, i.e., 0%, 3%, and 6%. At the end of the feeding trial, rumen fluid samples were collected from six sheep in each group for 16S amplicon sequencing. The results showed that the addition of prickly ash seeds significantly increased both Chao1 and ACE indices (P < 0.05), and the differences between groups were greater than those within groups. The relative content of Bacteriodota decreased, and the relative content of Fusobacteriota, Proteobacteria, Acidobacteriota, and Euryarchaeota increased. The relative content of Papillibacter and Saccharofermentans was increased at the genus level, and the relative content of Bacteroides and Ruminococcus was decreased. The test group given 3% of prickly ash seeds was superior to the test group given 6% of prickly ash seeds. In addition, the addition of 3% of prickly ash seeds improved the metabolism or immunity of sheep. Fusobacteriota and Acidobacteriota were positively correlated with total weight, dressing percentage, and average daily gain (ADG) and negatively correlated with average daily feed intake (ADFI), feed-to-gain ratio (F/G), and lightness (L*). Methanobrevibacter and Saccharofermentans were positively correlated with ADG and negatively correlated with ADFI and L*. In conclusion, under the present experimental conditions, the addition of prickly ash seeds increased the abundance and diversity of rumen microorganisms in Hu sheep and changed the relative abundance of some genera. However, the addition of 6% prickly ash seeds may negatively affect the digestive and immune functions in sheep rumen.

The identification of microorganisms with excellent flocculants-producing capability and optimization of the fermentation process are necessary for the wide-scale application of bioflocculants. Therefore, we isolated and identified a highly efficient flocculation performance strain of Stenotrophomonas pavanii GXUN74707 from the sludge. The optimal fermentation and flocculation conditions of strain S. pavanii GXUN74707 was in fermentation medium with glucose and urea as the carbon and nitrogen sources, respectively, at pH 7.0 for 36 h, which treatment of kaolin suspension with 0.5 mL of the fermentation broth resulted in a flocculation rate of 99.0%. The bioflocculant synthesized by strain S. pavanii GXUN74707 was found mainly in the supernatant of the fermentation broth. Chemical analysis revealed that the pure bioflocculant consisted of 79.70% carbohydrates and 14.38% proteins. The monosaccharide components of MBF-GXUN74707 are mainly mannose (5.96 μg/mg), galactose (1.86 μg/mg), and glucose (1.73 μg/mg). Infrared spectrometric analysis showed the presence of carboxyl (COO-), hydroxyl (-OH) groups. The SEM images showed clumps of rod-shaped bacteria with adhesion of extracellular products. Furthermore, the strain decolored dye wastewater containing direct black, direct blue, and Congo red by 89.2%, 95.1%, 94.1%, respectively. The chemical oxygen demand (COD) and biological oxygen demand (BOD) removal rates after treatment of aquaculture wastewater with the fermentation broth were 68% and 23%, respectively. This study is the first to report the performance and application of strain Stenotrophomonas pavanii in wastewater flocculation. The results indicate that strain S. pavanii is a good candidate for the production novel bioflocculants and demonstrates its potential industrial practicality in biotechnology processes.

BackgroundThe aim of the present study was to explore the potential of peripheral immune cells in predicting the response and prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving anti-PD-1 immunotherapy and platinum-based chemotherapy.Participants and MethodsWe utilized flow cytometry to examine the levels and dynamics of blood immune cells in 79 advanced NSCLC patients treated with the chemoimmunotherapy between December 2019 and January 2022. The pre- and post-treatment blood samples were collected within 3 days prior to the initiation of the first and third cycle of combination treatment, respectively. Progression-free survival (PFS) and overall survival (OS) analyses were conducted using Kaplan-Meier method and Cox regression models.ResultsThe pre-treatment CD4+/Total T cells ratio was significantly higher in responders than non-responders (P < 0.05). The levels of pre-treatment total lymphocytes (P = 0.012), total B lymphocytes (P = 0.025), and NK cells (P = 0.022), and post-treatment NK cells (P = 0.011) and NKT cells (P = 0.035) were significantly associated with OS. Post-treatment CD8+/Total T cells ratio was positively correlated with OS (P = 0.038). In multivariate analysis, post-treatment NK cells and post-treatment CD4+CD8+/Total T cells ratio were negatively associated with OS (hazard ratio [HR] = 10.30, P = 0.038) and PFS (HR = 1.95, P = 0.022), respectively. Notably, significantly positive correlations were observed between CD4+/Total T cells ratio and prognosis both before and after treatment (P < 0.05).ConclusionTo summarize, our finding reveals that high CD4+/total T cells ratio was associated with favorable response and prognosis, highlighting its potential as a predictive biomarker to guide the selection of likely responders to platinum and anti-PD-1 combination therapy.

BackgroundThe right atrial aneurysm is a rare cardiac malformation of unknown origin. It is typically asymptomatic but can occasionally lead to life-threatening and serious complications.Case descriptionWe present a case of a right atrial aneurysm in an eight-year-old child who experienced complications including rupture of the atrial aneurysm, thrombosis, and recurrent large pericardial effusions over a one-month period. Following surgical treatment, the child had a favorable prognosis.ConclusionA congenital right atrial aneurysm may manifest as either a widespread enlargement of the right atrium or a localized, smaller sac-like protrusion. In the latter case, diagnosis can be challenging to confirm through transthoracic echocardiography alone, and may require a cardiac computed tomography angiography examination for a definitive diagnosis. For patients experiencing recurrent large volumes of bloody pericardial effusion within one month, and exhibiting no atrial enlargement but showing abnormalities of the atrial wall in echocardiography, it is important to be vigilant about the potential for atrial aneurysm rupture in the heart. Timely treatment is essential to prevent the progression of the condition, which could otherwise result in a poor prognosis.

BackgroundSevere traumatic brain injuries (TBIs) are an important health issue worldwide, which are associated with harmful side effects. This meta-analysis investigates the cognitive and functional outcomes in severe brain trauma cases. It assesses the impact on memory, verbal and visual abilities, attention, learning, and the presence of depression. The study provides a comprehensive overview of the consequences of severe brain trauma injury on cognitive and functional domains.ObjectiveThe main objective of the current comprehensive meta-analysis study is to assess and analyze the impact of severe TBI on functional and cognitive outcomes, including verbal, visual, attention, learning, memory, and emotional stability.MethodsWe collected data from three online databases, including PubMed, Cochrane Library, and Embase. Case–control trials related to severe TBI association with cognitive and functional outcomes were included. Verbal strength, visual functions, learning abilities, attention, memory, and depression were considered primary outcomes.ResultsWe have included 13 case–control studies with 1,442 subjects in this meta-analysis, which provide adequate data to determine the pooled effect size for targeted outcomes. The effect of severe TBI on the inducement of depression and impairment of memory, verbal, visual, attention, and learning abilities compared to the control group showed statistically significant outcomes (p

In response to recent developments in adversarial attacks and defenses for object detection, relevant terms and concepts associated with object detection and adversarial learning were first introduced.Subsequently, according to the evolution process of the methods, a comprehensive retrospective analysis was conducted on the research achievements in the realm of adversarial attacks and defense methods for object detection.Particularly, attack methods and defense strategies were categorized based on the attacker knowledge and the deep learning lifecycle.Furthermore, an in-depth analysis and discussion of the characteristics and relationships among different approaches were provided.Lastly, considering the strengths and limitations of existing research, the imminent challenges and directions were summarized for further exploration in adversarial attack and defense of object detection.

Abstract Dementia, as an advanced diabetes-associated cognitive dysfunction (DACD), has become the second leading cause of death among diabetes patients. Given that little guidance is currently available to address the DACD process, it is imperative to understand the underlying mechanisms and screen out specific therapeutic targets. The excessive endogenous fructose produced under high glucose conditions can lead to metabolic syndrome and peripheral organ damage. Although generated by the brain, the role of endogenous fructose in the exacerbation of cognitive dysfunction is still unclear. Here, we performed a comprehensive study on leptin receptor-deficient T2DM mice and their littermate m/m mice and revealed that 24-week-old db/db mice had cognitive dysfunction and excessive endogenous fructose metabolism in the hippocampus by multiomics analysis and further experimental validation. We found that the rate-limiting enzyme of fructose metabolism, ketohexokinase, is primarily localized in microglia. It is upregulated in the hippocampus of db/db mice, which enhances mitochondrial damage and reactive oxygen species production by promoting nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) expression and mitochondrial translocation. Inhibiting fructose metabolism via ketohexokinase depletion reduces microglial activation, leading to the restoration of mitochondrial homeostasis, recovery of structural synaptic plasticity, improvement of CA1 pyramidal neuron electrophysiology and alleviation of cognitive dysfunction. Our findings demonstrated that enhanced endogenous fructose metabolism in microglia plays a dominant role in diabetes-associated cognitive dysfunction and could become a potential target for DACD.