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Light is a crucial environmental factor that influences the phenotypic development of plants. Despite extensive studies on the physiological, biochemical, and molecular mechanisms of the impact of light on phenotypes, genetic investigations regarding light-induced transgenerational plasticity in Arabidopsis thaliana remain incomplete. In this study, we used thaliana as the material, then gathered phenotypic data regarding leaf number and plant height under high- and low-light conditions from two generations. In addition to the developed genotype data, a functional mapping model was used to locate a series of significant single-nucleotide polymorphisms (SNPs). Under low-light conditions, a noticeable adaptive change in the phenotype of leaf number in the second generation suggests the presence of transgenerational genetic effects in thaliana under environmental stress. Under different lighting treatments, 33 and 13 significant genes associated with transgenerational inheritance were identified, respectively. These genes are largely involved in signal transduction, technical hormone pathways, light responses, and the regulation of organ development. Notably, genes identified under high-light conditions more significantly influence plant development, whereas those identified under low-light conditions focus more on responding to external environmental stimuli.

Abstract The face serves as a crucial cue for self-identification, while the sense of agency plays a significant role in determining our influence through actions in the environment. The current study investigates how self-identification through facial recognition may influence the perception of control via motion. We propose that self-identification might engender a belief in having control over one’s own face, leading to a more acute detection and greater emphasis on discrepancies between their actions and the sensory feedback in control judgments. We refer to the condition governed by the belief in having control as the exploitation mode. Conversely, when manipulating another individual’s face, the belief in personal control is absent. In such cases, individuals are likely to rely on the regularity between actions and sensory input for control judgments, exhibiting behaviors that are exploratory in nature to glean such information. This condition is termed the explorative mode. The study utilized a face-motion mixing paradigm, employing a deep generative model to enable participants to interact with either their own or another person’s face through facial and head movements. During the experiment, participants observed either their own face or someone else’s face (self-face vs. other-face) on the screen. The motion of the face was driven either purely by their own facial and head motion or by an average of the participant’s and the experimenter’s motion (full control vs. partial control). The results showed that participants reported a higher sense of agency over the other-face than the self-face, while their self-identification rating was significantly higher for the self-face. More importantly, controlling someone else’s face resulted in more movement diversity than controlling one’s own face. These findings support our exploration–exploitation theory: When participants had a strong belief in control triggered by the self-face, they became highly sensitive to any sensorimotor prediction errors, leading to a lower sense of agency. In contrast, when the belief of control was absent, the exploration mode triggered more explorative behaviors, allowing participants to efficiently gather information to establish a sense of agency.

In this study, we investigated the growth performance and early sex differentiation in Chinese longsnout catfish (Leiocassis longirostris), and further systematically evaluated its feminization by oral administration of various doses and treatment durations of 17β-estradiol (E2). Under the same breeding condition, the growth rate of male Chinese longsnout catfish was 20.8 % and 33.9 % faster than that of the female sibling at one- and two-year-old, respectively. The ovarian cavity began forming on 15 dph and completed by 21 dph, while the primary oocytes were at chromatin-nucleolus stage by 33 dph and at the peri-nucleolus stage oocytes by 65 dph. In presumptive testis, the seminiferous lobule appeared on 15 dph and the efferent duct anlage presented on 53 dph. Subsequently, germ cells entered into mitosis and formed the spermatogonia at 69 dph. Compared with the control group (no E2 diet), the fries treated with E2 at 10, 50, 100 or 150 mg/kg diet from 10 to 90 dph were 100 % female by morphology and histology observation. However, the growth and survival rate rapidly decreased as the E2 dosage rose. Furthermore, fries treated with10 mg/kg E2 during 15–85 dph, 20–80 dph, 25–75 dph, 30–70 dph, 35–65 dph and 40–60 dph were explored. 3.33 ± 3.33 % and 45.55 ± 5.09 % sex reversal ratio was identified in 30–70 dph and 35–65 dph group, respectively. All female populations were observed in 15–85 dph, 20–80 dph and 25–75 dph groups, despite slow development of ovary among them compared with the control group. Additionally, the growth performance of fries in 25–75 dph group was closest to that of the control group, while their serum E2 and 11-KT levels were consistent with XX females. Transcriptomic analyses were performed to assess gene expression difference among the XX females, XY males and feminized XY females, and most DEGs were shared between XY male vs XX female and XY male vs XY female. In addition, qRT-PCR validation of 12 DEGs associated with gonadal differentiation were consistent with RNA-Seq analysis (r=0.942, P

BackgroundA combination of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and immune checkpoint inhibitors (ICIs) yields a high tumor response rate and survival benefit in unresectable hepatocellular carcinoma (uHCC). However, the selection criteria for different ICIs remain unclear. This study aims to compare the efficacy and safety of PD-1/PD-L1 antibodies combined with HAIC and lenvatinib.MethodsThis retrospective study included 184 patients with uHCC treated with HAIC+lenvatinib+PD-1/PD-L1 antibody from June 2019 to January 2022. We utilized propensity score matching (PSM) to select and match 60 patients treated with HAIC + durvalumab + lenvatinib (HDL) against 60 patients treated with HAIC + PD-1 antibodies + lenvatinib (HPL) to compare the efficacy and safety profiles of these two groups.ResultsAfter PSM, the baseline characteristics were well-balanced between the HDL and HPL groups. The overall survival (p = 0.293) and progression-free survival (p = 0.146) showed no significant difference. The objective response rate (ORR) was higher in the HDL group compared to the HPL group according to modified RECIST (74.1% vs. 53.6%, p = 0.022) and RECIST 1.1 (60.3% vs. 41.1%, p = 0.040), respectively. The incidence of grade 3 or 4 adverse events (AEs) was 10.0% and 18.3% (p = 0.191) in the HDL and HPL groups, respectively.ConclusionsPD-L1 antibody appears to be a preferable companion in the combination therapy of HAIC + ICIs + lenvatinib compared to PD-1 antibody, showing higher ORR and relatively lower incidence of severe AEs. Further prospective studies involving a larger patient population are warranted.

Abstract The extracellular matrix (ECM) governs a wide spectrum of cellular fate processes, with a particular emphasis on anoikis, an integrin‐dependent form of cell death. Currently, anoikis is defined as an intrinsic apoptosis. In contrast to traditional apoptosis and necroptosis, integrin correlates ECM signaling with intracellular signaling cascades, describing the full process of anoikis. However, anoikis is frequently overlooked in physiological and pathological processes as well as traditional in vitro research models. In this review, we summarized the role of anoikis in physiological and pathological processes, spanning embryonic development, organ development, tissue repair, inflammatory responses, cardiovascular diseases, tumor metastasis, and so on. Similarly, in the realm of stem cell research focused on the functional evolution of cells, anoikis offers a potential solution to various challenges, including in vitro cell culture models, stem cell therapy, cell transplantation, and engineering applications, which are largely based on the regulation of cell fate by anoikis. More importantly, the regulatory mechanisms of anoikis based on molecular processes and ECM signaling will provide new strategies for therapeutic interventions (drug therapy and cell‐based therapy) in disease. In summary, this review provides a systematic elaboration of anoikis, thus shedding light on its future research.

Abstract Radiation‐induced heart disease (RIHD) is a heterogeneous, delayed, and potentially fatal adverse reaction to radiation that can damage all structures of the heart, including the pericardium, myocardium, coronary arteries, valves, and conduction system, leading to a series of diseases. Acute and chronic disease processes play a role in the development of RIHD, the onset times of which range from months to decades. However, the clinical manifestations of RIHD are usually insidious, overlap with several other diseases, and lack specificity. Cardiovascular imaging is essential for early diagnosis, follow‐up, and outcome assessment in patients with RIHD. This review first describes the pathogenesis and clinical manifestations of RIHD before providing an overview of the practical approaches and research advances in multimodal cardiovascular imaging in patients with RIHD, including echocardiography, cardiac magnetic resonance (CMR) and nuclear medicine, and cardiac computed tomography (CT). Then, the value of new cardiac imaging assessments for the early diagnosis of RIHD is described, particularly with relation to speckle‐tracking echocardiography, extracellular volume fraction assessment as a quantitative CMR technique, CMR myocardial strain assessment, positron emission tomography‐CT myocardial perfusion imaging, CT‐ECV, and CT strain assessment, amongst others. In addition, the advantages and disadvantages of each screening technique are compared with the aim of better guiding the follow‐up and diagnosis of subclinical RIHD and preventing cardiovascular events.

As a by-product of oil extraction, walnut meal was often used as feed or discarded, resulting in a waste of a large amount of high-quality protein resources. In this paper, for the high-value utilization of walnut meal resources, the highest content of glutelin was used as raw material to prepare walnut glutelin bacteriostatic peptide by solid-state fermentation with Bacillus subtilis and alkaline protease. The polypeptide content and the diameter of the inhibition zone of Staphylococcus aureus were used as the response values to optimize the optimal bacterial enzyme synergistic solid-state fermentation process parameters by single factor test. and response surface test. The thermal stability of the prepared glutelin bacteriostatic peptide was investigated. The results showed that the single factor test showed that the glutelin bacteriostatic peptide had a certain inhibitory effect on Escherichia coli and Staphylococcus aureus. The optimal fermentation process parameters under the response surface test were as follows: Inoculation amount 5%, solid-liquid ratio 1:1.5, fermentation temperature 43 ℃, fermentation time 3 d, and enzyme dosage 400 U/g. Under the optimal process conditions, the peptide content reached 26.35±1.29 mg/g, and the diameter of the inhibition zone against Staphylococcus aureus was 15.50±1.53 mm. Differential scanning calorimetry (DSC) analysis showed that glutelin antimicrobial peptides had higher thermal stability than glutelin. This study showed that the bacteriostatic peptide prepared by solid-state fermentation of walnut glutelin with enzyme has a good bacteriostatic effect and relatively stable structure.

Abstract Background Although CDKN2A alteration has been explored as a favorable factor for tumorigenesis in pan-cancers, the association between CDKN2A point mutation (MUT) and intragenic deletion (DEL) and response to immune checkpoint inhibitors (ICIs) is still disputed. This study aims to determine the associations of CDKN2A MUT and DEL with overall survival (OS) and response to immune checkpoint inhibitors treatment (ICIs) among pan-cancers and the clinical features of CDKN2A-altered gastric cancer. Methods This study included 45,000 tumor patients that underwent tumor sequencing across 33 cancer types from four cohorts, the MSK-MetTropism, MSK-IMPACT, OrigiMed2020 and TCGA cohorts. Clinical outcomes and genomic factors associated with response to ICIs, including tumor mutational burden, copy number alteration, neoantigen load, microsatellite instability, tumor immune microenvironment and immune-related gene signatures, were collected in pan-cancer. Clinicopathologic features and outcomes were assessed in gastric cancer. Patients were grouped based on the presence of CDKN2A wild type (WT), CDKN2A MUT, CDKN2A DEL and CDKN2A other alteration (ALT). Results Our research showed that CDKN2A-MUT patients had shorter survival times than CDKN2A-WT patients in the MSK MetTropism and TCGA cohorts, but longer OS in the MSK-IMPACT cohort with ICIs treatment, particularly in patients having metastatic disease. Similar results were observed among pan-cancer patients with CDKN2A DEL and other ALT. Notably, CDKN2A ALT frequency was positively related to tumor-specific objective response rates to ICIs in MSK MetTropism and OrigiMed 2020. Additionally, individuals with esophageal carcinoma or stomach adenocarcinoma who had CDKN2A MUT had poorer OS than patients from the MSK-IMPACT group, but not those with adenocarcinoma. We also found reduced levels of activated NK cells, T cells CD8 and M2 macrophages in tumor tissue from CDKN2A-MUT or DEL pan-cancer patients compared to CDKN2A-WT patients in TCGA cohort. Gastric cancer scRNA-seq data also showed that CDKN2A-ALT cancer contained less CD8 T cells but more exhausted T cells than CDKN2A-WT cancer. A crucial finding of the pathway analysis was the inhibition of three immune-related pathways in the CDKN2A ALT gastric cancer patients, including the interferon alpha response, inflammatory response, and interferon gamma response. Conclusions This study illustrates the CDKN2A MUT and DEL were associated with a poor outcome across cancers. CDKN2A ALT, on the other hand, have the potential to be used as a biomarker for choosing patients for ICI treatment, notably in esophageal carcinoma and stomach adenocarcinoma.

Abstract Nowadays, immunotherapy is one of the most promising anti-tumor therapeutic strategy. Specifically, immune-related targets can be used to predict the efficacy and side effects of immunotherapy and monitor the tumor immune response. In the past few decades, increasing numbers of novel immune biomarkers have been found to participate in certain links of the tumor immunity to contribute to the formation of immunosuppression and have entered clinical trials. Here, we systematically reviewed the oncogenesis and progression of cancer in the view of anti-tumor immunity, particularly in terms of tumor antigen expression (related to tumor immunogenicity) and tumor innate immunity to complement the cancer-immune cycle. From the perspective of integrated management of chronic cancer, we also appraised emerging factors affecting tumor immunity (including metabolic, microbial, and exercise-related markers). We finally summarized the clinical studies and applications based on immune biomarkers. Overall, immune biomarkers participate in promoting the development of more precise and individualized immunotherapy by predicting, monitoring, and regulating tumor immune response. Therefore, targeting immune biomarkers may lead to the development of innovative clinical applications.

Abstract Background Immune checkpoint blockade (ICB) has revolutionized the treatment of various cancer types. Despite significant preclinical advancements in understanding mechanisms, identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging. Recent evidence, both preclinical and clinical, underscores the pivotal role of the extracellular matrix (ECM) in modulating immune cell infiltration and behaviors. This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy. Methods We analyzed transcriptomic collagen activity and immune signatures in 649 patients with cancer undergoing ICB therapy. This analysis led to the identification of three distinct immuno‐collagenic subtypes predictive of ICB responses. We validated these subtypes using the transcriptome data from 9,363 cancer patients from The Cancer Genome Atlas (TCGA) dataset and 1,084 in‐house samples. Additionally, novel therapeutic targets were identified based on these established immuno‐collagenic subtypes. Results Our categorization divided tumors into three subtypes: “soft & hot” (low collagen activity and high immune infiltration), “armored & cold” (high collagen activity and low immune infiltration), and “quiescent” (low collagen activity and immune infiltration). Notably, “soft & hot” tumors exhibited the most robust response to ICB therapy across various cancer types. Mechanistically, inhibiting collagen augmented the response to ICB in preclinical models. Furthermore, these subtypes demonstrated associations with immune activity and prognostic predictive potential across multiple cancer types. Additionally, an unbiased approach identified B7 homolog 3 (B7‐H3), an available drug target, as strongly expressed in “armored & cold” tumors, relating with poor prognosis. Conclusion This study introduces histopathology‐based universal immuno‐collagenic subtypes capable of predicting ICB responses across diverse cancer types. These findings offer insights that could contribute to tailoring personalized immunotherapeutic strategies for patients with cancer.

BackgroundBiological age (BA) offers an effective assessment of true aging state. The progression of Osteoarthritis (OA) is closely associated with an increase in chronological age, the correlation between BA and OA has not been fully elucidated.MethodsThis study analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2005–2018. Thirteen commonly used clinical traits were employed to calculate two measures of BA: the Klemera-Doubal method age (KDM-Age) and phenotypic age (Pheno-Age). The residuals of the regression of these ages based on chronological age were calculated as KDM-Age or Pheno-Age acceleration, respectively. OA was determined through self-reported prior diagnoses. The prevalence of OA across different quartiles of BA was compared using weighted chi-square tests and linear trend tests. The association between BA and OA was assessed using weighted multivariate logistic regression models.ResultsA total of 30,547 participants aged ≥20 years were included in this study, 3,922 (14%) were diagnosed with OA. Participants with OA exhibited higher chronological age, KDM-Age, Pheno-Age, KDM-Age advance, and Pheno-Age advance compared to those without OA (p

Background Immune checkpoint blockade (ICB) has made remarkable achievements, but newly identified armored and cold tumors cannot respond to ICB therapy. The high prevalence of concomitant medications has huge impact on immunotherapeutic responses, but the clinical effects on the therapeutic outcome of armored and cold tumors are still unclear.Methods In this research, using large-scale transcriptomics datasets, the expression and potential biological functions of angiotensin II receptor 1 (AGTR1), the target of angiotensin receptor blocker (ARB), were investigated. Next, the roles of ARB in tumor cells and tumor microenvironment cells were defined by a series of in vitro and in vivo assays. In addition, the clinical impacts of ARB on ICB therapy were assessed by multicenter cohorts and meta-analysis.Results AGTR1 was overexpressed in armored and cold tumors and associated with poor response to ICB therapy. ARB, the inhibitor for AGTR1, only suppressed the aggressiveness of tumor cells with high AGTR1 expression, which accounted for a very small proportion. Further analysis revealed that AGTR1 was always highly expressed in cancer-associated fibroblasts (CAFs) and ARB inhibited type I collagen expression in CAFs by suppressing the RhoA-YAP axis. Moreover, ARB could also drastically reverse the phenotype of armored and cold to soft and hot in vivo, leading to a higher response to ICB therapy. In addition, both our in-house cohorts and meta-analysis further supported the idea that ARB can significantly enhance ICB efficacy.Conclusion Overall, we identify AGTR1 as a novel target in armored and cold tumors and demonstrate the improved therapeutic efficacy of ICB in combination with ARB. These findings could provide novel clinical insight into how to treat patients with refractory armored and cold tumors.

Summary: Physical activity reduces cancer-associated mortality through multiple mechanisms, including tumor immune microenvironment (TIME) reprogramming. However, whether and how physiological interventions promote anti-tumor immunity remain elusive. Here, we report that clinically relevant voluntary exercise promotes muscle-derived extracellular vesicle (EV)-associated miR-29a-3p for tumor extracellular matrix (ECM) inhibition in patients and mouse models, thereby permitting immune cell infiltration and immunotherapy. Mechanistically, an unbiased screening identifies EV-associated miR-29a-3p in response to leisure-time physical activity or voluntary exercise. MiR-29a-3p-containing EVs accumulate in tumors and downregulate collagen composition by targeting COL1A1. Gain- and loss-of-function experiments and cytometry by time of flight (CyTOF) demonstrate that myocyte-secreted miR-29a-3p promotes anti-tumor immunity. Combining immunotherapy with voluntary exercise or miR-29a-3p further enhances anti-tumor efficacy. Clinically, miR-29a-3p correlates with reduced ECM, increased T cell infiltration, and response to immunotherapy. Our work reveals the predictive value of miR-29a-3p for immunotherapy, provides mechanistic insights into exercise-induced anti-cancer immunity, and highlights the potential of voluntary exercise in sensitizing immunotherapy.

Introduction: A strong association was previously established between body mass index (BMI) and female reproductive system tumors; however, the causal relationship is unclear. We conducted a Mendelian randomization (MR) study to further explore this association. Methods: Genetic information for BMI was retrieved from a published genome-wide association study involving 339,224 participants. Genetic associations with five common female reproductive system tumors were obtained from the FinnGen, UK Biobank studies, and other large consortia. Results: Genetic predisposition towards BMI exhibits a significant association with multiple tumors of the female reproductive system. Specifically, for every 1-unit increase in BMI log-transformed odds ratio (OR). The OR fluctuations overall for patients with breast cancer ranged from 0.661 to 0.996 (95% confidence interval [CI],0.544-1.000, P

ObjectiveThe study aimed to explore the relationship between systemic inflammatory response index (SIRI) levels and osteoarthritis (OA) using cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2018.MethodsUsing cross-sectional data from the NHANES database from 2005 to 2018, we included 11,381 study participants divided into OA (n = 1,437) and non-OA (n = 9,944) groups. Weighted multivariable regression models and subgroup analyses were employed to investigate the relationship between SIRI and OA. Additionally, restricted cubic spline models were used to explore nonlinear relationships.ResultsThis study enrolled 11,381 participants aged ≥20 years, including 1,437 (14%) with OA. Weighted multivariable regression analysis in the fully adjusted Model 3 indicated a correlation between higher levels of SIRI (log2-transformed) and an increased OA risk (odds ratio: 1.150; 95% confidence interval: 1.000–1.323, p 0.05). Additionally, a restricted cubic spline model revealed a nonlinear relationship between log2(SIRI) and OA risk, with a threshold effect showing 4.757 as the critical value of SIRI. SIRI 4.757 showed rapidly increasing OA risk.ConclusionThe positive correlation between SIRI and OA risk, with a critical value of 4.757, holds clinical value in practical applications. Additionally, our study indicates that SIRI is a novel, clinically valuable, and convenient inflammatory biomarker that can be used to predict OA risk in adults.

ObjectiveThis study aims to compare the utilization of 3D-CT reconstruction in measuring pedicle outer width (POW) between younger/middle-aged patients ( 0.05). In the observation group, both male and female patients had significantly smaller POW compared to the control group (P 0.05). In the observation group, the POW was less than 5 mm in 9.33% (81/868) of cases and less than 7 mm in 49.88% (433/868) of cases, primarily observed from T11 to L3. In the control group, 4.81% (31/644) of cases had a POW of less than 5 mm, and 13.81% (88/644) had a POW of less than 7 mm.ConclusionUtilizing preoperative 3D-CT reconstruction to measure POW in patients with TSF not only facilitates the assessment of surgical feasibility but also aids in surgical pathway planning, thus potentially reducing the incidence of postoperative complications.

Abstract Proteins containing a ubiquitin regulatory X (UBX) domain are cofactors of Cell Division Cycle 48 (CDC48) and function in protein quality control. However, whether and how UBX-containing proteins participate in host–microbe interactions remain unclear. Here we show that MoNLE1, an effector from the fungal pathogen Magnaporthe oryzae, is a core virulence factor that suppresses rice immunity by specifically interfering with OsPUX8B.2. The UBX domain of OsPUX8B.2 is required for its binding to OsATG8 and OsCDC48-6 and controls its 26 S proteasome–dependent stability. OsPUX8B.2 and OsCDC48-6 positively regulate plant immunity against blast fungus, while the high-temperature tolerance heat-shock protein OsBHT, a putative cytoplasmic substrate of OsPUX8B.2–OsCDC48-6, negatively regulates defense against blast infection. MoNLE1 promotes the nuclear migration and degradation of OsPUX8B.2 and disturbs its association with OsBHT. Given the high conservation of MoNLE1 among fungal isolates, plants with broad and durable blast resistance might be generated by engineering intracellular proteins resistant to MoNLE1.

Abstract Background The objective of this research was to elucidate the association between the length of infertility and the outcomes of intrauterine insemination (IUI) in women of varying ages - a topic that has been the subject of investigation for numerous years, yet lacks a definitive consensus. Methods A retrospective cohort investigation involving 5268 IUI cycles was undertaken at the Reproductive Medicine Center of Nanjing Drum Tower Hospital from 2016 to 2022. Utilizing the smooth fitting curve along with threshold and saturation effect analysis, the correlation between infertility duration and IUI clinical pregnancy rates was discerned. Moreover, patients were bifurcated into two cohorts based on their respective infertility durations. A secondary examination was also performed employing propensity-score matching to mitigate the impact of confounding variables. Subsequent threshold and saturation effect analysis was carried out across various subgroups, segmented on the basis of age differentiation. Results When the duration of infertility was more than 5 years, the clinical pregnancy rate decreased with the increase of infertility duration (aOR: 0.894, 95%CI: 0.817–0.991, p = 0.043). The multivariate regression analysis suggested that longer duration of infertility (≥ 5 years) was significantly correlated with the lower clinical pregnancy rate (aOR: 0.782, 95% CI: 0.643–0.950, p = 0.01). After the propensity-score matching, the clinical pregnancy rate of women with longer infertility duration were also higher. When the duration of infertility was more than 5 years, the clinical pregnancy rate of women younger than 35 years old decreased with the increase of infertility duration (aOR: 0.906, 95%CI: 0.800–0.998, p = 0.043). Conclusions The clinical pregnancy rate and live birth rate of IUI in young women (

Abstract Evidence has revealed that DDOST plays an important role in cancer development and progression. However, there are no reports on functions of DDOST in cervical tumorigenesis. Hence, we investigated the relationship of DDOST with prognosis, mutation, promoter methylation, immune cell infiltration, and drug sensitivity using bioinformatics techniques. Our results demonstrated that DDOST was significantly upregulated in a variety of tumor types and correlated with poor prognosis, including cervical cancer. Cox regression analysis dissected that high DDOST expression was associated with poor survival in cervical cancer patients. Immune infiltration analysis defined that DDOST was negatively correlated with CD8 T cells and NK cells. Strikingly, the sensitivity to multiple drugs was negatively correlated with the expression of DDOST. Therefore, our findings uncovered that DDOST could play an essential role in the tumor microenvironment and tumor immune regulation in cervical cancer, which indicated that DDOST could be a useful biomarker for prognosis and a potential therapeutic target for cancer treatment.

The Ambient Internet of Things (A-IoT) has emerged as a critical direction for achieving effective connectivity as the IoT system evolves to 6G. However, the introduction of A-IoT technologies, particularly involving backscatter modulation, poses numerous challenges for system design and network operations. This paper surveys current standardization efforts, highlights potential challenges, and explores future directions for A-IoT. It begins with a comprehensive overview of ongoing standardization initiatives by the 3rd Generation Partnership Project (3GPP) on A-IoT, providing a solid foundation for further technical research in both industry and academia. Building upon this groundwork, the paper conducts an analysis of critical enabling technologies for A-IoT. Moreover, a comprehensive A-IoT demonstration system is designed to showcase the practical viability and efficiency of A-IoT techniques, supported by field experiments. We finally address ongoing challenges associated with A-IoT technologies, providing valuable insights for future research endeavors.

This paper proposes an Internet of Things (IoT) system to effectively monitor and analyze ecological environments in real time. Firstly, we present the overall architecture of the proposed IoT system including multiple layers. Then, focusing on several important modules within the cloud layer, this paper elaborates on the corresponding design concepts and implementation methods. Moreover, leveraging Geographic Information System technology, spatial data visualization is designed and implemented at the application layer to provide users with intuitive perceptions of ecological environment changes. Finally, this proposed IoT system is deployed and operated in a suburban environment while extensive experiments are conducted. The experimental results indicate that the system works well in terms of graphical user interface performance, network utilization efficiency, sensory data collection, demonstrating the feasibility and effectiveness of the system design.

Abstract Triple-negative breast cancer (TNBC) is generally regarded as the most aggressive subtype among breast cancers, but exhibits higher chemotherapeutic and immunotherapeutic responses due to its unique immunogenicity. Thus, appropriate discrimination of subtypes is critical for guiding therapeutic options in clinical practice. In this research, using multiple in-house and public cohorts, we investigated the expression features and immuno-correlations of B7-H3 in breast cancer and checked the anti-tumor effect of the B7-H3 monoclonal antibody in a mouse model. We also developed a novel classifier combining B7-H3 and PD-L1 expression in TNBC. B7-H3 was revealed to be related to immuno-cold features and accumulated collagen in TNBC. In addition, targeting B7-H3 using the monoclonal antibody significantly suppressed mouse TNBC growth, reversed the armored-cold phenotype, and also boosted anti-PD-1 immunotherapy. In addition, patients with B7-H3 high and PD-L1 low expression showed the lowest anti-tumor immune infiltration, the highest collagen level, and the lowest therapeutic responses to multiple therapies, which mostly belong to armored-cold tumors. Overall, this research provides a novel subtyping strategy based on the combination of B7-H3/PD-L1 expression, which leads to a novel approach for the management of TNBC.

Tibetan tea changes during microorganism fermentation. Research on microorganisms in Tibetan tea has focused on their identification, while studies on the influence of specific microorganisms on the components and health functions of Tibetan tea are lacking. Bacillus licheniformis was inoculated into Tibetan tea for intensive fermentation, and the components of B. licheniformis-fermented tea (BLT) were detected by liquid chromatography with tandem mass spectrometry (UHPLC-TOF-MS), and then the effects of BLT on intestinal probiotic functions were investigated by experiments on mice. The results revealed the metabolites of BLT include polyphenols, alkaloids, terpenoids, amino acids, and lipids. Intensified fermentation also improved the antioxidant capacity in vivo and the protective effect on the intestinal barrier of Tibetan tea. In addition, the enhanced fermentation of Tibetan tea exerted intestinal probiotic effects by modulating the relative abundance of short-chain fatty acid-producing bacteria in the intestinal flora. Therefore, intensive fermentation with B. licheniformis can improve the health benefits of Tibetan tea.

The Chinese mitten crab is an important aquaculture product in China. Currently, rice-crab co-culture is a novel model that can realize positive interactions. The feed for Chinese mitten crabs cultured in rice fields should be distinguished from other modes, since their culture environment is unique. Therefore, this study designed three experimental groups that were fed 15% (RC1), 25% (RC2), and 35% (RC3) protein, with a natural bait group (RC0) without artificial feeding as the control. The protein nutritional requirements of Chinese mitten crabs in a rice-crab co-culture model were investigated by exploring the indicators of growth performance, nutrient composition, immunity, antioxidant capacity, and economic benefits of different groups. Through a comprehensive discussion of one-way analysis of variance and regression analysis of the data, we obtained the following results: feeds with high-level protein improved the growth performance, quality, and economic benefits of Chinese mitten crabs and reduced their exposure to oxidative stress. Specifically, the contents of major nutrients and flavor-presenting substances, such as free amino acids (FAA), nucleotides, and essential amino acids (EAA), in the edible parts of female crabs in the 35% protein group were significantly higher than those in all other groups. Male crabs fed 25% − 28.08% protein diets showed higher production performance and FAA content. In conclusion, the optimal dietary protein levels for male and female crabs reared in rice fields are different: they are 35% for females, and at least 25% for males. Therefore, for actual crab production, male and female crabs could be cultured separately using different protein baits to reduce bait costs and achieve green and sustainable development.

Abstract Background Organoid technology is an emerging and rapidly growing field that shows promise in studying organ development and screening therapeutic regimens. Although organoids have been proposed for a decade, concerns exist, including batch‐to‐batch variations, lack of the native microenvironment and clinical applicability. Main body The concept of organoids has derived patient‐derived tumour organoids (PDTOs) for personalized drug screening and new drug discovery, mitigating the risks of medication misuse. The greater the similarity between the PDTOs and the primary tumours, the more influential the model will be. Recently, ‘tumour assembloids’ inspired by cell‐coculture technology have attracted attention to complement the current PDTO technology. High‐quality PDTOs must reassemble critical components, including multiple cell types, tumour matrix, paracrine factors, angiogenesis and microorganisms. This review begins with a brief overview of the history of organoids and PDTOs, followed by the current approaches for generating PDTOs and tumour assembloids. Personalized drug screening has been practised; however, it remains unclear whether PDTOs can predict immunotherapies, including immune drugs (e.g. immune checkpoint inhibitors) and immune cells (e.g. tumour‐infiltrating lymphocyte, T cell receptor‐engineered T cell and chimeric antigen receptor‐T cell). PDTOs, as cancer avatars of the patients, can be expanded and stored to form a biobank. Conclusion Fundamental research and clinical trials are ongoing, and the intention is to use these models to replace animals. Pre‐clinical immunotherapy screening using PDTOs will be beneficial to cancer patients. Key Points The current PDTO models have not yet constructed key cellular and non‐cellular components. PDTOs should be expandable and editable. PDTOs are promising preclinical models for immunotherapy unless mature PDTOs can be established. PDTO biobanks with consensual standards are urgently needed.

Abstract Background Mutations in the KEAP1-NFE2L2 signaling pathway were linked to increased tumorigenesis and aggressiveness. Interestingly, not all hotspot mutations on NFE2L2 were damaging; some even were activating. However, there was conflicting evidence about the association between NFE2L2 mutation and Nrf2-activating mutation and responsiveness to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) and other multiple cancers. Methods The study with the largest sample size (n = 49,533) explored the landscape of NFE2L2 mutations and their impact response/resistance to ICIs using public cohorts. In addition, the in-house WXPH cohort was used to validate the efficacy of immunotherapy in the NFE2L2 mutated patients with NSCLC. Results In two pan-cancer cohorts, Nrf2-activating mutation was associated with higher TMB value compared to wild-type. We identified a significant association between Nrf2-activating mutation and shorter overall survival in pan-cancer patients and NSCLC patients but not in those undergoing ICIs treatment. Similar findings were obtained in cancer patients carrying the NFE2L2 mutation. Furthermore, in NSCLC and other cancer cohorts, patients with NFE2L2 mutation demonstrated more objective responses to ICIs than patients with wild type. Our in-house WXPH cohort further confirmed the efficacy of immunotherapy in the NFE2L2 mutated patients with NSCLC. Lastly, decreased inflammatory signaling pathways and immune-depleted immunological microenvironments were enriched in Nrf2-activating mutation patients with NSCLC. Conclusions Our study found that patients with Nrf2-activating mutation had improved immunotherapy outcomes than patients with wild type in NSCLC and other tumor cohorts, implying that Nrf2-activating mutation defined a distinct subset of pan-cancers and might have implications as a biomarker for guiding ICI treatment, especially NSCLC.

Abstract The darkbarbel catfish (Pelteobagrus vachelli), an economically important aquaculture species in China, is extensively employed in hybrid yellow catfish production due to its superior growth rate. However, information on its genome has been limited, constraining further genetic studies and breeding programs. Leveraging the power of PacBio long-read sequencing and Hi-C technologies, we present a high-quality, chromosome-level genome assembly for the darkbarbel catfish. The resulting assembly spans 692.10 Mb, with an impressive 99.9% distribution over 26 chromosomes. The contig N50 and scaffold N50 are 13.30 Mb and 27.55 Mb, respectively. The genome is predicted to contain 22,109 protein-coding genes, with 96.1% having functional annotations. Repeat elements account for approximately 35.79% of the genomic landscape. The completeness of darkbarbel catfish genome assembly is highlighted by a BUSCO score of 99.07%. This high-quality genome assembly provides a critical resource for future hybrid catfish breeding, comparative genomics, and evolutionary studies in catfish and other related species.

Primary and metastatic lung cancers are malignant lung tumors each with of which has a different pathogenesis, although both threaten patient lives. Tumor development and progression involve communication between tumor cells and the host microenvironment. Neutrophils are the most abundant immune cells in the tumor microenvironment (TME); they participate in the generation of an inflammatory milieu and influence patient survival through their anti- and pro-tumor abilities. Neutrophils can be classified into various categories according to different criteria; frequent categories include N1 antitumor neutrophils and N2 immunosuppressive neutrophils. The antitumor effects of neutrophils are reported to be mediated through a combination of reactive oxygen species, tumor necrosis factor-related apoptosis-inducing ligand, and receptor for advanced glycation end-products–cathepsin G association, as well as the regulation of the activities of other immune cells. There have also been reports that neutrophils can function as tumor promoters that contribute to lung cancer progression and metastasis by influencing processes including carcinogenesis, angiogenesis, cancer cell proliferation, and invasion ability, as well as having similar roles in the lung metastasis of other cancers. The rapid development of nanotechnology has provided new strategies for cancer treatment targeting neutrophils.

The maize anthracnose stalk rot and leaf blight diseases caused by the fungal pathogen Colletotrichum graminicola is emerging as an important threat to corn production worldwide. In this work, we provide an improved genome assembly of a C. graminicola strain (TZ-3) by using the PacBio Sequel II and Illumina high-throughput sequencing technologies. The genome of TZ-3 consists of 36 contigs with a length of 59.3 Mb. After correction and evaluation with the Illumina sequencing data and BUSCO, this genome showed a high assembly quality and integrity. Gene annotation of this genome predicted 11,911 protein-coding genes, among which 983 secreted protein-coding genes and 332 effector genes were predicted. Compared with previous genomes of C. graminicola strains, TZ-3 genome is superior in nearly all parameters. The genome assembly and annotation will enhance our knowledge of the genetic makeup of the pathogen and molecular mechanisms underlying its pathogenicity and will provide valuable insights into genome variation across different regions. [Graphic: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Excessive salt intake is a widespread health issue observed in almost every country around the world. A high salt diet (HSD) has a strong correlation with numerous diseases, including hypertension, chronic kidney disease, and autoimmune disorders. However, the mechanisms underlying HSD-promotion of inflammation and exacerbation of these diseases are not fully understood. In this study, we observed that HSD consumption reduced the abundance of the gut microbial metabolite L-fucose, leading to a more substantial inflammatory response in mice. A HSD led to increased peritonitis incidence in mice, as evidenced by the increased accumulation of inflammatory cells and elevated levels of inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and monocyte chemotactic protein-1 (MCP-1, also known as C-C motif chemokine ligand 2 or CCL2), in peritoneal lavage fluid. Following the administration of broad-spectrum antibiotics, HSD-induced inflammation was abolished, indicating that the proinflammatory effects of HSD were not due to the direct effect of sodium, but rather to HSD-induced alterations in the composition of the gut microbiota. By using untargeted metabolomics techniques, we determined that the levels of the gut microbial metabolite L-fucose were reduced by a HSD. Moreover, the administration of L-fucose or fucoidan, a compound derived from brown that is rich in L-fucose, normalized the level of inflammation in mice following HSD induction. In addition, both L-fucose and fucoidan inhibited LPS-induced macrophage activation in vitro. In summary, our research showed that reduced L-fucose levels in the gut contributed to HSD-exacerbated acute inflammation in mice; these results indicate that L-fucose and fucoidan could interfere with HSD-promotion of the inflammatory response.

The regulatory mechanism of gonadal sex differentiation, which is complex and regulated by multiple factors, remains poorly understood in teleosts. Recently, we have shown that compromised androgen and estrogen synthesis with increased progestin leads to all-male differentiation with proper testis development and spermatogenesis in cytochrome P450 17a1 (cyp17a1)-/- zebrafish. In the present study, the phenotypes of female-biased sex ratio were positively correlated with higher Fanconi anemia complementation group L (fancl) expression in the gonads of doublesex and mab-3 related transcription factor 1 (dmrt1)-/- and cyp17a1-/-;dmrt1-/- fish. The additional depletion of fancl in cyp17a1-/-;dmrt1-/- zebrafish reversed the gonadal sex differentiation from all-ovary to all-testis (in cyp17a1-/-;dmrt1-/-;fancl-/- fish). Luciferase assay revealed a synergistic inhibitory effect of Dmrt1 and androgen signaling on fancl transcription. Furthermore, an interaction between Fancl and the apoptotic factor Tumour protein p53 (Tp53) was found in vitro. The interaction between Fancl and Tp53 was observed via the WD repeat domain (WDR) and C-terminal domain (CTD) of Fancl and the DNA binding domain (DBD) of Tp53, leading to the K48-linked polyubiquitination degradation of Tp53 activated by the ubiquitin ligase, Fancl. Our results show that testis fate in cyp17a1-/- fish is determined by Dmrt1, which is thought to stabilize Tp53 by inhibiting fancl transcription during the critical stage of sexual fate determination in zebrafish.

ObjectiveTo determine the difference in the prevalence of lymphopenia in the American population according to demographic characteristics, body mass index (BMI) and living habits.MethodsA total of 33,365 participants aged over 1 were included in the 2009-2018 National Health and Nutrition Survey (NHANES). All analyses used weighted samples and considered the layering and clustering of the design.ResultsUsing white participants as a reference, the prevalence of lymphopenia in Mexican-American participants was significantly lower than that of white participants (P = 0.018). There was no significant difference in the prevalence of lymphopenia between black participants (P = 0.376) and white participants. The prevalence of lymphopenia was 1.81% (95%CI, 1.53%-2.10%) for white participants, 1.08% (95%CI, 0.78%-1.39%) for black participants, and 0.42% (95%CI, 0.17%-0.68%) for Mexican-American participants. The prevalence of lymphopenia increases with age, reaching a peak of 6.84% among elderly participants aged 75 and above. In terms of the gender difference, the prevalence of lymphopenia in men is significantly higher than that in women (PConclusionIn the diagnosis and treatment of lymphopenia, clinicians should consider the influence of factors such as race, gender, age, sleep disorders, and other unhealthy lifestyle habits to improve the accuracy of diagnosis and treatment, thereby reducing the high mortality risk associated with lymphopenia. Consequently, we propose a novel perspective that the diagnosis and treatment of lymphopenia should be tailored to the lymphocyte levels of specific subpopulations, rather than applying a generalized approach.

Small bodies have the characteristics of noncooperative, irregular gravity, and complex terrain on the surface, which cause difficulties in successful landing for conventional landers. In this paper, a multinode flexible lander is put forward to address the problem. The dynamics of this new lander are constructed based on the port-Hamilton framework. The trajectory-tracking formation controller for the lander is designed in a passive way. The proposed dynamics and controller are further validated through numerical simulations. This research presents a fresh concept that holds inspiration for future design involving small-body landers.

This article proposes a new connection method of tapped inductors that works in the current source, which enables the current-mode power converter circuit to have a new topological relationship. Usually, in a switched-inductor circuit, a stable output multiple is obtained through the connection of the inductor and the switching devices. This is because the tapped point on the inductor varies, and the magnetomotive force (mmf) of inductance is adjusted. Thereby, the output current is controlled by the states of switching devices within a certain range. This optimized circuit structure can adjust the output current according to load changes in practical applications without changing the input power supply. The proposed method has been verified for its feasibility through detailed analysis and hardware work. The principal analysis based on the flux linkage and the PSIM simulation confirms that the theoretical circuit can be implemented. Finally, a hardware circuit is built to obtain real and feasible conclusions, and it is verified that the circuit can achieve a stable output and variable current within a specific range. The proposed work presents an alternative power conversion methodology using the active switching of mmf, and it is a stable and simple power conversion technique.

Under long-term hydro-mechanical coupling, the propagation of adjacent cracks present obvious time effect, and have significant influence on the progressive failure mode of rock-like materials. The creep tests were carried out based on the cement mortar specimen containing adjacent cracks, and the low-field Nuclear Magnetic Resonance (NMR) technology were used to evaluate the evolution of crack structure in the specimen. Based on the numerical simulation, the influences of the interaction behaviour between cracks on the time-dependent propagation of cracks and failure of specimens is revealed. The results show that: The specimen presents a tension-shear failure mode, and the macro fracture on its surface is Z-shaped; Crack interaction has an important role in promoting the formation and connection of microcracks, which increases the number of seepage channels and promotes the formation of the macro fracture; The propagation of adjacent cracks show significant asymmetry and non-uniformity, due to the stress superposition effects in the rock bridge area; The interaction between cracks is manifested as the inhibition of wing crack propagation in the rock bridge area at the initiation stage and then promotion effect at the later stage.

The nutritional quality of three edible parts (gonads, hepatopancreas and muscles) of Chinese mitten crabs (CMCs) from rice field culture and pond culture was firstly compared in our current study. It was found that the contents of mineral elements and volatile compounds in rice CMCs were superior to those in pond CMCs, and the antioxidant enzyme activities of rice CMCs were markedly higher than those of pond CMCs. Besides, the total free amino acid levels in the edible parts of pond CMCs were higher than those of rice CMCs. Compared with other tissues, the nucleotide and equivalent umami concentrations of the gonads in female rice CMCs were the maximum. Overall, both types of crabs demonstrated good nutritional quality, which met human nutrition and dietary needs. In comparison, the quality of rice CMCs was better than that of pond CMCs.

Objectives The Healthy China 2030 strategy outlines the government's plans for healthcare reform, emphasizing the need for increased awareness about infectious diseases to prevent and fight future infections. Information campaigns can be used as a medium to raise awareness and encourage citizens’ willingness to protect themselves against diseases, such as COVID-19. Extant studies have found that individual health behavior decision-making can be changed under different information frames. However, limited evidence is available about emerging infectious diseases. Based on the Prospect Theory and Theory of Planned Behavior, the impact of information frames on self-protective behavior—vaccination against COVID-19 is investigated in this study. Methods A 2(gain/loss frame)*2(factual/emotional frame) intergroup experimental design was designed to explore the effects of different information frames. 228 valid participants in China were recruited and the experiment was performed online. Results First, the gain frame was more effective in promoting public self-protection behavior than the loss frame under information frame intervention. Compared with the factual frame, the emotional frame is more effective in reducing individual risk perception. Second, perceptual behavior control has masking effects on self-protection behavior under the influence of the gain/loss frame. Third, age, subjective norms, attitudes, and the gain frame, have predictive effects on self-protection behavior. Conclusions This study provides empirical evidence on the impact of information framing interventions on public self-protection behavior during the COVID-19 pandemic and provides important practical implications for public administrators and media practitioners.

ObjectiveTumor in situ fluid (TISF) refers to the fluid within surgical cavities of glioma. Several studies preliminarily proved the value of cell-free tumor DNA (cf-tDNA) from TISF in the dynamic characterization of the glioma genome. Here, we assessed the potential utility of TISF cf-tDNA in broad aspects of tumor evolution under therapeutic pressure.MethodsThis study was conducted under an Institutional Review Board-approved protocol at Henan Provincial People’s Hospital (China). Cf-tDNA samples were sequenced with a designed 68-gene panel. A total of 205 cf-tDNA samples from 107 patients were studied. The clinical relevance of serial cf-tDNA profiling during the postoperative course was analyzed.ResultsAt least one tumor mutations were detected in 179/205 (87.3%) TISF cf-tDNA samples. Serial cf-tDNA was complementary to molecular residual disease and to initial tumors. Serial cf-tDNA revealed the selection of pre-existing mismatch repair-deficient cells by temozolomide as a resistant mechanism. Cf-tDNA parameters during treatment were predictive of recurrence, and serial cf-tDNA monitoring had diagnostic value for early recurrence. A total of 223 potentially actionable genomic alterations were assessed in cf-tDNA samples, wherein 78% were not found in any tumor tissue.ConclusionsIn conclusion, serial TISF cf-tDNA profiling is valuable in tracking the tumor evolution of glioma during treatment and may be a feasible non-invasive option for monitoring glioma in future prospective studies and clinical practice.

Abstract Recognizing dynamic variations on the ground, especially changes caused by various natural disasters, is critical for assessing the severity of the damage and directing the disaster response. However, current workflows for disaster assessment usually require human analysts to observe and identify damaged buildings, which is labor-intensive and unsuitable for large-scale disaster areas. In this paper, we propose a difference-aware attention network (D2ANet) for simultaneous building localization and multi-level change detection from the dual-temporal satellite imagery. Considering the differences in different channels in the features of pre- and post-disaster images, we develop a dual-temporal aggregation module using paired features to excite change-sensitive channels of the features and learn the global change pattern. Since the nature of building damage caused by disasters is diverse in complex environments, we design a difference-attention module to exploit local correlations among the multi-level changes, which improves the ability to identify damage on different scales. Extensive experiments on the large-scale building damage assessment dataset xBD demonstrate that our approach provides new state-of-the-art results. Source code is publicly available at https://github.com/mj129/D2ANet .

Abstract Background Egg quality is a major concern in fish reproduction and development. An effective evaluation of egg quality prior to fertilization is helpful in improving the fertilization rate and survival rate of the larva. In this study, we aim to identify quality instructors from the combination study of fertilization rate, hatching rate, embryo malformation rate and gene expression profile. Results Eggs from 25 female fish were fertilized with sperm from the same fish. The egg quality was determined by the fertilization rates, hatching rate and embryo malformation rate and divided into three categories, low-quality ( 75%). Due to the distinct difference in fertilization, hatching and embryo malformation rate between low-quality eggs and high-quality eggs, these two groups were considered for the identification of quality markers. Then RNA-seq was performed for the originally preserved eggs from the low-quality group and high-quality group. We profiled the differentially expressed genes and identified a group of RNA-binding proteins (RBPs) as potential regulators. Gene function analysis indicated that most of these genes were enriched in RNA-regulated pathways including RNA processing. The RBPs were more related to egg quality from the PLS-DA analysis. Finally, gene expression was validated by qRT-PCR. Conclusions We found a cluster of RBP genes including igf2bp3, zar1, elavl1, rbm25b and related regulatory factors including yy1, sirt1, anp32e, btg4 as novel biomarkers of egg quality.

Objective This study evaluated the effects of dandelion supplements on lactation performance, circulating antioxidative activity and plasma metabolomics in primiparous dairy cows. Methods A total of 60 mid-lactation dairy cows (milk yield = 34.29±0.34 kg/d; days in milk = 151.72±2.36 days) were divided into 4 treatment groups randomly, comprising the addition of dandelion at 0, 100, 200, 400 g/d per head. The experiment lasted for 8 weeks with an extra 10 days’ pre-feeding period. Milk and blood samples were collected, and plasma samples were selected to perform metabolomics analysis. Results Supplementing 200 g/d of dandelion increased the yield of milk and lactose (p≤ 0.05). The milk somatic cell counts (p≤0.05) were lower in all dandelion groups than those in the control group. The activity of glutathione peroxidase (p≤0.05) and superoxide dismutase (p≤0.05) were increased and plasma malondialdehyde (p = 0.01) was decreased when cows were fed 200 g/d dandelion. Plasma metabolomics analysis showed that 23 hub differential metabolites were identified in the 200 g/d dandelion group. These metabolites such as ribose, glutamic acid, valine, and phenylalanine were enriched in D-glutamine and D-glutamate metabolism (p = 0.06, impact value = 1), phenylalanine, tyrosine, and tryptophan biosynthesis (p = 0.05, impact value = 0.5), and starch and sucrose metabolism (p = 0.21, impact value = 0.13). Moreover, correlation analysis showed that circulating ribose, mannose, and glutamic acid were positively related to milk yield. Conclusion Dandelion supplementation could improve lactation performance and elevate the plasma carbohydrate and amino acids metabolism and antioxidative activity. Supplementation of 200 g/d dandelion is recommended for lactating dairy cows.

Unknown faults may occur in practical applications, necessitating an open-set classifier that can classify known classes as well as recognize unknown faults. The current deep open-set classification methods are implicit in optimizing the intra- or inter-class distances, which may result in performance degradation when the number of unknown classes far exceeds that of the known. In this study, the discriminative angle deep features for vibration signals are investigated. A novel normalized one-versus-all classification loss with center and contrastive regularization is proposed. The trained network can explicitly optimize deep features to ensure intra-class compactness and inter-class divergence. In this case, such discriminative features can be used for open-set fault classification. Furthermore, the effectiveness of the proposed method is verified using field-measured motor bearing and gear vibration signals. The results demonstrate the evident advantages of our proposed method over other approaches in practical fault diagnosis scenarios.

Objective There is a lack of effective treatment to improve the prognosis of intrahepatic cholangiocarcinoma (ICC). Programmed cell death protein-1 (PD-1)-targeted immunotherapy has shown promising results in a variety of malignant tumours. However, in patients with advanced ICC, the safety and efficacy of anti-PD-1 agents remain unclear.Methods Forty-two advanced ICC patients treated with anti-PD-1 agents from August 2018 to December 2020 were retrospectively analyzed. Tumour response, overall survival (OS), progression-free survival (PFS), and time to tumour progression (TTP) were evaluated. Adverse events were also recorded.Results The median duration of follow-up was 12.1 months, and the median time of treatment was 6.7 months for all patients. The median OS, median PFS, and median TTP for the whole cohort were 19.3 months, 11.6 months, and 11.6 months, respectively. The overall response rate (ORR) and disease control rate (DCR) for the whole cohort were 23.8% and 85.7%, respectively. Of the 42 evaluable individuals, two (4.8%) had hyperprogressive disease. The most common adverse events (AEs) were pain (n = 6; 14.3%), anorexia (n = 4; 9.5%), hypertension (n = 4; 9.5%), pyrexia (n = 3; 7.1%), cough (n = 3; 7.1%), and hypothyroidism (n = 3; 7.1%). The median OS of patients with albumin-bilirubin (ALBI) grade 1 was longer than that of patients with ALBI grade 2 (19.3 months vs. 14.7 months). The median PFS did not show a significant difference between ALBI grade 1 and grade 2 patients (13.6 months vs. 6.9 months).Conclusions PD‐1‐targeted immunotherapy showed promising efficacy and safety in advanced ICC patients.Key messagesPD-1-targeted immunotherapy is a safe and effective treatment for advanced ICC patients.This study provides therapeutic strategy for advanced ICC patients.