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Abstract Lung adenocarcinoma (LUAD), a prevalent type of non-small cell lung cancer (NSCLC), was known for its diversity and intricate tumor microenvironment (TME). Comprehending the interaction among human immune-related genes (IRGs) and the TME is vital in the creation of accurate predictive models and specific treatments. We created a risk score based on IRGs and designed a nomogram to predict the prognosis of LUAD accurately. This involved a thorough examination of TME and the infiltration of immune cells in both high-risk and low-risk LUAD groups. Furthermore, the examination of the association between characteristic genes (BIRC5 and BMP5) and immune cells, along with immune checkpoints in the TME, was also conducted. The findings of our research unveiled unique immune profiles and interactions among individuals in the high- and low-risk categories, which contribute to variations in prognosis. LUAD demonstrated significant associations between BIRC5, BMP5, immune cells, and checkpoints, suggesting their involvement in disease advancement and resistance to medication. Furthermore, by correlating our findings with a multidrug database, we identified specific LUAD patient subsets that might benefit from tailored treatments. Our study establishes a groundbreaking prognostic model for LUAD, which not only underscores the importance of the immune context in LUAD but also paves the way for advancing precision medicine strategies in this complex malignancy.

Abstract Background The cell development atlas of transition stage from late Carnegie to fetal development (7–9 weeks) remain unclear. It can be seen that the early period of human embryos (7–9 weeks) is a critical research gap. Therefore, we employed single‑cell RNA sequencing to identify cell types and elucidate differentiation relationships. Results The single‑cell RNA sequencing analysis determines eighteen cell clusters in human embryos during the 7–9 weeks period. We uncover two distinct pathways of cellular development and differentiation. Initially, mesenchymal progenitor cells differentiated into osteoblast progenitor cells and neural stem cells, respectively. Neural stem cells further differentiated into neurons. Alternatively, multipotential stem cells differentiated into adipocyte, hematopoietic stem cells and neutrophil, respectively. Additionally, COL1A2-(ITGA1 + ITGB1) mediated the cell communication between mesenchymal progenitor cells and osteoblast progenitor cells. NCAM1-FGFR1 facilitated the cell communication between mesenchymal progenitor cells and neural stem cells. Notably, NCAM1-NCAM1 as a major contributor mediated the cell communication between neural stem cells and neurons. Moreover, CGA-FSHR simultaneously mediated the communication between multipotential stem cells, adipocyte, hematopoietic stem cells and neutrophil. Distinct cell clusters activated specific transcription factors such as HIC1, LMX1B, TWIST1, and et al., which were responsible for their specific functions. These coregulators, such as HOXB13, VSX2, PAX5, and et al., may mediate cell development and differentiation in human embryos. Conclusions We provide the cell development atlas for human embryos (7–9 weeks). Two distinct cell development and differentiation pathways are revealed.

Abstract Introduction Alveolar echinococcosis (AE), caused by the larval forms of Echinococcus multilocularis, is a zoonotic disease affecting the liver, lungs, lymph nodes, kidneys, brain, bones, thyroid, and other organs. Diagnosing AE in a non-endemic area is usually challenging. With the rapid development and increasing application of sequencing techniques in recent years, metagenomic next-generation sequencing (mNGS) has become a powerful tool for diagnosing rare infectious diseases. Case Presentation A 45-year-old woman was admitted to the hospital for the presence of pulmonary shadows for more than 3 months. The lung computed tomography (CT) at a local hospital revealed scattered solid and quasi-circular nodules in the left upper lobe, left lower lobe, right middle lobe, and right lower lobe. The largest nodule was located in the dorsal part of the right lung, measuring 2.0 × 1.7 × 1.5 cm. Moreover, abdominal CT revealed one space-occupying lesion each in the left and right lobes. The pathological analysis of the lung biopsy specimen revealed infiltration of lymphocytes, plasma cells, and eosinophils in the alveolar wall and interstitial area. No pathogenic bacteria were observed in the sputum smear and culture tests. There were no parasite eggs in the stool. The mNGS of the lung puncture tissue revealed 6156 sequence reads matching E. multilocularis; thus, the condition was diagnosed as AE. Albendazole 400 mg was administered twice daily, and the patient was stable during follow-up. Conclusion This case emphasizes the role of mNGS in diagnosing AE. As a novel, sensitive, and accurate diagnostic method, mNGS could be an attractive approach for facilitating early diagnosis and prompt treatment of infectious diseases, especially when the infection was caused by rare pathogens.

BackgroundNocardiosis poses a diagnostic challenge due to its rarity in clinical practice, non-specific clinical symptoms and imaging features, and the limitations of traditional detection methods. Nocardia aobensis (N. aobensis) is rarely detected in clinical samples. Metagenomic next-generation sequencing (mNGS) offers significant advantages over traditional methods for rapid and accurate diagnosis of infectious diseases, especially for rare pathogens.Case presentationA 52-year-old woman with a history of immune thrombocytopenia for over 2 years was hospitalized for recurrent fever and cough lasting for 10 days. Her initial diagnosis on admission was community-acquired pneumonia, based on chest computed tomography findings of lung inflammation lesion. Empirical treatment with moxifloxacin and trimethoprim-sulfamethoxazole (TMP-SMZ) was initiated. However, her condition failed to improve significantly even after 1 week of treatment. Bronchoalveolar lavage fluid (BALF) subjected to mNGS revealed the presence of N. aobensis, resulting in a diagnosis of pulmonary nocardiosis caused by N. aobensis. This diagnosis was also supported by Sanger sequencing of the BALF. After adjusting the antibiotic regimen to include TMP-SMZ in combination with imipenem, the patient’s condition significantly improved. She was finally discharged with instructions to continue oral treatment with TMP-SMZ and linezolid for 6 months. The patient’s first follow-up 1 month after discharge showed good treatment outcomes but with obvious side effects of the drugs. Consequently, the antibiotic regimen was changed to doxycycline, and the patient continued to improve.ConclusionWe report the first detailed case of pulmonary nocardiosis caused by N. aobensis diagnosed by mNGS. mNGS could be an effective method that facilitates early diagnosis and timely decision-making for the treatment of nocardiosis, especially in cases that involve rare pathogens.

Ischemic heart disease (IHD) is a leading cause of disability and death worldwide, with immune regulation playing a crucial role in its pathogenesis. Various immune cells are involved, and as one of the key immune cells residing in the heart, macrophages play an indispensable role in the inflammatory and reparative processes during cardiac ischemia. Exosomes, extracellular vesicles containing lipids, nucleic acids, proteins, and other bioactive molecules, have emerged as important mediators in the regulatory functions of macrophages and hold promise as a novel therapeutic target for IHD. This review summarizes the regulatory mechanisms of different subsets of macrophages and their secreted exosomes during cardiac ischemia over the past five years. It also discusses the current status of clinical research utilizing macrophages and their exosomes, as well as strategies to enhance their therapeutic efficacy through biotechnology. The aim is to provide valuable insights for the treatment of IHD.

Study region: The Laohahe basin, north of China Study focus: In a changing environment, some river’s hydrological regimes have significantly changed and may threatened river ecosystem. Therefore, it is urgent to improve our understanding for the driving mechanism of the evolution of the hydrological regimes. In this study, a comprehensive comparison was carried out to assess the application of the Long Short-Term Memory (LSTM) and the Variable Infiltration Capacity (VIC) model in river ecohydrological regimes alteration attribution. Firstly, the ecohydrological indicators changes were evaluated, including streamflow, ecosurplus, ecodeficit, and hydrological health. Then, the VIC and LSTM models were applied to quantify the climatic and anthropic effects on river ecohydrological indicators, respectively. Finally, the attribution results were compared. New hydrological insights: The research results revealed that (1) the streamflow decreased since 1980 and dramatically decreased after 2000. The ecohydrological indicators also changed significantly (α < 0.05). (2) The alterations were mainly driven by human activities, contributed to more than 80 %. (3) The LSTM and VIC showed little performance difference in quantitative attribution at the monthly and yearly scale, while the LSTM performed a little bad in streamflow simulation at the daily scale. The convenient feature and better simulation capabilities of LSTM provides a new choice for the attribution of ecohydrological regimes evolution, providing a better service in managing local water resources and safeguarding river ecosystems.

The heavy fermion (HF) state of d-electron systems is of great current interest since it exhibits various exotic phases and phenomena that are reminiscent of the Kondo effect in f -electron HF systems. Here, we present a combined infrared spectroscopy and first-principles band structure calculation study of the 3d-electron HF compound YFe2Ge2. The infrared response exhibits several charge-dynamical hallmarks of HF and a corresponding scaling behavior that resemble those of the f -electron HF systems. In particular, the low-temperature spectra reveal a dramatic narrowing of the Drude response along with the appearance of a hybridization gap (Δ ~50 meV) and a strongly enhanced quasiparticle effective mass. Moreover, the temperature dependence of the infrared response indicates a crossover around T* ~100K from a coherent state at low temperature to a quasi-incoherent one at high temperature. Despite of these striking similarities, our band structure calculations suggest that the mechanism underlying the HF behavior in YFe2Ge2 is distinct from the Kondo scenario of the f -electron HF compounds and even from that of the d-electron iron-arsenide superconductor KFe2As2. For the latter, the HF state is driven by orbital-selective correlations due to a strong Hund's coupling. Instead, for YFe2Ge2 the HF behavior originates from the band flatness near the Fermi level induced by the combined effects of kinetic frustration from a destructive interference between the direct Fe-Fe and indirect Fe-Ge-Fe hoppings, band hybridization involving Fe 3d and Y 4d electrons, and electron correlations. This highlights that rather different mechanisms can be at the heart of the HF state in d-electron systems. [ABSTRACT FROM AUTHOR]

Abstract Radiation-induced oral mucositis (RIOM) is a prevalent oral complication that occurs in individuals undergoing radiotherapy or radiation treatment for head and neck tumors. The presence of oral mucosal rupture and ulcerative lesions, which are the defining features of this condition, can significantly affect the quality of life of patients. Additionally, it can interfere with tumor therapy and contribute to an unfavorable prognosis. Current evidence suggests that cellular inflammation and programmed cell death are important factors in disease development. Moreover, thalidomide (THD) has been revealed to reduce the incidence and severity of RIOM in patients undergoing chemoradiotherapy for nasopharyngeal carcinoma. However, the mechanism through which THD improves RIOM remains unknown. This study aimed to investigate the role of LZTS3 in RIOM by analyzing various sequencing datasets and conducting knockdown and overexpression experiments. We used small interfering RNA transfection and LZTS3 overexpression, followed by validation through polymerase chain reaction, western blotting, flow cytometry, and enzyme-linked immunosorbent assay. In this study, we identified LZTS3 as a potential target for THD regulation in RIOM. Through a series of experiments, we confirmed that LZTS3 has the ability to inhibit the inflammatory response and apoptosis of cells. In addition, we also found that THD can regulate the expression of LZTS3 by upregulating, thereby affecting inflammatory response and apoptosis. We repeated these results in a live animal model. In summary, THD has the potential to reduce the occurrence of oral mucositis in patients by upregulating LZTS3 levels. These findings provide a promising avenue for future drug research and development to treat RIOM.

Abstract The convergence of artificial intelligence and in-vehicle wireless communication technologies, promises to fulfill the pressing communication needs of the Internet of Vehicles (IoV) while promoting the development of vehicle applications. However, making real-time dependency-aware task offloading decisions is difficult due to the high mobility of vehicles and the dynamic nature of the network environment. This leads to additional application computation time and energy consumption, increasing the risk of offloading failures for computationally intensive and latency-sensitive applications. In this paper, an offloading strategy for vehicle applications that jointly considers latency and energy consumption in the base station cooperative computing model is proposed. Firstly, we establish a collaborative offloading model involving multiple vehicles, multiple base stations, and multiple edge servers. Transferring vehicular applications to the application queue of edge servers and prioritizing them based on their completion deadlines. Secondly, each vehicular application is modeled as a directed acyclic graph (DAG) task with data dependency relationships. Subsequently, we propose a task offloading method based on task dependency awareness in deep reinforcement learning (DAG-DQN). Tasks are assigned to edge servers at different base stations, and edge servers collaborate to process tasks, minimizing vehicle application completion time and reducing edge server energy consumption. Finally, simulation results show that compared with the heuristic method, our proposed DAG-DQN method reduces task completion time by 16%, reduces system energy consumption by 19%, and improves decision-making efficiency by 70%.

Background and aims: Hepatocellular carcinoma (HCC), which is prevalent worldwide and has a high mortality rate, needs to be effectively diagnosed. We aimed to evaluate the significance of plasma microRNA-15a/16-1 (miR-15a/16) as a biomarker of hepatitis B virus-related HCC (HBV-HCC) using the machine learning model. This study was the first large-scale investigation of these two miRNAs in HCC plasma samples. Methods: Using quantitative polymerase chain reaction, we measured the plasma miR-15a/16 levels in a total of 766 participants, including 74 healthy controls, 335 with chronic hepatitis B (CHB), 47 with compensated liver cirrhosis, and 310 with HBV-HCC. The diagnostic performance of miR-15a/16 was examined using a machine learning model and compared with that of alpha-fetoprotein (AFP). Lastly, to validate the diagnostic efficiency of miR-15a/16, we performed pseudotemporal sorting of the samples to simulate progression from CHB to HCC. Results: Plasma miR-15a/16 was significantly decreased in HCC than in all control groups (P

BackgroundMaternal obesity significantly influences fetal development and health later in life; however, the molecular mechanisms behind it remain unclear. This study aims to investigate signature genes related to maternal obesity and fetal programming based on a genomic-wide transcriptional placental study using a combination of different bioinformatics tools.MethodsThe dataset (GSE128381) was obtained from Gene Expression Omnibus (GEO). The data of 100 normal body mass index (BMI) and 27 obese mothers were included in the analysis. Differentially expressed genes (DEGs) were evaluated by limma package. Thereafter, functional enrichment analysis was implemented. Then, weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) analysis were used to further screening of signature genes. Simple linear regression analysis was used to assess the correlation between signature genes and newborn birth weight. Gene set enrichment analysis (GSEA) was implemented to study signaling pathways related to signature genes. The expression of the signature genes was also explored in 48 overweight mothers in the same dataset.ResultsA total of 167 DEGs were obtained, of which 122 were up-regulated while 45 were down-regulated. The dataset was then clustered into 11 modules by WGCNA, and the MEbrown was found as the most significant module related to maternal obesity and fetal programming (cor = 0.2, p = 0.03). The LASSO analysis showed that PTX3, NCF2, HOXB5, ABCA6, and C1orf162 are signature genes related to maternal obesity and fetal programming, which were increased in the placenta of obese mothers compared to those with normal BMI. The area under the curve (AUC) of the signature genes in the receiver operating characteristic curve (ROC) was 0.709, 0.660, 0.674, 0.667, and 0.717, respectively. Simple linear regression analysis showed that HOXB5 was associated with newborn birth weight. GSEA analysis revealed that these signature genes positively participate in various signaling pathways/functions in the placenta.ConclusionPTX3, NCF2, HOXB5, ABCA6, and C1orf162 are novel signature genes related to maternal obesity and fetal programming, of which HOXB5 is implicated in newborn birth weight.

Abstract Background Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. Methods Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. Results In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p

This research aims to explore the influencing mechanism of fashion brand cultural content marketing on consumers’ willingness to buy. The concept of content marketing for fashion brand culture was analyzed from the four dimensions of functional content, entertainment content, emotional content, and interactive content according to content marketing theory, and the influencing mechanism was studied based on the information adoption theory. Furthermore, it is verified for the mediating role of information content quality perception, information utility quality perception, information expression quality perception, information carrier quality perception, information adoption, and the moderating role of information involvement and brand trust. The structural equation model was developed and empirically tested the hypothesis. The results show that fashion brand culture content marketing can promote consumers’ willingness to buy. Consumers generate purchase intention by perceiving information content quality, information utility quality, information expression quality, information carrier quality, and information adoption. It was found that consumers with high involvement degrees are more likely to perceive information. Moreover, consumers with high brand trust will promote the effect of information adoption on consumers’ purchase intention. This research provides new ideas and references for the content marketing of fashion brand culture. It provides quantitative scientific data for fashion enterprises to grasp the direction of fashion brand culture content marketing and implement brand culture shaping and communication strategies.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the joints of the human body and is projected to have a prevalence age-standardized rate of 1.5 million new cases worldwide by 2030. Several conventional and non-conventional preventive and therapeutic interventions have been suggested but they have their side effects including nausea, abdominal pain, liver damage, ulcers, heightened blood pressure, coagulation, and bleeding. Interestingly, several food-derived peptides (FDPs) from both plant and animal sources are increasingly gaining a reputation for their potential in the management or therapy of RA with little or no side effects. In this review, the concept of inflammation, its major types (acute and chronic), and RA identified as a chronic type were discussed based on its pathogenesis and pathophysiology. The conventional treatment options for RA were briefly outlined as the backdrop of introducing the FDPs that potentiate therapeutic effects in the management of RA.

Thiocyanates are effective in inhibiting the growth of microorganisms in raw milk to extend shelf life, but excessive addition can cause human health problems. Currently, ion chromatography and spectrophotometry are the main methods used in industry to determine SCN, but the pre-treatment process is cumbersome and time-consuming and has low sensitivity. Aqueous two-phase flotation (ATPF) technology has the advantages of simplicity, rapidity and economy. In this study, an acetonitrile/ammonium sulfate ATPF–gold nanoparticle (AuNP) colorimetric method was developed for the determination of SCN− in raw milk, and ATPF was used to separate and concentrate SCN− in raw milk to improve the detection sensitivity under convenient and economical conditions. The separation conditions were optimized by single-factor experiments and RSM, while the detection conditions, effects of CTAB concentration, pH and reaction time, were investigated. The “aggregation–anti-aggregation” mechanism of the gold-nano colorimetric method for the determination of SCN− was investigated by UV-vis absorption spectroscopy (UV-vis) and transmission electron microscopy (TEM). Under the optimal separation and detection conditions, the SCN− concentration showed a linear relationship with A630/A520 values in the concentration range of 0–2.5 mg/L with R2 of 0.9933, limit of detection (LOD) of 0.0919 mg/L, limit of quantitation (LOQ) of 0.306 mg/L, intra-day precision of 5.3% and spiked recoveries of 80.91–101.25%. In addition, the ATPF-AuNP colorimetric method demonstrated high selectivity and stability.

Research on the role of paraprobiotics in ameliorating the pathology of ulcerative colitis and its intestinal homeostatic imbalance is still limited. In this study, we investigated the effects of the anti-inflammatory probiotic HF05 and HF06 derived paraprobiotics 5-PA and 6-PA on mice with ulcerative colitis and their intestinal homeostasis. 5-PA and 6-PA alleviated inflammation, intestinal damage, and weight loss in mice, suppressed the activation of the NF-κB/NLRP3 signaling pathway, and upregulated the expression of intestinal tight junction proteins (ZO-1, occludin, and claudin-1). Notably, the two paraprobiotic regulated the gut microbiota and their metabolic interactions with the host. Specific taxa of gut microbes, including unclassified f_Muribaculaceae, Lactobacillus, Adlercreutzia, and Candidatus_Homeothermus, as well as bile acids and glycerophospholipid metabolites, were closely associated with gut homeostasis. In conclusion, this study confirms the beneficial effects of 5-PA and 6-PA in alleviating ulcerative colitis and promoting intestinal homeostasis.

In order to achieve the ambitious goal of “carbon neutrality”, countries around the world are striving to develop clean energy. Against this background, this paper takes China and Italy as representatives of developing and developed countries to summarize the energy structure composition and development overview of the two countries. The paper analyzes the serious challenges facing the future energy development of both countries and investigates the possibilities of energy cooperation between the two countries, taking into account their respective advantages in energy development. By comparing the policies issued by the two governments to encourage clean energy development, this paper analyzes the severe challenges faced by the two countries’ energy development in the future and combines their respective energy development advantages to look forward to the possibility of energy cooperation between the two countries in the future. This lays the foundation for China and Italy to build an “Energy Road” after the “Silk Road”.

The heavy fermion (HF) state of d-electron systems is of great current interest since it exhibits various exotic phases and phenomena that are reminiscent of the Kondo effect in f -electron HF systems. Here, we present a combined infrared spectroscopy and first-principles band structure calculation study of the 3d-electron HF compound YFe2Ge2. The infrared response exhibits several charge-dynamical hallmarks of HF and a corresponding scaling behavior that resemble those of the f -electron HF systems. In particular, the low-temperature spectra reveal a dramatic narrowing of the Drude response along with the appearance of a hybridization gap (Δ ~50 meV) and a strongly enhanced quasiparticle effective mass. Moreover, the temperature dependence of the infrared response indicates a crossover around T* ~100K from a coherent state at low temperature to a quasi-incoherent one at high temperature. Despite of these striking similarities, our band structure calculations suggest that the mechanism underlying the HF behavior in YFe2Ge2 is distinct from the Kondo scenario of the f -electron HF compounds and even from that of the d-electron iron-arsenide superconductor KFe2As2. For the latter, the HF state is driven by orbital-selective correlations due to a strong Hund's coupling. Instead, for YFe2Ge2 the HF behavior originates from the band flatness near the Fermi level induced by the combined effects of kinetic frustration from a destructive interference between the direct Fe-Fe and indirect Fe-Ge-Fe hoppings, band hybridization involving Fe 3d and Y 4d electrons, and electron correlations. This highlights that rather different mechanisms can be at the heart of the HF state in d-electron systems. [ABSTRACT FROM AUTHOR]