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Background Minichromosome maintenance complex component 3 (MCM3) plays a key role in various tumours. However, it remains largely unknown what the specific role and clinical significance of MCM3 in pancreatic adenocarcinoma (PAAD) are.Materials and Methods We integrated high-throughput data from PAAD worldwide to analyse the expression level of MCM3 mRNA. We used immunohistochemistry to analyse MCM3 protein expression levels in 145 cases in the PAAD group and 29 cases in the non-PAAD group. We also mainly analysed the necessity of MCM3 for PAAD growth based on CRISPR screen data. In addition, we used enrichment analysis and protein–protein interaction networks to explore the molecular mechanism of MCM3 in PAAD. We also analysed the correlation between MCM3 expression, components of the immune microenvironment in PAAD tissue and clinical prognosis.Results In PAAD, we observed for the first time that MCM3 was significantly highly expressed at both the mRNA (SMD = 0.67, 95% CI: 0.38 ∼ 0.96) and the protein level (p

ABSTRACTIn this study, ultra-high performance liquid chromatography-tandem mass spectrometry was used to isolate and identify terpenoids in three types of pineapple fibers (pineapple leaf fiber, pineapple stem fiber, and pineapple root fiber). The research results showed that in the positive and negative ion modes, 9 and 26 terpenoid compounds were identified from the three types of pineapple fibers, totaling 35 species in 12 categories, among which triterpene saponins had the largest number of species. Pineapple root fiber contains the highest total terpenoid content, followed by pineapple stem fiber and leaf fiber. In the OPLS-DA model, the VIP and S-plot methods revealed the differences in terpenoid compounds in three pineapple fibers. The research results showed that there were 9, 8 and 7 significantly different terpenoid compounds in pineapple leaf fiber and pineapple stem fiber, pineapple leaf fiber and pineapple root fiber, and pineapple stem fiber and pineapple root fiber respectively. Functional terpenoids such as ivy saponin, dehydroabietic acid, myrcene and ginsenoside are distributed in different parts of pineapple with varying degrees of enrichment. This study provides a basis for differentiated utilization and value-added use of pineapple leaves, stems and roots. Utilization provides scientific basis.

Background and Objective The rapid development of computer technology has led to a revolutionary transformation in artificial intelligence (AI)-assisted healthcare. The integration of whole-slide imaging technology with AI algorithms has facilitated the development of digital pathology for lung cancer (LC). However, there is a lack of comprehensive scientometric analysis in this field. Methods A bibliometric analysis was conducted on 197 publications related to digital pathology in LC from 502 institutions across 39 countries, published in 97 academic journals in the Web of Science Core Collection between 2004 and 2023. Results Our analysis has identified the United States and China as the primary research nations in the field of digital pathology in LC. However, it is important to note that the current research primarily consists of independent studies among countries, emphasizing the necessity of strengthening academic collaboration and data sharing between nations. The current focus and challenge of research related to digital pathology in LC lie in enhancing the accuracy of classification and prediction through improved deep learning algorithms. The integration of multi-omics studies presents a promising future research direction. Additionally, researchers are increasingly exploring the application of digital pathology in immunotherapy for LC patients. Conclusions In conclusion, this study provides a comprehensive knowledge framework for digital pathology in LC, highlighting research trends, hotspots, and gaps in this field. It also provides a theoretical basis for the application of AI in clinical decision-making for LC patients.

Abstract BackgroundCardiovascular-kidney-metabolic (CKM) health is affected by social determinants of health, especially education. CKM syndrome has not been evaluated in Chinese population, and the association of education with CKM syndrome in different sexes and its intertwined relation with lifestyles have not been explored. ObjectiveWe aimed to explore the association between educational attainment and the prevalence of CKM syndrome stages in middle-aged and older Chinese men and women as well as the potential role of health behavior based on Life’s Essential 8 construct. MethodsThis study used data from the nationwide, community-based REACTION (Risk Evaluation of Cancers in Chinese diabetic individuals: a longitudinal study). A total of 132,085 participants with complete information to determine CKM syndrome stage and education level were included. Educational attainment was assessed by the self-reported highest educational level achieved by the participants and recategorized as low (elementary school or no formal education) or high (middle school, high school, technical school/college, or above). CKM syndrome was ascertained and classified into 5 stages according to the American Heart Association presidential advisory released in 2023. ResultsAmong 132,085 participants (mean age 56.95, SD 9.19 years; n=86,675, 65.62% women) included, most had moderate-risk CKM syndrome (stages 1 and 2), and a lower proportion were at higher risk of CKM (stages 3 and 4). Along the CKM continuum, low education was associated with 34% increased odds of moderate-risk CKM syndrome for women (odds ratio 1.36, 95% CI 1.23-1.49) with a significant sex disparity, but was positively correlated with high-risk CKM for both sexes. The association between low education and high-risk CKM was more evident in women with poor health behavior but not in men, which was also interactive with and partly mediated by behavior. ConclusionsLow education was associated with adverse CKM health for both sexes but was especially detrimental to women. Such sex-specific educational disparity was closely correlated with health behavior but could not be completely attenuated by behavior modification. These findings highlight the disadvantage faced by women in CKM health ascribed to low education, underscoring the need for public health support to address this inequality.

BackgroundThoracoscopic surgery is a primary treatment for lung cancer, with lobectomy and mediastinal lymph node dissection being the predominant surgical approaches for invasive lung cancer. While many thoracic surgeons can proficiently perform lobectomy, thorough and standardized lymph node dissection remains challenging. This study aimed to explore a safer and more efficient surgical method for mediastinal lymph node dissection in lung cancer.MethodsA prospective randomized controlled study was conducted, involving 100 patients with right lung cancer who were admitted to our hospital from January 2021 to April 2024 and met the inclusion criteria. These patients were randomly divided into an observation group (tissue pneumoperitoneum technique around lymph nodes group) and a control group (conventional surgery group). Thoracoscopic lobectomy and mediastinal lymph node dissection were performed. Intraoperative and postoperative related indicators were observed to validate the effectiveness and safety of the tissue pneumoperitoneum technique around lymph nodes.ResultsThe observation group showed a significantly shorter lymph node dissection surgery time compared to the control group, with a statistically significant difference (p < 0.05). The number of lymph nodes dissected in the observation group was significantly higher than that in the control group, with a statistically significant difference (p < 0.05). Although the observation group had slightly more mediastinal lymph node stations dissected than the control group, the difference was not statistically significant (p > 0.05). The total drainage volume within three days postoperatively was comparable between the two groups, with no statistically significant difference (p > 0.05). The observation group had shorter chest tube indwelling time and postoperative hospital stay than the control group, with statistically significant differences (p < 0.05). The incidence of surgical complications was similar between the two groups, and there were no perioperative deaths.ConclusionThe tissue pneumoperitoneum technique around lymph nodes is a more efficient method for mediastinal lymph node dissection in lung cancer, demonstrating safety and feasibility, and is worthy of promotion.

Chronic pain is a prevalent and persistent ailment that affects individuals worldwide. Conventional medications employed in the treatment of chronic pain typically demonstrate limited analgesic effectiveness and frequently give rise to debilitating side effects, such as tolerance and addiction, thereby diminishing patient compliance with medication. Consequently, there is an urgent need for the development of efficacious novel analgesics and innovative methodologies to address chronic pain. Recently, a growing body of evidence has suggested that multireceptor ligands targeting opioid receptors (ORs) are favorable for improving analgesic efficacy, decreasing the risk of adverse effects, and occasionally yielding additional advantages. In this study, the intrathecal injection of a recently developed peptide (VYWEMEDKN) at nanomolar concentrations decreased pain sensitivity in naïve mice and effectively reduced pain-related behaviors in nociceptive pain model mice with minimal opioid-related side effects. Importantly, the compound exerted significant rapid-acting antidepressant effects in both the forced swim test and tail suspension test. It is possible that the rapid antihyperalgesic and antidepressant effects of the peptide are mediated through the OR pathway. Overall, this peptide could both effectively provide pain relief and alleviate depression with fewer side effects, suggesting that it is a potential agent for chronic pain and depression comorbidities from the perspective of pharmaceutical development.

Abstract Background The presence of lymph node (LN) metastasis directly affects the treatment strategy for lung adenocarcinoma (LUAD). Next‐generation sequencing (NGS) has been widely used in patients with advanced LUAD to identify targeted genes, while early detection of pathologic LN metastasis using NGS has not been assessed. Methods Clinicopathologic features and molecular characteristics of 224 patients from Ruijin Hospital were analyzed to detect factors associated with LN metastases. Another 140 patients from Huashan Hospital were set as a test cohort. Results Twenty‐four out of 224 patients were found to have lymph node metastases (10.7%). Pathologic LN‐positive tumors showed higher mutant allele tumor heterogeneity (p

BackgroundMitochondrial dysfunction has been shown to play a critical role in cancer biology. However, its involvement in intrahepatic cholangiocarcinoma (iCCA) remains significantly understudied.MethodsRNA sequencing data of 30 pairs of iCCA and paracancerous tissues were collected from the First Affiliated Hospital of Wenzhou Medical University (WMU). The WMU cohort (n = 30) was integrated with public TCGA (n = 30) and GSE107943 (n = 30) datasets to establish a multi-center iCCA cohort. We merged the TCGA and GSE107943 cohorts into an exploration cohort to develop a mitochondria signature for prognosis assessment, and utilized the WMU cohort for external validation. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Hallmarker analyses were used for functional interpretation of iCCA associated mitochondria-related genes (MRGs). In addition, unsupervised clustering was performed to identify mitochondria-based iCCA subtypes with the data of three institutions. Further investigations were conducted to examine the impact of mitochondrial dysfunction on drug responses, alteration of the tumor immune microenvironment, and immune responses.ResultsTwo hundred and sixty-three iCCA-related MRGs were identified to be related to fatty acid metabolism, oxidative phosphorylation, and apoptosis. Through univariate and multivariate Cox, and LASSO analyses, a mitochondria signature with five optimal MRGs was established to evaluate the prognosis of iCCA patients with the AUC values ranged from 0.785 to 0.928 in the exploration cohort. The signature also exhibited satisfactory performance in the WMU cohort with AUC values of 0.817–0.871, and was identified as an independent risk predictor in both cohorts. Additionally, we found that patients with higher mitochondria score with poor prognosis presented lower infiltration levels of CD4+ T-cell, NK cells, and monocytes, and demonstrated higher sensitivity to targeted therapies, including sorafenib. Furthermore, two distant mitochondria-based subtypes were determined, and subtype 2 was associated with shorter survival time and immunosuppressive tumor microenvironment. Finally, the differential protein expression of five key MRGs was verified by Immunohistochemistry.ConclusionWe found mitochondrial dysfunction modulates aberrant metabolism, oxidative stress, immune responses, apoptosis, and drug sensitivity in iCCA. A mitochondria signature and two mitochondria-based iCCA subtypes were identified for clinical risk stratification and immunophenotyping.

BackgroundThe efficacy of large language models (LLMs) in domain-specific medicine, particularly for managing complex diseases such as osteoarthritis (OA), remains largely unexplored. ObjectiveThis study focused on evaluating and enhancing the clinical capabilities and explainability of LLMs in specific domains, using OA management as a case study. MethodsA domain-specific benchmark framework was developed to evaluate LLMs across a spectrum from domain-specific knowledge to clinical applications in real-world clinical scenarios. DocOA, a specialized LLM designed for OA management integrating retrieval-augmented generation and instructional prompts, was developed. It can identify the clinical evidence upon which its answers are based through retrieval-augmented generation, thereby demonstrating the explainability of those answers. The study compared the performance of GPT-3.5, GPT-4, and a specialized assistant, DocOA, using objective and human evaluations. ResultsResults showed that general LLMs such as GPT-3.5 and GPT-4 were less effective in the specialized domain of OA management, particularly in providing personalized treatment recommendations. However, DocOA showed significant improvements. ConclusionsThis study introduces a novel benchmark framework that assesses the domain-specific abilities of LLMs in multiple aspects, highlights the limitations of generalized LLMs in clinical contexts, and demonstrates the potential of tailored approaches for developing domain-specific medical LLMs.

Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy. Prior research has illuminated reasons behind drug resistance, including increased drug efflux, alterations in drug targets, and abnormal activation of oncogenic pathways. However, there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment (TME). Recent studies on extracellular vesicles (EVs) have provided valuable insights. EVs are membrane-bound particles secreted by all cells, mediating cell-to-cell communication. They contain functional cargoes like DNA, RNA, lipids, proteins, and metabolites from mother cells, delivered to other cells. Notably, EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs. This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance, covering therapeutic approaches like chemotherapy, targeted therapy, immunotherapy and even radiotherapy. Detecting EV-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance. Additionally, targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance. We highlight the importance of conducting in-depth mechanistic research on EVs, their cargoes, and functional approaches specifically focusing on EV subpopulations. These efforts will significantly advance the development of strategies to overcome drug resistance in anti-tumor therapy.

Summary: Despite the success of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibition in tumor therapy, many patients do not benefit. This failure may be attributed to the intrinsic functions of PD-L1. We perform a genome-wide CRISPR synthetic lethality screen to systematically explore the intrinsic functions of PD-L1 in head and neck squamous cell carcinoma (HNSCC) cells, identifying ferroptosis-related genes as essential for the viability of PD-L1-deficient cells. Genetic and pharmacological induction of ferroptosis accelerates cell death in PD-L1 knockout cells, which are also more susceptible to immunogenic ferroptosis. Mechanistically, nuclear PD-L1 transcriptionally activates SOD2 to maintain redox homeostasis. Lower reactive oxygen species (ROS) and ferroptosis are observed in patients with HNSCC who have higher PD-L1 expression. Our study illustrates that PD-L1 confers ferroptosis resistance in HNSCC cells by activating the SOD2-mediated antioxidant pathway, suggesting that targeting the intrinsic functions of PD-L1 could enhance therapeutic efficacy.

The combined cadmium (Cd) and acid rain pollution poses a significant threat to the global ecological environment. Previous studies on the combined adverse effects have predominantly focused on the aboveground plant physiological responses, with limited reports on the microbial response in the rhizosphere soil. This study employed Populus beijingensis seedlings and potting experiments to simulate the impacts of combined mild acid rain (pH=4.5, MA) or highly strong acid rain (pH=3.0, HA), and soil Cd pollution on the composition and diversity of microbial communities, as well as the physiochemical properties in the rhizosphere soil. The results showed that Cd decreased the content of inorganic nitrogen, resulting in an overall decrease of 49.10 % and 46.67 % in ammonium nitrogen and nitrate nitrogen, respectively. Conversely, acid rain was found to elevate the content of total potassium and soil organic carbon by 4.68 %-6.18 % and 8.64–19.16 %, respectively. Additionally, simulated acid rain was observed to decrease the pH level by 0.29–0.35, while Cd increased the pH level by 0.11. Moreover, Cd alone reduced the rhizosphere bacterial diversity, however, when combined with acid rain, regardless of its intensity, Cd was observed to increase the diversity. Fungal diversity was not influenced by the acid rain, but Cd increased fungal diversity to some extend under HA as observed in bacterial diversity. In addition, composition of the rhizosphere bacterial community was primarily influenced by the inorganic nitrogen components, while the fungal community was driven mainly by soil pH. Furthermore, “Metabolism” was emerged as the most significant bacterial function, which was markedly affected by the combined pollution, while Cd pollution led to a shift from symbiotroph to other trophic types for fungi. These findings suggest that simulated acid rain has a mitigating effect on the diversity of rhizosphere bacteria affected by Cd pollution, and also alters the trophic type of these microorganisms. This can be attributed to the acid rain-induced direct acidic environment, as well as the indirect changes in the availability or sources of carbon, nitrogen, or potassium.

Inhaling microplastics (MPs) and nanoplastics (NPs) in the air can damage lung function. Xenobiotics in the body can cause endoplasmic reticulum (ER) stress, and the unfolded protein response (UPR) activation alleviates ER stress. Degradation of unfolded or misfolded proteins is an important pathway for recovering cellular homeostasis. The UPR and protein degradation induced by MPs/NPs in lung tissues are not well understood. Here, we investigated the UPR and protein ubiquitination in the lungs of mice exposed to polystyrene (PS)-NPs and their possible molecular mechanisms leading to protein ubiquitination. Mice were intratracheally administered with 5.6, 17, and 51 mg/kg PS-NPs once for 24 h. Exposure to PS-NPs elevated protein ubiquitination in the lungs of mice in a dose-dependent manner. PS-NPs activated three branches of UPR including inositol-requiring protein 1α (IRE1α), eukaryotic translation initiator factor 2α (eIF2α), and activating transcription factor 6α (ATF6α) in the lungs of mice. However, activated IRE1α did not trigger X-box binding protein 1 (XBP1) mRNA splicing. Exposure to PS-NPs induced an increase in the levels of E3 ubiquitin ligase hydroxymethyl glutaryl-coenzyme A reductase degradation protein 1 (HRD1) and carboxy terminus of Hsc70 interacting protein (CHIP) in the lungs of mice and BEAS-2B cells. ATF6α siRNA inhibited the levels of HRD1 and CHIP proteins induced by PS-NPs in BEAS-2B cells. These results suggest that ATF6α plays a critical role in increasing ubiquitination of unfolded or misfolded proteins by alleviating PS-NPs induced ER stress through UPR to achieve ER homeostasis in the lungs of mice.

Underground coal gasification is of great strategic significance to the effective and clean development of coal resources and scale up production of natural gas worldwide. Selection evaluation is the foundation of the exploration and development of underground coal gasification. In this paper, the differences between mid-deep (500–2200 m) and shallow layer (

Neuronal intranuclear inclusion disease is an uncommon neurodegenerative disorder. The diagnosis of this condition has become more definitive based on current research. However, treatment options remain limited. Neurogenic lower urinary tract dysfunction is one of the prevalent and significant complications, which is the result of its multi-system effects. Here, we present the case of a 48-year-old man diagnosed with neuronal intranuclear inclusion disease based on existing evidence and was complicated by neurogenic lower urinary tract dysfunction. Despite undergoing some medical treatments, his lower urinary tract symptoms, including urinary incontinence, incomplete or intermittent voiding, etc, continued to worsen while upper urinary tract injury developed. Based on careful consideration of the patient's condition and the available findings, we performed an unprecedented sacral neuromodulation on him. Implementation of sacral neuromodulation led to significant improvement in his urination function and alleviate kidney function damage. Our case suggests a potential therapeutic role for sacral neuromodulation in the treatment of neurogenic lower urinary tract dysfunction associated with neuronal intranuclear inclusion disease. Additional research is required to determine the effectiveness of sacral neuromodulation in managing neurogenic lower urinary tract dysfunction caused by various etiologies.

ObjectiveTo review our single-institution experience in the surgical management of foramen magnum tumors via a far-lateral approach using an oblique straight incision.MethodsFrom October 2023 to January 2024, four cases of tumors in the foramen magnum area treated at the Capital Medical University-affiliated XuanWu hospital neurosurgery department were involved in this study. All cases were managed with a far-lateral approach using an oblique straight incision. We retrospectively reviewed the clinical and imaging data, as well as the surgical strategies employed.ResultsThree cases of foramen magnum meningiomas and one case of glioma of the ventral medulla. All cases underwent a far-lateral approach using an oblique straight incision; all cases had a gross total resection, and the wounds healed well without cerebral fluid leakage or scalp hydrops. Except for one case of right foramen magnum meningioma, which had dysphagia and pneumothorax, the other cases were without any postoperative complications.ConclusionA far-lateral approach using an oblique straight incision can preserve muscle integrity and minimize subcutaneous exposure, allowing for complete anatomical reduction of muscles. This craniectomy method is simple and replicable, making it worthy of further clinical practice.

BackgroundThe triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women.MethodsThis cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer.ResultsMultivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19–2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13–17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09–1.68), 1.27 (1.05–1.54), 1.26 (1.05–1.52), and 1.32 (1.08–1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44–3.87).ConclusionThe TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.

Rice cake is a common traditional food in China. In this study, the effect of Polygonatum cyrtonema (PC) on the qualities and characteristics of rice cake was investigated. The incorporation of PC powder in rice cakes endowed a light-yellow color and increased the water content and water absorption of products. Rheological analysis showed that the rice cake containing PC exhibited weak-gel properties. Additionally, PC (40%) inhibited the rice cake aging and lowered the hardness of rice cakes to 13.86 N after 4 h storage. In vitro starch digestion analysis showed that PC (40%) reduced the digestibility of rice cakes by decreasing the starch hydrolysis rate from 88.70 to 58.95%, displaying a low estimated glycemic index (eGI) of 52.14. The findings mentioned above indicated that the inclusion of PC powder in rice cakes enhanced their characteristics and attributes, which also provided an approach for the development of PC products.

Cellulose nanocrystals (CNCs) were extracted from waste corrugated cardboard (WCC), waste paper towel (WPT), and waste paper towel cardboard roll (WPTR) using modified chemical methods. Instead of being discarded in landfills, these household waste materials were recognized as cost-effective and readily available sources for producing CNCs, which can serve as efficient water adsorbents in agricultural applications. Despite the inherent impurities and contaminants in household waste, the pretreatment and acid hydrolysis processes were found to be effective in removing a significant portion of these undesirable substances, as confirmed by FTIR spectra analysis. The extracted CNCs displayed a needle/whisker-shaped morphology with diameters ranging from 4 to 15 nm. Crystallinity levels of the CNCs extracted from WCC, WPT, and WPTR were determined to be 81.11 %, 85.29 %, and 80.68 %, respectively. The CNCs were then tested for their role as promoters of seed germination in plant starter plugs under different relative humidity conditions. Results indicated that under high relative humidity (above 70 %), seeds exhibited rapid germination (within 3–4 days) when the plugs were coated with CNCs at a minimum concentration of 5 %. However, under moderate relative humidity (50 %), germination occurred within 5–6 days at CNC concentrations of 10–15 %.

Abstract Federated learning (FL) is a promising approach for learning a model from data distributed on massive clients without exposing data privacy. It works effectively in the ideal federation where clients share homogeneous data distribution and learning behavior. However, FL may fail to function appropriately when the federation is not ideal, amid an unhealthy state called Negative Federated Learning (NFL), in which most clients gain no benefit from participating in FL. Many studies have tried to address NFL. However, their solutions either (1) predetermine to prevent NFL in the entire learning life-cycle or (2) tackle NFL in the aftermath of numerous learning rounds. Thus, they either (1) indiscriminately incur extra costs even if FL can perform well without such costs or (2) waste numerous learning rounds. Additionally, none of the previous work takes into account the clients who may be unwilling/unable to follow the proposed NFL solutions when using those solutions to upgrade an FL system in use. This paper introduces FL-GUARD, a holistic framework that can be employed on any FL system for tackling NFL in a run-time paradigm. That is, to dynamically detect NFL at the early stage (tens of rounds) of learning and then to activate recovery measures when necessary. Specifically, we devise a cost-effective NFL detection mechanism, which relies on an estimation of performance gain on clients. Only when NFL is detected, we activate the NFL recovery process, in which each client learns in parallel an adapted model when training the global model. Extensive experiment results confirm the effectiveness of FL-GUARD in detecting NFL and recovering from NFL to a healthy learning state. We also show that FL-GUARD is compatible with previous NFL solutions and robust against clients unwilling/unable to take any recovery measures.

Due to their high bias in favor of the majority class, traditional machine learning classifiers face a great challenge when there is a class imbalance in biological data. More recently, generative adversarial networks (GANs) have been applied to imbalanced data classification. For GANs, the distribution of the minority class data fed into discriminator is unknown. The input to the generator is random noise ($ z $) drawn from a standard normal distribution $ N(0, 1) $. This method inevitably increases the training difficulty of the network and reduces the quality of the data generated. In order to solve this problem, we proposed a new oversampling algorithm by combining the Bootstrap method and the Wasserstein GAN Network (BM-WGAN). In our approach, the input to the generator network is the data ($ z $) drawn from the distribution of minority class estimated by the BM. The generator was used to synthesize minority class data when the network training is completed. Through the above steps, the generator model can learn the useful features from the minority class and generate realistic-looking minority class samples. The experimental results indicate that BM-WGAN improves the classification performance greatly compared to other oversampling algorithms. The BM-WGAN implementation is available at: https://github.com/ithbjgit1/BMWGAN.git

Abstract We compute the classical tree-level five-point amplitude for the two-to-two scattering of spinning celestial objects with the emission of a graviton. Using this five-point amplitude, we then turn to the computation of the leading-order time-domain gravitational waveform. The method we describe is suitable for arbitrary values of classical spin of Kerr black holes and does not require any expansion in powers of the spin. In this paper we illustrate it in the simpler case of the scattering of one Kerr and one Schwarzschild black hole. An important ingredient of our calculation is a novel form of the Compton amplitude with spinning particles including contact terms derived from matching to black-hole perturbation theory calculations. This ensures that our waveform is valid up to at least fourth order in the spin. Our method can be applied immediately to generate improved waveforms once higher-order contact terms in the Compton amplitude become available. Finally, we show the formula for the gravitational memory to all orders in the spin, which is in agreement with our results.

Abstract Recently it has been shown that Bern-Carrasco-Johansson (BCJ) numerators of colour-kinematic duality for tree-level scattering amplitudes in Yang-Mills theory (coupled with scalars) can be determined using a quasi-shuffle Hopf algebra. In this paper we consider the same theory, but with higher-derivative corrections of the forms α′F 3 and α′2 F 4, where F is the field strength. In the heavy mass limit of the scalars, we show that the BCJ numerators of these higher-derivative theories are governed by the same Hopf algebra. In particular, the kinematic algebraic structure is unaltered and the derivative corrections only arise when mapping the abstract algebraic generators to physical BCJ numerators. The underlying kinematic Hopf algebra enables us to obtain a compact expression for the BCJ numerators of any number of gluons and two heavy scalars for amplitudes with higher-derivative operators. The pure gluon BCJ numerators can also be obtained from our results by a simple factorisation limit where the massive particles decouple.

Abstract The ground state search of the Ising model can be used to solve many combinatorial optimization problems. Under the current computer architecture, an Ising ground state search algorithm suitable for hardware computing is necessary for solving practical problems. Inspired by the potential energy conversion of the springs, we propose the Spring-Ising Algorithm, a point convolutional neural network algorithm for ground state search based on the spring vibration model. Spring-Ising Algorithm regards the spin as a moving mass point connected to a spring and establishes the equation of motion for all spins. Spring-Ising Algorithm can be mapped on AI chips through the basic structure of the neural network for fast and efficient parallel computing. The algorithm has shown promising results in solving the Ising model and has been tested in the recognized test benchmark K2000. The optimal results of this algorithm after 10,000 steps of iteration are 2.9% of all results. The algorithm introduces the concept of dynamic equilibrium to achieve a more detailed local search by dynamically adjusting the weight of the Ising model in the spring oscillation model. Spring-Ising Algorithm offers the possibility to calculate the Ising model on a chip which focuses on accelerating neural network calculations.

Abstract Continuum Landau modes — predicted recently in a non-Hermitian Dirac Hamiltonian under a uniform magnetic field — are continuous bound states with no counterparts in Hermitian systems. However, they have still not been confirmed in experiments. Here, we report an experimental observation of continuum Landau modes in non-Hermitian electric circuits, in which the non-Hermitian Dirac Hamiltonian is simulated by non-reciprocal hoppings and the pseudomagnetic field is introduced by inhomogeneous complex on-site potentials. Through measuring the admittance spectrum and the eigenstates, we successfully verify key features of continuum Landau modes. Particularly, we observe the exotic voltage response acting as a rainbow trap or wave funnel through full-field excitation. This response originates from the linear relationship between the modes’ center position and complex eigenvalues. Our work builds a bridge between non-Hermiticity and magnetic fields, and thus opens an avenue to explore exotic non-Hermitian physics.

Abstract Background Combined small-cell lung carcinoma (cSCLC) represents a rare subtype of SCLC, the mechanisms governing the evolution of cancer genomes and their impact on the tumor immune microenvironment (TIME) within distinct components of cSCLC remain elusive. Methods Here, we conducted whole-exome and RNA sequencing on 32 samples from 16 cSCLC cases. Results We found striking similarities between two components of cSCLC-LCC/LCNEC (SCLC combined with large-cell carcinoma/neuroendocrine) in terms of tumor mutation burden (TMB), tumor neoantigen burden (TNB), clonality structure, chromosomal instability (CIN), and low levels of immune cell infiltration. In contrast, the two components of cSCLC-ADC/SCC (SCLC combined with adenocarcinoma/squamous-cell carcinoma) exhibited a high level of tumor heterogeneity. Our investigation revealed that cSCLC originated from a monoclonal source, with two potential transformation modes: from SCLC to SCC (mode 1) and from ADC to SCLC (mode 2). Therefore, cSCLC might represent an intermediate state, potentially evolving into another histological tumor morphology through interactions between tumor and TIME surrounding it. Intriguingly, RB1 inactivation emerged as a factor influencing TIME heterogeneity in cSCLC, possibly through neoantigen depletion. Conclusions Together, these findings delved into the clonal origin and TIME heterogeneity of different components in cSCLC, shedding new light on the evolutionary processes underlying this enigmatic subtype.

Abstract Pyrogen, often as a contaminant, is a key indicator affecting the safety of almost all parenteral drugs (including biologicals, chemicals, traditional Chinese medicines and medical devices). It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted ‘reduction, replacement and refinement’ principle, which has been highly considered by regulatory agencies from different countries. We used NF-κB, a central signalling molecule mediating inflammatory responses, as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence signal. Here, we show that this test can quantitatively and sensitively detect endotoxin (lipopolysaccharide from different strains) and nonendotoxin (lipoteichoic acid, zymosan, peptidoglycan, lectin and glucan), has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals (group A & C meningococcal polysaccharide vaccine; basiliximab; rabies vaccine (Vero cells) for human use, freeze-dried; Japanese encephalitis vaccine (Vero cells), inactivated; insulin aspart injection; human albumin; recombinant human erythropoietin injection (CHO Cell)). The within-laboratory reproducibility of the test in three independent laboratories was 85%, 80% and 80% and the interlaboratory reproducibility among laboratories was 83.3%, 95.6% and 86.7%. The sensitivity (true positive rate) and specificity (true negative rate) of the test were 89.9% and 90.9%, respectively. In summary, the test provides a novel alternative for pyrogen detection.

Abstract Myelin sheath abnormality is the cause of various neurodegenerative diseases (NDDs). G-proteins and their coupled receptors (GPCRs) play the important roles in myelination. Gnao1, encoding the major Gα protein (Gαo) in mammalian nerve system, is required for normal motor function. Here, we show that Gnao1 restricted to Schwann cell (SCs) lineage, but not neurons, negatively regulate SC differentiation, myelination, as well as re-myelination in peripheral nervous system (PNS). Mice lacking Gnao1 expression in SCs exhibit faster re-myelination and motor function recovery after nerve injury. Conversely, mice with Gnao1 overexpression in SCs display the insufficient myelinating capacity and delayed re-myelination. In vitro, Gnao1 deletion in SCs promotes SC differentiation. We found that Gnao1 knockdown in SCs resulting in the elevation of cAMP content and the activation of PI3K/AKT pathway, both associated with SC differentiation. The analysis of RNA sequencing data further evidenced that Gnao1 deletion cause the increased expression of myelin-related molecules and activation of regulatory pathways. Taken together, our data indicate that Gnao1 negatively regulated SC differentiation by reducing cAMP level and inhibiting PI3K-AKT cascade activation, identifying a novel drug target for the treatment of demyelinating diseases.

Introduction: Metastasis is an important cause of high mortality and lethality of oral cancer. Fusobacterium nucleatum (Fn) can promote tumour metastasis. Outer membrane vesicles (OMVs) are secreted by Fn. However, the effects of Fn-derived extracellular vesicles on oral cancer metastasis and the underlying mechanisms are unclear. Objectives: We aimed to determine whether and how Fn OMVs mediate oral cancer metastasis. Methods: OMVs were isolated from brain heart infusion (BHI) broth supernatant of Fn by ultracentrifugation. Tumour-bearing mice were treated with Fn OMVs to evaluate the effect of OMVs on cancer metastasis. Transwell assays were performed to determine how Fn OMVs affect cancer cell migration and invasion. The differentially expressed genes in Fn OMV-treated/untreated cancer cells were identified by RNA-seq. Transmission electron microscopy, laser confocal microscopy, and lentiviral transduction were used to detect changes in autophagic flux in cancer cells stimulated with Fn OMVs. Western blotting assay was performed to determine changes in EMT-related marker protein levels in cancer cells. Fn OMVs’ effects on migration after blocking autophagic flux by autophagy inhibitors were determined by in vitro and in vivo experiments. Results: Fn OMVs were structurally similar to vesicles. In the in vivo experiment, Fn OMVs promoted lung metastasis in tumour-bearing mice, while chloroquine (CHQ, an autophagy inhibitor) treatment reduced the number of pulmonary metastases resulting from the intratumoral Fn OMV injection. Fn OMVs promoted the migration and invasion of cancer cells in vivo, leading to altered expression levels of EMT-related proteins (E-cadherin downregulation; Vimentin/N-cadherin upregulation). RNA-seq showed that Fn OMVs activate intracellular autophagy pathways. Blocking autophagic flux with CHQ reduced in vitro and in vivo migration of cancer cells induced by Fn OMVs as well as reversed changes in EMT-related protein expression. Conclusion: Fn OMVs not only induced cancer metastasis but also activated autophagic flux. Blocking autophagic flux weakened Fn OMV-stimulated cancer metastasis.

Inpainting images that have sizable missing blocks presents a considerable challenge in terms of preserving visual consistency and attaining a convincing result. In this study, the multi-scale generative adversarial network with multi-head external attention for image inpainting (denoted as MGDAN) is proposed. First, an adaptive weight style loss is designed into the generator of multi-scale generative adversarial networks (GAN) to guide the inpainting of the style and structure in the image inpainting, which improves the inpainting effect of image contour and emoticon. Second, the Adaptive Mix model is introduced to address the imbalance in generator and discriminator training by reducing the distance between the difficult and easy samples. This approach is intended to improve the overall performance of the network and drive high-quality image generation. Third, the generator and local discriminator in the image inpainting process are enhanced by the introduction of a multi-head external attention mechanism. This addition aims to capture the long-distance and multi-level dependent relationships between different areas of the image. It is proved beneficial for the generating clear geometric contours in the restored images and improving the overall global consistency of the inpainted results. By employing specific experimental methods, we find the optimal number of heads. The effectiveness of the proposed approach also is demonstrated through the extensive experiments conducted on public datasets.

This paper presents a comprehensive survey on interpretable intelligent fault diagnosis for rotating machinery, addressing the challenge of the “black box” nature of machine learning techniques that hampers reliability in automated diagnostic processes. It underscores the growing importance of interpretability in intelligent fault diagnosis (IFD), marking a shift from traditional signal processing methods to machine learning-based approaches that necessitate transparency for trustworthiness. Our review systematically collates and examines the spectrum of interpretability in IFD, distinguishing between post-hoc and ante-hoc strategies. We detail mainstream post-hoc methods, their applications, and critique their limitations, particularly the absence of physical significance. The survey then explores ante-hoc methods that incorporate physical knowledge upfront, enhancing interpretability. By categorizing and evaluating three distinct knowledge embedding approaches, we shed light on their unique applications. Conclusively, we highlight emerging research directions and challenges in the field, aiming to equip readers with a nuanced understanding of current methodologies and inspire future studies in making IFD more reliable and interpretable.

Abstract Local ischemia and hypoxia are the most important pathological processes in the early phase of secondary spinal cord injury (SCI), in which mitochondria are the main target of ischemic injury. Mitochondrial autophagy, also known as mitophagy, acts as a selective autophagy that specifically identifies and degrades damaged mitochondria, thereby reducing mitochondria-dependent apoptosis. Accumulating evidence shows that the mitophagy receptor, FUN14 domain-containing 1 (FUNDC1), plays an important role in ischemic injury, but the role of FUNDC1 in SCI has not been reported. In this study, we aimed to investigate whether FUNDC1 can enhance mitophagy and inhibit neuronal apoptosis in the early stage of SCI. In a rat SCI model, we found that FUNDC1 overexpression enhanced neuronal autophagy and decreased neuronal apoptosis in the early stage of injury, thereby reducing spinal cord damage. In vitro studies showed that the neuroprotective effects of FUNDC1 were achieved by inhibiting mitochondria-dependent apoptosis and improving mitochondrial function. In addition, FUNDC1 enhanced mitophagy. The protective effects of FUNDC1 against apoptosis and mitochondrial dysfunction were reversed by 3-methyladenine (3-MA), an autophagy inhibitor. Taken together, our results confirm that FUNDC1 can protect against neuronal loss after SCI by inducing mitophagy, inhibiting mitochondria-dependent apoptosis, and improving mitochondrial function.

Abstract Purpose This study aimed to perform a systematic review and meta-analysis to compare the clinical outcomes of open surgery and arthroscopic release in gluteal muscle contracture (GMC). Methods Two independent reviewers YM and WL conducted a systematic search of PubMed, Embase, Cochrane Library, and Web of Science to identify clinical trials that adhered to the PRISMA guidelines (Appendix A), spanning from inception to July 2023. Search items included ((“gluteal” OR “gluteus”) AND (“contracture” OR “fibrosis”)). Research comparing open surgery or arthroscopic release was included. Clinical outcomes were compared using the risk ratio for dichotomous variables and the standardized mean difference for continuous variables. A P value

A novel adaptive robust hybrid force/position control (ARHFPC) strategy is proposed for robot manipulator systems subject to dynamic uncertainties and unknown matched and mismatched disturbances under input saturation. First, the position controller is designed based on the backstepping approach. The first-order low-pass filter and the auxiliary dynamic system are synthesized into the controller to overcome the complex derivative operation of virtual control and handle the effect of input saturation, respectively. Radial basis function neural networks (RBFNNs) are utilized to approximate the dynamic uncertainties and matched disturbances. Then, a disturbance observer is designed for the mismatched disturbances. To enhance control accuracy of the interaction force between the end-effector and the external environment, a fuzzy proportional-integral (FPI) control scheme is presented. Theoretical analysis proves that all signals in the closed-loop control system of robot manipulators are locally uniformly ultimately bounded (UUB). Simulation results demonstrate the effectiveness and robustness of the proposed control scheme.

Abstract The AE and damage characteristics of three types of pore-structured rock under the same working conditions are studied by means of uniaxial cyclic loading and unloading tests. The results suggest that with repeated loading and unloading, AE ringing increases as a “jump”, and the denser the structure, the earlier the “jump” occurs. The AE cumulative energy shows a “step” upward trend, but there is a significant difference in the “step” spacing. By comparing the energy distribution of rocks with different pore structures, it can be seen that the smaller the porosity and the smaller the pore size, the greater the energy input and storage, and the earlier the internal failure. Compared with the other two energy-based damage calculation methods, the damage calculation method defined in this paper is closer to the true internal damage level of the rock loading cycle. The NSE value of the modified damage variable calculation method was significantly improved and it was shown that the dissipated energy before pore compaction is the main energy causing damage, after pore compaction the combined effects of dissipated energy and plastic deformation energy result in rock damage.

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

Accurate prediction of shale gas production is important for the government to formulate energy policies. China’s shale gas production is characterized by limited data and unclear influencing factors. Grey prediction models hold advantages in solving problems with inadequate data and insufficient information. However, existing grey models for shale gas production prediction have drawbacks of insufficient characteristic expression and parameter optimization. Therefore, a new grey model with four parameters is proposed in this work. Firstly, the power index, accumulative order, and background value coefficient in the new model are optimized using the PSO algorithm. Then, based on an in-depth analysis of the model structure and tests using random samples, the new model’s compatibility and adaptability are demonstrated to be better than other similar grey models. Thirdly, the new model is applied to simulate China’s shale gas production. The results show that the comprehensive error of the new model is only 1.3626%, lower than that of the SGGM(1,1) and UGM(1,1) models, which are 1.6211% and 1.6575% respectively. Lastly, using the new model, China's shale gas production is predicted, which is expected to reach 752 hundred million cubic meters by 2030. After analyzing the rationality of the result, relevant suggestions are put forward.

An automated storage and retrieval system (AS/RS) is a key component of enterprise logistics. Its performance metrics include, e.g., order fulfillment time and energy consumption. A crane-based automated storage and retrieval system (CB-AS/RS) is used as the study subject in this paper to build a location allocation model with the goal of minimizing order fulfillment time and minimizing energy consumption. The two-objective problem is transformed into a single-objective problem by the weight method. A genetic algorithm (GA) is used to optimize and simulate the model using spatial mapping coding. A permutation-combination heuristics (PCH) is proposed that follows the coding method and cross-operation of the GA and conducts both arrange-operation and change-operation. During the simulation, the influence of different storage utilization rates and different output and input instruction quantities in a batch of orders on the results is considered. Experimental results show that the results of the PCH algorithm are better than the GA and the optimization results are more stable. In this paper, we provide an optimization idea for the CB-AS/RS researchers and managers.

[Objective] During the drilling construction of ground surface dewatering shaft in a metro operational interval shield tunnel, the tunnel segments were damaged due to being pierced, resulting in sudden water hazards to interrupt metro service. In light of this, it is necessary to study permanent repair technologies for damaged shield segments within the operational metro tunnel. [Method] Considering the stability characteristics of the gravel and mudstone formations in the interval, a technology for repairing damaged segments in open-excavation vertical shaft is proposed, and this repair construction technology is elaborated in details. A finite element model is established to study the stress changes at the positions of the segment damage during different construction stages, including dewatering, vertical shaft excavation, segment repair, and vertical shaft backfilling. [Result & Conclusion] The minimum compressive stress after repairing the segment damage position is 0.732 MPa. With the backfilling of the vertical shaft, the stresses at the edge and the center of the repair site gradually increase. Ultimately, the stress stabilizes at around 2.124 MPa at the edge, and around 0.732 MPa at the center. Safety requirements are met, indicating that the repair technology is reliable.

China and the United States have seen expeditious investment growth in renewable energy and climate-related industries. Due to differences in political environments and governance structures, monetary settings, and prevailing market technologies and geographic conditions, the two countries demonstrate varied strengths and weaknesses in promoting climate investment. Both countries can learn from each other’s distinctive strengths and weaknesses to identify potential opportunities both for domestic climate programmes and energy cooperation to jointly pursue pathways to achieve net zero carbon footprints.

Abstract Despite the remarkable efficacy of PD-1-associated immune checkpoint inhibitors in treating cutaneous melanoma (CM), the inconsistency in the expression of PD-1 and its ligand PD-L1, and resulting variability in the effectiveness of immunotherapy, present significant challenges for clinical application. Therefore, further research is necessary to identify tumor-related biomarkers that can predict the prognosis of immunotherapy. Tertiary lymphoid structures (TLSs) have been recognized as a crucial factor in predicting the response of immune checkpoint inhibitors in solid tumors, including CM. However, the study of TLSs in CM is not yet comprehensive. Gene expression profiles have been shown to correlate with CM risk stratification and patient outcomes. In this study, we identified TLS-related genes that can be used for prognostic purposes and developed a corresponding risk model. The impact of TLS-related genes on clinicopathological characteristics, immune infiltration and drug susceptibility was also explored. Our biological function enrichment analysis provided preliminary evidence of related signaling pathways. Our findings provide a new perspective on risk stratification and individualized precision therapy for CM.

Inauguration & 1st Annual Conference of CSA Cerebral Hemorrhage Minimal Invasive Treatment Society was successfully held at China Optics Valley Convention & Exhibition Center in Wuhan, Hubei, Chian. During the conference, many well-known neurology experts in China conducted in-depth discussions on the research progress of minimal invasive treatment of cerebral hemorrhage, which benefited the participants a lot.

In order to apply Co-WO3 composite coating to SUS 430 steel interconnects for solid oxide fuel cell (SOFC) interconnects, a combination of electrophoresis and electroplating is used, followed by thermal energy exposure to ambient temperature at 800 ℃ for up to 5 weeks. The thermal growth of the oxide scale displays a tri-layer structure with a Cr2O3 layer in the inner part, a CoWO4 layer in the middle and (Co,Fe)3O4 and Co3O4 layer in the outer part. Co-WO3 coating produces an oxide layer that not only prevents Cr2O3 development and outward transport of Cr species but also enhances the electrical behavior of the surface scale.

Abstract Background Although great progress has been made in anti-cancer therapy, the prognosis of laryngeal squamous cell carcinoma (LSCC) patients remains unsatisfied. Quantities of studies demonstrate that glycolytic reprograming is essential for the progression of cancers, where triosephosphate isomerase 1 (TPI1) serves as a catalytic enzyme. However, the clinicopathological significance and potential biological functions of TPI1 underlying LSCC remains obscure. Methods We collected in-house 82 LSCC tissue specimens and 56 non-tumor tissue specimens. Tissue microarrays (TMA) and immunohistochemical (IHC) experiments were performed. External LSCC microarrays and bulk RNA sequencing data were integrated to evaluate the expression of TPI1. We used a log-rank test and the CIBERSORT algorithm to assess the prognostic value of TPI1 and its association with the LSCC microenvironment. Malignant laryngeal epithelial cells and immune-stromal cells were identified using inferCNV and CellTypist. We conducted a comprehensive analysis to elucidate the molecular functions of TPI1 in LSCC tissue and single cells using Pearson correlation analysis, high dimensional weighted gene co-expression analysis, gene set enrichment analysis, and clustered regularly interspaced short palindromic repeats (CRISPR) screen. We explored intercellular communication patterns between LSCC single cells and immune-stromal cells and predicted several therapeutic agents targeting TPI1. Results Based on the in-house TMA and IHC analysis, TPI1 protein was found to have a strong positive expression in the nucleus of LSCC cells but only weakly positive activity in the cytoplasm of normal laryngeal cells (p

Abstract Background Tumor-infiltrating lymphocytes (TILs) by routine hematoxylin and eosin staining (H&E-TILs) are a robust prognostic biomarker in various cancers. However, the role of H&E-TILs in esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CCRT) has not been reported. The purpose of this study was to assess the prognostic value of H&E-TILs in ESCC treated with CCRT. Methods The clinical data of 160 patients with ESCC treated with CCRT in our center between Jan. 2014 and Dec. 2021 were collected and retrospectively reviewed, and propensity score matching (PSM) analyses were performed. The H&E-TILs sections before CCRT were reassessed by two experienced pathologists independently. The H&E-TILs sections were classified into a positive group (+, > 10%) and a negative group (-, ≤ 10%) using 10% as the cutoff. The effects of H&E-TILs on overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) were explored using the Kaplan‒Meier method, and the log-rank test was used to test the differences. Multivariable analysis was performed using the Cox proportion hazards model. Results The short-term response to CCRT and the OS (P

AbstractContext The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still spreading rapidly. Relevant research based on the antiviral effects of Thesium chinense Turcz (Santalaceae) was not found.Objective To investigate the antiviral and anti-inflammatory effects of extracts of T. chinense.Materials and methods To investigate the anti-entry and replication effect of the ethanol extract of T. chinense (drug concentration 80, 160, 320, 640, 960 μg/mL) against the SARS-CoV-2. Remdesivir (20.74 μM) was used as positive control, and Vero cells were used as host cells to detect the expression level of nucleocapsid protein (NP) in the virus by real-time quantitative polymerase chain reaction (RT-PCR) and Western blotting. RAW264.7 cells were used as an anti-inflammatory experimental model under lipopolysaccharide (LPS) induction, and the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA).Results The ethanol extract of T. chinense significantly inhibited the replication (half maximal effective concentration, EC50: 259.3 μg/mL) and entry (EC50: 359.1 μg/mL) of SARS-CoV-2 into Vero cells, and significantly reduced the levels of IL-6 and TNF-α produced by LPS-stimulated RAW264.7 cells. Petroleum ether (EC50: 163.6 μg/mL), ethyl acetate (EC50: 22.92 μg/mL) and n-butanol (EC50: 56.8 μg/mL) extracts showed weak inhibition of SARS-CoV-2 replication in Vero cells, and reduced the levels of IL-6 and TNF-α produced by LPS-stimulated RAW264.7 cells.Conclusion T. chinense can be a potential candidate to fight SARS-CoV-2, and is becoming a traditional Chinese medicine candidate for treating COVID-19.

A facile, effective and green method using Ginkgo Biloba leaf extract was applied and optimized for the preparation of well dispersed silver nanoparticles. In the method, Ginkgo Biloba leaf extract was employed as both stabilizing and reducing agent without the addition of a toxic agent. 0.1 % silver nitrate solution (w/v) was used silver source. The synthesized silver nanoparticles were investigated and examined by UV-vis absorption spectroscopy (UV-vis), Scanning electron microscope (SEM), Transmission electron microscopy (TEM), powder X-ray diffraction (XRD) and Dynamic light scattering (DLS). The formation of silver nanoparticles was found by a change of color from light yellow to red, which was further proved by absorbance peak at 456 nm in UV-vis spectroscopy. The prepared nanoparticles are global in shape, highly crystalline in nature with a narrow distribution from 10 nm to 40 nm. The silver nanoparticles were capped with extracts, which prevented them from agglomeration and oxidation. Different parameters affecting the generation performance of silver nanoparticles, such as time, amount of silver nitrate and extract were investigated. The results demonstrate that these reaction parameters play important roles in the synthesis of silver nanoparticles.

For a conventional droop-controlled islanded microgrid, the poor reactive power-sharing and drop of bus voltage and frequency caused by line impedance mismatch and droop characteristics are inevitable. So far, consensus-based distributed control algorithms, in which a secondary control layer with the integration of voltage and frequency restoration and reactive power-sharing compensation mechanisms, has been treated as a promising solution. However, for most of the currently available distributed algorithms, it is the active power-sharing rather than the reactive power-sharing that was made the control goal, which is opposite to the fact that accurate power-sharing could always hold considering the integration effect in the active power control loop. Although a few recently published distributed algorithms added the reactive power-sharing goal in the second control layer, the system efficiency and reliability may deteriorate because a large circulating current could be induced at the malfunction of the communication network since there is no virtual impedance injected at the bottom control layer to limit that. This paper proposes a voltage and frequency restoration method based on the dynamic average consensus algorithm and an accurate reactive power-sharing method based on a first-order consensus algorithm and virtual impedance method. A simple pseudo-unidirectional communication network with a narrow communication band is adopted for the proposed distributed control to lower the communication burden and system complexity. The operational principle is first analyzed in detail. The proposed strategy is easily implementable and features not breaking droop characteristics. Then simulations and hardware-in-the-loop (HIL) real-time experiments verify the proposed approach.