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BackgroundSpeech analysis has been expected to help as a screening tool for early detection of Alzheimer’s disease (AD) and mild-cognitively impairment (MCI). Acoustic features and linguistic features are usually used in speech analysis. However, no studies have yet determined which type of features provides better screening effectiveness, especially in the large aging population of China.ObjectiveFirstly, to compare the screening effectiveness of acoustic features, linguistic features, and their combination using the same dataset. Secondly, to develop Chinese automated diagnosis model using self-collected natural discourse data obtained from native Chinese speakers.MethodsA total of 92 participants from communities in Shanghai, completed MoCA-B and a picture description task based on the Cookie Theft under the guidance of trained operators, and were divided into three groups including AD, MCI, and heathy control (HC) based on their MoCA-B score. Acoustic features (Pitches, Jitter, Shimmer, MFCCs, Formants) and linguistic features (part-of-speech, type-token ratio, information words, information units) are extracted. The machine algorithms used in this study included logistic regression, random forest (RF), support vector machines (SVM), Gaussian Naive Bayesian (GNB), and k-Nearest neighbor (kNN). The validation accuracies of the same ML model using acoustic features, linguistic features, and their combination were compared.ResultsThe accuracy with linguistic features is generally higher than acoustic features in training. The highest accuracy to differentiate HC and AD is 80.77% achieved by SVM, based on all the features extracted from the speech data, while the highest accuracy to differentiate HC and AD or MCI is 80.43% achieved by RF, based only on linguistic features.ConclusionOur results suggest the utility and validity of linguistic features in the automated diagnosis of cognitive impairment, and validated the applicability of automated diagnosis for Chinese language data.

The type I interferon (IFN) pathway is important for eukaryotic cells to resist viral infection, as well as an impediment to efficient virus replication. Therefore, this study aims to create an IFNAR1 knockout (KO) Madin-Darby bovine kidney (MDBK) cell line using CRISPR/Cas9 and investigate its application and potential mechanism in increasing viral replication of bovines. The IFNAR1 KO cells showed increased titers of bovine viral diarrhea virus (BVDV) (1.5 log10), with bovine enterovirus and bovine parainfluenza virus type 3 (0.5–0.8 log10). RNA-seq revealed reduced expression of the genes related IFN-I pathways including IFNAR1, STAT3, IRF9, and SOCS3 in IFNAR1 KO cells compared with WT cells. In WT cells, 306 differentially expressed genes (DEGs) were identified between BVDV-infected and -uninfected cells. Of these, 128 up- and 178 down-regulated genes were mainly associated with growth cycle and biosynthesis, respectively. In IFNAR1 KO cells, 286 DEGs were identified, with 82 up-regulated genes were associated with signaling pathways, and 204 down-regulated genes. Further, 92 DEGs were overlapped between WT and IFNAR1 KO cells including ESM1, IL13RA2, and SLC25A34. Unique DEGs in WT cells were related to inflammation and immune regulation, whereas those unique in IFNAR1 KO cells involved in cell cycle regulation through pathways such as MAPK. Knocking down SLC25A34 and IL13RA2 in IFNAR1 KO cells increased BVDV replication by 0.3 log10 and 0.4 log10, respectively. Additionally, we constructed an IFNAR1/IFNAR2 double-knockout MDBK cell line, which further increased BVDV viral titers compared with IFNAR1 KO cells (0.6 log10). Overall, the IFNAR1 KO MDBK cell line can support better replication of bovine viruses and therefore provides a valuable tool for bovine virus research on viral pathogenesis and host innate immune response.

IntroductionWorkplace violence against healthcare workers has become a serious global public health problem. The incidence of workplace violence towards Psychiatric nurses is higher than in all other medical institutions, up to 84.2% per year. It not only negatively affects many aspects of healthcare workers’ lives, but also destroys the harmony of the nurse–patient relationship and reduces the quality of nursing care. The number of psychiatric nurses in China was approximately 96,000, far lower than most other countries and unable to meet the growing demand for mental health. However, the increase in workplace violence has future exacerbates the current shortage of nurses. Therefore, it is necessary to develop effective strategies to prevent psychiatric nurses from suffering from workplace violence, thereby to reduce nurse turnover and improve the quality of nursing care. A comprehensive understanding of psychiatric nurses’ preferences and priorities for preventing workplace violence is an important prerequisite before formulating strategies and taking measures. Unfortunately, to date, no research has investigated the psychiatric nurses’ preferences. Therefore, a discrete choice experiment (DCE) is conducting to explore the psychiatric nurses’ preferences for workplace violence prevention. This article reports on methodological details of the DCE.Methods and analysisSix attributes were developed through a literature review, one-on-one interviews and focus group discussions. D-efficient design in NGENE was used to generate choice sets. SPSS 24.0 will be used for descriptive analysis of social Demography, and Stata 16.0 will be used for analysis of DCE data. A multinomial logit model will be used to preliminarily explore trade-offs between workplace violence prevention characteristics included in the choice tasks. Then, in a mixed logit model, we plan to choose some arbitrarily defined base violence prevention program and will use the nlcom command to evaluate the probability of an alternative violence prevention program.Ethics and disseminationThe study was approved by the relevant ethics committees. Our findings will emphasize priority intervention areas based on the preferences of psychiatric nurses and provide references for hospitals to develop and improve workplace violence prevention strategies. The results will be shared through seminars, policy briefs, peer-reviewed journal articles and online blogs.

Cerebrospinal fluid-contacting neurons (CSF-cNs) represent a distinct group of interneurons characterized by their prominent apical globular protrusions penetrating the spinal cord’s central canal and their basal axons extending towards adjacent cells. Identified nearly a century back, the specific roles and attributes of CSF-cNs have just started to emerge due to the historical lack of definitive markers. Recent findings have confirmed that CSF-cNs expressing PKD2L1 possess attributes of neural stem cells, suggesting a critical function in the regeneration processes following spinal cord injuries. This review aims to elucidate the molecular markers of CSF-cNs as potential neural stem cells during spinal cord development and assess their roles post-spinal cord injury, with an emphasis on their potential therapeutic implications for spinal cord repair.

BackgroundThe association between depression and musculoskeletal diseases has long been a subject of contentious debate. However, the causal relationship between the two remains uncertain. This study employs a two-sample Mendelian randomization (MR) analysis to investigate the causality between depression and six musculoskeletal diseases.MethodsIn this study, we performed MR analysis to systematically explore the causal relationship between depression and six musculoskeletal disorders. Single nucleotide polymorphisms (SNPs) that are linked to depression were employed as instrumental variables. To ensure robust and reliable conclusions, multiple analytical approaches were utilized, including inverse variance weighting(IVW), weighted median, and MR-Egger regression. Additionally, sensitivity analysis methods such as the MR-Egger intercept test, Cochran’s Q test, leave-one-out analysis, and funnel plot were employed.ResultsOur MR analysis revealed a significant association between depression and cervical spondylosis (depression: OR 1.003, 95% CI 1.002–1.005, P = 8.32E-05; major depressive disorder: OR 1.003, 95% CI 1.001–1.005, P = 0.0052). Furthermore, a strong correlation was noted between major depressive disorder (MDD) and knee osteoarthritis (KOA) (OR 1.299, 95% CI 1.154–1.463, P = 1.50E−5). Sensitivity analysis confirmed the robustness of these findings. Our independent validation study also corroborated these results.ConclusionThe MR analysis conducted in this study provides evidence supporting a genetic link between depression and cervical spondylosis, as well as KOA. Targeted interventions to manage depression in susceptible populations may contribute to lowering the risk of cervical spondylosis and KOA in these cohorts.

BackgroundSarcopenia, common in the elderly, often linked to chronic diseases, correlates with inflammation.The association between SII and mortality in sarcopenia patients is underexplored, this study investigates this relationship in a U.S. adult cohort.MethodsWe analyzed 1999–2018 NHANES data, focusing on 2,974 adults with sarcopenia. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Using a weighted sampling design, participants were grouped into three groups by the Systemic Immune-Inflammation Index (SII). We used Cox regression models, adjusting for demographic and clinical variables, to explore SII’s association with all-cause and cause-specific mortality in sarcopenia, performing sensitivity analyses for robustness.ResultsOver a median follow-up of 9.2 years, 829 deaths occurred. Kaplan-Meier analysis showed significant survival differences across SII groups. The highest SII group showed higher hazard ratios (HRs) for all-cause and cause-specific mortality in both crude and adjusted models. The highest SII group had a higher HR for all-cause(1.57, 1.25–1.98), cardiovascular(1.61, 1.00–2.58), cancer(2.13, 1.32–3.44), and respiratory disease mortality(3.21, 1.66–6.19) in fully adjusted models. Subgroup analyses revealed SII’s association with all-cause mortality across various demographics, including age, gender, and presence of diabetes or cardiovascular disease. Sensitivity analyses, excluding participants with cardiovascular diseases, those who died within two years of follow-up, or those under 45 years of age, largely reflected these results, with the highest SII group consistently demonstrating higher HRs for all types of mortality in both unadjusted and adjusted models.ConclusionOur study is the first to demonstrate a significant relationship between SII and increased mortality risks in a sarcopenia population.

ObjectivesIn recent years, there has been an increase in the number of randomized clinical trials of BTX-A combined with ESWT for the treatment of post-stroke spasticity. This has made it possible to observe the benefits of combination therapy in clinical practice. Therefore, this paper reviews the effectiveness of BTX-A in combination with ESWT for the treatment of post-stroke spasticity.MethodsBy October 2023, a systematic review was conducted in the databases PubMed, Cochrane, Embase, Medline, Web of Science, China National Knowledge Infrastructure, Wan Fang Database, China Biology Medicine disc and China Science and Technology Journal Database were systematically searched. We included randomized controlled trials that reported outcome metrics such as MAS, FMA, and MBI score. Studies were excluded if MAS was not reported. The quality of the included studies was assessed by the Cochrane Collaboration’s tool for assessing risk of bias, and the AMSTAR quality rating scale was selected for self-assessment.ResultsA total of 70 articles were included in the initial search, and six were ultimately included. The results of the included studies showed that the combination therapy was effective in reducing MAS scores and improving FMA and MBI scores in patients with spasticity compared to the control group. Combination therapy has also been shown to improve joint mobility and reduce pain in spastic limbs.ConclusionCumulative evidence from clinical randomized controlled trial studies suggests that the combination therapy is effective in reducing lower limb spasticity and improving mobility after stroke. However, more clinical trials are still needed to corroborate the evidence regarding the efficacy of BTX-A combined with shockwave therapy.Systematic Review RegistrationThe system review can be searched in the PROSPERO database (CRD42023476654).

Kinesin motors are a large family of molecular motors that walk along microtubules to fulfill many roles in intracellular transport, microtubule organization, and chromosome alignment. Kinesin-7 CENP-E (Centromere protein E) is a chromosome scaffold-associated protein that is located in the corona layer of centromeres, which participates in kinetochore-microtubule attachment, chromosome alignment, and spindle assembly checkpoint. Over the past 3 decades, CENP-E has attracted great interest as a promising new mitotic target for cancer therapy and drug development. In this review, we describe expression patterns of CENP-E in multiple tumors and highlight the functions of CENP-E in cancer cell proliferation. We summarize recent advances in structural domains, roles, and functions of CENP-E in cell division. Notably, we describe the dual functions of CENP-E in inhibiting and promoting tumorigenesis. We summarize the mechanisms by which CENP-E affects tumorigenesis through chromosome instability and spindle assembly checkpoints. Finally, we overview and summarize the CENP-E-specific inhibitors, mechanisms of drug resistances and their applications.

Acute lymphocytic leukemia is a hematological malignancy that primarily affects children. Long-term chemotherapy is effective, but always causes different toxic side effects. With the application of a chemotherapy-free treatment strategy, we intend to demonstrate the most recent results of using one type of epigenetic drug, histone deacetylase inhibitors, in ALL and to provide preclinical evidence for further clinical trials. In this review, we found that panobinostat (LBH589) showed positive outcomes as a monotherapy, whereas vorinostat (SAHA) was a better choice for combinatorial use. Preclinical research has identified chidamide as a potential agent for investigation in more clinical trials in the future. In conclusion, histone deacetylase inhibitors play a significant role in the chemotherapy-free landscape in cancer treatment, particularly in acute lymphocytic leukemia.

Lung cancer remains the leading cause of cancer-related mortality, with 1.8 million deaths per year. Small cell lung cancer and non-small cell lung cancer (NSCLC) are the main cancer types. Approximately 85% of cases are NSCLC, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. In this reported treatment case, the tumor histological type changed after targeted therapy, which has not been previously well documented. The patient was a 67-year-old woman diagnosed with squamous cell carcinoma via bronchoscopy. She received five neoadjuvant immune monotherapies. The lesion shrank but then progressed, with a diagnosis of small cell carcinoma via bronchoscopy. This finding suggests that tumor acquisition of resistance as manifested by cancer-type changes needs consideration and study in the application of this particular type of immunotherapy.

Siloxanes are a group of substances characterized by Si-O-Si functional group. Siloxanes can react with alcohols to form Si-O-C bond. Siloxanes have been widely used as crossing linking agents and graft copolymers as well as additives for plastics. Lignin contains both phenolic and aliphatic hydroxy groups which have the potential to instigate bonding with siloxane compounds. However, there has not been any attempt to apply siloxanes as crosslinking agents for biobased composite formation. This manuscript presents the first study of applying siloxanes compounds to lignin and Cellulose nanofibers (CNF) with respective PLA, PETG, and HDPE to prepare biocomposites. Both Tetramethyl Tetraphenyl Trisiloxane (TTT) and Tetraethoxysilane (TEOS) were used as cross-linking agents. We have successfully incorporated 20 wt% lignin and 10 wt% CNF into the biocomposite filaments. The tensile properties of ensuing biocomposite were investigated. The objective of this work is to demonstrate the potential of lignin and CNF as a sustainable co-polymer to improve the properties of PLA/PETG/HDPE-based materials for 3D printing. This paper will also discuss the challenges and opportunities associated with the use of lignin in 3D printing, including the effect of lignin and CNF content on the mechanical and thermal properties, the compatibility of lignin and CNF with PLA/PETG/HDPE, and the potential for further optimization of the cross-linking chemistry using TTT and TEOS.

The U-steel support structures of underground caverns are prone to instability and failure under blast loads. The purpose of the underground cavern reinforcement is to mobilise the self-supporting capacity of the surrounding rock to resist the blast. To better understand the mechanical performance and failure mechanism of the U-steel support, the fracture process and vibration behaviour of the support structure under blast loading are investigated by the microseismic monitoring experiment. The dynamic responses of the cavern support structures under blast loading are investigated, and the potentially hazardous sections of the U-steel support structure are revealed by the theoretical analysis. The microseismic monitoring results show that the blast induced microseismic events are concentrated in the arch shoulder of the small chainage, correspondingly the U-steel structures in this region have been partially extruded and deformed. The failure mechanism of the supporting structure is presented. In order to effectively inhibit the internal fracture evolution or macroscopic failure of the rock mass, the synergetic reinforcement scheme of the structures is proposed. The results of the research can be used as a reference for the design and control method of the U-steel support in similar projects.

Background: Small extracellular vesicles (sEVs) mediate intercellular communication in the tumor microenvironment (TME) and contribute to the malignant transformation of tumors, including unrestricted growth, metastasis, or therapeutic resistance. However, there is a lack of agents targeting sEVs to overcome or reverse tumor chemotherapy resistance through sEVs-mediated TME reprogramming.Methods: The paclitaxel (PTX)-resistant A549T cell line was used to explore the inhibitory effect of alpha-hederin on impeding the transmission of chemoresistance in non-small cell lung cancer (NSCLC) through the small extracellular vesicles (sEVs) pathway. This investigation utilized the CCK-8 assay and flow cytometry. Transcriptomics, Western blot, oil red O staining, and targeted metabolomics were utilized to evaluate the impact of alpha-hederin on the expression of signaling pathways associated with chemoresistance transmission in NSCLC cells before and after treatment. In vivo molecular imaging and immunohistochemistry were conducted to assess how alpha-hederin influences the transmission of chemoresistance through the sEVs pathway. RT-PCR was employed to examine the expression of miRNA and lncRNA in response to alpha-hederin treatment.Results: The resistance to PTX chemotherapy in A549T cells was overcome by alpha-hederin through its dependence on sEV secretion. However, the effectiveness of alpha-hederin was compromised when vesicle secretion was blocked by the GW4869 inhibitor. Transcriptomic analysis for 463 upregulated genes in recipient cells exposed to A549T-derived sEVs revealed that these sEVs enhanced TGFβ signaling and unsaturated fatty acid synthesis pathways. Alpha-hederin inhibited 15 types of unsaturated fatty acid synthesis by reducing the signaling activity of the sEVs-mediated TGFβ/SMAD2 pathway. Further, we observed that alpha-hederin promoted the production of three microRNAs (miRNAs, including miR-21-5p, miR-23a-3p, and miR-125b-5p) and the sorting to sEVs in A549T cells. These miRNAs targeted the TGFβ/SMADs signaling activity in sEVs-recipient cells and sensitized them to the PTX therapy.Conclusion: Our finding demonstrated that alpha-hederin could sensitize PTX-resistant NSCLC cells by sEV-mediated multiple miRNAs accumulation, and inhibiting TGFβ/SMAD2 pathways in recipient cells.

Soft robotics is an emerging field showing immense potential for biomedical applications. This review summarizes recent advancements in soft robotics for in vitro and in vivo medical contexts. Their inherent flexibility, adaptability, and biocompatibility enable diverse capabilities from surgical assistance to minimally invasive diagnosis and therapy. Intelligent stimuli-responsive materials and bioinspired designs are enhancing functionality while improving biocompatibility. Additive manufacturing techniques facilitate rapid prototyping and customization. Untethered chemical, biological, and wireless propulsion methods are overcoming previous constraints to access new sites. Meanwhile, advances in tracking modalities like computed tomography, fluorescence and ultrasound imaging enable precision localization and control enable in vivo applications. While still maturing, soft robotics promises more intelligent, less invasive technologies to improve patient care. Continuing research into biocompatibility, power supplies, biomimetics, and seamless localization will help translate soft robots into widespread clinical practice.

This review examines advances in the metabolites, pharmacological research, and therapeutic applications of the medicinal fruit of Brucea javanica (L.) Merr. Brucea javanica (BJ) is derived from the fruit of the Brucea javanica (L.) Merr. There are nearly 200 metabolites present in BJ, and due to the diversity of its metabolites, BJ has a wide range of pharmacological effects. The traditional pharmacological effects of BJ include anti-dysentery, anti-malaria, etc. The research investigating the contemporary pharmacological impacts of BJ mainly focuses on its anti-tumor properties. In the article, the strong monomeric metabolites among these pharmacological effects were preliminarily screened. Regarding the pharmacological mechanism of action, current research has initially explored BJ’s pharmacological agent and molecular signaling pathways. However, a comprehensive system has yet to be established. BJ preparations have been utilized in clinical settings and have demonstrated effectiveness. Nevertheless, clinical research is primarily limited to observational studies, and there is a need for higher-quality research evidence to support its clinical application. There are still many difficulties and obstacles in studying BJ. However, it is indisputable that BJ is a botanical drugs with significant potential for application, and it is expected to have broader global usage.

BackgroundPancreatic cancer remains an extremely malignant digestive tract tumor, posing a significant global public health burden. Patients with pancreatic cancer, once metastasis occurs, lose all hope of cure, and prognosis is extremely poor. It is important to investigate liver metastasis of Pancreatic cancer in depth, not just because it is the most common form of metastasis in pancreatic cancer, but also because it is crucial for treatment planning and prognosis assessment. This study aims to delve into the mechanisms of pancreatic cancer liver metastasis, with the goal of providing crucial scientific groundwork for the development of future treatment methods and drugs.MethodsWe explored the mechanisms of pancreatic cancer liver metastasis using single-cell sequencing data (GSE155698 and GSE154778) and bulk data (GSE71729, GSE19279, TCGA-PAAD). Initially, Seurat package was employed for single-cell data processing to obtain expression matrices for primary pancreatic cancer lesions and liver metastatic lesions. Subsequently, high-dimensional weighted gene co-expression network analysis (hdWGCNA) was used to identify genes associated with liver metastasis. Machine learning algorithms and COX regression models were employed to further screen genes related to patient prognosis. Informed by both biological understanding and the outcomes of algorithms, we meticulously identified the ultimate set of liver metastasis-related gene (LRG). In the study of LRG genes, various databases were utilized to validate their association with pancreatic cancer liver metastasis. In order to analyze the effects of these agents on tumor microenvironment, we conducted an in-depth analysis, including changes in signaling pathways (GSVA), cell differentiation (pseudo-temporal analysis), cell communication networks (cell communication analysis), and downstream transcription factors (transcription factor activity prediction). Additionally, drug sensitivity analysis and metabolic analysis were performed to reveal the effects of LRG on gemcitabine resistance and metabolic pathways. Finally, functional experiments were conducted by silencing the expression of LRG in PANC-1 and Bx-PC-3 cells to validate its influence to proliferation and invasiveness on PANC-1 and Bx-PC-3 cells.ResultsThrough a series of algorithmic filters, we identified PAK2 as a key gene promoting pancreatic cancer liver metastasis. GSVA analysis elucidated the activation of the TGF-beta signaling pathway by PAK2 to promote the occurrence of liver metastasis. Pseudo-temporal analysis revealed a significant correlation between PAK2 expression and the lower differentiation status of pancreatic cancer cells. Cell communication analysis revealed that overexpression of PAK2 promotes communication between cancer cells and the tumor microenvironment. Transcription factor activity prediction displayed the transcription factor network regulated by PAK2. Drug sensitivity analysis and metabolic analysis revealed the impact of PAK2 on gemcitabine resistance and metabolic pathways. CCK8 experiments showed that silencing PAK2 led to a decrease in the proliferative capacity of pancreatic cancer cells and scratch experiments demonstrated that low expression of PAK2 decreased invasion capability in pancreatic cancer cells. Flow cytometry reveals that PAK2 significantly inhibited apoptosis in pancreatic cancer cell lines. Molecules related to the TGF-beta pathway decreased with the inhibition of PAK2, and there were corresponding significant changes in molecules associated with EMT.ConclusionPAK2 facilitated the angiogenic potential of cancer cells and promotes the epithelial-mesenchymal transition process by activating the TGF-beta signaling pathway. Simultaneously, it decreased the differentiation level of cancer cells, consequently enhancing their malignancy. Additionally, PAK2 fostered communication between cancer cells and the tumor microenvironment, augments cancer cell chemoresistance, and modulates energy metabolism pathways. In summary, PAK2 emerged as a pivotal gene orchestrating pancreatic cancer liver metastasis. Intervening in the expression of PAK2 may offer a promising therapeutic strategy for preventing liver metastasis of pancreatic cancer and improving its prognosis.

BackgroundThe past decade has witnessed advancements in mechanical thrombectomy (MT) for acute large-vessel occlusions (LVOs). However, only approximately half of the patients with LVO undergoing MT show the best/independent 90-day favorable outcome. This study aimed to develop a nomogram for predicting 90-day poor outcomes in patients with LVO treated with MT.MethodsA total of 187 patients who received MT were retrospectively analyzed. Factors associated with 90-day poor outcomes (defined as mRS of 4–6) were determined by univariate and multivariate logistic regression analyzes. One best-fit nomogram was established to predict the risk of a 90-day poor outcome, and a concordance index was utilized to evaluate the performance of the model. Additionally, 145 patients from a single stroke center were retrospectively recruited as the validation cohort to test the newly established nomogram.ResultsThe overall incidence of 90-day poor outcomes was 45.16%, affecting 84 of 186 patients in the training set. Moreover, five variables, namely, age (odds ratio [OR]: 1.049, 95% CI [1.016–1.083]; p = 0.003), glucose level (OR: 1.163, 95% CI [1.038–1.303]; p = 0.009), baseline National Institute of Health Stroke Scale (NIHSS) score (OR: 1.066, 95% CI [0.995–1.142]; p = 0.069), unsuccessful recanalization (defined as a TICI grade of 0 to 2a) (OR: 3.730, 95% CI [1.688–8.245]; p = 0.001), and early neurological deterioration (END, defined as an increase of ≥4 points between the baseline NIHSS score and the NIHSS score at 24 h after MT) (OR: 3.383, 95% CI [1.411–8.106]; p = 0.006), were included in the nomogram to predict the potential risk of poor outcomes at 90 days following MT in LVO patients, with a C-index of 0.763 (0.693–0.832) in the training set and 0.804 (0.719–0.889) in the validation set.ConclusionThe proposed nomogram provided clinical evidence for the effective control of these risk factors before or during the process of MT surgery in LVO patients.

In the context of climate change and human factors, the drought problem is a particularly serious one, and environmental pollution caused by the abuse of chemical fertilizers and pesticides is increasingly serious. Endophytic fungi can be used as a protection option, which is ecologically friendly, to alleviate abiotic stresses on plants, promote plant growth, and promote the sustainable development of agriculture and forestry. Therefore, it is of great significance to screen and isolate endophytic fungi that are beneficial to crops from plants in special habitats. In this study, endophytic fungi were isolated from Cotoneaster multiflorus, and drought-tolerant endophytic fungi were screened by simulating drought stress with different concentrations of PEG-6000, and the growth-promoting effects of these drought-tolerant strains were evaluated. A total of 113 strains of endophytic fungi were isolated and purified from different tissues of C. multiflorus. After simulated drought stress, 25 endophytic fungi showed strong drought tolerance. After ITS sequence identification, they belonged to 7 genera and 12 species, including Aspergillus, Fusarium, Colletotrichum, Penicillium, Diaporthe, Geotrichum, and Metarhizium. According to the identification and drought stress results, 12 strains of endophytic fungi with better drought tolerance were selected to study their abilities of dissolving inorganic phosphorus and potassium feldspar powder and producing indole-3-acetic acid (IAA). It was found that the amount of dissolved phosphorus in 7 strains of endophytic fungi was significantly higher than that of CK, and the content of soluble phosphorus was 101.98–414.51 μg. ml−1; 6 endophytic fungi had significantly higher potassium solubilization than CK, and the content of water-soluble potassium ranged from 19.17 to 30.94 mg·l−1; 6 strains have the ability to produce IAA, and the yield of IAA ranged between 0.04 and 0.42 mg. ml−1. This study for the first time identified the existence of endophytic fungi with drought tolerance and growth-promoting function in C. multiflorus, which could provide new direction for plant drought tolerance and growth promotion fungi strain resources. It also provides a theoretical basis for the subsequent application of endophytic fungi of C. multiflorus in agricultural and forestry production to improve plant tolerance.

PurposeMolting is a pivotal biological process regulated by the ecdysteroid signaling pathway that requires molecular coordination of two transcription factors, Ecdysone receptor (EcR) and ultraspiracle (USP) in arthropods. However, the molecular interplay of EcR and Retinoid X receptor (RXR), the crustacean homolog of USP in the ecdysteroid signaling pathway, is not well understood.MethodsIn this study, we conducted temporal and spatial expression, co-immunoprecipitation (CO-IP), and luciferase reporter assay experiments to investigate the molecular function and interplay of EcR and RXR during the molting process of the Chinese mitten crab, Eriocheir sinensis.ResultsThe results showed that the expression level of RXR was more stable and significantly higher than EcR during the entire molting process. However, the expression level of EcR fluctuated dynamically and increased sharply at the premolt stage. The CO-IP and luciferase reporter assay results confirmed the molecular interplay of EcR and RXR. The heterodimer complex formed by the two transcription factors significantly induced the transcription of E75, an essential gene in the ecdysteroid signaling pathway.ConclusionsOur study unveiled the diverse molecular function and molecular interplay of EcR and RXR; RXR is possibly a “constitutive-type” gene, and EcR is possibly a vital speed-limiting gene while both EcR and RXR are required to initiate the ecdysteroid signaling cascade, which may be indispensable for molting regulation in E. sinensis. The results provide a theoretical basis for the endocrine control of molting in E. sinensis and novel insights into the molecular mechanism of molting mediated by the ecdysteroid signaling pathway in crustaceans.

The Mae Ping shear zone (MPSZ), a major shear zone trending NW-SE in Thailand, is responsible for the left-lateral displacement of the N-S Triassic-Jurassic granitoid and gneiss belt. This displacement is postulated to have contributed to Cenozoic extrusion tectonics. Within the Lan Sang National Park, the MPSZ exposes several intensely deformed lithologies, collectively known as the Lan Sang gneisses. These gneisses have attracted considerable attention for their potential to substantiate the extrusion model. However, the timing of the emplacement of the orthogneiss protolith is still debated. Moreover, the origin and distribution of the Eocene syn-shearing granodiorite within this shear zone are not well understood. To shed light on the magmatic history of the MPSZ, this study utilized zircon U-Pb geochronology to systematically investigate the Lan Sang gneisses. Our findings demonstrate that these gneisses can be categorized into paragneiss and orthogneiss groups. Paragneiss samples feature zircons displaying rounded detrital cores ranging from 3,078 to 450 Ma, with metamorphic rim overgrowth of ca. 200 Ma (most Th/U

Identifying the key nodes in complicated networks is an essential topic. A number of methods have been developed in recent years to solve this issue more effectively. Multi-attribute ranking is a widely used and efficient method to increase the accuracy of identifying the key nodes. Using k-shell iteration information and propagation threshold differences, we thoroughly analyze the node’s position attribute and the propagation attribute to offer a hybrid influence method based on information entropy. The two attributes will be weighted using the information entropy weighting method, and then the nodes’ influence ranking will be calculated. Correlation experiments in nine different networks were carried out based on the Susceptible–Infected–Recovered (SIR) model. Among these, we use the imprecision function, Kendall’s correlation coefficient, and the complementary cumulative distribution function to validate the suggested method. The experimental results demonstrate that our suggested method outperforms previous node ranking methods in terms of monotonicity, relevance, and accuracy and performs well to achieve a more accurate ranking of nodes in the network.

The discovery of Carboniferous hydrocarbon source rocks in the Mahu-Shawan Sag has implied considerable exploration potential in the Carboniferous strata in the western Junggar Basin. However, controversy has long surrounded when and how the Junggar Ocean was eventually closed, leading to a poor understanding of the Carboniferous basin evolution and the continental growth of the Central Asian Orogenic Belt. We performed stratigraphic and geochronologic studies to establish the chronostratigraphic framework of the western Junggar Basin to better understand its tectonic-sedimentary evolution during the Carboniferous-Early Permian. Three tectonostratigraphic units in the southern West Junggar region have been identified as Early Carboniferous shallow-deep marine sequences, Late Carboniferous coast-shallow marine sequences, and Early Permian continental sequences. The Carboniferous strata are similar to forearc and backarc-rift sequences in the Western Fault Belt and the Mahu-Shawan Sag, respectively. The Lower Permian strata in the southern West Junggar region are all continental sequences. Seismic profiles indicate extensional settings in the early stage of Late Carboniferous and Early Permian but a compressional setting at the end of Late Carboniferous. Geochemical data have suggested a Carboniferous continental arc setting and an Early Permian within-plate extensional setting. Meanwhile, calc-alkaline arc magma migrated from the Zhongguai High to the Western Fault Belt at the end of the Late Carboniferous. Collectively, the tectonic-sedimentary evolution in the Carboniferous-Early Permian of the southern West Junggar region can be divided into three stages: 1) Early Carboniferous subduction, 2) Late Carboniferous slab roll-back, and 3) Early Permian intra-continental evolution stage. This model constrains the closure of the Junggar Ocean at the Late Carboniferous.

The identification of key nodes in complex networks is a hot topic. Therefore, it attracts increasing attention from different fields, like airline networks and social networks. To identify the key nodes in complex network, we suggest an improved gravity model method that takes propagation features into account. Relevant experiments were carried out in four actual airline networks based on the Susceptible Infected Recovered (SIR) model. First, we analyze the correlation between the proposed method and other benchmark methods.Then, Kendall’s correlation coefficient and the imprecision function were used as evaluation metrics to analyze and validate the proposed method. Empirical results reveal that the suggested method outperforms previous benchmark methods in terms of precision and effectiveness for identifying key nodes, especially in the US air network, where Kendall’s tau achieves a 107% improvement compared to the gravity centrality method.

Edge detection is one of the fundamental components of advanced computer vision tasks, and it is essential to preserve computational resources while ensuring a certain level of performance. In this paper, we propose a lightweight edge detection network called the Parallel and Hierarchical Network (PHNet), which draws inspiration from the parallel processing and hierarchical processing mechanisms of visual information in the visual cortex neurons and is implemented via a convolutional neural network (CNN). Specifically, we designed an encoding network with parallel and hierarchical processing based on the visual information transmission pathway of the “retina-LGN-V1” and meticulously modeled the receptive fields of the cells involved in the pathway. Empirical evaluation demonstrates that, despite a minimal parameter count of only 0.2 M, the proposed model achieves a remarkable ODS score of 0.781 on the BSDS500 dataset and ODS score of 0.863 on the MBDD dataset. These results underscore the efficacy of the proposed network in attaining superior edge detection performance at a low computational cost. Moreover, we believe that this study, which combines computational vision and biological vision, can provide new insights into edge detection model research.

Culture substrates display profound influence on biological and developmental characteristic of cells cultured in vitro. This study investigates the influence of polyvinyl alcohol (PVA) substrates blended with different concentration of collagen or/and gelatin on the cell adhesion, proliferation, shape, spreading, and differentiation of stem cells. The collagen/gelatin blended PVA substrates were prepared by air drying. During drying, blended collagen or/and gelatin can self-assemble into macro-scale nucleated particles or branched fibrils in the PVA substrates that can be observed under the optical microscope. These collagen/gelatin blended substrates revealed different surface topography, z-average, roughness, surface adhesion and Young’s modulus as examined by the atomic force microscope (AFM). The results of Fourier transform infrared spectroscopy (FTIR) analysis indicated that the absorption of amide I (1,600–1,700 cm−1) and amide II (1,500–1,600 cm−1) groups increased with increasing collagen and gelatin concentration blended and the potential of fibril formation. These collagen or/and gelatin blended PVA substrates showed enhanced NIH-3T3 fibroblast adhesion as comparing with the pure PVA, control tissue culture polystyrene, conventional collagen-coated and gelatin-coated wells. These highly adhesive PVA substrates also exhibit inhibited cell spreading and proliferation. It is also found that the shape of NIH-3T3 fibroblasts can be switched between oval, spindle and flattened shapes depending on the concentration of collagen or/and gelatin blended. For inductive differentiation of stem cells, it is found that number and ration of neural differentiation of rat cerebral cortical neural stem cells increase with the decreasing collagen concentration in the collagen-blended PVA substrates. Moreover, the PVA substrates blended with collagen or collagen and gelatin can efficiently support and conduct human pluripotent stem cells to differentiate into Oil-Red-O- and UCP-1-positive brown-adipocyte-like cells via ectodermal lineage without the addition of mitogenic factors. These results provide a useful and alternative platform for controlling cell behavior in vitro and may be helpful for future application in the field of regenerative medicine and tissue engineering.

BackgroundCerebral small vessel disease (CSVD) is common in the elderly population. Neutrophil gelatinase-associated lipocalin (NGAL) is closely related to cardiovascular and cerebrovascular diseases. NGAL causes pathological changes, such as damage to the vascular endothelium, by causing inflammation, which results in other related diseases. The purpose of this study was to investigate whether serum NGAL levels could predict disease severity in patients with CSVD.MethodsThe patients with CSVD who visited the Department of Neurology at the First Affiliated Hospital of Zhengzhou University between January 2018 and June 2022 were prospectively included. The total CSVD burden score was calculated using whole-brain magnetic resonance imaging (MRI), and the patients were divided into a mild group (total CSVD burden score < 2 points) and a severe group (total CSVD burden score ≥ 2 points). Age, sex, height, smoking and alcohol consumption history, medical history, and serological results of patients were collected to perform the univariate analysis. Multivariate logistic regression was used to analyze the risk factors that affect CSVD severity. The multiple linear regression method was used to analyze which individual CSVD markers (periventricular white matter hyperintensities, deep white matter hyperintensities, lacune, and cerebral microbleed) play a role in the association between total CSVD burden score and NGAL.ResultsA total of 427 patients with CSVD (140 in the mild group and 287 in the severe group) were included in the study. A multivariate logistic regression analysis showed that the following factors were significantly associated with CSVD severity: male sex [odds ratio(OR), 1.912; 95% confidence interval (CI), 1.150–3.179], age (OR, 1.046; 95% CI, 1.022–1.070), history of cerebrovascular disease (OR, 3.050; 95% CI, 1.764–5.274), serum NGAL level (OR, 1.005; 95% CI, 1.002–1.008), and diabetes (OR, 2.593; 95% CI, 1.424–4.722). A multivariate linear regression shows that periventricular white matter hyperintensities and cerebral microbleed are associated with serum NGAL concentrations (P < 0.05).ConclusionSerum NGAL level is closely related to CSVD severity and is a risk factor for the burden of CSVD brain damage. Serum NGAL has high specificity in reflecting the severity of CSVD.

Blueberry is a characteristic berry fruit shrub of the genus Vaccinium in the Rhododendron family. The fruit is rich in anthocyanins and has a variety of nutritional and health functions. This study aimed to systematically study the effect of exogenous abscisic acid (ABA) application on ripening and metabolites in blueberry fruits. Blueberry fruit ripening was divided into six stages for further analysis. In this study, nontarget metabolomics was performed to demonstrate the effect on metabolite levels. The results showed that 1000 mg/L ABA significantly promoted fruit ripening and increased anthocyanin content. Moreover, exogenous ABA treatment can affect endogenous ABA levels and improve its antioxidant capacity. Important metabolites of the flavonoid pathway were detected, and the results showed that anthocyanin synthesis increased, and some other bioactive metabolite levels decreased. After comprehensive assessments, we believe that 1000 mg/L exogenous ABA application will have positive impacts on blueberry fruit quality and economic benefits.

The second-largest transcription factor superfamily in plants is that of the basic helix-loop-helix (bHLH) family, which plays an important complex physiological role in plant growth, tissue development, and environmental adaptation. Systematic research on the Chenopodium quinoa bHLH family will enable a better understanding of this species. Herein, authors used a variety of bioinformatics methods and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) to explore the evolution and function of the 218 CqbHLH genes identified. A total of 218 CqbHLH transcription factor genes were identified in the whole genome, located on 18 chromosomes. A phylogenetic tree was constructed using the CqbHLH and AtbHLH proteins to determine their homology, and the members were divided into 20 subgroups and one unclustered gene. Authors also analyzed 218 CqbHLH genes, conservative motifs, chromosome diffusion, and gene replication. The author constructed one Neighbor-Joining (NJ) tree and a collinearity analysis map of the bHLH family in C. quinoa and six other plant species to study the evolutionary relationship and homology among multiple species. In addition, the expression levels of 20 CqbHLH members from different subgroups in various tissues, different fruit developmental stages, and six abiotic stresses were analyzed. Authors identified 218 CqbHLH genes and studied their biological functions, providing a basis for better understanding and further studying the bHLH family in quinoa.

In this study, a method of stabilizing the output beam of a large-mode-area fiber amplifier operating above the mode instability threshold is demonstrated. A mode control system based on the photonic lantern is used to excite dynamic mode beatings as the seeding stage of a 42/250 µm Yb-doped fiber amplifier. We propose a theoretical explanation for the validity of this method: provided that the mode interference patterns generated by input mode beatings are antisymmetric to those in the main amplifier caused by thermally induced non-linear effects, the refractive index grating will not be formed to indicate the onset of mode instability. Experimentally, significant mode stability and beam quality improvement have been achieved in this system at power levels of up to nearly four times the mode instabilities threshold.

PurposeThe present study aimed to investigate the clinical prognostic significance of radiomics signature (R-signature) in patients with gastric neuroendocrine neoplasm (GNEN).Methods and MaterialsA retrospective study of 182 patients with GNEN who underwent dual-phase enhanced computed tomography (CT) scanning was conducted. LASSO-Cox regression analysis was used to screen the features and establish the arterial, venous and the arteriovenous phase combined R-signature, respectively. The association between the optimal R-signature with the best prognostic performance and overall survival (OS) was assessed in the training cohort and verified in the validation cohort. Univariate and multivariate Cox regression analysis were used to identify the significant factors of clinicopathological characteristics for OS. Furthermore, the performance of a combined radiomics-clinical nomogram integrating the R-signature and independent clinicopathological risk factors was evaluated.ResultsThe arteriovenous phase combined R-signature had the best performance in predicting OS, and its C-index value was better than the independent arterial and venous phase R-signature (0.803 vs 0.784 and 0.803 vs 0.756, P

BackgroundEsophageal cancer is a highly malignant neoplasm with poor prognosis. Of its patients, upper gastrointestinal bleeding (UGIB) is one of the most challenging and threatening conditions in the emergency department (ED). However, no previous studies have analyzed the etiologies and clinical outcomes in this specific population. This study aimed to identify the clinical characteristics and risk factors for 30-day mortality in esophageal cancer patients with UGIB.MethodsThis retrospective cohort study enrolled 249 adult patients with esophageal cancer presenting with UGIB in the ED. Patients was divided into the survivor and non-survivor groups, and their demographic information, medical history, comorbidities, laboratory parameters, and clinical findings were recorded. The factors associated with 30-day mortality were identified using Cox’s proportional hazard model.ResultsAmong the 249 patients in this study, 30-day mortality occurred in 47 patients (18.9%). The most common causes of UGIB were tumor ulcer (53.8%), followed by gastric/duodenal ulcer (14.5%), and arterial-esophageal fistula (AEF) (12.0%). Multivariate analyses indicated that underweight (HR = 2.02, p = 0.044), history of chronic kidney disease (HR = 6.39, p < 0.001), active bleeding (HR = 2.24, p = 0.039), AEF (HR = 2.23, p = 0.046), and metastatic lymph nodes (HR = 2.99, p = 0.021) were independent risk factors for 30-day mortality.ConclusionsThe most common cause of UGIB in esophageal cancer patients was tumor ulcer. AEF, accounting for 12% of UGIB in our study, is not an uncommon cause. Underweight, underlying chronic kidney disease, active bleeding, AEF, and tumor N stage > 0 were independent risk factors for 30-day mortality.

An increasing body of evidence has suggested that reprogrammed metabolism plays a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC) by affecting the tumor and stromal cellular components in the tumor microenvironment (TME). By analyzing the KRAS pathway and metabolic pathways, we found that calcium and integrin-binding protein 1 (CIB1) corresponded with upregulation of glucose metabolism pathways and was associated with poor prognosis in patients with PDAC from The Cancer Genome Atlas (TCGA). Elevated CIB1 expression combined with upregulated glycolysis, oxidative phosphorylation (Oxphos), hypoxia pathway activation, and cell cycle promoted PDAC tumor growth and increased tumor cellular com-ponents. Furthermore, we confirmed the mRNA overexpression of CIB1 and co-expression of CIB1 and KRAS mutation in cell lines from the Expression Atlas. Subsequently, immunohistochemistry staining from the Human Protein Atlas (HPA) showed that high expression of CIB1 in tumor cells was associated with an increased tumor compartment and reduced stromal cellular abundance. Furthermore, using multiplexed immunohistochemistry (mIHC), we verified that low stromal abundance was correlated with low infiltration of CD8+ PD-1− T cells which led to suppressed anti-tumor immunity. Overall, our findings identify CIB1 as a metabolic pathway-mediated factor for the restriction of immune cell infiltration in the stromal compartment of PDAC and highlight the potential value of CIB1 as a prognostic biomarker involved in metabolic reprogramming and immune modulation.

Neuropathic pain (NP) is a frequent condition caused by a lesion in, or disease of, the central or peripheral somatosensory nervous system and is associated with excessive inflammation in the central and peripheral nervous systems. Repetitive transcranial magnetic stimulation (rTMS) is a supplementary treatment for NP. In clinical research, rTMS of 5–10 Hz is widely placed in the primary motor cortex (M1) area, mostly at 80%–90% RMT, and 5–10 treatment sessions could produce an optimal analgesic effect. The degree of pain relief increases greatly when stimulation duration is greater than 10 days. Analgesia induced by rTMS appears to be related to reestablishing the neuroinflammation system. This article discussed the influences of rTMS on the nervous system inflammatory responses, including the brain, spinal cord, dorsal root ganglia (DRG), and peripheral nerve involved in the maintenance and exacerbation of NP. rTMS has shown an anti-inflammation effect by decreasing pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, and increasing anti-inflammatory cytokines, including IL-10 and BDNF, in cortical and subcortical tissues. In addition, rTMS reduces the expression of glutamate receptors (mGluR5 and NMDAR2B) and microglia and astrocyte markers (Iba1 and GFAP). Furthermore, rTMS decreases nNOS expression in ipsilateral DRGs and peripheral nerve metabolism and regulates neuroinflammation.

BackgroundNeutrophil extracellular traps (NETs) are crucial in the progression of several cancers. The formation of NETs is closely related to reactive oxygen species (ROS), and the granule proteins involved in nucleosome depolymerization under the action of ROS together with the loosened DNA compose the basic structure of NETs. This study aims to investigate the specific mechanisms of NETs promoting gastric cancer metastasis in order to perfect the existing immunotherapy strategies.MethodsIn this study, the cells and tumor tissues of gastric cancer were detected by immunological experiments, real-time polymerase chain reaction and cytology experiments. Besides, bioinformatics analysis was used to analyze the correlation between cyclooxygenase-2 (COX-2) and the immune microenvironment of gastric cancer, as well as its effect on immunotherapy.ResultsExamination of clinical specimens showed that NETs were deposited in tumor tissues of patients with gastric cancer and their expression was significantly correlated with tumor staging. Bioinformatics analysis showed that COX-2 was involved in gastric cancer progression and was associated with immune cell infiltration as well as immunotherapy. In vitro experiments, we demonstrated that NETs could activate COX-2 through Toll-like receptor 2 (TLR2) and thus enhance the metastatic ability of gastric cancer cells. In addition, in a liver metastasis model of nude mice we also demonstrated the critical role of NETs and COX-2 in the distant metastasis of gastric cancer.ConclusionNETs can promote gastric cancer metastasis by initiating COX-2 through TLR2, and COX-2 may become a target for gastric cancer immunotherapy.

Introductionε-poly-L-lysine (ε-PL) is a high value, widely used natural antimicrobial peptide additive for foods and cosmetic products that is mainly produced by Streptomyces albulus. In previous work, we developed the high-yield industrial strain S. albulus WG-608 through successive rounds of engineering.MethodsHere, we use integrated physiological, transcriptomic, and proteomics association analysis to resolve the complex mechanisms underlying high ε-PL production by comparing WG-608 with the progenitor strain M-Z18.ResultsOur results show that key genes in the glycolysis, pentose phosphate pathway, glyoxylate pathway, oxidative phosphorylation, and L-lysine biosynthesis pathways are differentially upregulated in WG-608, while genes in the biosynthetic pathways for fatty acids, various branched amino acids, and secondary metabolite by-products are downregulated. This regulatory pattern results in the introduction of more carbon atoms into L-lysine biosynthesis and ε-PL production. In addition, significant changes in the regulation of DNA replication, transcription, and translation, two component systems, and quorum sensing may facilitate the adaptability to environmental pressure and the biosynthesis of ε-PL. Overexpression of ppk gene and addition of polyP6 further enhanced the ε-PL production.DiscussionThis study enables comprehensive understanding of the biosynthetic mechanisms of ε-PL in S. albulus WG-608, while providing some genetic modification and fermentation strategies to further improve the ε-PL production.

The number of patients with bone defects caused by various bone diseases is increasing yearly in the aging population, and people are paying increasing attention to bone tissue engineering research. Currently, the application of bone tissue engineering mainly focuses on promoting fracture healing by carrying cytokines. However, cytokines implanted into the body easily cause an immune response, and the cost is high; therefore, the clinical treatment effect is not outstanding. In recent years, some scholars have proposed the concept of tissue-induced biomaterials that can induce bone regeneration through a scaffold structure without adding cytokines. By optimizing the scaffold structure, the performance of tissue-engineered bone scaffolds is improved and the osteogenesis effect is promoted, which provides ideas for the design and improvement of tissue-engineered bones in the future. In this study, the current understanding of the bone tissue structure is summarized through the discussion of current bone tissue engineering, and the current research on micro-nano bionic structure scaffolds and their osteogenesis mechanism is analyzed and discussed.

ObjectivesProthrombin time (PT) and PT-INR are independent predictors of mortality in patients with cancer. The PT and PT-INR of cancer patients are independent predictive variables of mortality. However, whether the PT or PT-INR is related to in-hospital mortality in severely ill patients with tumors remains unknown.DesignThis was a case–control study based on a multicenter public database.SettingsThis study is a secondary analysis of data extracted from 2014 to 2015 from the Electronic Intensive Care Unit Collaborative Research Database.ParticipantsThe data relevant to seriously ill patients with tumors were obtained from 208 hospitals spread throughout the USA. This research included a total of 200,859 participants. After the samples were screened for patients with combination malignancies and prolonged PT-INR or PT, the remaining 1745 and 1764 participants, respectively, were included in the final data analysis.Primary and secondary outcome measuresThe key evaluation methodology was the PT count and PT-INR, and the main outcome was the in-hospital mortality rate.ResultsAfter controlling for confounding variables, we found a curvilinear connection between PT-INR and in-hospital mortality (p

The Permian–Triassic mass extinction has been considered the largest bio-crisis of the Phanerozoic, with more than 90% of marine species extinct. Previous studies showed that ostracods suffered various extinction patterns in different localities and were relatively enriched in the lowermost Triassic shallow marine microbialites. Multiple hypotheses have been put forward to explore the reasons for this phenomenon. Abundant ostracod fossils were collected from the microbialite-bearing Youping section in the Nanpanjiang Basin. 45 species in 22 genera from Wujiaping Formation increased dramatically to 104 species in 33 genera from the microbialites of basal Luolou Formation. However, Ostracods from the Youping section suffered severe extinction during the second phase of the Permian–Triassic crisis, i.e., the earliest Triassic mass extinction (ETME), rather than the first phase, i.e., the latest Permian mass extinction (LPEM). In addition, the Sørenson coefficient has been used to examine the similarity of faunal associations among different sections of the Permian–Triassic transitional beds. There was no significant differences for ostracods between microbialites and non-microbialites sections based on similarity analysis. Thus, we proposed that “Shallow marine refuge” hypothesis could explain the high diversity and high abundance of ostracods of the Permian–Triassic transitional beds. Besides, ostracods showed remarkable geographical differentiation at both regional and global scales during the Permian–Triassic transitional beds and were presumably controlled by geographical isolation.

BackgroundThe COVID pandemic has brought tremendous negative effects on the mental health of health care workers, such as anxiety, depression, and sleep disorders. We conducted this study to evaluate the sleep-related cognition of Chinese health care workers (HCWs) during the first wave of COVID-19 pandemic and analyze its association with sleep quality, so as to provide scientific reference for improving sleep of HCWs.Patients and methodsA total of 404 HCWs from Yijishan Hospital of Wuhu City, China were enrolled in the study, selected by randomized cluster sampling in May 2020. We made a questionnaire to collect the general demographic information of the participants. The Pittsburgh Sleep Quality Index (PSQI) and a brief version of Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16) were used to measure sleep quality and sleep-related cognition, respectively.ResultsThe results showed that 312 HCWs (77.2%) had false beliefs and attitudes about sleep, while only 92 HCWs (22.8%) had correct beliefs about sleep. In addition, we found that those HCWs who were older, married, with a bachelor’s degree or higher, nurses, more daily working hours (> 8 h) and monthly night shifts (≥ 5 times), had higher DBAS-16 scores (all p

Papillary thyroid cancer (PTC) is a common malignancy of the endocrine system, and its morbidity and mortality are increasing year by year. Traditional two-dimensional culture of cell lines lacks tissue structure and is difficult to reflect the heterogeneity of tumors. The construction of mouse models is inefficient and time-consuming, which is difficult to be applied to individualized treatment on a large scale. Clinically relevant models that recapitulate the biology of their corresponding parental tumors are urgently needed. Based on clinical specimens of PTC, we have successfully established patient-derived organoids by exploring and optimizing the organoid culture system. These organoids have been cultured stably for more than 5 passages and successfully cryopreserved and retried. Histopathological and genome analysis revealed a high consistency of the histological architectures as well as mutational landscapes between the matched tumors and organoids. Here, we present a fully detailed method to derive PTC organoids from clinical specimens. Using this approach, we have developed PTC organoid lines from thyroid cancer samples with a success rate of 77.6% (38/49) until now.

Objectives: Chronic low back pain (CLBP) accounts for a majority of the disability associated with LBP, which can produce long-term negative effects. This cross-sectional study aimed to investigate the association between smoking and pain, dysfunction and psychological status in patients with CLBP.Methods: The 54 patients with CLBP were recruited and divided into smoking and non-smoking groups. Their pain, dysfunction, anxiety, depression, fear and quality of life were evaluated. The amount of cigarettes smoked daily was recorded.Results: Significant differences in VAS, ODI, RMDQ and FABQ and the impact of LBP on life and work were found between smoking and non-smoking patients. In addition, a correlation was found between the daily cigarette smoking amount and VASmax, FABQtotal, SDS and FABQ-W. Moreover, a correlation was observed between the amount of cigarettes smoked daily and the degree of impact of low back pain on work.Conclusion: The study found that smoking affected the aggravation of symptoms in patients with CLBP, which indicated that patients with CLBP and people at risk of LBP should be aware of the harm caused by smoking.

IntroductionThe decomposition of plant litter mass is responsible for substantial carbon fluxes and remains a key process regulating nutrient cycling in natural and managed ecosystems. Litter decomposition has been addressed in agricultural monoculture systems, but not in intercropping systems, which produce species-diverse litter mass mixtures. The aim here is to quantify how straw type, the soil environment and their combined effects may influence straw decomposition in widely practiced maize/legume intercropping systems.MethodsThree decomposition experiments were conducted over 341 days within a long-term intercropping field experiment which included two nitrogen (N) addition levels (i.e. no-N and N-addition) and five cropping systems (maize, soybean and peanut monocultures and maize/soybean and maize/peanut intercropping). Experiment I was used to quantify litter quality effects on decomposition; five types of straw (maize, soybean, peanut, maize-soybean and maize-peanut) from two N treatments decomposed in the same maize plot. Experiment II addressed soil environment effects on root decomposition; soybean straw decomposed in different plots (five cropping systems and two N levels). Experiment III addressed ‘home’ decomposition effects whereby litter mass (straw) was remained to decompose in the plot of origin. The contribution of litter and soil effects to the home-field advantages was compared between experiment III (‘home’ plot) and I-II (‘away’ plot).Results and discussionsStraw type affected litter mass loss in the same soil environment (experiment I) and the mass loss values of maize, soybean, peanut, maize-soybean, and maize-peanut straw were 59, 77, 87, 76, and 78%, respectively. Straw type also affected decomposition in the ‘home’ plot environment (experiment III), with mass loss values of maize, soybean, peanut, maize-soybean and maize-peanut straw of 66, 74, 80, 72, and 76%, respectively. Cropping system did not affect the mass loss of soybean straw (experiment II). Nitrogen-addition significantly increased straw mass loss in experiment III. Decomposition of maize-peanut straw mixtures was enhanced more by ‘home-field advantage’ effects than that of maize-soybean straw mixtures. There was a synergistic mixing effect of maize-peanut and maize-soybean straw mixture decomposition in both 'home' (experiment III) and ‘away’ plots (experiment I). Maize-peanut showed greater synergistic effects than maize-soybean in straw mixture decomposition in their 'home' plot (experiment III). These findings are discussed in terms of their important implications for the management of species-diverse straw in food-production intercropping systems.

BackgroundThe epigenetic regulatory chemical lactate is a product of glycolysis. It can regulate gene expression through histone lactylation, thereby promoting tumor proliferation, metastasis, and immunosuppression.MethodsIn this study, a lactylation-related model for gastric cancer (GC) was constructed, and its relationships to prognosis, immune cell infiltration, and immunotherapy were investigated. By contrasting normal tissues and tumor tissues, four lactylation-related pathways that were substantially expressed in GC tissues were found in the GSEA database. Six lactylation-related genes were screened for bioinformatic analysis. The GC data sets from the TCGA and GEO databases were downloaded and integrated to perform cluster analysis, and the lactylation related model was constructed by secondary clustering.ResultsThe fingding demonstrated that the lactylation score has a strong correlation with the overall survival rate from GC and the progression of GC. Mechanistic experiments showed that abundant immune cell infiltration (macrophages showed the highest degree of infiltration) and increased genetic instability are traits of high lactylation scores. Immune checkpoint inhibitors (ICIs) demonstrated a reduced response rate in GC with high lactylation scores. At the same time, tumors with high lactylation scores had high Tumor Immune Dysfunction and Exclusion scores, which means that they had a higher risk of immune evasion and dysfunction.DiscussionThese findings indicate that the lactylation score can be used to predict the malignant progression and immune evasion of GC. This model also can guide the treatment response to ICIs of GC. The constructed model of the lactate gene is also expected to become a potential therapeutic target for GC and diagnostic marker.

Introduction: The proper operation of wastewater treatment plants is a key factor in maintaining a stable river and lake environment. Low purification efficiency in winter is a common problem in high-altitude wastewater treatment plants (WWTPs), and analysis of the microbial community involved in the sewage treatment process at high-altitude can provide valuable references for improving this problem.Methods: In this study, the bacterial communities of high- and low-altitude WWTPs were investigated using Illumina high-throughput sequencing (HTS). The interaction between microbial community and environmental variables were explored by co-occurrence correlation network.Results: At genus level, Thauera (5.2%), unclassified_Rhodocyclaceae (3.0%), Dokdonella (2.5%), and Ferribacterium (2.5%) were the dominant genera in high-altitude group. The abundance of nitrogen and phosphorus removal bacteria were higher in high-altitude group (10.2% and 1.3%, respectively) than in low-altitude group (5.4% and 0.6%, respectively). Redundancy analysis (RDA) and co-occurrence network analysis showed that altitude, ultraviolet index (UVI), pH, dissolved oxygen (DO) and total nitrogen (TN) were the dominated environmental factors (p < 0.05) affecting microbial community assembly, and these five variables explained 21.4%, 20.3%, 16.9%, 11.5%, and 8.2% of the bacterial assembly of AS communities.Discussion: The community diversity of high-altitude group was lower than that of low-altitude group, and WWTPs of high-altitude aeras had a unique microbial community structure. Low temperature and strong UVI are pivotal factors contributing to the reduced diversity of activated sludge microbial communities at high-altitudes.

IntroductionMoso bamboo (Phyllostachys edulis (Carrière) J. Houz.), the most widely distributed economic bamboo species in southern China, can easily invade adjacent communities due to its clonal reproduction. However, there is little information on the effects of its establishment and expansion to adjacent forest soil communities, particularly in planted forests.MethodsWe investigated the relationships between soil properties and the microbial community during bamboo invasion under different slope directions (shady or sunny slope) and positions (bottom, middle, or top slope), in three typical stand types (bottom: pure moso bamboo, middle: mixed stands of moso bamboo and Masson pine (Pinus massoniana Lamb.), and top: pure Masson pine) in the Lijiang River Basin. This study aimed to explore the effects of key environmental factors on soil microbial composition, diversity, and abundance.Results and DiscussionThe results showed that the abundance of Acidobacteria bacterium and Acidobacteria bacterium 13_2_20CM_58_27, and Verrucomicrobia bacterium decreased as the slope increased (p

T cells play a crucial role in the regulation of immune response and are integral to the efficacy of cancer immunotherapy. Because immunotherapy has emerged as a promising treatment for cancer, increasing attention has been focused on the differentiation and function of T cells in immune response. In this review, we describe the research progress on T-cell exhaustion and stemness in the field of cancer immunotherapy and summarize advances in potential strategies to intervene and treat chronic infection and cancer by reversing T-cell exhaustion and maintaining and increasing T-cell stemness. Moreover, we discuss therapeutic strategies to overcome T-cell immunodeficiency in the tumor microenvironment and promote continuous breakthroughs in the anticancer activity of T cells.

White spot lesions (WSLs) are common enamel infectious diseases in fixed orthodontic treatment, which might attribute to the dysbiosis of oral microbiome. However, the correlation of Candida albicans with oral bacteriome in WSLs still remains unrevealed. This study investigated the carriage of C. albicans and how it shaped the bacterial community in disease or healthy supragingival plaque, to explore the potential role of interkingdom interaction in orthodontic WSLs. In this study, 31 patients with WSLs (WSLs) and 23 healthy patients (Health) undergoing fixed orthodontic treatment were enrolled. The supragingival microbiota in both groups were determined using 16S rRNA gene sequencing. Colonization and abundance of C. albicans in the plaque were determined via culture-dependent and -independent methods. Among WSLs patients, the correlation of C. albicans and bacteriome was analyzed under QIIME2-based bioinformatics and Spearman’s correlation coefficient. The raw reads were deposited into the NCBI Sequence Read Archive (SRA) database (Accession Number: SRP404186). Significant differences in microbial diversity as well as composition were observed between WSLs and Health groups. Leptotrichia remarkably enriched in the WSLs group, while Neisseria and Cardiobacterium significantly enriched in the Health group. In addition, 45% of WSLs patients were C. albicans carriers but none in patients without WSLs. Among all WSLs patients, beta diversity and microbial composition were distinguished between C. albicans carriers and non-carriers. In C. albicans carriers, Corynebacterium matruchotii and Streptococcus mutans significantly enriched whereas Saccharibacteria_TM7_G-1 significantly depleted. The abundance of C. albicans was positively associated with bacteria such as Streptococcus mutans, while the negative correlation was detected between C. albicans and several bacteria such as Cardiobacterium hominis and Streptococcus sanguinis. Our study elucidated the distinguished supragingival plaque microbiome between orthodontic patients with and without WSLs. C. albicans frequently existed and enriched in orthodontic derived WSLs. The carriage of C. albicans shape plaque bacterial community in demineralized lesions and might play roles in WSLs pathogenesis.

ObjectsThis study aimed to elucidate the effect of cognitive bias modification on depression.MethodsThis research included 10 randomized studies searching four major databases: PubMed, Embase, PsycINFO, and Cochrane Library, with a total sample size of 467. Moreover, they were examined for quality and possible publication bias.ResultsCognitive bias modification (CBM) had statistically significant results, g = −0.64, 95% CI = [−0.97–0.32]. The interpretation of cognitive bias modification shows the highest effect size, g = −1.45, 95% CI = [−2.05–0.88]. When the training place is located in the laboratory, the training effect is significant, g = −1.11, 95% CI = [−1.62–0.61]. The difference is statistically significant when the training environment was changed to home, g = −0.28, 95% CI = [−0.51–0.05]. CBM has a statistical effect on moderate-to-severe depression, g = −0.70, 95% CI = [−1.04–0.36].ConclusionWe found that CBM had a moderate therapeutic effect on depression, whether the setting was at home or in the lab. Especially when the interpretation of cognitive bias modification (CBM-I) was used, we got the highest effect value. Furthermore, CBM has a statistical effect on moderate-to-severe depression.

As an increasingly prevalent form of human activity, roads drive the taxonomic homogenization of mountain plant assemblages, threatening global biodiversity. However, little is known about how mountain roads impact functional and phylogenetic beta diversity and how these effects are related to taxonomic homogenization. To understand the mechanism of taxonomic homogenization triggered by mountain roads, we used species absence/presence data from 76 plots (2 m*50 m) and values for 12 traits measured on 978 species from the interior and roadside communities in the Qionglai mountain range, one of the temperate regions with the highest plant species richness in the world. We used a structural equation modeling approach (SEM) to consider several surrogates of road disturbance (changes in soil physicochemical properties and the presence or absence of roads) and the causal relationship between three facets of beta diversity (taxonomic beta diversity, TBD; functional beta diversity, FBD and phylogenetic beta diversity, PBD). The results suggest that TBD, FBD and PBD respond inconsistently to mountain roads, despite strong positive correlations between the three facets of plant beta diversity in the study area. Compared with the interior community, the βtotal.tax and βtotal.func of the roadside community decreased by 2.54% and 2.22%, respectively, which were related to the reduction of species and trait richness differences and replacements; however, we did not find the same results when assessing the changes in βtotal.phy, which represents tip-weighted PBD (twPBD). Furthermore, the largest effect of roads on beta diversity was reflected in basal-weighted PBD (bwPBD), which decreased by 9.97%, indicating that those species with fewer extant relatives and longer evolutionary histories are more sensitive to mountain roads. Therefore, it is necessary to take targeted protection measures for ancient species in roadside communities. In addition, we believe that it is still necessary to take measures to prevent the further dispersal of nonnative species, although the presence of non-native species in roadside plots has led to small changes in three facets of beta diversity. There were causal relationships between the three facets of beta diversity, but their intensity and sign different in the SEM of different components of beta diversity (i.e., richness difference and replacement). Our findings suggest that the homogenization of community species composition at the landscape scale arises by a combination of adaptive responses of the functional traits of organisms to environmental consistency (e.g., reduced the differences in soil variables) caused by roads and resorting or reassembly of community clades composition due to environmental filtering. These results contribute to our comprehensive understanding of the impact of mountain roads on plant diversity, which highlights the complex relationship between human pressure and biodiversity loss.