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Abstract Background Spinal intradural tumors are rare and heterogeneous in histological type, aggressiveness, and symptomatology, and there is a lack of data about them. This study investigated the epidemiological features of spinal intradural tumors. Methods This retrospective analysis included patients with spinal intradural tumors who underwent surgical treatment at the Myelopathy and Spondylosis Ward Beijing Jishuitan Hospital between January 2012 and December 2022. Results This study included 1321 patients [aged 47.19 ± 14.90 years, 603 (45.65%) males] with spinal intradural tumors. The most common histological subtype was schwannoma [n = 511 (38.68%)], followed by spinal meningioma [n = 184 (13.93%)] and ependymoma [n = 101 (7.65%)]. Fifteen (1.14%) patients were diagnosed with metastatic spinal intradural tumors as a presentation of another primary cancer type. The spinal intradural tumors were mostly found in the lumbar region [n = 436 (33.01%)], followed by the thoracic vertebrae [n = 390 (29.52%)], cervical vertebrae [n = 154 (11.66%)], and thoracolumbar region [n = 111 (8.40%)]. Schwannomas mostly affected the lumbar region [n = 256 (52.64%)], spinal meningiomas in the thoracic region [n = 153 (83.15)], and ependymomas in the lumbar region [56 (55.45%)]. The de novo metastases were mostly found in the lumbar region [n = 8 (53.33%)]. Conclusion According to the results of our single-center study, the most common spinal intradural tumor in Northern China is schwannoma, followed by spinal meningioma and ependymoma.

Abstract In sedimentary basins, deep-seated overpressure conditions are frequently encountered. However, the precise origins of these overpressure conditions and the assessment of their formation times have long presented challenges. Previous studies have primarily relied on qualitative approaches to investigate overpressure origins, leading to substantial uncertainties in their findings. Based on theories such as the effective stress law, disequilibrium compaction, equilibrium depth, and nested fluid trapping containers in this paper, a new quantitative methodology is introduced for identifying the disequilibrium-compaction-induced origins of overpressure conditions. Additionally, the formation times of overpressure can be also estimated by nested fluid trapping container theory. This methodology is successfully applied to the northwestern Bozhong subbasin in the Bohai Bay Basin, China. The results indicate that the overpressure within the Dongying Formation of the northwestern Bozhong subbasin is primarily attributed to the disequilibrium compaction of mudstone, because the disequilibrium compaction of mudstone accounts for over 90% of the pressure in sandstone. Furthermore, the overpressure system in this area is not singular but comprises multiple nested relative fluid trapping containers. The application of nested fluid trapping container theory allows for an estimation of the overpressure’s formation time, although further validation of these estimates is required. It should be noted that the method proposed in this paper is particularly suited for sedimentary basins with relatively weak tectonic activity.

Abstract Background Diffuse large B-cell lymphomas (DLBCLs) display high molecular heterogeneity, but the International Prognostic Index (IPI) considers only clinical indicators and has not been updated to include molecular data. Therefore, we developed a widely applicable novel scoring system with molecular indicators screened by artificial intelligence (AI) that achieves accurate prognostic stratification and promotes individualized treatments. Methods We retrospectively enrolled a cohort of 401 patients with DLBCL from our hospital, covering the period from January 2015 to January 2019. We included 22 variables in our analysis and assigned them weights using the random survival forest method to establish a new predictive model combining bidirectional long-short term memory (Bi-LSTM) and logistic hazard techniques. We compared the predictive performance of our “molecular-contained prognostic model” (McPM) and the IPI. In addition, we developed a simplified version of the McPM (sMcPM) to enhance its practical applicability in clinical settings. We also demonstrated the improved risk stratification capabilities of the sMcPM. Results Our McPM showed superior predictive accuracy, as indicated by its high C-index and low integrated Brier score (IBS), for both overall survival (OS) and progression-free survival (PFS). The overall performance of the McPM was also better than that of the IPI based on receiver operating characteristic (ROC) curve fitting. We selected five key indicators, including extranodal involvement sites, lactate dehydrogenase (LDH), MYC gene status, absolute monocyte count (AMC), and platelet count (PLT) to establish the sMcPM, which is more suitable for clinical applications. The sMcPM showed similar OS results (P

Abstract Background To systematically analyze risk factors for delayed postpolypectomy bleeding (DPPB) in colorectum. Methods We searched seven large databases from inception to July 2022 to identify studies that investigated risk factors for DPPB. The effect sizes were expressed by relative risk (RR) and 95% confidence interval (95% CI). The heterogeneity was analyzed by calculating I 2 values and performing sensitivity analyses. Results A total of 15 articles involving 24,074 subjects were included in the study. The incidence of DPPB was found to be 0.02% (95% CI, 0.01–0.03), with an I 2 value of 98%. Our analysis revealed that male sex (RR = 1.64), history of hypertension (RR = 1.54), anticoagulation (RR = 4.04), polyp size (RR = 1.19), polyp size ≥ 10 mm (RR = 2.43), polyp size > 10 mm (RR = 3.83), polyps located in the right semicolon (RR = 2.48) and endoscopic mucosal resection (RR = 2.99) were risk factors for DPPB. Conclusions Male sex, hypertension, anticoagulation, polyp size, polyp size ≥ 10 mm, polyps located in the right semicolon, and endoscopic mucosal resection were the risk factors for DPPB. Based on our findings, we recommend that endoscopists should fully consider and implement effective intervention measures to minimize the risk of DPPB.

Abstract Cellulose is an important abundant renewable resource on Earth, and the microbial cellulose utilization mechanism has attracted extensive attention. Recently, some signalling molecules have been found to regulate cellulose utilization and the discovery of underlying signals has recently attracted extensive attention. In this paper, we found that the hydrogen sulfide (H2S) concentration under cellulose culture condition increased to approximately 2.3-fold compared with that under glucose culture condition in Ganoderma lucidum. Further evidence shown that cellulase activities of G. lucidum were improved by 18.2-27.6% through increasing H2S concentration. Then, we observed that the carbon repressor CreA inhibited H2S biosynthesis in G. lucidum by binding to the promoter of cbs, a key gene for H2S biosynthesis, at “CTGGGG”. In our study, we reported for the first time that H2S increased the cellulose utilization in G. lucidum, and analyzed the mechanism of H2S biosynthesis induced by cellulose. This study not only enriches the understanding of the microbial cellulose utilization mechanism but also provides a reference for the analysis of the physiological function of H2S signals.

Abstract Increasing evidence has revealed the large-scale nonstationary synchronizations as traveling waves in spontaneous neural activity. However, the interplay of various cell types in fine-tuning these spatiotemporal patters remains unclear. Here, we performed comprehensive exploration of spatiotemporal synchronizing structures across different cell types, states (awake, anesthesia, motion) and developmental axis in male mice. We found traveling waves in glutamatergic neurons exhibited greater variety than those in GABAergic neurons. Moreover, the synchronizing structures of GABAergic neurons converged toward those of glutamatergic neurons during development, but the evolution of waves exhibited varying timelines for different sub-type interneurons. Functional connectivity arises from both standing and traveling waves, and negative connections can be elucidated by the spatial propagation of waves. In addition, some traveling waves were correlated with the spatial distribution of gene expression. Our findings offer further insights into the neural underpinnings of traveling waves, functional connectivity, and resting-state networks, with cell-type specificity and developmental perspectives.

ABSTRACT Extracellular iodate reduction by Shewanella spp. contributes to iodide generation in the biogeochemical cycling of iodine. However, there is a disagreement on whether Shewanella spp. use different extracellular electron transfer pathways with dependence on electron donors in iodate reduction. In this study, a series of gene deletion mutants of Shewanella oneidensis MR-1 were created to investigate the roles of dmsEFABGH, mtrCAB, and so4357–so4362 operons in iodate reduction. The iodate-reducing activity of the mutants was tested with lactate, formate, and H2 as the sole electron donors, respectively. In the absence of single-dms gene, iodate reduction efficiency of the mutants was only 12.9%–84.0% with lactate at 24 hours, 22.1%–85.9% with formate at 20 hours, and 19.6%–57.7% with H2 at 42 hours in comparison to complete reduction by the wild type. Progressive inhibition of iodate reduction was observed when the dms homolog from the so4357–so4362 operon was deleted in the single-dms gene mutants. This result revealed complementation of dmsEFABGH by so4357–so4362 at the single-gene level, indicating modularity of the extracellular electron transfer pathway encoded by dmsEFABGH operon. Under the conditions of all electron donors, significant inhibition of iodate reduction and accumulation of H2O2 were detected for ΔmtrCAB. Collectively, these results demonstrated that the dmsEFABGH operon encodes an essential and modular iodate-reducing pathway without electron donor dependence in S. oneidensis MR-1. The mtrCAB operon was involved in H2O2 elimination with all electron donors. The findings in this study improved the understanding of molecular mechanisms underlying extracellular iodate reduction.IMPORTANCEIodine is an essential trace element for human and animals. Recent studies revealed the contribution of microbial extracellular reduction of iodate in biogeochemical cycling of iodine. Multiple reduced substances can be utilized by microorganisms as energy source for iodate reduction. However, varied electron transfer pathways were proposed for iodate reduction with different electron donors in the model strain Shewanella oneidensis MR-1. Here, through a series of gene deletion and iodate reduction experiments, we discovered that the dmsEFABGH operon was essential for iodate reduction with at least three electron donors, including lactate, formate, and H2. The so4357–so4362 operon was first demonstrated to be capable of complementing the function of dmsEFABGH at single-gene level.

BackgroundPulsed field ablation, as a non-thermal ablation modality, has received increasing attention. The aim of this study is to explore whether a reversible pulsed electric field (RPEF) can temporarily inhibit electrical conduction and provide a novel method for precise ablation of arrhythmia.MethodsRPEF energy was delivered from an ablation catheter to the atrium of six dogs, followed by a series of electrogram and histology assessments.ResultsRPEF ablation of ordinary myocardium resulted in an average reduction of 68.3% (range, 53.7%–83.8%) in electrogram amplitude, while 5 min later, the amplitude in eight electrograms returned to 77.9% (range, 72.4%–87.3%) of baseline. Similarly, the amplitude of the sinoatrial node electrograms reduced by an average of 73.0% (range, 60.2%–84.4%) after RPEF ablation, but recovered to 84.9% (range, 80.3%–88.5%) of baseline by 5 min. No necrotic change was detected in histopathology. Transient third-degree atrioventricular block occurred following the ablation of the maximum His potential sites with RPEF, the duration of which was voltage dependent. The histopathological results showed necrosis of the myocardium at the ablation sites but no injury to His bundle cells.ConclusionsRPEF can be applied to transiently block electrical conduction in myocardial tissues contributing to precise ablation.

Hydrogen sulfide (H2S) has recently been recognized as an important gaseous transmitter with multiple physiological effects in various species. Previous studies have shown that H2S alleviated heat-induced ganoderic acids (GAs) biosynthesis, an important quality index of Ganoderma lucidum. However, a comprehensive understanding of the physiological effects and molecular mechanisms of H2S in G. lucidum remains unexplored. In this study, we found that heat treatment reduced the mitochondrial membrane potential (MMP) and mitochondrial DNA copy number (mtDNAcn) in G. lucidum. Increasing the intracellular H2S concentration through pharmacological and genetic means increased the MMP level, mtDNAcn, oxygen consumption rate level and ATP content under heat treatment, suggesting a role for H2S in mitigating heat-caused mitochondrial damage in G. lucidum. Further results indicated that H2S activates sulfide-quinone oxidoreductase (SQR) and complex III (Com III), thereby maintaining mitochondrial homeostasis under heat stress in G. lucidum. Moreover, SQR also mediated the negative regulation of H2S to GAs biosynthesis under heat stress. Furthermore, SQR might be persulfidated under heat stress in G. lucidum. Thus, our study reveals a novel physiological function and molecular mechanism of H2S signalling under heat stress in G. lucidum with broad implications for research on the environmental response of microorganisms.

PurposeA systematic review and meta-analysis were conducted to evaluate the diagnostic precision of radiomics in the differential diagnosis of parotid tumors, considering the increasing utilization of radiomics in tumor diagnosis. Although some researchers have attempted to apply radiomics in this context, there is ongoing debate regarding its accuracy.MethodsDatabases of PubMed, Cochrane, EMBASE, and Web of Science up to May 29, 2024 were systematically searched. The quality of included primary studies was assessed using the Radiomics Quality Score (RQS) checklist. The meta-analysis was performed utilizing a bivariate mixed-effects model.ResultsA total of 39 primary studies were incorporated. The machine learning model relying on MRI radiomics for diagnosis malignant tumors of the parotid gland, demonstrated a sensitivity of 0.80 [95% CI: 0.74, 0.86], SROC of 0.89 [95% CI: 0.27-0.99] in the validation set. The machine learning model based on MRI radiomics for diagnosis malignant tumors of the parotid gland, exhibited a sensitivity of 0.83[95% CI: 0.76, 0.88], SROC of 0.89 [95% CI: 0.17-1.00] in the validation set. The models also demonstrated high predictive accuracy for benign lesions.ConclusionThere is great potential for radiomics-based models to improve the accuracy of diagnosing benign and malignant tumors of the parotid gland. To further enhance this potential, future studies should consider implementing standardized radiomics-based features, adopting more robust feature selection methods, and utilizing advanced model development tools. These measures can significantly improve the diagnostic accuracy of artificial intelligence algorithms in distinguishing between benign and malignant tumors of the parotid gland.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023434931.

Context and backgroundMicroplastics (MPs) and heavy metals (HMs) coexist in the farmland of China.MotivationIt still remains unclear the extent of their exposure and distribution in sweet potato fields.HypothesisPolyethylene (PE) or polyamide (PA) is the main MP pollutant in contaminated sweet potato sites, and the MP abundance in low-latitude and eastern areas is highest. Methods: In this study, saturated NaCl solution, a stereo microscope, a Fourier transform infrared spectrometer, and an electrothermal digester are used for the extraction, observation, identification of MPs, and analysis of Cd elements in soil, respectively.MethodsIn this study, saturated NaCl solution, a stereo microscope, a Fourier transform infrared spectrometer, and an electrothermal digester are used for the extraction, observation, identification of MPs, and analysis of Cd elements in soil, respectively.ResultsHere, we found an average MP level of 112,400 items/kg in 30 sweet potato field sites based on the items in 5 g soil and the magnification (200x), and the maximum abundance was 197,153 items/kg in Laiyang city, Shandong province, by field survey. The distribution characteristics of MPs are middle-latitude areas < low-latitude areas, and eastern areas > central areas. Most MPs are of the fragment and film shape, which account for 47.96 and 40.22%, respectively. In order to detect MP polymers in three cities named “Liancheng,” “Huanggang,” and “Laiyang” with different degrees of development, a laser infrared imaging system was used as a novel instrument to explore the MPs larger than 10 μm.ConclusionThe results showed that PA is the main MP pollutant in contaminated sweet potato sites, and soil texture, planting time, and urbanization processes may be the main factors affecting MP distribution. The average cadmium (Cd) concentration in 215 field sites is 0.15 mg/kg, and the local Cd pollution is existing, but the overall pollution is low. In addition, Cd concentration was negatively correlated with MP abundance. This study reveals the status of MP and also Cd pollution in sweet potato fields, which provides a theoretical basis for the safe production and utilization of sweet potato fields.

The negative pressure wave (NPW) signal caused by leakage of water supply pipeline contains a lot of noise due to the influence of water flow state and circuit noise, which will adversely affect the accuracy of leakage detection and leak location. To solve this problem, a novel pipeline pressure signal denoising method based on variational mode decomposition (VMD) is proposed in the paper. Firstly, the key parameters which affect the performance of VMD method: IMFs K and penalty factor $\alpha $ are optimized by genetic algorithm (GA) without prior knowledge. At the same time, different parameters are combined to form different reconstructed signals based on the correlation coefficient (CC). Secondly, the optimal combination of parameters is adaptively determined by using a fitness evaluation function based on the information entropy (IE). Thirdly, based on the optimal parameter combination, reconstruct the signal to achieve noise reduction. Finally, the denoised signal will be used for leak detection and leak location calculation. In order to verify the effectiveness of the proposed method, simulation analysis and laboratory experiments are carried out. Simulation analysis results show that the noise suppression effect of our method is better than that of wavelet, empirical mode decomposition (EMD) and VMD. The highest SNR obtained by our method is 16.187. The laboratory experiment results showed that the NPW signal denoised by proposed method had less error and more stable results in location, with an average relative error of 2.97%.

Background: Oncomelania hupensis (O. hupensis), the unique intermediate host for Schistosoma japonicum, exerts a substantial influence on the risk of schistosomiasis. Being amphibious freshwater snails, the growth, development, and reproductive distribution of O. hupensis are intricately tied to climatic environmental variables. This study aims to predict O. hupensis habitat risks along the Yangtze River in China, considering multiple environmental factors. Methods: Data pertaining to the distribution of O. hupensis, including both presence and absence records, with the Jiangsu section of the Yangtze River basin for the period 2017–2021, were retrieved from the Jiangsu Schistosomiasis Control Information Platform. Ten machine learning algorithms and an ensemble model were used to explore environmental drivers. Three datasets (Snail_CLIM, Snail_TOPO, and Snail_ALL) incorporating climatic and topographic variables were examined for their impact on model accuracy. We conducted validation using the AUC and TSS metrics. Moreover, we utilized the data from the 2022 snail field survey for model external validation. Results: The findings demonstrate that snail_ALL, which incorporates both climatic and topographic variables, exhibits superior performance (ensemble model: sensitivity = 98.000, specificity = 95.960, AUC = 0.994). Among the ten model algorithms, Random Forest (RF) exhibited the highest degree of accuracy and stability (Snail_ALL: AUC = 1.000 ± 0.000, TSS = 0.985 ± 0.005). The key environmental factors affecting snail distribution included the distance to the nearest river, elevation, annual precipitation, and annual average pressure. High-risk areas manifested as two distinct concentrations: downstream of the Luhe District in Nanjing and at the confluence of Zhenjiang and Yangzhou. The results of 2022 field validation showed that over 90 % of the data points for snail breeding sites are concentrated in medium to high-risk areas. Conclusion: By selecting pertinent environmental variables and employing ensemble modeling techniques, we can accurately predict O. hupensis habitats. The resulting risk distribution map for snail habitats not only provides valuable insights but also serves as a guiding tool for targeted monitoring and control measures. The holds particular significance within the contest of the Yangtze River protection and restoration projects.

BackgroundOsteoporotic vertebral compression fractures (OVCF) appear to be more common as the population ages. Previous studies have found that percutaneous vertebroplasty (PVP) can achieve better short-term clinical outcomes than conservative treatment (CT) for OVCF. However, the long-term outcomes of PVP compared with CT for OVCF has been rare explored. This study was designed to explore the clinical outcomes of PVP or CT within 3 years after OVCF.MethodsThis study reviewed the clinical outcomes of patients who underwent PVP or CT for OVCF in a single center from January 2015 to December 2019. The back pain visual analogue scale (VAS), Oswestry disability index (ODI) and satisfaction rate were compared between the two groups at baseline, 1 week, 1 month, 3 months, 6 months, 12 months, 24 months and 36 months after treatment.OutcomesThe baseline data including gender, age, bone mineral density, body mass index, back pain VAS, and ODI were not significantly different between the two groups. The back pain VAS and ODI of CT patients were significantly higher than those of PVP group at 1 week, 1 month, 3 months, 6 months and 12 months after treatment. The satisfaction rate in the PVP group were significantly higher than those in the CT group at 1 week, 1 month, 3 months and 6 months after treatment. Subsequently, the back pain VAS and ODI showed no significant difference between the two groups at 24 and 36 months. In addition, there was no significant difference in treatment satisfaction between the two groups at 36 months. There was no significant difference in the rate of new vertebral compression fractures between the two groups within 36 months after treatment.ConclusionThe clinical outcomes within 12 months after PVP and patient satisfaction rate within 6 months after PVP were significantly higher than CT. However, during 12 months to 36 months, this advantage generated by PVP was gradually diluted over time. Compared with CT, the long-term effect of PVP on OVCF should not be overestimated.

Abstract Microplastic (MP) pollution in agricultural soils, resulting from the use of plastic mulch, compost, and sewage sludge, jeopardizes the soil microbial populations. However, the effects of MPs on soil chemical properties and microbial communities remain largely unknown. Here, we investigated the effects of different concentration levels (0, 0.1, 1, 3, 5, and 7%; w:w) of low-density polyethylene (LDPE) MPs on the chemical properties and bacterial communities of agricultural soil in an incubation study. The addition of LDPE MPs did not drastically change soil pH (ranging from 8.22 to 8.42). Electrical conductivity increased significantly when the LDPE MP concentrations were between 1 and 7%, whereas the total exchangeable cations (Na+, K+, Mg2+, and Ca2+) decreased significantly at higher LDPE MP concentrations (3–7%). The highest available phosphorus content (2.13 mg kg−1) was observed in 0.1% LDPE MP. Bacterial richness (Chao1 and Ace indices) was the lowest at 0.1% LDPE MP, and diversity indices (Shannon and Invsimpson) were higher at 0 and 1% LDPE MP than at other concentrations. The effect of LDPE MP concentrations on bacterial phyla remained unchanged, but the bacterial abundance varied. The relative abundance of Proteobacteria (25.8–33.0%) was the highest in all treatments. The abundance of Acidobacteria (15.8–17.2%) was also high, particularly in the 0, 0.1, and 1% LDPE MPs. With the increase in LDPE MP concentration, the abundance of Actinobacteria gradually increased from 7.80 to 31.8%. Our findings suggest that different MP concentration levels considerably alter soil chemical properties and microbial composition, which may potentially change the ecological functions of soil ecosystems.

Abstract Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with FASN is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC.

Background: Recent advancements in artificial intelligence (AI) have significantly improved atrial fibrillation (AF) detection using electrocardiography (ECG) data obtained during sinus rhythm (SR). However, the utility of printed ECG (pECG) records for AF detection, particularly in developing countries, remains unexplored. This study aims to assess the efficacy of an AI-based screening tool for paroxysmal AF (PAF) using pECGs during SR. Methods: We analyzed 5688 printed 12-lead SR-ECG records from 2192 patients admitted to Beijing Chaoyang Hospital between May 2011 to August 2022. All patients underwent catheter ablation for PAF (AF group) or other electrophysiological procedures (non-AF group). We developed a deep learning model to detect PAF from these printed SR-ECGs. The 2192 patients were randomly assigned to training (1972, 57.3% with PAF), validation (108, 57.4% with PAF), and test datasets (112, 57.1% with PAF). We developed an applet to digitize the printed ECG data and display the results within a few seconds. Our evaluation focused on sensitivity, specificity, accuracy, F1 score, the area under the receiver-operating characteristic curve (AUROC), and precision-recall curves (PRAUC). Results: The PAF detection algorithm demonstrated strong performance: sensitivity 87.5%, specificity 66.7%, accuracy 78.6%, F1 score 0.824, AUROC 0.871 and PRAUC 0.914. A gradient-weighted class activation map (Grad-CAM) revealed the model’s tailored focus on different ECG areas for personalized PAF detection. Conclusions: The deep-learning analysis of printed SR-ECG records shows high accuracy in PAF detection, suggesting its potential as a reliable screening tool in real-world clinical practice.

Shafting alignment plays an important role in the marine propulsion system, which affects the safety and stability of ship operation. Air spring vibration isolation systems (ASVISs) for marine shafting can not only reduce mechanical noise but also help control alignment state by actively adjusting air spring pressures. Alignment prediction is the first and a key step in the alignment control of ASVISs. However, in large-scale ASVISs, due to factors such as strong interference and raft deformation, alignment prediction faces problems such as alignment measurement sensors failure and difficulty in establishing a mathematical model. To address this problem, a data model for predicting alignment state is developed based on a back propagation (BP) neural network, fully taking advantage of its self-learning and self-adaption abilities. The proposed model exploits the collected data in the ASVIS instead of the alignment measurement data to calculate the alignment state, providing another alignment prediction approach. Then, in order to solve the local optimum issue of BP neural network, we introduce the genetic algorithm (GA) to optimize the weights and thresholds of the BP neural network, and an improved GA-BP model is designed. The GA-BP model can leverage the advantages of the global search capability of GA as well as the BP neural network’s fast convergence in local search. Finally, we conduct experiments on a real ASVIS and evaluate the prediction models using different criteria. The experimental results show that the proposed prediction model with the GA-BP neural network can accurately predict the alignment state, with a mean-square error (MSE) of 0.0114. And compared to the BP neural network, the GA-BP neural network reduces the MSE by approximately 74%.

Background: Thyroid dysfunction is common in critical illness and may influence prognosis. However, the value of TSH in patients with severe diseases remains unclear. The aim of this study was to investigate the association between TSH and the clinical prognosis of critically ill patients. Methods: This retrospective study identified patients who were admitted to the ICU in the Medical Information Mart for Intensive Care (MIMIC-IV) database (version 2.2). A total of 6432 patients were divided into four groups based on TSH quartiles (Q1, 3.10 mIU/L). The clinical outcomes were defined as all-cause 7-, 30-, and 90-year mortality after ICU admission. Restricted cubic splines (RCSs) for nonlinear associations were generated to visualize the relationship between TSH levels and clinical outcomes. The survival differences among the four groups were also analyzed using Kaplan‒Meier curves and log rank tests. Univariable and multivariable Cox proportional hazards regression were further used to assess the association between TSH levels and clinical outcomes. Results: After multivariate adjustment, a U-shaped relationship was observed between TSH levels and all-cause 7-, 30-, and 90- mortality among patients with severe disease (all P

Abstract IGF2BP2 is a new identified N6‐methyladenosine (m6A) reader and associated with poor prognosis in many tumors. However, its role and related mechanism in breast cancer, especially in triple‐negative breast cancer (TNBC), remains unclear. In this study, it is found that IGF2BP2 is highly expressed in TNBC due to the lower methylation level in its promoter region. Functional and mechanical studies displayed that IGF2BP2 could promote TNBC proliferation and the G1/S phase transition of the cell cycle via directly regulating CDK6 in an m6A‐dependent manner. Surprising, the regulation of protein levels of CDK6 by IGF2BP2 is related to the changes in translation rate during translation initiation, rather than mRNA stability. Moreover, EIF4A1 is found to be recruited by IGF2BP2 to promote the translation output of CDK6, providing new evidence for a regulatory role of IGF2BP2 between m6A methylation and translation. Downregulation of IGF2BP2 in TNBC cell could enhance the sensitivity to abemaciclib, a CDK4/6 inhibitor. To sum up, our study revealed IGF2BP2 could facilitate the translation output of CDK6 via recruiting EIF4A1 and also provided a potential therapeutic target for the diagnosis and treatment of TNBC, as well as a new strategy for broadening the drug indications for CDK4/6 inhibitors.

Abstract A prominent feature of the western North Pacific tropical cyclone genesis frequency (TCGF) anomaly in response to El Niño‐Southern Oscillation (ENSO) is a distinct west‐east dipole structure in the present‐day (PD) climate. Here, large ensemble high‐resolution simulations show that the current dipole may transform into a monopole under global warming (GW). In the PD climate, the ENSO‐induced dipole effect on TCGF is mainly observed in late autumn. However, GW accelerates this effect into the summer by amplifying atmospheric circulation anomalies. Consequently, this leads to a significant increase in the coastal TCGF during the development phase of El Niño under GW. Meanwhile, it weakens the anomalous anticyclonic circulation during late autumn, leading to an increase in coastal TCGF during the mature phase of El Niño, and vice versa. Therefore, the combined effect suggests a potential trend toward spatial homogenization during ENSO phases under GW.

Cuproptosis, a distinct form of programmed cell death, is an emerging field in oncology with promising implications. This novel mode of cell death has the potential to become a regulatory target for tumor therapy, thus expanding the currently limited treatment options available for patients with cancer. Our research team focused on investigating the role of functional long non-coding RNA (lncRNAs) in hepatocellular carcinoma (HCC). We were particularly intrigued by the potential implications of HCC-lncRNAs on cuproptosis. Through a comprehensive analysis, we identified three cuproptosis-related lncRNAs (CRLs): AC018690.1, AL050341.2, and LINC02038. These lncRNAs were found to influence the sensitivity of HCC to cuproptosis. Based on our results, we constructed a risk model represented by the equation: risk score = 0.82 * AC018690.1 + 0.65 * AL050341.2 + 0.61 * LINC02038. Notably, significant disparities were observed in clinical features, such as the response rate to immunotherapy and targeted therapy, as well as in cellular characteristics, including the composition of the tumor immune microenvironment (TIME), when comparing the high- and low-risk groups. Most importantly, knockdown of these CRLs was confirmed to significantly weaken the resistance to cuproptosis in HCC. This effect resulted from the accelerated accumulation of lipoacylated-DLAT and lipoacylated-DLST. In summary, we identified three CRLs in HCC and established a novel risk model with potential clinical applications. Additionally, we proposed a potential therapeutic method consisting of sorafenib-copper ionophores-immunotherapy.

Abstract Circular RNAs (circRNAs) have emerged as crucial regulators in physiology and human diseases. However, evolutionarily conserved circRNAs with potent functions in cancers are rarely reported. In this study, a mammalian conserved circRNA circLARP1B is identified to play critical roles in hepatocellular carcinoma (HCC). Patients with high circLARP1B levels have advanced prognostic stage and poor overall survival. CircLARP1B facilitates cellular metastatic properties and lipid accumulation through promoting fatty acid synthesis in HCC. CircLARP1B deficient mice exhibit reduced metastasis and less lipid accumulation in an induced HCC model. Multiple lines of evidence demonstrate that circLARP1B binds to heterogeneous nuclear ribonucleoprotein D (HNRNPD) in the cytoplasm, and thus affects the binding of HNRNPD to sensitive transcripts including liver kinase B1 (LKB1) mRNA. This regulation causes decreased LKB1 mRNA stability and lower LKB1 protein levels. Antisense oligodeoxynucleotide complementary to theHNRNPD binding sites in circLARP1B increases the HNRNPD binding to LKB1 mRNA. Through the HNRNPD–LKB1–AMPK pathway, circLARP1B promotes HCC metastasis and lipid accumulation. Results from AAV8‐mediated hepatocyte‐directed knockdown of circLARP1B or Lkb1 in mouse models also demonstrate critical roles of hepatocytic circLARP1B regulatory pathway in HCC metastasis and lipid accumulation, and indicate that circLARP1B may be potential target of HCC treatment.

Objective: This study aimed to investigate brain activity changes in patients suffering from neuropathic pain (NP) following brachial plexus avulsion (BPA). Methods: Fifteen patients with NP following BPA and eight healthy participants (HP) were recruited for this study. All participants underwent examination using resting-state functional MRI. The amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were calculated and compared between the BPA group, left-BPA subgroup, right-BPA subgroup, and the HP group using independent samples t-tests. Results: In the BPA group, there were notable increases in ALFF/ReHo observed in the left rolandic operculum, insula, and supramarginal gyrus, while decreases were observed in the left paracentral lobule, fusiform gyrus, calcarine fissure and surrounding cortex, lingual gyrus, precuneus, as well as the bilateral anterior/median cingulate and paracingulate gyri, supplementary motor area, and cerebellum. In the left-BPA subgroup, elevated ALFF/ReHo levels were identified in the left middle/inferior frontal gyri, rolandic operculum, and supramarginal gyrus, with corresponding decreases in the left calcarine fissure and surrounding cortex, inferior occipital gyrus, fusiform gyrus, lingual gyrus, as well as the bilateral anterior/median cingulate and paracingulate gyri, postcentral gyri, supplementary motor area, paracentral lobules, and cerebellum. The right-BPA subgroup displayed increased ALFF/ReHo in the left frontal lobe, rolandic operculum, insula, fusiform gyrus, and lingual gyrus, as well as the right cerebellum. Conversely, decreases in ALFF/ReHo were observed in the bilateral anterior/median cingulate and paracingulate gyri, calcarine fissure and surrounding cortex, cuneus, and occipital lobes. Conclusions: The NP after BPA caused spontaneous activity changes in brain regions associated with linguistic, visual, somatosensory, and motor coordination and processing function. The majority of these abnormal areas were situated in the left cerebral hemisphere, while the effect of cingulate gyri and cerebellum seemed to be bilateral.

As the body's first line of defense, neutrophils play an important role in the early stages of infection. Neutrophil extracellular traps (NETs), a novel way to kill pathogens, are released from activated neutrophils to trap and kill microorganisms and protect the body from invasion. However, studies have shown that NETs not only play a role in self-defense in vivo but also participate in some pathological processes. Current studies have found that excessive or abnormally activated NETs play a pathogenic role in a variety of diseases. NETs, in addition to killing pathogens during the pathology of sepsis, affect on coagulation function, and blood endothelium. Additionally, NETs have a wide range of effects in other inflammatory, immune, and other related diseases. NETs are involved in the pathology of atherosclerosis. NETs also play a role in systemic lupus erythematosus, diabetes mellitus, Alzheimer's disease, and tumors, but there are relatively few NETs studies on bone and joint diseases. This article discusses NETs, their formation, and their association with bone and joint disorders. New targets for the effective treatment of joint diseases may be identified by studying the relationship between NETs and bone and joint diseases.

Cold adapted live attenuated influenza vaccines can effectively prevent human disease and death caused by influenza virus. Since chicken embryos are used as the culture substrate for the large-scale production of influenza vaccines, cold adapted live attenuated influenza vaccines may be contaminated by exogenous avian viruses. Rapid and sensitive methods such as TaqMan-based quantitative PCR are needed for the detection of exogenous avian viruses during cold adapted live attenuated influenza vaccines production. In this study, a TaqMan-based quantitative PCR method was established for the detection of three common exogenous avian viruses, including fowl adenovirus type I, type Ⅲ and avian leukosis virus. Avian virus-encoding plasmids purified in high-performance liquid chromatography were essential for sensitivity analysis. The sensitivity reached 1 copy per reaction for each of the avian virus plasmids. Standard curves showed a strong linear relationship. The TaqMan-based quantitative PCR method had high specificity and no cross-reactivity with other irrelevant viruses. Furthermore, the established TaqMan-based quantitative PCR can effectively detect 0.1 TCID50 of each avian virus without or with interference from the influenza virus nucleic acid. Ultimately, this method was used to test three master seed lots of monovalent cold adapted live attenuated influenza vaccine, and the results showed that no fowl adenovirus type I, type Ⅲ or avian leukosis virus contamination, which were consistent with serological methods. The TaqMan-based quantitative PCR method for the determination of extraneous avian viruses in cold adapted live attenuated influenza vaccines met the requirement for both conventional and emergency inspection on cold adapted live attenuated influenza vaccines.

ABSTRACT In the current study, the silencing of protein arginine methyltransferase 5 (PRMT5) decreased the polysaccharide content of Ganoderma lucidum compared to that of the wild-type (WT) strain. Furthermore, RNA-seq screening showed that the glycan degradation process-related gene thaumatin-like protein (TLP) was alternatively spliced in WT strains via retained introns, leading to the production of a longer TLP1 isoform and a shorter TLP2 isoform; however, only the TLP2 isoform was observed in PRMT5i strains. Experiments examining the polysaccharide content of the TLP silencing, TLP1 overexpression (OE-TLP1), and TLP2 overexpression (OE-TLP2) transformants revealed that TLP2 plays a more important role than TLP1 in polysaccharide degradation. Through a combination of yeast two-hybrid, bimolecular fluorescence complementation and surface plasmon resonance assays, we found that TLP2 directly physically interacted with phosphoglucose isomerase (PGI), a key enzyme in polysaccharide synthesis, and thereby increased PGI activity. However, TLP1 failed to interact with PGI, and PGI activity was not affected. Further inspection showed that the polysaccharide content was decreased in the OE-TLP2 strains but not significantly changed in the OE-TLP1 strains compared with that in the WT strains. In addition, the polysaccharide content of the PRMT5-TLP-cosilenced strains was not significantly different from that of the WT strains. These results demonstrate that PRMT5 modulates TLP processing of pre-mRNA transcripts and thereby decreases the polysaccharide content. IMPORTANCE PRMT5 contributes to secondary metabolite biosynthesis in Ganoderma lucidum. However, the mechanism through which PRMT5 regulates the biosynthesis of secondary metabolites remains unclear. In the current study, PRMT5 silencing led to a significant decrease in the biosynthesis of polysaccharides from G. lucidum through the action of the alternative splicing of TLP. A shorter TLP2 isoform can directly bind to PGI and regulated polysaccharide biosynthesis. These results suggest that PRMT5 enhances PGI activity by regulating TLP binding to PGI. The results of the current study reveal a novel target gene for PRMT5-mediated alternative splicing and provide a reference for the identification of PRMT5 regulatory target genes.

Dielectric ceramics are promising in large-scale commercial millimeter-wave communication technology, such as 5G and the upcoming 6G, thanks to their excellent frequency selection characteristics and environmental stability. In this work, various contents of SbO bonds were introduced into the MgTa2O6 lattice using the solid-phase reaction method to investigate the effects on the lattice and microwave dielectric properties. XRD confirms that Sb ions successfully occupy Ta sites in the lattice and cause lattice shrinkage and crystallinity deterioration, which leads to a slight decrease in the quality factor. Furthermore, DFT calculations reveal that the doping leads to electron-biased aggregation toward O atoms, causing higher SbO ionicity, but also attenuates the degree of ionization of Ta and Mg ions, which makes the dielectric constant of the doped samples vary non-monotonically with gradient doping. Satisfactorily, Sb doping substantially enhanced the thermal stability of the ceramics, with TCF values reduced from 36 × 10−6 °C-1 to 15 × 10−6 °C-1.

Abstract Background This study used next‐generation sequencing (NGS) to investigate the genetic profiles in cerebrospinal fluid (CSF), plasma, and tumor tissue to explore alternative detection methods for anaplastic lymphoma kinase (ALK) rearrangement status and potential resistance mechanisms to ALK inhibitors. Methods From January 2016 to January 2021, 19 non‐small cell lung cancer (NSCLC) patients with brain metastases (BMs) and ALK‐positive primary tumors were enrolled at Beijing Chest Hospital. CSF, plasma, and primary tumor samples from patients with BMs of NSCLC were tested using NGS with a 168‐gene panel. The intracranial response and prognosis were also investigated. Results The study included 19 patients, seven females and 12 males, aged between 29 and 68 (median age 44). CSF cytology was negative in all cases. NGS results showed ALK fusion genes detected in 26.3% (5/19) of CSF cfDNA samples, 78.9% (15/19) of plasma samples, and 89.5% (17/19) of tumor samples from ALK‐positive patients. ALK‐positive CSF samples had significantly higher allele fractions in CSF cfDNA compared with the other two sample types. In five patients with ALK‐positive in CSF, after receiving ALK inhibitors ± local treatment, one case achieved an intracranial complete response, and two had an intracranial partial response. In CSF samples, the intracranial median progression‐free survival was 8.0 and 18.0 months for ALK‐positive (n = 5) and ALK‐negative (n = 14), respectively (p = 0.077). Conclusion CSF may serve as a liquid biopsy for ALK‐positive lung cancer with BMs by detecting cfDNA within CSF to characterize driver and resistant genes.

Inflammatory bowel disease (IBD) is a chronic relapsing gastrointestinal disorder, while the treatment effect is not satisfactory. Immune responsive gene 1 (IRG1) is a highly expressed gene in macrophage in response to inflammatory response and catalyzes the production of itaconate. Studies have reported that IRG1/itaconate has a significant antioxidant effect. This study aimed to investigate the effect and mechanism of IRG1/itaconate on dextran sulfate sodium (DSS)-induced colitis in vivo and in vitro. In vivo experiments, we found IRG1/itaconate exerted protective effects against acute colitis by increasing mice weight, the length of colon, reducing disease activity index and colonic inflammation. Meanwhile, IRG1 deletion aggravated the macrophages/CD4+/CD8+ T-cell accumulation, and increased the release of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-6, the activation of nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, and gasdermin D (GSDMD) mediated pyroptosis. Four-octyl itaconate (4-OI), a derivative of itaconate, attenuated these changes, therefore relieved DSS-induced colitis. In vitro experiment, we found 4-OI inhibited the reactive oxygen species production, thereby inhibiting the activation of MAPK/NF-κB signaling pathway in RAW264.7 and murine bone-marrow-derived macrophages. Simultaneously, we found 4-OI inhibited caspase1/GSDMD-mediated pyroptosis to reduce the release of cytokines. Finally, we found anti-TNF-α agent reduced the severity of DSS-induced colitis and inhibited gasdermin E (GSDME)-mediated pyroptosis in vivo. Meanwhile, our study revealed that 4-OI inhibited caspase3/GSDME-mediated pyroptosis induced by TNF-α in vitro. Taken together, IRG1/itaconate exerted a protective role in DSS-induced colitis by inhibiting inflammatory response and GSDMD/GSDME-mediated pyroptosis, which could be a promising candidate for IBD therapy.

Abstract The ship floating raft system adopts the integrated design of large liquid tanks and rafts, which can optimize the arrangement in the cabin and increase the intermediate mass of the system to achieve efficient vibration isolation of equipment. One of the major challenges is that the change of liquid mass in the tank will cause displacement of the raft, which will change the modal characteristics of the system and affect the stability of the vibration isolation system performance. This paper establishes a mechanical analysis model of a floating raft system under time-varying liquid mass conditions. Taking a ship variable mass floating raft system as the research object, the effect of mass change on the characteristics of raft displacement, isolator load distribution, and modal frequency of the vibration isolation system is analyzed. The analysis shows that when the liquid tank goes from full load to no-load state, its mass change accounts for 40% of the total mass of the raft, which will cause a large displacement of the raft and change the low order modal frequency of the system, bringing the risk of equipment safety and vibration isolation performance degradation. Therefore, an adaptive variable load control method is proposed to realize the raft attitude balance and load equalization optimization under the variable mass condition of the floating raft air spring system. The test results show that the proposed control method can automatically adapt to the large mass gradual change from full load to no load of the liquid tank on the raft, and control the displacement of the raft structure from about 10 mm to 1.5 mm, which effectively ensures the stability of the air spring system performance.

Abstract Background Prior drought stress may change plants response patterns and subsequently increase their tolerance to the same condition, which can be referred to as “drought memory” and proved essential for plants well-being. However, the mechanism of transcriptional drought memory in psammophytes remains unclear. Agriophyllum squarrosum, a pioneer species on mobile dunes, is widely spread in Northern China’s vast desert areas with outstanding ability of water use efficiency. Here we conducted dehydration-rehydration treatment on A. squarrosum semi-arid land ecotype AEX and arid land ecotype WW to dissect the drought memory mechanism of A. squarrosum, and to determine the discrepancy in drought memory of two contrasting ecotypes that had long adapted to water heterogeneity. Result Physiological traits monitoring unveiled the stronger ability and longer duration in drought memory of WW than that of AEX. A total of 1,642 and 1,339 drought memory genes (DMGs) were identified in ecotype AEX and WW, respectively. Furthermore, shared DMGs among A. squarrosum and the previously studied species depicted that drought memory commonalities in higher plants embraced pathways like primary and secondary metabolisms; while drought memory characteristics in A. squarrosum were mainly related to response to heat, high light intensity, hydrogen peroxide, and dehydration, which might be due to local adaptation to desert circumstances. Heat shock proteins (HSPs) occupied the center of the protein-protein interaction (PPI) network in drought memory transcription factors (TF), thus playing a key regulatory role in A. squarrosum drought memory. Co-expression analysis of drought memory TFs and DMGs uncovered a novel regulating module, whereby pairs of TFs might function as molecular switches in regulating DMG transforming between high and low expression levels, thus promoting drought memory reset. Conclusion Based on the co-expression analysis, protein-protein interaction prediction, and drought memory metabolic network construction, a novel regulatory module of transcriptional drought memory in A. squarrosum was hypothesized here, whereby recurrent drought signal is activated by primary TF switches, then amplified by secondary amplifiers, and thus regulates downstream complicated metabolic networks. The present research provided valuable molecular resources on plants’ stress-resistance basis and shed light on drought memory in A. squarrosum.

Abstract Protein nanowires are critical electroactive components for electron transfer of Geobacter sulfurreducens biofilm. To determine the applicability of the nanowire proteins in improving bioelectricity production, their genes including pilA, omcZ, omcS and omcT were overexpressed in G. sulfurreducens. The voltage outputs of the constructed strains were higher than that of the control strain with the empty vector (0.470–0.578 vs. 0.355 V) in microbial fuel cells (MFCs). As a result, the power density of the constructed strains (i.e. 1.39–1.58 W m−2) also increased by 2.62‐ to 2.97‐fold as compared to that of the control strain. Overexpression of nanowire proteins also improved biofilm formation on electrodes with increased protein amount and thickness of biofilms. The normalized power outputs of the constructed strains were 0.18–0.20 W g−1 that increased by 74% to 93% from that of the control strain. Bioelectrochemical analyses further revealed that the biofilms and MFCs with the constructed strains had stronger electroactivity and smaller internal resistance, respectively. Collectively, these results demonstrate for the first time that overexpression of nanowire proteins increases the biomass and electroactivity of anode‐attached microbial biofilms. Moreover, this study provides a new way for enhancing the electrical outputs of MFCs.

Abstract Owing to the specific merits of low cost, abundant sources, and high physicochemical stability, carbonaceous materials are promising anode candidates for K+/Na+ storage, whereas their limited specific capacity and unfavorable rate capability remain challenging for future applications. Herein, the sulfur implantation in N‐coordinated hard carbon hollow spheres (SN‐CHS) has been realized for evoking a surface‐driven capacitive process, which greatly improves K+/Na+ storage performance. Specifically, the SN‐CHS electrodes deliver a high specific capacity of 480.5/460.9 mAh g−1 at 0.1 A g−1, preferred rate performance of 316.8/237.4 mAh g−1 at 5 A g−1, and high‐rate cycling stability of 87.9%/87.2% capacity retention after 2500/1500 cycles at 2 A g−1 for K+/Na+ storage, respectively. The underlying ion storage mechanisms are studied by systematical experimental data combined with theoretical simulation results, where the multiple active sites, improved electronic conductivity, and fast ion absorption/diffusion kinetics are major contributors. More importantly, the potassium ion hybrid capacitor consisting of SN‐CHS anode and activated carbon cathode deliver an outstanding energy/power density (189.8 Wh kg−1 at 213.5 W kg−1 and 9495 W kg−1 with 53.9 Wh kg−1 retained) and remarkable cycling stability. This contribution not only flourishes the prospective synthesis strategies for advanced hard carbons but also facilitates the upgrading of next‐generation stationary power applications.

ABSTRACT Fungi actively alter their metabolic and synthetic pathways to cope with changing environmental conditions. The mitochondrial pyruvate carrier (MPC) plays a vital role in transporting pyruvate into mitochondria and regulating carbon metabolic homeostasis. However, the mechanism by which MPC regulates carbon metabolism in response to environmental stress in fungi remains unclear. In this study, yeast one-hybrid library screening assays were employed to screen for transcription factors in Ganoderma lucidum that may interact with GlMPC. General control non-derepressible 4 (GCN4), a key transcription factor responding to nitrogen metabolism, was found to interact with the GlMPC promoter region. This interaction was further confirmed by electrophoretic mobility shift assays and chromatin immunoprecipitation quantitative PCR assays, demonstrating that GCN4 is capable of binding to the GlMPC promoter region in vitro and in vivo. Further results indicated that GCN4 could activate GlMPC expression and participate in regulating the tricarboxylic acid (TCA) cycle and ganoderic acid (GA) biosynthesis under low nitrogen conditions in G. lucidum. These findings revealed a specific regulatory mechanism by which GCN4-activated GlMPC regulates the TCA cycle and secondary metabolism under nitrogen limitation conditions in G. lucidum, providing crucial insights into the regulation of carbon and nitrogen metabolism in fungi. IMPORTANCE Mitochondrial pyruvate carrier (MPC) is a pyruvate transporter that plays a crucial role in regulating the carbon metabolic flow and is considered an essential mechanism for microorganisms to adapt to environmental changes. However, it remains unclear how MPC responds to environmental stress in organisms. General control non-derepressible 4 (GCN4), a key regulator of nitrogen metabolism, plays a pivotal role in the growth and development of fungi. In this study, we report that GCN4 can directly bind to the promoter region and activate the expression of GlMPC, thereby regulating the tricarboxylic acid cycle and secondary metabolism under nitrogen limitation conditions in Ganoderma lucidum. These findings provide significant insights into the regulation of carbon and nitrogen metabolism in fungi, highlighting the critical role of GCN4 in coordinating metabolic adaptation to environmental stresses.

Geobacter sulfurreducens mediates extracellular electron transfer (EET) reactions with different substrates, such as solid-phase Fe(III)-containing minerals, anodes and the cells of Geobacter metallireducens. To compare their roles in EET, the pilA-N, omcE, omcS, omcT and omcZ genes of G. sulfurreducens were systematically deleted. All mutants showed impaired and varied ability to form biofilms on nonconductive surface. Deletion of omcE also impaired bacterial ability to reduce ferrihydrite, but its impacts on the ability for anode reduction and the co-culture of G. metallireducens-G. sulfurreducens were minimal. The mutant without omcS showed diminished ability to reduce ferrihydrite and to form the co-culture, but was able to regain its ability to reduce anodes. Deletion of omcT, omcZ or pilA-N alone impaired bacterial ability to reduce ferrihydrite and anodes and to form the co-culture. Deletion of all tested genes abolished bacterial ability to reduce ferrihydrite and anodes. Triple-deletion of all omcS, omcT and omcZ abolished the ability of G. sulfurreducens to co-culture with G. metallireducens. However, deletion of only omcZ or pilA-N or both omcS and omcT abolished the ability of G. sulfurreducens without hydrogenase gene hybL to co-culture with G. metallireducens, which show their indispensable roles in direct electron transfer from G. metallireducens to G. sulfurreducens. Thus, the roles of pilA-N, omcE, omcS, omcT and omcZ for G. sulfurreducens in EET vary substantially, which also suggest that possession of PilA-N and multiple cytochromes of different structures enables G. sulfurreducens to mediate EET reactions efficiently with substrates of different properties.

Abstract Background N6‐methyladenosine (m6A) is an abundant reversible modification in eukaryotic mRNAs. Emerging evidences indicate that m6A modification plays a vital role in tumourigenesis. As a crucial reader of m6A, IGF2BP3 usually mediates the stabilisation of mRNAs via an m6A‐dependent manner. But the underlying mechanism of IGF2BP3 in the tumourigenesis of triple‐negative breast cancer (TNBC) is unclear. Methods TCGA cohorts were analysed for IGF2BP3 expression and IGF2BP3 promoter methylation levels in different breast cancer subtypes. Colony formation, flow cytometry assays and subcutaneous xenograft were performed to identify the phenotype of IGF2BP3 in TNBC. RNA/RNA immunoprecipitation (RIP)/methylated RNA immunoprecipitation (MeRIP) sequencing and luciferase assays were used to certify the target of IGF2BP3 in TNBC cells. Results IGF2BP3 was highly expressed in TNBC cell lines and tissues. TET3‐mediated IGF2BP3 promoter hypomethylation led to the upregulation of IGF2BP3. Knocking down IGF2BP3 markedly reduced the proliferation of TNBC in vitro and in vivo. Intersection co‐assays revealed that IGF2BP3 decreased neurofibromin 1 (NF1) stabilisation via an m6A‐dependent manner. NF1 knockdown could rescue the phenotypes of IGF2BP3 knockdown cells partially. Conclusion TET3‐mediated IGF2BP3 accelerated the proliferation of TNBC by destabilising NF1 mRNA via an m6A‐dependent manner. This suggests that IGF2BP3 could be a potential therapeutic target for TNBC.

Abstract Abnormal activities of distal cis-regulatory elements (CREs) contribute to the initiation and progression of cancer. Gain of super-enhancer (SE), a highly active distal CRE, is essential for the activation of key oncogenes in various cancers. However, the mechanism of action for most tumor-specific SEs still largely remains elusive. Here, we report that a candidate oncogene ETS2 was activated by a distal SE in inflammatory bowel disease (IBD) and colorectal cancer (CRC). The SE physically interacted with the ETS2 promoter and was required for the transcription activation of ETS2. Strikingly, the ETS2-SE activity was dramatically upregulated in both IBD and CRC tissues when compared to normal colon controls and was strongly correlated with the level of ETS2 expression. The tumor-specific activation of ETS2-SE was further validated by increased enhancer RNA transcription from this region in CRC. Intriguingly, a known IBD-risk SNP resides in the ETS2-SE and the genetic variant modulated the level of ETS2 expression through affecting the binding of an oncogenic transcription factor MECOM. Silencing of MECOM induced significant downregulation of ETS2 in CRC cells, and the level of MECOM and ETS2 correlated well with each other in CRC and IBD samples. Functionally, MECOM and ETS2 were both required for maintaining the colony-formation and sphere-formation capacities of CRC cells and MECOM was crucial for promoting migration. Taken together, we uncovered a novel disease-specific SE that distantly drives oncogenic ETS2 expression in IBD and CRC and delineated a mechanistic link between non-coding genetic variation and epigenetic regulation of gene transcription.

Due to the special hydrogeological features of the sea islands, the distribution of groundwater is difficult to assess. In order to improve the accuracy of the predicting groundwater potential assessment(GPA) in islands region. We tried to use the convolutional neural networks(CNN) and took lithology, aspect, slope, water density, vegetation fraction, soil humidity and land surface temperature as the remote sensing assessment indicators. The island area of Pearl River Estuary, China was selected as the study area. The groundwater situation of Wailingding Island was taken as the sample data of the total area, and the map of this island was divided into 24 × 22 grids. The levels of GPA of each small grid was determined by hydrogeological maps with results of geophysical method and wells or springs data. Meanwhile, the corresponding data were enlarged and the sample label data set was made. Using the CNN model of learning, training and testing, analysis of groundwater potential and each coupling correlation between remote sensing indicators constantly. After 1500 times of training, loss of model dropped to 0.3113, the accuracy of model was 96.96%. A good 5 levels classification prediction of GPA model was received. The AUC of ROC curve and significance level (P) of the CNN model were 0.855 and 0.001 respectively, which were better than the results of the classic GRSFAI model. The results showed that the prediction of GPA based on CNN model can effectively assess the groundwater distribution levels in the Pearl River Estuary island area, which can provide a certain reference value or a GPA model for the other water-deficient islands. Moreover, the obtained sample set of groundwater volume distribution of bedrock islands can be used as a valuable data source for further in-depth research.

Despite the notable achievements of programmed death 1 (PD-1) antibodies in treating various cancers, the overall efficacy remains limited in the majority of colorectal cancer (CRC) cases. Metabolism reprogramming of tumors inhibits the tricarboxylic acid (TCA) cycle, leading to down-regulation of fumarate hydratase (FH), which is related to poor prognosis in CRC patients. By establishing a tumor-bearing mouse model of CRC with Fh1 expression deficiency, we confirmed that the therapeutic effect of PD-1 antibodies alone was suboptimal in mice with low Fh1 expression, which was improved by combination with a protein invertase subtilisin/kexin 9 (PCSK9) inhibitor. Mechanistically, FH binds to Ras-related nucleoprotein (RAN), which inhibits the nuclear import of the PCSK9 transcription factor SREBF1/2, thus reducing the expression of PCSK9. This leads to increased clonal expansion of CD8+ T cells while the number of Tregs remains unchanged, and the expression of PD-L1 does not change significantly, thus enhancing the immunotherapy response. On the contrary, the expression of PCSK9 increased in CRC cells with low FH expression, which antagonized the effects of immunotherapy. Overall, CRC patients with low FH expression may benefit from combinatorial therapy with PD-1 antibodies and PCSK9 inhibitors to enhance the curative effect.

Ectomycorrhizal (ECM) fungi play fundamental roles in host plant growth and terrestrial ecosystems. Cedrus deodara is cultivated in several regions in China, has high ecological, economic and medicinal value, for its afforestation and providing timber and wood oil. Here, we investigated ECM colonization status of four urban C. deodara forests in Nantong, East China. We also characterized soil spore banks by conducting bioassay experiments using soils collected from these forests. In total, we identified 19 ECM fungal species, of which 13 species were found in mature forests and 9 species were identified in bioassay experiments, with only 3 species shared. Soil pH and available P content had significant effects on species occurrence in both mature trees and bioassay seedlings on local scales. ECM communities clearly (A = 0.391, p = 0.006) separated mature forests from spore banks. Thelephoracae was the richest family we detected associated with C. deodara, while Trichophaea sp. was the most dominant in mature forests, and Wilcoxina sp. was dominant in spore banks. ECM richness affected the growth of bioassay seedlings, especially after inoculation with 2 ECM species, promoting root growth, significantly (F = 3.028, p = 0.050), but it had no effects on shoots (F = 1.778, p = 0.177). No effect of inoculation rate was found on seedlings growth. To conserve this important tree species, the ECM fungi that are associated with it should be considered.

Bismuth sulfide (Bi2S3) is a dominant anode material for sodium-ion batteries due to its high theoretical capacity. However, extreme volume fluctuations as well as low electrical conductivity and reaction kinetics still limit its practical applications. Herein, we construct an abundant heterointerface of Bi/Bi2S3 by engineering the structure of Bi nanoparticles embedded on Bi2S3 nanorods (denoted as Bi–Bi2S3 NRs) to effectively solve the abovementioned obstacles. Theoretical and systematic characterization results reveal that the constructed heterointerface of Bi/Bi2S3 has a built-in electric field, significantly boosts the electrical conductivity, enhances the Na+ diffusion kinetics, and buffers the volume variation. With this modification, it can deliver long cycling life, with an ultra-high capacity of 500 mAh g−1 over 500 cycles at 1 ​A ​g−1, and outstanding rate capability, with a capacity of 456 mAh g−1 even at 15 ​A ​g−1. Moreover, a full cell can achieve a high energy density of 180 ​Wh kg−1 at a power density of 40 ​W ​kg−1. Our research opens up a fresh path for improving the dynamics and structural stability of metal sulfide-based electrode materials for SIBs.

Alkaline ferrous slags pose global environmental issues and long-term risks to ambient environments. To explore the under-investigated microbial structure and biogeochemistry in such unique ecosystems, combined geochemical, microbial, ecological and metagenomic analyses were performed in the areas adjacent to a ferrous slag disposal plant in Sichuan, China. Different levels of exposure to ultrabasic slag leachate had resulted in a significant geochemical gradient of pH (8.0–12.4), electric potential (−126.9 to 437.9 mV), total organic carbon (TOC, 1.5–17.3 mg/L), and total nitrogen (TN, 0.17–1.01 mg/L). Distinct microbial communities were observed depending on their exposure to the strongly alkaline leachate. High pH and Ca2+ concentrations were associated with low microbial diversity and enrichment of bacterial classes Gamma-proteobacteria and Deinococci in the microbial communities exposed to the leachate. Combined metagenomic analyses of 4 leachate-unimpacted and 2-impacted microbial communities led to the assembly of one Serpentinomonas pangenome and 81 phylogenetically diversified metagenome assembled genomes (MAGs). The prevailing taxa in the leachate-impacted habitats (e.g., Serpentinomonas and Meiothermus spp.) were phylogenetically related to those in active serpentinizing ecosystems, suggesting the analogous processes between the man-made and natural systems. More importantly, they accounted for significant abundance of most functional genes associated with environmental adaptation and major element cycling. Their metabolic potential (e.g., cation/H+ antiporters, carbon fixation on lithospheric carbon source, and respiration coupling sulfur oxidization and oxygen or nitrate reduction) may support these taxa to survive and prosper in these unique geochemical niches. This study provides fundamental understandings of the adaptive strategies of microorganisms in response to the strong environmental perturbation by alkali tailings. It also contributes to a better comprehension of how to remediate environments affected by alkaline industrial material.

Summary: The impacts of low soil moisture (SM) and high vapour pressure deficit (VPD) on tree’s photosynthesis and productivity are ultimately realized by changing water content in the canopy leaves. In this study, variations in canopy water content (CWC) that can be detected from microwave remotely sensed vegetation optical depth (VOD) have been proposed as a promising measure of vegetation water status, and we first reported that the regulation of CWC on productivity stability is universally applicable for global forests. Results of structural equation model (SEM) also confirmed the significant negative effect of CWC on coefficient of variation (CV) of productivity, indicating that the decrease in CWC could inevitably induce the instability of forest productivity under climate change. The most significant decrease (p

IntroductionThis study was designed to investigate the effect of running exercise on improving bone health in aging mice and explore the role of the SIRT1 in regulating autophagy and osteogenic differentiation of Bone marrow Mesenchymal Stem Cells (BMSCs).MethodsTwelve-month-old male C57BL/6J mice were used in this study as the aging model and were assigned to treadmill running exercise for eight weeks. Non-exercise male C57BL/6J mice of the same old were used as aging control and five-month-old mice were used as young controls. BMSCs were isolated from mice and subjected to mechanical stretching stimulation in vitro.ResultsThe results showed that aging mice had lower bone mass, bone mineral density (BMD), and autophagy than young mice, while running exercise improved BMD and bone mass as well as upregulated autophagy in bone cells. Mechanical loading increased osteogenic differentiation and autophagy in BMSCs, and knockdown of SIRT1 in BMSCs demonstrated that SIRT1-regulated autophagy involved the mechanical loading activation of osteogenic differentiation.ConclusionTaken together, this study revealed that exercise improved bone health during aging by activating bone formation, which can be attributed to osteogenic differentiation of BMSCs through the activation of SIRT1-mediated autophagy. The mechanisms underlying this effect may involve mechanical loading.

Paroxysmal atrial fibrillation originates most commonly in the pulmonary veins. However, the superior vena cava has proved to be arrhythmogenic in some cases. Pulsed field ablation, an emerging ablation technology, selectively affects myocardial tissue. Herein, we present a case of paroxysmal atrial fibrillation in a 64-year-old man who was admitted to our hospital for pulsed field ablation. The tachycardia was recurrent despite four successful pulmonary vein isolations. The superior vena cava was determined to be involved in arrhythmogenesis. The atrial fibrillation terminated immediately after the pulsed field ablation discharge at the superior vena cava.

ObjectiveDespite the promising efficacy and tolerability of alectinib in treating advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC), the role of alectinib in neoadjuvant setting remains understudied in ALK-rearranged resectable lung cancer.MethodsOur report concerns two cases of early-stage NSCLC with complete pathologic responses to off-label use of long-course neoadjuvant alectinib. PubMed, Web of Science, and Cochrane Library were searched comprehensively for ALK-positive resectable cases with neoadjuvant alectinib. The papers were chosen following PRISMA recommendations. Seven cases from the literature and two present cases were evaluated.ResultsTwo cases with stage IIB (cT3N0M0) EML4-ALK lung adenocarcinoma received long-course (more than 30 weeks) of neoadjuvant alectinib followed by R0 lobectomy with the complete pathological response. In our systematic review, 74 studies were included in the original search. Application of the screening criteria resulted in 18 articles deemed eligible for full-text reading. Following the application of the exclusion criteria, out of six papers, seven cases were selected for inclusion in the final analysis and were included in the systematic review. None of the studies were included in the quantitative analysis.ConclusionWe report two cases of lung adenocarcinoma with resectable ALK-positive that achieved pCR with long-course neoadjuvant alectinib. Our cases and a systematic review of the literature support the feasibility of neoadjuvant alectinib treatment for NSCLC. However, large clinical trials must be conducted in the future to determine the treatment course and efficacy of the neoadjuvant alectinib modality.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42022376804.

This study tried to explore the ground movement induced by triple stacked tunneling (TST) with different construction sequences. A case study in Tianjin, China was used to investigate the ground movement during the TST (upper tunneling (UT)). For this, a modified Peck formula was proposed to predict the surface settlement induced by TST. Next, three sets of finite element analyses (FEA) were used to compare the effects of construction sequences (i.e. UT, middle tunneling (MT), and lower tunneling (LT)) on vertical and lateral ground displacements. The results of Tianjin case and UT reveal that compared to a Gaussian distribution for a single tunnel, the surface settlement curve of triple stacked tunnels is a bimodal distribution. It seems that the proposed modified Peck formula can effectively predict the surface settlement induced by TST. The results of the three sets of FEA demonstrate that the construction sequence has a significant influence on the ground movement. Among the three construction sequences, the largest lateral displacement is observed in the MT and the smallest one in UT. The existing tunnel has an inhibitory effect on the vertical displacement. The maximum value of the lateral displacement occurs at the depth of the new tunnel in each construction sequence.