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Microorganisms, particularly extremophiles, have evolved multiple adaptation mechanisms to address diverse stress conditions during survival in unique environments. Their responses to environmental coercion decide not only survival in severe conditions but are also an essential factor determining bioproduction performance. The design of robust cell factories should take the balance of their growing and bioproduction into account. Thus, mining and redesigning stress-tolerance elements to optimize the performance of cell factories under various extreme conditions is necessary. Here, we reviewed several stress-tolerance elements, including acid-tolerant elements, saline-alkali-resistant elements, thermotolerant elements, antioxidant elements, and so on, providing potential materials for the construction of cell factories and the development of synthetic biology. Strategies for mining and redesigning stress-tolerance elements were also discussed. Moreover, several applications of stress-tolerance elements were provided, and perspectives and discussions for potential strategies for screening stress-tolerance elements were made.

Abstract Introduction Working memory (WM) is suggested to play a pivotal role in relearning and neural restoration during stroke rehabilitation. Using EEG, this study investigated the oscillatory mechanisms of WM in subacute stroke. Methods This study included 48 first subacute stroke patients (26 good-recovery, 22 poor-recovery, based on prognosis after a 4-week period) and 24 matched health controls. We examined the oscillatory characteristics and functional connectivity of the 0-back WM paradigm and assessed their associations with prognosis. Results Patients of poor recovery are characterised by a loss of significant beta rebound, beta-band connectivity, as well as impaired working memory speed and performances. Meanwhile, patients with good recovery have preserved these capacities to some extent. Our data further identified beta rebound to be closely associated with working memory speed and performances. Conclusions We provided novel findings that beta rebound and network connectivity as mechanistic evidence of impaired working memory in subacute stroke. These oscillatory features could potentially serve as a biomarker for brain stimulation technologies in stroke recovery.

Abstract Manipulation C-C coupling pathway is of great importance for selective CO2 electroreduction but remain challenging. Herein, two model Cu-based catalysts, by modifying Cu nanowires with Ag nanoparticles (AgCu NW) and Ag single atoms (Ag1Cu NW), respectively, are rationally designed for exploring the C-C coupling mechanisms in electrochemical CO2 reduction reaction (CO2RR). Compared to AgCu NW, the Ag1Cu NW exhibits a more than 10-fold increase of C2 selectivity in CO2 reduction to ethanol, with ethanol-to-ethylene ratio increased from 0.41 over AgCu NW to 4.26 over Ag1Cu NW. Via a variety of operando/in-situ techniques and theoretical calculation, the enhanced ethanol selectivity over Ag1Cu NW is attributed to the promoted H2O dissociation over the atomically dispersed Ag sites, which effectively accelerated *CO hydrogenation to form *CHO intermediate and facilitated asymmetric *CO-*CHO coupling over paired Cu atoms adjacent to single Ag atoms. Results of this work provide deep insight into the C-C coupling pathways towards target C2+ product and shed light on the rational design of efficient CO2RR catalysts with paired active sites.

Abstract Transition metal carbide shows excellent performance in selective hydrogenation of acetylene, however, the carburization of Pd-based intermetallic compounds remains infeasible. Here we report the successful synthesis of an unprecedented Pd3ZnCx intermetallic carbide, via co-infiltration of zinc and carbon in one-step carburization by syngas. Utilizing state-of-the-art in situ characterizations and theoretical calculation, we unveil the dynamic evolution of Pd3ZnCx during carburization, forming a Pd3Zn like cubic phase carbide structure. A unique transitional state (Pdt) with low content of Zn/C co-infiltration is clearly identified facilitating phase transition and sustain incorporation of carbon and zinc at elevated temperatures. The Pd3ZnCx carbide shows by far the best catalytic performance in the selective hydrogenation of acetylene with a high selectivity (>90%) even at a high H2/C2H2 ratio. Our results therefore provide a co-infiltration strategy and dynamic insights for the one-step synthesis of Pd based intermetallic carbides, towards high-performance intermetallic compound for selective hydrogenation of acetylene.

Abstract The run-up velocity and jumping ground reaction force directly influence gymnasts’ ability to perform more difficult manoeuvres and win competitions on vault. However, the variables influencing them among elite female gymnasts remain inadequately understood and warrant detailed investigation. This study aimed to analyse critical variables including run-up velocity and jumping ground reaction force, and to compare these factors across different vault types while further exploring the correlations among them. The study hypothesized that there are significant differences in run-up velocity and jumping ground reaction force across vaulting types, and that these differences will affect athletes’ performance. To test this hypothesis, the study analyzed data from performance tests on 16 elite Chinese female gymnasts, focusing on vaulting run-up velocity and jumping ground reaction force. Descriptive statistics were used to summarize the data, and binary logistic regression analysis was employed to investigate the relationships between the variables. The study found significant differences in interval run-up velocities between the Front handspring vaults and the Tsukahara vaults, particularly before the last 10 m (p = 0.04) and the last 5 m (p = 0.03). Specifically, the Front handspring vaults had higher velocities before the last 10 m, while the Tsukahara vaults had higher velocities within the last 5 m. Differences were also noted in the lengths of the penultimate (p = 0.03), last (p = 0.01), and hurdle steps (p = 0.04). The jumping ground reaction force showed a strong negative correlation with run-up velocity before the last 10 m (ρ = -0.469, p

Background: The combination of oral pentoxifylline (Ptx) and vitamin E (VitE) has been used to treat radiation-induced fibrosis and soft tissue injury. Here, we review outcomes and perform a radiomic analysis of treatment effects in patients prescribed Ptx + VitE at our institution for the treatment of radiation necrosis (RN). Methods: A total of 48 patients treated with stereotactic radiosurgery (SRS) had evidence of RN and had MRI before and after starting Ptx + VitE. The radiation oncologist’s impression of the imaging in the electronic medical record was used to score response to treatment. Support Vector Machine (SVM) was used to train a model of radiomics features derived from radiation necrosis on pre- and 1st post-treatment T1 post-contrast MRIs that can classify the ultimate response to treatment with Ptx + VitE. Results: A total of 43.8% of patients showed evidence of improvement, 18.8% showed no change, and 25% showed worsening RN upon imaging after starting Ptx + VitE. The median time-to-response assessment was 3.17 months. Nine patients progressed significantly and required Bevacizumab, hyperbaric oxygen therapy, or surgery. Patients who had multiple lesions treated with SRS were less likely to show improvement (p = 0.037). A total of 34 patients were also prescribed dexamethasone, either before (7), with (16), or after starting (11) treatment. The use of dexamethasone was not associated with an improved response to Ptx + VitE (p = 0.471). Three patients stopped treatment due to side effects. Finally, we were able to develop a machine learning (SVM) model of radiomic features derived from pre- and 1st post-treatment MRIs that was able to predict the ultimate treatment response to Ptx + VitE with receiver operating characteristic (ROC) area under curve (AUC) of 0.69. Conclusions: Ptx + VitE appears safe for the treatment of RN, but randomized data are needed to assess efficacy and validate radiomic models, which may assist with prognostication.

Abstract Background Microbial organisms hold significant potential for converting renewable substrates into valuable chemicals. Low pH fermentation in industrial settings offers key advantages, including reduced neutralizer usage and decreased wastewater generation, particularly in the production of amino acids and organic acids. Engineering acid-tolerant strains represents a viable strategy to enhance productivity in acidic environments. Synthetic biology provides dynamic regulatory tools, such as gene circuits, facilitating precise expression of acid resistance (AR) modules in a just-in-time and just-enough manner. Results In this study, we aimed to enhance the robustness and productivity of Escherichia coli, a workhorse for amino acid and organic acid production, in industrial fermentation under mild acidic conditions. We employed an Esa-type quorum sensing circuit to dynamically regulate the expression of an AR module (DsrA-Hfq) in a just-in-time and just-enough manner. Through careful engineering of the critical promoter PesaS and stepwise evaluation, we developed an optimal Esa-PBD(L) circuit that conferred upon an industrial E. coli strain SCEcL3 comparable lysine productivity and enhanced yield at pH 5.5 compared to the parent strain at pH 6.8. Conclusions This study exemplifies the practical application of gene circuits in industrial environments, which present challenges far beyond those of well-controlled laboratory conditions.

In industrial fermentation processes, microorganisms often encounter acid stress, which significantly impact their productivity. This study focused on the acid-resistant module composed of small RNA (sRNA) DsrA and the sRNA chaperone Hfq. Our previous study had shown that this module improved the cell growth of Escherichia coli MG1655 at low pH, but failed to obtain this desired phenotype in industrial strains. Here, we performed a quantitative analysis of DsrA-Hfq module to determine the optimal expression mode. We then assessed the potential of the CymR-based negative auto-regulation (NAR) circuit for industrial application, under different media, strains and pH levels. Growth assay at pH 4.5 revealed that NAR-05D04H circuit was the best acid-resistant circuit to improve the cell growth of E. coli MG1655. This circuit was robust and worked well in the industrial lysine-producing strain E. coli SCEcL3 at a starting pH of 6.8 and without pH control, resulting in a 250 % increase in lysine titer and comparable biomass in shaking flask fermentation compared to the parent strain. This study showed the practical application of NAR circuit in regulating DsrA-Hfq module, effectively and robustly improving the acid tolerance of industrial strains, which provides a new approach for breeding industrial strains with tolerance phenotype.

Ebola virus (EBOV) belongs to Filoviridae family possessing single-stranded negative-sense RNA genome, which is a serious threat to human health. Nowadays, no therapeutics have been proven to be successful in efficiently decreasing the mortality rate. RNA binding proteins (RBPs) are reported to participate in maintaining cell integrity and regulation of viral replication. However, little is known about whether and how RBPs participate in regulating the life cycle of EBOV. In our study, we found that RNA binding motif protein 4 (RBM4) inhibited the replication of EBOV in HEK293T and Huh-7 cells by suppressing viral mRNA production. Such inhibition resulted from the direct interaction between the RRM1 domain of RBM4 and the “CU” enrichment elements located in the PE1 and TSS of the 3′-leader region within the viral genome. Simultaneously, RBM4 could upregulate the expression of some cytokines involved in the host innate immune responses to synergistically exert its antiviral function. The findings therefore suggest that RBM4 might serve as a novel target of anti-EBOV strategy.

Nipah virus (NiV), a highly pathogenic Henipavirus in humans, has been responsible for annual outbreaks in recent years. Experiments involving live NiV are highly restricted to biosafety level 4 (BSL-4) laboratories, which impedes NiV research. In this study, we developed transcription and replication-competent NiV-like particles (trVLP-NiV) lacking N, P, and L genes. This trVLP-NiV exhibited the ability to infect and continuously passage in cells ectopically expressing N, P, and L proteins while maintaining stable genetic characteristics. Moreover, the trVLP-NiV displayed a favourable safety profile in hamsters. Using the system, we found the NiV nucleoprotein residues interacting with viral RNA backbone affected viral replication in opposite patterns. This engineered system was sensitive to well-established antiviral drugs, innate host antiviral factors, and neutralizing antibodies. We then established a high-throughput screening platform utilizing the trVLP-NiV, leading to the identification of tunicamycin as a potential anti-NiV compound. Evidence showed that tunicamycin inhibited NiV replication by decreasing the infectivity of progeny virions. In conclusion, this trVLP-NiV system provided a convenient and versatile molecular tool for investigating NiV molecular biology and conducting antiviral drug screening under BSL-2 conditions. Its application will contribute to the development of medical countermeasures against NiV infections.

Satellite ocean transparency data have low spatial coverage due to cloud shading, sun glint, swath width, and temporal revisit. Merging multiple satellite ocean transparency data can improve spatial coverage and create a high-accuracy data set. This study proposed a new satellite ocean transparency merging model based on dual generative adversarial networks (ZSD-merging GAN), and the products of full-coverage and high-accuracy ocean transparency were produced. The ZSD-merging GAN comprises the guess GAN and the merging GAN. The guess GAN is used to generate the guess of the ocean transparency merged product, while the merging GAN combines the guess and satellite ocean transparency data to produce the merged product. The experiments show that the spatial coverage of the ZSD-merging GAN product is 100%. The root-mean-square error (RMSE) and average relative error (ARE) between the ZSD-merging GAN product and unmerged ocean transparency data from the Visible Infrared Imaging Radiometer Suite (VIIRS) on JPSS1 are 4.31 m and 11%, respectively, which are better than 5.59 m and 17% for historical average, 5.55 m and 19% for guess product, 5.08 m and 17% for Poisson blending product, and 5.12 m and 21% for Kriging interpolation product.

ABSTRACTIn this study, we used high-throughput sequencing technology to analyze the diversity and predict gene function of intestinal bacteria from captive black-capped capuchin in two wildlife parks. The results showed that the composition of intestinal gut bacterial diversity was significantly higher in black-capped capuchins monkeys from ES than HT. Moreover, high similarity of intestinal bacteria of black-capped capuchins at the same site was found by sample stratum clustering. Black-capped capuchins intestinal bacteria can be clustered into 2296 ASVs, belonging to 16 phyla, 99 families and 210 genera, respectively. The dominant phyla were Bacteroidota and Firmicutes in the intestinal bacteria of black-capped capuchins, but there were differences in the dominant bacterial families and dominant bacterial genera between ES and HT, and the bacterial families with significant differences had correspondence with bacterial genera. The results provide a basis for the study of intestinal bacteria in black-capped capuchins and the isolation and purification of dominant bacteria. The results of this study fill the gap in the study of intestinal bacterial diversity and its gene functions in black-capped capuchins, and provide a reference for the isolation of dominant bacteria in black-capped capuchins’ intestinal microbes and the discovery and study of novel functional genes.

Background Preeclampsia/eclampsia is a severe pregnancy-related disorder associated with hypertension and organ damage. While observational studies have suggested a link between maternal iron status and preeclampsia/eclampsia, the causal relationship remains unclear. The aim of this study was to investigate the genetic causality between iron status and preeclampsia/eclampsia using large-scale genome-wide association study (GWAS) summary data and Mendelian randomization (MR) analysis.Methods Summary data for the GWAS on preeclampsia/eclampsia and genetic markers related to iron status were obtained from the FinnGen Consortium and the IEU genetic databases. The “TwoSampleMR” software package in R was employed to test the genetic causality between these markers and preeclampsia/eclampsia. The inverse variance weighted (IVW) method was primarily used for MR analysis. Heterogeneity, horizontal pleiotropy, and potential outliers were evaluated for the MR analysis results.Results The random-effects IVW results showed that ferritin (OR = 1.11, 95% CI: .89–1.38, p = .341), serum iron (OR = .90, 95% CI: .75–1.09, p = .275), TIBC (OR = .98, 95% CI: .89–1.07, p = .613), and TSAT (OR = .94, 95% CI: .83–1.07, p = .354) have no genetic causal relationship with preeclampsia/eclampsia. There was no evidence of heterogeneity, horizontal pleiotropy, or possible outliers in our MR analysis (p > .05).Conclusions Our study did not detect a genetic causal relationship between iron status and preeclampsia/eclampsia. Nonetheless, this does not rule out a relationship between the two at other mechanistic levels.

Traditional photovoltaic (PV) forecasting methods often overlook the impact of the correlation between different power fluctuations and weather factors on short-term forecasting accuracy. To address this, this paper proposes a PV output forecasting method based on Variational Mode Decomposition (VMD) disturbance feature extraction and the WaveNet model. First, to extract different feature variations of the output and enhance the model’s ability to capture PV power fluctuation details, VMD is used to decompose the PV output time series, obtaining IMFs modes representing output disturbances and quasi-clear sky IMF modes. Then, to reveal power changes, especially the underlying patterns of disturbances and their relationship with weather factors, K-means clustering is applied to the IMF modes representing output disturbances, clustering the disturbance IMFs into different power change feature clusters. This is combined with Spearman correlation analysis of weather factors and the construction of an experimental dataset. Finally, to enhance the model’s learning ability and improve short-term output forecasting accuracy, the WaveNet model is employed during the forecasting phase. Separate WaveNet models are constructed and trained with the corresponding datasets, and the total PV output forecast is obtained by superimposing the predictions of different IMF modes. Experimental results are compared with traditional methods, demonstrating a significant improvement in forecasting accuracy, with a Mean Absolute Percentage Error (MAPE) error of 6.94%, highlighting the effectiveness of our method and providing strong technical support for the refined management and intelligent forecasting of PV energy.

Pathological transdifferentiation, where differentiated cells aberrantly transform into other cell types that exacerbate disease rather than promote healing, represents a novel and significant concept. This perspective discusses its role and potential targeting in cardiovascular diseases and chronic inflammation. Current therapies mainly focus on mitigating early inflammatory response through proinflammatory cytokines and pathways targeting, including corticosteroids, TNF-α inhibitors, IL-1β monoclonal antibodies and blockers, IL-6 blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs), along with modulating innate immune memory (trained immunity). However, these approaches often fail to address long-term tissue damage and functional regeneration. For instance, fibroblasts can transdifferentiate into myofibroblasts in cardiac fibrosis, and endothelial cells may undergo endothelial to mesenchymal transition (EndMT) in vascular remodeling, resulting in fibrosis and impaired tissue function. Targeting pathological transdifferentiation represents a promising therapeutic avenue by focusing on key signaling pathways that drive these aberrant cellular phenotypic and transcriptomic transitions. This approach seeks to inhibit these pathways or modulate cellular plasticity to promote effective tissue regeneration and prevent fibrosis. Such strategies have the potential to address inflammation, cell death, and the resulting tissue damage, providing a more comprehensive and sustainable treatment solution. Future research should focus on understanding the mechanisms behind pathological transdifferentiation, identifying relevant biomarkers and master regulators, and developing novel therapies through preclinical and clinical trials. Integrating these new therapies with existing anti-inflammatory treatments could enhance efficacy and improve patient outcomes. Highlighting pathological transdifferentiation as a therapeutic target could transform treatment paradigms, leading to better management and functional recovery of cardiovascular tissues in diseases and chronic inflammation.

BackgroundIatrogenic nerve injury is a consequential complication during surgery. Thus, real-time imaging of peripheral nerve (PN) possesses significant clinical implications. In recent years, the rapid advancements in optical molecular imaging (OMI) technology have provided essential technical foundations for the implementation of PN fluorescence imaging. This study aimed to realize real-time OMI of PNs via Rhodamine B.MethodsPhosphate buffered saline (PBS), normal saline (NS), 5% glucose solution (GS), and fetal bovine serum (FBS) were selected for measuring the fluorescence spectra of Rhodamine B solutions prepared in each formulation. Rhodamine B solutions, with varying doses dissolved in 100 μL of each formulation, were prepared and applied to the exposed PNs of the mice for incubation later. To ascertain the optimal formulation and dose of Rhodamine B, an analysis was performed on the signal-to-background ratio (SBR) of the nerves. Based on the experimental results, we proceeded to incubate Rhodamine B solution on the PN tissue of mice and human subjects, as well as on neuronal cells, to verify the binding sites of Rhodamine B with nerve. Subsequently, histological studies were conducted to validate the binding site between Rhodamine B and the nerves. Finally, we injected the optimal combination of Rhodamine B solution into mice via the tail vein and collected the SBR of mouse nerve tissues at different time intervals to determine the optimal pre-injection time. Fluorescence images of various tissues were collected, and Hematoxylin and Eosin (H&E) staining results were observed to determine the metabolism of Rhodamine B in mice and its toxicity.ResultsThe excitation peak of Rhodamine B in PBS, NS, 5% GS, and FBS formulations was 554 nm, and the emission peak was 576 nm. In PBS group, the maximum SBR was 15.37 ± 0.68 while the dose of Rhodamine B was 8 nmol. Through ex-vivo validation on fresh human nerve tissue and verification using mouse and human tissue sections, we observed fluorescent signals of Rhodamine Bin the regions of nerve tissue and the fluorescence signals were all concentrated on the neuronal cell membranes. After injection, the fluorescent signal in nerve tissue reached its peak at 24 hours (h), coinciding with the highest SBR (5.93 ± 0.92) in mouse nerve tissues at this time point. Additionally, the fluorescence signal could be maintained for at least 48 h. Within 24 h, lung dilation and fusion of alveoli occurred. Then these pathological manifestations gradually diminished, returning to normal at 2 weeks (w), with no significant acute or chronic adverse reactions observed in other tissues.ConclusionRhodamine B enables fluorescence imaging of PNs and has the potential for clinical translation.

Abstract With the rapid development of urban rail transit, the issue of stray current due to incomplete insulation between the rail and the earth is attracting increasing attention. Stray current seriously affects the safe operation of urban rail transit, pipelines and power grids, and pose challenges to the development of urban energy security. However, there are significant differences among the various methods for the analysis and verification of stray currents, and existing research works thus lack a mature theoretical framework. To address this, this paper presents an in-depth review on the study of stray current including the mechanism, technical standards, modelling, simulation and mitigation technologies. Firstly, the principle and standards of stray current are introduced from multiple perspectives (i.e. metro side, pipeline side and grid side). Then, the typical modelling and simulation of stray current are summarized and compared in detail. The representative stray current mitigation measures, together with the stray current hardware simulation technologies, are also discussed. In conclusion, this paper provides a comprehensive overview of key technologies involved in the modelling and simulation of stray current, and highlights the valuable research direction in stray current mitigation.

Abstract Background Cervical cancer has extremely high morbidity and mortality, and its pathogenesis is still in the exploratory stage. This study aimed to screen and identify differentially expressed genes (DEGs) related to cervical cancer through bioinformatics analysis. Methods GSE63514 and GSE67522 were selected from the GEO database to screen DEGs. Then GO and KEGG analysis were performed on DEGs. PPI network of DEGs was constructed through STRING website, and the hub genes were found through 12 algorithms of Cytoscape software. Meanwhile, GSE30656 was selected from the GEO database to screen DEMs. Target genes of DEMs were screened through TagetScan, miRTarBase and miRDB. Next, the hub genes screened from DEGs were merged with the target genes screened from DEMs. Finally, ROC curve and nomogram analysis were performed to assess the predictive capabilities of the hub genes. The expression of these hub genes were verified through TCGA, GEPIA, qRT-PCR, and immunohistochemistry. Results Six hub genes, TOP2A, AURKA, CCNA2, IVL, KRT1, and IGFBP5, were mined through the protein-protein interaction network. The expression of these hub genes were verified through TCGA, GEPIA, qRT-PCR, and immunohistochemistry, and it was found that TOP2A, AURKA as well as CCNA2 were overexpressed and IGFBP5 was low expression in cervical cancer. Conclusions This study showed that TOP2A, AURKA, CCNA2 and IGFBP5 screened through bioinformatics analysis were significantly differentially expressed in cervical cancer samples compared with normal samples, which might be biomarkers of cervical cancer.

Abstract RNA-binding proteins (RBPs) are a class of proteins that primarily function by interacting with different types of RNAs and play a critical role in regulating the transcription and translation of cancer-related genes. However, their role in the progression of hepatocellular carcinoma (HCC) remains unclear. In this study, we analyzed RNA sequencing data and the corresponding clinical information of patients with HCC to screen for prognostic RBPs. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was identified as an independent prognostic factor for liver cancer. It is upregulated in HCC and is associated with a poor prognosis. Elevated IGF2BP3 expression was validated via immunohistochemical analysis using a tissue microarray of patients with HCC. IGF2BP3 knockdown inhibited the proliferation of Hep3B and HepG2 cells, whereas IGF2BP3 overexpression promoted the expansion of HuH-7 and MHCC97H cells. Mechanistically, IGF2BP3 modulates cell proliferation by regulating E2F1 expression. DNA hypomethylation of the IGF2BP3 gene may increase the expression of IGF2BP3, thereby enhancing cell proliferation in HCC. Therefore, IGF2BP3 may act as a novel prognostic biomarker and a potential therapeutic target for HCC.

This paper contrasts predicted X-band sea surface backscattering from slick-free and oil-covered sea surfaces with actual measurements acquired by the X-band satellite TerraSAR-X and COSMO-SkyMed Synthetic Aperture Radar (SAR) missions. Two SAR scenes were acquired with a temporal difference of about 36 minutes, under similar met-ocean conditions, during the North Sea’s Gannet Alpha oil spill accident. The normalized radar cross section of the slick-free sea surface is predicted using the Advanced Integral Equation Model (AIEM) while the backscatter from the oiled sea surface is predicted by the AIEM augmented with the Model of Local Balance (MLB) to include the damping effect of oil slicks. Experimental results show that X-band co-polarized numerical predictions agree reasonably well with both TSX and CSK actual measurements collected over slick-free sea surfaces. When dealing with oil-covered sea surfaces, the predicted backscattering reasonably agrees with TSX measurements, while it overestimates the CSK ones. This is likely due to the different spreading conditions of the oil imaged by the two satellite missions.

Abstract Magnetic Resonance Imaging (MRI) is increasingly being used in treatment planning due to its superior soft tissue contrast, which is useful for tumor and soft tissue delineation compared to computed tomography (CT). However, MRI cannot directly provide mass density or relative stopping power (RSP) maps, which are required for calculating proton radiotherapy doses. Therefore, the integration of artificial intelligence (AI) into MRI-based treatment planning to estimate mass density and RSP directly from MRI has generated significant interest. A deep learning (DL) based framework was developed to establish a voxel-wise correlation between MR images and mass density as well as RSP. To facilitate the study, five tissue substitute phantoms were created, representing different tissues such as skin, muscle, adipose tissue, 45% hydroxyapatite (HA), and spongiosa bone. The composition of these phantoms was based on information from ICRP reports. Additionally, two animal tissue phantoms, simulating pig brain and liver, were prepared for DL training purposes. The phantom study involved the development of two DL models. The first model utilized clinical T1 and T2 MRI scans as input, while the second model incorporated zero echo time (ZTE) MRI scans. In the patient application study, two more DL models were trained: one using T1 and T2 MRI scans as input, and another model incorporating synthetic dual-energy computed tomography (sDECT) images to provide accurate bone tissue information. The DECT empirical model was used as a reference to evaluate the proposed models in both phantom and patient application studies. The DECT empirical model was selected as the reference for evaluating the proposed models in both phantom and patient application studies. In the phantom study, the DL model based on T1, and T2 MRI scans demonstrated higher accuracy in estimating mass density and RSP for skin, muscle, adipose tissue, brain, and liver. The mean absolute percentage errors (MAPE) were 0.42%, 0.14%, 0.19%, 0.78%, and 0.26% for mass density, and 0.30%, 0.11%, 0.16%, 0.61%, and 0.23% for RSP, respectively. The DL model incorporating ZTE MRI further improved the accuracy of mass density and RSP estimation for 45% HA and spongiosa bone, with MAPE values of 0.23% and 0.09% for mass density, and 0.19% and 0.07% for RSP, respectively. These results demonstrate the feasibility of using an MRI-only approach combined with DL methods for mass density and RSP estimation in proton therapy treatment planning. By employing this approach, it is possible to obtain the necessary information for proton radiotherapy directly from MRI scans, eliminating the need for additional imaging modalities.

Summary: Elevated levels of androgen are risk factors for disrupted follicular maturation in the polycystic ovary syndrome (PCOS), a reproductive disease in women. As essential cell types for follicular maturation, granulosa and thecal cells respond to androgen, but their responses are unclear at the subpopulation level. Using single-cell RNA sequencing and spatial transcriptomics, we examined the subpopulation and function alterations in an androgen-induced PCOS-like mouse model. The results demonstrated that the granulosa cell subset 5 (GC5) was active in inflammation and the thecal cell subtype 2 (TC2) had an enhanced activity in lipid metabolism. The two subsets were expanded in population size and intercellular signaling pathways, such as Ptn-Ncl and Mdk-Ncl. The results reveal that androgen induced landscape and function shifts in the two cell types under the condition of impaired follicular maturation. The study characterizes the ovarian microenvironment in responses to androgen in PCOS mice.

Fluorescence imaging is a relatively new imaging method used to visualize different tissue structures to help guide intraoperative operations, which has potential advantages with high sensitivity and contrast compared to conventional imaging. In this work, we review fluorescent contrast agents and devices used for lymphatic system imaging. Indocyanine green is the most widely utilized due to its high sensitivity, specificity, low background fluorescence, and safety profile. In prostate and bladder cancer lymph node dissection, the complex lymphatic drainage can result in missed metastatic nodes and extensive dissection increases the risk of complications like lymphocele, presenting a significant challenge for urologists. Fluorescence-guided sentinel lymph node dissection facilitates precise tumor staging. The combination of fluorescence and radiographic imaging improves the accuracy of lymph node staging. Multimodal imaging presents new potential for precisely identifying metastatic pelvic lymph nodes.

Extracellular protein coronas (exPCs), which have been identified in various biofluids, are recognized for their pivotal role in mediating the interaction between nanoparticles and the cytomembrane. However, it is still unclear whether various exPCs can induce different levels of intracellular proteostasis, which is of utmost importance in preserving cellular function, and eliciting distinct intracellular biological behaviors. To investigate this, two types of exPC-coated iron oxide nanoparticles (IONPs) are prepared and used to investigate the influence of exPCs on extracellular and intracellular biological outcomes. The results demonstrate that the formation of exPCs promotes the colloidal stability of IONPs, and the discrepancies in the components of the two exPCs, including opsonin, dysopsonin, and lipoprotein, are responsible for the disparities in cellular uptake and endocytic pathways. Moreover, the differential evolution of the two exPCs during cellular internalization leads to distinct autophagy and glycolysis activities, which can be attributed to the altered depletion of angiopoietin 1 during the formation of intracellular protein coronas, which ultimately impacts the PI3K/AKT-mTOR signaling. These findings offer valuable insights into the dynamic characteristics of exPCs during cellular internalization, and their consequential implications for cellular internalization and intracellular metabolism activity, which may facilitate the comprehension of PCs on biological effects of NPs and expedite the design and application of biomedical nanoparticles.

Mitochondria, traditionally recognized as cellular 'powerhouses' due to their pivotal role in energy production, have emerged as multifunctional organelles at the intersection of bioenergetics, metabolic signaling, and immunity. However, the understanding of their exact contributions to immunity and inflammation is still developing. This review first introduces the innovative concept of intracellular immunity, emphasizing how mitochondria serve as critical immune signaling hubs. They are instrumental in recognizing and responding to pathogen and danger signals, and in modulating immune responses. We also propose mitochondria as the leading immune organelles, drawing parallels with the broader immune system in their functions of antigen presentation, immune regulation, and immune response. Our comprehensive review explores mitochondrial immune signaling pathways, their therapeutic potential in managing inflammation and chronic diseases, and discusses cutting-edge methodologies for mitochondrial research. Targeting a broad readership of both experts in mitochondrial functions and newcomers to the field, this review sets forth new directions that could transform our understanding of intracellular immunity and the integrated immune functions of intracellular organelles.

Abstract Objective The objective of this study was to establish a methodology for determining carboxymethyl lysine (CML) and carboxyethyl lysine (CEL) concentrations in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The test results were also used for clinical aging research. Methods Human plasma samples were incubated with aqueous perfluorovaleric acid (NFPA), succeeded by precipitation utilizing trichloroacetic acid, hydrolysis facilitated by hydrochloric acid, nitrogen drying, and ultimate re-dissolution utilizing NFPA, followed by filtration. Cotinine-D3 was added as an internal standard. The separation was performed on an Agela Venusil ASB C18 column (50 mm × 4.6 mm, 5 μm) with a 5 mmol/L NFPA and acetonitrile/water of 60:40 (v/v) containing 0.15% formic acid. The multiple reaction monitoring mode was used for detecting CML, CEL, and cotinine-D3, with ion pairs m/z 205.2 > 84.1 (for quantitative) and m/z 205.2 > m/z 130.0 for CML, m/z 219.1 > 84.1 (for quantitative) and m/z 219.1 > m/z 130.1 for CEL, and m/z 180.1 > 80.1 for cotinine-D3, respectively. Results The separation of CML and CEL was accomplished within a total analysis time of 6 minutes. The retention times of CML, CEL, and cotinine-D3 were 3.43 minutes, 3.46 minutes, and 4.50 minutes, respectively. The assay exhibited linearity in the concentration range of 0.025–1.500 μmol/L, with a lower limit of quantification of 0.025 μmol/L for both compounds. The relative standard deviations of intra-day and inter-day were both below 9%, and the relative errors were both within the range of ±4%. The average recoveries were 94.24% for CML and 97.89% for CEL. Conclusion The results indicate that the developed methodology is fast, highly sensitive, highly specific, reproducible, and suitable for the rapid detection of CML and CEL in clinical human plasma samples. The outcomes of the clinical research project on aging underscored the important indicative significance of these two indicators for research on human aging.

Background Medical imaging datasets frequently encounter a data imbalance issue, where the majority of pixels correspond to healthy regions, and the minority belong to affected regions. This uneven distribution of pixels exacerbates the challenges associated with computer-aided diagnosis. The networks trained with imbalanced data tends to exhibit bias toward majority classes, often demonstrate high precision but low sensitivity. Method We have designed a new network based on adversarial learning namely conditional contrastive generative adversarial network (CCGAN) to tackle the problem of class imbalancing in a highly imbalancing MRI dataset. The proposed model has three new components: (1) class-specific attention, (2) region rebalancing module (RRM) and supervised contrastive-based learning network (SCoLN). The class-specific attention focuses on more discriminative areas of the input representation, capturing more relevant features. The RRM promotes a more balanced distribution of features across various regions of the input representation, ensuring a more equitable segmentation process. The generator of the CCGAN learns pixel-level segmentation by receiving feedback from the SCoLN based on the true negative and true positive maps. This process ensures that final semantic segmentation not only addresses imbalanced data issues but also enhances classification accuracy. Results The proposed model has shown state-of-art-performance on five highly imbalance medical image segmentation datasets. Therefore, the suggested model holds significant potential for application in medical diagnosis, in cases characterized by highly imbalanced data distributions. The CCGAN achieved the highest scores in terms of dice similarity coefficient (DSC) on various datasets: 0.965 ± 0.012 for BUS2017, 0.896 ± 0.091 for DDTI, 0.786 ± 0.046 for LiTS MICCAI 2017, 0.712 ± 1.5 for the ATLAS dataset, and 0.877 ± 1.2 for the BRATS 2015 dataset. DeepLab-V3 follows closely, securing the second-best position with DSC scores of 0.948 ± 0.010 for BUS2017, 0.895 ± 0.014 for DDTI, 0.763 ± 0.044 for LiTS MICCAI 2017, 0.696 ± 1.1 for the ATLAS dataset, and 0.846 ± 1.4 for the BRATS 2015 dataset.

ABSTRACT Monkeypox virus (MPXV) poses a global health threat. Droplet digital PCR (ddPCR) holds potential as an accurate diagnostic tool for clinical microbiology. However, there is limited literature on the applicability of ddPCR in clinical settings. In this study, the clinical features of patients with MPXV during the initial outbreak in China in June 2023 were reviewed, and an optimized ddPCR method with dilution and/or inhibitor removal was developed to enhance MPXV detection efficiency. Eighty-two MPXV samples were tested from nine different clinical specimen types, including feces, urine, pharyngeal swabs, anal swabs, saliva, herpes fluid, crust, and semen, and the viral load of each specimen was quantified. A comparative analysis was performed with qPCR to assess sensitivity and specificity and to investigate the characteristics of MPXV infection by analyzing viral loads in different clinical specimens. Consequently, common pharyngeal and gastrointestinal symptoms were observed in patients with MPXV. The optimized ddPCR method demonstrated relatively high sensitivity for MPXV quantification in the clinical materials, with a limit of detection of 0.1 copies/μL. This was particularly evident in low-concentration samples like whole blood, semen, and urine. The optimized ddPCR demonstrated greater detection accuracy compared with normal ddPCR and qPCR, with an area under the curve (AUC) of 0.939. Except for crust samples, viral loads in the specimens gradually decreased as the disease progressed. Virus levels in feces and anal swabs kept a high detection rate at each stage of post-symptom onset, and feces and anal swabs samples may be suitable for clinical diagnosis and continuous monitoring of MPXV.IMPORTANCEThe ddPCR technique proved to be a sensitive and valuable tool for accurately quantifying MPXV viral loads in various clinical specimen types. The findings provided valuable insights into the necessary pre-treatment protocols for MPXV diagnosis in ddPCR detection and the potentially suitable sample types for collection. Therefore, such results can aid in comprehending the potential characteristics of MPXV infection and the usage of ddPCR in clinical settings.

In order to address the disposal challenge of waste glass fiber composite materials and provide a feasible reference for the utilization of recycled glass fiber (RGF), contributing to the sustainable development of concrete engineering. This study focuses on the reuse of RGF to reinforce the impermeability of concrete. The effects of thermal treatment temperature on the properties of RGF are studied and the microstructural morphology of RGF and its reinforcement effect to concrete are evaluated. Additionally, the permeability resistance of recycled glass fiber reinforced concrete (RGFRC) is investigated, and the mechanism of elevated permeability resistance in RGFRC is revealed. Results indicate that with increasing thermal treatment temperature, the diameter of the thermal treated RGF is notably reduced and the surface of the fiber is covered with a significant amount of impurity. When thermal treated under 600 °C, the RGF presents the optimal structure with appropriate surface roughness, higher crystallinity, stable molecular structure, good compactness. Thus the concrete with RGF calcinated under 600 °C demonstrates the highest compressive strength, demonstrating that the optimal thermal treatment temperature is around 600 °C. Furthermore, the concrete exhibits a continuous reduction in internal water penetration height and sustained improvement in permeability resistance as the fiber content increases. The mechanism behind the improved impermeability of RGF to RGFRC lies in the interweaving of RGF within the concrete matrix, forming a three-dimensional network structure. This structure partially inhibits crack formation and pore expansion, effectively reducing the continuity of interconnected pores, decreasing the size of voids and cracks, and slowing down water permeation, thereby enhancing the impermeability of concrete.

IRC+10216 is the typical carbon-rich asymptotic giant branch star, and more than 100 species have been observed in its circumstellar envelope so far. The use of interferometric arrays to map molecular emission in this source has been widely reported, but to study the angular extent of molecular emission, single-dish mapping must be employed. We report here the mapping of the 13CO J = 1–0 and CS J = 2–1 lines towards IRC+10216 using the 13.7 m mm-wave radio telescope at Purple Mountain Observatory. As far as we know, these maps are the largest published 13CO J = 2–1 and CS J = 2–1 images to date. Both molecules have roughly spherically symmetric distribution, with 13CO having an emission radius of over 80″and CS extending up to ∼50″. Assuming that the two molecules are in local thermodynamic equilibrium, the column density and fractional abundance relative to H2 for 13CO and the lower limits for CS are obtained. They are 4.35 × 1016 cm−2 and > 4.72 × 1014 cm−2, and 5.25 × 10−5 and > 2.56 × 10−7 for 13CO and CS, respectively.

In carbon-rich environment, C2H emission is seen to be associated with HC3N, but whether it can trace the HC3N molecule in oxygen-rich environment is unknown. Here, we have searched for rotational emission from ethynyl radical (C2H) in the oxygen-rich circumstellar envelope (CSE) of the post-asymptotic giant branch (post-AGB) star OH 231.8+4.2, a renowned galactic proto-planetary nebula (PPN) known to display cyanoacetylene (HC3N) emission. Our observations were conducted using the James Clerk Maxwell Telescope (JCMT), and the total on-source time is 11.9 h. Base on local thermodynamic equilibrium (LTE) excitation analysis, we have calculated the column density and the abundance relative to H2 for C2H. The calculated column density for C2H is less than 1.4 × 1013 cm-2, which corresponds to a fractional abundance, f (C2H), less than 4.5 × 10–9. This inference suggests that the typical transformation pathway from C2H and C2H2 to HC3N may not play a significant role in O-rich environments. It indicates the presence of alternative, unidentified pathways that contribute to the formation of HC3N in O-rich circumstellar envelopes.

IntroductionThe gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear.MethodsWe aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models.ResultsWe observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation.ConclusionIn summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.

ObjectiveTo assess the effects of COVID-19 pandemic on the epidemiology of neonatal sepsis and the antibiotic resistance profiles of pathogens involved.MethodsThis retrospective cohort study analyzed infants diagnosed with culture-proven sepsis at the neonatal department of a tertiary children’s hospital in East China from January 2016 to December 2022. We compared the clinical and microbiological characteristics of neonatal sepsis cases between the pre-pandemic Phase I (2016–2019) and during the COVID-19 pandemic Phase II (2020–2022).ResultsA total of 507 infants with 525 sepsis episodes were included, with 343 episodes in Phase I and 182 in Phase II. The incidence of early-onset sepsis (EOS) was significantly lower during Phase II (p < 0.05). Infants in Phase II had lower gestational ages and birth weights compared to Phase I. Clinical signs such as mottled skin, severe anemia, thrombocytopenia were more prevalent in Phase II, alongside a higher incidence of complications. Notably, necrotizing enterocolitis (NEC) (p < 0.05) and meningitis (p < 0.1) occurred more frequently during Phase II. Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the predominant pathogens isolated from infants of death and cases with complications. A significant decrease in the proportion of K. pneumoniae was observed in Phase II, alongside increased antibiotic resistance in both E. coli and K. pneumoniae. The period of the COVID-19 pandemic (Phase II) was identified as an independent risk factor for complications in infants with neonatal sepsis.ConclusionCOVID-19 pandemic response measures correlated with a decrease in EOS and an increase in neonatal sepsis complications and antibiotic resistance.

Ovarian mucinous tumors with sarcomatous mural nodules are rare. Sarcomatous nodules have a bad prognosis. Its diagnosis and treatment are controversial.It is still controversial whether malignant mural nodules represent a dedifferentiated form of mucinous tumors or collisional tumors. This is a case report of a 32-year-old female diagnosed with ovarian mucinous tumor recurred as a mucinous carcinoma combined with sarcomatoid and undifferentiated sarcoma mural nodules after surgery and chemotherapy. The primary lesion did not have a sarcomatous component after comprehensive sampling and repeated review, while the recurrent lesion had a predominantly sarcomatous component. The patient received a second operation and postoperative chemotherapy plus Anlotinib with no progression at 16 months of follow-up. Primary mucinous carcinoma and sarcomatous mural nodules revealed the same K-RAS mutation(c.35G>T, pG12V), TP53 mutation (c.817C>T, p.R273C), MLL2 mutation(c.13450C>T, p.R4484) and NF1 mutation(c.7876A>G, p.S2626G). We present a comprehensive analysis on morphologic characteristics, molecular detection results, clinical management, and prognosis of ovarian mucinous tumors with mural nodules of sarcomatoid and undifferentiated sarcoma. Mutation sharing between primary mucinous carcinoma and recurrent sarcomatous nodules supports monoclonal origin of primary and recurrent tumors, suggesting a tendency for sarcomatous differentiation during the progression of epithelial tumors. Malignant mural nodules represent dedifferentiation in mucinous ovarian tumors rather than collision of two different tumor types. Therefore, it is imperative to conduct comprehensive sampling, rigorous clinical examination, and postoperative follow-up in order to thoroughly evaluate all mural nodules of ovarian mucinous tumors due to their potential for malignancy and sarcomatous differentiation.

ObjectiveThis study aimed to investigate the feasibility and effectiveness of using indocyanine green (ICG) injected intracutaneously through the lower limbs and perineum for visualized tracking, localization, and qualitative assessment of pelvic lymph nodes (LNs) in bladder cancer to achieve their accurate resection.MethodsFirst, ICG was injected into the LN metastasis model mice lower limbs, and real-time and dynamic in vivo and ex vivo imaging was conducted by using a near-infrared fluorescence imaging system. Additionally, 26 patients with bladder cancer were enrolled and divided into intracutaneous group and transurethral group. A near-infrared fluorescence imaging device with internal and external imaging probes was used to perform real-time tracking, localization, and resection of the pelvic LNs.ResultsThe mice normal LNs and the metastatic LNs exhibited fluorescence. The metastatic LNs showed a significantly higher signal-to-background ratio than the normal LNs (3.9 ± 0.2 vs. 2.0 ± 0.1, p < 0.05). In the intracutaneous group, the accuracy rate of fluorescent-labeled LNs was 97.6%, with an average of 11.3 ± 2.4 LNs resected per patient. Six positive LNs were detected in three patients (18.8%). In the transurethral group, the accuracy rate of fluorescent-labeled LNs was 84.4%, with an average of 8.6 ± 2.3 LNs resected per patient. Two positive LNs were detected in one patient (12.5%).ConclusionFollowing the intracutaneous injection of ICG into the lower limbs and perineum, the dye accumulates in pelvic LNs through lymphatic reflux. By using near-infrared fluorescence laparoscopic fusion imaging, physicians can perform real-time tracking, localization, and precise resection of pelvic LNs.

BackgroundIntestinal malrotation is a rare condition, and its delayed diagnosis can lead to fatal consequences. This study aimed to investigate the identification and treatment of malrotation in children.MethodsClinical data, imaging, operative findings, and early postoperative outcomes of 75 children with malrotation were retrospectively analyzed.ResultsThe mean age was 6.18 ± 4.93 days and 51.26 ± 70.13 months in the neonatal group (56 patients) and non-neonatal group (19 patients), respectively. Sixty-seven patients were under the age of 1 year at the time of diagnosis. The occurrence of bilious vomiting and jaundice was significantly higher in the neonatal group (89.29%) than that in the non-neonatal group (37.5%), p 10% of neonates and nearly 40% of non-neonates. This highlights the importance for emergency physicians and surgeons to be cautious about ruling out malrotation in patients with non-bilious vomiting. Utilizing US can obviate the need for contrast examinations owing to its higher diagnostic accuracy and rapid diagnosis and can be recommended as a first-line imaging technique. Additionally, open surgery is still an option for neonatal patients.

Background: Lung adenocarcinoma (LUAD) is a pulmonary malignant disease that poses a high risk of mortality and morbidity. Previous study indicated that ORC1 plays an oncogenic function. However, the precise regulatory function that ORC1 serves in the progression of LUAD is still not clearly known. Methods: Bioinformatics analyses were performed using TCGA and GEO datasets. The human LUAD cell line NCIH1355, NCIH1568 as well as BEAS-2B cell line (human normal lung epithelial cell) were utilized for in vitro study. LUAD cell proliferation were determined via CCK-8 assays and RT-qPCR for ki-67. The relation of ORC1 and SLC7A11 was detected by Western blot and qPCR with or without sh-RNA. The expression level ACSL4, the biomarker of ferroptosis, were detected using RT-qPCR. Results: ORC1 and SLC7A11 exhibit high expression levels in both LUAD patients and cell lines, and are strongly associated with poor prognosis. In vitro experiments demonstrate that ORC1 and SLC7A11 promote proliferation of LUAD cell lines while inhibiting gefitinib-induced ferroptosis. Additionally, the function of ORC1 in LUAD cells is dependent on SLC7A11. Conclusion: ORC1 promotes LUAD cell proliferation and inhibits ferroptosis in a SLC7A11-dependent manner. This implies that ORC1 could potentially serve as a useful diagnosis biomarker and treatment target.

Scalp high-frequency oscillations (sHFOs) are a promising non-invasive biomarker of epilepsy. However, the visual marking of sHFOs is a time-consuming and subjective process, existing automatic detectors based on single-dimensional analysis have difficulty with accurately eliminating artifacts and thus do not provide sufficient reliability to meet clinical needs. Therefore, we propose a high-performance sHFOs detector based on a deep learning algorithm. An initial detection module was designed to extract candidate high-frequency oscillations. Then, one-dimensional (1D) and two-dimensional (2D) deep learning models were designed, respectively. Finally, the weighted voting method is used to combine the outputs of the two model. In experiments, the precision, recall, specificity and F1-score were 83.44%, 83.60%, 96.61% and 83.42%, respectively, on average and the kappa coefficient was 80.02%. In addition, the proposed detector showed a stable performance on multi-centre datasets. Our sHFOs detector demonstrated high robustness and generalisation ability, which indicates its potential applicability as a clinical assistance tool. The proposed sHFOs detector achieves an accurate and robust method via deep learning algorithm.

Medical image datasets, particularly those comprising Magnetic Resonance (MR) images, are essential for accurate diagnosis and treatment planning. However, these datasets often suffer from class imbalance, where certain classes of abnormalities have unequal representation. Models trained on imbalanced datasets can be biased towards the prominent class, leading to misclassification. Addressing class imbalance problems is crucial to developing robust deep-learning MR image analysis models. This research focuses on the class imbalance problem in MR image datasets and proposes a novel approach to enhance deep learning models. We have introduced a unified approach equipped with a selective attention mechanism, unified loss function, and progressive resizing. The selective attention strategy identifies prominent regions within the underlying image to find the feature maps, retaining only the relevant activations of the minority class. Fine-tuning of the multiple hyperparameters was achieved using a novel unified loss function that plays a vital role in enhancing the overwhelming error performance for minority classes and accuracy for common classes. To address the class imbalances phenomenon, we incorporate progressive resizing that can dynamically adjust the input image size as the model trains. This dynamic nature helps handle class imbalances and improve overall performance. The research evaluates the effectiveness of the proposed approach by embedding it into five state-of-the-art CNN models: UNet, FCN, RCNN, SegNet, and Deeplab-V3. For experimental purposes, we have selected five diverse MR image datasets, BUS2017, MICCAI 2015 head and neck, ATLAS, BRATS 2015, and Digital Database Thyroid Image (DDTI), to evaluate the performance of the proposed approach against state-of-the-art techniques. The assessment of the proposed approach reveals improved performance across all metrics for five different MR imaging datasets. DeepLab-V3 demonstrated the best performance, achieving IoU, DSC, Precision, and Recall scores of 0.893, 0.953, 0.943, and 0.944, respectively, on the BUS dataset. These scores indicate an improvement of 5% in DSC, 6% in IoU, 4% in precision, and approximately 4% in recall compared to the baseline. The most significant increases were observed in the ATLAS and LiTS MICCAI 2017 datasets, with a 5% and 7% increase in IoU and DSC over the baseline (DSC = 0.628, DSC = 0.695) for the ATLAS dataset and a 5% and 9% increase in IoU and DSC for the LiTS MICCAI 2017 dataset.

Introduction: Both innate and adaptive immune system undergo evolution from low to high vertebrates. Due to the limitation of conventional approaches in identifying broader spectrum of immune cells and molecules from various vertebrates, it remains unclear how immune molecules evolve among vertebrates. Objectives: Here, we utilized carry out comparative transcriptome analysis in various immune cells across seven vertebrate species. Methods: Single-cell RNA sequencing (scRNA-seq). Results: We uncovered both conserved and species-specific profiling of gene expression in innate and adaptive immunity. Macrophages exhibited highly-diversified genes and developed sophisticated molecular signaling networks along with evolution, indicating effective and versatile functions in higher species. In contrast, B cells conservatively evolved with less differentially-expressed genes in analyzed species. Interestingly, T cells represented a dominant immune cell populations in all species and unique T cell populations were identified in zebrafish and pig. We also revealed compensatory TCR cascade components utilized by different species. Inter-species comparison of core gene programs demonstrated mouse species has the highest similarity in immune transcriptomes to human. Conclusions: Therefore, our comparative study reveals gene transcription characteristics across multiple vertebrate species during the evolution of immune system, providing insights for species-specific immunity as well as the translation of animal studies to human physiology and disease.

Abstract Background This study was conducted to develop and validate an individualized prediction model for spontaneous preterm birth (sPTB) in twin pregnancies. Methods This a retrospective cohort study included 3845 patients who gave birth at the Chongqing Maternal and Child Health Hospital from January 2017 to December 2022. Both univariable and multivariable logistic regression analyses were performed to find factors associated with sPTB. The associations were estimated using the odds ratio (OR) and the 95% confidence interval (CI). Model performance was estimated using sensitivity, specificity, accuracy, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). Results A total of 1313 and 564 cases were included in the training and testing sets, respectively. In the training set, univariate and multivariate logistic regression analysis indicated that age ≥ 35 years (OR, 2.28; 95% CI 1.67–3.13), pre-pregnancy underweight (OR, 2.36; 95% CI 1.60–3.47), pre-pregnancy overweight (OR, 1.67; 95% CI 1.09–2.56), and obesity (OR, 10.45; 95% CI, 3.91–27.87), nulliparity (OR, 0.58; 95% CI 0.41–0.82), pre-pregnancy diabetes (OR, 5.81; 95% CI 3.24–10.39), pre-pregnancy hypertension (OR, 2.79; 95% CI 1.44–5.41), and cervical incompetence (OR, 5.12; 95% CI 3.08–8.48) are independent risk factors for sPTB in twin pregnancies. The AUC of the training and validation set was 0.71 (95% CI 0.68–0.74) and 0.68 (95% CI 0.64–0.73), respectively. And then we integrated those risk factors to construct the nomogram. Conclusions The nomogram developed for predicting the risk of sPTB in pregnant women with twins demonstrated good performance. The prediction nomogram serves as a practical tool by including all necessary predictors that are readily accessible to practitioners.

In the process of driving, the steering, braking, and driving conditions and different road conditions affect the vibration characteristics of the vehicle in the vertical, roll, and pitch directions. These factors greatly impact the riding comfort of the vehicle. Among them, the uneven distribution of vertical load between the left and right or the front and rear suspension is one of the important factors affecting the performance indicators of the vehicle’s roll angle acceleration and pitch angle acceleration. In order to improve the ride comfort of the vehicle in vertical, roll, and pitch motion, the inerter is introduced in this paper to form a new type of suspension structure with the “spring-damping” base element, inertial suspension. It breaks away from the traditional “spring-damping” base element of the inherent suspension structure. In this paper, the mechatronic inerter is taken as the actual controlled object, and the inertial suspension structure is considered as the controlled model based on the dynamic surface control theory and the pseudo-inverse matrix principle. Thus, the coordinated control of the inertial suspension can be achieved. Under random road input, compared with passive suspension, the ride comfort performance indicators of the vehicle with inertial suspension based on dynamic surface control are significantly improved. Finally, a Hardware-in-the-Loop (HiL) test of the controller based on dynamic surface control is carried out to verify that the performance of the vehicle inertial suspension using the dynamic surface control algorithm had improved in terms of vehicle ride comfort. The error between the experimental results and the simulation results is about 8%, which verifies the real-time performance and effectiveness of the dynamic surface controller in the real controller.

Abstract The present study investigated the composition, abundance, and diversity of gut microbes in full-term and late-preterm infants from a medical center in eastern China. A total of 144 genomes of stool samples were captured for 16S rRNA metagenomic analyses. A high abundance of commensal intestinal bacteria was detected in these samples such as Phocaeicola vulgatus, Escherichia coli, and Faecalibacterium prausnitzii, indicating a relatively consistent diversity of gut microbes in the present full-term infants aged 38–40 weeks. However, late preterm infants (n = 50) with mandatory antimicrobials feeding exhibited lower diversity but a higher composition of opportunistic pathogens such as Enterococcus species. Centralized on the situation, we explored the regulatory effect of Clostridium butyricum as probiotics on these late preterm infants. The consumption of C. butyricum did not restore the composition of gut microbes altered by antimicrobials to normal levels, although several opportunistic pathogens decreased significantly after probiotic therapy including Staphylococcus aureus, Sphingomonas echinoides, and Pseudomonas putida. We also compared the effects of day-fed versus night-fed probiotics. Intriguingly, the nighttime feeding showed a higher proportion of C. butyricum compared with probiotic day-feeding. Finally, fecal metabolome and metabolites were analyzed in late preterm infants with (n = 20) or without probiotic therapy (n = 20). The KEGG enrichment analysis demonstrated that vitamin digestion and absorption, synaptic vesicle cycle, and biotin metabolism were significantly increased in the probiotic-treated group, while MSEA indicated that a series of metabolism were significantly enriched in probiotic-treated infants including glycerolipid, biotin, and lysine, indicating the complex effects of probiotic therapy on glutathione metabolism and nutrients digestion and absorption in late preterm infants. Overall, this study provided metagenomic and metabolomic profile of the gut microbes in full-term newborns and late preterm infants in eastern China. Further studies are needed to support and elucidate the role of probiotic feeding in late preterm infants with mandatory antimicrobial treatment.

Abstract Background Protein purification remains a critical need for biosciences and biotechnology. It frequently requires multiple rounds of chromatographic steps that are expensive and time-consuming. Our lab previously reported a cleavable self-aggregating tag (cSAT) scheme for streamlined protein expression and purification. The tag consists of a self-assembling peptide (SAP) and a controllable self-cleaving intein. The SAP drives the target protein into an active aggregate, then by intein-mediated cleavage, the target protein is released. Here we report a novel cSAT scheme in which the self-assembling peptide is replaced with a salt inducible self-assembling peptide. This allows a target protein to be expressed first in the soluble form, and the addition of salt then drives the target protein into the aggregated form, followed by cleavage and release. Results In this study, we used MpA (MKQLEDKIEELLSKAAMKQLEDKIEELLSK) as a second class of self-assembling peptide in the cSAT scheme. This scheme utilizes low salt concentration to keep the fusion protein soluble, while eliminating insoluble cellular matters by centrifugation. Salt then triggers MpA-mediated self-aggregation of the fusion, removing soluble background host cell proteins. Finally, intein-mediated cleavage releases the target protein into solution. As a proof-of-concept, we successfully purified four proteins and peptides (human growth hormone, 22.1 kDa; LCB3, 7.7 kDa; SpyCatcherΔN-ELP-SpyCatcherΔN, 26.2 kDa; and xylanase, 45.3 kDa) with yields ranging from 12 to 87 mg/L. This was comparable to the classical His-tag method both in yield and purity (72–97%), but without the His-tag. By using a further two-step column purification process that included ion-exchange chromatography and size-exclusion chromatography, the purity was increased to over 99%. Conclusion Our results demonstrate that a salt-inducible self-assembling peptide can serve as a controllable aggregating tag, which might be advantageous in applications where soluble expression of the target protein is preferred. This work also demonstrates the potential and advantages of utilizing salt inducible self-assembling peptides for protein separation.

Abstract Traditional total mesorectal excision (TME) for rectal cancer requires partial resection of Denonvilliers’ fascia (DVF), which leads to injury of pelvic autonomic nerve and postoperative urogenital dysfunction. It is still unclear whether entire preservation of DVF has better urogenital function and comparable oncological outcomes. We conducted a randomized clinical trial to investigate the superiority of DVF preservation over resection (NCT02435758). A total of 262 eligible male patients were randomized to Laparoscopic TME with DVF preservation (L-DVF-P group) or resection procedures (L-DVF-R group), 242 of which completed the study, including 122 cases of L-DVF-P and 120 cases of L-DVF-R. The initial analysis of the primary outcomes of urogenital function has previously been reported. Here, the updated analysis and secondary outcomes including 3-year survival (OS), 3-year disease-free survival (DFS), and recurrence rate between the two groups are reported for the modified intention-to-treat analysis, revealing no significant difference. In conclusion, L-DVF-P reveals better postoperative urogenital function and comparable oncological outcomes for male rectal cancer patients.

Abstract Background Hyperhomocysteinemia (HHcy) has been linked to development of Alzheimer’s disease (AD) neuropathologically characterized by the accumulation of amyloid β (Aβ). Microglia (MG) play a crucial role in uptake of Aβ fibrils, and its dysfunction worsens AD. However, the effect of HHcy on MG Aβ phagocytosis remains unstudied. Methods We isolated MG from the cerebrum of HHcy mice with genetic cystathionine-β-synthase deficiency (Cbs −/− ) and performed bulk RNA-seq. We performed meta-analysis over transcriptomes of Cbs −/− mouse MG, human and mouse AD MG, MG Aβ phagocytosis model, human AD methylome, and GWAS AD genes. Results HHcy and hypomethylation conditions were identified in Cbs −/− mice. Through Cbs −/− MG transcriptome analysis, 353 MG DEGs were identified. Phagosome formation and integrin signaling pathways were found suppressed in Cbs −/− MG. By analyzing MG transcriptomes from 4 AD patient and 7 mouse AD datasets, 409 human and 777 mouse AD MG DEGs were identified, of which 37 were found common in both species. Through further combinatory analysis with transcriptome from MG Aβ phagocytosis model, we identified 130 functional-validated Aβ phagocytic AD MG DEGs (20 in human AD, 110 in mouse AD), which reflected a compensatory activation of Aβ phagocytosis. Interestingly, we identified 14 human Aβ phagocytic AD MG DEGs which represented impaired MG Aβ phagocytosis in human AD. Finally, through a cascade of meta-analysis of transcriptome of AD MG, functional phagocytosis, HHcy MG, and human AD brain methylome dataset, we identified 5 HHcy-suppressed phagocytic AD MG DEGs (Flt1, Calponin 3, Igf1, Cacna2d4, and Celsr) which were reported to regulate MG/MΦ migration and Aβ phagocytosis. Conclusions We established molecular signatures for a compensatory response of Aβ phagocytosis activation in human and mouse AD MG and impaired Aβ phagocytosis in human AD MG. Our discoveries suggested that hypomethylation may modulate HHcy-suppressed MG Aβ phagocytosis in AD.