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Abstract This research uses CFD (computational fluid dynamics) to simulate an axial-flow pump and analyzes its internal flow dissipation. The results show that under different operating conditions, with increasing tip cascade density, the pump head gradually increases. With increasing tip cascade density, the pump efficiency gradually decreases under small discharge conditions, and the high-efficiency zone of the axial-flow pump gradually narrows when the pump is operated under large discharge conditions. Under the design operating conditions, the highest efficiency of the axial-flow pump reaches 86.15%. The total entropy generation of the impeller, guide vane, and outlet pipe decreases and then increases with increasing discharge. Meanwhile, the total entropy generation of the impeller is 3.37 W/K, which is the largest among different over-water flow components, accounting for 47%. The turbulence entropy generation (EGTD) ratios of the impeller, guide vane and outlet pipe are 42%, 59%, and 65% under the design operating conditions, respectively. Finally, the results of numerical simulation are reliable as verified by a model test. The research results have implications for improving the efficiency of axial-flow pumps.

Abstract Autophagy has both protective and pathogenetic effects on injury caused by cerebral ischemia/reperfusion (I/R). Our previous research has indicated that stimulator of interferon genes (STING) could orchestrate microglia polarization following middle cerebral artery occlusion. However, it remains largely unexplored whether STING balances microglial polarization by regulating autophagy in brain I/R injury. Here, STING was observed to show an up-regulation in the microglia from mice subjected to experimental ischemic stroke. Strikingly, the deletion of STING led to the significant skewness of microglia activated by ischemia from a pro- to anti-inflammatory state and substantially alleviated ischemia-induced infarction and neuronal injury. In addition, STING-null mice can restore long-term neurobehavioral function. Then, the crosstalk between neuroinflammation and microglia autophagy was analyzed. The differential activity of autophagy in wild-type and STING-knockout (KO) mice or primary microglia was largely reversed when STING was restored in microglia. Irritating autophagy by rapamycin skewed the anti‑inflammatory state induced by STING-KO to a pro‑inflammatory state in microglia. Furthermore, microtubule-associated protein light-chain-3 (LC3) was identified as the key factor in the STING regulation of autophagy by glutathione-S-transferase (GST) pull-down analysis. Mechanically, STING can directly interact with LC3 through the STING transmembrane domain (1-139aa). Herein, current data determine the pivotal role of autophagy, specifically via LC3 protein, in the regulation of microglial phenotypic transformation by STING. These findings may provide a possible treatment target for delaying the progression of ischemic stroke.

Abstract The nematode Caenorhabditis elegans is widely employed as a model organism to study basic biological mechanisms. However, transgenic C. elegans are generated by manual injection, which remains low-throughput and labor-intensive, limiting the scope of approaches benefitting from large-scale transgenesis. Here, we report a robotic microinjection system, integrating a microfluidic device capable of reliable worm immobilization, transfer, and rotation, for high-speed injection of C. elegans. The robotic system provides an injection speed 2-3 times faster than that of experts with 7–22 years of experience while maintaining comparable injection quality and only limited trials needed by users to become proficient. We further employ our system in a large-scale reverse genetic screen using multiplexed alternative splicing reporters, and find that the TDP-1 RNA-binding protein regulates alternative splicing of zoo-1 mRNA, which encodes variants of the zonula occludens tight junction proteins. With its high speed, high accuracy, and high efficiency in worm injection, this robotic system shows great potential for high-throughput transgenic studies of C. elegans.

Abstract Factor XII (FXII) is the zymogen of the plasma protease FXIIa that activates the intrinsic coagulation pathway and the kallikrein kinin-system. The role of FXII in inflammation has been obscure. Here, we report a single-domain antibody (nanobody, Nb) fused to the Fc region of a human immunoglobulin (Nb-Fc) that recognizes FXII in a conformation-dependent manner and interferes with FXIIa formation. Nb-Fc treatment inhibited arterial thrombosis in male mice without affecting hemostasis. In a mouse model of extracorporeal membrane oxygenation (ECMO), FXII inhibition or knockout reduced thrombus deposition on oxygenator membranes and systemic microvascular thrombi. ECMO increased circulating levels of D-dimer, alkaline phosphatase, creatinine and TNF-α and triggered microvascular neutrophil adherence, platelet aggregation and their interaction, which were substantially attenuated by FXII blockade. Both Nb-Fc treatment and FXII knockout markedly ameliorated immune complex-induced local vasculitis and anti-neutrophil cytoplasmic antibody-induced systemic vasculitis, consistent with selectively suppressed neutrophil migration. In human blood microfluidic analysis, Nb-Fc treatment prevented collagen-induced fibrin deposition and neutrophil adhesion/activation. Thus, FXII is an important mediator of inflammatory responses in vasculitis and ECMO, and Nb-Fc provides a promising approach to alleviate thrombo-inflammatory disorders.

Abstract The kidney is vulnerable to ischemia and reperfusion (I/R) injury that can be fatal after major surgery. Currently, there are no effective treatments for I/R-induced kidney injury. Trimethylamine N-oxide (TMAO) is a gut-derived metabolite linked to many diseases, but its role in I/R-induced kidney injury remains unclear. Here, our clinical data reveals an association between preoperative systemic TMAO levels and postoperative kidney injury in patients after post-cardiopulmonary bypass surgery. By genetic deletion of TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) and dietary supplementation of choline to modulate TMAO levels, we found that TMAO aggravated acute kidney injury through the triggering of endoplasmic reticulum (ER) stress and worsened subsequent renal fibrosis through TGFβ/Smad signaling activation. Together, our study underscores the negative role of TMAO in I/R-induced kidney injury and highlights the therapeutic potential through the modulation of TMAO levels by targeting FMO3, thereby mitigating acute kidney injury and preventing subsequent renal fibrosis.

Abstract Cranial sutures separate neighboring skull bones and are sites of bone growth. A key question is how osteogenic activity is controlled to promote bone growth while preventing aberrant bone fusions during skull expansion. Using single-cell transcriptomics, lineage tracing, and mutant analysis in zebrafish, we uncover key developmental transitions regulating bone formation at sutures during skull expansion. In particular, we identify a subpopulation of mesenchyme cells in the mid-suture region that upregulate a suite of genes including BMP antagonists (e.g. grem1a) and pro-angiogenic factors. Lineage tracing with grem1a:nlsEOS reveals that this mid-suture subpopulation is largely non-osteogenic. Moreover, combinatorial mutation of BMP antagonists enriched in this mid-suture subpopulation results in increased BMP signaling in the suture, misregulated bone formation, and abnormal suture morphology. These data reveal establishment of a non-osteogenic mesenchyme population in the mid-suture region that restricts bone formation through local BMP antagonism, thus ensuring proper suture morphology.

Abstract N-Myc is a key driver of neuroblastoma and neuroendocrine prostate cancer (NEPC). One potential way to circumvent the challenge of undruggable N-Myc is to target the protein homeostasis (proteostasis) system that maintains N-Myc levels. Here, we identify heat shock protein 70 (HSP70) as a top partner of N-Myc, which binds a conserved “SELILKR” motif and prevents the access of E3 ubiquitin ligase, STIP1 homology and U-box containing protein 1 (STUB1), possibly through steric hindrance. When HSP70’s dwell time on N-Myc is increased by treatment with the HSP70 allosteric inhibitor, STUB1 is in close proximity with N-Myc and becomes functional to promote N-Myc ubiquitination on the K416 and K419 sites and forms polyubiquitination chains linked by the K11 and K63 sites. Notably, HSP70 inhibition significantly suppressed NEPC tumor growth, increased the efficacy of aurora kinase A (AURKA) inhibitors, and limited the expression of neuroendocrine-related pathways.

Abstract Objectives A higher reperfusion grade after endovascular thrombectomy (EVT) is associated with a good prognosis. However, the effect of the number of retrievals has not yet been investigated in vertebrobasilar occlusion (VBAO). Therefore, the aim of this study was to investigate whether to continue retrieval after early modified thrombolysis in cerebral infarction (mTICI) 2b to achieve a better reperfusion grade. Methods We retrospectively analyzed the data of patients who underwent EVT caused by VBAO in a multicenter registry dataset. Patients who underwent successful reperfusion were included (mTICI 2b/3). Regression models were used to analyze the correlation of different reperfusion grades stratified by the number of retrieval attempts with clinical prognosis and hemorrhage transition. Results We included 432 patients: 34.5% (n = 149) had a final mTICI score of 2b and 65.5% (n = 283) had a final mTICI score of 3. Patients who obtained a mTICI of 3 after the first pass had significantly increased odds of having a good prognosis. As the number of passes increases, the chances of obtaining a good prognosis decreases. After three or more passes, the odds of achieving functional independence and favorable outcomes were comparable to those of the first mTICI 2b, regardless of the 90‐day (OR 1.132 95% CI 0.367–3.487 p = 0.829; OR 1.070 95% CI 0.375–3.047 p = 0.900) or 1‐year follow‐up (OR 1.217 95% CI 0.407–3.637 p = 0.725; OR 1.068 95% CI 0.359–3.173 p = 0.906). Interpretation Within two retrieval attempts, mTICI 3 was better than the first retrieval to mTICI 2b. After early mTICI 2b, each retrieval should be undertaken with caution to pursue a higher reperfusion grade.

Abstract Pregnane X receptor (PXR) has been reported to regulate glycolipid metabolism. The dysfunction of intestinal barrier contributes to metabolic disorders. However, the role of intestinal PXR in metabolic diseases remains largely unknown. Here, we show that activation of PXR by tributyl citrate (TBC), an intestinal-selective PXR agonist, improves high fat diet (HFD)-induced obesity. The metabolic benefit of intestinal PXR activation is associated with upregulation of β-1,3 galactosyltransferase 5 (B3galt5). Our results reveal that B3galt5 mainly expresses in the intestine and is a direct PXR transcriptional target. B3galt5 knockout exacerbates HFD-induced obesity, insulin resistance and inflammation. Mechanistically, B3galt5 is essential to maintain the integrity of intestinal mucus barrier. B3galt5 ablation impairs the O-glycosylation of mucin2, destabilizes the mucus layer, and increases intestinal permeability. Furthermore, B3galt5 deficiency abolishes the beneficial effect of intestinal PXR activation on metabolic disorders. Our results suggest the intestinal-selective PXR activation regulates B3galt5 expression and maintains metabolic homeostasis, making it a potential therapeutic strategy in obesity.

Abstract T-cell receptor (TCR) detection can examine the extent of T-cell immune responses. Therefore, the article analyzed characteristic data of glioma obtained by DNA-based TCR high-throughput sequencing, to predict the disease with fewer biomarkers and higher accuracy. We downloaded data online and obtained six TCR-related diversity indices to establish a multidimensional classification system. By comparing actual presence of the 602 correlated sequences, we obtained two-dimensional and multidimensional datasets. Multiple classification methods were utilized for both datasets with the classification accuracy of multidimensional data slightly less to two-dimensional datasets. This study reduced the TCR β sequences through feature selection methods like RFECV (Recursive Feature Elimination with Cross-Validation). Consequently, using only the presence of these three sequences, the classification AUC value of 96.67% can be achieved. The combination of the three correlated TCR clones obtained at a source data threshold of 0.1 is: CASSLGGNTEAFF_TRBV12_TRBJ1-1, CASSYSDTGELFF_TRBV6_TRBJ2-2, and CASSLTGNTEAFF_TRBV12_TRBJ1-1. At 0.001, the combination is: CASSLGETQYF_TRBV12_TRBJ2-5, CASSLGGNQPQHF_TRBV12_TRBJ1-5, and CASSLSGNTIYF_TRBV12_TRBJ1-3. This method can serve as a potential diagnostic and therapeutic tool, facilitating diagnosis and treatment of glioma and other cancers.

Urban areas are major sources of carbon emissions, making it crucial to understand their emission characteristics for effective carbon reduction and sustainable development. Using carbon emission data from mainland China (2001–2021), we analyzed the spatio-temporal dynamics and future trends of city-level emissions and explored influencing factors using machine learning methods. Results indicate significant fluctuations in carbon emissions, with over 40 % of mainland Chinese cities experiencing a doubling in total emissions. Geospatially, cities in South Coast (SC), East Coast (EC), Northeast (NE), and NorthCoast (NC) show stronger intensity and increasing trends in carbon emissions compared to other regions, with over 80 % of cities in these regions experiencing high or higher increases. Additionally, a continued rise in carbon emissions was detected in most Chinese cities, with an average Hurst index of 0.64, indicating persistent trends. Using the XGBoost method, factors such as population density, built-up area, urban green coverage rate, and GDP were found to strongly correlate with urban carbon emissions, exhibiting significant spatial heterogeneity. This research uncovers the characteristics and influencing factors of urban-scale carbon emissions, offering valuable insights for policymakers to tailor carbon reduction strategies to the specific needs and conditions of various urban areas.

Eliciting anti-tumor immune responses and improving the tumor microenvironment crucial for boosting the effectiveness of anti-PD-1 immunotherapy. Tumor-associated macrophages (TAMs), the primary types of immune cells infiltrating tumors, play a critical role in the formation of an immunosuppressive microenvironment. In this study, we constructed a novel Evans Blue (EB)-based in vivo self-assembled nanocarrier system, mUNO-EB-ICG-Fc@Alb nanoparticles (designated as MA NPs), for targeted imaging and clearance of M2-TAMs to elicit antitumor immunotherapy of PD-1 inhibitor. In vitro experiments demonstrated the specific fluorescence imaging and killing effect of MA NPs on M2-TAMs. In vivo experiments shown that MA NPs-induced chemodynamic therapy (CDT) successfully reversed the tumor immunosuppressive microenvironment (ITM), promoted intratumoral infiltration of T lymphocytes, and ultimately enhancing the anti-tumor immunotherapy effect of PD-1 inhibitors. This study might provide good inspiration for improving the therapeutic efficacy of cancer immunotherapy.

Amyotrophic lateral sclerosis as a fatal neurodegenerative disease currently lacks effective therapeutic agents. Thus, finding new therapeutic targets to drive disease treatment is necessary. In this study, we utilized brain and plasma proteins as genetic instruments obtained from genome-wide association studies to conduct a Mendelian randomization analysis to identify potential drug targets for amyotrophic lateral sclerosis. Additionally, we validated our results externally using other datasets. We also used Bayesian co-localization analysis and phenotype scanning. Furthermore, we constructed a protein-protein interaction network to elucidate potential correlations between the identified proteins and existing targets. Mendelian randomization analysis indicated that elevated levels of ANO5 (OR = 1.30; 95 % CI, 1.14–1.49; P = 1.52E-04), SCFD1 (OR = 3.82; 95 % CI, 2.39–6.10; P = 2.19E-08), and SIGLEC9 (OR = 1.05; 95% CI, 1.03–1.07; P = 4.71E-05) are associated with an increased risk of amyotrophic lateral sclerosis, with external validation supporting these findings. Co-localization analysis confirmed that ANO5, SCFD1, and SIGLEC9 (coloc.abf-PPH4 = 0.848, 0.984, and 0.945, respectively) shared the same variant with amyotrophic lateral sclerosis, further substantiating potential role of these proteins as a therapeutic target. There are interactive relationships between the potential proteins and existing targets of amyotrophic lateral sclerosis. Our findings suggested that elevated levels of ANO5, SCFD1, and SIGLEC9 are connected with an increased risk of amyotrophic lateral sclerosis and might be promising therapeutic targets. However, further exploration is necessary to fully understand the underlying mechanisms involved.

Non-invasive neuroimaging has revealed specific network-based resting-state dynamics in the human brain, yet the underlying neurophysiological mechanism remains unclear. We employed intracranial electroencephalography to characterize local field potentials within the default mode network (DMN), frontoparietal network (FPN), and salience network (SN) in 42 participants. We identified stronger within-network phase coherence at low frequencies (θ and α band) within the DMN, and at high frequencies (γ band) within the FPN. Hidden Markov modeling indicated that the DMN exhibited preferential low frequency phase coupling. Phase-amplitude coupling (PAC) analysis revealed that the low-frequency phase in the DMN modulated the high-frequency amplitude envelopes of the FPN, suggesting frequency-dependent characterizations of intrinsic brain networks at rest. These findings provide intracranial electrophysiological evidence in support of the network model for intrinsic organization of human brain and shed light on the way brain networks communicate at rest.

Abstract Nanoelectromechanical system accelerometers have the potential to be utilized in next-generation consumer electronics, inertial navigation, and seismology due to their low cost, small size, and low power consumption. There is an urgent need to develop resonant accelerometer with high sensitivity, precision and robustness. Here, a zinc oxide resonant nano-accelerometer with high sensitivity has been designed and prototyped using zinc oxide nanowires. Within a device two nanowires were symmetrically placed close to a notched flexure to evaluate acceleration based on differential resonant frequencies. Additionally, microleverages were integrated in the accelerometer to enhance its sensitivity by amplifying the inertial force. High performance of the accelerometer has been demonstrated by the measured absolute sensitivity (16.818 kHz/g), bias instability (13.13 μg at 1.2 s integration time) and bandwidth (from 4.78 to 29.64 kHz), respectively. These results suggest that zinc oxide nanowires could be a candidate to develop future nanoelectromechanical resonant accelerometer potentially used for inertial navigation, tilt measurement, and geophysical measurements.

Abstract Biopolymers such as nucleic acids and proteins exhibit dynamic backbone folding, wherein site-specific intramolecular interactions determine overall structure. Proteins then hierarchically assemble into supramolecular polymers such as microtubules, that are robust yet dynamic, constantly growing or shortening to adjust to cellular needs. The combination of dynamic, energy-driven folding and growth with structural stiffness and length control is difficult to achieve in synthetic polymer self-assembly. Here we show that highly charged, monodisperse DNA-oligomers assemble via seeded growth into length-controlled supramolecular fibers during heating; when the temperature is lowered, these metastable fibers slowly disassemble. Furthermore, the specific molecular structures of oligomers that promote fiber formation contradict the typical theory of block copolymer self-assembly. Efficient curling and packing of the oligomers – or ‘curlamers’ – determine morphology, rather than hydrophobic to hydrophilic ratio. Addition of a small molecule stabilises the DNA fibers, enabling temporal control of polymer lifetime and underscoring their potential use in nucleic-acid delivery, stimuli-responsive biomaterials, and soft robotics.

Abstract Nanopore direct RNA sequencing (DRS) has emerged as a powerful tool for RNA modification identification. However, concurrently detecting multiple types of modifications in a single DRS sample remains a challenge. Here, we develop TandemMod, a transferable deep learning framework capable of detecting multiple types of RNA modifications in single DRS data. To train high-performance TandemMod models, we generate in vitro epitranscriptome datasets from cDNA libraries, containing thousands of transcripts labeled with various types of RNA modifications. We validate the performance of TandemMod on both in vitro transcripts and in vivo human cell lines, confirming its high accuracy for profiling m6A and m5C modification sites. Furthermore, we perform transfer learning for identifying other modifications such as m7G, Ψ, and inosine, significantly reducing training data size and running time without compromising performance. Finally, we apply TandemMod to identify 3 types of RNA modifications in rice grown in different environments, demonstrating its applicability across species and conditions. In summary, we provide a resource with ground-truth labels that can serve as benchmark datasets for nanopore-based modification identification methods, and TandemMod for identifying diverse RNA modifications using a single DRS sample.

Abstract Background Oral mucosal diseases are similar to the surrounding normal tissues, i.e., their many non-salient features, which poses a challenge for accurate segmentation lesions. Additionally, high-precision large models generate too many parameters, which puts pressure on storage and makes it difficult to deploy on portable devices. Methods To address these issues, we design a non-salient target segmentation model (NTSM) to improve segmentation performance while reducing the number of parameters. The NTSM includes a difference association (DA) module and multiple feature hierarchy pyramid attention (FHPA) modules. The DA module enhances feature differences at different levels to learn local context information and extend the segmentation mask to potentially similar areas. It also learns logical semantic relationship information through different receptive fields to determine the actual lesions and further elevates the segmentation performance of non-salient lesions. The FHPA module extracts pathological information from different views by performing the hadamard product attention (HPA) operation on input features, which reduces the number of parameters. Results The experimental results on the oral mucosal diseases (OMD) dataset and international skin imaging collaboration (ISIC) dataset demonstrate that our model outperforms existing state-of-the-art methods. Compared with the nnU-Net backbone, our model has 43.20% fewer parameters while still achieving a 3.14% increase in the Dice score. Conclusions Our model has high segmentation accuracy on non-salient areas of oral mucosal diseases and can effectively reduce resource consumption.

The stratification of soil in land surface models is a crucial aspect that requires careful consideration.Typically， the surface layer of soil， which is significantly influenced by the atmosphere-ground interface， should be subdivided.Furthermore， as the soil goes deeper， the thickness of the soil layers can be increased accordingly.Previous studies have demonstrated that the thickness of soil below the root zone has varying effects on simulation results under different weather and climate integration conditions.Therefore， the soil stratification mode should be adjusted based on the research requirements.However， the optimal soil stratification mode in land surface models remains uncertain.This paper aims to explore the sensitivity of different soil vertical discretization schemes to the simulation of soil hydrothermal properties， surface radiation flux， sensible heat flux， and latent heat flux using the BCC_AVIM land surface model.The original scheme of soil stratification in the BCC_AVIM land model consists of 10 layers.In this study， the node depth， soil layer thickness， and interface depth of soil layers were interpolated from the original 10 layers to 20 layers， which is referred to as scheme 1.Additionally， the vertical soil discretization scheme in CLM5.0 was used as a reference and improved for the BCC_AVIM land model.Consequently， the original soil layer was increased from 10 to 20， which is referred as scheme 2.After comparing the results of the improved schemes 1 and 2 with those of the original scheme， it is evident that： （1） The simulation results of schemes 1 and 2 are more consistent with the measured data， and the simulation accuracy of the numerical value and changing trend of soil temperature in each layer is improved.Scheme 1 performs better in simulating shallow soil temperature.（2） The three schemes have good simulation effects on shallow soil moisture， but relatively poor simulation effects on deep soil moisture.The simulation of the variation trend and numerical value of soil moisture curve in each layer in Scheme 1 is closer to the measured data.（3） Scheme 1 is more reasonable in determining whether each layer of soil freezes or melts， which is closer to the measured data.Overall， Scheme 1 has the best simulation effect.Therefore， it can be concluded that the simulation effect of the first scheme is improved compared to the original scheme， indicating that denser and more detailed soil stratification under the same soil depth is beneficial in improving the simulation ability of the model for soil water and heat transport.Additionally， the simulation effect of scheme 1 is generally better than that of scheme 2， indicating that the shallow middle layer with more dense soil stratification under the same soil level has a positive impact on improving the simulation ability of the model on soil water-heat transport.

Abstract Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

Sulfation is a crucial and prevalent conjugation reaction involved in cellular processes and mammalian physiology. 3′-Phosphoadenosine 5′-phosphosulfate (PAPS) synthase 2 (PAPSS2) is the primary enzyme to generate the universal sulfonate donor PAPS. The involvement of PAPSS2-mediated sulfation in adenomatous polyposis coli (APC) mutation-promoted colonic carcinogenesis has not been reported. Here, we showed that the expression of PAPSS2 was decreased in human colon tumors along with cancer stages, and the lower expression of PAPSS2 was correlated with poor prognosis in advanced colon cancer. Gut epithelial-specific heterozygous Apc deficient and Papss2-knockout (ApcΔgut-HetPapss2Δgut) mice were created, and the phenotypes were compared to the spontaneous intestinal tumorigenesis of ApcΔgut-Het mice. ApcΔgut-HetPapss2Δgut mice were more sensitive to gut tumorigenesis, which was mechanistically accounted for by the activation of Wnt/β-catenin signaling pathway due to the suppression of chondroitin sulfation and inhibition of the farnesoid X receptor (FXR)-transducin-like enhancer of split 3 (TLE3) gene regulatory axis. Chondroitin sulfate supplementation in ApcΔgut-HetPapss2Δgut mice alleviated intestinal tumorigenesis. In summary, we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids–FXR–TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/β-catenin signaling. Chondroitin sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis.

Abstract Purpose Gasless robot-assisted transaxillary hemithyroidectomy (RATH) is regarded as an alternative surgical option for thyroid operations. However, the associated steep learning curve is a clinical concern. This study evaluated the learning curve of RATH for surgeons without experience of endoscopic surgery and the early surgical outcomes of RATH. Methods We conducted a retrospective study of patients who underwent gasless RATH and conventional hemithyroidectomy (CH) at Sun Yat-sen University Cancer Center, Guangzhou, China, from June 2021 to August 2022. The learning curve and early surgical outcomes of gasless RATH were evaluated. And the early surgical outcomes of gasless RATH were compared to CH. Results In total, 105 patients who underwent gasless RATH and 104 patients who underwent CH were matched and assessed. The cumulative sum techniques (CUSUM) analysis showed that the peak point of gasless RATH operative time occurred at the 31st case. No clear single peak was identified in the CUSUM plot for drainage amount and blood loss. No significant difference in perioperative complications was observed between these two groups. Moreover, the number of postoperative patients who got sense of thyroid area traction were fewer in the gasless RATH group (n = 11, 10.5%) than in the CH group (n = 32, 30.8%). Conclusion Gasless RATH can be considered as an alternative approach to the conventional open procedure, as it is an easy remote access technique, with shorter learning curves and certain advantage such as less sense of thyroid area traction.

AbstractOur previous study found that Cullin 4B (CUL4B) inhibited rheumatoid arthritis (RA) pathology through glycogen synthase kinase-3beta (GSK3β)/canonical Wnt signalling pathway. In this work, pre-experiment and bioinformatics analysis suggested that circ_0011058 may lead to the up-regulation of CUL4B expression by inhibiting miR-335-5p. Therefore, we studied whether circ_0011058 can promote the expression of CUL4B through sponging the miR-335-5p and further promote the pathological development of RA. Bioinformatics prediction, real-time quantitative PCR (RT-qPCR), western blot (WB), double luciferase reporter gene and other relevant methods were used to study the inhibition of circ_0011058 on RA pathology and its molecular mechanism. Results showed that the expression of circ_0011058 was significantly increased in adjuvant arthritis (AA) rats and RA fibroblast-like synoviocytes (FLS). The knockout of circ_0011058 inhibited the proliferation of AA FLS and RA FLS, decreased the levels of interleukin-1 beta (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), and inhibited the expression of matrix metalloproteinase 3 (MMP3), fibronectin, which showed that circ_0011058 had a strong role in promoting RA pathology. Furthermore, miR-335-5p expression was reduced in AA rats and RA FLS. The highly expressed circ_0011058 directly sponged the miR-335-5p, which led to the increase of CUL4B expression and promoted the activation of the GSK3β/canonical signalling pathway. Finally, we confirmed that miR-335-5p mediated the roles of circ_0011058 in promoting RA pathological development, which showed that the circ_0011058/miR-335-5p/CUL4B signal axis was involved in RA pathology. This work was of great significance for clarifying the roles of circ_0011058 in RA pathology, and further work was needed to establish whether circ_0011058 was a potential therapeutic target or diagnostic marker for RA.

Developing mathematical models for dynamic systems presents challenges in selecting state variables, crucial for minimizing computational operations during filter implementation. The paper addresses active identification of dynamic systems amid noise and measurement errors, using the Fisher information matrix. Additionally, it introduces Cholesky decomposition for generating correlated noise, demonstrating its applicability in practical problem-solving.

The removal of lignin from natural cellulose fibers is a crucial step in preparing high-performance materials, such as compressed high-toughness composites. This process can eliminate non-cellulosic impurities, create abundant compressible pores, and expose a greater number of active functional groups. In this study, biomass waste windmill palm fiber was used as the raw material to prepare holocellulose fibers through various chemical treatments. The structure, chemical composition, Fourier transform infrared spectroscopy analysis, X-ray diffraction analysis, thermal properties, and mechanical properties, particularly fatigue performance, were studied. The sodium chlorite treated fiber had the highest crystallinity index (61.3%) and the most complete appearance structure. The sodium sulfite treated fiber had the highest tensile strength (227.34 ± 52.27) MPa. Hydroxide peroxide treatment removed most of the lignin and hemicellulose, increasing the cellulose content to 68.83% ± 0.65%. However, all the chemical treatments decreased the thermal property of the fibers.

An all-optical format conversion (AOFC) scheme for the input 30 Gbit/s rectangular 8-ary quadrature amplitude modulation (8QAM) signal is proposed and numerically investigated based on phase-sensitive amplification (PSA) and nonlinear Mach-Zehnder interferometer (MZI). Firstly, the input rectangular 8QAM signal is orthogonal decomposed into the in-phase and quadrature components based on PSA, respectively. The in-phase component is the 4-ary amplitude and phase shift keying (4APSK) signal and the quadrature component is the binary phase shift keying (BPSK) signal. Secondly, the converted 4APSK signal is transmitted into one piece of highly nonlinear fiber (HNLF) to obtain the phase-distorted two-amplitude and two-phase (2A-2P) signal based on the self-phase modulation (SPM) effect. After adjusting the power of the 2A-2P signal, it is injected into one nonlinear MZI to eliminate the amplitude difference of the inner and the outer rings of the 2A-2P signal. The 2A-2P signal can be converted into the regular quadrature phase shift keying (QPSK) signal by the nonlinear MZI with phase preservation. Thirdly, the converted BPSK and QPSK signals are coherently superposed in one 3-dB optical coupler (OC) to get the aggregated rectangular 8QAM signal and other types of 8QAM signals. The proposed scheme can also be extended to realize the AOFC from the 16-ary quadrature amplitude modulation (16QAM) signal to two QPSK signals. The constellation diagrams, amplitude and phase histograms, error vector magnitude (EVM) and bit error rate (BER) of the relevant optical signals are measured to evaluate the system performance. The proposed scheme can be equipped with the optical gateway to enable all-optical interconnection of optical networks with different modulation formats.

Abstract Background Hepatic inflammation is the major risk factor of hepatocellular carcinoma (HCC). However, the underlying mechanism by which hepatic inflammation progresses to HCC is poorly understood. This study was designed to investigate the role of ETS translocation variant 4 (ETV4) in linking hepatic inflammation to HCC. Methods Quantitative real‐time PCR and immunoblotting were used to detect the expression of ETV4 in HCC tissues and cell lines. RNA sequencing and luciferase reporter assays were performed to identify the target genes of ETV4. Hepatocyte‐specific ETV4‐knockout (ETV4fl/fl, alb‐cre) and transgenic (ETV4Hep‐TG) mice and diethylnitrosamine‐carbon tetrachloride (DEN‐CCL4) treatment experiments were applied to investigate the function of ETV4 in vivo. The Cancer Genome Atlas (TCGA) database mining and pathological analysis were carried out to determine the correlation of ETV4 with tumor necrosis factor‐alpha (TNF‐α) and mitogen‐activated protein kinase 11 (MAPK11). Results We revealed that ETV4 was highly expressed in HCC. High levels of ETV4 predicted a poor survival rate of HCC patients. Then we identified ETV4 as a transcription activator of TNF‐α and MAPK11. ETV4 was positively correlated with TNF‐α and MAPK11 in HCC patients. As expected, an increase in hepatic TNF‐α secretion and macrophage accumulation were observed in the livers of ETV4Hep‐TG mice. The protein levels of TNF‐α, MAPK11, and CD68 were significantly higher in the livers of ETV4Hep‐TG mice compared with wild type mice but lower in ETV4fl/fl, alb‐cre mice compared with ETV4fl/fl mice as treated with DEN‐CCL4, indicating that ETV4 functioned as a driver of TNF‐α/MAPK11 expression and macrophage accumulation during hepatic inflammation. Hepatocyte‐specific knockout of ETV4 significantly prevented development of DEN‐CCL4‐induced HCC, while transgenic expression of ETV4 promoted growth of HCC. Conclusions ETV4 promoted hepatic inflammation and HCC by activating transcription of TNF‐α and MAPK11. Both the ETV4/TNF‐α and ETV4/MAPK11 axes represented two potential therapeutic targets for highly associated hepatic inflammation and HCC. ETV4+TNF‐α were potential prognostic markers for HCC patients.

ObjectiveThis retrospective study analyzed the efficacy of PD-1 inhibitors combined with albumin-bound paclitaxel and cisplatin (TP regimen) in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma (RMHSCC/RMLSCC).MethodsPatients diagnosed and treated at the Sun Yat-sen University Cancer Center from August 1, 2020, to August 15, 2023, with histologically confirmed RMHSCC/RMLSCC were included. All patients received PD-1 inhibitors combined with albumin-bound paclitaxel (260mg/m2) and cisplatin (60mg/m2) for 3–4 cycles. The primary endpoints were overall survival (OS) and progression-free survival (PFS).ResultsA total of 50 patients with RMHSCC/RMLSCC who received TP+PD-1 inhibitor therapy were included, with an objective response rate (ORR) of 56.0% (28/50). The 1-year and 2-year OS rates were 80.2% (95% CI: 69.3%-92.9%) and 68.6% (95% CI: 52.6%-89.5%), respectively, while the 1-year and 2-year PFS rates were 44.7% (95% CI: 31.9%-62.5%) and 26.0% (95% CI: 12.6%-53.4%), respectively. Treatment-related adverse events mainly included rash, myelosuppression, gastrointestinal reactions, and hypothyroidism.ConclusionIn the treatment of RMHSCC/RMLSCC with TP + PD-1 inhibitors, survival rates of patients can be improved while ensuring the safety of the treatment regimen.

IntroductionInsomnia, a common clinical disorder, significantly impacts the physical and mental well-being of patients. Currently, available hypnotic medications are unsatisfactory due to adverse reactions and dependency, necessitating the identification of new drug targets for the treatment of insomnia.MethodsIn this study, we utilized 734 plasma proteins as genetic instruments obtained from genome-wide association studies to conduct a Mendelian randomization analysis, with insomnia as the outcome variable, to identify potential drug targets for insomnia. Additionally, we validated our results externally using other datasets. Sensitivity analyses entailed reverse Mendelian randomization analysis, Bayesian co-localization analysis, and phenotype scanning. Furthermore, we constructed a protein-protein interaction network to elucidate potential correlations between the identified proteins and existing targets.ResultsMendelian randomization analysis indicated that elevated levels of TGFBI (OR = 1.01; 95% CI, 1.01–1.02) and PAM ((OR = 1.01; 95% CI, 1.01–1.02) in plasma are associated with an increased risk of insomnia, with external validation supporting these findings. Moreover, there was no evidence of reverse causality for these two proteins. Co-localization analysis confirmed that PAM (coloc.abf-PPH4 = 0.823) shared the same variant with insomnia, further substantiating its potential role as a therapeutic target. There are interactive relationships between the potential proteins and existing targets of insomnia.ConclusionOverall, our findings suggested that elevated plasma levels of TGFBI and PAM are connected with an increased risk of insomnia and might be promising therapeutic targets, particularly PAM. However, further exploration is necessary to fully understand the underlying mechanisms involved.

Exposure to environmental endocrine disruptors (EEDs) has become a global health concern, and EEDs are known to be potent inducers of constitutive androstane receptor (CAR). 1,4-bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP, hereafter abbreviated as TC), a specific ligand for CAR, has been considered as a potential EED. Here, we analyzed the effect of TC exposure to female mice on the histological morphology of their alveoli in the basic unit of lactation. We quantified differences in the milk metabolome of the control and TC-exposed group while assessing the correlations between metabolites and neonatal growth. Mammary histological results showed that TC exposure inhibited alveolar development. Based on the milk metabolomic data, we identified a total of 1505 differential metabolites in both the positive and negative ion mode, which indicated that TC exposure affected milk composition. As expected, the differential metabolites were significantly enriched in the drug metabolism pathway. Further analyses revealed that differential metabolites were significantly enriched in multiple lipid metabolic pathways, such as fatty acid biosynthesis, suggesting that most differential metabolites were concentrated in lipids. Simultaneously, a quantitative analysis showed that TC exposure led to a decrease in the relative abundance of total milk lipids, affecting the proportion of some lipid subclasses. Notably, a portion of lipid metabolites were associated with neonatal growth. Taken together, these findings suggest that TC exposure may affect milk lipidomes, resulting in the inability of mothers to provide adequate nutrients, ultimately affecting the growth and health of their offspring.

Abstract Background Ovarian cancer (OC) causes the highest rates of mortality among women’s genital tract malignancies. Micro-ribonucleic acid (miRNA), the most abundant long noncoding RNAs transmitted by exosomes, has been revealed to be a potential marker for OC since 2008. In this study, we aimed to determine the possible roles of miRNAs derived from exosomes in the early diagnosis of OC through miRNA microarray, besides, exploring the underlying mechanisms of miRNAs in the OC progression. Methods We isolated exosomes from high invasive OC cell line HO8910PM and its parent cell line HO8910 using transmission electron microscopy and western blot, and performed miRNA microarray to identify the exosome-transmitted miRNA from the two cell lines, respectively. The expression profile was obtained by quantitative analysis, and then the differentially expressed individuals were screened. miRNA-30a-5p, a stable miRNA in both cells of our sequencing data was set for further study. MiR-30a-5p mimics, inhibitor and their corresponding negative controls were applied in OC cells. Then the cell proliferation, migration, and invasion of different groups were analyzed via cell counting-kit 8 (CCK8), wound healing, and Transwell analyses. Besides, ZBE2 and LDH2 expressions were detected by qRT-PCR. Results Combined with the data report of miRNA microarray technology, we set miR-30a-5p as our target miRNA to analyze its molecular function in regulating proliferation, migration, and invasion in OC cells. Our results showed that the miR-30a-5p overexpression could significantly enhance the capability of proliferation, migration, and invasion of HO8910 and HO8910PM cells, whereas the miR-30a-5p inhibition showed the opposite tendency (all P

Considering the important influence of freeze-thaw processes on land-air interactions， this paper couples an improved freeze-thaw parameterization scheme into the BCC_CSM2_MR model and conducts a one-year simulation experiment， dividing the simulation period into four stages： beginning of freezing， complete freezing， beginning of ablation and complete ablation according to the annual change of soil layer， and analyzing the soil temperature， soil temperature， near-surface wind field on the plateau and the meteorological elements of soil temperature， soil temperature， near-surface wind field and precipitation were analyzed.The results show that the new freeze-thaw scheme has good improvements for both shallow and deep soil temperatures， especially in the central part of the plateau.The improvement of the optimized freeze-thaw parameterization scheme for soil moisture is significant， and the root mean square error and bias of the new scheme are significantly reduced across the Tibetan Plateau in all four freeze-thaw periods， mainly in the central part of the plateau.The wind speed deviation in the northern and central parts of the plateau is reduced during the freezing and thawing phases， which is closer to the comparison data.The correlation coefficients have been improved.The results of the study show that the improved soil freeze-thaw parameterization scheme has a corresponding improvement over the original scheme in the BCC_CSM， and has a positive impact on the simulation of the climate and major circulation systems in China.

Background and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. Methods This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. Results Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). Conclusion In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.

Abstract Polymyxin resistance is conferred by MCR‐1 (mobile colistin resistance 1)‐induced lipopolysaccharide (LPS) modification of G− bacteria. However, the peptide MSI‐1 exerts potent antimicrobial activity against mcr‐1‐carrying bacteria. To further investigate the potential role of MCR‐1 in improving bacterial virulence and facilitating immune evasion, and the immunomodulatory effect of peptide MSI‐1, we first explored outer membrane vesicle (OMV) alterations of mcr‐1‐carrying bacteria in the presence and absence of sub‐MIC MSI‐1, and host immune activation during bacterial infection and OMV stimulation. Our results demonstrated that LPS remodelling induced by MCR‐1 negatively affected OMV formation and protein cargo by E. coli. In addition, MCR‐1 diminished LPS‐stimulated pyroptosis but facilitated mitochondrial dysfunction, further aggravating apoptosis in macrophages induced by OMVs of E. coli. Similarly, TLR4‐mediated NF‐κB activation was markedly alleviated once LPS was modified by MCR‐1. However, peptide MSI‐1 at the sub‐MIC level inhibited the expression of MCR‐1, further partly rescuing OMV alteration and attenuation of immune responses in the presence of MCR‐1 during both infection and OMV stimulation, which can be exploited for anti‐infective therapy.

Defect-engineering accelerates the conduction of lithium ions in the cathode materials of lithium-ion batteries. However, the effects of defect-engineering on ion conduction and its mechanisms in humid environments remain unclear in the academic discourse. Here, we report on the effect of vacancy defects on the electronic properties of and Li-ion diffusion in a LiFePO4 material in humid environments. The research findings indicate that vacancy defects reduce the lattice constant and unit cell volume of LiFePO4. Additionally, the water molecules occupy the Li-ion vacancies, leading to an increase in the lattice constant of LiFePO4. The computational results of the electronic properties show that the introduction of water molecules induces a transition in LiFePO4 from a semiconductor to a metallic behavior, with a transfer of 0.38 e of charge from the water molecules to LiFePO4. Additionally, the migration barrier for Li ions in the H2O + LiFePO4 system is found to be 0.50 eV, representing an 11.1% increase compared to the pristine LiFePO4 migration barrier. Our findings suggest that water molecules impede the migration of Li ions and provide important insights into the effect of defect-engineering on electronic properties and ion conduction under humid conditions.

Due to the inherent intermittency, variability, and randomness, photovoltaic (PV) power generation faces significant challenges in energy grid integration. To address these challenges, current research mainly focuses on developing more efficient energy management systems and prediction technologies. Through optimizing scheduling and integration in PV power generation, the stability and reliability of the power grid can be further improved. In this study, a new prediction model is introduced that combines the strengths of convolutional neural networks (CNNs), long short-term memory (LSTM) networks, and attention mechanisms, so we call this algorithm CNN-LSTM-Attention (CLA). In addition, the Crested Porcupine Optimizer (CPO) algorithm is utilized to solve the short-term prediction problem in photovoltaic power generation. This model is abbreviated as CPO-CLA. This is the first time that the CPO algorithm has been introduced into the LSTM algorithm for parameter optimization. To effectively capture univariate and multivariate time series patterns, multiple relevant and target variables prediction patterns (MRTPPs) are employed in the CPO-CLA model. The results show that the CPO-CLA model is superior to traditional methods and recent popular models in terms of prediction accuracy and stability, especially in the 13 h timestep. The integration of attention mechanisms enables the model to adaptively focus on the most relevant historical data for future power prediction. The CPO algorithm further optimizes the LSTM network parameters, which ensures the robust generalization ability of the model. The research results are of great significance for energy generation scheduling and establishing trust in the energy market. Ultimately, it will help integrate renewable energy into the grid more reliably and efficiently.

Abstract Sterol carrier protein 2 (SCP2) is highly expressed in human osteoarthritis (OA) cartilage, accompanied by ferroptosis hallmarks, especially the accumulation of lipid hydroperoxides (LPO). However, the role of SCP2 in chondrocyte ferroptosis remains unexplored. Here, we identify that SCP2 transports cytoplasmic LPO to mitochondria in RSL3-induced chondrocyte ferroptosis, resulting in mitochondrial membrane damage and release of reactive oxygen species (ROS). The localization of SCP2 on mitochondria is associated with mitochondrial membrane potential, but independent of microtubules transport or voltage-dependent anion channel. Moreover, SCP2 promotes lysosomal LPO increase and lysosomal membrane damage through elevating ROS. However, SCP2 is not directly involved in the cell membrane rupture caused by RSL3. Inhibition of SCP2 markedly protects mitochondria and reduces LPO levels, attenuating chondrocyte ferroptosis in vitro and alleviating the progression of OA in rats. Our study demonstrates that SCP2 mediates the transport of cytoplasmic LPO to mitochondria and the spread of intracellular LPO, accelerating chondrocyte ferroptosis.

Abstract Background Neuroinflammation is a vital pathophysiological process during ischemic stroke. Activated astrocytes play a major role in inflammation. Lipocalin-2 (LCN2), secreted by activated astrocytes, promotes neuroinflammation. Pyroptosis is a pro-inflammatory form of programmed cell death that has emerged as a new area of research in stroke. Nevertheless, the potential role of LCN2 in astrocyte pyroptosis remains unclear. Methods An ischemic stroke model was established by middle cerebral artery occlusion (MCAO) in vivo. In this study, in vitro, oxygen–glucose deprivation and reoxygenation (O/R) were applied to cultured astrocytes. 24p3R (the LCN2 receptor) was inhibited by astrocyte-specific adeno-associated virus (AAV-GFAP-24p3Ri). MCC950 and Nigericin sodium salt (Nig) were used to inhibit or promote the activation of NLRP3 inflammasome pharmacologically, respectively. Histological and biochemical analyses were performed to assess astrocyte and neuron death. Additionally, the neurological deficits of mice were evaluated. Results LCN2 expression was significantly induced in astrocytes 24 h after stroke onset in the mouse MCAO model. Lcn2 knockout (Lcn2 −/−) mice exhibited reduced infarct volume and improved neurological and cognitive functions after MCAO. LCN2 and its receptor 24p3R were colocalized in astrocytes. Mechanistically, suppression of 24p3R by AAV-GFAP-24p3Ri alleviated pyroptosis-related pore formation and the secretion of pro-inflammatory cytokines via LCN2, which was then reversed by Nig-induced NLRP3 inflammasome activation. Astrocyte pyroptosis was exacerbated in Lcn2 −/− mice by intracerebroventricular administration of recombinant LCN2 (rLCN2), while this aggravation was restricted by blocking 24p3R or inhibiting NLRP3 inflammasome activation with MCC950. Conclusion LCN2/24p3R mediates astrocyte pyroptosis via NLRP3 inflammasome activation following cerebral ischemia/reperfusion injury.

Abstract Polymer nanowire (NW) organic field-effect transistors (OFETs) integrated on highly aligned large-area flexible substrates are candidate structures for the development of high-performance flexible electronics. This work presents a universal technique, coaxial focused electrohydrodynamic jet (CFEJ) printing technology, to fabricate highly aligned 90-nm-diameter polymer arrays. This method allows for the preparation of uniformly shaped and precisely positioned nanowires directly on flexible substrates without transfer, thus ensuring their electrical properties. Using indacenodithiophene-co-benzothiadiazole (IDT-BT) and poly(9,9-dioctylfluorene-co-benzothiadiazole) (F8-BT) as example materials, 5 cm2 arrays were prepared with only minute size variations, which is extremely difficult to do using previously reported methods. According to 2D-GIXRD analysis, the molecules inside the nanowires mainly adopted face-on π-stacking crystallite arrangements. This is quite different from the mixed arrangement of thin films. Nanowire-based OFETs exhibited a high average hole mobility of 1.1 cm2 V−1 s−1 and good device uniformity, indicating the applicability of CFEJ printing as a potential batch manufacturing and integration process for high-performance, scalable polymer nanowire-based OFET circuits. This technique can be used to fabricate various polymer arrays, enabling the use of organic polymer semiconductors in large-area, high-performance electronic devices and providing a new path for the fabrication of flexible displays and wearable electronics in the future.

Evidence regarding the role of dietary patterns in metabolic syndrome (MetS) is limited. The mechanistic links between dietary patterns, insulin resistance, and MetS are not fully understood. This study aimed to evaluate the associations between dietary patterns and the risk of MetS in a Chinese population using a longitudinal design. Data from the China Health and Nutrition Survey, a nationally representative survey, were analyzed. MetS cases were identified based on biomarker data collected in 2009. Factor analysis was employed to identify dietary patterns, while logistic regression models were utilized to examine the association between dietary patterns and MetS. Mediation models were applied to assess multiple mediation effects. Two dietary patterns were revealed by factor analysis. Participants in the higher quartiles of the traditional Chinese dietary pattern had lower odds of MetS than those in the lowest quartile (Q1) (OR = 0.58, 95%CI: 0.48, 0.69 for Q4; OR = 0.75, 95%CI: 0.63, 0.89 for Q3). Conversely, participants in the higher quartiles of the modern Chinese dietary pattern had higher odds of MetS compared to those in the lowest quartile (Q1) (OR = 1.40, 95%CI: 1.17, 1.68 for Q4; OR = 1.27, 95%CI: 1.06, 1.52 for Q3). Significant associations between dietary patterns and MetS were mediated by insulin resistance. Therefore, dietary patterns in Chinese adults are associated with MetS, and these associations appear to be mediated through insulin resistance. These findings underscore the critical role of dietary patterns in the development of MetS and establish a foundation for culturally tailored dietary interventions aimed at reducing rates the prevalence of MetS among Chinese adults.

There are totally 93 fluorine aromatic scaffolds containing drugs approved by U.S. Food and Drug Administration from 2002 to 2022. The proportion of drugs containing fluorinated aromatic skeleton in approved drugs is increasing in recent ten years, which indicates the unique and important attributes of the fluorine atom. The introduction of fluorinated fragments into molecules can influence structure conformation, intrinsic potency and selectivity and pharmacokinetic properties productively. Additionally, 18F has been applied as a significant and useful positron emission tomography isotope for in vivo imaging technology. This review is mainly concentrated on the application and synthesis methods of 93 fluorine aromatic scaffolds containing drugs approved by the US FDA from 2002 to 2022. We hoped that this deep insight perspective into the synthetic methods for the delivery of these fluorine aromatic scaffolds containing drugs could offer practical and creative inspirations for the application and development of fluorine atom in new drug discovery.

Background: Acute severe hepatitis with unknown aetiology in children (ASHep-UA) has become a global health alert. This article reported clinicopathological characteristics of 3 probable ASHep-UA cases. Methods: We respectively collected serological data and liver biopsies of 3 suspected cases of ASHep-UA. Neutralizing antibodies titer for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants were determined by virus neutralization test (VNT). Histological assessment, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for cytomegalovirus (CMV), Epstein-Barr virus (EBV), human adenoviruses (HAdV), adeno-associated virus (AAV2), human herpes virus type 6 (HHV-6) were performed to identify possible aetiologies. Results: Remarkable elevation of transaminase (median ALT level, 1100 IU/liter; median AST level, 500 IU/liter) were revealed with undetectable hepatitis A-E and non-hepatotropic virus in both sera and tissues. Weakness, jaundice, pale stools and splenomegaly were observed. Interestingly, two individuals had SARS-CoV-2 Omicron variants infection. Histologically, moderate or severe lobular necroinflammation, active interface hepatitis and portal inflammatory infiltrate with lymphocytic, plasma cells, neutrophils and eosinophilic cells were noted. Conclusions: The exact aetiology of ASHep-UA was still unknown. By reporting the 3 probable cases, we expect to enrich the clinical experience in diagnosis and treatment of ASHep-UA as well as the pathological characteristics.

Osteosarcoma is a highly metastatic malignant bone tumor, necessitating the development of new treatments to target its metastasis. Recent studies have revealed the significance of VAMP8 in regulating various signaling pathways in various types of cancer. However, the specific functional role of VAMP8 in osteosarcoma progression remains unclear. In this study, we observed a significant downregulation of VAMP8 in osteosarcoma cells and tissues. Low levels of VAMP8 in osteosarcoma tissues were associated with patients’ poor prognosis. VAMP8 inhibited the migration and invasion capability of osteosarcoma cells. Mechanically, we identified DDX5 as a novel interacting partner of VAMP8, and the conjunction of VAMP8 and DDX5 promoted the degradation of DDX5 via the ubiquitin-proteasome system. Moreover, reduced levels of DDX5 led to the downregulation of β-catenin, thereby suppressing the epithelial–mesenchymal transition (EMT). Additionally, VAMP8 promoted autophagy flux, which may contribute to the suppression of osteosarcoma metastasis. In conclusion, our study anticipated that VAMP8 inhibits osteosarcoma metastasis by promoting the proteasomal degradation of DDX5, consequently inhibiting WNT/β-catenin signaling and EMT. Dysregulation of autophagy by VAMP8 is also implicated as a potential mechanism. These findings provide new insights into the biological nature driving osteosarcoma metastasis and highlight the modulation of VAMP8 as a potential therapeutic strategy for targeting osteosarcoma metastasis.

In this study, a non-contact electrical resistivity method is employed to investigate the hydration process of calcium aluminate cement (CAC) pastes incorporating silica fume (SF) at an early age. The CAC-SF pastes have a water-to-binder ratio (w/b) of 0.6 and a replacement of SF for CAC at 0, 5, 10, and 20% (by weight of the binder). The pastes are tested for electrical resistivity, thermal analysis (internal temperature), setting time, and compressive strength, and the hydration products of the pastes are also examined. The results indicate that the evolution of electrical resistivity is closely related to the hydration process of the CAC pastes, and the conversion stage is closely associated with the setting time of pastes. As the increase of SF replacement, the hydration process of CAC pastes was accelerated within 24 h, and the development of compressive strength was hampered at an early age but increased later. SF replacement inhibits the conversion of metastable CAC hydrates (CAH10 and C2AH8) to C3AH6 through filling, seeding, and reacting with CAC, thus reducing the heat of hydration.

Abstract With the continuous development of information technology and the running speed of computers, the development of informatization has led to the generation of increasingly more medical data. Solving unmet needs such as employing the constantly developing artificial intelligence technology to medical data and providing support for the medical industry is a hot research topic. Cytomegalovirus (CMV) is a kind of virus that exists widely in nature with strict species specificity, and the infection rate among Chinese adults is more than 95%. Therefore, the detection of CMV is of great importance since the vast majority of infected patients are in a state of invisible infection after the infection, except for a few patients with clinical symptoms. In this study, we present a new method to detect CMV infection status by analyzing high-throughput sequencing results of T cell receptor beta chains (TCRβ). Based on the high-throughput sequencing data of 640 subjects from cohort 1, Fisher’s exact test was performed to evaluate the relationship between TCRβ sequences and CMV status. Furthermore, the number of subjects with these correlated sequences to different degrees in cohort 1 and cohort 2 were measured to build binary classifier models to identify whether the subject was CMV positive or negative. We select four binary classification algorithms: logistic regression (LR), support vector machine (SVM), random forest (RF), and linear discriminant analysis (LDA) for side-by-side comparison. According to the performance of different algorithms corresponding to different thresholds, four optimal binary classification algorithm models are obtained. The logistic regression algorithm performs best when Fisher's exact test threshold is 10−5, and the sensitivity and specificity are 87.5% and 96.88%, respectively. The RF algorithm performs better at the threshold of 10−5, with a sensitivity of 87.5% and a specificity of 90.63%. The SVM algorithm also achieves high accuracy at the threshold value of 10−5, with a sensitivity of 85.42% and specificity of 96.88%. The LDA algorithm achieves high accuracy with 95.83% sensitivity and 90.63% specificity when the threshold value is 10−4. This is probably because the two-dimensional distribution of CMV data samples is linearly separable, and linear division models such as LDA are more effective, while the division effect of nonlinear separable algorithms such as random forest is relatively inaccurate. This new finding may be a potential diagnostic method for CMV and may even be applicable to other viruses, such as the infectious history detection of the new coronavirus.