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The silicon nanowire field-effect transistor (SiNW FET) has been developed for over two decades as an ultrasensitive, label-free biosensor for biodetection. However, inconsistencies in manufacturing and surface functionalization at the nanoscale have led to poor sensor-to-sensor consistency in performance. Despite extensive efforts to address this issue through process improvements and calibration methods, the outcomes have not been satisfactory. Herein, based on the strong correlation between the saturation response of SiNW FET biosensors and both their feature size and surface functionalization, we propose a calibration strategy that combines the sensing principles of SiNW FET with the Langmuir-Freundlich model. By normalizing the response of the SiNW FET biosensors (Δ I / I 0 ) with their saturation response (Δ I / I 0 ) max , this strategy fundamentally overcomes the issues mentioned above. It has enabled label-free detection of nucleic acids, proteins, and exosomes within 5 min, achieving detection limits as low as attomoles and demonstrating a significant reduction in the coefficient of variation. Notably, the nucleic acid test results exhibit a strong correlation with the ultraviolet-visible (UV-vis) spectrophotometer measurements, with a correlation coefficient reaching 0.933. The proposed saturation response calibration strategy exhibits good universality and practicability in biological detection applications, providing theoretical and experimental support for the transition of mass-manufactured nanosensors from theoretical research to practical application.

Helicases, which utilize ATP hydrolysis to separate nucleic acid duplexes, play crucial roles in DNA and RNA replication, repair, recombination, and transcription. Categorized into the major groups superfamily 1 (SF1) and superfamily 2 (SF2), alongside four minor groups, these proteins exhibit a conserved catalytic core indicative of a shared evolutionary origin while displaying functional diversity through interactions with various substrates. This review summarizes the structures, functions and mechanisms of SF1 and SF2 helicases, with an emphasis on conserved ATPase sites and RecA-like domains essential for their enzymatic and nucleic acid binding capabilities. It highlights the unique 1B and 2B domains in SF1 helicases and their impact on enzymatic activity. The DNA unwinding process is detailed, covering substrate recognition, ATP hydrolysis, and conformational changes, while addressing debates over the active form of UvrD helicase and post-unwinding dissociation. More importantly, this review discusses the biotechnological potential of helicases in emerging technologies such as nanopore sequencing, protein sequencing, and isothermal amplification, focusing on their use in pathogen detection, biosensor enhancement, and cancer treatment. As understanding deepens, innovative applications in genome editing, DNA sequencing, and synthetic biology are anticipated., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The role of mast cell (MC), a common myeloid-derived immune cell, in the development of oral squamous cell carcinoma (OSCC) is unclear. The aim of this study was to investigate MC infiltration in oral precancer and oral cancer. The evaluation of immune cell infiltration and its association with prognosis in OSCC used RNA sequencing and multiple public datasets. Multiplex immunofluorescence was used to explore the infiltration of MC in the microenvironment of OSCC and oral precancer and the interaction with CD8+ cells. The role of MC in OSCC progression was verified by in vivo experiments. The resting MC infiltration was mainly present in oral precancer, whereas activated MC infiltration was significantly higher in OSCC. Activated MC was associated with malignant transformation of oral precancer and poor prognosis of OSCC. In vivo studies showed that MC promoted the growth of OSCC. The infiltration of activated MC was negatively correlated with the infiltration of CD8+ T cells. The subtype of MC containing tryptase without chymase (MCT) was significantly higher in OSCC compared with oral precancer and was associated with poor survival. Furthermore, spatial distance analysis revealed a greater distance between MCT and CD8+ cells, which was also linked to poor prognosis in OSCC. Cox regression analysis showed that MCT could be a potential diagnostic and prognostic biomarker. This study provides new insights into the role of MC in the immune microenvironment of OSCC. It might enhance the immunotherapeutic efficacy of OSCC by developing targeted therapies against MC., Significance: In this study, we investigated the role of mast cells (MC) in oral precancer and oral cancer and demonstrated that MCs are involved in oral cancer progression and may serve as a potential diagnostic and prognostic marker. It might improve the immunotherapeutic efficacy through developing targeted therapies against MCs., (©2024 The Authors; Published by the American Association for Cancer Research.)

Left hemisphere injury can cause right spastic arm paralysis and aphasia, and recovery of both motor and language functions shares similar compensatory mechanisms and processes. Contralateral cervical seventh cross transfer (CC7) surgery can provide motor recovery for spastic arm paralysis by triggering interhemispheric plasticity, and self-reports from patients indicate spontaneous improvement in language function but still need to be verified. To explore the improvements in motor and language function after CC7 surgery, we performed this prospective observational cohort study. The Upper Extremity part of Fugl-Meyer scale (UEFM) and Modified Ashworth Scale were used to evaluate motor function, and Aphasia Quotient calculated by Mandarin version of the Western Aphasia Battery (WAB-AQ, larger score indicates better language function) was assessed for language function. In 20 patients included, the average scores of UEFM increased by .40 and 3.70 points from baseline to 1-week and 6-month post-surgery, respectively. The spasticity of the elbow and fingers decreased significantly at 1-week post-surgery, although partially recurred at 6-month follow-up. The average scores of WAB-AQ were increased by 9.14 and 10.69 points at 1-week and 6-month post-surgery (P < .001 for both), respectively. Post-surgical fMRI scans revealed increased activity in the bilateral hemispheres related to language centrals, including the right precentral cortex and right gyrus rectus. These findings suggest that CC7 surgery not only enhances motor function but may also improve the aphasia quotient in patients with right arm paralysis and aphasia due to left hemisphere injuries., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: There is inconsistent evidence regarding the accuracy of GNAS mutations identification for the diagnosis of FD/MAS. This study was performed to estimate the prevalence and diagnostic accuracy of GNAS mutations detection and to preliminarily investigate the genotype-phenotype correlation in FD patients., Methods: Five electronic databases were searched from 1995 to 2024 using search terms related to GNAS and fibrous dysplasia. Observational studies of FD patients undergoing GNAS mutation detection in FD were included., Results: A total of 878 FD patients were included. The pooled prevalence of GNAS mutations in FD based on the random effects model was 74% (95% CI = 64%-83%). Regarding diagnostic accuracy, a sensitivity of 0.83 (95% CI, 0.65-0.96), specificity of 0.99 (95% CI, 0.98-1.00) and the area under the receiver operating characteristic curve of 98.38% were found. Additionally, meta-analysis and Fisher's test showed the GNAS mutation types were significantly associated with FD types (OR = 3.51, 95% CI = 1.05 to 11.72; p < 0.05)., Conclusion: A high detection rate of GNAS mutations occurred in FD, and its detection is reliable for diagnosing FD. Additionally, GNAS mutation type was types were significantly associated with FD type., Systematic Review Registration: Identifier CRD42024553469., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhang, Xue, Wu, Xu, Sun and Li.)

Tin oxide is a promising channel material, offering the advantages of being low-cost and environmentally friendly and having a wide band gap. However, despite the high electron mobility of SnO 2 in bulk, the corresponding thin-film transistors (TFTs) generally exhibit moderate performance, hindering their widespread application. Herein, we proposed a codoping strategy to improve both the electrical property and the stability of SnO 2 TFTs. A comparative analysis between doped and undoped SnO 2 was conducted. It is observed that taking advantage of the difference in ionic radii between two dopants (indium and gallium) and the tin ions in the host lattice can effectively reduce impurity-induced strain. Additionally, we investigated the effect of codoping content on SnO 2 TFTs. The optimal codoped SnO 2 (TIGO) TFTs demonstrate high performance, featuring a field-effect mobility of 15.9 cm 2 /V·s, a threshold voltage of 0.2 V, a subthreshold swing of 0.5 V/decade, and an on-to-off current ratio of 2.2 × 10 7 . Furthermore, the devices show high stability under both positive and negative bias stress conditions with a small threshold voltage shift of 1.8 and -1.2 V, respectively. Utilizing the TIGO TFTs, we successfully constructed a resistor-loaded unipolar inverter with a high gain of 10.76. This study highlights the potential of codoped SnO 2 TFTs for advanced applications in electronic devices.

Flexible sensors are essential components in emerging fields such as epidermal electronics, biomedicine, and human-computer interactions, and creating high-performance sensors through simple structural design for practical applications is increasingly needed. Presently, challenges still exist in establishing efficient models of flexible piezoresistive pressure sensors to predict the design required for achieving target performance. This work establishes a theoretical model of a flexible pressure sensor with a simple laminated and enclosed structure. In the modeling, the electrical constriction effect is innovatively introduced to explain the sensitization mechanism of the laminated structure to a broad range of pressures and to predict the sensor performance. The experimental results confirmed the effectiveness of the theoretical model. The sensor exhibited excellent stability for up to three million cycles and superior durability when exposed to salt solution owing to its simple laminated and enclosed structural design. Finally, a wearable sensing system for real-time collection and analysis of plantar pressure is constructed for exercise and rehabilitation monitoring applications. This work aims to provide theoretical guidance for the rapid design and construction of flexible pressure sensors with target performance for practical applications., Competing Interests: Conflict of interestTing Zhang is an editor for the journal, no other author has reported any competing interest., (© The Author(s) 2024.)

Endometriosis, identified by the abnormal growth of endometrial cells beyond the inner lining of the uterus, often manifests through symptoms like painful menstruation and challenges in conceiving. Observational studies suggest that endometriosis is often comorbid with mental disorders, including anxiety and depression. The nature of these connections, whether they are causal, is still debated and calls for further empirical evidence. We utilized a bidirectional 2-sample Mendelian randomization (MR) approach, harnessing genome-wide association study data to explore the connections among depression, anxiety, neuroticism, and endometriosis. To scrutinize the causative connections between mental health issues and endometriosis, Inverse Variance Weighting (IVW) was employed as the primary analytical tool, complemented by Weighted Median Estimation, Simple mode, Weighted mode, and MR-Egger regression for additional analysis. To examine the potential for reverse causation, reverse MR was applied. To strengthen the reliability of our findings, we carried out sensitivity analyses that included heterogeneity tests, tests for pleiotropy, and leave-one-out analyses. The IVW analysis revealed a significant correlation between the genetic inclination towards depression and a heightened risk of developing endometriosis [Odds Ratio (OR) = 1.151, 95% Confidence Interval (CI) = 1.025-1.293, P = .017]. Similarly, a genetic predisposition to neuroticism was significantly associated with an increased risk of endometriosis (OR = 1.128, 95% CI = 1.038-1.226, P = .004). However, no causative link was found between genetic susceptibility to anxiety and the occurrence of endometriosis. Reverse MR analysis did not support a bidirectional genetic susceptibility between endometriosis and psychiatric disorders. The MR analysis presents genetic data supporting the notion that depression and neuroticism are risk factors for endometriosis. Conversely, it found no evidence of a causal connection between anxiety and the development of endometriosis. Enhancing mental health treatment should be considered a preventive measure against endometriosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This article summarizes and discusses the collaborative effects of acupuncture and medication in treatment, including four aspects, named "acupuncture synergizing the effects of medication", "medication advancing the effects of acupuncture", "coordination of acupuncture and medication", and "antagonism of acupuncture and medication". Regarding "acupuncture synergizing the effects of medication", the actions of acupuncture are predominant, which affects the absorption and metabolism of drugs in the body, increases drug concentration in blood, enhances the targeting effect of drugs, guides meridian tropism, alleviates the drug dose and adverse reactions, avoids the first pass effect and accelerates the drug bioavailability. As for "medication advancing the effects of acupuncture", the synergistic effect of acupuncture is obtained by medication, besides, the medication itself may supplement the drug property to the needles during acupuncture pretreatment so as to increase the therapeutic effect. In terms of "coordination of acupuncture and medication", and "antagonism of acupuncture and medication", there are the underlying co-effects of acupuncture and medication in the body, and the action targets may be same or different between them, thus, it needs to be further explored.

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder, but its diagnosis and treatment remain obscure. Non-coding RNAs (ncRNAs), as potential biomarkers, have attracted increasing attention in digestive diseases. Here, we present a comprehensive research status, development trends, and valuable insights in this subject area. The literature search was performed using Web of Science Core Collection. VOSviewer 1.6.20, Citespace 6.2.R4, and Microsoft Excel 2021 were used for bibliometric analysis. A total of 124 articles were included in the analysis. Overall, publication patterns fluctuated. Globally, People's Republic of China, the USA, and Germany were the top three contributors of publications. Guangzhou University of Chinese Medicine, University of California, Mayo Clinic, and University of California, Los Angeles contributed the highest number of publications. The pathways and specific mechanisms by which ncRNAs regulate transcription and translation and thus regulate the pathophysiological processes of IBS are the main research hotspots in this field. We found that microRNA (miRNAs) are intricately involved in the regulation of key pathologies such as viscera sensitivity, intestinal permeability, intestinal mucosal barrier, immunoinflammatory response, and brain-gut axis in the IBS, and these topics have garnered significant attention in research community. Notably, microecological disorders are also associated with IBS pathogenesis, and ncRNA may play an important role in the interactions between host and intestinal flora. This is the first bibliometric study to comprehensively summarize the research hotspots and trends related to IBS and ncRNAs (especially miRNAs). Our findings will help understand the role of ncRNAs in IBS and provide guidance to future studies., (© 2024. The Author(s).)

A key feature distinguishing high-grade glioma (HG) from low-grade glioma (LG) is the extensive neovascularization and endothelial hyperproliferation. Prior work has shown that tumor-associated vasculature from HG is molecularly and functionally distinct from normal brain vasculature and expresses higher levels of protumorigenic factors that promote glioma growth and progression. However, it remains unclear whether vessels from LG also express protumorigenic factors, and to what extent they functionally contribute to glioma growth. Here, we profile the transcriptomes of glioma-associated vascular cells (GVC) from IDH-mutant (mIDH) LG and IDH-wild-type (wIDH) HG and show that they exhibit significant molecular and functional differences. LG-GVC show enrichment of extracellular matrix-related gene sets and sensitivity to antiangiogenic drugs, whereas HG-GVC display an increase in immune response-related gene sets and antiangiogenic resistance. Strikingly, conditioned media from LG-GVC inhibits the growth of wIDH glioblastoma cells, whereas HG-GVC promotes growth. In vivo cotransplantation of LG-GVC with tumor cells reduces growth, whereas HG-GVC enhances tumor growth in orthotopic xenografts. We identify ASPORIN (ASPN), a small leucine-rich repeat proteoglycan, highly enriched in LG-GVC as a growth suppressor of wIDH glioblastoma cells in vitro and in vivo. Together, these findings indicate that GVC from LG and HG are molecularly and functionally distinct and differentially regulate tumor growth. Implications: This study demonstrated that vascular cells from IDH-mutant LG and IDH-wild-type HG exhibit distinct molecular signatures and have differential effects on tumor growth via regulation of ASPN-TGFβ1-GPM6A signaling., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Central nervous system (CNS) disorders, such as stroke, often lead to spasticity, which result in limb deformities and significant reduction in quality of life. Spasticity arises from disruptions in the normal functioning of cortical and descending inhibitory pathways in the brainstem, leading to abnormal muscle contractions. Contralateral seventh cervical nerve cross transfer (CC7) surgery has been proven to effectively reduce spasticity, but the specific mechanism for its effectiveness is unclear., Methods: This study aimed to investigate the changes in the dorsal root ganglia (DRG) following CC7 surgery. A comprehensive anatomical analysis was conducted through cadaveric study and magnetic resonance imaging (MRI) study, to accurately measure the regional anatomy of the C7 DRG. DRG perfusion changes were quantitatively assessed by comparing pre- and postoperative dynamic contrast-enhanced (DCE) MRI., Results: In CC7 surgery, the C7 nerve root on the affected side is cut close to the DRG (3.6 ± 1.0 mm), while the C7 nerve root on the healthy side is cut further away from the DRG (65.0 ± 10.0 mm). MRI studies revealed that after C7 proximal neurotomy on the affected side, there was an increase in DRG volume, vascular permeability, and perfusion; after C7 distal neurotomy on the healthy side, there was a decrease in DRG volume, with no significant changes in vascular permeability and perfusion., Conclusion: This study provides preliminary insights into the mechanisms of spasticity reduction following CC7 surgery, indicating that changes in the DRG, such as increased vascular permeability and perfusion, could disrupt abnormal spinal γ-circuits. The resulting high-perfusion state of DRG, possibly due to heightened neuronal activity and metabolic demands, necessitating further research to verify this hypothesis., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Objective: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy., Materials and Methods: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation., Results: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups., Conclusions: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Glioblastoma (GBM) is the most common malignant primary brain tumor and remains incurable. Previous work has shown that systemic administration of Decitabine (DAC) induces sufficient expression of cancer-testis antigens (CTA) in GBM for targeting by adoptive T-cell therapy in vivo. However, the mechanisms by which DAC enhances immunogenicity in GBM remain to be elucidated. Using New York esophageal squamous cell carcinoma 1 (NY-ESO-1) as a representative inducible CTA, we demonstrate in patient tissue, immortalized glioma cells, and primary patient-derived gliomaspheres that basal CTA expression is restricted by promoter hypermethylation in gliomas. DAC treatment of glioma cells specifically inhibits DNA methylation silencing to render NY-ESO-1 and other CTA into inducible tumor antigens at single-cell resolution. Functionally, NY-ESO-1 T-cell receptor-engineered effector cell targeting of DAC-induced antigen in primary glioma cells promotes specific and polyfunctional T-cell cytokine profiles. In addition to induction of CTA, DAC concomitantly reactivates tumor-intrinsic human endogenous retroviruses, interferon response signatures, and MHC-I. Overall, we demonstrate that DAC induces targetable tumor antigen and enhances T-cell functionality against GBM, ultimately contributing to the improvement of targeted immune therapies in glioma., Significance: This study dissects the tumor-intrinsic epigenetic and transcriptional mechanisms underlying enhanced T-cell functionality targeting decitabine-induced cancer-testis antigens in glioma. Our findings demonstrate concomitant induction of tumor antigens, reactivation of human endogenous retroviruses, and stimulation of interferon signaling as a mechanistic rationale to epigenetically prime human gliomas to immunotherapeutic targeting., (©2024 The Authors; Published by the American Association for Cancer Research.)

The proliferation and differentiation of skeletal muscle satellite cells is a complex physiological process involving various transcription factors and small RNA molecules. This study aimed to understand the regulatory mechanisms underlying these processes, focusing on interferon-related development factor 2 (IFRD2) as a target gene of miRNA-2400 in bovine skeletal MuSCs (MuSCs). IFRD2 was identified as a target gene of miRNA-2400 involved in regulating the proliferation and differentiation of bovine skeletal MuSCs. Our results indicate that miR-2400 can target binding the 3'UTR of IFRD2 and inhibit its translation. mRNA and protein expression levels of IFRD2 increased significantly with increasing days of differentiation. Moreover, overexpression of the IFRD2 gene inhibited proliferation and promoted differentiation of bovine MuSCs. Conversely, the knockdown of the gene had the opposite effect. Overexpression of IFRD2 resulted in the inhibition of ERK1/2 phosphorylation levels in bovine MuSCs, which in turn promoted differentiation. In summary, IFRD2, as a target gene of miR-2400, crucially affects bovine skeletal muscle proliferation and differentiation by precisely regulating ERK1/2 phosphorylation., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing and immunohistochemical staining for markers NR4A3/NR4A2, DOG-1, S100, and mammaglobin were utilized on 41 AciCCs and 11 secretory carcinoma (SC) samples. NR4A3 was evident in 35 AciCCs, while the residual 6 were NR4A3-negative and NR4A2-positive; SC samples were consistently NR4A3-negative. A novel fusion, PON3 exon 1- LCN1 exon 5, was detected in 9/41 (21.9%) AciCCs, exhibiting a classical histologic pattern with serous cell components growing in solid sheets alongside the intercalated duct-like component. Clinical follow-up of 39 patients over a median of 59 months revealed diverse prognostic outcomes: 34 patients exhibited no disease evidence, whereas the remaining 5 experienced poorer prognosis, involving local recurrence, lymph node, and distant metastasis, and disease-associated death, 4 of which harbored the PON3::LCN1 fusion. In addition, the HTN3::MSANTD3 fusion was recurrently identified in 7/41 AciCC cases. SC patients lacked both fusions. Immunohistochemistry uncovered differential expression of DOG-1, S100, and mammaglobin across samples, providing nuanced insights into their roles in AciCC. This study accentuates PON3::LCN1 and HTN3::MSANTD3 fusions as recurrent molecular events in AciCC, offering potential diagnostic and prognostic utility and propelling further research into targeted therapeutic strategies., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to compare the effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide content and quality characteristics of fried potato chips. The hydrolyzed pectin with molecular weight (Mw) of 8.81 ± 0.49 kDa was obtained through partial degradation of pectin (Mw: 747.57 ± 6.73 kDa) using pectinase. Results showed that both pectin and hydrolyzed pectin coating significantly inhibited acrylamide formation and inhibition rates exceeded 90 %. Hydrolyzed pectin had stronger inhibitory activity against acrylamide formation than pectin, especially when the concentration of hydrolyzed pectin was >2 %, its inhibitory rate exceeded 95 %. Compared to pectin coating, hydrolyzed pectin coating endow fried potato chips with smaller browning, higher crispness, less moisture but higher oil content. Overall, hydrolyzed pectin had better application prospects than pectin in inhibiting acrylamide formation of fried potato chips., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bloom-induced macroalgal enrichment on the seafloor can substantially facilitate dissolved sulfide (DS) production through sulfate reduction. The reaction of DS with sedimentary reactive iron (Fe) is the main mechanism of DS consumption, which however usually could not effectively prevent DS accumulation caused by pulsed macroalgal enrichment. Here we used incubations to investigate the performance of Fe-rich red soil for buffering of DS produced from macroalgae (Ulva prolifera)-enriched sediment. Based on our results, a combination of red soil additions (6.8 kg/m 2 ) before and immediately after pulsed macroalgal deposition (455 g/m 2 ) can effectively cap DS within the red soil layer. The effective DS buffering is mainly due to ample Fe-oxide surface sites available for reaction with DS. Only a small loss (4 %) of buffering capacity after 18-d incubation suggests that the red soil is capable of prolonged DS buffering in macroalgae-enriched sediments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

To understand the influences of emulsified fuel on ship exhaust emissions more comprehensively, the emissions of particulate matter (PM), nitrated, oxygenated and parent polycyclic aromatic hydrocarbons (PAHs) were studied on a ship main engine burning emulsified heavy fuel oil (EHFO) and heavy fuel oil (HFO) as a reference. The results demonstrate that EHFO (emulsified heavy fuel oil) exhibits notable abilities to significantly reduce emissions of particulate matter (PM) and low molecular weight PAHs (polycyclic aromatic hydrocarbons) in the gas phase, particularly showcasing maximum reductions of 13.99% and 40.5%, respectively. Nevertheless, burning EHFO could increase the emission of high molecular weight PAHs in fine particles and pose a consequent higher carcinogenic risk for individual particles. The total average (gaseous plus particulate) ΣBEQ of EHFO exhausts (41.5 μg/m 3 ) was generally higher than that of HFO exhausts (18.7 μg/m 3 ). Additionally, the combustion of EHFO (extra-heavy fuel oil) can significantly alter the emission quantity, composition, and particle-size distribution of PAH derivatives. These changes may be linked to molecular structures, such as zigzag configurations in C=O bonds. Our findings may favor the comprehensive environmental assessments on the onboard application of EHFO.

Objective: In this study, our aim was to develop and validate the effectiveness of diverse radiomic models for distinguishing between gnathic fibrous dysplasia (FD) and ossifying fibroma (OF) before surgery., Materials and Methods: We enrolled 220 patients with confirmed FD or OF. We extracted radiomic features from nonenhanced CT images. Following dimensionality reduction and feature selection, we constructed radiomic models using logistic regression, support vector machine, random forest, light gradient boosting machine, and eXtreme gradient boosting. We then identified the best radiomic model using receiver operating characteristic (ROC) curve analysis. After combining radiomics features with clinical features, we developed a comprehensive model. ROC curve and decision curve analysis (DCA) demonstrated the models' robustness and clinical value., Results: We extracted 1834 radiomic features from CT images, reduced them to eight valuable features, and achieved high predictive efficiency, with area under curves (AUC) exceeding 0.95 for all the models. Ultimately, our combined model, which integrates radiomic and clinical data, displayed superior discriminatory ability (AUC: training cohort 0.970; test cohort 0.967). DCA highlighted its optimal clinical efficacy., Conclusion: Our combined model effectively differentiates between FD and OF, offering a noninvasive and efficient approach to clinical decision-making., (© 2024 Wiley Periodicals LLC.)

Graphene-based warm uterus acupoint paste (GWUAP) is an emerging non-drug alternative therapy for the treatment of primary dysmenorrhea (PD), but the underlying mechanism is still unclear. SD female rats were randomly divided into control group, model group and treatment group to explore the mechanism of GWUAP in the treatment of PD. Combined with 16S rDNA and fecal metabolomics, the diversity of microbiota and metabolites in each group was comprehensively evaluated. In this study, GWUAP reduced the torsion score of PD model rats, improved the pathological morphology of uterine tissue, reduced the pathological damage score of uterine tissue, and reversed the expression levels of inflammatory factors, pain factors and sex hormones. The 16 S rDNA sequencing of fecal samples showed that the abundance of Lactobacillus in the intestinal flora of the model group decreased and the abundance of Romboutsia increased, while the abundance of Lactobacillus in the intestinal flora of the treatment group increased and the abundance of Romboutsia decreased, which improved the imbalance of flora diversity in PD rats. In addition, 32 metabolites related to therapeutic effects were identified by metabolomics of fecal samples. Moreover, there is a close correlation between fecal microbiota and metabolites. Therefore, the mechanism of GWUAP in the treatment of PD remains to be further studied., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Li, Cao, Zhao, Xu, Chai, Zhang, Liu and Wang.)

Background: Advanced prosthetic hands may embed nanosensors and microelectronics in their cosmetic skin. Heat influx may cause damage to these delicate structures. Protecting the integrity of the prosthetic hand becomes critical and necessary to ensure sustainable function. This study aims to mimic the sensorimotor control strategy of the human hand in perceiving nociceptive stimuli and triggering self-protective mechanisms and to investigate how similar neuromorphic mechanisms implemented in prosthetic hand can allow amputees to both volitionally release a hot object upon a nociceptive warning and achieve reinforced release via a bionic withdrawal reflex., Methods: A steady-state temperature prediction algorithm was proposed to shorten the long response time of a thermosensitive temperature sensor. A hybrid sensory strategy for transmitting force and a nociceptive temperature warning using transcutaneous electrical nerve stimulation based on evoked tactile sensations was designed to reconstruct the nociceptive sensory loop for amputees. A bionic withdrawal reflex using neuromorphic muscle control technology was used so that the prosthetic hand reflexively opened when a harmful temperature was detected. Four able-bodied subjects and two forearm amputees randomly grasped a tube at the different temperatures based on these strategies., Results: The average prediction error of temperature prediction algorithm was 8.30 ± 6.00%. The average success rate of six subjects in perceiving force and nociceptive temperature warnings was 86.90 and 94.30%, respectively. Under the reinforcement control mode in Test 2, the median reaction time of all subjects was 1.39 s, which was significantly faster than the median reaction time of 1.93 s in Test 1, in which two able-bodied subjects and two amputees participated. Results demonstrated the effectiveness of the integration of nociceptive sensory strategy and withdrawal reflex control strategy in a closed loop and also showed that amputees restored the warning of nociceptive sensation while also being able to withdraw from thermal danger through both voluntary and reflexive protection., Conclusion: This study demonstrated that it is feasible to restore the sensorimotor ability of amputees to warn and react against thermal nociceptive stimuli. Results further showed that the voluntary release and withdrawal reflex can work together to reinforce heat protection. Nevertheless, fusing voluntary and reflex functions for prosthetic performance in activities of daily living awaits a more cogent strategy in sensorimotor control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Xie, Li, Chou, Li, Dai and Lan.)

Background/purpose: There is inconsistent evidence regarding whether the botulinum toxin A (BTA) injection can relieve pain caused by bruxism. This study aimed to estimate the efficiency of BTA injection in relieving pain caused by bruxism at different follow-up periods., Materials and Methods: Five electronic databases were searched from 2005 to 2022 using search terms related to botulinum toxin and bruxism. Only controlled clinical trials were included. Two investigators reviewed each article and discussed any disagreements until a consensus was reached. Pain outcomes as evaluated by the visual analogue scale (VAS) were subjected to single-arm and Bayesian network meta-analyses. Pooling data were measured by a random-effects model., Results: Eleven studies with a total of 365 bruxism patients were included. According to the single-arm analyses of the pooled data, the reduction in bruxism-related pain after BTA injection measured 4.06 points (95% CI = 3.37 to 4.75) on the VAS, and the pain relief was significant in the first 6 months after treatment ( P  < 0.01). According to the Bayesian analysis, BTA also resulted in significantly greater pain relief than oral splinting (mean difference (MD), -1.5; 95% credible interval (CrI) = -2.7 to -0.19) or saline injection (MD, -3.3; 95% CrI = -6.2 to -0.32)., Conclusion: BTA significantly relieves the pain of bruxism for 6 months after injection, and its therapeutic efficacy was higher than that of oral splinting. Nevertheless, further long-term follow-up randomized controlled trials comparing BTA with other management or drugs are warranted., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Objectives: We aimed to investigate bone metastasis induced by Notch signalling pathway dysregulation and to demonstrate that SPARC is a potential therapeutic target in adenoid cystic carcinoma (AdCC) with Notch dysregulation., Materials and Methods: This retrospective study enrolled 144 AdCC patients. RNA-sequencing and enrichment analyses were performed using 32 AdCC samples. Osteonectin/SPARC and the Notch activation indicator Notch intracellular domain (NICD) were detected using immunohistochemistry. Cell proliferation and migration assays were conducted using stably NICD over-expressing cells. The effect of SPARC on osteoclast differentiation in NICD cells was investigated using western blotting, quantitative reverse transcription PCR, tartrate-resistant acid phosphatase staining and resorption assays., Results: RNA-sequencing analysis showed that genes down-regulated in Notch-mutant AdCCs, such as SPARC, were enriched in ossification and osteoblast differentiation. Most (75/110, 68.2%) Notch1-wild-type AdCCs showed SPARC over-expression, whereas 30 out of 34 (88.2%) Notch1-mutant tumours showed low SPARC expression. SPARC over-expression was then found negatively to be correlated with NICD expression in 144 AdCCs. NICD over-expression promoted cell growth, migration and osteoclast differentiation, which could be partly reversed by exogenous SPARC., Conclusions: Notch activation in AdCC contributes to bone metastasis through SPARC inhibition. The study results suggest that SPARC may represent a prognostic biomarker and potential therapeutic target., (© 2023 Wiley Periodicals LLC.)

IDH1mut gliomas produce high levels of D-2-hydroxyglutarate (D-2-HG), an oncometabolite capable of inhibiting α-ketoglutarate-dependent dioxygenases critical to a range of cellular functions involved in gliomagenesis. IDH1mut gliomas also exhibit slower growth rates and improved treatment sensitivity compared with their IDH1wt counterparts. This study explores the mechanism driving apparent reduced growth in IDH1mut gliomas. Specifically, we investigated the relationship between IDH1mut and the RNA N6-methyladenosine (m6A) demethylases FTO and ALKBH5, and their potential for therapeutic targeting. We investigated the role of D-2-HG and m6A in tumor proliferation/viability using glioma patient tumor samples, patient-derived gliomaspheres, and U87 cells, as well as with mouse intracranial IDH1wt gliomasphere xenografts. Methylation RNA immunoprecipitation sequencing (MeRIP-seq) RNA sequencing was used to identify m6A-enriched transcripts in IDH1mut glioma. We show that IDH1mut production of D-2-HG is capable of reducing glioma cell growth via inhibition of the m6A epitranscriptomic regulator, FTO, with resultant m6A hypermethylation of a set of mRNA transcripts. On the basis of unbiased MeRIP-seq epitranscriptomic profiling, we identify ATF5 as a hypermethylated, downregulated transcript that potentially contributes to increased apoptosis. We further demonstrate how targeting this pathway genetically and pharmacologically reduces the proliferative potential of malignant IDH1wt gliomas, both in vitro and in vivo. Our work provides evidence that selective inhibition of the m6A epitranscriptomic regulator FTO attenuates growth in IDH1wt glioma, recapitulating the clinically favorable growth phenotype seen in the IDH1mut subtype., Significance: We show that IDH1mut-generated D-2-HG can reduce glioma growth via inhibition of the m6A demethylase, FTO. FTO inhibition represents a potential therapeutic target for IDH1wt gliomas and possibly in conjunction with IDH1mut inhibitors for the treatment of IDH1mut glioma. Future studies are necessary to demonstrate the role of ATF5 downregulation in the indolent phenotype of IDH1mut gliomas, as well as to identify other involved gene transcripts deregulated by m6A hypermethylation., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Pilot-diesel-ignition ammonia combustion engines have attracted widespread attentions from the maritime sector, but there are still bottleneck problems such as high unburned NH 3 and N 2 O emissions as well as low thermal efficiency that need to be solved before further applications. In this study, a concept termed as in-cylinder reforming gas recirculation is initiated to simultaneously improve the thermal efficiency and reduce the unburned NH 3 , NO x , N 2 O and greenhouse gas emissions of pilot-diesel-ignition ammonia combustion engine. For this concept, one cylinder of the multi-cylinder engine operates rich of stoichiometric and the excess ammonia in the cylinder is partially decomposed into hydrogen, then the exhaust of this dedicated reforming cylinder is recirculated into the other cylinders and therefore the advantages of hydrogen-enriched combustion and exhaust gas recirculation can be combined. The results show that at 3% diesel energetic ratio and 1000 rpm, the engine can increase the indicated thermal efficiency by 15.8% and reduce the unburned NH 3 by 89.3%, N 2 O by 91.2% compared to the base/traditional ammonia engine without the proposed method. At the same time, it is able to reduce carbon footprint by 97.0% and greenhouse gases by 94.0% compared to the traditional pure diesel mode., (© 2024. The Author(s).)

The relationship between various patterns of mucin-producing salivary adenocarcinomas, including invasive salivary adenocarcinomas with mucinous differentiation, such as colloid and papillary carcinomas, remains unclear. Herein, we aimed to describe the clinicopathologic characteristics, immunophenotypes, molecular underpinnings, and clinical behavior of salivary mucinous adenocarcinomas (MA) to clarify their classification. We described a broad series of colloid and papillary patterns of MAs, indicating that papillary pattern presented papillary cystic proliferation of mucinous columnar cells as salivary intraductal papillary mucinous neoplasms with recurrent AKT1 E17K mutations, whereas colloid adenocarcinomas containing large mucinous pools or lakes around the malignant epithelial nests or islands harbored BRAF V600E mutations with worse prognosis. Typical morphologic structures, CK7(+), CK20(-), CDX2(-), p63(-), p40(-), MAML2 fluorescence in situ hybridization (-), AR(-), TTF-1(-), S100(-), mammaglobin(-), or S100/mammaglobin(+) with ETV6 fluorescence in situ hybridization (-) immunophenotype, and recurrent AKT1 E17K or BRAF V600E mutations may be defined. To our knowledge, this small series represents the first genetic study on a typical colloid pattern of MA, and our study with the spectrum documentation for MA in clinicopathologic characteristics, histologic and immunophenotypes, molecular features, and clinical behavior will allow for a better understanding of these rare but distinctive tumors., Competing Interests: Conflicts of Interest and Source of Funding: This research was supported by research grants from the National Natural Science Foundation of China (82103061). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The inadequacy of tactile perception systems in humanoid robotic manipulators limits the breadth of available robotic applications. Here, we designed a multifunctional flexible tactile sensor for robotic fingers that provides capabilities similar to those of human skin sensing modalities. This sensor utilizes a novel PI-MXene/SrTiO 3 hybrid aerogel developed as a sensing unit with the additional abilities of electromagnetic transmission and thermal insulation to adapt to certain complex environments. Moreover, polyimide (PI) provides a high-strength skeleton, MXene realizes a pressure-sensing function, and MXene/SrTiO 3 achieves both thermoelectric and infrared radiation response behaviors. Furthermore, via the pressure response mechanism and unsteady-state heat transfer, these aerogel-derived flexible sensors realize multimodal sensing and recognition capabilities with minimal cross-coupling. They can differentiate among 13 types of hardness and four types of material from objects with accuracies of 94% and 85%, respectively, using a decision tree algorithm. In addition, based on the infrared radiation-sensing function, a sensory array was assembled, and different shapes of objects were successfully recognized. These findings demonstrate that this PI-MXene/SrTiO 3 aerogel provides a new concept for expanding the multifunctionality of flexible sensors such that the manipulator can more closely reach the tactile level of the human hand. This advancement reduces the difficulty of integrating humanoid robots and provides a new breadth of application scenarios for their possibility., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Introduction: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). This study aimed to identify LN specific-genes and potential therapeutic targets., Methods: We performed high-throughput transcriptome sequencing on peripheral blood mononuclear cells (PBMCs) from LN patients. Healthy individuals and SLE patients without LN were used as controls. To validate the sequencing results, qRT-PCR was performed for 5 upregulated and 5 downregulated genes. Furthermore, the effect of the TNFRSF17-targeting drug IBI379 on patient plasma cells and B cells was evaluated by flow cytometry., Results: Our analysis identified 1493 and 205 differential genes in the LN group compared to the control and SLE without LN groups respectively, with 70 genes common to both sets, marking them as LN-specific. These LN-specific genes were significantly enriched in the 'regulation of biological quality' GO term and the cell cycle pathway. Notably, several genes including TNFRSF17 were significantly overexpressed in the kidneys of both LN patients and NZB/W mice. TNFRSF17 levels correlated positively with urinary protein levels, and negatively with complement C3 and C4 levels in LN patients. The TNFRSF17-targeting drug IBI379 effectively induced apoptosis in patient plasma cells without significantly affecting B cells., Discussion: Our findings suggest that TNFRSF17 could serve as a potential therapeutic target for LN. Moreover, IBI379 is presented as a promising treatment option for LN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zou, Yang, Ye, Li, Jiang, Xia, Tan, Long and Wang.)

Although intranasal oxytocin administration to tap into central functions is the most commonly used non-invasive means for exploring oxytocin's role in human cognition and behavior, the way by which intranasal oxytocin acts on the brain is not yet fully understood. Recent research suggests that brain regions densely populated with oxytocin receptors may play a central role in intranasal oxytocin's action mechanisms in the brain. In particular, intranasal oxytocin may act directly on (subcortical) regions rich in oxytocin receptors via binding to these receptors while only indirectly affecting other (cortical) regions via their neural connections to oxytocin receptor-enriched regions. Aligned with this notion, the current study adopted a novel approach to test 1) whether the connections between oxytocin receptor-enriched regions (i.e., the thalamus, pallidum, caudate nucleus, putamen, and olfactory bulbs) and other regions in the brain were responsive to intranasal oxytocin administration, and 2) whether oxytocin-induced effects varied as a function of age. Forty-six young (24.96 ± 3.06 years) and 44 older (69.89 ± 2.99 years) participants were randomized, in a double-blind procedure, to self-administer either intranasal oxytocin or placebo before resting-state fMRI. Results supported age-dependency in the effects of intranasal oxytocin administration on connectivity between oxytocin receptor-enriched regions and other regions in the brain. Specifically, compared to placebo, oxytocin decreased both connectivity density and connectivity strength of the thalamus for young participants while it increased connectivity density and connectivity strength of the caudate for older participants. These findings inform the mechanisms underlying the effects of exogenous oxytocin on brain function and highlight the importance of age in these processes., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To investigate the effects of graphene-based warm uterus acupoint paste on uterine Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-kappa B p65 (NF-κB p65) signaling pathway and Th1/Th2 immune balance in primary dysmenorrhea ( PD ) model rats, so as to reveal its immunological mechanisms of relieving dysmenorrhea., Methods: Thirty SD female rats were randomly divided into 3 groups：normal group, model group and acupoint paste group, with 10 rats in each group. PD rat model was established by subcutaneous injection of estradiol benzoate for 10 consecutive days. At the same time of modeling, graphene-based warm uterus acupoint paste was applied to the acupoints of "Guanyuan" (CV4), bilateral "Zigong" (EX-CA1) and "Sanyinjiao" (SP6) of rats in the acupoint paste group. The application was continuously applied once daily for 10 d, 5 h each time. On the 11 th day, oxytocin was injected intraperitoneally to observe the writhing latency, writhing times within 30 min and writhing score of rats in each group. The spleen and thymus indexes were calculated. The pathological changes of spleen and thymus tissue were observed after HE staining. The contents of serum immunoglobulin (Ig) A, IgG, tumor necrosis factor-α (TNF-α), interleukin (IL)-2, interferon-γ (IFN-γ), IL-4 and IL-10 were detected by ELISA . The protein and mRNA expression levels of TLR4, MyD88 and NF-κB p65 in rat uterine tissue were detected by Western blot and real-time quantitative PCR, respectively., Results: Compared with the normal group, the writhing times and writhing scores within 30 min of rats in the model group were significantly increased( P <0.001), and the rats showed writhing reaction ( P <0.01). The spleen index and thymus index were significantly decreased( P <0.01, P <0.05). The spleen and thymus had obvious pathological changes. The contents of IgA, IgG, TNF-α, IL-2 and IFN-γ in serum were significantly increased, while the contents of serum IL-4 and IL-10 were significantly decreased( P <0.001, P <0.01). The expression levels of TLR4, MyD88, NF-κB p65 protein and corresponding mRNA in uterine tissue were significantly increased( P <0.001). Following intervention, compared with the model group, the writhing latency time of rats in the acupoint paste group was prolonged, and the writhing times and writhing scores within 30 min were significantly decreased ( P <0.001). The spleen index and thymus index were significantly increased( P <0.01, P <0.05). The pathological changes of spleen and thymus were improved. The contents of serum IgA, IgG, TNF-α, IL-2 and IFN-γ were significantly decreased, while the contents of IL-4 and IL-10 were significantly increased( P <0.001, P <0.05, P <0.01). The expression of TLR4, MyD88, NF-κB p65 protein and the corresponding mRNA levels in uterine tissue were decreased( P <0.001, P <0.01)., Conclusions: Graphene-based warm uterus acupoint paste can regulate the immune balance of Th1/ Th2 by regulating TLR4/ MyD88/ NF-κB p65 signaling pathway, repair the pathological damage of immune tissue, improve immune function, and effectively relieve the pain symptoms of PD rats.

Background and Aim: The most effective among the acupoints remains to be determined for treating diabetic gastroparesis (DGP). This study aimed to compare single and combination acupoints for their effectiveness in DGP., Experimental Procedure: A prospective, patient-assessor-blinded randomised controlled trial was designed to compare the efficacy of 8-week acupuncture at a single acupoint (Zhongwan, CV-12), combination acupoints (Zhongwan, CV-12 and Zusanli, ST-36), and a sham-acupoint, in 99 adults with DGP. The primary clinical outcome was measured using the Gastroparesis Cardinal Symptom Index (GCSI), while barium meal examination, fasting plasma glucose, the 2-h plasma glucose, short-form health survey (SF-36), and GCSI subscales were performed for evaluating secondary clinical outcomes. These results were analysed by two factorial analysis of variance (ANOVA) test, Chi-Square, Fisher Exact, Kruskal-Wallis tests and Tukey's Honest Significant Difference (HSD) test., Results: After randomization, 97 patients completed the study. GCSI scores of all groups decreased during both post-treatment and the follow-up period, they were statistically significant compared to the baseline period ( p  < 0.01), but there was no significant difference among the groups ( p  > 0.05) during the post-treatment period. GCSI scores improved more in the combination acupoints group than in the single acupoint group which was better than the sham group after treatment. During the follow-up period, the same trend was observed., Conclusions: Among patients with DGP, the combination acupoints were more beneficial compared with single and sham acupoints., Trial Registration Number: NCT02452489., (© 2024 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Objective: To explore functional connectivity after intensive attention training in the chronic phase after traumatic brain injury as clinical evidence indicates that intensive attention training improves attention dysfunction in persons with traumatic brain injury., Design and Subjects: A case series study. Two young adults, 13- and 18-months post traumatic brain injury, with traumatic brain injury induced attention deficits were assigned to 20 h of intensive attention training and neuroimaging., Methods: Functional magnetic resonance imaging during a psychomotor vigilance test was conducted pre- and post-intervention., Results: The neuroimaging indicated both increased and decreased connectivity density in frontal, posterior and subcortical brain regions, for some regions with separate change patterns for left and right hemisphere respectively, and an overall reduction in variability in functional connectivity., Conclusion: The changed and decreased variability of functional connectivity in various brain regions, captured by fMRI during a psychomotor vigilance test after direct attention training in a small sample of persons with traumatic brain injury, suggests further studies of functional connectivity changes in neural networks., (© Published by Medical Journals Sweden, on behalf of the Foundation for Rehabilitation Information.)

Brachial plexus avulsion injury (BPAI) is a severe peripheral nerve injury that leads to functional reorganization of the brain. However, the interhemispheric coordination following contralateral cervical 7 nerve transfer remains unclear. In this study, 69 BPAI patients underwent resting-state functional magnetic resonance imaging examination to assess the voxel-mirrored homotopic connectivity (VMHC), which reveals the interhemispheric functional connection. The motor function of the affected upper extremity was measured using the Fugl-Meyer Assessment of Upper Extremity (FMA-UE) scale. The VMHC analysis showed significant differences between the bilateral precentral gyrus, supplementary motor area (SMA), middle frontal gyrus (MFG), and insula. Compared to the preoperative group, the VMHC of the precentral gyrus significantly increased in the postoperative short-term group (PO-ST group) but decreased in the postoperative long-term group (PO-LT group). Additionally, the VMHC of the SMA significantly increased in the PO-LT group. Furthermore, the VMHC of the precentral gyrus in the PO-ST group and the SMA in the PO-LT group were positively correlated with the FMA-UE scores. These findings highlight a positive relationship between motor recovery and increased functional connectivity of precentral gyrus and SMA, which provide possible therapeutic targets for future neuromodulation interventions to improve rehabilitation outcomes for BPAI patients., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Histone deacetylases (HDACs) have a wide range of targets and can rewire both the chromatin and lipidome of cancer cells. In this study, we show that valproic acid (VPA), a brain penetrant anti-seizure medication and histone deacetylase inhibitor, inhibits the growth of IDH1 mutant tumors in vivo and in vitro, with at least some selectivity over IDH1 wild-type tumors. Surprisingly, genes upregulated by VPA showed no enhanced chromatin accessibility at the promoter, but there was a correlation between VPA-downregulated genes and diminished promoter chromatin accessibility. VPA inhibited the transcription of lipogenic genes and these lipogenic genes showed significant decreases in promoter chromatin accessibility only in the IDH1 MT glioma cell lines tested. VPA inhibited the mTOR pathway and a key lipogenic gene, fatty acid synthase (FASN). Both VPA and a selective FASN inhibitor TVB-2640 rewired the lipidome and promoted apoptosis in an IDH1 MT but not in an IDH1 WT glioma cell line. We further find that HDACs are involved in the regulation of lipogenic genes and HDAC6 is particularly important for the regulation of FASN in IDH1 MT glioma. Finally, we show that FASN knockdown alone and VPA in combination with FASN knockdown significantly improved the survival of mice in an IDH1 MT primary orthotopic xenograft model in vivo. We conclude that targeting fatty acid metabolism through HDAC inhibition and/or FASN inhibition may be a novel therapeutic opportunity in IDH1 mutant gliomas., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Background: Malignant glioma carries a poor prognosis despite current therapeutic modalities. Standard of care therapy consists of surgical resection, fractionated radiotherapy concurrently administered with temozolomide (TMZ), a DNA-alkylating chemotherapeutic agent, followed by adjuvant TMZ. O-6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme, removes alkylated lesions from tumor DNA, thereby promoting chemoresistance. MGMT promoter methylation status predicts responsiveness to TMZ; patients harboring unmethylated MGMT (~60% of glioblastoma) have a poorer prognosis with limited treatment benefits from TMZ., Methods: Via lentiviral-mediated delivery into LN18 glioma cells, we employed deactivated Cas9-CRISPR technology to target the MGMT promoter and enhancer regions for methylation, as mediated by the catalytic domain of the methylation enzyme DNMT3A. Methylation patterns were examined at a clonal level in regions containing Differentially Methylation Regions (DMR1, DMR2) and the Methylation Specific PCR (MSP) region used for clinical assessment of MGMT methylation status. Correlative studies of genomic and transcriptomic effects of dCas9/CRISPR-based methylation were performed via Illumina 850K methylation array platform and bulk RNA-Seq analysis., Results: We used the dCas9/DNMT3A catalytic domain to achieve targeted MGMT methylation at specific CpG clusters in the vicinity of promoter, enhancer, DMRs and MSP regions. Consequently, we observed MGMT downregulation and enhanced glioma chemosensitivity in survival assays in vitro, with minimal off-target effects., Conclusion: dCas9/CRISPR is a viable method of epigenetic editing, using the DNMT3A catalytic domain. This study provides initial proof-of-principle for CRISPR technology applications in malignant glioma, laying groundwork for subsequent translational studies, with implications for future epigenetic editing-based clinical applications., (© 2024. The Author(s).)

Dementia is a brain disease which results in irreversible and progressive loss of cognition and motor activity. Despite global efforts, there is no simple and reliable diagnosis or treatment option. Current diagnosis involves indirect testing of commonly inaccessible biofluids and low-resolution brain imaging. We have developed a portable, wireless readout-based Graphene field-effect transistor (GFET) biosensor platform that can detect viruses, proteins, and small molecules with single-molecule sensitivity and specificity. We report the detection of three important amyloids, namely, Amyloid beta (Aβ), Tau (τ), and α-Synuclein (αS) using DNA aptamer nanoprobes. These amyloids were isolated, purified, and characterized from the autopsied brain tissues of Alzheimer's Disease (AD) and Parkinson's Disease (PD) patients. The limit of detection (LoD) of the sensor is 10 fM, 1-10 pM, 10-100 fM for Aβ, τ, and αS, respectively. Synthetic as well as autopsied brain-derived amyloids showed a statistically significant sensor response with respect to derived thresholds, confirming the ability to define diseased vs. nondiseased states. The detection of each amyloid was specific to their aptamers; Aβ, τ, and αS peptides when tested, respectively, with aptamers nonspecific to them showed statistically insignificant cross-reactivity. Thus, the aptamer-based GFET biosensor has high sensitivity and precision across a range of epidemiologically significant AD and PD variants. This portable diagnostic system would allow at-home and POC testing for neurodegenerative diseases globally.

Standard management protocols are lacking and specific antidotes are unavailable for acute carbamazepine (CBZ) poisoning. The objective of this review is to provide currently available information on acute CBZ poisoning, including its management, by describing and summarizing various therapeutic methods for its treatment according to previously published studies. Several treatment methods for CBZ poisoning will be briefly introduced, their advantages and disadvantages will be analyzed and compared, and suggestions for the clinical treatment of CBZ poisoning will be provided. A literature search was performed in various English and Chinese databases. In addition, the reference lists of identified articles were screened for additional relevant studies, including non-indexed reports. Non-peer-reviewed sources were also included. In the present review, 154 articles met the inclusion criteria including case reports, case series, descriptive cohorts, pharmacokinetic studies, and in vitro studies. Data on 67 patients, including 4 fatalities, were reviewed. Based on the summary of cases reported in the included articles, the cure rate of CBZ poisoning after symptomatic treatment was 82% and the efficiency of hemoperfusion was 58.2%. Based on the literature review, CBZ is moderately dialyzable and the recommendation for CBZ poisoning is supportive management and gastric lavage. In severe cases, extracorporeal treatment is recommended, with hemodialysis as the first choice., Competing Interests: Conflict-of-interest statement: The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted and entitled ‘Management of Acute Carbamazepine Poisoning: A Narrative Review’., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Contralateral cervical seventh (cC7) nerve to C7 transfer has been proven effective for treating spastic upper limb. However, for those whose major impairment is not in the C7 area, cC7 nerve transfer to other nerve(s) may achieve a better outcome. The aim of this study was to explore the optimal surgical approach for transferring cC7 to one or two nerves by cadaveric study and to discuss the possible applications for hemiplegic patients., Methods: Modified cC7 transfer to one (five procedures) or two nonadjacent (three procedures) nerve roots was proposed, and success rates of direct coaptation through two surgical approaches were compared: the superficial surface of longus colli (sLC) and the deep surface of longus colli (dLC) approaches. The length, diameter and distance of relevant nerves were also measured in 25 cadavers., Results: Compared with the sLC approach, the distance of the dLC approach was 1.1 ± 0.3 cm shorter. The success rates for the sLC and dLC approaches were as follows, respectively: cC7-C5 surgery, 94% and reached 98%; cC7-C6 surgery, 54% and 96%; cC7-C7 surgery, 42% and 94%; cC7-C8 surgery, 34% and 94%; cC7-T1 surgery, 24% and 62%; cC7-C5C7 surgery, 74% and 98%; cC7-C6C8 surgery, 54% and 98%. cC7-C7T1 surgery, 42% and 88%., Conclusions: The dLC approach greatly improved direct coaptation rate for cC7 nerve transfer. The modified cC7 nerve transfer procedures are technically feasible for further application in clinic., Competing Interests: Conflicts of interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Human physiological metabolic status can be obtained by monitoring exhaled CO 2 concentration, but current CO 2 sensors have disadvantages such as large size, high power consumption, and slow response time, which limit their application in wearable devices and portable instruments. In this article, we report a small size, good performance, and large range CO 2 infrared gas sensor that integrates a high emissivity MEMS emitter chip, a high detectivity thermopile chip, and a high coupling efficiency optical chamber to achieve high efficiency optical-thermal-electrical conversion. Compared with typical commercial sensors, the size of the sensor can be reduced by approximately 80% to only 10 mm × 10 mm × 6.5 mm, with the advantages of low power consumption and fast response speed. Further, a monitoring system for end-tidal CO 2 concentration installed on a mask was developed using this sensor, and good results were achieved., Competing Interests: T.L. is the inventor of a patent filed for the CO2 sensor and the authors of this article declare no competing interests., (© 2023 The Authors.)

The detection of β-galactosidase (β-gal) activity produced by Escherichia coli ( E. coli ) can quickly analyze the pollution degree of seawater bodies in bathing and fishing grounds to avoid large-scale outbreaks of water pollution. Here, a functionalized biosensor based on graphene-based field effect transistor (GFET) modified with heat-denatured casein was developed for the ultrasensitive and label-free detection of the β-gal produced by E. coli in real water samples. The heat-denatured casein coated on the graphene surface, as a probe linker and blocker, plays an important role in fabricating GEFT biosensor. The GFET biosensor response to the β-gal produced by E. coli has a wide concentration dynamic range spanning nine orders of magnitude, in a concentration range of 1 fg·mL -1 -100 ng·mL -1 , with a limit of detection (LOD) 0.187 fg·mL -1 (1.61 aM). In addition to its attomole sensitivity, the GFET biosensor selectively recognized the β-gal in the water sample and showed good selectivity. Importantly, the detection process of the β-gal produced by E. coli can be completed by a straightforward one-step specific immune recognition reaction. These results demonstrated the usefulness of the approach, meeting environmental monitoring requirements for future use.

Background/purpose: Cancer is an important part of the global burden of childhood diseases. Head and neck carcinoma in children is rare and related research is limited. This study aimed to investigate the clinicopathological features of childhood head and neck carcinoma., Materials and Methods: Forty-two cases of childhood head and neck carcinoma treated in our institution were reviewed and analyzed., Results: Median age overall was 11 years. Twenty-three patients (54.8%) were male and 19 (45.2%) were female. Parotid gland location was most common (54.8%). Mucoepidermoid carcinoma and squamous cell carcinoma were the most common histological types (57.1% and 11.9%, respectively). Two patients had a history of bone marrow transplantation and two had a history of odontogenic keratocyst. The recurrence rate after treatment was 8.6%., Conclusion: Early diagnosis and treatment and close follow-up of childhood head and neck carcinoma are warranted to prevent recurrence and improve clinical outcome., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Background: Tumor-associated macrophages (TAMs) are an important subset of innate immune cells in the tumor microenvironment, and they are pivotal regulators of tumor-promoting inflammation and tumor progression. Evidence has proven that TAM numbers are substantially increased in cancers, and most of these TAMs are polarized toward the alternatively activated M2 phenotype; Thus, these TAMs strongly promote the progression of cancer diseases. Type 1 innate lymphocytes (ILC1s) are present in high numbers in intestinal tissues and are characterized by the expression of the transcription factor T-bet and the secretion of interferon (IFN)-γ, which can promote macrophages to polarize toward the classically activated antitumor M1 phenotype. However, the relationship between these two cell subsets in colon cancer remains unclear., Methods: Flow cytometry was used to determine the percentages of M1-like macrophages, M2-like macrophages and ILC1s in colon cancer tissues and paracancerous healthy colon tissues in the AOM/DSS-induced mouse model of colon cancer. Furthermore, ILC1s were isolated and bone marrow-derived macrophages were generated to analyze the crosstalk that occurred between these cells when cocultured in vitro. Moreover, ILC1s were adoptively transferred or inhibited in vivo to explore the effects of ILC1s on tumor-infiltrating macrophages and tumor growth., Results: We found that the percentages of M1-like macrophages and ILC1s were decreased in colon cancer tissues, and these populations were positively correlated. ILC1s promoted the polarization of macrophages toward the classically activated M1-like phenotype in vitro, and this effect could be blocked by an anti-IFN-γ antibody. The in vivo results showed that the administration of the Group 1 innate lymphocyte-blocking anti-NK1.1 antibody decreased the number of M1-like macrophages in the tumor tissues of MC38 tumor-bearing mice and promoted tumor growth, and adoptive transfer of ILC1s inhibited tumors and increased the percentage of M1-like macrophages in MC38 tumor-bearing mice., Conclusions: Our studies preliminarily prove for the first time that ILC1s promote the activation of M1-like macrophages by secreting IFN-γ and inhibit the progression of colon cancer, which may provide insight into immunotherapeutic approaches for colon cancer., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Compressed sensing (CS) MRI has shown great potential in enhancing time efficiency. Deep learning techniques, specifically generative adversarial networks (GANs), have emerged as potent tools for speedy CS-MRI reconstruction. Yet, as the complexity of deep learning reconstruction models increases, this can lead to prolonged reconstruction time and challenges in achieving convergence. In this study, we present a novel GAN-based model that delivers superior performance without the model complexity escalating. Our generator module, built on the U-net architecture, incorporates dilated residual (DR) networks, thus expanding the network's receptive field without increasing parameters or computational load. At every step of the downsampling path, this revamped generator module includes a DR network, with the dilation rates adjusted according to the depth of the network layer. Moreover, we have introduced a channel attention mechanism (CAM) to distinguish between channels and reduce background noise, thereby focusing on key information. This mechanism adeptly combines global maximum and average pooling approaches to refine channel attention. We conducted comprehensive experiments with the designed model using public domain MRI datasets of the human brain. Ablation studies affirmed the efficacy of the modified modules within the network. Incorporating DR networks and CAM elevated the peak signal-to-noise ratios (PSNR) of the reconstructed images by about 1.2 and 0.8 dB, respectively, on average, even at 10× CS acceleration. Compared to other relevant models, our proposed model exhibits exceptional performance, achieving not only excellent stability but also outperforming most of the compared networks in terms of PSNR and SSIM. When compared with U-net, DR-CAM-GAN's average gains in SSIM and PSNR were 14% and 15%, respectively. Its MSE was reduced by a factor that ranged from two to seven. The model presents a promising pathway for enhancing the efficiency and quality of CS-MRI reconstruction.

Multifunctional selectivity and mechanical properties are always a focus of attention in the field of flexible sensors. In particular, the construction of biomimetic architecture for sensing materials can endow the fabricated sensors with intrinsic response features and extra-derived functions. Here, inspired by the asymmetric structural features of human skin, a novel tannic acid (TA)-modified MXene-polyurethane film with a bionic Janus architecture is proposed, which is prepared by gravity-driven self-assembly for the gradient dispersion of 2D TA@MXene nanosheets into a PU network. This obtained film reveals strong mechanical properties of a superior elongation at a break of 2056.67% and an ultimate tensile strength of 50.78 MPa with self-healing performance. Moreover, the Janus architecture can lead to a selective multifunctional response of flexible sensors to directional bending, pressure, and stretching. Combined with a machine learning module, the sensor is endowed with high recognition rates for force detection (96.1%). Meanwhile, direction identification in rescue operations and human movement monitoring can be realized by this sensor. This work offers essential research value and practical significance for the material structures, mechanical properties, and application platforms of flexible sensors., (© 2023 Wiley-VCH GmbH.)

Tuberculosis (TB), the second (after COVID-19) deadliest infectious killer, is a chronic infectious disease caused by infection with Mycobacterium tuberculosis (M.T.), where early diagnosis and management are the key to containing the condition. Here, we report a novel biosensor for the detection of M.T. DNA based on magnetic separation, urease catalysis and silicon nanowire field effect transistor (SiNW FET) detection. M.T. DNA is sequence-specifically captured by magnetic nanoparticles and urease-labelled silica nanoparticles simultaneously to form a sandwich complex and urea is catalyzed into ammonium carbonate by urease modified on a sandwich complex. By using SiNW FET, the detection of M.T. DNA is realized indirectly by the detection of ammonium carbonate. The limit of detection (LOD) was determined to be 78.541 fM. The specificity of the biosensor was confirmed by detecting a panel of bacterial species. The utility of the biosensor was demonstrated in real-sample analysis and the recovery study of M.T. DNA was done in the genomic DNA extracted from cultured Mycobacterium tuberculosis . The biosensor holds promise to become a rapid, sensitive and accurate method for clinical diagnosis.

We developed a rapid and accurate biosensor to detect SARS-CoV-2 and distinguish its mutations. Benefitting from a DNA framework-modified ordered interface and a dual signal amplification strategy, our biosensor could detect SARS-CoV-2 with a detection limit down to 10 fM. It performed well on pseudo virus and SARS-CoV-2 RNA standard materials, revealing the potential application in disease diagnosis and spread, in combination with a home-made smartphone.