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Abstract Prophylactic dissection of paratracheal lymph nodes in clinically lymph node-negative (cN0) papillary thyroid carcinoma (PTC) remains controversial. This study aims to integrate preoperative and intraoperative variables to compare traditional nomograms and machine learning (ML) models, developing and validating an interpretable predictive model for paratracheal lymph node metastasis (PLNM) in cN0 PTC patients. We retrospectively selected 3213 PTC patients treated at the First Affiliated Hospital of Chongqing Medical University from 2016 to 2020. They were randomly divided into the training and test datasets with a 7:3 ratio. The 533 PTC patients treated at the Guangyuan Central Hospital from 2019 to 2022 were used as an external test sets. We developed and validated nine ML models using 10-fold cross-validation and grid search for hyperparameter tuning. The predictive performance was evaluated using ROC curves, decision curve analysis (DCA), calibration curves, and precision-recall curves. The best model was compared to a traditional logistic regression-based nomogram. The XGBoost model achieved AUC values of 0.935, 0.857, and 0.775 in the training, validation, and test sets, respectively, significantly outperforming the traditional nomogram model with AUCs of 0.85, 0.844, and 0.769, respectively. SHapley Additive exPlanations (SHAP)-based visualization identified the top 10 predictive features of the XGBoost model, and a web-based calculator was created based on these features. ML is a reliable tool for predicting PLNM in cN0 PTC patients. The SHAP method provides valuable insights into the XGBoost model, and the resultant web-based calculator is a clinically useful tool to assist in the surgical planning for paratracheal lymph node dissection.

Abstract Astrocyte swelling is implicated in various neurological disorders. However, whether astrocyte swelling contributes to neuropathic pain remains elusive. This study elucidates the pivotal role of the nuclear factor of activated T‐cells 5 (NFAT5) emerges as a master regulator of astrocyte swelling in the spinal dorsal horn (SDH) during neuropathic pain. Despite the ubiquitous expression of NFAT5 protein in SDH cell types, it selectively induces swelling specifically in astrocytes, not in microglia. Mechanistically, NFAT5 directly controls the expression of the water channel aquaporin‐4 (AQP4), a key regulator exclusive to astrocytes. Additionally, aurora kinase B (AURKB) orchestrates NFAT5 phosphorylation, enhancing its protein stability and nuclear translocation, thereby regulating AQP4 expression. The findings establish NFAT5 as a crucial regulator for neuropathic pain through the modulation of astrocyte swelling. The AURKB‐NFAT5‐AQP4 pathway in astrocytes emerges as a potential therapeutic target to combat neuropathic pain.

Neuropathic pain often leads to negative emotions, which in turn can enhance the sensation of pain. This study aimed to investigate the molecular mechanisms mediating neuropathic pain and negative emotions. Chronic constriction injury (CCI) rats were used as model animals and behavioral tests were conducted to assess pain and negative emotions. Then, the rat anterior cingulate cortex (ACC) was analyzed using UPLC-MS/MS and subsequently integrated with our previously published transcriptome data. Metabolomics analysis revealed that 68 differentially expressed metabolites (DEMs) were identified, mainly in amino acid metabolites and fatty acyls. Combined with our previously published transcriptome data, we predicted two genes that potentially exhibited associations with these metabolites, respectively Apolipoprotein L domain containing 1 (Apold1) and WAP four-disulfide core domain 1 (Wfdc1). Taken together, our results indicated that peripheral nerve injury contributing to neuropathic pain and pain-related depression may be associated with these metabolites and genes. This research provides new insights into the molecular regulatory mechanism, which could serve as a reference for the treatment of neuropathic pain and pain-related depression.

Regulation of gene transcription in the spinal dorsal horn (SDH) plays a critical role in the pathophysiology of neuropathic pain. In this study, we investigated whether the transcription factor STAT2 affects neuropathic pain and evaluated its possible mechanisms. A proteomic analysis showed that the nuclear fraction of STAT2 protein in the SDH was downregulated after chronic constriction injury of the rat sciatic nerve, which was associated with the development of neuropathic pain. Similarly, siRNA-induced downregulation of STAT2 in the SDH of naïve rats also resulted in pain hypersensitivity. Using RNA-sequencing analysis, we showed that reduction of nuclear STAT2 after chronic constriction injury was associated with increased expression of microglial activation markers, including the class II transactivator and major histocompatibility complex class II proteins. In addition, siRNA-induced downregulation of STAT2 promoted microglial activation and pro-inflammatory cytokine expression in the SDH. Taken together, these results showed that chronic constriction injury caused downregulation of nuclear STAT2 in the SDH, which may result in microglial activation and development of neuropathic pain. Our findings indicate that restoration of nuclear expression of STAT2 could be a potential pathway for the treatment of neuropathic pain.

Herein, an ultrasensitive DNAzyme-based fluorescence biosensor for detecting Cu2+ was designed using the cascade signal amplification strategy, coupling λ-exonuclease-assisted target recycling and mismatched catalytic hairpin assembly (MCHA). In the designed detection system, the target, Cu2+, can activate the Cu2+-dependent DNAzyme to cause a cleavage reaction, releasing ssDNA (tDNA). Then, tDNA binds to hairpin DNA (H0) with an overhanging 5′-phosphorylated terminus to form dsDNA with a blunt 5′-phosphorylated terminus, which activates the dsDNA to be digested by λ-Exo and releases tDNA along with another ssDNA (iDNA). Subsequently, the iDNA initiates MCHA, which can restore the fluorescence of carboxyfluorescein (FAM) previously quenched by tetramethylrhodamine (TAMRA), resulting in a strong fluorescent signal. Furthermore, MCHA efficiently improves the signal-to-noise ratio of the detection system. More importantly, tDNA recycling can be achieved with the λ-Exo digestion reaction to release more iDNA, efficiently amplifying the fluorescent signal and further improving the sensitivity to Cu2+ with a detection limit of 60 fM. The practical application of the developed biosensor was also demonstrated by detecting Cu2+ in real samples, proving it to be an excellent analytical strategy for the ultrasensitive quantification of heavy metal ions in environmental water sources.

Morphine is widely used in the treatment of moderate to severe pain. Long-term use of morphine leads to various adverse effects, such as tolerance and hyperalgesia. Vesicular glutamate transporter 2 (VGluT2) accumulates glutamate into synaptic vesicles and plays multiple roles in the central nervous system. However, the specific role of VGluT2 in morphine tolerance has not been fully elucidated. Here, we investigated the regulatory role of VGluT2 in morphine tolerance and assessed the potential role of the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) pathway in VGluT2 mediated morphine antinociceptive tolerance in mice. In the present study, we found that VGluT2 is upregulated in the spinal cord after the development of morphine tolerance. Furthermore, inhibition of VGluT2 with its antagonist (Chicago sky blue 6 B, CSB6B) or knockdown of VGluT2 by lentivirus restored the analgesic effect of morphine, suppressed the activation of astrocytes and microglia, and decreased glial-derived pro-inflammatory cytokines. Overexpression of VGluT2 by lentivirus facilitated morphine tolerance and mechanical hyperalgesia. In addition, we found the expression of BDNF is correlated with VGluT2 expression in the spinal cord after chronic morphine administration. Intrathecal injection of the BDNF/TrkB pathway antagonist K252a attenuated the development of morphine tolerance and decreased the expression of VGluT2 in the spinal cord, which suggested the BDNF/TrkB pathway participates in the regulation of VGluT2 in morphine tolerance. This study elucidates the functional capability of VGluT2 in modulating morphine tolerance and identifies a novel mechanism and promising therapeutic target for morphine tolerance.

Abstract Background Urosepsis is a catastrophic complication, which can easily develop into septic shock and lead to death if not diagnosed early and effectively treated in time. However, there is a lack of evidence on the risk factors and outcomes in calculous pyonephrosis patients. Therefore, this study was conducted to identify risk factors and outcomes of intra- and postoperative urosepsis in this particular population. Methods Clinical data of 287 patients with calculous pyonephrosis were collected. In the univariate and multivariate analysis, all patients were divided into urosepsis group and non-urosepsis group. The diagnosis of urosepsis was mainly on the basis of the criteria of American College of Chest Physicians (ACCP)/Society of Critical Care Medicine (SCCM). Patient characteristics and outcomes data were analyzed, and risk factors were assessed by binary logistic regression analysis. Results Of 287 patients, 41 (14.3%) acquired urosepsis. Univariate analysis showed that white blood cell (WBC > 10*10^9/L) before surgery (P = 0.027), surgery types (P = 0.009), hypotension during surgery (P

Non-layered two-dimensional (2D) materials have sparked much interest recently due to their atomic thickness, large surface area, thickness- and facet-dependent properties. Currently, these materials are mainly grown from wet-chemistry methods but suffer from small size, low quality, and multi-facets, which is a major challenge hindering their facet-dependent property studies and applications. Here, we report the facet-engineered growth (FEG) of non-layered 2D manganese chalcogenides (MnX, X = S, Se, Te) based on the chemical vapor deposition method. The as-grown samples exhibit large-area surfaces of single facet, high-crystallinity, and ordered domain orientation. As a proof-of-concept, we show the facet-dependent electrocatalytic property of non-layered 2D MnSe, proving they are ideal candidates for fundamental research. Furthermore, we elucidate the underlying mechanism of FEG during the vapor growth process by the interfacial energy derived nucleation models. The method developed in this work provides new opportunities for regulating and designing the structure of 2D materials. [ABSTRACT FROM AUTHOR]

A convenient and portable smartphone-assisted method for the colorimetric detection of uranyl ions (UO2 2+) in aqueous solutions is proposed using rifampicin and 2-(5-bromo-2-pyridylazo)-5- diethylaminophenol (Br-PADAP) as chromogenic agents. The addition of UO2 2+ would cause reaction with chromogenic agents to form complexes, changing the colour from orange to dark red in the rifampicin system and from yellow to light pink in the Br-PADAP system. To achieve the on-site estimation of the trace UO2 2+ concentration range, digital images of colour changes captured by the smartphone under fixed lighting conditions were imported into the built-in application named "Detect" to obtain HSV (hue, saturation, and value) and HSL (hue, saturation, lightness) information, which could be associated with the concentration of uranyl ions. For more precise laboratory-level detection, ultraviolet-visible (UV-vis) spectroscopy was employed as well. The absorbance of the rifampicin system exhibited strong linearity with the UO2 2+ concentration in the range from 4 to 50 µM at 375 nm with a method detection limit (MDL) of 3.17 µM by the UV-vis-based method, while that of Br-PADAP system had a linear relationship with the concentration from 0.9 to 7 &#181, M at 562 nm with an MDL of 0.89 µM. The two strategies may be combined to detect UO2 2+ across a larger concentration range, and this method has been successfully used to analyze real samples including soil around uranium mines. [ABSTRACT FROM AUTHOR]