A new nomogram based on ultrasound and clinical features for distinguishing epididymal tuberculosis and nontuberculous epididymitis.

Using ultrasound findings and clinical characteristics, we constructed and validated a new nomogram for distinguishing epididymal tuberculosis from nontuberculous epididymitis, both of which share similar symptoms. We retrospectively examined data of patients with epididymal tuberculosis and nontuberculous epididymitis hospitalized between January 1, 2013, and March 31, 2023. Eligible patients were randomly assigned to derivation and validation cohorts (ratio, 7:3). We drew a nomogram to construct a diagnostic model through multivariate logistic regression and visualize the model. We used concordance index, calibration plots, and decision curve analysis to assess the discrimination, calibration, and clinical usefulness of the nomogram, respectively. In this study, 136 participants had epididymal tuberculosis and 79 had nontuberculous epididymitis. Five variables-C-reactive protein level, elevated scrotal skin temperature, nodular lesion, chronic infection, and scrotal skin ulceration-were significant and used to construct the nomogram. Concordance indices of the derivation and validation cohorts were 0.95 and 0.96, respectively (95% confidence intervals, 0.91-0.98 and 0.92-1.00, respectively). Decision curve analysis of this nomogram revealed that it helped differentiate epididymal tuberculosis from nontuberculous epididymitis. This nomogram may help clinicians distinguish between epididymal tuberculosis and nontuberculous epididymitis, thereby increasing diagnosis accuracy.

The value of synthetic MRI for quantitative analysis in the diagnosis of cervical lymph node metastasis in thyroid cancer.

BACKGROUND: Preoperative effective assessment of cervical lymph node metastasis in thyroid cancer plays an important role in formulating the surgical plan. PURPOSE: To investigate the significance of synthetic magnetic resonance imaging (MRI) for quantitatively analyzing cervical lymph node metastasis in thyroid cancer. MATERIAL AND METHODS: A retrospective analysis was conducted on 30 patients with thyroid cancer, consisting of 19 thyroid cancer nodules, 45 metastatic lymph nodes, and 47 non-metastatic lymph nodes. Regions of interest (ROIs) for each type of nodule were manually delineated using a workstation. Quantitative parameters, such as T1, T2, and proton density (PD) values, were automatically extracted from synthetic MRI scans. Statistical tests and regression analysis were performed to assess differences and correlations among the quantitative parameters. RESULTS: There were no significant differences in the quantitative parameter values between the primary tumor and metastatic lymph node tissues (P > 0.05). However, significant differences were observed in the quantitative parameters between the primary tumor and non-metastatic lymph node tissues and between the metastatic and non-metastatic lymph node tissues (P < 0.05). The diagnostic accuracy for cervical lymph node metastasis in thyroid cancer was 94.4% for the T1 and T2 combined index, 91.9% for T2, 86.8% for T1, and 71.7% for PD values. CONCLUSION: The application of quantitative parameters from synthetic MRI can assist clinicians in accurately planning surgical interventions for thyroid cancer patients before surgery.

Self-Powered Terahertz Modulators Based on Metamaterials, Liquid Crystals, and Triboelectric Nanogenerators.

6G communication mainly occurs in the THz band (0.1-10 THz), which can achieve excellent performance. Self-powered THz modulators are essential for achieving better conduction, modulation, and manipulation of THz waves. Herein, a self-powered terahertz modulator, which is based on metamaterials, liquid crystals (LCs), and rotary triboelectric nanogenerators (R-TENGs), is proposed to realize the driving of different array elements. The corresponding designs can achieve an integrated design and preparation method for dynamic spectrum-reconfigurable liquid crystal metamaterials. In addition, for the type of cross-structure metamaterial liquid crystal box, a phase modulation of 1 GHz is achieved at frequencies of 0.117 and 0.161 THz with modulation depths of 13 and 11%, respectively. Because the R-TENG with a multifan blade and circular electrodes can generate 18 peaks of electric output in every rotation, it can successfully provide sufficient frequency alternating-current electric energy to drive the terahertz modulator and achieve a self-powered function. Our findings lay a solid theoretical foundation for further building self-powered THz communication systems and promote the development of a theoretical system for LC-driving spectrum-reconfigurable devices in the THz domain.

Divergent and gram-scale syntheses of (-)-veratramine and (-)-cyclopamine.

Veratramine and cyclopamine, two of the most representative members of the isosteroidal alkaloids, are valuable molecules in agricultural and medicinal chemistry. While plant extraction of these compounds suffers from uncertain supply, efficient chemical synthesis approaches are in high demand. Here, we present concise, divergent, and scalable syntheses of veratramine and cyclopamine with 11% and 6.2% overall yield, respectively, from inexpensive dehydro-epi-androsterone. Our synthesis readily provides gram quantities of both target natural products by utilizing a biomimetic rearrangement to form the C-nor-D-homo steroid core and a stereoselective reductive coupling/(bis-)cyclization sequence to establish the (E)/F-ring moiety.

Chemoproteomics enables identification of coatomer subunit zeta-1 targeted by a small molecule for enterovirus A71 inhibition.

Human enterovirus A71 (EV-A71) is a significant etiological agent responsible for epidemics of hand, foot, and mouth disease (HFMD) in Asia-Pacific regions. There are presently no licensed antivirals against EV-A71, and the druggable target for EV-A71 remains very limited. The phenotypic hit 10,10'-bis(trifluoromethyl) marinopyrrole A derivative, herein termed MPA-CF3, is a novel potent small-molecule inhibitor against EV-A71, but its pharmacological target(s) and antiviral mechanisms are not defined. Here, quantitative chemoproteomics deciphered the antiviral target of MAP-CF3 as host factor coatomer subunit zeta-1 (COPZ1). Mechanistically, MPA-CF3 disrupts the interaction of COPZ1 with the EV-A71 nonstructural protein 2C by destabilizing COPZ1 upon binding. The destruction of this interaction blocks the coatomer-mediated transport of 2C to endoplasmic reticulum, and ultimately inhibits EV-A71 replication. Taken together, our study disclosed that MPA-CF3 can be a structurally novel host-targeting anti-EV-A71 agent, providing a structural basis for developing the COPZ1-targeting broad-spectrum antivirals against enteroviruses. The mechanistic elucidation of MPA-CF3 against EV-A71 may offer an alternative COPZ1-involved therapeutic pathway for enterovirus infection.

Gene expression and immune infiltration analysis comparing lesioned and preserved subchondral bone in osteoarthritis.

Background: Osteoarthritis (OA) is a degenerative disease requiring additional research. This study compared gene expression and immune infiltration between lesioned and preserved subchondral bone. The results were validated using multiple tissue datasets and experiments. Methods: Differentially expressed genes (DEGs) between the lesioned and preserved tibial plateaus of OA patients were identified in the GSE51588 dataset. Moreover, functional annotation and protein-protein interaction (PPI) network analyses were performed on the lesioned and preserved sides to explore potential therapeutic targets in OA subchondral bones. In addition, multiple tissues were used to screen coexpressed genes, and the expression levels of identified candidate DEGs in OA were measured by quantitative real-time polymerase chain reaction. Finally, an immune infiltration analysis was conducted. Results: A total of 1,010 DEGs were identified, 423 upregulated and 587 downregulated. The biological process (BP) terms enriched in the upregulated genes included "skeletal system development", "sister chromatid cohesion", and "ossification". Pathways were enriched in "Wnt signaling pathway" and "proteoglycans in cancer". The BP terms enriched in the downregulated genes included "inflammatory response", "xenobiotic metabolic process", and "positive regulation of inflammatory response". The enriched pathways included "neuroactive ligand-receptor interaction" and "AMP-activated protein kinase signaling". JUN, tumor necrosis factor α, and interleukin-1ß were the hub genes in the PPI network. Collagen XI A1 and leucine-rich repeat-containing 15 were screened from multiple datasets and experimentally validated. Immune infiltration analyses showed fewer infiltrating adipocytes and endothelial cells in the lesioned versus preserved samples. Conclusion: Our findings provide valuable information for future studies on the pathogenic mechanism of OA and potential therapeutic and diagnostic targets.

Design, synthesis, and biological evaluation of new bis-benzylisoquinoline-based analogues as potential neuromuscular blocking agents.

Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure-activity and configuration-activity relationships of these derivatives and 29a's binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.

A Spatiotemporal Probabilistic Graphical Model Based on Adaptive Expectation-Maximization Attention for Individual Trajectory Reconstruction Considering Incomplete Observations.

Spatiotemporal information on individual trajectories in urban rail transit is important for operational strategy adjustment, personalized recommendation, and emergency command decision-making. However, due to the lack of journey observations, it is difficult to accurately infer unknown information from trajectories based only on AFC and AVL data. To address the problem, this paper proposes a spatiotemporal probabilistic graphical model based on adaptive expectation maximization attention (STPGM-AEMA) to achieve the reconstruction of individual trajectories. The approach consists of three steps: first, the potential train alternative set and the egress time alternative set of individuals are obtained through data mining and combinatorial enumeration. Then, global and local potential variables are introduced to construct a spatiotemporal probabilistic graphical model, provide the inference process for unknown events, and state information about individual trajectories. Further, considering the effect of missing data, an attention mechanism-enhanced expectation-maximization algorithm is proposed to achieve maximum likelihood estimation of individual trajectories. Finally, typical datasets of origin-destination pairs and actual individual trajectory tracking data are used to validate the effectiveness of the proposed method. The results show that the STPGM-AEMA method is more than 95% accurate in recovering missing information in the observed data, which is at least 15% more accurate than the traditional methods (i.e., PTAM-MLE and MPTAM-EM).

Piezotronic Transistors Based on GaN Wafer for Highly Sensitive Pressure Sensing with High Linearity and High Stability.

Piezotronic effect utilizing strain-induced piezoelectric polarization to achieve interfacial engineering in semiconductor nanodevices exhibits great advantages in applications such as human-machine interfacing, micro/nanoelectromechanical systems, and next-generation sensors and transducers. However, it is a big challenge but highly desired to develop a highly sensitive piezotronic device based on piezoelectric semiconductor wafers and thus to push piezotronics toward wafer-scale applications. Here, we develop a bicrystal barrier-based piezotronic transistor for highly sensitive pressure sensing by p-GaN single-crystal wafers. Its pressure sensitivity can be as high as 19.83 meV/MPa, which is more than 15 times higher than previous bulk-material-based piezotronic transistors and reaches the level of nanomaterial-based piezotronic transistors. Moreover, it can respond to a very small strain of 3.3 × 10-6 to 1.1 × 10-5 with high gauge factors of 1.45 × 105 to 1.38 × 106, which is a very high value among various strain sensors. Additionally, it also exhibits high stability (current stability of 97.32 ± 2.05% and barrier height change stability of 95.85 ± 3.43%) and high linearity (R2 ∼ 0.997 ± 0.002) in pressure sensing. This work proves the possibility of designing a bicrystal barrier as the interface to obtain a strong piezotronic effect and highly sensitive piezotronic devices based on wafers, which contributes to their applications.

Electric pulse-tuned piezotronic effect for interface engineering.

Investigating interface engineering by piezoelectric, flexoelectric and ferroelectric polarizations in semiconductor devices is important for their applications in electronics, optoelectronics, catalysis and many more. The interface engineering by polarizations strongly depends on the property of interface barrier. However, the fixed value and uncontrollability of interface barrier once it is constructed limit the performance and application scenarios of interface engineering by polarizations. Here, we report a strategy of tuning piezotronic effect (interface barrier and transport controlled by piezoelectric polarization) reversibly and accurately by electric pulse. Our results show that for Ag/HfO2/n-ZnO piezotronic tunneling junction, the interface barrier height can be reversibly tuned as high as 168.11 meV by electric pulse, and the strain (0-1.34‰) modulated current range by piezotronic effect can be switched from 0-18 nA to 44-72 nA. Moreover, piezotronic modification on interface barrier tuned by electric pulse can be up to 148.81 meV under a strain of 1.34‰, which can totally switch the piezotronic performance of the electronics. This study provides opportunities to achieve reversible control of piezotronics, and extend them to a wider range of scenarios and be better suitable for micro/nano-electromechanical systems.

Genome-Wide Identification and Characterization of the GRAS Gene Family in Lettuce Revealed That Silencing LsGRAS13 Delayed Bolting.

Lettuce is susceptible to high-temperature stress during cultivation, leading to bolting and affecting yield. Plant-specific transcription factors, known as GRAS proteins, play a crucial role in regulating plant growth, development, and abiotic stress responses. In this study, the entire lettuce LsGRAS gene family was identified. The results show that 59 LsGRAS genes are unevenly distributed across the nine chromosomes. Additionally, all LsGRAS proteins showed 100% nuclear localization based on the predicted subcellular localization and were phylogenetically classified into nine conserved subfamilies. To investigate the expression profiles of these genes in lettuce, we analyzed the transcription levels of all 59 LsGRAS genes in the publicly available RNA-seq data under the high-temperature treatment conducted in the presence of exogenous melatonin. The findings indicate that the transcript levels of the LsGRAS13 gene were higher on days 6, 9, 15, 18, and 27 under the high-temperature (35/30 °C) treatment with melatonin than on the same treatment days without melatonin. The functional studies demonstrate that silencing LsGRAS13 accelerated bolting in lettuce. Furthermore, the paraffin sectioning results showed that flower bud differentiation in LsGRAS13-silenced plants occurred significantly faster than in control plants. In this study, the LsGRAS genes were annotated and analyzed, and the expression pattern of the LsGRAS gene following melatonin treatment under high-temperature conditions was explored. This exploration provides valuable information and identifies candidate genes associated with the response mechanism of lettuce plants high-temperature stress.

Synchronous Switching Strategy to Enhance the Real-Time Powering and Charging Performance of Triboelectric Nanogenerator.

Triboelectric nanogenerators (TENGs) are of great significance as sustainable power sources that harvest energy from the human body and environment. Nevertheless, due to TENG's impedance-dependent output voltage characteristics, in traditional strategy (TS), real-timely powering a sensor with TENG has a poor sensing on/off ratio (or response), and directly charging a capacitor with TENG shows a low charging efficiency. This degraded real-time powering and charging performance of TENG compared to a commercial constant voltage source has been a huge challenge of the TENG field for a long time. Here, we propose a synchronous switching strategy (SSS) for TENG to real-timely power sensors or charge capacitors without degrading its performance. Compared with TS, this new strategy enables sensors to have 5-7 times sensing on/off ratio enhancement when using TENG as a power source, reaching the powering ability of a commercial constant voltage source, it makes the powering performance of TENG stable under different driving frequency, improving the powering robustness of TENG. In addition, compared with TS, SSS can also enhance the charging efficiency of TENG in every charging cycle by up to 2.4 times when charging capacitors. This work contributes to real-timely powering or charging the distributed, mobile and wireless electronics using TENG. This article is protected by copyright. All rights reserved.

Influence of preoperative antituberculosis chemotherapy duration on perioperative complications in patients treated with epididymectomy for epididymal tuberculosis.

OBJECTIVES: We aimed to investigate the influence of preoperative antituberculosis chemotherapy duration on perioperative epididymectomy complications in patients with epididymal tuberculosis (ETB). METHODS: This retrospective study examined patients with ETB between January 1, 2013, and March 31, 2023, who underwent unilateral epididymectomy at our hospital. We selected preoperative antituberculosis chemotherapy duration of 2, 4, and 8 weeks as the cutoffs for this study, to explore whether there are differences in the incidence of intraoperative and 30-day postoperative complications among the patients with different preoperative antituberculosis chemotherapy durations. Intraoperative complications were graded according to the Satava classification, and 30-day postoperative complications were defined according to the Clavien-Dindo classification. The study groups were compared using the unpaired t-test, Wilcoxon rank-sum test, Pearson's chi-square test, or Fisher's exact test, as appropriate. RESULTS: Overall, 155 patients were included. Statistical analysis revealed that there were no significant differences in the incidence of intraoperative and 30-day postoperative complications between patients with shorter preoperative antituberculosis chemotherapy duration and those with longer preoperative antituberculosis chemotherapy duration. CONCLUSIONS: In patients with ETB, preoperative antituberculosis chemotherapy duration did not significantly affect the incidence of perioperative complications after epididymectomy.

Gamma oscillations induced by 40-Hz visual-auditory stimulation for the treatment of acute-phase limb motor rehabilitation after stroke: study protocol for a prospective randomized controlled trial.

BACKGROUND: The incidence of hemiparetic limb dysfunction reaches 85% in stroke patients, emerging as a critical factor influencing their daily lives. However, the effectiveness of current rehabilitation treatments is considerably limited, particularly in patients with upper extremity impairment. This study aims to conduct a prospective clinical trial to validate the safety and effectiveness of gamma oscillations induced by 40-Hz visual-auditory stimulation in treating post-stroke upper limb dysfunction and to explore the relevant mechanisms. METHODS: This trial is a prospective, randomized controlled, double-blind study. All enrolled patients were randomly assigned to two groups. The experimental group received intervention through 40-Hz visual-auditory stimulation, while the control group underwent intervention with randomly matched visual-auditory stimulation frequencies. The primary efficacy endpoint is the change in motor function. Secondary efficacy endpoints include motor-evoked potentials, cerebral hemodynamic changes, neural network connectivity, and alterations in synaptic-related genes. Safety evaluation included major adverse events, all-cause mortality, and photosensitive epilepsy. Assessments will be conducted at baseline, after a 14-day treatment period, and during subsequent follow-up visits (at 3 and 6 months) post-treatment. The differences between the two groups will be compared. DISCUSSION: This study will evaluate the safety and efficacy of gamma oscillations induced by 40-Hz visual-auditory stimulation in treating patients with upper extremity dysfunction after an acute cerebral stroke. Concurrently, we will explore potential mechanisms, including changes in synaptic-related genes and neural network connectivity. This trial is expected to provide evidence for the effectiveness of this new technique in treating upper extremity dysfunction after a stroke and improving patients' quality of life. TRIAL REGISTRATION: The study protocol has been registered with the Chinese Clinical Trial Registry (ChiCTR) under registration number ChiCTR2300076579 on October 12, 2023.

Chondroprotective effects of Apolipoprotein D in knee osteoarthritis mice through the PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Because the pathophysiology of osteoarthritis (OA) has not been fully elucidated, targeted treatments are lacking. In this study, we assessed the role and underlying mechanism apolipoprotein D (APOD) on the development of OA. METHODS: To establish an in vitro OA model, we extracted primary chondrocytes from the cartilage of C57BL/6 mice and stimulated the chondrocytes with IL-1ß. After APOD intervention or incubation with an overexpressing plasmid, we detected inflammatory-related markers using RT-qPCR, Western blotting, and ELISA. To detect apoptosis and autophagy-related markers, we used flow cytometry, immunofluorescence, and transmission electron microscopy (TEM). Finally, we measured the level of oxidative stress. We also used RNA-seq to identify the APOD-regulated downstream signaling pathways. We used an in vivo mice OA model of the anterior cruciate ligament transection (ACLT) and administered intra-articular adenovirus overexpressing APOD. To examine cartilage damage severity, we used immunohistochemical analysis (IHC), micro-CT, scanning electron microscopy (SEM), and Safranin O-fast green staining. RESULTS: Our results showed that APOD inhibited chondrocyte inflammation, degeneration, and apoptosis induced by IL-1ß. Additionally, APOD reversed autophagy inhibition and oxidative stress and also blocked activation of the PI3K/AKT/mTOR signaling pathway induced by IL-1ß. Finally, overexpression of the APOD gene through adenovirus was sufficient to mitigate OA progression. CONCLUSIONS: Our findings revealed that APOD had a chondroprotective role in OA progression by the PI3K/AKT/mTOR signaling pathway.

Sema3A ameliorates the pathological progression of osteoarthritis by modulating mitochondrial damage in chondrocytes.

Osteoarthritis (OA) is a major disease that causes disability in middle-aged and elderly people. A comprehensive understanding of its pathogenesis is of great significance in finding new clinical diagnosis and treatment schemes. The role of Semaphorin 3A (Sema3A) in OS has attracted attention recently, and the purpose of this study is to analyze the mechanisms underlying its impact on OS. First, a rat model of OS was established. Hematoxylin-eosin (HE) and TUNEL staining showed that the modeled rats presented typical pathological manifestations of OS, confirming the success of the modeling. Sema3A was significantly underexpressed in OS rats. Subsequently, Sema3A abnormal expression vectors were constructed to intervene in chondrocytes isolated from OS rats. It was found that the proliferation of chondrocytes was decreased, the apoptosis was increased, and the mitochondrial damage and autophagy were intensified after silencing Sema3A expression, while the above pathological processes were reversed when Sema3A expression was increased. In conclusion, Sema3A has an important influence on the pathological progression of OS, and molecular therapies targeting to increase Sema3A expression may become a new treatment for OS in the future.

Automated measurement and grading of knee cartilage thickness: a deep learning-based approach.

Background: Knee cartilage is the most crucial structure in the knee, and the reduction of cartilage thickness is a significant factor in the occurrence and development of osteoarthritis. Measuring cartilage thickness allows for a more accurate assessment of cartilage wear, but this process is relatively time-consuming. Our objectives encompass using various DL methods to segment knee cartilage from MRIs taken with different equipment and parameters, building a DL-based model for measuring and grading knee cartilage, and establishing a standardized database of knee cartilage thickness. Methods: In this retrospective study, we selected a mixed knee MRI dataset consisting of 700 cases from four datasets with varying cartilage thickness. We employed four convolutional neural networks-UNet, UNet++, ResUNet, and TransUNet-to train and segment the mixed dataset, leveraging an extensive array of labeled data for effective supervised learning. Subsequently, we measured and graded the thickness of knee cartilage in 12 regions. Finally, a standard knee cartilage thickness dataset was established using 291 cases with ages ranging from 20 to 45 years and a Kellgren-Lawrence grading of 0. Results: The validation results of network segmentation showed that TransUNet performed the best in the mixed dataset, with an overall dice similarity coefficient of 0.813 and an Intersection over Union of 0.692. The model's mean absolute percentage error for automatic measurement and grading after segmentation was 0.831. The experiment also yielded standard knee cartilage thickness, with an average thickness of 1.98 mm for the femoral cartilage and 2.14 mm for the tibial cartilage. Conclusion: By selecting the best knee cartilage segmentation network, we built a model with a stronger generalization ability to automatically segment, measure, and grade cartilage thickness. This model can assist surgeons in more accurately and efficiently diagnosing changes in patients' cartilage thickness.

Asymmetric Synthesis of Triazole Antifungal Agents Enabled by an Upgraded Strategy for the Key Epoxide Intermediate.

A streamlined and efficient approach to the key epoxide intermediate for the asymmetric synthesis of triazole antifungal agents is presented. This synthesis highlights a P(NMe2)3-mediated nonylidic olefination of α-keto ester, ensuring the exclusive formation of the requisite (Z)-alkene, followed by a highly enantioselective Jacobsen epoxidation to establish the two vicinal stereocenters in a single step. The versatility of this strategy is exemplified through the efficient synthesis of efinaconazole and ravuconazole.