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This article discusses how a new APRS service-learning model was implemented in a new service-learning project in the traditional Chinese medicine (TCM) orthopedics curriculums at three Hong Kong institutions. The APRS model adopting flipped learning approach consists of four cyclic stages, including Application, Practice, Reflection and Self-regulated learning. Qualitative and quantitative findings in this study reveal that TCM students gained confidence in applying discipline knowledge/skills and improved in various areas, including cross-cultural competence, communication, problem-solving and collaboration. Drawing evidence from this study, possible factors contributing to positive impacts on student learning in the APRS model are the "strong connectivity" (including clear alignment with programme, profession, institutional missions and traditional Chinese philosophy "xiushen"), "reinforced motivation" (student autonomy and buy in) and "structured organisation" (strong network among participating parties and use of a centralised electronic platform). The APRS service-learning model is a culture-based approach helping students reconnect Confucian "xiushen" to the discipline knowledge and the real-life application in the Hong Kong context. This model may also be applicable to other Asian contexts where the Confucian culture prevails.

Abstract Background Babesia duncani is a pathogen within the phylum Apicomplexa that causes human babesiosis. It poses a significant threat to public health, as it can be transmitted not only through tick bites but also via blood transfusion. Consequently, an understanding of the gene functions of this pathogen is necessary for the development of drugs and vaccines. However, the absence of conditional gene knockdown tools has hindered the research on this pathogen. The auxin-inducible degron (AID) system is a rapid, reversible conditional knockdown system widely used in gene function studies. Thus, there is an urgent need to establish the AID system in B. duncani to study essential gene functions. Methods The endogenous genes of the Skp1-Cullin-F-box (SCF) complex in B. duncani were identified and confirmed through multiple sequence alignment and conserved domain analysis. The expression of the F-box protein TIR1 from Oryza sativa (OsTIR1) was achieved by constructing a transgenic parasite strain using a homologous recombination strategy. Polymerase chain reaction (PCR), western blot, and indirect immunofluorescence assay (IFA) were used to confirm the correct monoclonal parasite strain. The degradation of enhanced green fluorescent protein (eGFP) tagged with an AID degron was detected through western blot and live-cell fluorescence microscopy after treatment of indole-3-acetic acid (IAA). Results In this study, Skp1, Cul1, and Rbx1 of the SCF complex in B. duncani were identified through sequence alignment and domain analysis. A pure BdTIR1 strain with expression of the OsTIR1 gene was constructed through homologous recombination and confirmed. This strain showed no significant differences from the wild type (WT) in terms of growth rate and proportions of different parasite forms. The eGFP tagged with an AID degron was successfully induced for degradation using 500 μM IAA. Grayscale analysis of western blot indicated a 61.3% reduction in eGFP expression levels, while fluorescence intensity analysis showed a 77.5% decrease in fluorescence intensity. Increasing the IAA concentration to 2 mM accelerated eGFP degradation and enhanced the extent of degradation. Conclusions This study demonstrated the functionality of the AID system in regulating protein levels by inducing rapid degradation of eGFP using IAA, providing an important research tool for studying essential gene functions related to invasion, egress, and virulence of B. duncani. Moreover, it also offers a construction strategy for apicomplexan parasites that have not developed an AID system. Graphical Abstract

Abstract MAT2B works together with MAT2A to synthesize S-Adenosyl methionine (SAM) as the primary methyl donor. MAT2B, despite lacking catalytic activity, exerts regulatory control over the enzymatic activity of MAT2A. In addition to the enzymatic activity regulation, we find that, in an NADP+-dependent manner, MAT2B binds and stabilizes MAT2A. Disruption of the cellular NADP+ remodels the protein level of MAT2A. The pentose phosphatase pathway regulates the level of MAT2A protein through the interaction of NADP+ with MAT2B. Additionally, MAT2B-MAT2A interaction regulates the mRNA m6A modification and stability. In liver tumors, the Mat2a mRNA level is elevated but the protein level is decreased by the restricted NADP+. Blocking the interaction between MAT2B and MAT2A by the keto diet can suppress liver tumor growth. These findings reveal that MAT2B is essential for regulating the protein levels of MAT2A and connecting SAM synthesis to mRNA m6A.

Abstract New coupling scheme substrate‐integrated waveguide (SIW) diplexers based on dual‐mode cavities are proposed for millimetre‐wave applications. Dual‐mode SIW cavities are simultaneously employed in common input and coupling cavity to produce filtering transmission poles and transmission zero (TZ). A common input SIW cavity with two orthogonal modes is employed instead of the traditional T‐junction for circuit miniaturisation, insertion‐loss reduction, and intrinsically high isolation. A critical dual‐mode SIW cavity with diagonally distributed modes has been employed in each channel to realise a controllable stopband TZ for high selectivity of passband's skirt. To further improve channel isolation and passbands' selectivity, a SIW diplexer based on dual‐ and single‐mode cavities is proposed, and four‐pole responses for each passband channel are designed. For the verification, two millimetre‐wave diplexers have been fabricated and tested.

Abstract Understanding the Li-ions conduction network and transport dynamics in polymer electrolyte is crucial for developing reliable all-solid-state batteries. In this work, advanced nano- X-ray computed tomography combined with Raman spectroscopy and solid state nuclear magnetic resonance are used to multi-scale qualitatively and quantitatively reveal ion conduction network of poly(ethylene) oxide (PEO)-based electrolyte (from atomic, nano to macroscopic level). With the clear mapping of the microstructural heterogeneities of the polymer segments, aluminium-oxo molecular clusters (AlOC) are used to reconstruct a high-efficient conducting network with high available Li-ions (76.7%) and continuous amorphous domains via the strong supramolecular interactions. Such superionic PEO conductor (PEO-LiTFSI-AlOC) exhibites a molten-like Li-ion conduction behaviour among the whole temperature range and delivers an ionic conductivity of 1.87 × 10−4 S cm−1 at 35 °Ϲ. This further endows Li electrochemical plating/stripping stability under 50 μA cm−2 and 50 μAh cm−2 over 2000 h. The as-built Li|PEO-LiTFSI-AlOC|LiFePO4 full batteries show a high rate performance and a capacity retention more than 90% over 200 cycling at 250 μA cm−2, even enabling a high-loading LiFePO4 cathode of 16.8 mg cm−2 with a specific capacity of 150 mAh g−1 at 50 °Ϲ.

Abstract Chemotherapy in combination with immunotherapy has gradually shown substantial promise to increase T cell infiltration and antitumor efficacy. However, paclitaxel in combination with immune checkpoint inhibitor targeting PD-1/PD-L1 was only used to treat a small proportion of metastatic triple-negative breast cancer (TNBC), and the clinical outcomes was very limited. In addition, this regimen cannot prevent paclitaxel-induced peripheral neuropathy. Therefore, there was an urgent need for a novel target to enhance the antitumor activity of paclitaxel and alleviate chemotherapy-induced peripheral neuropathy in breast cancer. Here, we found that Dickkopf-1 (DKK1) expression was upregulated in multiply subtypes of human breast cancer specimens after paclitaxel-based chemotherapy. Mechanistic studies revealed that paclitaxel promoted DKK1 expression by inducing EGFR signaling in breast cancer cells, and the upregulation of DKK1 could hinder the therapeutic efficacy of paclitaxel by suppressing the infiltration and activity of CD8+ T cells in tumor microenvironment. Moreover, paclitaxel treatment in tumor-bearing mice also increased DKK1 expression through the activation of EGFR signaling in the primary sensory dorsal root ganglion (DRG) neurons, leading to the development of peripheral neuropathy, which is charactered by myelin damage in the sciatic nerve, neuropathic pain, and loss of cutaneous innervation in hindpaw skin. The addition of an anti-DKK1 antibody not only improved therapeutic efficacy of paclitaxel in two murine subtype models of breast cancer but also alleviated paclitaxel-induced peripheral neuropathy. Taken together, our findings providing a potential chemoimmunotherapy strategy with low neurotoxicity that can benefit multiple subtypes of breast cancer patients.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a growing health crisis in the general population of the United States (U.S.), but the relationship between systemic immune-inflammation (SII) index and NAFLD is not known. Methods We collected data from the National Health and Nutrition Examination Survey 2017–2018. Next, propensity score matching (PSM), collinearity analysis, restricted cubic spline (RCS) plot, logistic regression, quantile regression analysis, subgroup analysis, mediation analysis, and population attributable fraction were used to explore the association of the SII with risk of NAFLD. Results A total of 665 participants including the 532 Non-NAFLD and 133 NAFLD were enrolled for further analysis after PSM analysis. The RCS results indicated that there was a linear relationship between the SII and controlled attenuation parameter (p for nonlinear = 0.468), the relationship also existed after adjustment for covariates (p for nonlinear = 0.769). The logistic regression results indicated that a high SII level was an independent risk factor for NAFLD (OR = 3.505, 95% CI: 1.092–11.249, P

AIM: To investigate Omicron's impact on clinical presentation of acute primary angle closure (APAC) in China. METHODS: A consecutive case series with historical controls was conducted at Shenzhen Eye Hospital, the largest specialized hospital in Shenzhen, China. Medical records from a two-month period during the Omicron pandemic (December 1, 2022, to January 31, 2023) were compared with records from two control groups (12/2018–1/2019 and 12/2021–1/2022) before pandemic. Patients with APAC were included, and the prevalence of APAC and demographic characteristics in Omicron-infected and non-infected patients were compared. RESULTS: Seventy-one (23.43%) out of 303 patients were diagnosed with APAC in the pandemic cohort, which was 2.98 and 2.61 times higher than that in control cohorts (7.87% in 2019, 8.96% in 2022, P

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) protect against diabetic cardiovascular diseases and nephropathy. However, their activity in diabetic retinopathy (DR) remains unclear. Our retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications, suggesting their advantage in DR treatment. By single-cell RNA-sequencing analysis and immunostaining, we observed a high expression of GLP-1R in retinal endothelial cells, which was down-regulated under diabetic conditions. Treatment of GLP-1 RAs significantly restored the receptor expression, resulting in an improvement in retinal degeneration, vascular tortuosity, avascular vessels, and vascular integrity in diabetic mice. GO and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 RAs. Additionally, the treatment attenuated STING signaling activation in retinal endothelial cells, which is typically activated by leaked mitochondrial DNA. Expression of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular membranes. Further investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING signaling. This study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

Key Clinical Message Cemento‐osseous dysplasia (COD) belongs to a group of fibrous osseous disorders that can masquerade as periapical inflammatory conditions in the jawbones. We present a rare case of COD occurring in a patient who also had periapical periodontitis concurrently. When faced with a patient exhibiting no symptoms, diagnosis may be challenging. Abstract COD is a fibrous osseous disorder similar to periapical chronic inflammatory conditions and other cysts in the jaw bones on the radiograph. There is a rare case of COD occurring in a 49‐year‐old Chinese woman who also had chronic periapical periodontitis concurrently. The lesions were incidentally discovered in the mandibular anterior tooth region during the patient's imaging examination. The patient exhibited no symptoms, and diagnosing the conditions may be challenging due to the confusingly similar radiological features that present as a radiolucent lesion in the periapical region. The final diagnosis was made through pulp vitality tests, cone beam computed tomography (CBCT), and clinical examinations. The COD was recommended for annual follow‐up. Root canal therapy has been performed for chronic apical periodontitis. According to the diagnostic process of COD, a thorough history check, multiple clinical examinations, and imaging studies should be emphasized to prevent misdiagnosis and avoid unnecessary or inappropriate therapies. The patient was followed up for 6 years. The recovery of chronic apical periodontitis in tooth #31 and the transformation of osteolytic and osteogenesis of COD had been observed in CBCT.

BackgroundPathologic myopia (PM) associated with myopic maculopathy (MM) is a significant cause of visual impairment, especially in East Asia, where its prevalence has surged. Early detection and accurate classification of myopia-related fundus lesions are critical for managing PM. Traditional clinical analysis of fundus images is time-consuming and dependent on specialist expertise, driving the need for automated, accurate diagnostic tools.MethodsThis study developed a deep learning-based system for classifying five types of MM using color fundus photographs. Five architectures—ResNet50, EfficientNet-B0, Vision Transformer (ViT), Contrastive Language-Image Pre-Training (CLIP), and RETFound—were utilized. An ensemble learning approach with weighted voting was employed to enhance model performance. The models were trained on a dataset of 2,159 annotated images from Shenzhen Eye Hospital, with performance evaluated using accuracy, sensitivity, specificity, F1-Score, Cohen’s Kappa, and area under the receiver operating characteristic curve (AUC).ResultsThe ensemble model achieved superior performance across all metrics, with an accuracy of 95.4% (95% CI: 93.0–97.0%), sensitivity of 95.4% (95% CI: 86.8–97.5%), specificity of 98.9% (95% CI: 97.1–99.5%), F1-Score of 95.3% (95% CI: 93.2–97.2%), Kappa value of 0.976 (95% CI: 0.957–0.989), and AUC of 0.995 (95% CI: 0.992–0.998). The voting ensemble method demonstrated robustness and high generalization ability in classifying complex lesions, outperforming individual models.ConclusionThe ensemble deep learning system significantly enhances the accuracy and reliability of MM classification. This system holds potential for assisting ophthalmologists in early detection and precise diagnosis, thereby improving patient outcomes. Future work could focus on expanding the dataset, incorporating image quality assessment, and optimizing the ensemble algorithm for better efficiency and broader applicability.

Background: Deficits in prepulse inhibition may be a common feature in first- episode schizophrenia, bipolar disorder (BD) and major depressive disorder (MDD). We sought to explore the levels and viability of prepulse inhibition to differentiate first- episode schizophrenia, BD and MDD in patient populations. Methods: We tested patients with first- episode schizophrenia, BD or MDD and healthy controls using prepulse inhibition paradigms, namely perceived spatial co-location (PSC-PPI) and perceived spatial separation (PSS-PPI). Results: We included 53 patients with first-episode schizophrenia, 30 with BD and 25 with MDD, as well as 82 healthy controls. The PSS-PPI indicated that the levels of prepulse inhibition were smallest to largest, respectively, in the first-episode schizophrenia, BD, MDD and control groups. Relative to the healthy controls, the prepulse inhibition deficits in the first-episode schizophrenia group were significant (p < 0.001), but the prepulse inhibitions were similar between patients with BD and healthy controls, and between patients with MDD and healthy controls. The receiver operating characteristic curve analysis showed that PSS-PPI (area under the curve [AUC] 0.73, p < 0.001) and latency (AUC 0.72, p < 0.001) were significant for differentiating patients with first-episode schizophrenia or BD from healthy controls. Limitations: The demographics of the 4 groups were not ideally matched. We did not perform cognitive assessments. The possible confounding effect of medications on prepulse inhibition could not be eliminated. Conclusion: The level of prepulse inhibition among patients with first-episode schizophrenia was the lowest, with levels among patients with BD, patients with MDD and healthy controls increasingly higher. The PSS-PPI paradigm was more effective than PSC-PPI to recognize deficits in prepulse inhibition. These results provide a basis for further research on biological indicators that can assist differential diagnoses in psychosis., Introduction Patients with schizophrenia and patients with bipolar disorder (BD) overlap in clinical manifestations, physiology and genetics, (1,2) and studies on cognitive impairments, neural circuit disruptions and electrophysiologic deficits indicate [...]

ObjectiveBased on machine learning method, four types of early postoperative frailty risk prediction model of enterostomy patients were constructed to compare the performance of each model and provide the basis for preventing early postoperative frailty of elderly patients with enterostomy.MethodsThe prospective convenience sampling method was conducted and 362 early postoperative enterostomy patients were selected in three hospitals from July 2020 to November 2023 in Shanghai, four different prediction models of Support Vector Machine (SVM), Bayes, XG Boost, and Logistic regression were used and compared the test effects of the four models (MCC, F1, AUC, and Brier index) to judge the classification performance of the four models in the data of this study.ResultsA total of 21 variables were included in this study, and the predictors mainly covered demographic information, stoma-related information, quality of life, anxiety and depression, and frailty. The validated models on the test set are XGBoost, Logistic regression, SVM prediction model, and Bayes on the MCC and F1 scores; on the AUC, XGBoost, Logistic regression, Bayes, and SVM prediction model; on the Brier scores, Bayes, Logistic regression, and XGBoost.ConclusionXGBoost based on machine learning method is better than SVM prediction model, Logistic regression model and Bayes in sensitivity and accuracy. Quality of life in the early postoperative period can help guide clinical patients to identify patients at high risk of frailty and reduce the incidence of early postoperative frailty in elderly patients with enterostomy.

ABSTRACT There are significant differences in the quantities of Camellia oleifera fruits growing within and outside the canopy distribution, meaning that a single mode of picking has drawbacks. To improve the harvesting efficiency for the inner and outer layers, this article proposes a synergistic mode of harvesting based on a vibration comb brush, and presents a design for a harvesting device based on this principle. The overall structure and working principle of the proposed device are explained, and the operational processes of the vibration and comb parts of the device are analyzed. ADAMS software is used to construct a rigid-flexible coupling model of the device and the fruiting branch, and simulation results are presented to show that the fruit drop and flower loss rates for Camellia oleifera are related to the vibration frequency, the amplitude, and the spacing between the teeth and comb plates. Finally, a three factor and three level field orthogonal experiment was conducted, and the results showed that under the conditions of vibration frequency 5.85Hz, amplitude 60.43mm, and comb spacing 45mm, the flower loss rate was the lowest and it had good picking performance. Under these conditions, the fruit drop rate is 87.32% and the flower loss rate is 8.06%, values that meet the requirements for mechanized picking of Camellia oleifera fruits.