Targeting SIRT2 in Aging-Associated Fibrosis Pathophysiology.

Aging is a complex biological process that involves multi-level structural and physiological changes. Aging is a major risk factor for many chronic diseases. The accumulation of senescent cells changes the tissue microenvironment and is closely associated with the occurrence and development of tissue and organ fibrosis. Fibrosis is the result of dysregulated tissue repair response in the development of chronic inflammatory diseases. Recent studies have clearly indicated that SIRT2 is involved in regulating the progression of fibrosis, making it a potential target for anti-fibrotic drugs. SIRT2 is a NAD+ dependent histone deacetylase, shuttling between nucleus and cytoplasm, and is highly expressed in liver, kidney and heart, playing an important role in the occurrence and development of aging and fibrosis. Therefore, we summarized the role of SIRT2 in liver, kidney and cardiac fibrosis during aging.

Theoretical study of adsorption of gas (CO, CO2, NH3) by metal (Au, Ag, Cu)-doped single-layer WS2.

CONTEXT: The adsorptions of gas (CO, CO2, NH3) by metal (Au, Ag, Cu)-doped single layer WS2 are studied by density functional theory. The doping of metal atoms makes WS2 behave as n-type semiconductors. The final adsorption sites for CO, CO2, and NH3 are close to the atomic sites of the doped metal. The adsorptions of CO and NH3 gases on Cu/WS2, Ag/WS2, and Au/WS2 are dominated by chemisorption. The doped metal atoms enhance the hybridization of the substrate with the gas molecular orbitals, which contributes to the charge transfer and enhances the adsorption of the gas with the material surface. The adsorptions of CO and NH3 on Cu/WS2 and Ag/WS2 allow favorable desorption in a short time after heating. The single-layer Cu/WS2 is proved to have the potential to be used as a reliable recyclable sensor for CO. This work provides a theoretical basis for developing high-performance WS2-based gas sensors. METHODS: In this paper, the adsorption energy, electronic structure, charge transfer, and recovery time of CO, CO2, and NH3 in the doped system have been investigated based on the CASTEP code of density functional theory. The exchange correlation function used is the Perdew-Burke-Ernzerhof (PBE) generalized gradient approximation (GGA). The TS (Tkatchenko-Scheffler) dispersion correction method was used to involve the effects of van der Waals interaction on the adsorption energies for all adsorption system. The ultrasoft pseudopotentials are chosen and the plane-wave cut-off energies are set to 500 eV. The k-point mesh generated by the Monkhorst package scheme is used to perform the numerical integration of the Brillouin zone and 5 × 5 × 1 k-point grid is used. The tolerances of total energy convergence, maximum ionic force, ionic displacement, and stress component are 1.0 × 10-5 eV/atom, 0.03 eV/Å, 0.001 Å, and 0.05 GPa, respectively.

Genome-wide identification of actin-depolymerizing factor family genes in melon (Cucumis melo L.) and CmADF1 plays an important role in low temperature tolerance.

Actin depolymerizing factors (ADFs), as the important actin-binding proteins (ABPs) with depolymerizing/severing actin filaments, play a critical role in plant growth and development, and in response to biotic and abiotic stresses. However, the information and function of the ADF family in melon remains unclear. In this study, 9 melon ADF genes (CmADFs) were identified, distributed in 4 subfamilies, and located on 6 chromosomes respectively. Promoter analysis revealed that the CmADFs contained a large number of cis-acting elements related to hormones and stresses. The similarity of CmADFs with their Arabidopsis homologue AtADFs in sequence, structure, important sites and tissue expression confirmed that ADFs were conserved. Gene expression analysis showed that CmADFs responded to low and high temperature stresses, as well as ABA and SA signals. In particular, CmADF1 was significantly up-regulated under above all stress and hormone treatments, indicating that CmADF1 plays a key role in stress and hormone signaling responses, so CmADF1 was selected to further study the mechanism in plant tolerance low temperature. Under low temperature, virus-induced gene silencing (VIGS) of CmADF1 in oriental melon plants showed increased sensitivity to low temperature stress. Consistently, the stable genetic overexpression of CmADF1 in Arabidopsis improved their low temperature tolerance, possibly due to the role of CmADF1 in the depolymerization of actin filaments. Overall, our findings indicated that CmADF genes, especially CmADF1, function in response to abiotic stresses in melon.

Biological activity, limitations and steady-state delivery of functional substances for precision nutrition.

Food-related functional substances with biological activity serve as a crucial material foundation for achieving precision nutrition, which has gained increasing attraction in regulating physiological functions, preventing chronic diseases, and maintaining human health. Nutritional substances typically include bioactive proteins, peptides, polysaccharides, polyphenols, functional lipids, carotenoids, probiotics, vitamins, saponins, and terpenes. These functional substances play an essential role in precise nutrition. This chapter introduces and summarizes typical functional substances to demonstrate the challenges in precision nutrition for their stability, solubility, and bioavailability. The current status of delivery systems of functional substances is described to give an insight into the development of desirable characteristics, such as food grade status, high loading capacity, site targeting, and controlled release capacity. Finally, the applications of food-borne delivery systems of functional substances for precision nutrition are emphasized to meet the requirement for precision nutrition during nutritional intervention for chronic diseases.

Smooth Muscle Cells-Expressed Bmal1 Regulates Vascular Calcification Independent of the Canonical Circadian Pathway.

Vascular calcification is a major cardiovascular issue that increases morbidity and mortality in diabetes patients. While dysregulation of the circadian master regulator Basic Helix-Loop-Helix ARNT-Like Protein 1 (Bmal1) in vascular smooth muscle cells (VSMC) under diabetic conditions has been suggested, its role in vascular calcification is unclear. In VSMC, Bmal1 was upregulated under high glucose treatment and in aortic tissues from a diabetic mouse model. RNA sequencing from isolated VSMC between Bmal1 deletion and wildtype mice indicated Bmal1's pro-calcification role. Indeed, reduced levels of the osteogenic master regulator, Runt-Related Transcription Factor 2 (Runx2), were found in Bmal1 deletion VSMC under diabetic conditions. Alizarin red staining showed reduced calcification in Bmal1 deletion VSMC in vitro and vascular rings ex vivo . Furthermore, in a diabetic mouse model, SMC-Bmal1 deletion showed reduced calcium deposition in aortas. Collectively, diabetes-upregulated circadian regulator Bmal1 in VSMC contributes to vascular calcification. Maintaining normal circadian regulation may improve vascular health in diabetes.

Comparison of visual quality after wavefront-guided LASIK in patients with different levels of preoperative total ocular higher-order aberrations: a retrospective study.

Purpose: To compare the visual quality after wavefront-guided femtosecond LASIK (WFG FS-LASIK) in patients with different levels of preoperative total ocular higher-order aberrations to guide clinical decision-making regarding patient selection and treatment strategies. Methods: This study included 112 right eyes of 112 patients who previously underwent WFG FS-LASIK for correcting myopia and myopic astigmatism. The patients were divided into two groups based on the mean values of preoperative total ocular HOAs (0.30 ± 0.09 µm): HOA ≤ 0.3 and > 0.3 groups. The visual acuity, manifest refraction, corneal Strehl ratio (SR), root mean square (RMS) of corneal and ocular aberrations, and area under the log contrast sensitivity function (AULCSF) of both groups were compared preoperatively and at 1, 3, 6, and 12 months postoperatively. Results: The induced ocular HOAs and coma (Δ = 1 mo - Preop) were significantly lower in the HOAs > 0.3 group than in the HOAs ≤ 0.3 group (ΔHOAs: 0.39 ± 0.19 vs. 0.29 ± 0.18 µm, t = 2.797, P = 0.006; Δ coma: 0.30 ± 0.19 vs. 0.20 ± 0.21 µm, t = 2.542, P = 0.012). In the HOAs > 0.3 group, ΔHOAs were negatively correlated with the preoperative ocular HOAs (r = -0.315, P = 0.019). In the HOAs ≤ 0.3 group, the regression equation for Δ HOAs = 0.098 + 0.053 |SE| (F = 21.756, P < 0.001). In the HOAs > 0.3 group, the regression equation for ΔHOAs = 0.534 - 1.081 HOAs + 0.038|Sphere| (F = 7.954, P = 0.001). The postoperative uncorrected distance visual acuity, spherical equivalent, corneal aberrations, SR and AULCSF of both groups were similar (all P > 0.05). Furthermore, the ocular aberrations were not significantly different between both groups at 3, 6, and 12 months postoperatively (all P > 0.05). In addition, compared with the preoperative period, the AULCSF of both groups were significantly increased in the postoperative period (all P < 0.05). Conclusions: The induced ocular HOAs and coma in HOAs > 0.3 group were lower. However, both groups achieved equivalent and excellent visual quality after WFG FS-LASIK. WFG FS-LASIK may provide significant visual benefits for a wider range of patients.

Unraveling the Dynamic Reconstruction of Active Co(IV)-O Sites on Ultrathin Amorphous Cobalt-Iron Hydroxide Nanosheets for Efficient Oxygen-Evolving.

Highly-efficient and cost-effective electrocatalysts toward the oxygen evolution reaction (OER) are crucial for advancing sustainable energy technologies. Herein, a novel approach leveraging corrosion engineering is presented to facilitate the in situ growth of amorphous cobalt-iron hydroxides on nickel-iron foam (CoFe(OH)x-m/NFF) within a NaCl-CoCl2 aqueous solution. By adjusting the concentration of the solution, the compositions can tailored and morphologies of these hydroxides to optimize the OER electrocatalytic performance. Specifically, the CoFe(OH)x-500/NFF electrode manifests as distinctive 3D flower-like clusters composed of remarkably thin nanosheets, measuring a mere 1 nm in thickness. By virtue of the amorphous and ultrathin nanosheet structure, the CoFe(OH)x-500/NFF electrode exhibits superior OER activity, characterized by notably low overpotentials (η100, 274 mV) and an exceptionally small Tafel slope of 40.54 mV dec-1. Moreover, the electrode's performance remains robust, maintaining low overpotentials for 168 h at 100 mA cm-2. In situ Raman spectroscopy indicates that the hydroxides experience surface structural reconstruction and transform into high-valent CoFeO2 with active Co(IV)-O sites during the OER. Theoretical calculations underscore the critical role of the NiFe substrate in enhancing the electrode's OER activity by improving electrical conductivity and modifying the adsorption energy of reaction intermediates, thereby reducing the energy barrier for the reaction.

Microscopic Study on Superexchange Dynamics of Composite Spin-1 Bosons.

We report on an experimental simulation of the spin-1 Heisenberg model with composite bosons in a one-dimensional chain based on the two-component Bose-Hubbard model. Exploiting our site- and spin-resolved quantum gas microscope, we observed faster superexchange dynamics of the spin-1 system compared to its spin-1/2 counterpart, which is attributed to the enhancement effect of multi-bosons. We further probed the nonequilibrium spin dynamics driven by the superexchange and single-ion anisotropy terms, unveiling the linear expansion of the spin-spin correlations, which is limited by the Lieb-Robinson bound. Based on the superexchange process, we prepared and verified the entangled qutrits pairs with these composite spin-1 bosons, potentially being applied in qutrit-based quantum information processing.

Dynamic Recyclable High-Performance Epoxy Resins via Triazolinedione-Indole Click Reaction and Cation-π Interaction Synergistic Crosslinking.

Thermosetting plastics exhibit remarkable mechanical properties and high corrosion resistance, yet the permanent covalent crosslinked network renders these materials challenging for reshaping and recycling. In this study, a high-performance polymer film (EI25-TAD5-Mg) was synthesized by combining click chemistry and cation-π interactions. The internal network of the material was selectively constructed through flexible triazolinedione (TAD) and indole via a click reaction. Cation-π interactions were established between Mg2+ and electron-rich indole units, leading to network contraction and reinforcement. Dynamic non-covalent interactions improved the covalent crosslinked network, and the reversible dissociation of cation-π interactions during loading provided effective energy dissipation. Finally, the epoxy resin exhibited excellent mechanical properties (tensile strength of 91.2 MPa) and latent dynamic behavior. Additionally, the thermal reversibility of the C-N click reaction and dynamic cation-π interaction endowed the material with processability and recyclability. This strategy holds potential value in the field of modifying covalent thermosetting materials.

Roles of lipid droplets and related proteins in metabolic diseases.

Lipid droplets (LDs), which are active organelles, derive from the monolayer membrane of the endoplasmic reticulum and encapsulate neutral lipids internally. LD-associated proteins like RAB, those in the PLIN family, and those in the CIDE family participate in LD formation and development, and they are active players in various diseases, organelles, and metabolic processes (i.e., obesity, non-alcoholic fatty liver disease, and autophagy). Our synthesis on existing research includes insights from the formation of LDs to their mechanisms of action, to provide an overview needed for advancing research into metabolic diseases and lipid metabolism.

Malignant glaucoma treated by low-dose laser cycloplasty: a 1-year multicenter prospective non-comparative study.

AIM: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients. METHODS: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo. Intraocular pressure (IOP), number of glaucoma medications, anterior chamber depth (ACD), and complications were recorded. Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy. Recurrence was defined by the presence of a shallow or flat anterior chamber after initial recovery from treatment. RESULTS: A total of 34 eyes received LCP. Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg (P<0.001) with 2.9±1.6 medications (P=0.046) at 1d, and 17.4±6.7 mm Hg (P<0.001) with 1.3±1.7 medications (P<0.001) at 12mo. The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo, respectively. A total of 32 (94.1%) eyes achieved initial anatomical success. During follow-up, 2 (5.9%) eyes failed and 8 (23.5%) eyes relapsed, yielding a 12-month anatomical success rate of 64.3%. Complications including anterior synechia (8.82%), choroidal/ciliary detachment (5.88%) and hypopyon (2.94%) were observed within 1wk. CONCLUSION: LCP is simple, safe, and effective in reforming the anterior chamber in malignant glaucoma.

Heterozygous Variants in KCNJ10 Cause Paroxysmal Kinesigenic Dyskinesia Via Haploinsufficiency.

OBJECTIVE: Most paroxysmal kinesigenic dyskinesia (PKD) cases are hereditary, yet approximately 60% of patients remain genetically undiagnosed. We undertook the present study to uncover the genetic basis for undiagnosed PKD patients. METHODS: Whole-exome sequencing was performed for 106 PRRT2-negative PKD probands. The functional impact of the genetic variants was investigated in HEK293T cells and Drosophila. RESULTS: Heterozygous variants in KCNJ10 were identified in 11 individuals from 8 unrelated families, which accounted for 7.5% (8/106) of the PRRT2-negative probands. Both co-segregation of the identified variants and the significantly higher frequency of rare KCNJ10 variants in PKD cases supported impacts from the detected KCNJ10 heterozygous variants on PKD pathogenesis. Moreover, a KCNJ10 mutation-carrying father from a typical EAST/SeSAME family was identified as a PKD patient. All patients manifested dystonia attacks triggered by sudden movement with a short episodic duration. Patch-clamp recordings in HEK293T cells revealed apparent reductions in K+ currents of the patient-derived variants, indicating a loss-of-function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock-in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia-specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes. INTERPRETATION: Our study established haploinsufficiency resulting from heterozygous variants in KCNJ10 can be understood as a previously unrecognized genetic cause for PKD and provided evidence of glial involvement in the pathophysiology of PKD. ANN NEUROL 2024.

Acute primary angle closure concurrent with coronavirus disease 2019 recurrence in Northern China: A retrospective multi-centre study.

Aims and objectives: During the new coronavirus disease 2019 (COVID-19) outbreak period, there was increasing presentation in the number of patients with acute primary angle closure (APAC). This study aimed to report the occurrence of APAC during the COVID-19 post-restriction period and investigate the related characteristics of these patients with APAC. Methods: This retrospective, multi-center study included consecutive patients seeking APAC treatment at two eye centers in China from December 7, 2022 to January 13, 2023 (post-restriction period) and from December 7, 2021 to January 13, 2022 (control period). Electronic medical records were reviewed, and ocular data of the affected eye(s) were analyzed for patients with unilateral or bilateral APAC. Information including COVID-19 related symptoms, medications used for COVID-19 infection, and living habits and emotions related to the COVID-19 outbreak during the post restriction period were collected using a questionnaire. Results: Overall, 189 (219 APAC eyes) and 51 (54 APAC eyes) patients with APAC were identified during the post-restriction and control periods, respectively. The patients identified during the post-restriction period were younger (P = 0.043) and had a longer duration from symptoms to treatment (P = 0.039), shorter axial length (P = 0.002), larger pupil diameter (P = 0.004), larger vertical cup disc ratio (P = 0.004), poorer mean deviation values (P = 0.003), and more glaucomatous optic neuropathy diagnoses (P = 0.032) compared with the patients with APAC identified during the control period. Among 151 included patients with APAC who completed the questionnaires, 130 patients with APAC were diagnosed with concurrent COVID-19 infection, of which 54 (41.5 %) had coughing and/or vomiting as the main symptoms. Of these, 89.2 % spent 0 h per day on outdoor activity; 44.6 % drank more water than usual, with 14.6 % drinking more than twice the amount of water than usual; 91.5 % used antipyretics; and 20.0 % had mood swings, including anxiety, depression, and tension, during the concurrent COVID-19 infection. Conclusion: In our study, a significant increase in the number of patients presenting with APAC with certain characteristics was observed during the COVID-19 post-restriction period. And whether COVID-19 symptoms, such as coughing and vomiting, and behavioral and psychological changes caused by COVID-19 infection contributing to the concurrence of APAC and COVID-19 recurrence require further investigation.

Targeting Smurf1 to block PDK1-Akt signaling in KRAS-mutated colorectal cancer.

The phosphoinositide 3-kinase (PI3K)-Akt axis is one of the most frequently activated pathways and is demonstrated as a therapeutic target in Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated colorectal cancer (CRC). Targeting the PI3K-Akt pathway has been a challenging undertaking through the decades. Here we unveiled an essential role of E3 ligase SMAD ubiquitylation regulatory factor 1 (Smurf1)-mediated phosphoinositide-dependent protein kinase 1 (PDK1) neddylation in PI3K-Akt signaling and tumorigenesis. Upon growth factor stimulation, Smurf1 immediately triggers PDK1 neddylation and the poly-neural precursor cell expressed developmentally downregulated protein 8 (poly-Nedd8) chains recruit methyltransferase SET domain bifurcated histone lysine methyltransferase 1 (SETDB1). The cytoplasmic complex of PDK1 assembled with Smurf1 and SETDB1 (cCOMPASS) consisting of PDK1, Smurf1 and SETDB1 directs Akt membrane attachment and T308 phosphorylation. Smurf1 deficiency dramatically reduces CRC tumorigenesis in a genetic mouse model. Furthermore, we developed a highly selective Smurf1 degrader, Smurf1-antagonizing repressor of tumor 1, which exhibits efficient PDK1-Akt blockade and potent tumor suppression alone or combined with PDK1 inhibitor in KRAS-mutated CRC. The findings presented here unveil previously unrecognized roles of PDK1 neddylation and offer a potential strategy for targeting the PI3K-Akt pathway and KRAS mutant cancer therapy.

FGL1: a novel biomarker and target for non-small cell lung cancer, promoting tumor progression and metastasis through KDM4A/STAT3 transcription mechanism.

Non-small cell lung cancer (NSCLC) is characterized by a high incidence rate and poor prognosis worldwide. A deeper insight into the pathogenesis of NSCLC and identification of novel therapeutic targets are essential to improve the prognosis of NSCLC. In this study, we revealed that fibrinogen-like protein 1 (FGL1) promotes proliferation, migration, and invasion of NSCLC cells. Mechanistically, we found that Stat3 acts as a transcription factor and can be recruited to the FGL1 promoter, enhancing FGL1 promoter activity. Lysine-specific demethylase 4A (KDM4A) interacts with Stat3 and facilitates the removal of methyl groups from H3K9me3, thereby enhancing Stat3-mediated transcription of FGL1. Furthermore, we observed that Stat3 and KDM4A promote NSCLC cell proliferation, migration, and invasion partly by upregulating FGL1 expression. Additionally, the expression of FGL1 was significantly higher in cancer tissues (n = 90) than in adjacent non-cancerous tissues (n = 90). Furthermore, patients with high FGL1 expression had a shorter overall survival (OS) compared to those with low FGL1 expression. We measured the expression levels of FGL1 on circulating tumor cells (CTCs) in 65 patients and found that patients with a dynamic decrease in FGL1 expression on CTCs exhibited a better therapeutic response. These findings suggest that the dynamic changes in FGL1 expression can serve as a potential biomarker for predicting treatment efficacy in NSCLC. Overall, this study revealed the significant role and regulatory mechanisms of FGL1 in the development of NSCLC, suggesting its potential as a therapeutic target for patients with NSCLC. Future studies should provide more personalized and effective treatment options for patients with NSCLC to improve clinical outcomes.

Mechanisms of inflammation after ischemic stroke in brain-peripheral crosstalk.

Stroke is a devastating disease with high morbidity, disability, and mortality, among which ischemic stroke is more common. However, there is still a lack of effective methods to improve the prognosis and reduce the incidence of its complications. At present, there is evidence that peripheral organs are involved in the inflammatory response after stroke. Moreover, the interaction between central and peripheral inflammation includes the activation of resident and peripheral immune cells, as well as the activation of inflammation-related signaling pathways, which all play an important role in the pathophysiology of stroke. In this review, we discuss the mechanisms of inflammatory response after ischemic stroke, as well as the interactions through circulatory pathways between peripheral organs (such as the gut, heart, lung and spleen) and the brain to mediate and regulate inflammation after ischemic stroke. We also propose the potential role of meningeal lymphatic vessels (MLVs)-cervical lymph nodes (CLNs) as a brain-peripheral crosstalk lymphatic pathway in ischemic stroke. In addition, we also summarize the mechanisms of anti-inflammatory drugs in the treatment of ischemic stroke.

Highly Dispersive Gold Nanoclusters Confined within Micropores of Defective UiO-66 for Highly Efficient Aldehyde Oxidation at Mild Conditions.

The oxidative esterification of aldehydes under mild conditions remains a significant challenge. This study introduces a unique defective UiO-66 to achieve gold nanoclusters (AuNCs) for efficient aldehyde oxidation under mild conditions. The construction and characterization of these materials are thoroughly investigated by techniques of XRD, SEM and TEM images, FT-IR, Raman, and XPS spectrum, emphasizing the unique microporous in defective UiO-66 are conducive to the fabrication of AuNCs. The catalytic performance of the prepared materials in aldehyde oxidation reactions is systematically evaluated, demonstrating the remarkable efficiency of dispersed Au@UiO-66-25 with high-content (9.09 wt%) Au-loading and ultra-small size (~2.7 nm). Moreover, mechanistic insights into the catalytic process under mild conditions (70 °C for 1 h) are provided, elucidating the determination of defective UiO-66 in the confined fabrication of AuNCs and subsequent furfural adsorption, which underlie the principles governing the observed enhancements. This study establishes the groundwork for the synthesis of highly dispersed and catalytically active metal nanoparticles using defective MOFs as a platform, advancing the catalytic esterification reaction of furfural to the next level.

Enhancing General Surgery Clerkships: The Application and Value of Standardized Patient-Based Situational Simulation Teaching.

OBJECTIVE: We explored the value of a standardized patient-based situational simulation teaching method in general surgery internships. METHODS: A prospective, single-blind, randomized controlled trial was conducted with clinical medicine undergraduates from the 2020 cohort of our university as subjects. These students were randomly divided into a traditional teaching (TT) group and a combined teaching (CT) group based on their internship schedules. The TT group followed the conventional teaching model, while the CT group engaged in the standardized patient-based situational simulation teaching method. The study compared differences in pre-internship theoretical scores, post-internship theoretical scores, medical record writing quality, and student satisfaction between the two groups. RESULTS: The CT group (n=108) significantly outperformed the TT group (n=104) in post-internship theoretical scores and medical record writing quality (all P<0.05) and showed marked improvement in stimulating students' interest in learning (P=0.015), enhancing clinical diagnostic and treatment abilities (P<0.001), improving doctor‒patient communication skills (P<0.001), strengthening medical mission sense (P<0.001), reinforcing physicians' sense of responsibility (P<0.001), and facilitating the application of learned knowledge (P<0.001). These differences were statistically significant. CONCLUSION: The standardized patient-based situational simulation teaching method (CT) in general surgery internships has been highly recognized by students and can enhance their clinical competency, offering considerable value for broader.

Targeting Ser78 phosphorylation of Hsp27 achieves potent antiviral effects against enterovirus A71 infection.

A positive-sense (+) single-stranded RNA (ssRNA) virus (e.g. enterovirus A71, EV-A71) depends on viral polypeptide translation for initiation of virus replication after entry. We reported that EV-A71 hijacks Hsp27 to induce hnRNP A1 cytosol redistribution to initiate viral protein translation, but the underlying mechanism is still elusive. Here, we show that phosphorylation-deficient Hsp27-3A (Hsp27S15/78/82A) and Hsp27S78A fail to translocate into the nucleus and induce hnRNP A1 cytosol redistribution, while Hsp27S15A and Hsp27S82A display similar effects to the wild type Hsp27. Furthermore, we demonstrate that the viral 2A protease (2Apro) activity is a key factor in regulating Hsp27/hnRNP A1 relocalization. Hsp27S78A dramatically decreases the IRES activity and viral replication, which are partially reduced by Hsp27S82A. However, Hsp27S15A displays the same activity as the wild-type Hsp27. Peptide S78 potently suppresses EV-A71 protein translation and reproduction through blockage of EV-A71-induced Hsp27 phosphorylation and Hsp27/hnRNP A1 relocalization. A point mutation (S78A) on S78 impairs its inhibitory functions on Hsp27/hnRNP A1 relocalization and viral replication. Taken together, we demonstrate the importance of Ser78 phosphorylation of Hsp27 regulated by virus infection in nuclear translocation, hnRNP A1 cytosol relocation, and viral replication, suggesting a new path (such as peptide S78) for target-based antiviral strategy.