1.The Structure and Function of The YopJ Family Effectors in The Bacterial Type III Secretion System
Ao-Ning LI ; Wen-Bo LI ; Yu-Ying LU ; Min-Hui ZHU ; Yu-Long QIN ; Yong ZHAO ; Zhao-Huan ZHANG
Progress in Biochemistry and Biophysics 2026;53(3):516-533
The Type III Secretion System (T3SS) serves as a pivotal virulence apparatus for numerous Gram-negative bacterial pathogens, enabling them to infect both animal and plant hosts. Functioning as a molecular syringe, the T3SS directly translocates bacterial effector proteins from the bacterial cytoplasm into the interior of eukaryotic host cells. These effectors are central weapons that precisely manipulate a wide spectrum of host cellular physiological processes, ranging from cytoskeletal dynamics to immune signaling, to establish a favorable niche for bacterial survival and proliferation. Among the diverse arsenal of T3SS effectors, the YopJ family constitutes a critical group of virulence factors. Members of this family are characterized by a conserved catalytic triad structure—a hallmark of the CE clan of cysteine proteases that has been evolutionarily repurposed to confer acetyltransferase activity. A defining and intriguing feature of these enzymes is their stringent dependence on a host-derived eukaryotic cofactor, inositol hexakisphosphate (IP6), for allosteric activation. This requirement acts as a sophisticated molecular safeguard, ensuring enzymatic activity only within the appropriate host environment, thereby preventing detrimental effects on the bacterium itself. While seminal studies on individual members such as Yersinia’s YopJ and Salmonella’s AvrA have provided deep mechanistic insights, a systematic and integrative understanding of the structure-function relationships across the entire family remains fragmented. Key questions persist regarding how a conserved catalytic core has diverged to recognize distinct host substrates in different kingdoms of life. To address this gap, this article provides a systematic review of the YopJ family, focusing on three interconnected aspects: their structural features, their catalytic mechanism, and their divergent immunosuppressive strategies in animal versus plant hosts. By conducting a comparative analysis of the sequences and resolved three-dimensional structures of three representative members (e.g., HopZ1a, PopP2, AvrA), we elucidate regions of significant variation embedded within the conserved core catalytic architecture. These variable regions, often involving surface loops and substrate-binding interfaces, are crucial determinants of target specificity and functional specialization. The functional divergence of this effector family is most apparent when comparing their modes of action in different hosts. In animal hosts, YopJ-family effectors primarily sabotage innate immune signaling pathways. They achieve this by acetylating key serine and threonine residues within the activation loops of critical kinases in the MAPK and NF‑κB pathways. This post-translational modification blocks the phosphorylation and subsequent activation of these kinases, leading to potent suppression of inflammatory cytokine production. Conversely, in plant hosts, the strategy broadens to dismantle the two-tiered plant immune system. YopJ homologs target a more diverse set of substrates, including immune-associated receptor-like cytoplasmic kinases (RLCKs), microtubule networks via tubulin acetylation (which disrupts cellular trafficking and signaling), and transcription factors central to defense gene regulation. This multi-target approach effectively suppresses both Pattern-Triggered Immunity (PTI) and Effector-Triggered Immunity (ETI). In conclusion, this synthesis aims to deepen the mechanistic understanding of YopJ family-mediated pathogenesis by integrating structural biology with cellular function across host kingdoms. Elucidating the precise molecular basis for substrate selection—how conserved platforms achieve target diversity—is a major frontier. Furthermore, this knowledge provides a vital theoretical foundation for developing novel anti-virulence strategies. Targeting the conserved IP6-binding pocket or the catalytic acetyltransferase activity itself represents a promising avenue for designing broad-spectrum inhibitors that could disarm this critical family of bacterial effectors, potentially offering new therapeutic approaches against a range of pathogenic bacteria.
2.Quantitative Determination of Taurine in Functional Drinks by Pre-Column Derivatization Capillary Electrochromatography Coupled with Electrochemiluminescence Detection
Xin TIAN ; Min ZHOU ; Lin XIE ; De-Xia BAI ; Miao-Miao ZHU ; Yong-Jun MA
Chinese Journal of Analytical Chemistry 2025;53(6):1010-1018
Using a novel(OH)n-C60@SiO2@Tm2O3@Ca5(PO4)3(OH)quaternary nano-particles/cross-linked chitosan coated open-tubular capillary column(QNPsC-OTCC)as the analytical column,a new method for highly selective determination of taurine(TAU)in functional drinks using pre-column derivatization capillary electrochromatography coupled with electrochemiluminescence(CEC-ECL)detection was established.In the experiments,it was found that adding hexamethylenetetramine as a co-catalyst in N-methylation derivative reaction could quantitatively convert TAU into a single derivative product that cuold be detected by ECL.With the help of Ru(bpy)32+reagent,the ECL peak intensity of TAU derivative was increased by more than 1000 times compared to the original TAU.In addition,a Ru-containing d-f cyano-bridged heterometallic coordination polymer modified platinum electrode was used instead of a bare platinum electrode as working electrode for ECL detection,which resulted in a further increase of the peak response of TAU derivatives about 5.7 times.Under optimized analytical conditions,by using betastatin hydrochloride(BSH)as the internal standard and simultaneously derivatized with TAU,the relative ratio of peak intensity of TAU and BSH derivatives showed a linear relationship with the initial TAU concentration in a two-segment ranges of 0.2-6.0 mmol/L and 6.0-10 mmol/L.The limit of detection of TAU was 0.09 mmol/L(S/N=3).The developed method was applied to determination of TAU contents in four commercial functional drink samples,and the relative standard deviations(RSDs)for relative intensity ratio were less than 0.9%,and the recoveries were in the range of 95.0%~102.0%,indicating good practicability of the method.
4.Human amniotic mesenchymal stem cells overexpressing neuregulin-1 promote skin wound healing in mice
Taotao HU ; Bing LIU ; Cheng CHEN ; Zongyin YIN ; Daohong KAN ; Jie NI ; Lingxiao YE ; Xiangbing ZHENG ; Min YAN ; Yong ZOU
Chinese Journal of Tissue Engineering Research 2025;29(7):1343-1349
BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.
5.Effect of oxymatrine on expression of stem markers and osteogenic differentiation of periodontal ligament stem cells
Jing LUO ; Min YONG ; Qi CHEN ; Changyi YANG ; Tian ZHAO ; Jing MA ; Donglan MEI ; Jinpeng HU ; Zhaojun YANG ; Yuran WANG ; Bo LIU
Chinese Journal of Tissue Engineering Research 2025;29(19):3992-3999
BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.
6.Anterior Shoulder Instability with Epilepsy:Bankart Repair Versus Latarjet Procedure
Sung Min RHEE ; Chang Woo WOO ; Cheol Hwan KIM ; Dong Hyun KIM ; Yong Girl RHEE
Clinics in Orthopedic Surgery 2025;17(1):157-165
Background:
Anterior dislocation in epilepsy patients is relatively severe, difficult to treat, and prone to recurrence. The purpose of this study was to compare the results of arthroscopic Bankart repair and the open Latarjet procedure in epilepsy patients who had anterior shoulder instability and to compare the results of the open Latarjet procedure in epilepsy and non-epileptic groups.
Methods:
A total of 57 shoulders (34 dominant) in 55 patients (18–50 years, 45 men and 10 women) with anterior glenohumeral instability were included in the study and the average follow-up was 24 months. Out of 21 epilepsy patients (23 shoulders), 11 were treated with the open Latarjet procedure and 12 with arthroscopic Bankart repair. Additionally, comparisons were made between the 34 non-epileptic patients who underwent the open Latarjet procedure and the epilepsy patients who underwent the same procedure.
Results:
In the epilepsy group, all 12 patients who underwent Bankart repair had on-track lesions, and all 11 patients who underwent the Latarjet procedure had off-track lesions. In the non-epilepsy group, all cases were off-track lesions. In the epilepsy group, there was no significant difference in the postoperative clinical outcome and recurrence rate between the Bankart repair and Latarjet procedure groups. In the Latarjet group, postoperative re-dislocation rate in the non-epilepsy patients was 14% (5/34 cases), compared to 45% (5/11 cases) in the epilepsy patients, 4 of which 4 occurred during seizures. It was 41% in the Bankart repair group for on-track lesions, which was similar to the recurrence rate after the Latarjet for off-track lesions in the epilepsy group.
Conclusions
After the Latarjet procedure, the functional outcomes in the epilepsy group were similar to those in the non-epilepsy group, except for the higher re-dislocation rate. With either of the surgical procedures, the re-dislocation rate secondary to seizures was very high. Despite the presence of on-track lesions, the Latarjet procedure would be more preferrable for anterior stabilization in epilepsy patients, in view of the high recurrence rate with arthroscopic Bankart repair.
7.Does the Proximal Humerus Nail with 2 Distal Screws Provide Sufficient Rotational Stability?
Ki Yong AN ; Tae Gyu PARK ; Min Young KIM
Clinics in Orthopedic Surgery 2025;17(1):148-156
Background:
Proximal humerus nails, frequently used for managing proximal humerus fractures, significantly enhance rotational stability and reinforce fractured fragments. Few research exists regarding the optimal number and positioning of distal screws.This study aimed to assess the stability of diverse screw configurations and scrutinize screw distribution and bone stress via finite element analysis.
Methods:
The humerus intramedullary nail (Humerus Interlocking Nail System; TDM) underwent assessment using finite element analysis applied to a humerus model. Three groups were established based on varying distal screw numbers and locations: all 3 distal locking holes were used in group 1; 2 screws (dynamic hole and proximal static hole) in group 2, and 2 screws (dynamic hole and distal static hole) in group 3. Finite element analysis computed stress distribution within the implant and bone for each group.A 1-mm fracture gap was simulated at the surgical neck, and stress distributions were analyzed in both normal and osteoporotic bone models.
Results:
Using two screws did not compromise rotational stability. Stress distribution analysis revealed stability across all groups without reaching failure strength. Group 3 exhibited a minor rise in component 11 (direct stress [force per unit area] acting on the positive and negative 1 faces in the 1-axis. direction) and component 22 (direct stress [force per unit area] acting on the positive and negative 2 faces in the 2-axis direction) stress, remaining below failure strength thresholds. Group 1 exhibited the lowest von Mises stress in the nail and screws, while groups 2 and 3 did not reach failure strength levels. Findings remained consistent in the osteoporotic model.
Conclusions
All 3 groups demonstrated rotational stability concerning stress distribution, indicating that using 2 screws for distal fixation does not adversely affect stability. This suggests the potential for saving surgical time and reducing radiation exposure without compromising stability.
8.Concomitant Rotator Cuff Tear with Frozen Shoulder: A Contemplation on the Necessity and Legitimacy of Magnetic Resonance Imaging Stratified by Age
Hsien-Hao CHANG ; Tae-Hwan YOON ; Joon-Ryul LIM ; Yong-Min CHUN
Clinics in Orthopedic Surgery 2025;17(3):453-459
Background:
Frozen shoulder (FS) is often accompanied by a rotator cuff tear (RCT), but it can be challenging to diagnose a concomitant RCT without imaging studies. Therefore, having practical criteria to identify patients requiring imaging studies at initial presentation with FS would lead to more cost-effective use of these studies. This study investigated the relationship between RCT and stiffness in patients with FS and whether this relationship was modified by patient age.
Methods:
This study included 540 adults with shoulder pain who had ≥ 10° of limited passive range of motion in forward flexion, compared to the contralateral side. Patients were categorized into 2 groups depending on the degree of forward flexion stiffness: overhead stiffness (OHS) group, patients with ≥ 110° forward flexion (n = 349); and non-OHS group, patients with forward flexion < 110° (n = 191). The presence of concomitant RCT was determined by magnetic resonance imaging and compared between groups before and after stratification by age.
Results:
The OHS group had increased odds of concomitant RCT, compared to the non-OHS group (odds ratio [OR], 4.99; 95% CI, 3.36–7.42). OHS was also significantly associated with a more severe grade of RCT (no tear, partial-thickness tear, or full-thickness tear) (OR, 4.42; 95% CI, 3.05–6.39). The odds of RCT in the OHS group, compared to the non-OHS group, increased with age (50–59 years: OR, 3.83; 95% CI, 1.96–7.48; 60–69 years: OR, 5.94; 95% CI, 3.14–11.26; and 70–79 years: OR, 7.67; 95% CI, 2.71–21.66).
Conclusions
Patients with FS and forward flexion range of motion ≥ 110° (i.e., OHS) at initial presentation had approximately 5-fold higher odds of concurrent RCT than patients with non-OHS. Moreover, in patients aged 50 years or above, these odds increased up to almost 8-fold. Therefore, we recommend confirming the rotator cuff integrity with magnetic resonance imaging in patients with FS and OHS.
9.Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP)
Jae Hoon MOON ; Eun Kyung LEE ; Wonjae CHA ; Young Jun CHAI ; Sun Wook CHO ; June Young CHOI ; Sung Yong CHOI ; A Jung CHU ; Eun-Jae CHUNG ; Yul HWANGBO ; Woo-Jin JEONG ; Yuh-Seog JUNG ; Kyungsik KIM ; Min Joo KIM ; Su-jin KIM ; Woochul KIM ; Yoo Hyung KIM ; Chang Yoon LEE ; Ji Ye LEE ; Kyu Eun LEE ; Young Ki LEE ; Hunjong LIM ; Do Joon PARK ; Sue K. PARK ; Chang Hwan RYU ; Junsun RYU ; Jungirl SEOK ; Young Shin SONG ; Ka Hee YI ; Hyeong Won YU ; Eleanor WHITE ; Katerina MASTROCOSTAS ; Roderick J. CLIFTON-BLIGH ; Anthony GLOVER ; Matti L. GILD ; Ji-hoon KIM ; Young Joo PARK
Endocrinology and Metabolism 2025;40(2):236-246
Background:
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods:
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.
10.Deep Learning Technology for Classification of Thyroid Nodules Using Multi-View Ultrasound Images: Potential Benefits and Challenges in Clinical Application
Jinyoung KIM ; Min-Hee KIM ; Dong-Jun LIM ; Hankyeol LEE ; Jae Jun LEE ; Hyuk-Sang KWON ; Mee Kyoung KIM ; Ki-Ho SONG ; Tae-Jung KIM ; So Lyung JUNG ; Yong Oh LEE ; Ki-Hyun BAEK
Endocrinology and Metabolism 2025;40(2):216-224
Background:
This study aimed to evaluate the applicability of deep learning technology to thyroid ultrasound images for classification of thyroid nodules.
Methods:
This retrospective analysis included ultrasound images of patients with thyroid nodules investigated by fine-needle aspiration at the thyroid clinic of a single center from April 2010 to September 2012. Thyroid nodules with cytopathologic results of Bethesda category V (suspicious for malignancy) or VI (malignant) were defined as thyroid cancer. Multiple deep learning algorithms based on convolutional neural networks (CNNs) —ResNet, DenseNet, and EfficientNet—were utilized, and Siamese neural networks facilitated multi-view analysis of paired transverse and longitudinal ultrasound images.
Results:
Among 1,048 analyzed thyroid nodules from 943 patients, 306 (29%) were identified as thyroid cancer. In a subgroup analysis of transverse and longitudinal images, longitudinal images showed superior prediction ability. Multi-view modeling, based on paired transverse and longitudinal images, significantly improved the model performance; with an accuracy of 0.82 (95% confidence intervals [CI], 0.80 to 0.86) with ResNet50, 0.83 (95% CI, 0.83 to 0.88) with DenseNet201, and 0.81 (95% CI, 0.79 to 0.84) with EfficientNetv2_ s. Training with high-resolution images obtained using the latest equipment tended to improve model performance in association with increased sensitivity.
Conclusion
CNN algorithms applied to ultrasound images demonstrated substantial accuracy in thyroid nodule classification, indicating their potential as valuable tools for diagnosing thyroid cancer. However, in real-world clinical settings, it is important to aware that model performance may vary depending on the quality of images acquired by different physicians and imaging devices.

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