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.Setup Error and Its Influencing Factors in Radiotherapy for Spinal Metastasis
Wenhua QIN ; Xin FENG ; Zengzhou WANG ; Shangnan CHU ; Hong WANG ; Shiyu WU ; Cheng CHEN ; Fukui HUAN ; Bin LIANG ; Tao ZHANG
Cancer Research on Prevention and Treatment 2025;52(5):400-404
Objective To investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT). Methods A total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded. Results The patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant. Conclusion When grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.
3.Microglia mediate neuroinflammation and immune cell recruitment in blue light-damaged retina
Bin SUN ; Ni LI ; Lin YAN ; Qizhao WANG ; Min ZHANG ; Yuehan YANG ; Huan QIN
The Journal of Practical Medicine 2025;41(23):3666-3675
Objective To investigate the mechanism by which blue light irradiation-activated microglia mediate immune cell recruitment and exacerbate retinal damage,and to explore the role of microglial depletion in inhibiting immune infiltration and protecting the retina.Methods SPF-grade C57BL/6J mice were randomly divided into control group,blue light irradiation group,and PLX5622 pretreatment blue light irradiation group.A retinal injury model was established by continuous LED blue light irradiation for 2 days.In the PLX5622 pretreatment group,microglia were specifically depleted before blue light irradiation.After modeling,HE staining and OCT examination were used to examine retinal histomorphological changes;ERG examination was performed to evaluate retinal function;DHE staining and RT-qPCR were used to detect oxidative stress and inflammatory responses,and Iba1,CD68,CD11b immunofluorescence staining and flow cytometry were used to analyze microglial activation status and immune cell infiltration.Results After blue light irradiation,the retinal outer nuclear layer thickness was significantly reduced;ERG a-wave and b-wave amplitudes decreased;expression of oxidative stress-related genes Nrf2,Sod2,and HO-1 was upregulated;expression of inflammatory factors IL-1β,TNF-α,and ICAM-1 increased;the number of Iba1-positive microglia increased and migrated extensively to the outer nuclear layer;the proportion of CD68+cells and CD11b+immune cells was elevated;and activated microglia aggregated around blood vessels to mediate immune cell infiltration.After PLX5622 pretreatment to deplete microglia,immune cell infiltration was significantly reduced;inflammatory responses were alleviated;retinal structural damage was markedly improved,and visual function was protected.Conclusions Blue light irradiation activates microglia and promotes their migration to the injury area.Activated microglia mediate immune cell recruitment and infiltration,exacerbating retinal inflammatory damage.Microglial depletion can effectively inhibit immune infiltration,rescue retinal structure and function,and provide new therapeutic strategies for the prevention and treatment of blue light-related ocular diseases.
4.Study on Mortality Rate of COPD and its Trend in Sichuan Province based on Joinpoint and ARIMA Models
Xiaoli WU ; Qin ZHANG ; Huan LUO
Chinese Journal of Health Statistics 2025;42(4):527-531
Objective To analyze the mortality rate and trend of chronic obstructive pulmonary disease(COPD)among residents in Sichuan Province from 2011 to 2023.Methods The collected mortality monitoring data of residents from 2011 to 2023 were analyzed using Joinpoint regression the trend of COPD mortality rate in Sichuan Province from 2011 to 2023.Based on the COPD mortality rate data of residents from 2011 to 2023 to established an autoregressive integrated moving average method(ARIMA)to predict the trend of mortality rate changes.Results From 2011 to 2023,the crude mortality rate of males was 79.74/100,000,which was higher than that of females(64.82/105),and the standardized mortality rate of males(48.02/105)was higher than that of females(40.51/105)(P<0.05).From 2011 to 2023,the annual percentage change(APC)of male mortality rate and female mortality rate were-4.51% and-5.59%(P<0.05),and the APC of standardized mortality rate of male and female were-9.35%,and-9.91%,with a significant downward trend(P<0.05).From 2011 to 2023,the COPD mortality rates of residents aged 45~54,55~64,65~74 and≥75 years in Sichuan Province were-12.04%,-10.88%,-13.87% and-7.19%,respectively,and with an obvious downward trend in different age groups(P<0.05).The crude mortality rate of COPD in urban decreased from 100.67/105 to 52.93/105,and APC of the crude mortality rate was-5.71%;while the crude mortality rate of rural residents decreased from 86.13/105 to 60.10/105,and APC of the crude mortality rate was-3.69%,with an obvious downward trend(P<0.05%).The standardized COPD mortality rate of urban residents in Sichuan Province from 2011 to 2023 decreased from 79.13/105 to 24.09/105,and APC of the standardizedmortality rate was-10.09%;while the rural residents decreased from83.99/105 to 31.58/105,and APCwas-7.98%,with an obvious downward trend(P<0.05%).The ARIMA model was used to fit the COPD mortality rate in Sichuan Province in 2011~2023,and the COPD mortality rates in Sichuan Province in 2024~2028 were predicted to be 53.49/105,49.28/105,46.11/105,42.59/105 and 41.68/105,respectively.Conclusion The mortality rate of COPD among residents in Sichuan Province showed a downward trend from 2011 to 2023,with rural,male,and elderly populations being high-risk groups for COPD mortality.The ARIMA model had certain reference value for short-term prediction of COPD mortality rate.
5.Correlation between brain gray matter volume changes and neurotransmitter receptors/transporters in patients with first-episode schizophrenia
Huan HUANG ; Xiaowei WANG ; Cheng CHEN ; Wei YUAN ; Yunlong PENG ; Xuan QIN ; Ying XIONG ; Rui XU ; Huiling WANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(10):885-890
Objective:To explore the spatial correlation between gray matter volume (GMV) changes and neurotransmitter receptors/transporters in patients with first-episode schizophrenia (FES) .Methods:Fifty-four FES patients(FES group) and fifty-nine healthy controls (HC group) were selected from June 2014 to May 2020 in the Psychiatry Department of Renmin Hospital of Wuhan University. Structural magnetic resonance imaging (sMRI) was conducted on all subjects. Differences of GMV were compared across 400 cortical regions and 32 subcortical regions. Based on the positron emission tomography(PET) data from Neuromaps, which provides the density of 19 different neurotransmitter receptors and transporters, Spearman correlation analysis was performed to evaluate the spatial correlation between GMV changes and neurotransmitter systems.Results:Compared to the HC group, FES group exhibited significant GMV reductions in widespread cortical (90/400) and subcortical (6/32) regions (all FDR-corrected P<0.05). The effect size of GMV reduction (Cohen’s d) showed significant positive correlations with the density of 5-hydroxytryptamine 1a(5HT1a) ( r=0.400, Pspin=0.002), γ-aminobutyric acid type A receptor(GABA A)( r=0.307, Pspin=0.002), and metabotropic glutamate receptor 5(mGluR5) ( r=0.275, Pspin=0.020) receptors (all FDR-corrected P<0.05). Conclusion:GMV reductions in a wide range of brain regions existed in patients with FES. There are significant correlations between 5HT1a, GABA A and mGluR5 receptors and gray matter reduction in patients with FES. The disorder of these neurotransmitter receptors may be the potential neurobiological mechanism of gray matter structural abnormalities in the early stage of schizophrenia.
6.Effect of decentration and tilt on in vitro optical quality of intraocular lenses with different focus designs
Ruolin PAN ; Xuan LIAO ; Changjun LAN ; Lixuan XIE ; Qingqing TAN ; Suyun QIN ; Huan HUANG ; Yan WANG
Chinese Journal of Experimental Ophthalmology 2025;43(3):211-218
Objective:To observe the effect of different degrees of decentration and tilt on the optical quality of the intraocular lenses (IOLs) with different focus designs.Methods:The UV 3300 PC UV-visible spectrophotometer was employed to measure the spectral transmittance of the monofocal IOL CT ASPHINA 509M (509M), bifocal IOL AT LISA 809M (809M), and trifocal IOL AT LISA Tri 839MP (839MP) within Zeiss MICS platform with a refractive power of + 20 D. The modulation transfer function (MTF) values at a spatial frequency of 50 lp/mm along with MTF curves and United States Air Force (USAF) resolution test charts for each IOL at the focal point were measured at apertures of 3.0 mm and 4.5 mm using the in vitro optical quality testing system OptiSpheric IOL R&D under centered, decentered (0.3, 0.5, 0.7, 0.9 and 1.1 mm) and tilted (3°, 5°, 7°, 9° and 11°) conditions. Results:All three IOLs filtrated the ultraviolet (UV) spectrum below 400 nm.When each IOL was in the centered position, at the 3.0 mm aperture, the MTF values were 0.772 at the far focus of the monofocal IOL 509M, 0.467 and 0.282 at the far and near focus of the bifocal IOL 809M, and 0.416, 0.147, and 0.229 at the far, intermediate, and near focus of the trifocal IOL 839MP, respectively.Whereas at the 4.5 mm aperture, the monofocal IOL 509M MTF value at the far focus was 0.664, the bifocal IOL 809M MTF values at the far and near focus were 0.506 and 0.264, and the trifocal IOL 839MP MTF values at the far, intermediate, and near focus were 0.392, 0.107, and 0.210, respectively.Among the three centered IOLs, the 509M demonstrated the highest MTF value at the far focus, followed by the 809M and then the 839MP; at the near focus, the MTF value of the 809M surpassed that of the 839MP.For decentration and tilt, the difference in MTF values of the three IOLs at the far and near focus was consistent with the differences observed when they were centered.At the same degree of decentration and tilt, all three IOLs exhibited superior optical quality at the 3.0 mm aperture compared to the 4.5 mm aperture.The optical quality of all three IOLs exhibited an overall decline as decentration and tilt increased.All three IOLs demonstrated a decrease in optical quality at the decentration of 0.3 mm or the tilt of 5°.Conclusions:The IOLs within the Zeiss MICS platform design exhibits identical spectral transmittance and UV filtering properties.Among the three IOLs, when centered, the 509M, the 839MP, and the 809M exhibit superior optical quality at the far, intermediate, and near focal points, respectively.Under decentered and tilted conditions, the 509M and the 809M demonstrate better resistance against decentration and tilt, respectively, at both far and near focuses.Additionally, all three IOLs demonstrate better optical quality at smaller apertures, given equivalent degrees of decentration or tilt.However, the optical quality at each focal point of the three IOLs decreases compared to the centered position when subjected to a decentration of 0.3 mm or a tilt of 5°.
7.Disseminated infection caused by Enterocytozoon bieneusi in a child with leukemia:a case report and literature review
Huihong QIN ; Fen PAN ; Fangyuan YU ; Huan WANG ; Chun WANG ; Hong ZHANG ; Wenhao WENG
Chinese Journal of Infection and Chemotherapy 2025;25(1):15-19
Objective To examine the diagnosis and treatment of disseminated infection caused by Enterocytozoon bieneusi in a child with leukemia and improve the awareness of the pathogen in clinical and laboratory practice.Methods A case of disseminated infection caused by Enterocytozoon bieneusi in a child with leukemia in Shanghai Children's Hospital was retrospectively analyzed,including diagnosis and treatment details.Similar cases were identified from PubMed,Wanfang Data,VIP,and CNKI databases since database establishment until June 30,2024,using search terms"Enterocytozoon bieneusi".The relevant literature was reviewed.Results This child had acute lymphoblastic leukemia as the underlying disease and was admitted to hospital for antimicrobial treatment due to fever and abdominal discomfort.The case was considered bacterial infection complicated with Enterocytozoon bieneusi infection,confirmed by detection of Klebsiella pneumoniae in blood and detection of Enterocytozoon bieneusi in blood and ascites by metagenomic next-generation sequencing(mNGS).The treatment was switched to tigecycline plus trimethoprim-sulfamethoxazole at a sufficient dose,which resulted in resolution of symptoms.Six months later,the patient suffered from acute lymphoblastic leukemia and bone marrow depression,Enterocytozoon bieneusi disseminated infection,septic shock.Her family gave up treatment and the child died.Literature review indicated that most patients infected with Enterocytozoon bieneusi had underlying conditions such as organ transplantation,AIDS,and leukemia associated with poor immunity.The onset symptoms are diarrhea,abdominal discomfort,and fever.Enterocytozoon bieneusi was detected by using methods such as modified Masson's trichrome stain,fluorescent calcofluor white staining,molecular detection techniques,and immunofluorescence.The patients were treated with drugs such as albendazole,nitazoxanide,fumagillin,and trimethoprim-sulfamethoxazole.Conclusions Enterocytozoon bieneusi is an opportunistic pathogenic fungus that infects immunocompromised patients and can cause abdominal discomfort,diarrhea,fever,and even disseminated infection and death.Conventional laboratory methods cannot culture Enterocytozoon bieneusi.Molecular detection techniques can be used to identify the pathogen early.
8.Evidence-based practice for non-pharmacological prevention and management of venous thromboembolism in ischemic stroke patients
Yanhong ZHANG ; Yingchun HUAN ; Liqun ZHU ; Jie QIN
Chinese Journal of Modern Nursing 2025;31(5):628-633
Objective:To explore non-pharmacological prevention and management methods for venous thromboembolism (VTE) in ischemic stroke (IS) patients based on the best evidence and evaluate the effectiveness of their application.Methods:Based on evidence acquisition, this study was guided by the Ottawa model of research use to dissect the barriers and facilitators of evidence application through clinical review, and to implement intervention strategies and effect evaluation. Convenience sampling method was used to select inpatients and nurses in the Department of Neurology of Affiliated Hospital of Jiangsu University before and after evidence application as study subjects. The baseline review period was from March 1 to May 31, 2023, and the review subjects were 100 patients hospitalised in the Department of Neurology and 32 nurses working in the Department of Neurology during this period, and the evidence application review period was from December 1, 2023 to February 29, 2024, and the review subjects were 100 patients hospitalised in the Department of Neurology and 32 nurses working in the Department of Neurology during this period. Nurses and patients knowledge of non-pharmacological prevention of VTE, implementation of the review indicators, and the incidence of VTE in patients were compared before and after the application of the evidence.Results:After evidence application, most of the evidence implementation rates were higher than those before evidence application, and the differences were statistically significant ( P<0.05). The VTE non-pharmacological prevention knowledge scores of IS patients and nurses were higher than those before evidence application, and the differences were statistically significant ( P<0.05) ; the VTE incidence rate of IS patients was lower than that before evidence application, and the differences were statistically significant ( P<0.05) . Conclusions:Evidence-based practice of non-pharmacological prevention and management of VTE in patients with IS, guided by the Ottawa model of research use, can effectively improve nurses evidence-based adherence to non-pharmacological prevention and management of VTE, as well as enhance patients knowledge of non-pharmacological prevention of VTE, thereby reducing the incidence of VTE.
9.Microglia mediate neuroinflammation and immune cell recruitment in blue light-damaged retina
Bin SUN ; Ni LI ; Lin YAN ; Qizhao WANG ; Min ZHANG ; Yuehan YANG ; Huan QIN
The Journal of Practical Medicine 2025;41(23):3666-3675
Objective To investigate the mechanism by which blue light irradiation-activated microglia mediate immune cell recruitment and exacerbate retinal damage,and to explore the role of microglial depletion in inhibiting immune infiltration and protecting the retina.Methods SPF-grade C57BL/6J mice were randomly divided into control group,blue light irradiation group,and PLX5622 pretreatment blue light irradiation group.A retinal injury model was established by continuous LED blue light irradiation for 2 days.In the PLX5622 pretreatment group,microglia were specifically depleted before blue light irradiation.After modeling,HE staining and OCT examination were used to examine retinal histomorphological changes;ERG examination was performed to evaluate retinal function;DHE staining and RT-qPCR were used to detect oxidative stress and inflammatory responses,and Iba1,CD68,CD11b immunofluorescence staining and flow cytometry were used to analyze microglial activation status and immune cell infiltration.Results After blue light irradiation,the retinal outer nuclear layer thickness was significantly reduced;ERG a-wave and b-wave amplitudes decreased;expression of oxidative stress-related genes Nrf2,Sod2,and HO-1 was upregulated;expression of inflammatory factors IL-1β,TNF-α,and ICAM-1 increased;the number of Iba1-positive microglia increased and migrated extensively to the outer nuclear layer;the proportion of CD68+cells and CD11b+immune cells was elevated;and activated microglia aggregated around blood vessels to mediate immune cell infiltration.After PLX5622 pretreatment to deplete microglia,immune cell infiltration was significantly reduced;inflammatory responses were alleviated;retinal structural damage was markedly improved,and visual function was protected.Conclusions Blue light irradiation activates microglia and promotes their migration to the injury area.Activated microglia mediate immune cell recruitment and infiltration,exacerbating retinal inflammatory damage.Microglial depletion can effectively inhibit immune infiltration,rescue retinal structure and function,and provide new therapeutic strategies for the prevention and treatment of blue light-related ocular diseases.
10.Effect of Shenqi Dihuang decoction on AMPK/Sirt1/Nrf2 mediated ferroptosis in rats with Henoch Purpura nephritis
Fang-li XU ; Ke XU ; Li-qin GUO ; Hai-xia BU ; Huan WANG
Chinese Pharmacological Bulletin 2025;41(12):2379-2385
Aim To investigate the effect of Shenqi Dihuang decoction(SQDH)on henoch-schonlein pur-pura nephritis(HSPN)rats by regulating AMPK/Sirt1/Nrf2 mediated ferroptosis and the possible mech-anism.Methods Thirty SD rats were randomly divid-ed into a control group(Control),HSPN group,SQDH low-dose group(SQDH-L,5.4 g·kg-1),SQDH high-dose group(SQDH-H,21.6 g·kg-1),and SQDH high-dose+AMPK inhibitor group(SQDH-H+CC,20 mg·kg-1),with six rats in each group.Except for the control group,all other groups of rats were injected intraperitoneally with ovalbumin and complete Freund's adjuvant to establish HSPN rat models.After the successful construction of the model,each group of rats was orally administered with the cor-responding dosage or physiological saline once a day for five weeks.HE staining was used to observe the his-topathological changes in renal tissues;immunohisto-chemistry(IHC)was employed to detect the deposition of IgA and IgG in renal tissues;serum biochemical pa-rameters of renal function and urinary protein levels were measured;commercial assay kits were utilized to determine oxidative stress markers and Fe2+levels in renal tissues;Western blot analysis was performed to assess ferroptosis-related proteins and the protein ex-pression of the AMPK/Sirt1/Nrf2 signaling pathway in renal tissues.Results Compared with the control group,the HSPN group showed significant pathological damage in kidney tissue,with significantly increased scores,increased deposition of IgA and IgG in kidney tissue,decreased serum total protein(TP)and albu-min(ALB),and average increases in serum creatinine(Cre),urea nitrogen(BUN),and urinary protein levels(P<0.05).The levels of MDA,ROS,Fe2+,and ACSL4 protein expression in the kidney tissue sig-nificantly increased,while SOD activity,SLC7A11,GPX4,p-AMPK/AMPK,Sirt1,and Nrf2 protein ex-pression significantly decreased(P<0.05).Com-pared with the HSPN group,the pathological damage to renal tissue was reduced,IgA and IgG deposition in renal tissue decreased,TP and ALB decreased,Cre,BUN,and urinary protein levels were all reduced(P<0.05),and the levels of MDA,ROS,Fe2+,and ACSL4 protein expression in renal tissue were signifi-cantly reduced in each dose group of SQDH rats.SOD activity,SLC7A11,GPX4,p-AMPK/AMPK,Sirt1,and Nrf2 protein expression significantly increased(P<0.05).Compared with the SQDH-H group,the AMPK inhibitor CC could inhibit the AMPK/Sirt1/Nrf2 signaling pathway induced ferroptosis and reverse the protective effect of SQDH on renal injury in HSPN rats.Conclusions SQDH can improve renal injury in HSPN rats,and its mechanism may be related to the activation of AMPK/Sirt1/Nrf2 signaling pathway to in-hibit ferroptosis.

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