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.Herbal Textual Research on Quisqualis Fructus in Famous Classical Formulas
Xiuping WEN ; Shiying CHEN ; Ying TAN ; Guanwen ZHENG ; Huilong XU ; Wen XU ; Chengzi YANG ; Zehao HUANG ; Yu LIN ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):225-237
This article systematically analyzed the historical evolution of the origin, scientific name, producing area, quality evaluation, harvesting and processing, and other aspects of Quisqualis Fructus by consulting the ancient materia medica, medical books, prescription books, local literature and combining with the modern literature and standards, summarized and explored the development rules of its medicinal properties and efficacy along with their underlying causes, in order to provide support for the development and utilization of famous classical formulas containing this herb. According to the textual research, Shijunzi was first recorded as Liuqiuzi in Nanfang Caomuzhuang of the Jin dynasty, and the name of Shijunzi was first used in Kaibao Bencao of the Song dynasty, which has been consistently used throughout subsequent dynasties, and there were also aliases such as Junziren, Sijunzi, and Dujilizi. The mainstream source of Quisqualis Fructus used in the past dynasties has been the dried mature fruits of Quisqualis indica, a plant belonging to the family Combretaceae. In modern times, its variety Q. indica var. villosa has also been recorded as the medicinal material of Quisqualis Fructus. In 2007, the Flora of China(English edition) designated Q. indica var. villosa as a synonym of Q. indica. Today, the accepted name of Shijunzi is updated to Combretum indicum. According to ancient herbal records, the producing areas of Quisqualis Fructus were Guangdong, Hong Kong, Macao, Guangxi, Hainan, Sichuan and Fujian, and then gradually expanded to Yunnan, Taiwan, Jiangxi and Guizhou. Since the Song dynasty, two major production regions have gradually emerged in Sichuan, Chongqing and Fujian. Currently, it is primarily cultivated in Chongqing, Guangxi and other areas, with Chongqing yielding the highest output. Since modern times, superior quality has been defined by large size, a purple-black surface, plump grains, and a yellowish-white kernel. According to ancient herbal records, the harvesting period of Quisqualis Fructus was the July and August of the lunar calendar, mostly used raw after shelling or with the shell intact, it underwent processing methods such as cleaning, slicing, mixing, steaming, roasting, stewing, and frying. Currently, the harvesting period is autumn, followed by sun-drying or low-heat drying, with processing methods including cleaning, stir-frying, and stewing. In ancient and modern literature, the records of the properties, functions and indications of Quisqualis Fructus are basically the same, that is, sweet in taste, warm in nature, predominantly non-toxic, belonging to the spleen and stomach meridians. It possesses effects of insecticide, decontamination and invigorating spleen for ascariasis, enterobiasis, abdominal pain due to worm accumulation and infantile malnutrition.The contraindications for use primarily include avoiding consumption by individuals without parasitic infestations, limiting use for those with spleen-stomach deficiency-cold, refraining from drinking hot tea during medication, and avoiding excessive intake. Based on the textual research, it is suggested that the dried mature fruits of Q. indica should be used as the medicinal material for the development of famous classical formulas containing Quisqualis Fructus. Processing methods may be chosen according to prescription requirements, and the raw products is recommended for medicinal use if not specified.
3.Differences in mercury dissolution from HgS-containing traditional medicines under simulated gastrointestinal conditions
Ming ZHANG ; Yuan-can XIAO ; Jing ZHAO ; Hai-ying TONG ; Xiao-yu WANG ; Wen-bin ZHOU ; Hong-tao BI ; Li-xin WEI
Chinese Traditional Patent Medicine 2025;47(8):2607-2611
AIM To investigate the variations in mercury dissolution from HgS-containing traditional medicines in three kinds of simulated gastrointestinal dissolution media.METHODS 39 batches of 15 types of HgS-containing traditional medicines were collected,total mercury content and dissolved mercury concentrations in simulated gastric fluid,simulated intestinal fluid,and L-cysteine-containing simulated intestinal fluid were measured.The maximum daily intake of total mercury and soluble mercury was calculated based on the maximum daily clinical dosage.RESULTS Among the 15 types of medicines,the maximum daily intake of total mercury varied by 156 times,the daily intake of soluble mercury varied by 3 502 times in simulated gastric fluid,313 times in simulated intestinal fluid,and 10 663 times in L-cysteine-containing simulated intestinal fluid,approximately.CONCLUSION For the 15 types of HgS-containing traditional medicines,the daily maximum intake of soluble mercury showed greater variations than that of total mercury.Soluble mercury concentration is more closely correlated with intestinal absorption of mercury and thus represents a more rational quality control indicator for HgS-containing traditional medicines.
4.Evaluation of chemical constituent consistency in formula granules and traditional decoctions of Gouteng Jiangya Formula
Qing-gang ZHANG ; Dai-liang ZHANG ; Hong QI ; Shu-wen DING ; Yu-zhuo WANG ; Yun-lun LI ; Ji-fu HE ; Huan-ying GUO ; Gui-yun CAO ; Zhao-qing MENG
Chinese Traditional Patent Medicine 2025;47(11):3555-3565
AIM To evaluate the chemical constituent consistency in formula granules and traditional decoctions of Gouteng Jiangya Formula.METHODS HPLC characteristic chromatograms were established,the analysis was performed on a 30 ℃ thermostatic YMC-Triart C18 column(4.6 mm× 250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.Puerarin was used as an internal standard to calculate the relative correction factors of 3'-methoxy puerarin,puerarin apioside,magnolflorine,paeoniflora,daidzin,baicalin,palmatine,berberine,wogonoside and benzoylpaeoniflorin,after which the content detemination was made by quantitative analysis of multi-components by single-marker(QAMS).RESULTS The characteristic chromatograms of 9 batches of formula granules and 15 bacthes of traditional decoctions demonstrated the similarities of more than 0.90 at the detection wavelengths of 192,210,240,260,280,300,320,360 nm,along with similar total peak areas.Eleven constituents showed good linear relationships within their own ranges(r>0.999 0),whose average recoveries were 97.27%-101.64%with the RSDs of 0.36%-1.11%,the result obtained by QAMS and external standard method demonstrated no significant differences(P>0.05).The contents of various constituents in the formula granules approximated those in the traditional decoctions.CONCLUSION The consistent kinds and contents of various constituents are obversable in formula granules and traditional decoctions of Gouteng Jiangya Formula,which can provide a reference for the reasonable clinical application of this formula.
5.Synthesis of A New Naphthalenesulfonamide-based"Turn-on"Fluorescent Probe for Rapid Detection of Glyphosate
Rong-Rong ZHAO ; Hong-Lin LIU ; Ying-Ping HUANG ; Cui-Wen DENG ; Song-Yan LI ; Shui-Lian YU ; Mao-Sheng TAO ; Yi-Qun TIAN ; Xi YUAN
Chinese Journal of Analytical Chemistry 2025;53(6):903-913
Widespread utilization of glyphosate has led to environmental residues,posing potential threats to ecological systems and human health.Traditional methods for detection of glyphosate are limited by specialized equipment and operational techniques,resulting in inefficient responses.Therefore,it is urgent to develop a convenient,sensitive and accurate detection method for detection of glyphosate.Herein,a new naphthalenesulfonamide-based"Turn-on"fluorescent probe was synthesized using 2-chloroaniline and dansyl chloride as raw materials through a one-step process,which showed a good linear relationship between the glyphosate concentration in concentration range of 0.003-70 μmol/L and the fluorescence intensity(R2=0.995),with a detection limit of 2.73 nmol/L(S/N=3).Analytical techniques such as nuclear magnetic resonance(NMR)spectroscopy and high-resolution mass spectrometry(HRMS)were used to investigate the interaction mechanism between the fluorescent probe and glyphosate.The results indicated that a nucleophilic substitution reaction occurred between the probe and the secondary amine(—NH—)of glyphosate,inducing a photoinduced electron transfer(PET)effect which enhanced the fluorescence intensity by 11.2 times.The probe showed good anti-interference ability towards coexisting metal ions,anions and pesticides in water.When applied to determination of glyphosate in the samples such as tap water,river water(Xiangxi River Reservoir),soil,soybeans,and corn,the spiking recoveries ranged from 94.7%to 109.9%,demonstrating the high accuracy and broad applicability of this detection method.A portable test strip based on this fluorescent probe was developed for rapid semi-quantitative analysis of glyphosate.The developed method was rapid,sensitive,and portable,providing theoretical and technical support for on-site measurement of environmental contaminants.
6.A Sensitive Lateral Flow Immunoassay for Detection of Interleukin-6 Using Carbon Dots-Mesoporous Silica Nanocomposite Fluorescent Probes
Yue-Qian YANG ; Peng-Yue WANG ; Jia-Qi REN ; Xiao PAN ; Feng-Hua TAN ; Yu-Jie MA ; Cong-Ying WEN ; Jing-Bin ZENG
Chinese Journal of Analytical Chemistry 2025;53(9):1467-1475
In this study,a sensitive lateral flow immunoassay(LFIA)platform based on carbon dots-mesoporous silica nanocomposite(CD-MSNs)fluorescent probes was constructed for high-performance detection of inflammatory marker interleukin-6(IL-6).Green fluorescent carbon dots(CDs)were prepared by hydrothermal method with 3,9-perylenic acid and 3-aminopropyltriethoxysilane(APTES)as raw materials,and highly fluorescent CD-MSNs composites were then constructed by encapsulating the prepared CDs in mesoporous silica nanoparticles(MSNs).Fluorescent probes were prepared by covalent coupling of CD-MSNs with IL-6 antibody.Fluorescent immunochromatographic test strips were constructed by spraying IL-6 capture antibody and goat anti-mouse IgG on nitrocellulose membrane as detection line(T-line)and quality control line(C-line),respectively.The fluorescence immunoassay analyzer was used to quantitatively detect the fluorescence intensity of T-line,and the experimental results showed that the LFIA platform based on this probe had a good linear relationship in IL-6 concentration range of 102-106 pg/mL,and the detection limit was 64 pg/mL,which was two orders of magnitude more sensitive than that of the traditional colloidal gold test strips.This method effectively solved the issue of insufficient sensitivity of traditional LFIA technique,and provided a rapid and highly sensitive detection method for early diagnosis of inflammatory diseases.
7.American military medical support equipment system digitalizatioin and its inspiration
Xin-ying WANG ; Xian-wen WANG ; Kai-yu YAO ; Xiao-liang LI
Chinese Medical Equipment Journal 2025;46(11):71-77
American military medical support equipment system digitalization were introduced in terms of connotation and development history,the development status of digitalization of four kinds of equipment was analyzed including the ambulance,hospital ship,medical helicopter and medical shelter,and the characteristics and implementation paths of American military medical support equipment system digitalization were described.The inspiration for the military medical support equipment system of the PLA were put forward from the aspects of top-level design,standard and specification,data and modeling,technology integration,construction of independent platform tools and personnel training.
8.Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways.
Ying HUANG ; Chen-Ling CHU ; Wen-Hui QIU ; Jia-Yi CHEN ; Lu-Xi CAO ; Shui-Yu JI ; Bin ZHU ; Guo-Kun WANG ; Quan-Quan SHEN
Journal of Integrative Medicine 2025;23(6):694-705
OBJECTIVE:
Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF.
METHODS:
The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations.
RESULTS:
Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells.
CONCLUSION
AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects*
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Animals
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Saponins/pharmacology*
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Triterpenes/pharmacology*
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Mice
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Peritoneal Fibrosis/pathology*
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Proto-Oncogene Proteins c-akt/metabolism*
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ErbB Receptors/metabolism*
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Phosphatidylinositol 3-Kinases/metabolism*
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Signal Transduction/drug effects*
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Male
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Humans
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Molecular Docking Simulation
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Cell Line
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Mice, Inbred C57BL
9.Influence of Outdoor Light at Night on Early Reproductive Outcomes of In Vitro Fertilization and Its Threshold Effect: Evidence from a Couple-Based Preconception Cohort Study.
Wen Bin FANG ; Ying TANG ; Ya Ning SUN ; Yan Lan TANG ; Yin Yin CHEN ; Ya Wen CAO ; Ji Qi FANG ; Kun Jing HE ; Yu Shan LI ; Ya Ning DAI ; Shuang Shuang BAO ; Peng ZHU ; Shan Shan SHAO ; Fang Biao TAO ; Gui Xia PAN
Biomedical and Environmental Sciences 2025;38(8):1009-1015
10.Association between PM 2.5 Chemical Constituents and Preterm Birth: The Undeniable Role of Preconception H19 Gene Variation.
Ya Long WANG ; Pan Pan SUN ; Xin Ying WANG ; Jun Xi ZHANG ; Xiang Yu YU ; Jian CHAI ; Ruo DU ; Wen Yi LIU ; Fang Fang YU ; Yue BA ; Guo Yu ZHOU
Biomedical and Environmental Sciences 2025;38(8):1016-1022

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