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.

AIM To investigate the effects of Rutong Ruanjian Tablets on angiogenesis in cancer tissues of rats with preneoplastic breast cancer(PBC).METHODS 60 female SD rats were randomly divided into a blank group of 10 rats and a model group of 50 rats for the establishment of the PBC models of Liver-Qi Stagnation and Blood Stasis Pattern with 9 weeks of oral administration of 7,12-dimethylbenz[a]anthracene(DMBA)and cervical ligation.After successful modeling,the rats were randomly divided into the model group,the tamoxifen group(3.2 mg/kg),the Rutong Ruanjian Tablets group(128 mg/kg),the 3,5-difluorobenzoyl group(DAPT,5 mg/kg),and the Rutong Ruanjian Tablets(128 mg/kg via gavage)+DAPT(5 mg/kg intraperitoneal injection)group,for 1 month corresponding drug administration,with 10 rats in each group.Then the rats had their cancer progression and syndrome scores observed;their angiogenesis evaluated by assessment of microvascular density(MVD);their vascular endothelial growth factor(VEGF)expression assessed by immunohistochemistry;and their mRNA and protein expressions of proteins related to the DLL4/Notch1/Hes1 pathway measured using RT-qPCR,immunohistochemistry and Western blot.RESULTS During carcinogenesis of rats induced by DMBA,there was gradual disappearance of E-cadherin expression and consistency of HE staining result with the PBC progression confirming the success of the modeling.Compared with the blank group,the model group showed increased MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).Compared with the model group,the Rutong Ruanjian Tablets group exhibited reduced MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).The Rutong Ruanjian Tablets+DAPT group showed reduced mRNA expression of Notch1 and Hes1,and protein expressions of DLL4,Notch1 and Hes1 compared to the Rutong Ruanjian Tablets group(P＜0.05,P＜0.01).CONCLUSION Rutong Ruanjian Tablets can inhibit angiogenesis and attenuate cancer progression in PBC rats of Liver-Qi Stagnation and Blood Stasis Pattern,and the mechanism may lie in the downregulation of DLL4/Notch1/Hes1 signaling pathway related proteins.

Objective To explore the pharmacokinetic(PK)characteristics of desloratadine tablets and reference drugs in healthy subjects,and evaluate their bioequivalence and safety.Methods The random,open,two-period,cross-over pharmacokinetic study method was adopted,each subject received a single oral dose of desloratadine tablets test drug(T)or reference drug(R)for 5 mg.The concentrations of desloratadine and 3-hydroxy desloratadine in plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS);and the PK parameters were calculated by WinNonlin 8.1 software to evaluate the bioequivalence.Results The main PK parameters of T and R of desloratadine were as follows:the fasting condition Cmax were respectively(3 809.82±1 016.54)and(3 642.36±777.07)pg·mL-1;AUC0-120h were respectively(5.75 ×104±5.03 ×104)and(5.51 × 104±4.00 × 104)pg·h·mL-1;AUC0-∞ were respectively(6.85× 104±1.03× 104)and(6.37 × 104±7.92 × 104)pg·h·mL-1.The fed condition Cmax were respectively(4 398.98±1 191.22)and(4 744.4±1 511.97)pg·mL-1;AUC0-120h were respectively(5.25 × 104±1.82 × 104)and(5.55 × 104±1.98 × 104)pg·h·mL-1;AUC0-∞ were respectively(5.37 × 104±1.86 × 104)and(5.68 × 104±2.04 × 104)pg·h·mL-1.The 90％confidence interval of Cmax,AUC0-t and AUC0-∞ of desloratadine were all within 80.00％～125.00％.Conclusion There was no significant difference in the main PK parameters between T tablets and R under fasting or high-fat postprandial conditions,and desloratadine tablets were bioequivalent,safe and well tolerated.

Objective:To investigate the differences in dosimetric parameters for target volumes and organs at risk (OARs), radiation doses to reconstructed tissues, and beam-on time in radiotherapy among helical tomotherapy (HT), volumetric modulated arc therapy (VMAT), and fixed-field intensity-modulated radiotherapy (F_IMRT) following immediate breast reconstruction for breast cancer, thereby providing a reference for the selection of clinical radiotherapy techniques.Methods:This study retrospectively investigated 15 breast cancer patients who underwent radiotherapy following modified radical mastectomy and immediate breast reconstruction at the Liuzhou Worker′s Hospital from August 2018 to July 2023. During target volume delineation, precautions were taken to avoid the reconstructed tissues, which were delineated separately. Customized HT, VMAT, and F_IMRT treatment plans were designed for each patient. The plans were categorized into the HT, VMAT, and F_IMRT groups based on different radiotherapy techniques employed. They were comparatively analyzed through one-way analysis of variance (ANOVA), with multiple comparisons further conducted in the case of significant differences.Results:Statistical analyses reveal significant differences in various parameters of target volumes among the three groups of plans ( F = 38.73, 14.95, 37.01, 48.05, 35.55, 22.56, 34.30, P < 0.05). Pairwise comparisons indicate that the maximum dose ( D2%), minimum dose ( D98%), mean dose ( Dmean), and the proportion of high-dose volumes within the target volume ( V107%and V110%) in both the HT and VMAT groups were significantly better than those in the F_IMRT group. The HT group demonstrated the optimal conformity index (CI), while the VMAT group displayed the superior homogeneity index (HI) compared to the other two groups. In terms of OAR, the V20 of the ipsilateral lung was the lowest in the HT group ( F = 14.31, P < 0.05) and the highest in the F_IMRT group ( F = 14.31, P < 0.05). However, the V5 and Dmean for both the ipsilateral and contralateral lungs in the HT group significantly surpassed those of the other groups ( F = 39.16, 31.91, P < 0.05). The mean dose Dmean ( F = 5.57, P < 0.05) of the contralateral breast was significantly reduced in the VMAT group compared to the other two groups. No statistically significant differences were observed for other OARs, including the heart, spinal cord PRV, thyroid, and humeral head ( P > 0.05). The radiation doses to reconstructed tissues ( Dmax, V53.5, Dmean) ascended in the order of HT, VMAT, and F_IMRT groups ( F = 17.69, 17.53, 15.11, P < 0.05). The HT and F_IMRT groups showed similar beam-on times ( P > 0.05), both exceeding that of the VMAT group by several folds ( F = 28.72, P < 0.05). Conclusions:The comparative analysis indicates that the three radiotherapy techniques exhibit distinct advantages and limitations, with F_IMRT demonstrating the least comprehensive advantage. HT can enhance the conformity of target volumes while reducing the overall radiation doses to reconstructed tissues and the crucial indicator V20 in the ipsilateral lung. VMAT demonstrates the highest treatment efficiency, yielding improved dose uniformity in the target volume and reduced radiation doses to the contralateral breast. It is advisable to prioritize HT or VMAT based on actual clinical conditions.

Diabetic kidney disease(DKD)is one of the common microvascular complications of diabetes mellitus,and it has become the main cause of chronic kidney disease and end stage renal disease.Traditional Chinese medicine can delay the progress of DKD by inhibiting oxidative stress,improving renal tissue damage,restoring renal function.This paper will summarize the relationship between oxidative stress and DKD and the prevention and treatment of DKD by traditional Chinese medicine,so as to provide reference for clinical drug application,basic research and new drug research and development of DKD.

Objective To explore the pharmacokinetic(PK)characteristics of desloratadine tablets and reference drugs in healthy subjects,and evaluate their bioequivalence and safety.Methods The random,open,two-period,cross-over pharmacokinetic study method was adopted,each subject received a single oral dose of desloratadine tablets test drug(T)or reference drug(R)for 5 mg.The concentrations of desloratadine and 3-hydroxy desloratadine in plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS);and the PK parameters were calculated by WinNonlin 8.1 software to evaluate the bioequivalence.Results The main PK parameters of T and R of desloratadine were as follows:the fasting condition Cmax were respectively(3 809.82±1 016.54)and(3 642.36±777.07)pg·mL-1;AUC0-120h were respectively(5.75 ×104±5.03 ×104)and(5.51 × 104±4.00 × 104)pg·h·mL-1;AUC0-∞ were respectively(6.85× 104±1.03× 104)and(6.37 × 104±7.92 × 104)pg·h·mL-1.The fed condition Cmax were respectively(4 398.98±1 191.22)and(4 744.4±1 511.97)pg·mL-1;AUC0-120h were respectively(5.25 × 104±1.82 × 104)and(5.55 × 104±1.98 × 104)pg·h·mL-1;AUC0-∞ were respectively(5.37 × 104±1.86 × 104)and(5.68 × 104±2.04 × 104)pg·h·mL-1.The 90％confidence interval of Cmax,AUC0-t and AUC0-∞ of desloratadine were all within 80.00％～125.00％.Conclusion There was no significant difference in the main PK parameters between T tablets and R under fasting or high-fat postprandial conditions,and desloratadine tablets were bioequivalent,safe and well tolerated.

Diabetic kidney disease(DKD)is one of the common microvascular complications of diabetes mellitus,and it has become the main cause of chronic kidney disease and end stage renal disease.Traditional Chinese medicine can delay the progress of DKD by inhibiting oxidative stress,improving renal tissue damage,restoring renal function.This paper will summarize the relationship between oxidative stress and DKD and the prevention and treatment of DKD by traditional Chinese medicine,so as to provide reference for clinical drug application,basic research and new drug research and development of DKD.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.

The electrocatalytic nitrate reduction reaction(NO3RR)presents a sustainable pathway for large-scale ammonia production,yet it faces significant challenges due to proton supply limitations caused by the high energy barrier for water dissociation,which slows ammonia(NH3)generation.Herein,a palladium(Pd)-modified copper-cobalt(CuCo)hollow fiber penetration electrode that enabled H2 injection through its hollow structures,thereby enhancing proton availability for NO3RR was developed.The active Pd component efficiently dissociated H2,facilitating active hydrogen(*H)spillover and speeding up the cascade NO3RR process on Cu and Co sites.As a result,a half-cell energy efficiency of 39.53%and an NH3 Faradaic efficiency(FE)of 97.11%±1.17%at-0.1 V(vs RHE)were achieved,comparable to state-of-the-art systems.Importantly,the H2-assisted approach prevented the oxidation of active Cu and Co phases,demonstrating exceptional stability with less than 5.6%decay in current density(267 mA/cm2)and retention of NH3 FE at 94.8%after over 70 h of electrolysis.These findings offered valuable insights into proton supply pathways and design of NO3RR electrodes.

The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids (UAs) as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C₁₈ column and a conventional C₁₈ column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, 13 2D fractions of UAs were prepared, and their components were characterized using mass spectrometry (MS). Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether (GSM) serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the 13 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine (IV), corynoxeine N-oxide (CO-N), and cadambine (CAD) demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H₂O₂ measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H₂O₂ clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.