Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

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.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Objective:To investigate the prevalence and risk factors of cornea guttata in patients with age-related cataract.Methods:A cross-sectional study was conducted.A total of 1 472 patients aged 50-89 years with complete medical records, who were diagnosed with age-related cataract and to undergo surgery, were enrolled at Peking University People's Hospital from August 2018 to July 2019.The presence of guttata was determined according to the specular microscopy images and the overall prevalence of guttata was calculated, as well as the prevalence rates of different gender, eye, and age distribution.Patients were divided into a guttata group (96 cases 130 eyes) and a non-guttata group (1 376 cases 2 814 eyes), and the differences in general information between groups were compared.The corneal endothelial cell density (CD), coefficient of variation of cell size (CV), fraction of hexagonal cells (6A), axial length (AL), white to white (WTW), anterior chamber depth, and corneal vertex thickness were compared between the two groups, and only the right eye of the patient with both eyes affected was included for analysis.The risk factors of guttata were analyzed by multivariate logistic regression.Differences in influencing factors among different guttata grades were compared, and the differences in biometric parameters of each eye in both eyes of guttata patients were compared.This study adhered to the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Peking University People's Hospital (No.2023PHB198-001).Results:Of the 1 472 patients, 96(6.52%) patients had cornea guttata.The prevalence rate of guttata in males was 4.04%, which was significantly lower than 8.20% in females ( χ2=10.058, P=0.002).The average age of patients in the guttata group was (71.19±8.57) years old, with 24 males and 72 females, including 62 patients with monocular guttata and 39 patients with isolated guttata.Multivariate logistic regression analysis showed that female (odds ratio [ OR]=2.124, 95% confidence interval [ CI]: 1.306-3.455), greater AL ( OR=1.201, 95% CI: 1.083-1.332), shallow anterior chamber depth ( OR=0.439, 95% CI: 0.252-0.766), and greater corneal vertex thickness ( OR=1.008, 95% CI: 1.001-1.015) were risk factors for guttata.There were statistically significant differences in the proportion of monocular guttata and biocular guttata among different grades groups, and between isolated guttata and non-isolated guttata ( χ2=25.492, 15.362; both P<0.05).Differences in CD and corneal vertex thickness among different grades groups were statistically significant ( F=3.264, 5.784; both P<0.05).The CD was significanty higher and the corneal vertex thickness was significantly thinner in the grade 1 than in the grade ≥3 (both P<0.017).There was no statistically significant difference in binocular CD, CV, 6A, AL, WTW, anterior chamber depth, and corneal vertex thickness between both eyes of monocular or binocular guttata patients (all P>0.05). Conclusions:The risk factors of guttata include female, long AL, shallow anterior chamber depth, and thick corneal vertex thickness.The guttata grade of monocular guttata and isolated guttata patients is lower.With the increase of grade, the corneal vertex thickness increases.There is no difference in ocular structure between both eyes of guttata patients.

Objective To investigate the therapeutic efficacy of inspiratory muscle training(IMT)combined with external diaphragm pacing(EDP)in elderly patients with chronic heart failure(CHF).Methods 147 patients with CHF admitted to the Department of Cardiology of the Second Affiliated Hospital of Xi'an Jiaotong University from March 2024 to October 2024 were selected,of which 38 patients were in the conventional drug therapy group(standard care group),52 patients were in the conventional drug therapy+EDP therapy(dual therapy group),and 57 patients were in the conventional drug therapy+EDP therapy+IMT therapy(triple therapy group).Com-parative analyses were performed for maximum inspiratory pressure(MIP),maximum expiratory pressure(MEP),handgrip strength,6-minute walk distance(6MWD),modified Medical Research Council(mMRC)scores,resting heart rate,and blood pressure before treatment and 4 weeks post-intervention.Results After treatment,The dual therapy group demonstrated higher MIP,6MWD,and lower mMRC scores than the standard care group(P<0.05).The triple therapy group exhibited superior improvements in MIP,MEP,handgrip strength,6MWD,and lower mMRC scores compared to both standard care and dual therapy groups(P<0.05),with additional benefits including lower resting systolic blood pressure versus dual therapy group(P<0.05)and reduced resting heart rate compared to standard care group(P<0.05).Conclusion The combined IMT and EDP significantly enhances respiratory and upper limb muscle strength in CHF patients,effectively improves cardiopulmonary function,alleviates dys-pnea,and reduces resting heart rate and blood pressure,thus improving the quality of life.It is worthy of clinical promotion and application.

Objective To investigate the factors influencing the persistence of residual low back pain following percutaneous vertebroplasty(PVP)in patients with osteoporotic vertebral fractures(OVF),in order to provide a scientific basis for clinical intervention strategies.Methods A retrospective analysis was conducted on data from 1 120 patients diagnosed with OVF who received PVP treatment between July 2020 and June 2025.Among them,61 patients who experienced residual low back pain in the early postoperative period(defined as 2 days to 1 month after surgery)with a postoperative visual analog scale(VAS)score greater than 3 points were selected as the observation group.An additional 61 control subjects were matched to the observation group at a 1∶1 ratio based on age(±5 years),gender,and preoperative bone mineral density(±0.5 standard deviation).Univariate and logistic regression analyses were subsequently performed to evaluate potential influencing factors.Results Univariate analysis revealed statistically significant differences between the two groups with respect to preoperative thoracolumbar fascia injury(TFI),MRI-detected liquefaction signals in the affected vertebrae,the number of involved vertebrae(≥2),and suboptimal bone cement distribution(P<0.05).Multivariate regression analysis confirmed that these factors were independent risk factors,with corresponding odds ratios(ORs)of 5.378,6.111,3.245,and 2.890(all P<0.05).The area under the curve(AUC)of the predictive model was 0.929,indicating a high level of predictive accuracy.Conclusion Preoperative TFI,MRI-demonstrated liquefaction signals in the affected vertebrae,the presence of multiple responsible vertebrae,and suboptimal bone cement distribution may contribute to an increased risk of early residual low back pain following PVP.

Objective To propose a multiple regression-variational auto-encoders(MR-VAE)model to realize precise and non-invasive prediction of intra-abdominal pressure(IAP)in critically ill patients.Methods At first,a dataset was constructed by retrospectively analysing baseline characteristics and clinical indicators of 100 critically ill patients admitted to the Intensive Care Unit of Daping Hospital of Army Medical University between 30 August 2019 and 30 March 2021.Then,a MR-VAE prediction model was developed by integrating a feedforward neural network for supervised regression onto a variational autoencoder(VAE)framework and incorporating multiple regression strategies to mitigate feature interference.Finally,the MR-VAE model had its performance evaluated by its comparison with five classical models including support vector machines(SVM),convolutional neural networks(CNN),Scikit-learn integrated model(SIM),multi-layer perceptron(MLP)and K-nearest neighbors(KNN),and its prediction accuracy verified by testing the data of 10 randomly selected patients.Results The MR-VAE model behaved the best when compared with the five classical models,with a mean squared error(MSE)of 0.207,a root mean square error(RMSE)of 0.454,a mean absolute error(MAE)of 0.361,a median absolute deviation(MAD)of 0.243,an explained variance score(EVS)of 0.814 and a R2of 0.823,which also outperformed the five models in fitting performance,convergence and final loss.In random sample testing,the MR-VAE model exhibited high consistency between predicted and actual values.Conclusion The MR-VAE model proposed can accurately predict IAP,which has great potential in reducing the repeated measurements of IAP in critically ill patients and providing new ideas for the early diagnosis and treatment of IAH.

Objective:To investigate the prevalence and risk factors of cornea guttata in patients with age-related cataract.Methods:A cross-sectional study was conducted.A total of 1 472 patients aged 50-89 years with complete medical records, who were diagnosed with age-related cataract and to undergo surgery, were enrolled at Peking University People's Hospital from August 2018 to July 2019.The presence of guttata was determined according to the specular microscopy images and the overall prevalence of guttata was calculated, as well as the prevalence rates of different gender, eye, and age distribution.Patients were divided into a guttata group (96 cases 130 eyes) and a non-guttata group (1 376 cases 2 814 eyes), and the differences in general information between groups were compared.The corneal endothelial cell density (CD), coefficient of variation of cell size (CV), fraction of hexagonal cells (6A), axial length (AL), white to white (WTW), anterior chamber depth, and corneal vertex thickness were compared between the two groups, and only the right eye of the patient with both eyes affected was included for analysis.The risk factors of guttata were analyzed by multivariate logistic regression.Differences in influencing factors among different guttata grades were compared, and the differences in biometric parameters of each eye in both eyes of guttata patients were compared.This study adhered to the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Peking University People's Hospital (No.2023PHB198-001).Results:Of the 1 472 patients, 96(6.52%) patients had cornea guttata.The prevalence rate of guttata in males was 4.04%, which was significantly lower than 8.20% in females ( χ2=10.058, P=0.002).The average age of patients in the guttata group was (71.19±8.57) years old, with 24 males and 72 females, including 62 patients with monocular guttata and 39 patients with isolated guttata.Multivariate logistic regression analysis showed that female (odds ratio [ OR]=2.124, 95% confidence interval [ CI]: 1.306-3.455), greater AL ( OR=1.201, 95% CI: 1.083-1.332), shallow anterior chamber depth ( OR=0.439, 95% CI: 0.252-0.766), and greater corneal vertex thickness ( OR=1.008, 95% CI: 1.001-1.015) were risk factors for guttata.There were statistically significant differences in the proportion of monocular guttata and biocular guttata among different grades groups, and between isolated guttata and non-isolated guttata ( χ2=25.492, 15.362; both P<0.05).Differences in CD and corneal vertex thickness among different grades groups were statistically significant ( F=3.264, 5.784; both P<0.05).The CD was significanty higher and the corneal vertex thickness was significantly thinner in the grade 1 than in the grade ≥3 (both P<0.017).There was no statistically significant difference in binocular CD, CV, 6A, AL, WTW, anterior chamber depth, and corneal vertex thickness between both eyes of monocular or binocular guttata patients (all P>0.05). Conclusions:The risk factors of guttata include female, long AL, shallow anterior chamber depth, and thick corneal vertex thickness.The guttata grade of monocular guttata and isolated guttata patients is lower.With the increase of grade, the corneal vertex thickness increases.There is no difference in ocular structure between both eyes of guttata patients.