Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

ObjectiveColorectal cancer (CRC) is a highly heterogeneous malignancy, and traditional Chinese medicine (TCM) syndrome differentiation is widely used in its clinical management. However, the biological basis underlying different TCM syndromes remains insufficiently understood. This study aimed to investigate the proteomic differences between qi-blood deficiency syndrome (QBDS) and damp-heat syndrome (DHS) in CRC patients and to establish a “syndrome-differential protein-herbal component” network for exploring potential molecular mechanisms and therapeutic targets associated with syndrome-specific treatment strategies. MethodsTumor tissue samples were collected from 10 patients with pathologically confirmed CRC, including 5 patients diagnosed with QBDS and 5 with DHS according to standardized TCM syndrome differentiation criteria. Tandem mass tag (TMT)-based quantitative proteomics was employed to identify differentially expressed proteins (DEPs) between the two syndrome groups. Functional enrichment analyses, including Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were performed to characterize the biological functions and signaling pathways associated with the identified DEPs. Least absolute shrinkage and selection operator (LASSO) regression analysis was further applied to screen key syndrome-related proteins and construct a core protein prediction model. Subsequently, molecular docking was conducted to evaluate the binding affinities between representative herbal compounds, astragaloside IV and berberine, and the identified core proteins. Finally, cell counting kit-8 (CCK-8) assays were performed in HCT 116 and HT-29 colorectal cancer cell lines to validate the anti-proliferative activities of these compounds in vitro. ResultsA total of 44 DEPs were identified between QBDS and DHS tissues, including 21 upregulated and 23 downregulated proteins in the QBDS group relative to the DHS group. Functional enrichment analyses revealed that these proteins were primarily associated with antiviral immune responses, regulation of inflammatory signaling, NF‑κB signaling pathways, cholesterol metabolism, and other biological processes relevant to tumor progression and host immune regulation. LASSO regression analysis identified eight core proteins with potential syndrome-specific significance. Among them, ST7, GPCPD1, and PODXL were closely associated with QBDS, whereas FAT1, GRB7, KRT7, MAFF, and MMP8 were associated with DHS. Molecular docking demonstrated favorable interactions between astragaloside IV and QBDS-related proteins, with binding energies lower than -5 kcal/mol, indicating stable binding activity. Berberine exhibited even lower binding energies and stronger binding specificity toward DHS-related core proteins. In vitro experiments further confirmed that both compounds inhibited CRC cell proliferation, while berberine displayed significantly greater anti-proliferative efficacy. The lowest 48 h IC₅₀ value of berberine reached 15.21 mg/L in CRC cells, indicating a stronger growth-inhibitory effect than astragaloside IV. ConclusionCRC patients with QBDS and DHS exhibit distinct proteomic characteristics, suggesting that different TCM syndromes possess unique molecular signatures. The identified core proteins may serve as potential biomarkers for syndrome differentiation, while astragaloside IV and berberine may exert therapeutic effects through targeting syndrome-specific molecular networks. These findings provide preliminary proteomic evidence supporting syndrome-guided precision integrative medicine in CRC and offer new insights into the biological basis of TCM syndrome differentiation and individualized therapeutic strategies.

Purpose: To investigate whether a new phospholipid-releasing soft contact lens can improve symptoms of dry eyes. Methods: The study used 2.5-3.0 kg New Zealand rabbits including both normal non-dry eye rabbits and dry eye rabbits, the latter having undergone electrocauterization of the meibomian glands to block the gland orifices. Each rabbit wore a control contact lens on one eye and a phospholipid-releasing contact lens on the other eye daily. Phospholipid-releasing and control contact lenses were provided by NEOVISION Co., Ltd. The parameters assessed included tear film break-up time, tear osmolarity, ocular surface staining, and central corneal thickness. After the experiment, the rabbits were euthanized and their conjunctival tissue was stained with Periodic Acid Schiff (PAS) to observe conjunctival goblet cells. Results: In both dry eye and normal non-dry eye rabbits, tear film break-up time was longer and tear osmolarity was lower when using the phospholipid-releasing contact lens compared to the control contact lens. The ocular surface remained unstained in normal non-dry eye rabbits while staining was observed in dry eye rabbits. There was no significant difference in central corneal thickness between the control and phospholipid-releasing contact lenses in either group. PAS staining showed no difference in conjunctival goblet cell density between the two lens types in normal non-dry eye rabbits. However, in dry eye rabbits, the conjunctival goblet cell density tended to be slightly higher with the phospholipid-releasing contact lens compared to the control lens. Conclusions Phospholipid-releasing contact lenses may help reduce dry eye symptoms and minimize contact lens-related complications by stabilizing the tear film and lowering tear osmolarity.

Objective: : Korea’s healthcare system and policy promotes early, actively stroke treatment to improve prognosis. This study represents stroke epidemiology and outcomes in Korea. Methods: : This study investigated data from the Acute Stroke Assessment Registry. The registry collects data from over 220 hospitals nationwide, focusing on quality stroke service management. Data analysis included patient demographics, stroke severity assessment, and discharge prognosis measurement using standardized scales. Results: : Eighty-six thousand five hundred sixty-eight acute stroke patients were collected with demographic and clinical characteristics during 18 months from 2016, 2018, and between 2020 to 2021, focusing on acute subarachnoid hemorrhage (SAH), acute intracerebral hemorrhage (ICH), and acute ischemic stroke. Of these 86568 patients, 8.3% was SAH, 16.3% ICH, and 74.9% ischemic stroke. Trends showed decreasing SAH and increasing ICH cases over the years. 68.3% stroke patients had the clear onset time. 49.6% stroke patients arrived within 4.5 hours of symptom onset, with more patients treated at general hospitals. Good functional outcomes at discharge was obtained with 58.3% of acute stroke patients, 55.9% of SAH patients, 34.6% of ICH patients, and 63.8% of ischemic stroke patients. Conclusion : The results showed that ischemic stroke was the most common subtype, followed by ICH and SAH. Prognosis differed among subtypes, with favorable outcomes more common in ischemic stroke and SAH compared to ICH.

Objective: : Korea’s healthcare system and policy promotes early, actively stroke treatment to improve prognosis. This study represents stroke epidemiology and outcomes in Korea. Methods: : This study investigated data from the Acute Stroke Assessment Registry. The registry collects data from over 220 hospitals nationwide, focusing on quality stroke service management. Data analysis included patient demographics, stroke severity assessment, and discharge prognosis measurement using standardized scales. Results: : Eighty-six thousand five hundred sixty-eight acute stroke patients were collected with demographic and clinical characteristics during 18 months from 2016, 2018, and between 2020 to 2021, focusing on acute subarachnoid hemorrhage (SAH), acute intracerebral hemorrhage (ICH), and acute ischemic stroke. Of these 86568 patients, 8.3% was SAH, 16.3% ICH, and 74.9% ischemic stroke. Trends showed decreasing SAH and increasing ICH cases over the years. 68.3% stroke patients had the clear onset time. 49.6% stroke patients arrived within 4.5 hours of symptom onset, with more patients treated at general hospitals. Good functional outcomes at discharge was obtained with 58.3% of acute stroke patients, 55.9% of SAH patients, 34.6% of ICH patients, and 63.8% of ischemic stroke patients. Conclusion : The results showed that ischemic stroke was the most common subtype, followed by ICH and SAH. Prognosis differed among subtypes, with favorable outcomes more common in ischemic stroke and SAH compared to ICH.

Objective: : Korea’s healthcare system and policy promotes early, actively stroke treatment to improve prognosis. This study represents stroke epidemiology and outcomes in Korea. Methods: : This study investigated data from the Acute Stroke Assessment Registry. The registry collects data from over 220 hospitals nationwide, focusing on quality stroke service management. Data analysis included patient demographics, stroke severity assessment, and discharge prognosis measurement using standardized scales. Results: : Eighty-six thousand five hundred sixty-eight acute stroke patients were collected with demographic and clinical characteristics during 18 months from 2016, 2018, and between 2020 to 2021, focusing on acute subarachnoid hemorrhage (SAH), acute intracerebral hemorrhage (ICH), and acute ischemic stroke. Of these 86568 patients, 8.3% was SAH, 16.3% ICH, and 74.9% ischemic stroke. Trends showed decreasing SAH and increasing ICH cases over the years. 68.3% stroke patients had the clear onset time. 49.6% stroke patients arrived within 4.5 hours of symptom onset, with more patients treated at general hospitals. Good functional outcomes at discharge was obtained with 58.3% of acute stroke patients, 55.9% of SAH patients, 34.6% of ICH patients, and 63.8% of ischemic stroke patients. Conclusion : The results showed that ischemic stroke was the most common subtype, followed by ICH and SAH. Prognosis differed among subtypes, with favorable outcomes more common in ischemic stroke and SAH compared to ICH.

Purpose: To investigate whether a new phospholipid-releasing soft contact lens can improve symptoms of dry eyes. Methods: The study used 2.5-3.0 kg New Zealand rabbits including both normal non-dry eye rabbits and dry eye rabbits, the latter having undergone electrocauterization of the meibomian glands to block the gland orifices. Each rabbit wore a control contact lens on one eye and a phospholipid-releasing contact lens on the other eye daily. Phospholipid-releasing and control contact lenses were provided by NEOVISION Co., Ltd. The parameters assessed included tear film break-up time, tear osmolarity, ocular surface staining, and central corneal thickness. After the experiment, the rabbits were euthanized and their conjunctival tissue was stained with Periodic Acid Schiff (PAS) to observe conjunctival goblet cells. Results: In both dry eye and normal non-dry eye rabbits, tear film break-up time was longer and tear osmolarity was lower when using the phospholipid-releasing contact lens compared to the control contact lens. The ocular surface remained unstained in normal non-dry eye rabbits while staining was observed in dry eye rabbits. There was no significant difference in central corneal thickness between the control and phospholipid-releasing contact lenses in either group. PAS staining showed no difference in conjunctival goblet cell density between the two lens types in normal non-dry eye rabbits. However, in dry eye rabbits, the conjunctival goblet cell density tended to be slightly higher with the phospholipid-releasing contact lens compared to the control lens. Conclusions Phospholipid-releasing contact lenses may help reduce dry eye symptoms and minimize contact lens-related complications by stabilizing the tear film and lowering tear osmolarity.

Interferon stimulating factor STING, a transmembrane protein residing in the endoplasmic reticulum, is extensively involved in the sensing and transduction of intracellular signals and serves as a crucial component of the innate immune system. STING is capable of directly or indirectly responding to abnormal DNA originating from diverse sources within the cytoplasm, thereby fulfilling its classical antiviral and antitumor functions. Structurally, STING is composed of 4 transmembrane helices, a cytoplasmic ligand binding domain (LBD), and a C terminal tail structure (CTT). The transmembrane domain (TM), which is formed by the transmembrane helical structures, anchors STING to the endoplasmic reticulum, while the LBD is in charge of binding to cyclic dinucleotides (CDNs). The classical second messenger, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), represents a key upstream molecule for STING activation. Once cGAMP binds to LBD, STING experiences conformational alterations, which subsequently lead to the recruitment of Tank-binding kinase 1 (TBK1) via the CTT domain. This, in turn, mediates interferon secretion and promotes the activation and migration of dendritic cells, T cells, and natural killer cells. Additionally, STING is able to activate nuclear factor-κB (NF-κB), thereby initiating the synthesis and release of inflammatory factors and augmenting the body’s immune response. In recent years, an increasing number of studies have disclosed the non-classical functions of STING. It has been found that STING plays a significant role in organelle regulation. STING is not only implicated in the quality control systems of organelles such as mitochondria and endoplasmic reticulum but also modulates the functions of these organelles. For instance, STING can influence key aspects of organelle quality control, including mitochondrial fission and fusion, mitophagy, and endoplasmic reticulum stress. This regulatory effect is not unidirectional; rather, it is subject to organelle feedback regulation, thereby forming a complex interaction network. STING also exerts a monitoring function on the nucleus and ribosomes, which further enhances the role of the cGAS-STING pathway in infection-related immunity. The interaction mechanism between STING and organelles is highly intricate, which, within a certain range, enhances the cells’ capacity to respond to external stimuli and survival pressure. However, once the balance of this interaction is disrupted, it may result in the occurrence and development of inflammatory diseases, such as aseptic inflammation and autoimmune diseases. Excessive activation or malfunction of STING may trigger an over-exuberant inflammatory response, which subsequently leads to tissue damage and pathological states. This review recapitulates the recent interactions between STING and diverse organelles, encompassing its multifarious functions in antiviral, antitumor, organelle regulation, and immune regulation. These investigations not only deepen the comprehension of molecular mechanisms underlying STING but also offer novel concepts for the exploration of human disease pathogenesis and the development of potential treatment strategies. In the future, with further probing into STING function and its regulatory mechanisms, it is anticipated to pioneer new approaches for the treatment of complex diseases such as inflammatory diseases and tumors.

In recent years, China has been facing the dual challenges of declining fertility rates and births, with male reproductive health issues, especially the decline in semen quality, identified as a pivotal contributor to this phenomenon. Meanwhile, accumulating evidence indicates that air pollutants, an increasingly severe environmental problem, can damage semen quality not only directly through their biological toxicity but also indirectly by disrupting the composition of microbial communities in the gut and semen, thereby dysregulating immune function, endocrine homeostasis, and oxidative stress responses. The gut microbiota and semen microbiota, as important components of the human microecosystem, play crucial roles in maintaining reproductive health. This article comprehensively reviewed the research progress on the potential effects of air pollutants (particulate matter and gaseous pollutants), gut microbiota, and semen microbiota on semen quality. Specifically, it elucidated the mechanisms of interaction between these factors and explored how they affect male fertility.

Objective: : Korea’s healthcare system and policy promotes early, actively stroke treatment to improve prognosis. This study represents stroke epidemiology and outcomes in Korea. Methods: : This study investigated data from the Acute Stroke Assessment Registry. The registry collects data from over 220 hospitals nationwide, focusing on quality stroke service management. Data analysis included patient demographics, stroke severity assessment, and discharge prognosis measurement using standardized scales. Results: : Eighty-six thousand five hundred sixty-eight acute stroke patients were collected with demographic and clinical characteristics during 18 months from 2016, 2018, and between 2020 to 2021, focusing on acute subarachnoid hemorrhage (SAH), acute intracerebral hemorrhage (ICH), and acute ischemic stroke. Of these 86568 patients, 8.3% was SAH, 16.3% ICH, and 74.9% ischemic stroke. Trends showed decreasing SAH and increasing ICH cases over the years. 68.3% stroke patients had the clear onset time. 49.6% stroke patients arrived within 4.5 hours of symptom onset, with more patients treated at general hospitals. Good functional outcomes at discharge was obtained with 58.3% of acute stroke patients, 55.9% of SAH patients, 34.6% of ICH patients, and 63.8% of ischemic stroke patients. Conclusion : The results showed that ischemic stroke was the most common subtype, followed by ICH and SAH. Prognosis differed among subtypes, with favorable outcomes more common in ischemic stroke and SAH compared to ICH.