Reactive oxygen species (ROS) act as a double-edged sword in bacterial infections, possessing both potent antimicrobial effectors and sophisticated signaling rheostats that dictate the trajectory of host-pathogen interactions. Spatiotemporal concentration gradients of ROS at the infection sites dynamically remodel the host-pathogen interface, cellular adhesion, extracellular matrix architecture, and bacterial virulence programs. The concentration-dependent redox microenvironment serves as a critical determinant of infection progression and provides a unique physicochemical trigger for the design of next-generation therapeutic platforms. This review comprehensively elucidates the multifaceted roles of ROS during bacterial adhesion and invasion and further explores precise intervention strategies targeting the ROS-related microenvironments. These strategies comprise three interrelated levels: (i) pharmacological modulation of host NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) activity and adhesion molecules to maintain redox equilibrium and prevent pathogen invasion; (ii) metabolic reactivation and targeting of antioxidant genes to increase bacterial susceptibility to endogenous ROS, thereby overcoming bacterial tolerance and resistance; and (iii) the development of ROS-responsive biomaterials, including borate ester- and thioketal-based nanocarriers, hierarchically structured hydrogels, and nanozyme systems, which facilitate on-demand drug release, spatiotemporal bidirectional ROS regulation (generation versus scavenging), and adaptation to specific lesions in chronic wounds, biofilms, and respiratory infections. Additionally, we address significant translational challenges, such as off-target oxidative damage, response threshold selectivity, and comprehensive biosafety evaluation using specific probes and oxidative biomarkers. Together, these ROS-targeted interventions offer a versatile and translatable platform for the development of next-generation anti-infective therapies. STATEMENT OF SIGNIFICANCE: ROS exert dual, context-dependent effects at the host-pathogen interface, which act not only as antimicrobial effectors but also as key signaling mediators that govern bacterial adhesion, invasion, biofilm formation and host immunity. ROS mediate bidirectional host-bacteria crosstalk that shapes infection outcomes via tightly regulated concentration and spatiotemporal dynamics. In the review, we present an integrated therapeutic framework that combines host-directed redox modulation, bacterial ROS sensitization, and engineered intelligent biomaterials. We highlight ROS-responsive carriers specifically designed for heterogeneous infection microenvironments as well as materials capable of spatiotemporally controlled, bidirectional ROS regulation. By integrating redox biology with materials design, this work advances precision anti-infective strategies to address the global challenge of antimicrobial resistance.

Bacterial keratitis (BK), particularly deep interlamellar infections, is a sight-threatening condition marked by progressive biofilm formation and high levels of antibiotic resistance, often culminating in irreversible vision loss. Current therapies remain largely ineffective because of limited corneal drug penetration and metabolic dormancy of bacteria within the three-dimensional (3D) corneal microenvironment. Here, we proposed a metabolic modulation strategy using fumarate-based metal-organic frameworks (Zr/Fe@FA) to reverse antibiotic resistance in three-dimensional (3D) bacterial biofilms. Zr/Fe@FA functions as a tricarboxylic acid (TCA) cycle activator to restore bacterial metabolic activity and increase antibiotic uptake, while concurrently disrupting biofilm integrity via metal ions. When administered through microneedles to ensure targeted delivery and enhanced penetration of deep corneal biofilms, fumarate-based Zr/Fe@FA synergized with low-dose levofloxacin in a pathogenic bacteria-induced rabbit keratitis model, achieving substantial biofilm reduction, attenuation of inflammation, and accelerated corneal epithelial repair. These results elucidate the mechanisms by which metabolic reprogramming potentiates antibiotic efficacy and establish a broadly applicable therapeutic platform with high translational potential for treating refractory bacterial keratitis.

Mechanoporation-based intracellular delivery has emerged as an effective technique for transporting materials into living cells through the application of mechanical loading and deformation. Although this technique holds significant potential for large-scale cell manufacturing without the need for additional carriers, there exist several challenges, including a high degree of size dependence, inconsistencies due to cellular heterogeneity, and the risk of channel clogging and cell damage. Here, we developed a flexible mechanoporation chip system that integrated a three-layer pneumatic microvalve array for high-throughput intracellular delivery. Both our simulation data and experimental results indicated that it could minimize cell damage and enhance delivery efficiency through volume exchange and molecular convection. The adaptive deformation design of the microvalve array allowed it to accommodate variations in the geometric sizes and mechanical properties of cell populations, thereby optimizing intracellular delivery. Furthermore, we demonstrated that the flexible mechanoporation chip system could effectively deliver various biomolecules, including drugs, mRNA, and plasmid DNA, into diverse cell types like mouse embryonic fibroblasts (MEFs), adipose-derived stem cells (ASCs), and primary T cells. This flexible mechanoporation chip platform presents a promising tool for efficient, high-throughput, and low-damage mechanical transfection in biomanufacturing, cell therapy and regenerative medicine.

Gelatin-based biomaterials have emerged as promising candidates for bioadhesives due to their biodegradability and biocompatibility. However, they often face limitations due to the uncontrollable phase transition of gelatin, which is dominated by hydrogen bonds between peptide chains. Here, we developed controllable phase transition gelatin-based (CPTG) bioadhesives by regulating the dynamic balance of hydrogen bonds between the peptide chains using 2-hydroxyethylurea (HU) and punicalagin (PA). These CPTG bioadhesives exhibited significant enhancements in adhesion energy and injectability even at 4 °C compared to traditional gelatin bioadhesives. The developed bioadhesives could achieve self-reinforcing interfacial adhesion upon contact with moist wound tissues. This effect was attributed to HU diffusion, which disrupted the dynamic balance of hydrogen bonds and therefore induced a localized structural densification. This process was further facilitated by the presence of pyrogallol from PA. Furthermore, the CPTG bioadhesive could modulate the immune microenvironment, offering antibacterial, antioxidant, and immune-adjustable properties, thereby accelerating diabetic wound healing, as confirmed in a diabetic wound rat model. This proposed design strategy is not only crucial for developing controllable phase-transition bioadhesives for diverse applications, but also paves the way for broadening the potential applications of gelatin-based biomaterials.

Local electrical stimulation (LES) is a widely used clinical method to treat peripheral nerve injury. However, existing plate electrodes (PE) usually suffer from low electronic transport efficiency, whereas acupuncture electrical stimulation may cause damage to normal tissues. There is an urgent need to develop an innovative LES technique with efficient electronic transport, minimal tissue injury and enhanced biosafety. Here, we present a new stretchable transcutaneous electrical stimulation system (STESS) that integrates dissolvable conductive microneedles (DCMN) for optimal skin penetration and electronic transport, along with snake-like electrodes that offer superior flexibility, which can effectively penetrate the stratum corneum, enabling deep tissue electrostimulation with minimal injury. In vitro studies and 3D finite-element analysis demonstrate that the DCMN-based electrotherapy significantly enhances subcutaneous nerve stimulation compared to the conventional PE-based technique. By diminishing the electrical resistance of the stratum corneum, the DCMN-based electrotherapy has shown remarkable in vivo therapeutic efficacy in a rat facial nerve crush injury model. This will pave the way for innovative physiotherapeutic methodologies in the realm of neurological rehabilitation.

Radiation-induced lymphopenia (RIL) has been demonstrated in types of solid tumors. This study aimed to assess the association between dosimetric and clinical variables and RIL in patients with brain metastases after brain radiotherapy (RT). The craniofacial bones of 140 patients were retrospectively delineated, and absolute lymphocyte counts (ALC) were collected both prior to RT (pre-RT) and 1 month after completing RT (post-RT). Linear regression analyses were conducted to identify associations between dosimetric variables of the craniofacial bones (V5-V40), mean dose, clinical parameters, and post-RT ALC. Logistic regression analysis was used to evaluate independent predictors of RIL (ALC < 1000 cells/µL). The relationships between dosimetric and clinical variables and overall survival (OS) were analyzed using a Cox regression model. After completing RT, ALC decreased in both the whole brain RT (WBRT) and focal RT subgroups (p < 0.05). Linear regression analysis suggested that pre-RT ALC, gross tumor volume (GTV), and the V5 of the craniofacial bones were independent risk factors for the decrease in post-RT ALC. Logistic regression analysis demonstrated that lower pre-RT ALC (OR: 31.969, 95

Refractory infections caused by pathogenic bacteria, particularly multidrug-resistant bacteria, pose a significant threat to global human health. Emerging host-directed antimicrobial strategies have the potential to prolong the effectiveness of existing treatments or eliminate the development of antibiotic resistance, representing a promising avenue for addressing infections caused by resistant bacteria. Here, we propose a mechanobiology-based host-directed antimicrobial strategy that utilizes an inhibitory fibronectin (Fn) peptide, Arg-Gly-Asp-Ser (RGDS), to regulate bacterial-host interfacial adhesion forces and thereby effectively combat multidrug-resistant bacterial infections. The RGDS peptides can competitively interfere with the physicochemical interactions at the bacterial-host adhesion interfaces, thereby inhibiting bacterial colonization on host surfaces. The alterations in bacterial-host adhesion forces regulated by RGDS peptides are quantified via single-cell force spectroscopy (SCFS), which elucidate the mechanobiological mechanisms underlying the presented host-targeted antimicrobial strategy. Furthermore, we reveal the antimicrobial potential of the RGDS peptide as an antibiotic adjuvant, achieving a 75 % reduction in antibiotic dosage. The in vivo antimicrobial efficacy of RGDS-enhanced low-dose antibiotics is also validated in three animal models. It is expected that a mechanobiology-based host-directed antimicrobial strategy could be broadly employed to address the global incidence and progression of drug-resistant bacteria.

The electroadhesion strategy driven by hydrated ion diffusion in functional hydrogels enables controllable soft interface adhesion, offering a new solution for smart interfacial interactions. This is crucial for various engineering applications such as tissue repair, soft robotics, and wearable electronics. However, the intrinsic mechanisms of interfacial adhesion and failure associated with the electroadhesion strategy remain unclear. With an incremental digital image correlation (DIC) technique, we comprehensively investigated the spatiotemporal dynamics of interfacial deformation and failure modulated by electrically controllable hydrated ion diffusion in electroadhesive hydrogels. We also visualized the spatiotemporal evolution of mechanical properties near adhesion interfaces, including interfacial toughness, initial elastic modulus, and nominal secant modulus, under various electrical stimulations. Furthermore, we recognized the transition of adhered specimens from adhesive failure to cohesive failure, driven by the applied external electrical stimulation. This work not only presents a DIC-based characterization method for quantifying the mechanical responses of adhesive interfaces in functional hydrogels, but also provides insights into how electrically regulated hydrated ions dominate interfacial adhesion and failure dynamics in electroadhesive hydrogels, which paves the way to guide the design of future high-performance electroadhesive hydrogels.

Adipose tissue adhesion remains challenging due to the difficulty in breaking through hydrophobic energy barriers created by fatty acids and other hydrophobic compounds to form effective adipose tissue closure. Here, we developed a cascaded diffusion-driven adhesive hydrogel capable of achieving the closure of subcutaneous adipose tissues through a competitive multi-hydrogen-bonded network, which was modulated by the controllable spatiotemporal diffusion of gelatin, tea polyphenols, and nicotinamide at the adhesion interfaces. We showed that nicotinamide-triggered cascade diffusion could promote the penetration of tea polyphenols and gelatin networks into adjacent adipose tissues in a topologically entangled manner, achieving self-reinforced interfacial adhesion with a peak adhesion strength greater than 100 kPa. Further, we demonstrated that the hydrogel could effectively close subcutaneous adipose tissues in pig models and activate immune and lipid metabolism-related pathways to prevent fat liquefaction, thereby promoting wound healing and inhibiting excessive adipose tissue fibrosis. This work not only presents a new solution for clinical closure of adipose tissues, but also provides innovative ideas for developing bioactive materials with hydrophobic interface adhesion functions.

There is increasing awareness of radiotherapy's potential side effects, such as lymphopenia. Therefore, this study aimed to establish the association between WBRT and the development of lymphopenia in patients with brain metastases undergoing brain radiotherapy (RT), along with evaluating the corresponding clinical outcomes. Including 116 patients with brain metastases undergoing brain radiotherapy, the study collected the absolute lymphocyte counts (ALC) within 2 weeks before brain radiotherapy (pre-radiotherapy, pre-RT), as well as ones at 1 and 2 months after completing RT (post-RT). Univariate and multivariate analyses were performed to identify associations between radiation modality and post-RT ALC. The relationships between post-RT ALC and overall survival were evaluated with Kaplan-Meier analysis and a multivariate Cox regression model. The median ALC definitely decreased at 1 month post-RT, but at 2 months post-RT, gradually rose but not to the pre-RT ALC. The multivariate analysis identified WBRT and lower pre-RT ALC as independent risk factors associated with the decrease in post-RT ALC at 1 month. It also revealed more than 4 brain metastases, G3-4 lymphopenia at 1 month and lower post-RT ALC at 2 months exhibited significantly worse prognosis regardless of the radiation modality. However, there was indeed an independent correlation between radiation modality and the outcome of intracranial progression-free survival (PFS). To approach the feasibility and reasonableness of treatment, clinicians should carefully consider various factors to achieve long-term survival of patients.

肿瘤科涉及的疾病广泛、病情复杂多变、肿瘤相关知识更新快,这些特征对临床实践提出了更高的要求及更大的挑战.因此,在肿瘤教学工作中,培养缜密的临床思维对于肿瘤专业研究生胜任临床肿瘤工作具有重要的现实意义.以问题为基础的教学法(PBL)目前得到大家的一致认可.然而,如何在PBL教学中培养肿瘤专业学生良好的临床思维值得探索.考虑不同肿瘤、不同个体导致患者的诊治存在本质性差别,因此,该文将从器官功能和形态的差异化表现、肿瘤进程时间节点的临床差异化表现、肿瘤患者治疗方式差异化表现、肿瘤患者合并基础疾病的差异化表现4个方面,探讨以肿瘤差异化表现为导向的PBL教学法在肿瘤科专业型研究生临床思维培养的应用价值.

目的 探讨早期弥散性血管内凝血(DIC)诊断中中国DIC诊断积分系统(CDSS)的价值.方法 以2017年版CDSS作为DIC的诊断标准,对2019年1月至2022年4月入住该院重症监护病房(ICU)且疑似DIC的患者进行评分和分组.以首次确诊为DIC患者的前1天CDSS评分来判断是否为早期DIC,连续3次均未达到DIC诊断标准的评分者作为对照组.共纳入疑似患者183例;其中早期DIC组66例,男48例,女18例,平均年龄62.8岁;对照组117例,其中男73例,女44例,平均年龄59.1岁.结果 早期DIC组的CDSS评分为(5.4±0.8)分,显著高于于对照组第1、2、3天的评分[分别为(3.9±1.2)分、(4.3±1.1)分、(4.5±1.1)分];第1、2、3天CDSS评分用于诊断早期DIC的受试者工作特征(ROC)曲线下面积(AUC)依次递减,分别为0.850(95％CI:0.793～0.908)、0.784(95％CI:0.716～0.853)和0.715(95％CI:0.641～0.789);首次CDSS评分值≥4分时的诊断比值比最高,为22.26,诊断灵敏度和阴性预测值均较高,分别为95.5％、96.0％;首次评分值≥6分时的诊断比值比为16.62,诊断特异度和阳性预测值相对较高,分别为91.5％和80.4％.结论 对于疑似DIC的ICU患者,CDSS积分诊断标准具备较高的早期诊断价值.

Cells living in geometrically confined microenvironments are ubiquitous in various physiological processes, e.g., wound closure. However, it remains unclear whether and how spatially geometric constraints on host cells regulate bacteria-host interactions. Here, we reveal that interactions between bacteria and spatially constrained cell monolayers exhibit strong spatial heterogeneity, and that bacteria tend to adhere to these cells near the outer edges of confined monolayers. The bacterial adhesion force near the edges of the micropatterned monolayers is up to 75 nN, which is ~3 times higher than that at the centers, depending on the underlying substrate rigidities. Single-cell RNA sequencing experiments indicate that spatially heterogeneous expression of collagen IV with significant edge effects is responsible for the location-dependent bacterial adhesion. Finally, we show that collagen IV inhibitors can potentially be utilized as adjuvants to reduce bacterial adhesion and thus markedly enhance the efficacy of antibiotics, as demonstrated in animal experiments.

Bioglues have great potential in the field of biomedical engineering concerning interfacial adhesion. Based on naturally extracted chitosan and benzoic acids, we developed low-viscosity bioglues capable of achieving an efficient and strong interfacial adhesion to wet skin tissues without any additional post-treatment. Owing to the synergy of topology, electrostatic interaction and self-hydrophobization, the adhesive strength could reach as high as 110 kPa when two pieces of fresh porcine skin were adhered together with the bioglues for one minute. Subsequently, we showed that the bioglueregulated interfacial adhesion was essentially sensitive to external electrical fields with voltages less than 1 V, which might thus cause an electrically responsive adhesion. Likewise, we revealed that the phenol-quinone transition played a dominant role in inducing changes in interfacial adhesion strength modulated by the applied electric fields. By introducing a circuit model to mimic electric stimulation, we further recognized that an electric field of similar to 2500 V/m was the threshold required for the electrically regulated phenol-quinone transition. Further, the bioglues were biocompatible, antibacterial and promoted wound healing, making them more suitable for applications in smart interfacial adhesion-related areas like biomedicine, flexible electronics and soft robotics. (c) 2022 Elsevier Ltd. All rights reserved.

Microgels that can be assembled into granular hydrogels have been served as building blocks to promote healing of irregularly shaped wounds. However, current granular hydrogels are non-adhesive and un-stretchable with low Young’s moduli and toughness, which greatly limits their ability to instantly seal the wounds and subsequently provide physical support for further tissue regeneration. Here, we put forward a novel in situ fusion strategy for granular hydrogels, which combined hydration-induced physical interactions and covalent bonds triggered by coupling reagents to achieve ultrastretchability and strong adhesion among fused granular hydrogels (FGHs). Specifically, we developed Zn2+ functionalized nanocomposite microgels (Zn NanoM) that could be in situ assembled into ultrastretchable and strongly adhesive FGHs to in situ fill irregularly shaped wounds, instantly and firmly adhere to tissue wounds. With its remarkable biocompatibility, antibacterial activity, and potent regulation of inflammatory responses through sustained release of Zn2+ ions, the developed FGH could also significantly accelerate wound healing processes in the diabetic rat full-thickness wound models, infected rat full-thickness wound models, and preclinical porcine full-thickness wound models. This work presents a new methodology for in situ fabricating modularized functional hydrogels with high performances, which provides great convenience for various biomedical applications like clinical chronic wound care.

Oral potentially malignant disorders (OPMDs) are precursor lesions with an increased risk of malignant transformation. Topical photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) (ALA-PDT) is a promising therapeutic method in the treatment of OPMDs. However, the clinical application of topical ALA-PDT is restricted by several limitations, including low delivery efficiency, poor comfort, and easy influence by saliva. Here, we designed a highly adhesion-strength dry polyacrylic acid (PAA)-chitosan (CHI)-ALA interpenetrating network hydrogel (PACA) patch after investigating the spatiotemporal dynamics of ALA drug delivery via diffusion-based finite-element models. The PACA patch could adhere to the moist oral mucosa fast and stably and deliver ALA. PACA hydrogel-mediated PDT (PACA-PDT) effectively improved OPMDs in vitro and in a hamster oral carcinogenesis model. In particular, we conducted a trial to recruit 60 OPMD volunteers to demonstrate the feasibility and comfort of the PACA hydrogel patch. This study provides evidence that PACA hydrogel-mediated PDT could be a patient-friendly treatment modality for OPMDs.

Objective:To select the appropriate quality control (QC) strategy for the detection of urine forming components through the application of Westgard Sigma analysis batch length rules to reduce the risk of missed and false detection.Methods:The internal quality control (IQC) data of urine forming components analyzer and the data of bias of IQC relative to the group mean values in SNCS (Sysmex Network Communication System) were collected from January to August 2020 in our laboratory. The total allowable error (TEa) of urine visible components stipulated in "Quality Management Standard for Clinical Laboratories of Medical Institutions in Shanghai" was adopted as the quality objective in this study.Results:The quality control strategy for white blood cell and red blood cell analysis appears "World class", σ=8.19 for WBC and σ=8.00 for RBC, Selected 13s (N=2). The analysis batch length of 200 patients were used as the quality control strategy for bacterial detection, and its performance was good (BACT, σ=4.71), Selected13s/22s/R4s/41s(N=4). The analysis batch length of 45 patients were used as the quality control strategy for epithelial cells tesing, whose results was "critical", σ=3.29, selected 13S/22S/R4S/41S/6x(N=6). However, the quality control strategy of CAST, σ＜3, needs to be improved. By the way, the QGI of EC and BACT is less than 0.8 in the detection items with σ＜6, and the precision should be improved as priority.Conclusions:The Westgard Sigma analysis batch length rule help us to optimize and improve the urine forming components analysis easily. In addition, QGI can be used to identify specific reasons for poor performance and formulate effective and prioritized improvement strategies.

The amount of dopamine (DA) in the body is closely related to the occurrence and development of Parkinson's disease. However, DA detection in real body fluids is still challenging. Here, we developed a high-selectivity and high-sensitivity label-free lanthanide metal organic frameworks (MOFs) to monitor DA in urine samples from Parkinson's patients. The fluorescent MOF Eu-alpha-cyclodextrin (CD), prepared by biomineralization under mild conditions, exhibited DA concentration-dependent fluorescence intensity via host-guest complexation. Furthermore, molecular dynamics (MD) simulation analyses quantitatively dissect thermodynamic interactions of cyclodextrin and guest molecules, which systematically reveals the specific recognition mechanism of cyclodextrin and dopamine molecules. A good response for DA in the range of 10(-9) to 10(-4) M and a limit of detection (LOD) of 0.65 nM were obtained, consistent with the detection range of DA in a variety of biological fluids. Because of the good anti-interference properties of this complex, visual test strips were prepared by the in-situ growth of Eu-alpha CD nanoparticles on a nitrocellulose (NC) membrane at room temperature, owing to the protein absorbability of NC membranes. The resultant test strips possess the potential for semiquantitative detection of DA by the naked eye. Moreover, we applied Eu-alpha CD nanoparticles to analyze clinical urine samples from Parkinson's patients, and achieved a low relative error compared with those of commercial HPLC methods. Our work offers an efficient strategy for visual and on-site detection of DA in the clinic, which can assist in early diagnosis of Parkinson's disease.

It is challenging for injectable hydrogels to achieve high underwater adhesiveness. Based on this concern, we report a fully physically crosslinked injectable hydrogel composed of gelatin, tea polyphenols and urea, capable of realising smart adhesion to various materials, like glass and porcine skin, in diverse aqueous environments. The urea molecules are designed as crosslinking disruptors for interfering with the formation of hydrogen bonds in the hydrogel, therefore modulating its crosslinking density and mechanical properties such as tensile strength, toughness and adhesive strength. Triggered by physical diffusion of the urea molecules towards the surrounding liquid environment, the hydrogel can achieve efficient (∼10 s), self-strengthening and long-lasting (>2 weeks) underwater adhesion. Remarkably, for fresh porcine skin, the instantaneous underwater adhesive strength is 10.4 kPa whereas the peak strength is as high as 152.9 kPa with the aid of the self-strengthening effect. More interestingly, it can simultaneously form controllable underwater non-adhesive surfaces, regulated by changes in the diffusion-triggered local concentration of urea. Further, it is also biocompatible, antibacterial, biodegradable and 3D printable in water, which offers great convenience for various applications concerning smart interfacial adhesion, like biomedicine and flexible electronics. Likewise, the physical diffusion-mediated mechanism represents an innovative strategy for developing next-generation smart hydrogels.

In this study, a method to improve the detection accuracy of a “weak measurement” system of optical rotation was proposed by determining the optimal total phase difference of the system. Analysis of the characteristics of weak measurement regime of the system under different total phase differences provided the total phase difference corresponding to the regime with the smallest ratio of system noise level to sensitivity (that is, the highest system resolution). In this regime, an optical rotation resolution of 5.522 × 10 -6 ° was obtained, which is nearly an order of magnitude higher than the original system.