Theoretical study on the effect of temperature gradient on contact-free scanning for scanning ion conductance microscopy.

Scanning ion-conductance microscopy (SICM) is a non-contact, high-resolution, and in-situ scanning probe microscope technique, it can be operated in probing the physical and chemical properties of biological samples such as living cells. Recently, using SICM to study the effects of microenvironment changes such as temperature changes on response of the biological samples has attracted significant attention. However, in this temperature gradient condition, one of the crucial but still unclear issues is the scanning feedback types and safe threshold. In this paper, a theoretical study of effect of the temperature gradient in electrolyte or sample surface on the SICM safe ion-current threshold is conducted using three-dimensional Poisson-Nernst-Planck, Navier-Stokes and energy equations. Two temperature gradient types, sample surface and two types of pipettes with different ratio of inner and outer radii are included, respectively. The results demonstrate that the local temperature of the electrolyte and then sample surface significantly affect the ion flow, shape of the approach curves and thus safe threshold in SICM pipette probe for contact-free scanning. There is a current-increased and decreased phases for approaching the surface with higher temperature and two current-decreased phases for surface with lower temperature. Based on this shape feature of approach curves, the change rate of current is analysis to illustrate the possibility for contact-free scanning of slope object. The results indicate that with the decrease of the normalized tip-surface distance, the coupling effect of large slope angle and local high temperature makes the increase in change rate of ion current not significant and then it challenging to realize contact-free scanning especially for higher surface temperature.

Relationship between fundamental motor skills and physical fitness in children with global developmental delay.

Importance: Understanding the significance of motor skills in promoting physical fitness (PF) can offer valuable insights for devising comprehensive intervention and clinical rehabilitation programs for children with global developmental delay (GDD). However, it remains unclear whether fundamental motor skills (FMS) can improve the PF of children with GDD. Objective: To investigate the correlation between FMS and PF in children with GDD. Methods: A total of 180 children with GDD and 180 typically developing (TD) children aged 3-5 years were selected. All participants completed the Gesell Developmental Schedule, FMS, and PF tests at Beijing Children's Hospital between September 2022 and August 2023. Partial correlation and regression analyses were performed to examine the relationship between FMS and PF. Results: Children with GDD had significantly lower FMS and PF scores compared to TD children (P < 0.05). No significant differences were found between males and females with GDD in FMS and PF score (P > 0.05). A more severe developmental delay was associated with lower FMS and PF scores. The correlation coefficients between individual FMS items and individual PF items, as well as the total PF score, ranged from 0.20 to 0.56. Regression analysis indicated that manual dexterity (ß = 0.241, P = 0.029) and body balance (ß = 0.399, P = 0.001) significantly predicted the total PF score. Interpretation: In children with GDD, both FMS and PF are underdeveloped. Focusing on motor skills development is vital for promoting their PF.

NIR Enhanced pH-Responsive Microneedles for Synergetic Therapy of Melanoma.

Melanoma has emerged as a significant threat to human life and health. Microneedle (MN)-mediated transdermal drug delivery (TDD) has garnered attention in melanoma treatment for bypassing the first-pass effect. However, the propensity of melanoma to metastasize presents substantial challenges for MN mediated local treatment. Developing systemic therapies, such as immunotherapy in combination with TDD, is crucial for achieving effective melanoma treatment. Herein, a polyvinyl alcohol (PVA) MN-mediated multifunctional TDD system, designated MN@PDA@1-MT/CUR/DOX@HA (MN@PMCDH), was developed for synergetic chemotherapy/photothermal/immunotherapy of melanoma. PMCDH nanomedicines penetrate deep skin layers through MNs, accumulate at tumor sites guided by hyaluronic acid (HA), and selectively release drugs in response to the acidic tumor microenvironment and near-infrared (NIR) stimulation. Released curcumin (CUR) significantly enhances the efficacy of photothermal therapy (PTT) and chemotherapy, as well as improves the induction of immunogenic cell death (ICD) by increasing melanoma sensitivity to polydopamine (PDA)-mediated photothermal effects and doxorubicin (DOX). Moreover, the incorporation of 1-methyltryptophan (1-MT) to reverse the tumor immunosuppressive microenvironment can further enhance the effects of immunotherapy. In vitro studies revealed that the MN@PMCDH system can effectively induce ICD and inhibit tumor cell growth. Additionally, remarkable deep tumor cell inhibition effects are also achieved in 3D tumor models.

A hydrogel sensor based on cellulose nanofiber/polyvinyl alcohol with colorimetric-fluorescent bimodality for non-invasive detection of urea in sweat.

The concentration of urea in sweat serves as a valuable indicator of an individual's overall health. In this study, we present a novel hydrogel sensor (BAF-CPu), based on cellulose nanofiber and polyvinyl alcohol, designed to achieve non-invasive in situ and highly sensitive detection of urea in sweat by combining the dual-mode response of colorimetric and ratiometric fluorescence techniques. The bright red fluorescent gold­copper bimetallic nanoclusters and green fluorescent fluorescein isothiocyanate-modified cellulose nanofibers endowed BAF-CPu with proportional fluorescence responsive properties. Under the catalytic action of urease, the hydrolysis of urea raises the pH, resulting in diminished red fluorescence along with enhanced green fluorescence, and the fluorescence color of BAF-CPu changes from red to green. Moreover, BAF-CPu hydrogel encapsulates pH-responsive bromothymol blue (BTB), which changes from yellow to blue in the presence of urea. Importantly, BAF-CPu absorbs sweat by adhering directly to the skin surface, avoiding the complicated sampling process and improving the maneuverability of the detection process. With both ratiometric fluorescence and colorimetric modes, BAF-CPu is not only able to detect sweat in situ, but also can reduce the interference of the complex sweat environment on the urea detection, and realize the high sensitivity detection of urea in sweat.

[Influence of Postoperative Diet Type and Regimen on Hospital Comfort
and Rehabilitation of Lung Cancer Patients].

BACKGROUND: A reasonable and standardized dietary plan and procedure can help patients recovering quickly from lung cancer surgery. The aim of this study is to optimize the diet plan and procedure mainly based on medium chain triglyceride (MCT) diet and explore its clinical advantages for postoperative lung cancer patients. METHODS: From October 2023 to December 2023, a total of 156 patients were collected, who underwent lung cancer surgery in Lung Cancer Center, West China Hospital of Sichuan University. The patients were randomized into MCT group (76 cases) and routine diet (RD) group (80 cases). Clinical symptoms, biochemical index, postoperative hospitalization time and cost, dietary satisfaction and hospitalization comfort between the two groups were analyzed. RESULTS: The mean anus exhausting time in MCT group [24.00 (9.75, 36.97) h] was significantly shorter than that in RD group [28.50 (24.00, 48.00) h] (P<0.001). And the incidence of dizziness (18.42%), nausea and vomiting (6.58%) in MCT group were remarkably lower than those in RD group (51.25%, 31.25%) (P<0.001). Hospitalization comfort score in MCT group [(16.74±1.70)] was significantly higher than that in RD group [(14.83±2.34)] (P=0.016). Meanwhile, the average hospitalization cost in MCT group [(39,701.82±8105.47)¥] showed an obvious decrease compared with RD group [(44,511.79±9593.19)¥] (P=0.007). CONCLUSIONS: Optimizing the dietary plan and procedure mainly based on MCT diet for postoperative lung cancer patients can help the recovery of gastrointestinal function and improve hospitalization comfort, which promoted overall postoperative rehabilitation of patients with lung cancer surgery.

Yolov8n-FADS: A Study for Enhancing Miners' Helmet Detection Accuracy in Complex Underground Environments.

A new algorithm, Yolov8n-FADS, has been proposed with the aim of improving the accuracy of miners' helmet detection algorithms in complex underground environments. By replacing the head part with Attentional Sequence Fusion (ASF) and introducing the P2 detection layer, the ASF-P2 structure is able to comprehensively extract the global and local feature information of the image, and the improvement in the backbone part is able to capture the spatially sparsely distributed features more efficiently, which improves the model's ability to perceive complex patterns. The improved detection head, SEAMHead by the SEAM module, can handle occlusion more effectively. The Focal Loss module can improve the model's ability to detect rare target categories by adjusting the weights of positive and negative samples. This study shows that compared with the original model, the improved model has 29% memory compression, a 36.7% reduction in the amount of parameters, and a 4.9% improvement in the detection accuracy, which can effectively improve the detection accuracy of underground helmet wearers, reduce the workload of underground video surveillance personnel, and improve the monitoring efficiency.

Identification of exosomal circSLC26A4 as a liquid biopsy marker for cervical cancer.

OBJECTIVE: Circular RNA SLC26A4 (circSLC26A4) functions as an oncogene in the initiation and progression of cervical cancer (CC). However, the clinical role of plasma exosomal circSLC26A4 in CC is poorly known. This study aims to develop an accurate diagnostic method based on circulating exosomal circSLC26A4. METHODS: In this study, exosomal circSLC26A4 derived from CC cell lines (CaSki, SiHa, and HeLa) and human cervical epithelial cells (HcerEpic) was measured and compared using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Additionally, 56 volunteers, including 18 CC patients, 18 cervical high-grade squamous intraepithelial lesion (HSIL) patients, and 20 healthy volunteers, were enrolled. qRT-PCR was also performed to measure the plasma exosomal circSLC26A4 levels in all participants. RESULTS: The exosomal circSLC26A4 expression level derived from CC cells was significantly elevated compared to it derived from HcerEpic cells. Plasma exosomal circSLC26A4 levels in CC patients were significantly higher than in healthy women and HSIL patients (P < 0.05). In addition, high plasma exosomal circSLC26A4 expression was positively associated with lymph node metastasis and FIGO stage (all P < 0.05). However, no significant correlation was found between plasma exosomal circSLC26A4 expression and age, intravascular cancerous embolus, and perineural invasion (P > 0.05). CONCLUSIONS: The high exosomal circSLC26A4 expression is closely related to the occurrence of CC. Plasma exosomal circSLC26A4 can be used as a diagnostic marker for CC.

Application of biomacromolecule-based passive penetration enhancement technique in superficial tumor therapy: A review.

Transdermal drug delivery (TDD) has shown great promise in superficial tumor therapy due to its noninvasive and avoidance of the first-pass effect. Especially, passive penetration enhancement technique (PPET) provides the technical basis for TDD by temporarily altering the skin surface structure without requiring external energy. Biomacromolecules and their derived nanocarriers offer a wide range of options for PPET development, with outstanding biocompatibility and biodegradability. Furthermore, the abundant functional groups on biomacromolecule surfaces can be modified to yield functional materials capable of targeting specific sites and responding to stimuli. This enables precise drug delivery to the tumor site and controlled drug release, with the potential to replace traditional drug delivery methods and make PPET-related personalized medicine a reality. This review focuses on the mechanism of biomacromolecules and nanocarriers with skin, and the impact of nanocarriers' surface properties of nanocarriers on PPET efficiency. The applications of biomacromolecule-based PPET in superficial tumor therapy are also summarized. In addition, the advantages and limitations are discussed, and their future trends are projected based on the existing work of biomacromolecule-based PPET.

Factors influencing pathological changes in the liver tissue in hepatitis B virus carriers with low-level viremia.

OBJECTIVES: To investigate the optimal timing for initiating antiviral therapy in hepatitis B virus (HBV) carriers with low-level viremia (LLV). METHODS: We retrospectively enrolled 126 HBV carriers with LLV who underwent liver biopsy. Patients' clinical data, routine blood test results, portal vein diameter, splenic vein diameter and thickness, and measurements (LSM) within 1 week before liver biopsy were obtained. Single-factor and multifactor statistical methods were used to analyze factors that affected inflammation and fibrosis in pathological liver tissues. The receiver operating characteristic curve was used to analyze liver stiffness and HBV DNA levels to determine liver tissue inflammation and fibrosis. R -Studio software was used to draw nomograms, calibration plots, and model decision curves. RESULTS: Infection duration and HBV DNA levels affected liver tissue inflammation. Albumin(ALB), aspartate aminotransferase (AST), HBV DNA, liver stiffness, age, and splenic thickness affected liver fibrosis. The best cutoff value of the LSM for diagnosing liver inflammation and fibrosis was 7.45 (specificity, 92%). The best cutoff value of HBV DNA for diagnosing liver inflammation and fibrosis was 39.5 (specificity, 96%). HBV DNA,and splenic thickness affected the treatment decision in naive chronic hepatitis Bpatients with LLV CONCLUSIONS: HBV carriers with LLV have high incidences of liver tissue inflammation and fibrosis. The infection duration and HBV DNA levels affected liver inflammation whereas the ALB, AST levels, HBV DNA, LSM, age, and splenic thickness affected liver fibrosis. Eligible expansion of antiviral treatment indications is necessary, however, a universal treatment approach may be inefficient. HBV DNA can be a reference for initiating antiviral therapy.

Activation of RIG-I signaling in the early stage of Paragonimus proliferus infection causes lung injury via type I immune response in rat.

Paragonimiasis is a common zoonotic parasitic disease. The retinoic acid-inducible gene I (RIG-I) signaling is very important for the host to recognize invading pathogens (especially viruses and bacteria). However, the role of RIG-I signaling in the early stages of P. proliferus infection remains unclear. Therefore, in this study, Sprague-Dawley (SD) rat models with lung damage caused by P. proliferus were established. Experimental methods including Enzyme-linked Immuno Sorbent Assay (ELISA), real-time fluorescent quantitative polymerase chain reaction (PCR), western blotting, and hematoxylin and eosin (HE) staining were used to explore the mechanisms of lung injury caused by P. proliferus. As a result, the expression of the mRNA and proteins of RIG-I signal-related key target molecules, including RIG-I, tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6), interferon regulatory Factor 7 (IRF7), IPS-1, and downstream C-X-C chemokine ligand 10 (CXCL10), were significantly up-regulated immediately after infection, peaked at 3 or 7 days, and showed a downward trend on after 14 days. The levels of pro-inflammatory cytokines interleukin-1 (IL-1), interferon (IFN)-α, -ß, and -γ, which represent type 1 immune response, gradually increased and reached a peak by 14 days, which was consistent with the changes in the degree of inflammatory damage observed under HE staining of lung tissues. In conclusion, RIG-I signaling is activated in the early stage (before 14 days) of P. proliferus infection, it is inferred that the lung injury of the host may be related to the activation of RIG-I like signaling to induce type I immune response.

A novel FA1-targeting fluorescent probe for specific discrimination and identification of human serum albumin from bovine serum albumin.

A novel probe C1 combining benzothiazole with a spiropyran section was developed for the specific detection of human serum albumin (HSA). The molecular docking suggested that the sulphonic acid group modification allowed C1 to form specific hydrogen bonds with lysine (Lys137) at fatty acid site 1 (FA1) of HSA, thus enabling fluorescence differentiation between HSA and BSA.

Construction of porous flower-like Ru-doped CoNiFe layered double hydroxide for supercapacitors and oxygen evolution reaction catalysts.

In recent years, ternary layered double hydroxide (LDH) has become a research hotspot for electrode materials and oxygen evolution reaction (OER) catalyst due to the enhanced synergistic effect between individual elements. However, the application of LDH is greatly limited by its low electrical conductivity and the disadvantage that nanosheets tend to accumulate and mask the active sites. Herein, a novel Ru-doped CoNiFe - LDH was prepared via a facile hydrothermal method. According to the density functional theory (DFT) calculations, the doping of Ru element could improve electron state density and band gaps of LDH and consequently boosted the electrochemical reaction kinetics as well as electrical conductivity. Furthermore, introduction of Ru atom induced the formation of porous flower-like structures in nanosheets. Compared to CoNiFe - LDH (28.9 m2/g), Ru-doped CoNiFe - LDH performed larger specific surface area of 53.1 m2/g, resulting in more electrochemically active sites. In these case, Ru-doped CoNiFe - LDH demonstrated better energy storage performance of 176.0 mAh/g at 1 A/g compared to original CoNiFe - LDH (78.9 mAh/g at 1 A/g). Besides, the assembled Ru-doped CoNiFe - LDH//activated carbon (AC) device delivered a maximum energy density of 36.4 W h kg-1 at the power density of 740.3 W kg-1 and an outstanding cycle life (78.7 % after 10,000 cycles). Meanwhile, Ru-doped CoNiFe - LDH exhibited lower overpotential (339 mV at 50 mA cm-2) and Tafel slope (93.2 mV dec-1). Therefore, this work provided novel and valuable insights into the rational doping of Ru elements for the controlled synthesis of supercapacitor electrode materials and OER catalysts.

Engineering a hyaluronic acid-encapsulated tumor-targeted nanoplatform with sensitized chemotherapy and a photothermal effect for enhancing tumor therapy.

Chemotherapy remains one of the most widely used cancer treatment modalities in clinical practice. However, the characteristic microenvironment of solid tumors severely limits the anticancer efficacy of chemotherapy. In addition, a single treatment modality or one death pathway reduces the antitumor outcome. Herein, tumor-targeting O2 self-supplied nanomodules (CuS@DOX/CaO2-HA) are proposed that not only alleviate tumor microenvironmental hypoxia to promote the accumulation of chemotherapeutic drugs in tumors but also exert photothermal effects to boost drug release, penetration and combination therapy. CuS@DOX/CaO2-HA consists of copper sulfide (CuS)-loaded calcium peroxide (CaO2) and doxorubicin (DOX), and its surface is further modified with HA. CuS@DOX/CaO2-HA underwent photothermal treatment to release DOX and CaO2. Hyperthermia accelerates drug penetration to enhance chemotherapeutic efficacy. The exposed CaO2 reacts with water to produce Ca2+, H2O2 and O2, which sensitizes cells to chemotherapy through mitochondrial damage caused by calcium overload and a reduction in drug efflux via the alleviation of hypoxia. Moreover, under near infrared (NIR) irradiation, CuS@DOX/CaO2-HA initiates a pyroptosis-like cell death process in addition to apoptosis. In vivo, CuS@DOX/CaO2-HA demonstrated high-performance antitumor effects. This study provides a new strategy for synergistic enhancement of chemotherapy in hypoxic tumor therapy via combination therapy and multiple death pathways.

Constructing Hierarchical CoGa2O4-S@NiCo-LDH Core-Shell Heterostructures with Crystalline/Amorphous/Crystalline Heterointerfaces for Flexible Asymmetric Supercapacitors.

The rational design and construction of composite electrodes are crucial for overcoming the issues of poor working stability and slow ionic electron mobility of a single component. Nevertheless, it is a big challenge to construct core-shell heterostructures with crystalline/amorphous/crystalline heterointerfaces in straightforward and efficient methods. Here, we have successfully converted a portion of crystalline CoGa2O4 into the amorphous phase by employing a facile sulfidation process (denoted as CoGa2O4-S), followed by anchoring crystalline NiCo-layered double hydroxide (denoted as NiCo-LDH) nanoarrays onto hexagonal plates and nucleation points of CoGa2O4-S, synthesizing dual-type hexagonal and flower-like 3D CoGa2O4-S@NiCo-LDH core-shell heterostructures with crystalline/amorphous/crystalline heterointerfaces on carbon cloth. Furthermore, we further adjust the Ni/Co ratio in LDH, achieving precise and controllable core-shell heterostructures. Benefiting from the abundant crystalline/amorphous/crystalline heterointerfaces and synergistic effect among various components, the CoGa2O4-S@Ni2Co1-LDH electrode exhibits a specific capacity of 247.8 mAh·g-1 at 1 A·g-1 and good rate performance. A CoGa2O4-S@Ni2Co1-LDH//AC flexible asymmetric supercapacitor provides an energy density of 58.2 Wh·kg-1 at a power density of 850 W·kg-1 and exhibits an impressive capacitance retention of 105.7% after 10,000 cycles at 10 A·g-1. Our research provides profound insights into the design of other similar core-shell heterostructures.

Electrochemical Biosensor for Protein Concentration Monitoring Using Natural Wood Evaporation for Power Generation.

A high-sensitivity, low-cost, self-powered biomass electrochemical biosensor based on the "evaporating potential" theory is developed for protein detection. The feasibility of experimental evaluation methods was verified with a probe protein of bovine serum albumin. The sensor was then used to detect lung cancer marker CYFRA21-1, and the potential of our sensor for clinical diagnosis was demonstrated by serum analysis. This work innovatively exploits the osmotic power generation capability of natural wood to construct a promising electrochemical biosensor that was driven by kinetics during testing. The detection methods used for this sensor, chronoamperometry and AC impedance, showed potential for quantitative analysis and specific detection, respectively. Furthermore, the sensor could facilitate new insights into the development of high-sensitivity, low-cost, and easy-to-use electrochemical biosensors.

Acceleration or retardation by a magnetic field of the anodic processes of iron in molybdate-bearing chloride solutions.

The modulation by a horizontal magnetic field of the anodic processes of iron in molybdate-bearing chloride solutions is determined. The magnetic field can accelerate or retard the anodic reaction depending on the rate-controlling steps at specified electrode potentials. The anodic current density arising from uniform dissolution from open or semi-open pits is increased by the magnetic field. The current density originating from occluded pits can be decreased by the magnetic field, where autocatalysis has a dominant effect on the pitting rate. The effect of the magnetic field on the pitting corrosion is a combination of the influence on electrochemical reactions at the interfaces of the pits and the disturbance of the autocatalysis process inside the pit enclave through the magnetohydrodynamic (MHD) effect. Micro-MHD effects for specific locations and macro-MHD effects for pitting systems are recommended to illustrate the magnetic effect on localized corrosion phenomena at various combinations of potentials and solution compositions.

Breviscapine attenuates lead­induced myocardial injury by activating the Nrf2 signaling pathway.

The present study investigated the therapeutic potential of breviscapine (Bre) in mitigating lead (Pb)-induced myocardial injury through activation of the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway. Rat cardiomyocytes (H9C2 cells) were exposed to Pb to model Pb poisoning, and various parameters, including cell viability, apoptosis and reactive oxygen species (ROS) production, were assessed using Cell Counting Kit-8, flow cytometry and 2',7'-dichlorfluoresceindiacetate assays, respectively. Additionally, a rat model of Pb poisoning was established in which blood Pb levels were measured using a graphite furnace atomic absorption spectrophotometer, and alterations in myocardial tissue, oxidative stress markers, inflammatory indicators, protein expression related to apoptosis and the Nrf2 pathway were evaluated via histopathology, ELISA and western blotting. The results showed that Bre treatment enhanced cell viability, decreased apoptosis, and reduced ROS production in Pb-exposed H9C2 cells. Moreover, Bre modulated oxidative stress markers and inflammatory factors while enhancing the expression of proteins in the Nrf2 pathway. In a rat model, Bre mitigated the lead-induced increase in blood Pb levels and myocardial injury biomarkers, and reversed the downregulation of Nrf2 pathway proteins. In conclusion, the current findings suggested that Bre mitigates Pb-induced myocardial injury by activating the Nrf2 signaling pathway, highlighting its potential as a therapeutic agent for protecting the heart from the harmful effects of Pb exposure. Further research is required to elucidate the exact mechanisms and explore the clinical applicability of Bre in mitigating Pb-induced myocardial damage.

The relationship between the expression of Stathmin and tumor immune cell infiltration in primary cervical carcinoma and its prognostic diagnostic value.

To analyse the relationship between the Stathmin expression and the tumor immune cell infiltration in primary cervical carcinoma (CC), and its prognostic diagnostic value. Cervical tissue samples from 128 patients admitted to our hospital from February 2021 to February 2022 who underwent hysterectomy or cervical biopsy were selected as the observation objects, and then divided into control group (normal cervical tissue specimen, n = 30), cervical intraepithelial neoplasia (CIN) group (CIN neoplasia cervical tissue specimen, n = 30), and cervical cancer group (cervical tissue specimen of cervical cancer lesion, n = 68) according to pathological results. The expression of Stathmin was detected by Immunohistochemistry (IHC). The numbers of infiltrated neutrophils (TINs) were measured by the specific esterase staining. The pathological data of CC patients were collected, and the protein expression of Stathmin was compared with different pathological data. According to the protein expression of Stathmin, the samples were divided into Stathmin positive group and negative group. The infiltration numbers, the levels of CD3+T, CD4+T and CD8+T of TINs were compared in each group, and CD4+/CD8+ were calculated. Kaplan-Meier survival curve was used for the analysis of the relationship between the Stathmin expression and the clinical prognosis in CC. COX analysis was used to determine the factors affecting the prognosis of patients with CC. The proportion of positive expression of cervical tissue Stathmin in CIN group and cervical cancer group was significantly higher than that in the control group, and the proportion of positive expression of cervical tissue Stathmin in cervical cancer group was significantly higher than that in CIN group (P < 0.001). The ratio of the clinical stage II + III, tissue grade low and medium differentiation, and lymph node metastasis in Stathmin positive group was significantly higher than that in the Stathmin negative group (P < 0.05). Compared with the Stathmin negative group, the numbers of TINs infiltration and the level of CD4+/CD8+ were visibly higher, and the content of CD3+T, CD4+T and CD8+T were sharply lower in the Stathmin positive group (P < 0.001). Compared with the Stathmin negative group, the numbers of TINs infiltration were higher, but the content of CD4+T and CD8+T were lower in Stathmin-positive group (P < 0.001). The 68 CC patients were followed up, with a median follow-up time of 25 months (5-60 months) and an overall survival rate of 66.18 % (45/68). The results of Kaplan-Meier survival curve showed that the median survival time of patients with the Stathmin positive expression was 30 months, which was significantly lower than that of 46 months (P < 0.05) in patients with the Stathmin negative expression. Multivariate analysis of COX proportional regression risk model showed that the Stathmin positive expression, TINs infiltration numbers≥55, CD3+<5.5 %, CD4+<4.5 %, CD8+<3 %, CD4+/CD8+≥1.3 were independent factors affecting the prognosis of CC patients (P < 0.05). Stathmin in the primary tissue of CC had a significantly high expression state, which was involved in the occurrence and development of CC, thus affecting the immune microenvironment balance damaged by tumor immune cell infiltration. Detecting its expression level might help the diagnosis and prognosis assessment of CC, and Stathmin might become a new target of CC immunotherapy.

The construction of hierarchical assemblies with in situ generation of chemotherapy drugs to enhance the efficacy of chemodynamic therapy for multi-modal anti-tumor treatments.

The effectiveness of chemodynamic therapy (CDT) in cancer treatment is limited by insufficient endogenous H2O2 levels in tumor tissue and an increasing ratio of high valence metal ions. To overcome these challenges, a novel nanotherapeutic approach, named GOx-CuCaP-DSF, has been proposed. This approach involves the design of nanotherapeutics that aim to self-supply H2O2 within cancer cells and provide a supplement of low valence metal ions to enhance the performance of CDT. GOx-CuCaP-DSF nanotherapeutics are engineered by incorporating glucose oxidase (GOx) into Ca2+-doped calcium phosphate (CaP) nanoparticles and loading disulfiram (DSF) through surface adsorption. Under the tumor microenvironment, GOx catalyzes the conversion of tumor-overexpressed glucose (Glu) to liberate H2O2. The degradation of CaP further lowers the pH, facilitating the release of Cu2+ ions and DSF. The rapid reaction between Cu2+ and DSF leads to the generation of Cu+, increasing the Cu+/Cu2+ ratio and promoting the Cu+-based Fenton reaction, which enhances the efficiency of CDT. Simultaneously, DSF undergoes conversion to diethyldithiocarbamate acid (ET), forming a copper(II) complex (Cu(II)ET) by strong chelation with Cu ions. This Cu(II)ET complex, a potent chemotherapeutic drug, exhibits a synergistic therapeutic effect in combination with CDT. Moreover, the elevated Cu+ species resulting from DSF reaction promotes the aggregation of toxic mitochondrial proteins, leading to cell cuproptosis. Overall, the strategy of integrating the chemodynamic therapy efficiency of the Fenton reaction with the activation of efficacious cuproptosis using a chemotherapeutic drug presents a promising avenue for enhancing the effectiveness of multi-modal anti-tumor treatments.