An ion channel-based prognostic model identified TRPV2 and GJB3 as immunotherapy determinants in pancreatic cancer.

Background: Less than 10% of people who have pancreatic ductal adenocarcinoma (PDAC) will survive the malignancy for five years. The ion channel genes-related biomarker and predictive model were needed for exploitation. Methods: Differentially expressed ion channel genes (DEICGs) were detected in PDAC patients. GO and KEGG enrichment analysis was conducted on DEICGs. The prognostic genes were found using Cox regression analysis. After that, a risk model was created and examined. A nomogram was created based on independent predictive analysis. The molecular functions of two risk groups were explored. Immune checkpoint molecule expression was compared in two risk groups. We evaluated the possible cancer immunotherapy response in two risk groups using the TIDE method. We further examined how TRPV2 functions in PDAC as a potent oncogene and regulates the activity of macrophages by in vitro validation, including CCK8, EdU, and Transwell assays. Results: A total of twenty-four DEICGs were found. Next, we discovered that two DEICGs (TRPV2 and GJB3) were connected to PDAC patients' overall survival (OS). The risk model was created and validated, and a nomogram was used to forecast the overall survival of PDAC patients. The high-risk group considerably accumulated oncogenic pathways. Furthermore, we discovered a correlation between the expression of critical immunological checkpoints and the risk score. Furthermore, patients in the high-risk category had a lower chance of benefiting from immune therapy. The HPA database confirmed that TRPV2 is expressed as a protein. Lastly, TRPV2 controls macrophage activity and acts as a potent oncogene in PDAC. Conclusion: Altogether, this study suggested that two ion channel genes, TRPV2 and GJB3, were potential biomarkers for the prognosis of PDAC and immunotherapy targets, and the research will be crucial for creating novel PDAC treatment targets and predictive molecular indicators.

An integrated ceRNA network identifies miR-375 as an upregulated miRNA playing a tumor suppressive role in aggressive prostate cancer.

Prostate cancer (PCa) remains a significant cause of morbidity and mortality among men worldwide. A number of genes have been implicated in prostate tumorigenesis, but the mechanisms underlying their dysregulation are still incompletely understood. Evidence has established the competing endogenous RNA (ceRNA) theory as a novel regulatory mechanism for post-transcriptional alterations. Yet, a comprehensive characterization of ceRNA network in PCa lacks. Here we utilize stringent in-silico methods to construct a large ceRNA network across different PCa stages, and provide experimental demonstration for the competing regulation among protumorigenic SEC23A, PHTF2, and their corresponding ceRNA pairs. Using machine learning, we establish a ceRNA-based signature (ceRNA_sig) predictive of androgen receptor (AR) activity, tumor aggressiveness, and patient outcomes. Importantly, we identify miR-375 as a key node in PCa ceRNA network, which is upregulated in PCa relative to normal tissues. Forced expression of miR-375 significantly inhibits, while its inhibition promotes, aggressive behaviors of both AR+ and AR- PCa cells in vitro and in vivo. Mechanistically, we show that miR-375 predominantly targets genes possessing oncogenic roles (e.g., proliferation, DNA repair, and metastasis), and thus release targets with tumor suppressive functions. This action model well clarifies why an upregulated miRNA plays a tumor suppressive role in PCa. Together, our study provides new insights into understanding of transcriptomic aberrations during PCa evolution, and nominates miR-375 as a potential therapeutic target for combating aggressive PCa.

Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk.

BACKGROUND: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk. METHODS: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated. RESULTS: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10-8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%-4.0%) vs 6.1% (5.7%-6.5%) (difference 2.4%, P-value = 1.83 × 10-14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%-1.8%) vs 2.2% (1.9%-2.4%) (difference 0.6%, P-value = 1.01 × 10-3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk. CONCLUSIONS: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.

Risk factors of 30-day and long-term mortality and outcomes in open repair of thoracoabdominal aortic aneurysm.

BACKGROUND: Open repair of thoracoabdominal aortic aneurysm (TAAA) was characterized by significant risk of postoperative mortality and morbidity. The aim of this study was to determine the perioperative predictors of early and long-term mortality in patients undergoing open repair of TAAA. Besides, the postoperative outcomes in patients with open repair of TAAA were described. METHODS: This is a single-center retrospective study, and 146 patients with open repair of TAAA from January 4, 2011, to November 22, 2018 was involved. Categorical variables were analyzed by the Chi-square test or Fisher's exact test, and continuous variables were analyzed by the independent sample t-test and the WilCoxon rank-sum test. Multivariate Logistic regression and Cox regression were applied to identify the predictors of 30-day and long-term mortality, respectively. The Kaplan Meier curves were used to illustrate survival with the Log-rank test. RESULTS: The 30-day mortality was 9.59% (n = 14). Older than 50 years, the intraoperative volume of red blood cell (RBC) and epinephrine use were independently associated with postoperative 30-day mortality in open repair of TAAA. Long-term mortality was 17.12% (n = 25) (median of 3.5 years (IQR = 2-5 years) of follow-up). Prior open thoracoabdominal aortic aneurysm (TAAA) repair, aortic cross-clamping (ACC) time, intraoperative volume of RBC and use of epinephrine were independently correlated with long-term mortality. CONCLUSIONS: Identifying perioperative risk factors of early and long-term mortaliy is crucial for surgeons. Intraoperative volume of RBC and use of epinephrine were predictors of both early and long-term mortality. In addition, patients of advanced age, prior open repair of TAAA and prolonged ACC time should be paid more attention.

HHLA2 promotes hepatoma cell proliferation, migration, and invasion via SPP1/PI3K/AKT signaling pathway.

Hepatocellular carcinoma (HCC) stands as one of the most malignant tumors characterized by poor prognosis and high mortality rates. Emerging evidence underscores the crucial role of the B7 protein family in various cancers, including HCC. However, the involvement of the human endogenous retrovirus H long-terminal repeat-associated protein 2 (HHLA2, or B7-H5) in HCC remains unclear. Immunohistochemistry was employed to assess the differential expression of HHLA2 between HCC and normal liver tissues. A battery of assays, including CCK8, EdU, tablet clone-forming, Transwell, and wound healing assays, were conducted to elucidate the function and potential mechanisms of HHLA2 in the malignant biological behaviors of HCC. Additionally, a xenograft mouse model was established to evaluate the tumorigenicity of hepatoma cell lines exhibiting different HHLA2 expression levels in vivo. Western blot analysis was used to analyze HHLA2, secretory phosphoprotein 1 (SPP1), and PI3K/AKT/mTOR levels. HHLA2 exhibited elevated expression in HCC tissues, correlating with poor tumor differentiation and shortened overall survival in HCC patients. In vitro experiments demonstrated that HHLA2 overexpression (OE) promoted the proliferation, migration, and invasion of hepatoma cells, while in vivo experiments revealed that HHLA2 OE enhanced HCC tumor growth. Conversely, inhibition of HHLA2 expression yielded the opposite effect. Downregulation of SPP1 inhibited the proliferation, migration, and invasion induced by HHLA2 OE, and this effect was linked to the PI3K/AKT/mTOR signaling pathway. Our findings indicate that HHLA2 promotes the proliferation, migration, and invasion of hepatoma cells via the SPP1/PI3K/AKT signaling pathway, establishing it as a potential therapeutic target for HCC.

Differential diagnosis of Crohn's disease and intestinal tuberculosis based on ATR-FTIR spectroscopy combined with machine learning.

BACKGROUND: Crohn's disease (CD) is often misdiagnosed as intestinal tuberculosis (ITB). However, the treatment and prognosis of these two diseases are dramatically different. Therefore, it is important to develop a method to identify CD and ITB with high accuracy, specificity, and speed. AIM: To develop a method to identify CD and ITB with high accuracy, specificity, and speed. METHODS: A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB. Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis. RESULTS: The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm-1 and 1234 cm-1 bands, and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy, specificity, and sensitivity of 91.84%, 92.59%, and 90.90%, respectively, for the differential diagnosis of CD and ITB. CONCLUSION: Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level, and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.

Large-Area Preparation of a Robust Superamphiphobic Coating for Chemical Mechanical Polishing Application.

In the chemical-mechanical polishing (CMP) process, the abrasive particles in the polishing slurry tend to agglomerate easily and crystallize on the equipment surfaces during recycling, which can lead to poor wafer processing quality and additional tedious cleaning work. To overcome this issue, a simple and cost-effective self-cleaning surface preparation method has been developed. In this study, elastic and stretchable hydroxyl polydimethylsiloxane (PDMS-OH) was selected as the functional material, it was chelated with pentaerythritol tetra(3-mercapto propionate), and then 2-(perfluorooctyl)ethyl methacrylate was further grafted in situ to the polymer chains via a photoinduced thiol-ene click reaction. Hydrophobically modified micronanoscale silica particles were used to construct robust hierarchical micronanostructures while imparting stable mechanical wear resistance to the coating. The resulting superamphiphobic film exhibits the "lotus effect" and exceptional self-cleaning ability, repelling liquids such as water, hexadecane, and polishing slurry. Furthermore, the coating demonstrated outstanding chemical resistance and antifouling ability. Thus, it provides a feasible solution for preventing abrasive crystallization at critical locations where the polishing slurry flows in the CMP equipment. This work contributes to the enhanced application of superrepellent coatings in the CMP stage of semiconductor material processing.

Conductive Hyaluronic Acid/Deep Eutectic Solvent Composite Hydrogel as a Wound Dressing for Promoting Skin Burn Healing Under Electrical Stimulation.

Burns can cause severe damage to the skin due to bacterial infection and severe inflammation. Although conductive hydrogels as electroactive burn-wound dressings achieve remarkable effects on accelerating wound healing, issues such as imbalance between their high conductivity and mechanical properties, easy dehydration, and low transparency must be addressed. Herein, a double-network conductive eutectogel is fabricated by integrating polymerizable deep eutectic solvents (PDESs)including acrylamide/choline chloride/glycerol (acrylamide-polymerization crosslink) and thiolated hyaluronic acid (disulfide-bonding crosslink). The introduction of PDESs provides the eutectogel with a conductivity (up to 0.25 S·m-1) and mechanical strength (tensile strain of 59-77%) simulating those of natural human skin, as well as satisfactory tissue adhesiveness, self-healing ability, and antibacterial properties. When combined with exogenous electrical stimulation, the conductive eutectogel exhibits the ability to reduce inflammation, stimulate cell proliferation and migration, promote collagen deposition and angiogenesis, and facilitate skin tissue remodeling. This conductive eutectogel shows great potential as a dressing for healing major burn wounds.

Influence of Surface Basic sites and Oxygen Vacancies on the Performance of Metal-Modified Rod-Like Ceria Catalysts for Low-Temperature Hydrolysis of Carbonyl Sulfide.

This study utilized a hydrothermal method to synthesize various metal-modified rod-like ceria catalysts (Fe, Co, Cu, Ni, La), achieving efficient COS removal at low temperatures. The research identified surface oxygen vacancies and basic sites as critical factors that influence the catalytic performance of COS hydrolysis. The addition of different metals to pristine ceria rods increased the specific surface area, oxygen vacancy content (Ov), and basicity, which enhanced the catalysts' sulfur resistance and stability. Among all the catalysts tested, 10La-CeO2 demonstrated the highest COS removal rate. This is because La doping significantly augmented Ov, providing more H2O adsorption and activation sites. Furthermore, 10La-CeO2 showed enhanced Lewis basicity, making it easier for COS to adsorb and promote hydrolysis. The in situ DRIFTS results confirmed that appropriate oxygen vacancies and basic sites favored the formation of intermediates such as HCO3- and HSCO2-, promoting the decomposition of COS into H2S and CO2.

[Mechanism of Kuntai Capsules in treatment of polycystic ovary syndrome rat models based on AGE-RAGE signal pathway].

This study aims to investigate the impact of Kuntai Capsules(KTC) on polycystic ovarian syndrome(PCOS) rat models and explore the underlying mechanism. Fifty female SD rats were randomly divided into five groups(10 rats in each group), including control group, model group, low-, medium-, and high-dose KTC group. Except for the control group, the other groups were injected with dehydroepiandrosterone(DHEA) combined with a high-fat diet(HFD) to induce the PCOS rat model for 28 days. 0.315, 0.63, and 1.26 g·kg~(-1)·d~(-1) KTC was dissolved in the same amount of normal saline and given to low-, medium-, and high-dose KTC groups by gavage. Both control group and model group were given the same amount of normal saline for 15 days. After administration, fasting blood glucose(FBG) was measured by a glucose meter. Fasting insulin(FINS), luteinizing hormone(LH), testosterone(T), and follicle-stimulating hormone(FSH) were detected by enzyme-linked immunosorbent assay(ELISA), and LH/FSH ratio and insulin resistance index(HOMA-IR) were calculated. The pathological morphology of ovarian tissue was observed by hematoxylin-eosin(HE) staining. The expression levels of collagen α type Ⅲ 1 chain(COL3A1), apoptotic factors Bax, and Bcl-2 were detected using Western blot and immunofluorescence. The mRNA expressions of COL3A1, Bax, and Bcl-2 in ovarian tissue were performed by real-time PCR(RT-PCR). The results show that compared with the control group, the body weight, serum levels of FBG, FINS, LH, T, LH/FSH, and HOMA-IR are higher in model group(P<0.05 or P<0.01), and the level of FSH is lower(P<0.05). In model group, a large number of white blood cells are found in the vaginal exfoliated cells, mainly in the interictal phase. There are more cystic prominences on the surface of the ovary. The thickness of the granular cell layer is reduced, and oocytes are absent. COL3A1 and Bax protein expression levels are increased(P<0.01), while Bcl-2 protein expression levels are decreased(P<0.05) in the ovarian tissue COL3A1 and Bax mRNA expression levels are increased in ovarian tissue(P<0.05). Compared with the model group, the body weight, FBG, FINS, LH, T, LH/FSH, and HOMA-IR in low-, medium-, and high-dose KTC groups are decreased(P<0.05 or P<0.01), while the levels of FSH in medium-, and high-dose KTC groups are increased(P<0.05 or P<0.01). Low-, medium-, and high-dose KTC groups gradually show a stable interictal phase. The surface of the ovary is smooth. Oocytes and mature follicles can be seen in ovarian tissue, and the thickness of the granular cell layer is increased. The expression level of COL3A1 protein decreases in low-and medium-dose KTC groups(P<0.05 or P<0.01), and that of Bax protein decreases in low-dose KTC group(P<0.05 or P<0.01), and the expression level of Bcl-2 protein increases in low-dose KTC group(P<0.01). The expression levels of COL3A1 and Bax mRNA decreased in the low-dose KTC group(P<0.05), while the expression levels of Bcl-2 mRNA increased(P<0.05). In summary, KTC can inhibit ovarian granulosa cell apoptosis and reduce follicular atresia by regulating the AGE-RAGE signaling pathway. It can promote insulin secretion, reduce blood sugar and body weight, restore serum hormone levels, improve symptoms of PCOS, alleviate morphological damage of the ovary, and restore ovarian function, which is of great value in the treatment of PCOS.

Discovery of ganoderic acid A (GAA) PROTACs as MDM2 protein degraders for the treatment of breast cancer.

Breast cancer is one of the most common female malignant tumors, with triple-negative breast cancer (TNBC) being the most specific, highly invasive, metastatic and associated with a poor prognosis. Our previous study showed that the natural product ganoderic acid A (GAA) has a certain affinity for MDM2. In this study, two series of novel GAA PROTACs C1-C10 and V1-V10 were designed and synthesized for the treatment of breast cancer. The antitumor activity of these compounds was evaluated against four human tumor cell lines (MCF-7, MDA-MB-231, SJSA-1, and HepG2). Among them, V9 and V10 showed stronger anti-proliferative effects against breast cancer cells, and V10 showed the best selectivity in MDA-MB-231 cells (TNBC), which was 5-fold higher than that of the lead compound GAA. Preliminary structure-activity analysis revealed that V-series GAA PROTACs had better effects than C-series, and the introduction of 2O-4O PEG linkers could significantly improve the antitumor activity. Molecular docking, surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), and Western blot researches showed that both V9 and V10 could bind with MDM2, and degrade the protein through the ubiquitin-proteasome system. Molecular dynamics simulation (MD) revealed that V10 is a bifunctional molecule that can bind to von Hippel-Lindau (VHL) at one end and target MDM2 at the other. In addition, V10 promoted the upregulation of p21 in p53-mutant MDA-MB-231 cells, and induced apoptosis via down-regulation of the bcl-2/bax ratio and the expression of cyclin B1. Finally, in vivo experiments showed that, V10 also exhibited good tumor inhibitory activity in xenografted TNBC zebrafish models, with an inhibition rate of 27.2% at 50 µg/mL. In conclusion, our results suggested that V10 has anti-tumor effects on p53-mutant breast cancer in vitro and in vivo, and may be used as a novel lead compound for the future development of TNBC.

Speeding up the classical simulation of Gaussian boson sampling with limited connectivity.

Gaussian boson sampling (GBS) plays a crucially important role in demonstrating quantum advantage. As a major imperfection, the limited connectivity of the linear optical network weakens the quantum advantage result in recent experiments. In this work, we introduce an enhanced classical algorithm for simulating GBS processes with limited connectivity. It computes the loop Hafnian of an n × n symmetric matrix with bandwidth w in O ( n w 2 w ) time. It is better than the previous fastest algorithm which runs in O ( n w 2 2 w ) time. This classical algorithm is helpful on clarifying how limited connectivity affects the computational complexity of GBS and tightening the boundary for achieving quantum advantage in the GBS problem.

Unraveling DDIT4 in the VDR-mTOR pathway: a novel target for drug discovery in diabetic kidney disease.

Introduction: Diabetic kidney disease (DKD) necessitates innovative therapeutic strategies. This study delves into the role of DNA damage-inducing transcription factor 4 (DDIT4) within the VDR-mTOR pathway, aiming to identify a novel target for DKD drug discovery. Methods: Transcriptome data from the Gene Expression Omnibus Database were analyzed to assess the expression of mTOR and VDR expression in human renal tissues. Clinical samples from DKD patients and minimal change disease (MCD) controls were examined, and a DKD animal model using 20-week-old db/db mice was established. DDIT4 plasmid transfection was employed to modulate the VDR-mTOR pathway, with its components evaluated using immunohistochemistry, real-time quantitative PCR (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). Results: Changes in the expression of the VDR-mTOR pathway were observed in both DKD patients and the animal model. Overexpression of DDIT4 increased VDR expression and decreased levels of mTOR, p70s6k, and 4E-BP1. Furthermore, DDIT4 treatment regulated autophagy by upregulating LC3I expression and downregulating LC3II expression. Notably, DDIT4 alleviated oxidative stress by reducing the levels of lipid peroxidation product MDA, while simultaneously increasing the levels of superoxide dismutase (SOD) and glutathione (GSH), underscoring the role of DDIT4 in the pathological process of DKD and its potential as a therapeutic target. Conclusion: Unraveling DDIT4's involvement in the VDR-mTOR pathway provides insights for innovative DKD drug discovery, emphasizing its potential as a therapeutic target for future interventions.

Carrier-Free Self-Assembly Nano-Sonosensitizers for Sonodynamic-Amplified Cuproptosis-Ferroptosis in Glioblastoma Therapy.

Cuproptosis is a newly discovered form of programmed cell death significantly depending on the transport efficacy of copper (Cu) ionophores. However, existing Cu ionophores, primarily small molecules with a short blood half-life, face challenges in transporting enough amounts of Cu ions into tumor cells. This work describes the construction of carrier-free nanoparticles (Ce6@Cu NPs), which self-assembled by the coordination of Cu2+ with the sonosensitizer chlorin e6 (Ce6), facilitating sonodynamic-triggered combination of cuproptosis and ferroptosis. Ce6@Cu NPs internalized by U87MG cells induce a sonodynamic effect and glutathione (GSH) depletion capability, promoting lipid peroxidation and eventually inducing ferroptosis. Furthermore, Cu+ concentration in tumor cells significantly increases as Cu2+ reacts with reductive GSH, resulting in the downregulation of ferredoxin-1 and lipoyl synthase. This induces the oligomerization of lipoylated dihydrolipoamide S-acetyltransferase, causing proteotoxic stress and irreversible cuproptosis. Ce6@Cu NPs possess a satisfactory ability to penetrate the blood-brain barrier, resulting in significant accumulation in orthotopic U87MG-Luc glioblastoma. The sonodynamic-triggered combination of ferroptosis and cuproptosis in the tumor by Ce6@Cu NPs is evidenced both in vitro and in vivo with minimal side effects. This work represents a promising tumor therapeutic strategy combining ferroptosis and cuproptosis, potentially inspiring further research in developing logical and effective cancer therapies based on cuproptosis.

Visible light-induced photocatalytic and antibacterial adhesion properties of superhydrophilic TiO2 nanoparticles.

Bacterial infections triggered by patient or healthcare worker contact with surfaces are a major cause of medically acquired infections. By controlling the kinetics of tetrabutyl titanate hydrolysis and condensation during the sol-gel process, it is possible to regulate the content of Ti3+ and oxygen vacancies (OVs) in TiO2, and adjust the associated visible light-induced photocatalytic performance and anti-bacterial adhesion properties. The results have shown that the Ti3+ content in TiO2 was 9.87% at the calcination temperature of the reaction system was 300 °C and pH was 1.0, corresponding to optimal photocatalytic and hydrophilic properties. The formation of a hydrated layer on the superhydrophilic surface provided resistance to bacterial adhesion, preventing cross-contamination on high-touch surfaces. The excellent photocatalytic self-cleaning performance and anti-bacterial adhesion properties can be attributed to synergistic effects associated with the high specific surface area of TiO2 nanoparticles, the mesoporous structure, and the presence of Ti3+ and OVs. The formation of superhydrophilic self-cleaning surfaces under visible light can serve as the basis for the development of a new class of anti-bacterial adhesion materials.

Sensitive electrochemical flow injection analysis of H2O2 released from cells with a pass-through mode.

Conventional plate electrodes were commonly used in electrochemical flow injection analysis and only part of molecules diffused to the plane of electrodes could be detected, which would limit the performance of electrochemical detection. In this study, a low-cost native stainless steel wire mesh (SSWM) electrode was integrated into a 3D-printed device for electrochemical flow injection analysis with a pass-through mode, which is different compared with previous flow-through mode. This strategy was applied for sensitive analysis of hydrogen peroxide (H2O2) released from cells. Under the optimal conditions (the applied potentials, the flow rate and the sample volume), the device exhibits high sensitivity toward H2O2. Linear relationships could be achieved between electrochemical responses and the concentration of H2O2 ranging from 1 nM to 1 mM. The excellent analytical performance of the SSWM-based device could be attributed to the pass-through mode based on the mesh microstructure and intrinsic catalytic properties for H2O2 by stainless steel. This approach could be further successfully extended for screening of H2O2 released from HeLa cells with electrochemical responses linear to the number of cells in a range of 3 - 1.35 × 104 cells with an injection volume of 30 µL. This study revealed the potential of mesh electrodes in electrochemical flow injection analysis for cellular function and pathology and its possible extension in cell counting and on-line analysis.

Characteristics and risk factors for invasive fungal infection in hospitalized patients with acute-on-chronic hepatitis B liver failure: a retrospective cohort study from 2010 to 2023.

Background and aim: The global burden of invasive fungal infections (IFIs) is emerging in immunologic deficiency status from various disease. Patients with acute-on-chronic hepatitis B liver failure (ACHBLF) are prone to IFI and their conditions are commonly exacerbated by IFI. However, little is known about the characteristics and risk factors for IFI in hospitalized ACHBLF patients. Methods: A total of 243 hospitalized ACHBLF patients were retrospectively enrolled from January 2010 to July 2023. We performed restricted cubic spline analysis to determine the non-linear associations between independent variables and IFI. The risk factors for IFI were identified using logistic regression and the extreme gradient boosting (XGBoost) algorithm. The effect values of the risk factors were determined by the SHapley Additive exPlanations (SHAP) method. Results: There were 24 ACHBLF patients (9.84%) who developed IFI on average 17.5 (13.50, 23.00) days after admission. The serum creatinine level showed a non-linear association with the possibility of IFI. Multiple logistic regression revealed that length of hospitalization (OR = 1.05, 95% CI: 1.02-1.08, P = 0.002) and neutrophilic granulocyte percentage (OR = 1.04, 95% CI: 1.00-1.09, P = 0.042) were independent risk factors for IFI. The XGBoost algorithm showed that the use of antibiotics (SHAP value = 0.446), length of hospitalization (SHAP value = 0.406) and log (qHBV DNA) (SHAP value = 0.206) were the top three independent risk factors for IFI. Furthermore, interaction analysis revealed no multiplicative effects between the use of antibiotics and the use of glucocorticoids (P = 0.990). Conclusion: IFI is a rare complication that leads to high mortality in hospitalized ACHBLF patients, and a high neutrophilic granulocyte percentage and length of hospitalization are independent risk factors for the occurrence of IFI.

Recent advances of focused ultrasound induced blood-brain barrier opening for clinical applications of neurodegenerative diseases.

With the aging population on the rise, neurodegenerative disorders have taken center stage as a significant health concern. The blood-brain barrier (BBB) plays an important role to maintain the stability of central nervous system, yet it poses a formidable obstacle to delivering drugs for neurodegenerative disease therapy. Various methods have been devised to confront this challenge, each carrying its own set of limitations. One particularly promising noninvasive approach involves the utilization of focused ultrasound (FUS) combined with contrast agents-microbubbles (MBs) to achieve transient and reversible BBB opening. This review provides a comprehensive exploration of the fundamental mechanisms behind FUS/MBs-mediated BBB opening and spotlights recent breakthroughs in its application for neurodegenerative diseases. Furthermore, it addresses the current challenges and presents future perspectives in this field.

Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy.

Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME, have shown promising results in enhancing immunotherapy by facilitating targeted delivery and immune modulation. These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, and encourage T cell infiltration. Biomimetic nanoparticles further enhance immunotherapy by increasing the internalization of immunomodulatory agents in immune cells such as dendritic cells. Moreover, exosomes, whether naturally secreted by cells in the body or bioengineered, have been explored to regulate the TME and immune-related cells to affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated by pH, redox, and light conditions, exhibit the potential to accelerate immunotherapy. The co-application of nanoparticles with immune checkpoint inhibitors is an emerging strategy to boost anti-tumor immunity. With their ability to induce long-term immunity, nanoarchitectures are promising structures in vaccine development. This review underscores the critical role of nanoparticles in overcoming current challenges and driving the advancement of cancer immunotherapy and TME modification.

NETosis in tumour microenvironment of liver: From primary to metastatic hepatic carcinoma.

BACKGROUND: Hepatocellular carcinoma is a common and highly lethal tumour. The tumour microenvironment (TME) plays an important role in the progression and metastasis of hepatocellular carcinoma (HCC). A cell death mechanism, termed NETosis, has been found to play an important role in the TME of HCC. SUMMARY: This review article focuses on the role of NETosis in the TME of HCC, a novel form of cell death in which neutrophils capture and kill microorganisms by releasing a type of DNA meshwork fibres called "NETs". This process is associated with neutrophil activation, local inflammation and cytokines. The study suggests that NETs play a multifaceted role in the development and metastasis of HCC. The article also discusses the role of NETs in tumour proliferation and metastasis, epithelial-mesenchymal transition (EMT), and surgical stress. In addition, the article discusses the interaction of NETosis with other immune cells in the TME and related therapeutic strategies. A deeper understanding of NETosis can help us better understand the complexity of the immune system and provide a new therapeutic basis for the treatment and prevention of HCC. KEY INFORMATION: In conclusion, NETosis is important in the TME of liver. NETs have been shown to contribute to the progression and metastasis of liver cancer. The interaction between NETosis and immune cells in the TME, as well as related therapies, are important areas of research.