One-Pot Synthesis of Fe-Norepinephrine Nanoparticles for Synergetic Thermal-Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT) is an innovative and burgeoning strategy that utilizes Fenton-Fenton-like chemistry and specific microenvironments to produce highly toxic hydroxyl radicals (•OH), with numerous methods emerging to refine this approach. Herein, we report a coordination compound, Fe-norepinephrine nanoparticles (Fe-NE NPs), via a one-pot synthesis. The Fe-NE NPs are based on ferrous ions (Fe2+) and norepinephrine, which are capable of efficient Fe2+/Fe3+ delivery. Once internalized by tumor cells, the released Fe2+/Fe3+ exerts the Fenton reaction to specifically produce toxic •OH. Moreover, the internal photothermal conversion ability of Fe-NE NPs allows us to simultaneously introduce light to trigger local heat generation and then largely improve the Fenton reaction efficiency, which enables a synergetic photothermal and chemodynamic therapy to realize satisfactory in vivo antitumor efficiency. This proof-of-concept work offers a promising approach to developing nanomaterials and refining strategies for enhanced CDT against tumors.

Multifunctional Glycopeptide-Based Hydrogel via Dual-Modulation for the Prevention and Repair of Radiation-Induced Skin Injury.

The radiation-induced skin injury (RISI) remains a great challenge for clinical wound management and care after radiotherapy, as patients will suffer from the acute radiation injury and long-term chronic inflammatory damage during the treatment. The excessive ROS in the early acute stage and prolonged inflammatory response in the late healing process always hinder therapeutic efficiency. Herein, we developed an extracellular matrix (ECM)-mimetic multifunctional glycopeptide hydrogel (oCP@As) to promote and accelerate RISI repair via a dual-modulation strategy in different healing stages. The oCP@As hydrogel not only can form an ECM-like nanofiber structure through the Schiff base reaction but also exhibits ROS scavenging and DNA double-strand break repair abilities, which can effectively reduce the acute radiation damage. Meanwhile, the introduction of oxidized chondroitin sulfate, which is the ECM polysaccharide-like component, enables regulation of the inflammatory response by adsorption of inflammatory factors, accelerating the repair of chronic inflammatory injury. The animal experiments demonstrated that oCP@As can significantly weaken RISI symptoms, promote epidermal tissue regeneration and angiogenesis, and reduce pro-inflammatory cytokine expression. Therefore, this multifunctional glycopeptide hydrogel dressing can effectively attenuate RISI symptoms and promote RISI healing, showing great potential for clinical applications in radiotherapy protection and repair.

A glycopolymersome strategy for 'drug-free' treatment of diabetic nephropathy.

Diabetic nephropathy is a severe complication of diabetes. Treatment of diabetic nephropathy is an important challenge due to persistent hyperglycemia and elevated levels of reactive oxygen species (ROS) in the kidney. Herein, we designed a glycopolymersome that can treat type 2 diabetic nephropathy by effectively inhibiting hyperglycemia and ROS-associated diabetic nephropathy pathogenesis. The glycopolymersome is self-assembled from phenylboronic acid derivative-containing copolymer, poly(ethylene oxide)45-block-poly[(aspartic acid)13-stat-glucosamine24-stat-(phenylboronic acid)18-stat-(phenylboronic acid pinacol ester)3] [PEO45-b-P(Asp13-stat-GA24-stat-PBA18-stat-PAPE3)]. PBA segment can reversibly bind blood glucose or GA segment for long-term regulation of blood glucose levels; PAPE segment can scavenge excessive ROS for renoprotection. In vitro studies confirmed that the glycopolymersomes exhibit efficient blood glucose responsiveness within 2 h and satisfactory ROS-scavenging ability with 500 µM H2O2. Moreover, the glycopolymersomes display long-acting regulation of blood glucose levels in type 2 diabetic nephropathy mice within 32 h. Dihydroethidium staining revealed that these glycopolymersomes reduced ROS to normal levels in the kidney, which led to 61.7% and 76.6% reduction in creatinine and urea levels, respectively, along with suppressing renal apoptosis, collagen accumulation, and glycogen deposition in type 2 diabetic nephropathy mice. Notably, the polypeptide-based glycopolymersome was synthesized by ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs), thereby exhibiting favorable biodegradability. Overall, we proposed a new glycopolymersome strategy for 'drug-free' treatment of diabetic nephropathy, which could be extended to encompass the design of various multifunctional nanoparticles targeting diabetes and its associated complications.

Heme-Mimetic Photosensitizer with Iron-Targeting and Internalizing Properties for Enhancing PDT Activity and Promoting Infected Diabetic Wound Healing.

The management of multibacterial infections remains clinically challenging in the care and treatment of chronic diabetic wounds. Photodynamic therapy (PDT) offers a promising approach to addressing bacterial infections. However, the limited target specificity and internalization properties of traditional photosensitizers (PSs) toward Gram-negative bacteria pose significant challenges to their antibacterial efficacy. In this study, we designed an iron heme-mimetic PS (MnO2@Fe-TCPP(Zn)) based on the iron dependence of bacteria that can be assimilated by bacteria and retained in different bacteria strains (Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus) and which shows high PDT antibacterial efficacy. For accelerated wound healing after antibacterial treatment, MnO2@Fe-TCPP(Zn) was loaded into a zwitterionic hydrogel with biocompatibility and antifouling properties to form a nanocomposite antibacterial hydrogel (PSB-MnO2@Fe-TCPP(Zn)). In the multibacterial infectious diabetic mouse wound model, the PSB-MnO2@Fe-TCPP(Zn) hydrogel dressing rapidly promoted skin regeneration by effectively inhibiting bacterial infections, eliminating inflammation, and promoting angiogenesis. This study provides an avenue for developing broad-spectrum antibacterial nanomaterials for combating the antibiotic resistance crisis and promoting the healing of complex bacterially infected wounds.

Integrated micro/nano drug delivery system based on magnetically responsive phase-change droplets for ultrasound theranostics.

Phase-change droplets (PCDs) are intelligent responsive micro and nanomaterials developed based on micro/nano bubbles. Subject to external energy inputs such as temperature and ultrasound, the core substance, perfluorocarbon (PFC), undergoes a phase transition from liquid to gas. This transformation precipitates alterations in the PCDs' structure, size, ultrasound imaging capabilities, drug delivery efficiency, and other pertinent characteristics. This gives them the ability to exhibit "intelligent responses". This study utilized lipids as the membrane shell material and perfluorohexane (PFH) as the core to prepare lipid phase-change droplets. Superparamagnetic nanoparticles (PEG-functionalized Fe3O4 nanoparticles) and the anti-tumor drug curcumin (Cur) were loaded into the membrane shell, forming magnetic drug-loaded phase-change droplets (Fe-Cur-NDs). These nanoscale phase-change droplets exhibited excellent magnetic resonance/ultrasound imaging capabilities and thermal/ultrasound-mediated drug release. The Fe-Cur-NDs showed excellent anti-tumor efficacy for the MCF-7 cells under low-intensity focused ultrasound (LIFU) guidance in vitro. Therefore, Fe-Cur-NDs represent a promising smart responsive theranostic integrated micro/nano drug delivery system.

Small-molecule inhibitor HI-TOPK-032 improves NK-92MI cell infiltration into ovarian tumours.

The effectiveness of natural killer (NK) cells transferred adoptively in combating solid tumours is limited by challenges such as their difficulty in penetrating tumours from the bloodstream and maintaining viability without the support of interleukin-2 (IL-2). Genetically modified NK-92MI cells, which can release IL-2 to sustain their viability, have been identified as a promising alternative. This adaptation addresses the negative consequences of systemic IL-2 administration. The role of PSD-95/discs large/ZO-1 (PDZ)-binding kinase (PBK) in cancer development is recognized, but its effects on immunity are not fully understood. This study explores how PBK expression influences the ability of NK-92MI cells to infiltrate ovarian tumours. Elevated levels of PBK expression have been found in various cancers, including ovarian cancer (OV), with analyses showing higher PBK mRNA levels in tumour tissues compared to normal ones. Immunohistochemistry has confirmed increased PBK expression in OV tissues. Investigations into PBK's role in immune regulation reveal its association with immune cell infiltration, indicating a potentially compromised immune environment in OV with high PBK expression. The small-molecule inhibitor HI-TOPK-032, which inhibits PBK, enhances the cytotoxicity of NK-92MI cells toward OV cells. It increases the production of interferon-γ and tumour necrosis factor-α, reduces apoptosis and encourages cell proliferation. Mechanistic studies showed that contact with OV cells treated with HI-TOPK-032 upregulates CD107a on NK-92 cells. In vivo studies demonstrated that HI-TOPK-032 improves the antitumour effects of NK-92MI cells in OVCAR3Luc xenografts, extending survival without significant side effects. Safety assessments in mice confirm HI-TOPK-032's favourable safety profile, highlighting its potential as a viable antitumour therapy. These results suggest that combining NK-92MI cells with HI-TOPK-032 enhances antitumour effectiveness against OV, indicating a promising, safe and effective treatment strategy that warrants further clinical investigation.

Single-cell RNA sequencing of cervical exfoliated cells reveals potential biomarkers and cellular pathogenesis in cervical carcinogenesis.

Cervical cancer (CC) is a common gynecological malignancy. Despite the current screening methods have been proved effectively and significantly decreased CC morbidity and mortality, deficiencies still exist. Single-cell RNA sequencing (scRNA-seq) approach can identify the complex and rare cell populations at single-cell resolution. By scRNA-seq, the heterogeneity of tumor microenvironment across cervical carcinogenesis has been mapped and described. Whether these alterations could be detected and applied to CC screening is unclear. Herein, we performed scRNA-seq of 56,173 cervical exfoliated cells from 15 samples, including normal cervix, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and malignancy. The present study delineated the alteration of immune and epithelial cells derived during the cervical lesion progression. A subset of lipid-associated macrophage was identified as a tumor-promoting element and could serve as a biomarker for predicting the progression of LSIL into HSIL, which was then verified by immunofluorescence. Furthermore, cell-cell communication analysis indicated the SPP1-CD44 axis might exhibit a protumor interaction between epithelial cell and macrophage. In this study, we investigated the cervical multicellular ecosystem in cervical carcinogenesis and identified potential biomarkers for early detection.

Vemurafenib induces senescence in acute myeloid leukemia and myelodysplastic syndrome by activating the HIPPO signaling pathway: implications for potential targeted therapy.

BACKGROUND: The outcome of Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remain dismal despite the development of treatment. Targeted therapy is gaining more and more attention in improving prognosis. METHODS: Expression of BRAF was analyzed by RT-qPCR in AML and MDS patients. Cells viability treated by drugs was measured by CCK-8 assay. Network pharmacology and RNA-sequence were used to analyze the mechanism of drugs and verified in vitro and xenograft tumor model. RESULTS: Here we showed that BRAF was overexpressed in AML and MDS patients, and correlated with poor prognosis. The BRAF inhibitor-Vemurafenib (VEM) could significantly induce senescence, proliferation inhibition and apoptosis in AML cells, which can be enhanced by Bortezomib (BOR). This inhibitory effect was also verified in CD34 + cells derived from AML patients. Mechanistically, we showed that VEM combined with BOR could turn on HIPPO signaling pathway, thereby inducing cellular senescence in AML cells and xenograft mouse. CONCLUSIONS: Taken together, our findings demonstrate a significant upregulation of BRAF expression in AML and MDS patients, which is associated with unfavorable clinical outcomes. We also discovered that the BRAF inhibitor Vemurafenib induces cellular senescence through activation of the HIPPO signaling pathway. Analysis of BRAF expression holds promise as a prognostic indicator and potential therapeutic target for individuals with AML and MDS.

MR imaging findings of stage I intravenous leiomyomatosis: a retrospective single-center study in 19 cases.

OBJECTIVES: The aim was to explore the magnetic resonance imaging (MRI) features of stage-I intravenous leiomyomatosis (IVL). MATERIALS AND METHODS: From January 2019 to January 2023, clinical, pathological, and MRI data were collected from 19 cases confirmed by surgical pathology. Two radiologists retrospectively measured the tumor sizes, T1WIs, T2WIs, and ADC values and evaluated contrast-enhanced T1WIs, DWIs, complications and parauterine infiltrations. The number of tumor cells and the total nuclear area were measured. The percentage of tumor cell area out of the total area was used as the tumor cell density. RESULTS: Nineteen patients with stage-I IVL aged 33 to 66 years (mean age: 46 ± 7.6 years) were included in this study. All 19 cases were located in the myometrium or parametrium, with a mean diameter of 11.2 ± 4.8 cm. Among these cases, 14 (73.6%) were associated with leiomyoma, and six (31.6%) involved the broad ligament. Isointensity was observed in the T1WIs of 12 cases (63.2%), while slight hypointensity was seen in five patients (26.3%). Isointensity was observed in the on T2WIs of four cases (21.1%), and iso- or slight hyperintensity was observed in 15 cases (78.9%). A significant difference was detected between the normalized T2WIs of IVL and myometrium (p < 0.001). A Pearson correlation test showed demonstrated a negative correlation between the ADC and tumor cell density values (r = - 0.946, p < 0.001). Tortuous vessels were present in 17 cases (89.5%) within or next to the lesions, and multiple winding cord-like filling defects were seen in 11 cases (57.9%) within the tortuous vessels on the T2WIs. CONCLUSION: Identifying the characteristic MRI features of stage-I IVL helped improve the diagnostic accuracy achieves for this rare tumor. Stage-I IVL often presents as a large mass accompanied by leiomyoma, and it easily invades the broad ligament. TIWI signals exhibited isointensity, and T2WI signals contained iso- or slight hyperintensity. Tortuous vessels were present within or next to the lesions, and multiple winding cord-like filling defects were observed within the tortuous vessels on the T2WIs.

Surgical treatment and prognosis of recurrent and radiotherapy insensitive nasopharyngeal carcinoma.

OBJECTIVE: To explore the effect of surgical treatment and related prognostic factors for recurrent Nasopharyngeal Carcinoma (NPC) after radiotherapy and the pathological types of nasopharyngeal carcinoma insensitive to radiotherapy. METHODS: A total of 70 NPC patients who underwent surgery at the Department of Otolaryngology, head and neck surgery, from January 2005 to December 2020 were retrospectively included: 41 males and 29 females, aged 21-75 years, 47 patients were pathologically classified as NPC (nonkeratinizing, undifferentiated type), 10 patients as adenoid cystic carcinoma, 13 patients as other types, 45 patients had received radiotherapy preoperatively, and 25 patients had not received radiotherapy preoperatively. All patients underwent surgical treatment under general anesthesia. Fifty-six patients underwent nasoendoscopic NPC resection, seven patients underwent open surgery, and seven patients underwent combined nasoendoscopic and open surgery. The median follow-up was 39 months. Tumor volume, extent of involvement, lymph node metastasis, imaging characteristics, surgical approach and efficacy, postoperative complications, and 2-, 3-, and 5-year postoperative survival rates were calculated for all patients. Statistical analysis was performed using spss22 Kaplan Meier survival analysis and Cox regression analysis were performed. RESULTS: Among the 70 patients, the overall 2-year survival rate was 93.4%, the 3-year survival rate was 90.8%, and the 5-year survival rate was 80.3%. Multivariate analysis showed that TNM stage and age at onset were independent prognostic factors for NPC outcome. CONCLUSION: Depending on the size and location of the tumor, endoscopic surgery, open surgery, and combined open surgery with nasoendoscopy may be considered for recurrent and radiotherapy insensitive NPC. LEVEL OF EVIDENCE: Level 4.

Surgical treatment and prognosis of recurrent and radiotherapy insensitive nasopharyngeal carcinoma

Abstract Objective To explore the effect of surgical treatment and related prognostic factors for recurrent Nasopharyngeal Carcinoma (NPC) after radiotherapy and the pathological types of nasopharyngeal carcinoma insensitive to radiotherapy. Methods A total of 70 NPC patients who underwent surgery at the Department of Otolaryngology, head and neck surgery, from January 2005 to December 2020 were retrospectively included: 41 males and 29 females, aged 21-75 years, 47 patients were pathologically classified as NPC (nonkeratinizing, undifferentiated type), 10 patients as adenoid cystic carcinoma, 13 patients as other types, 45 patients had received radiotherapy preoperatively, and 25 patients had not received radiotherapy preoperatively. All patients underwent surgical treatment under general anesthesia. Fifty-six patients underwent nasoendoscopic NPC resection, seven patients underwent open surgery, and seven patients underwent combined nasoendoscopic and open surgery. The median follow-up was 39 months. Tumor volume, extent of involvement, lymph node metastasis, imaging characteristics, surgical approach and efficacy, postoperative complications, and 2-, 3-, and 5-year postoperative survival rates were calculated for all patients. Statistical analysis was performed using spss22 Kaplan Meier survival analysis and Cox regression analysis were performed. Results Among the 70 patients, the overall 2-year survival rate was 93.4%, the 3-year survival rate was 90.8%, and the 5-year survival rate was 80.3%. Multivariate analysis showed that TNM stage and age at onset were independent prognostic factors for NPC outcome. Conclusion Depending on the size and location of the tumor, endoscopic surgery, open surgery, and combined open surgery with nasoendoscopy may be considered for recurrent and radiotherapy insensitive NPC. Level of Evidence: Level 4.

Clinical Effect of Platelet-Rich Fibrin Combined with BIO-GENE Artificial Bone Meal in Bone Defects After Jaw Cyst Surgery.

Purpose: To compare the clinical repair effects of leaving the defect empty and using Platelet-Rich Fibrin (PRF) combined with BIO-GENE artificial bone powder in patients with bone defects 6 months after jaw cystectomy. Patients and Methods: From June 2021 to June 2022, 70 patients who were admitted to the Department of Stomatology, Affiliated Hospital of Yanbian University, and were diagnosed with jaw cysts postoperatively were selected. All of the patients were divided into two groups according to random method, among which 35 patients who underwent cystectomy alone were recorded as group A, which served as blank control; 35 patients who underwent cystectomy and PRF combined with BIO-GENE artificial bone meal repaired bone defects during the same period were recorded as group B. 3D Slicer 5.0.3 software was used to reconstruct Cone Beam Computed Tomography (CBCT) after operation. In this study, the preoperative and postoperative CBCT data of the patients were analyzed using 3D Slicer 5.0.3 software in DICOM format to calculate the cleft volume before surgery and the newly formed bone volume after surgery. The osteogenesis rate was measured based on these calculations.The bone formation percentage in the bone defect area was recorded at 6 months, and the clinical curative effects of the two groups were compared. Results: After 6 months of surgery, the patients showed varying degrees of restoration in the jaw cyst area.The osteogenesis rate at 6 months in group A was 76.06±13.38%, while group B had a rate of 92.87±5.72%.The CBCT values in group B were higher than those in group A at 6 months post-surgery (P<0.05), t=-6.84.Group A and Group B showed a statistically significant difference. Conclusion: Compared with simple cystectomy, PRF combined with BIO-GENE artificial bone powder has a better effect on the speed of bone repair after cystectomy within 6 months and provides more favorable effects for the repair of postoperative dentition defects, and provides support to repair teeth after defects such as dental implants.

Clinical Effects of Pulsed Dye Laser Dynamically Combined with Triamcinolone Acetonide in the Treatment of Postoperative Recurrence Keloids.

Purpose: This study aimed to explore the clinical effects of pulsed dye laser (PDL) dynamically combined with triamcinolone acetonide (TAC) in the treatment of post-operative keloids recurrence. Materials and Methods: This study retrospectively analysed the clinical data of 29 keloid patients (with 39 keloids) from April 2014 to February 2020. The patients were divided into TAC group (14 patients with 19 keloids) and dynamic treatment group (15 patients with 20 keloids) according to the post-operative treatment that they received. The keloids were assessed by Vancouver scar scale (VSS), patient and observer scar assessment scale (POSAS) and the effect of keloids on the quality of life of patients was evaluated with dermatology life quality index (DLQI) scale before the surgical treatment, at any time of relapse, and 24 months after the surgical treatment. The recurrence-free interval, relative cure time, and the cumulative times of TAC injection when the relative cure could be assessed as achieved, and the incidence of adverse reactions were calculated. Results: Patients experiencing a recurrence within 2 years after surgery included 19 keloids (25.33%) that developed a recurrent event within 6 months, 34 keloids (45.33%) that within 12 months, and 39 keloids (52.00%) that within 24 months after surgery. Anterior chest keloid had the highest recurrence rate and ear keloid had the lowest recurrence rate. The total pigmentation and vascularity (VSS and POSAS) scores of patients' keloids in TAC group and dynamic treatment group 24 months after treatment were significantly lower than those before treatment and at relapse (P < 0.05), the total VSS and POSAS scores were significantly lower at 24 months than before treatment and at relapse (P < 0.05), and the DLQI scale score was significantly lower at 24 months than before treatment (P < 0.05). The VSS and POSAS scores of patients' keloids at 24 months after treatment were significantly lower in the dynamic treatment group than in the TAC group. The relative cure time of patients' keloids in the dynamic treatment group was 6.47 ± 2.72 months, which was significantly shorter than 8.65 ± 3.67 months in the TAC group (P < 0.05). The cumulative number of TAC injections that were given to achieve a relative cure of patients' keloids in dynamic treatment group was 3.60 ± 1.76, which was significantly less than 5.24 ± 2.25 in TAC group. The total incidence of adverse reactions was lower in the dynamic group than in TAC group, but this difference did not reach statistical significance (P > 0.05). Conclusions: Compared with TAC injection alone, PDL dynamically combined with TAC in the treatment of keloid with post-operative recurrence can shorten the relative cure time, reduce the number of TAC injections and improve the clinical efficacy.

Copine 1 predicts poor clinical outcomes by promoting M2 macrophage activation in ovarian cancer.

OBJECTIVE: Copine 1 (CPNE1), a membrane-binding protein, influences the prognosis of various cancers. According to cBioPortal, CPNE1 amplification is a prevalent genetic mutation in ovarian cancer but with unknown oncogenic mechanism. METHODS: This study analysed the CPNE1 expression in ovarian cancer using online datasets, as validated by immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR) and western blotting. Concurrently, the prognostic value of CPNE1 was accessed. Cell Counting Kit-8, colony formation, transwells and xenograft experiments were performed to evaluate the functions of CPNE1 during ovarian cancer carcinogenesis. CPNE1 and its related genes were analysed by g:Profiler and Tumour Immune Estimation Resource. Furthermore, human monocytic THP-1 cells were co-cultured with ES2 cells to investigate the effect of CPNE1 on macrophage polarization. RESULTS: The results of bioinformatic analysis, IHC, qPCR and western blotting indicated a higher CPNE1 in ovarian cancer. CPNE1 overexpression demonstrated an association with a poor prognosis of ovarian cancer. Functionally, CPNE1 overexpression increased ES2 and SKOV3 cell proliferation, invasion and migration in vitro and promoted ovarian tumour xenograft growth in vivo, while CPNE1 knockdown led to opposite effects. Additionally, CPNE1 expression demonstrated an association with immune cell infiltration in ovarian cancer, especially macrophage. CPNE1 promoted protumour M2 macrophage polarization by upregulating cluster of differentiation 163 (CD163), CD206 and interleukin-10. CONCLUSIONS: Our study revealed that CPNE1 mediated M2 macrophage polarization and provided a therapeutic target for ovarian cancer.

Emerging role of METTL3 in inflammatory diseases: mechanisms and therapeutic applications.

Despite improvements in modern medical therapies, inflammatory diseases, such as atherosclerosis, diabetes, non-alcoholic fatty liver, chronic kidney diseases, and autoimmune diseases have high incidence rates, still threaten human health, and represent a huge financial burden. N6-methyladenosine (m6A) modification of RNA contributes to the pathogenesis of various diseases. As the most widely discussed m6A methyltransferase, the pathogenic role of METTL3 in inflammatory diseases has become a research hotspot, but there has been no comprehensive review of the topic. Here, we summarize the expression changes, modified target genes, and pathogenesis related to METTL3 in cardiovascular, metabolic, degenerative, immune, and infectious diseases, as well as tumors. In addition to epithelial cells, endothelial cells, and fibroblasts, METTL3 also regulates the function of inflammation-related immune cells, including macrophages, neutrophils, dendritic cells, Th17 cells, and NK cells. Regarding therapeutic applications, METTL3 serves as a target for the treatment of inflammatory diseases with natural plant drug components, such as emodin, cinnamaldehyde, total flavonoids of Abelmoschus manihot, and resveratrol. This review focuses on recent advances in the initiation, development, and therapeutic application of METTL3 in inflammatory diseases. Knowledge of the specific regulatory mechanisms involving METTL3 can help to deepen understanding of inflammatory diseases and lay the foundation for the development of precisely targeted drugs to address inflammatory processes.

Ceruloplasmin is associated with the infiltration of immune cells and acts as a prognostic biomarker in patients suffering from glioma.

Glioma is regarded as a prevalent form of cancer that affects the Central Nervous System (CNS), with an aggressive growth pattern and a low clinical cure rate. Despite the advancement of the treatment strategy of surgical resection, chemoradiotherapy and immunotherapy in the last decade, the clinical outcome is still grim, which is ascribed to the low immunogenicity and tumor microenvironment (TME) of glioma. The multifunctional molecule, called ceruloplasmin (CP) is involved in iron metabolism. Its expression pattern, prognostic significance, and association with the immune cells in gliomas have not been thoroughly investigated. Studies using a variety of databases, including Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Gliovis, showed that the mRNA and protein expression levels of CP in patients suffering from glioma increased significantly with an increasing glioma grade. Kaplan-Meier (KM) curves and statistical tests highlighted a significant reduction in survival time of patients with elevated CP expression levels. According to Cox regression analysis, CP can be utilized as a stand-alone predictive biomarker in patients suffering from glioma. A significant association between CP expression and numerous immune-related pathways was found after analyzing the data using the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Tumor Immune Estimation Resource (TIMER) and CIBERSORT analyses indicated a substantial correlation between the CP expression and infiltration of immunocytes in the TME. Additionally, immune checkpoints and CP expression in gliomas showed a favorable correlation. According to these results, patients with glioma have better prognoses and levels of tumor immune cell infiltration when their CP expression is low. As a result, CP could be used as a probable therapeutic target for gliomas and potentially anticipate the effectiveness of immunotherapy.

Pretreatment of free nitrous acid combined with calcium hypochlorite for enhancement of hydrogen production in waste activated sludge.

A variety of variables limit the recovery of resources from anaerobic fermentation of waste activated sludge (WAS), hence pretreatment strategies are necessary to be investigated to increase its efficiency. A combination of free nitrous acid (FNA) and calcium hypochlorite [Ca(ClO)2] was employed in this investigation to significantly improve sludge fermentation performance. The yields of cumulative hydrogen for the blank and FNA treatment group were 1.09 ± 0.16 and 7.36 ± 0.21 mL/g VSS, respectively, and 6.59 ± 0.24 [0.03 g Ca(ClO)2/g TSS], 7.75 ± 0.20 (0.06), and 8.58 ± 0.22 (0.09) mL/g VSS for the Ca(ClO)2 groups. The co-treatment greatly boosted hydrogen generation, ranging from 39.97 ± 2.26 to 76.20 ± 4.78 % as compared to the solo treatment. Mechanism analysis demonstrated that the combined treatment disturbed sludge structure and cell membrane permeability even more, which released more organic substrates and enhanced biodegradability of fermentation broth. This paper describes a unique strategy to sludge pretreatment that expands the use of Ca(ClO)2 and FNA in anaerobic fermentation, with implications for sludge disposal and energy recovery.

PSMD4 drives progression of hepatocellular carcinoma via Akt/COX2 pathway and p53 inhibition.

The ubiquitin-dependent proteolytic pathway is crucial for cellular regulation, including control of the cell cycle, differentiation, and apoptosis. Proteasome 26S Subunit Ubiquitin Receptor, Non-ATPase 4, (PSMD4) is a member of the ubiquitin proteasome family that is upregulated in multiple solid tumors, including hepatocellular carcinoma (HCC), and the existence of PSMD4 is associated with unfavorable prognosis. In this study, transcriptome sequencing of HCC tissues and non-tumor hepatic tissues from the public database Cancer Genome Atlas (TGCA) revealed a high expression of PSMD4. Additionally, PSMD4 loss in HCC cells suppressed the tumor development in mouse xenograft model. PSMD4, which is maintained by inflammatory factors secreted from tumor matrix cells, positively mediates cell growth and is associated with Akt/GSK-3ß/ cyclooxygenase2 (COX2) pathway activation, inhibition of p53 promoter activity, and increased p53 degradation. However, the domain without the C-terminus (VWA+UIM1/2) sustained the activation of p53 transcription. Thus, our findings suggest that PSMD4 is involved in HCC tumor growth through COX2 expression and p53 downregulation. Therapeutic strategies targeting PSMD4 and its downstream effectors could be used for the treatment of PSMD4-abundant HCC patients.

Nano-chitin reinforced agarose hydrogels: Effects of nano-chitin addition and acidic gas-phase coagulation.

Hydrogels based on natural polymers such as agarose usually show low applicability due to their weak mechanical properties. In this work, we developed a dual cross-linked agarose hydrogel by adding different amounts of TEMPO-oxidized nano-chitin (0-0.2 %) to agarose hydrogel matrices and then physically cross-linked under acidic gas-phase coagulation. The prepared hydrogels were characterized by FTIR, XRD, TGA, and SEM. The effects of nano-chitin addition and acidic gas-phase coagulation on the properties of agarose hydrogels, such as gel strength, swelling degree, rheological properties, and methylene blue (MB) adsorption capacity, were also studied. Structural characterizations confirmed that nano-chitin was successfully introduced into agarose hydrogels. The gel strength, storage modulus, and MB adsorption capacity of agarose hydrogels gradually increased with the increasing nano-chitin addition, whereas the swelling degree decreased. After acidic gas-phase coagulation, agarose/nano-chitin nanocomposite hydrogels exhibited improved gel strength and storage modulus, while the swelling degree and MB adsorption capacity were slightly reduced. The combination of oxidized nano-chitin and acidic gas-phase coagulation is expected to be an effective way to improve the properties of natural polymer hydrogels.

Diagnosis of gastric cancer based on hybrid genes selection approach.

Gastric cancer (GC) is the third leading cause of cancer death worldwide. In the field of medicine, machine learning is widely used in genetic data mining and the construction of diagnostic models. This study proposed an intelligent model DERFS-XGBoost for rapid and accurate diagnosis of GC based on gene expression data. Firstly, the data of GC were collected and preprocessed. Secondly, ANOVA, t-test and fold chang (FC) were used to select genes that had significant differentially expressed genes (DEGs), and random forest (RF) was used to calculate their importance, and then sequential forward selection (SFS) was used to obtain the optimal feature subset. Finally, XGBoost was used for classification after synthetic minority oversampling technique (SMOTE) balanced between tumor and normal samples. In order to objectively evaluate the results, the 10-fold cross-validation and 10 repeated experiments were used in the experiment, and the average value of the evaluation indexes was used to evaluate the classification effect. Based on the experiment, DERFS-XGBoost model accuracy rate was 97.6%, precision was 100%, the recall rate was 97.3%, F1 was 99%, and the area under the ROC receiver operating characteristic curve AUC was 98.7%. The DERFS-XGBoost model has new characteristics which are different from existing diagnostic models, and has achieved a high classification effect with a small number of genes in comparison tests, which provides a new method and basis for the diagnosis of GC.