Protocol to synthesize sequence-controlled glycooligomers for tumor targeting in mice.

Due to the higher and more rapid consumption of carbohydrates by cancer cells compared to normal cells, carbohydrates can be effectively employed as a targeted therapeutic strategy for tumor treatment. Here, we present a protocol for synthesizing sequence-controlled glycooligomers using both solution-phase and solid-phase systems. We outline detailed procedures for evaluating the safety and tumor-targeting properties of the sequence-controlled glycooligomers in vivo. For complete details on the use and execution of this protocol, please refer to Chen et al.1.

Clinical Outcomes and Prognostic Factors in Stage III C Cervical Cancer Patients Treated with Radical Radiotherapy or Radiochemotherapy.

Objective: Since the update of the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria, there have been few reports on the prognosis of stage III C cervical cancer. Moreover, some studies have drawn controversial conclusions, necessitating further verification. This study aims to evaluate the clinical outcomes and determine the prognostic factors for stage III C cervical cancer patients treated with radical radiotherapy or radiochemotherapy. Methods: The data of 117 stage III C cervical cancer patients (98 III C1 and 19 III C2) who underwent radical radiotherapy or radiochemotherapy were retrospectively analyzed. We evaluated 3-year overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. Prognostic factors were analyzed using the Log-rank test and Cox proportional hazard regression model. The risk of para-aortic lymph node metastasis (LNM) in all patients was assessed through Chi-squared test and logistic regression analysis. Results: For stage III C1 and III C2 patients, the 3-year OS rates were 77.6% and 63.2% (P = .042), and the 3-year DFS rates were 70.4% and 47.4% (P = .003), respectively. The pretreatment location of pelvic LNM, histological type, and FIGO stage was associated with OS (P = .033, .003, .042, respectively); the number of pelvic LNM and FIGO stage were associated with DFS (P = .015, .003, respectively). The histological type was an independent prognostic indicator for OS, and the numbers of pelvic LNM and FIGO stage were independent prognostic indicators for DFS. Furthermore, a pelvic LNM largest short-axis diameter ≥ 1.5 cm and the presence of common iliac LNM were identified as high-risk factors influencing para-aortic LNM in stage III C patients (P = .046, .006, respectively). Conclusions: The results of this study validated the 2018 FIGO staging criteria for stage III C cervical cancer patients undergoing concurrent chemoradiotherapy. These findings may enhance our understanding of the updated staging criteria and contribute to better management of patients in stage III C.

Construction of BaTiO3-TiO2 hollow sphere heterojunctions for enhanced microwave dynamic therapy in cancer treatment.

Cancer is one of the primary health concerns among humans due to its high incidence rate and lack of effective treatment. Currently, medical techniques to achieve the precise elimination of local cancer lesions with negligible damage to normal tissues are still intensely desired. Herein, we synthesized BaTiO3-TiO2 hollow spheres (BTHSs) for use in microwave dynamic therapy (MWDT) for cancer. Under UV irradiation, BTHSs can mediate the production of multiple reactive oxygen species (ROS), mainly 1O2, which results in a rapid photocatalytic degradation rate (97%), 1.6-fold that of commercial P25. Importantly, the ROS production process can be triggered by microwaves to effectively execute MWDT for cancer. Under microwave irradiation, BTHSs exhibit a remarkable therapeutic effect and slight cytotoxicity. In terms of mechanism, the enhanced ROS production efficiency of BTHSs can be attributed to their unique hollow structure and the formation of a type-II heterojunction by the incorporation of BaTiO3. The hollow structure increases the availability of active sites and enhances light scattering, while the BaTiO3-TiO2 heterojunction enhances the photocatalytic activity of TiO2 through charge transfer and electron-hole separation. Overall, this study provides important insights into the design and optimization of sensitizers for MWDT applications.

Risk Factors for Intracerebral Hemorrhage: Genome-Wide Association Study and Mendelian Randomization Analyses.

BACKGROUND: The genetic and nongenetic causes of intracerebral hemorrhage (ICH) remain obscure. The present study aimed to uncover the genetic and modifiable risk factors for ICH. METHODS: We meta-analyzed genome-wide association study data from 3 European biobanks, involving 7605 ICH cases and 711 818 noncases, to identify the genomic loci linked to ICH. To uncover the potential causal associations of cardiometabolic and lifestyle factors with ICH, we performed Mendelian randomization analyses using genetic instruments identified in previous genome-wide association studies of the exposures and ICH data from the present genome-wide association study meta-analysis. We performed multivariable Mendelian randomization analyses to examine the independent associations of the identified risk factors with ICH and evaluate potential mediating pathways. RESULTS: We identified 1 ICH risk locus, located at the APOE genomic region. The lead variant in this locus was rs429358 (chr19:45411941), which was associated with an odds ratio of ICH of 1.17 (95% CI, 1.11-1.20; P=6.01×10-11) per C allele. Genetically predicted higher levels of body mass index, visceral adiposity, diastolic blood pressure, systolic blood pressure, and lifetime smoking index, as well as genetic liability to type 2 diabetes, were associated with higher odds of ICH after multiple testing corrections. Additionally, a genetic increase in waist-to-hip ratio and liability to smoking initiation were consistently associated with ICH, albeit at the nominal significance level (P<0.05). Multivariable Mendelian randomization analysis showed that the association between body mass index and ICH was attenuated on adjustment for type 2 diabetes and further that type 2 diabetes may be a mediator of the body mass index-ICH relationship. CONCLUSIONS: Our findings indicate that the APOE locus contributes to ICH genetic susceptibility in European populations. Excess adiposity, elevated blood pressure, type 2 diabetes, and smoking were identified as the chief modifiable cardiometabolic and lifestyle factors for ICH.

Bortezomib in previously treated phosphatase and tension homology-deficient patients with advanced intrahepatic cholangiocarcinoma: An open-label, prospective and single-centre phase II trial.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic alternatives. To explore phosphatase and tension homolog (PTEN) as a biomarker for proteasome inhibition in ICC, we conducted a phase II trial to assess the second-line efficacy of bortezomib in PTEN-deficient advanced ICC patients. METHODS: A total of 130 patients with advanced ICC in our centre were screened by PTEN immunohistochemical staining between 1 July 2017, and 31 December 2021, and 16 patients were ultimately enrolled and treated with single-agent bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. RESULTS: The median follow-up was 6.55 months (95% confidence interval [CI]: 0.7-19.9 months). Among the 16 enrolled patients, the ORR was 18.75% (3/16) and the disease control rate was 43.75% (7/16). The median progress-free survival was 2.95 months (95% CI: 2.1-5.1 months) and the median overall survival (mOS) was 7.2 months (95% CI: 0.7-21.6 months) in the intent-to-treat-patients. Treatment-related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining scores of 0 were more likely to benefit from bortezomib than those with staining scores > 0. CONCLUSIONS: Bortezomib yielded an encouraging objective response and a favourable OS as a second-line agent in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising therapeutic option for patients with PTEN-deficient ICC. HIGHLIGHTS: There is a limited strategy for the second-line option of intrahepatic cholangiocarcinoma (ICC). This investigator-initiated phase 2 study evaluated bortezomib in ICC patients with phosphatase and tension homology deficiency. The overall response rate was 18.75% and the overall survival was 7.2 months in the intent-to-treat cohort. These results justify further developing bortezomib in ICC patients with PTEN deficiency.

Exploring the Key Amino Acid Residues Surrounding the Active Center of Lactate Dehydrogenase A for the Development of Ideal Inhibitors.

Lactate dehydrogenase A (LDHA) primarily catalyzes the conversion between lactic acid and pyruvate, serving as a key enzyme in the aerobic glycolysis pathway of sugar in tumor cells. LDHA plays a crucial role in the occurrence, development, progression, invasion, metastasis, angiogenesis, and immune escape of tumors. Consequently, LDHA not only serves as a biomarker for tumor diagnosis and prognosis but also represents an ideal target for tumor therapy. Although LDHA inhibitors show great therapeutic potential, their development has proven to be challenging. In the development of LDHA inhibitors, the key active sites of LDHA are emphasized. Nevertheless, there is a relative lack of research on the amino acid residues around the active center of LDHA. Therefore, in this study, we investigated the amino acid residues around the active center of LDHA. Through structure comparison analysis, five key amino acid residues (Ala30, Met41, Lys131, Gln233, and Ala259) were identified. Subsequently, the effects of these five residues on the enzymatic properties of LDHA were investigated using site-directed mutagenesis. The results revealed that the catalytic activities of the five mutants varied to different degrees in both the reaction from lactic acid to pyruvate and pyruvate to lactic acid. Notably, the catalytic activities of LDHAM41G and LDHAK131I were improved, particularly in the case of LDHAK131I. The results of the molecular dynamics analysis of LDHAK131I explained the reasons for this phenomenon. Additionally, the optimum temperature of LDHAM41G and LDHAQ233M increased from 35 °C to 40 °C, whereas in the reverse reaction, the optimum temperature of LDHAM41G and LDHAK131I decreased from 70 °C to 60 °C. These findings indicate that Ala30, Met41, Lys131, Gln233, and Ala259 exert diverse effects on the catalytic activity and optimum temperature of LHDA. Therefore, these amino acid residues, in addition to the key catalytic site of the active center, play a crucial role. Considering these residues in the design and screening of LDHA inhibitors may lead to the development of more effective inhibitors.

Analysis of trajectory changes and predictive factors of sense of coherence in patients after colorectal cancer surgery.

OBJECTIVE: To investigate the trajectories and potential categories of changes in the sense of coherence (SOC) in patients after colorectal cancer surgery and to analyze predictive factors. METHODS: From January to July 2023, 175 patients with colorectal cancer treated at a tertiary Grade A oncology hospital in Jiangsu Province were selected as the study subjects. Prior to surgery, SOC-13 scale, Patient-Generated Subjective Global Assessment (PG-SGA), Brief Illness Perception Questionnaire (BIPQ), and Social Support Rating Scale (SSRS) were used to survey the patients. SOC levels were measured multiple times at 1 week, 1 month, and 3 months post-surgery. Growth Mixture Modeling (GMM) was applied to fit the trajectory changes of SOC in patients after colorectal cancer surgery. Multinomial logistic regression was used to analyze the predictive factors of SOC trajectory changes. RESULTS: The SOC scores of patients at points T1-T4 were (65.27 ± 9.20), (63.65 ± 10.41), (63.85 ± 11.84), and (61.56 ± 12.65), respectively. Multinomial logistic regression results indicated that gender, employment status, disease stage, household monthly income, intestinal stoma, nutritional status, illness perception, and social support were predictors of SOC trajectory changes (P < 0.05). CONCLUSION: There is heterogeneity in the trajectory changes of SOC in patients after colorectal cancer surgery. Healthcare professionals should implement early precision interventions based on the patterns of changes and predictive factors in each trajectory category.

Sedentary lifestyle, physical activity, and gastrointestinal diseases: evidence from mendelian randomization analysis.

BACKGROUND: The causal associations of physical activity and sedentary behavior with the risk of gastrointestinal disease are unclear. We performed a Mendelian randomization analysis to examine these associations. METHODS: Genetic instruments associated with leisure screen time (LST, an indicator of a sedentary lifestyle) and moderate-to-vigorous intensity physical activity (MVPA) at the genome-wide significance (P < 5 × 10-8) level were selected from a genome-wide association study. Summary statistics for gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analyses were conducted for genetically determined LST with adjustment for MVPA and vice versa. We also performed multivariable MR with adjustment for genetically proxied smoking, body mass index (BMI), waist-to-hip ratio, type 2 diabetes, and fasting insulin for both exposures. FINDINGS: Genetically proxied longer LST was associated with an increased risk of gastrointestinal reflux, gastric ulcer, duodenal ulcer, chronic gastritis, irritable bowel syndrome, diverticular disease, Crohn's disease, ulcerative colitis, non-alcoholic fatty liver disease, alcoholic liver disease, cholangitis, cholecystitis, cholelithiasis, acute pancreatitis, chronic pancreatitis, and acute appendicitis. Most associations remained after adjustment for genetic liability to MVPA. Genetic liability to MVPA was associated with decreased risk of gastroesophageal reflux, gastric ulcer, chronic gastritis, irritable bowel syndrome, cholecystitis, cholelithiasis, acute and chronic pancreatitis. The associations attenuated albeit directionally remained after adjusting for genetically predicted LST. Multivariable MR analysis found that BMI and type 2 diabetes mediated the associations of LST and MVPA with several gastrointestinal diseases. INTERPRETATION: The study suggests that a sedentary lifestyle may play a causal role in the development of many gastrointestinal diseases. FUNDING: Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001), Natural Science Foundation of Hunan Province (2021JJ30999), Swedish Heart-Lung Foundation (Hjärt-Lungfonden, 20210351), Swedish Research Council (Vetenskapsrådet, 2019-00977), Swedish Cancer Society (Cancerfonden), the Wellcome Trust (225790/7/22/Z), United Kingdom Research and Innovation Medical Research Council (MC_UU_00002/7) and National Institute for Health Research Cambridge Biomedical Research Centre (NHIR203312).

A Reconfigurable DNA Framework Nanotube-Assisted Antiangiogenic Therapy.

A major limitation of tumor antiangiogenic therapy is the pronounced off-target effect, which can lead to unavoidable injury in multiple organs. Ensuring sufficient delivery and controlled release of these antiangiogenic agents at tumor sites is crucial for realizing their clinical application. Here, we develop a smart DNA-based nanodrug, termed Endo-rDFN, by precisely assembling the antiangiogenic agent, endostar (Endo), into a reconfigurable DNA framework nanotube (rDFN) that could recognize tumor-overexpressed nucleolin to achieve the targeted delivery and controllable release of Endo. Endo-rDFN can not only effectively enhance the tumor-targeting capability of Endo and maintain its efficient accumulation in tumor tissues but also achieve on-demand release of Endo at tumor sites via the specific DNA aptamer for tumor-overexpressed nucleolin, named AS1411. We also found that Endo-rDFN exhibited significant inhibition of angiogenesis and tumor growth, while also providing effective protection against multiorgan injury (heart, liver, spleen, kidney, lung, etc.) to some extent, without compromising the function of these organs. Our study demonstrates that rDFN represents a promising vector for reducing antiangiogenic therapy-induced multiorgan injury, highlighting its potential for promoting the clinical application of antiangiogenic agents.

Nucleic acid-sensing-related gene signature in predicting prognosis and treatment efficiency of small cell lung cancer patients.

Introduction: Nucleic acid-sensing (NAS) pathways could induce innate and adaptive immune responses. However, rare evidence exhibited how the core genes of the NAS pathways affected the immune response and prognosis of small cell lung cancer (SCLC) patients. Methods: We conducted a comprehensive bioinformatic analysis based on the RNA profiles of 114 SCLC patients, including 79 from cBioPortal, 21 from GSE30219, and 14 from our sequencing data. The multiplex immunohistochemistry (mIHC) was used to characterize the role of NAS related genes in the tumor microenvironment (TME) of SCLC. Results: A prognostic model (7NAS risk model) was constructed based on 7 NAS-related genes which was demonstrated as an independent prognostic index. The low-risk group was identified to have a better prognosis and an immune-activated microenvironment in both the public datasets and our dataset. Intriguingly, mIHC data showed that CD45+ immune cells, CD8+ T lymphocytes, and CD68+ macrophages were prevalently enriched in low-risk SCLC patients and positively correlated with IRF1 expression. Additionally, Patients in the low-risk group might have superior responses to chemotherapy and immunotherapy. Conclusion: Conclusively, this study created a new risk model based on genes associated with NAS pathways which could predict the prognosis and response of treatment in patients with SCLC.

Droplet Microfluidics-Assisted Fabrication of Shape Controllable Iron-Alginate Microgels with Fluorescent Property.

Droplet-based microfluidics-assisted fabrication of alginate microgels has extensive applications in biomaterials, biomedicines, and related fields. This approach is typically achieved by crosslinking droplets of an aqueous solution of sodium alginate with various divalent and trivalent ions, such as Ca2+, Ba2+, Sr2+, etc. Despite the exceptional features exhibited by bulk alginate hydrogels when using iron ions as the crosslinking reagent, including stimulus responsiveness and complex chemistry, no attention has been given to studying the fabrication of Fe-alginate microgels through droplet microfluidics. In this work, a facile method is presented for fabricating Fe-alginate microgels using single emulsion droplets as templates and an off-chip crosslinking technique to solidify the droplets. The morphologies of the resulting microgels can be systematically adjusted by manipulating different parameters such as viscosities and ionic strength of the collecting solutions. It should be noted that these resulting microgels undergo a color change from light brown to dark brown due to presumed self-oxidation of iron ions within their skeleton structure. Furthermore, these Fe-alginate microgels are functionalized by decorating them with a positively charged linear polymer via electrostatic interactions to impart them with stable fluorescent property. These functionalized Fe-alginate microgels may find potential applications in drug delivery carriers and biomimetic structures.

Characterization of a novel T cell-engaging bispecific antibody for elimination of L1CAM-positive tumors.

Neural cell adhesion molecule L1 (L1CAM) is a cell-surface glycoprotein involved in cancer occurrence and migration. Up to today, L1CAM-targeted therapy appeared limited efficacy in clinical trials although quite a few attempts by monoclonal antibody (mAb) or chimeric antigen receptor T-cell therapy (CAR-T) have been reported. Therefore, the development of new effective therapies targeting L1CAM is highly desirable. It has been demonstrated that T cell-engaging bispecific antibody (TCE) plays an effective role in cancer immunotherapy by redirecting the cytotoxic activity of CD3+ T cells to tumor cells, resulting in tumor cell death. In this study, we designed and characterized a novel bispecific antibody (CE7-TCE) based on the IgG-(L)-ScFv format, which targets L1CAM and CD3 simultaneously. In vitro, CE7-TCE induced specific killing of L1CAM-positive tumor cells through T cells. In vivo, CE7-TCE inhibited tumor growth in human peripheral blood mononuclear cell/tumor cell co-grafting models. To overcome the adaptive immune resistance (AIR) that impairs the efficacy of TCEs, we conducted a combination therapy of CE7-TCE with Pembrolizumab (anti-PD1 mAb), which enhanced the anti-tumor activity of CE7-TCE. Our results confirmed the feasibility of using L1CAM as a TCE target for the treatment of solid tumors and revealed the therapeutic potential of CE7-TCE combined with immune checkpoint inhibitors.

Association of residential exposure to hazardous air pollutants with risk of non-Hodgkin lymphoma and multiple myeloma.

BACKGROUND: Certain hazardous air pollutants (HAPs) are known or suspected to pose immunological or cancer risk to humans, but evidence is limited from the general population. METHODS: We assessed associations between residential exposure to HAPs at the Census tract level and incident non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) in the Nurses' Health Study (NHS, 1986-2012) and NHSII (1989-2019). We used covariate-adjusted proportional hazards models to estimate hazard ratios (HRs) of NHL, major NHL subtypes, and MM per interquartile range increase in exposure to a given HAP and pooled the cohort-specific estimates using fixed-effects meta-analyses. RESULTS: There were 810 NHL and 158 MM cases in NHS (1,700,707 person-years), and 379 NHL and 59 MM cases in NHSII (2,820,772 person-years). Most HRs approximated unity. Meta-analyses did not show consistent evidence of associations between any HAP exposure and risk of NHL or MM. CONCLUSIONS: Exposure to HAPs was not consistently associated with risks of NHL or MM in these nationwide prospective cohorts of women. IMPACT: This is the first nationwide study assessing associations between residential HAP exposures and risk of lymphoid malignances in prospective cohorts and focuses on women, who have frequently been underrepresented in (primarily occupational) studies of exposure to HAPs.

The Effect of Low-Intensity Pulsed Ultrasound on Bone Regeneration and the Expression of Osterix and Cyclooxygenase-2 during Critical-Size Bone Defect Repair.

Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound that utilizes low-intensity pulsed waves. Its effect on bones that heal by intramembranous ossification has not been sufficiently investigated. In this study, we examined LIPUS and the autologous bone, to determine their effect on the healing of the critical-size bone defect (CSBD) of the rat calvaria. The bone samples underwent histological, histomorphometric and immunohistochemical analyses. Both LIPUS and autologous bone promoted osteogenesis, leading to almost complete closure of the bone defect. On day 30, the bone volume was the highest in the autologous bone group (20.35%), followed by the LIPUS group (19.12%), and the lowest value was in the control group (5.11%). The autologous bone group exhibited the highest intensities of COX-2 (167.7 ± 1.1) and Osx (177.1 ± 0.9) expression on day 30. In the LIPUS group, the highest intensity of COX-2 expression was found on day 7 (169.7 ±1.6) and day 15 (92.7 ± 2.2), while the highest Osx expression was on day 7 (131.9 ± 0.9). In conclusion, this study suggests that LIPUS could represent a viable alternative to autologous bone grafts in repairing bone defects that are ossified by intramembranous ossification.

Association Between Preoperative Sleep Disturbance and Postoperative Delirium in Elderly: A Retrospective Cohort Study.

Purpose: Postoperative sleep disturbance, characterized by diminished postoperative sleep quality, is a risk factor for postoperative delirium (POD); however, the association between pre-existing sleep disturbance and POD remains unclear. This study aimed to evaluate the association between preoperative sleep disturbance and POD in elderly patients after non-cardiac surgery. Patients and methods: This retrospective cohort study was conducted at a single center and enrolled 489 elderly patients who underwent surgery between May 1, 2020, and March 31, 2021. Patients were divided into the sleep disorder (SD) and non-sleep disorder (NSD) groups according to the occurrence of one or more symptoms of insomnia within one month or sleep- Numerical Rating Scale (NRS)≥6 before surgery. The primary outcome was the incidence of POD. Propensity score matching analysis was performed between the two groups. Multiple logistic regression analysis was performed to identify the risk factors for POD. Results: In both the unmatched cohort (16.0% vs 6.7%, P=0.003) and the matched cohort (17.0% vs 6.2%, P=0.023), the incidence of POD was higher in the SD group than in the NSD group. In addition, the postoperative sleep quality and the VAS score at postoperative 24 h were significantly lower in the SD group than in the NSD group. Multivariate logistic regression analysis indicated that age (Odds Ratio, 1.13 [95% CI: 1.04-1.23], P=0.003) and preoperative sleep disturbance (Odds Ratio, 3.03 [95% CI: 1.09-9.52], P=0.034) were independent risk factors for the development of POD. Conclusion: The incidence of POD was higher in patients with pre-existing sleep disturbance than those without it. Whether improving sleep quality for preoperative sleep disturbance may help prevent POD remains to be determined.

Low Expression MCEMP1 Promoting Lung Adenocarcinoma Progression by and its Clinical Value.

BACKGROUND: Lung cancer is a highly prevalent tumor with a lack of biological markers that reflect its progression. Mast cell surface membrane protein 1 (MCEMP1, also known as C19ORF59) has not been reported in lung adenocarcinoma (LUAD). OBJECTIVE: We aimed to investigate the role of MCEMP1 in LUAD. METHODS: MCEMP1 expression in LUAD was analyzed using The Cancer Genome Atlas (TCGA) data, and conducted univariate and multivariate Cox regression analyses to evaluate the prognostic significance of MCEMP1 expression in TCGA. Tumor Immune Estimation Resource (TIMER) was used for examining the correlation between MCEMP1 expression and immune cell infiltration in LUAD. Furthermore, proliferation, migration, invasion, and colony-forming ability were investigated using LUAD cell lines. RESULTS: MCEMP1 had low expression in LUAD patient tissues and was correlated with lymph node metastasis, differentiation level, and tumor status. The Area under Curve (AUC) value of MCEMP1 for the Receiver Operating Characteristic (ROC) curve analysis was 0.984. The immune infiltration analysis revealed a correlation between MCEMP1 expression and the extent of macrophages and neutrophil infiltration in LUAD. Additionally, MCEMP1 has low expression in clinical samples, MCEMP1 overexpressed in LUAD cells substantially reduced cell growth, migration, and invasion of malignant cells. CONCLUSION: Low expression MCEMP1 promotes LUAD progression, which provides new insights and a potential biological target for future LUAD therapies.

Epigallocatechin-3-gallate derived polymer coated Prussian blue for synergistic ROS elimination and antibacterial therapy.

Reactive oxygen species (ROS) play a vital role in wound healing process by fighting against invaded bacteria. However, excess ROS at the wound sites lead to oxidative stress that can trigger deleterious effects, causing cell death, tissue damage and chronic inflammation. Therefore, we fabricated a core-shell structured nanomedicine with antibacterial and antioxidant properties via a facile and green strategy. Specifically, Prussian blue (PB) nanozyme was fabricated and followed by coating a layer of epigallocatechin-3-gallate (EGCG)-derived polymer via polyphenolic condensation reaction and self-assembly process, resulting in PB@EGCG. The introduction of PB core endowed EGCG-based polyphenol nanoparticles with excellent NIR-triggered photothermal properties. Besides, owing to multiple enzyme-mimic activity of PB and potent antioxidant capacity of EGCG-derived polymer, PB@EGCG exhibited a remarkable ROS-scavenging ability, mitigated intracellular ROS level and protected cells from oxidative damage. Under NIR irradiation (808 nm, 1.5 W/cm2), PB@EGCG (50 µg/mL) exerted synergistic EGCG-derived polymer-photothermal antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). In vivo therapeutic effect was evaluated using a S. aureus-infected rat model indicated PB@EGCG with a prominent bactericidal ability could modulate the inflammatory microenvironment and accelerate wound healing. Overall, this dual-functional nanomedicine provides a promising strategy for efficient antibacterial therapy.

Single cell analysis unveils B cell-dominated immune subtypes in HNSCC for enhanced prognostic and therapeutic stratification.

Head and neck squamous cell carcinoma (HNSCC) is characterized by high recurrence or distant metastases rate and the prognosis is challenging. There is mounting evidence that tumor-infiltrating B cells (TIL-Bs) have a crucial, synergistic role in tumor control. However, little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade. Using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, the study identified distinct gene expression patterns in TIL-Bs. HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering. This classification was further validated with TCGA HNSCC data, correlating with patient prognosis, immune cell infiltration, and response to immunotherapy. We found that the B cells activation group exhibited a better prognosis, higher immune cell infiltration, and distinct immune checkpoint levels, including elevated PD-L1. A prognostic model was also developed and validated, highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients. Overall, this study provides a foundational approach for B cells-based tumor classification in HNSCC, offering insights into targeted treatment and immunotherapy strategies.

M2-Type Macrophages and Cancer-Associated Fibroblasts Combine to Promote Colorectal Cancer Liver Metastases.

Purpose: This research explored the association between CD163-labeled M2-type macrophages and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) of 38 colorectal cancer (CRC) liver metastases. In addition, we investigated the correlation differences between M2-type macrophages and CAFs in the tumor microenvironments of 38 primary colorectal cancer patients with confirmed liver metastases and 946 colorectal cancer patients, as well as possible mechanisms of action between the two cells. Methods: The Immunohistochemistry (IHC) method was applied to detect the expression levels of M2-type macrophages and CAFs in the tissues of 984 cases of CRC and to analyze the correlation between M2-type macrophages and CAFs in colorectal cancer tissues. The IHC method was also applied to detect the expression levels of M2-type macrophages and CAFs in the liver metastases of 38 cases of CRC in the experimental group and to analyze the correlation between the two cells in liver metastases. Results: 1. M2-type macrophages and CAFs expression were significantly higher in 38 primary colorectal cancer patients compared to 946 controls, and the expression of M2-type macrophages was significantly positively correlated with CAFs. 2. In 984 CRC cases, M2-type macrophages and CAFs expression levels were significantly higher in the cancer tissues than in the paired paracancerous tissues. 3. The expression levels of M2-type macrophages and CAFs in primary colorectal cancer were significantly higher in the experimental group than in colorectal cancer tissues without distant metastasis. Conclusion: M2-type macrophages and CAFs are involved in the development of the colorectal cancer tumor microenvironment, and their interaction influences the initiation and progression of liver metastasis in colorectal cancer. It may provide new clinical ideas for early diagnosis of CRC liver metastases and searching for immune targets.