Comprehensive analysis identifies ubiquitin ligase FBXO42 as a tumor-promoting factor in neuroblastoma.

Neuroblastoma, the deadliest solid tumor in children, exhibits alarming mortality rates, particularly among high-risk cases. To enhance survival rates, a more precise risk stratification for patients is imperative. Utilizing proteomic data from 34 cases with or without N-Myc amplification, we identified 28 differentially expressed ubiquitination-related proteins (URGs). From these, a prognostic signature comprising 6 URGs was constructed. A nomogram incorporating clinical-pathological parameters yielded impressive AUC values of 0.88, 0.93, and 0.95 at 1, 3, and 5 years, respectively. Functional experiments targeting the E3 ubiquitin ligase FBXO42, a component of the prognostic signature, revealed its TP53-dependent promotion of neuroblastoma cell proliferation. In conclusion, our ubiquitination-related prognostic model robustly predicts patient outcomes, guiding clinical decisions. Additionally, the newfound pro-proliferative role of FBXO42 offers a novel foundation for understanding the molecular mechanisms of neuroblastoma.

Impact of Extracellular Matrix-Related Genes on the Tumor Microenvironment and Prognostic Indicators in Esophageal Cancer: A Comprehensive Analytical Study.

Esophageal cancer is a major global health challenge with a poor prognosis. Recent studies underscore the extracellular matrix (ECM) role in cancer progression, but the full impact of ECM-related genes on patient outcomes remains unclear. Our study utilized next-generation sequencing and clinical data from esophageal cancer patients provided by The Cancer Genome Atlas, employing the R package in RStudio for computational analysis. This analysis identified significant associations between patient survival and various ECM-related genes, including IBSP, LINGO4, COL26A1, MMP12, KLK4, RTBDN, TENM1, GDF15, and RUNX1. Consequently, we developed a prognostic model to predict patient outcomes, which demonstrated clear survival differences between high-risk and low-risk patient groups. Our comprehensive review encompassed clinical correlations, biological pathways, and variations in immune response among these risk categories. We also constructed a nomogram integrating clinical information with risk assessment. Focusing on the TENM1 gene, we found it significantly impacts immune response, showing a positive correlation with T helper cells, NK cells, and CD8+ T cells, but a negative correlation with neutrophils and Th17 cells. Gene Set Enrichment Analysis revealed enhanced pathways related to pancreatic beta cells, spermatogenesis, apical junctions, and muscle formation in patients with high TENM1 expression. This research provides new insights into the role of ECM genes in esophageal cancer and informs future research directions.

Enhancing prognostic prediction in hepatocellular carcinoma post-TACE: a machine learning approach integrating radiomics and clinical features.

Objective: This study aimed to investigate the use of radiomics features and clinical information by four machine learning algorithms for predicting the prognosis of patients with hepatocellular carcinoma (HCC) who have been treated with transarterial chemoembolization (TACE). Methods: A total of 105 patients with HCC treated with TACE from 2002 to 2012 were enrolled retrospectively and randomly divided into two cohorts for training (n = 74) and validation (n = 31) according to a ratio of 7:3. The Spearman rank, random forest, and univariate Cox regression were used to select the optimal radiomics features. Univariate Cox regression was used to select clinical features. Four machine learning algorithms were used to develop the models: random survival forest, eXtreme gradient boosting (XGBoost), gradient boosting, and the Cox proportional hazard regression model. The area under the curve (AUC) and C-index were devoted to assessing the performance of the models in predicting HCC prognosis. Results: A total of 1,834 radiomics features were extracted from the computed tomography images of each patient. The clinical risk factors for HCC prognosis were age at diagnosis, TNM stage, and metastasis, which were analyzed using univariate Cox regression. In various models, the efficacy of the combined models generally surpassed that of the radiomics and clinical models. Among four machine learning algorithms, XGBoost exhibited the best performance in combined models, achieving an AUC of 0.979 in the training set and 0.750 in the testing set, demonstrating its strong prognostic prediction capability. Conclusion: The superior performance of the XGBoost-based combined model underscores its potential as a powerful tool for enhancing the precision of prognostic assessments for patients with HCC.

Combining CD38 antibody with CD47 blockade is a promising strategy for treating hematologic malignancies expressing CD38.

Background: CD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs). Methods: Five suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 "mAb-trap" platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems. Results: Using hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a "mAb-trap" platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605-26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605-12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605-12C10 efficiently eradicated all established tumors in all mice. Conclusion: A panel of BsAbs targeting CD38 and CD47 developed based on the "mAb-tarp" platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.

Relating caregiver experiences to personalized "push" content in mobile applications among caregivers of pediatric patients with oncology conditions.

OBJECTIVE: With the evolution of data algorithms and personalized push systems in mobile applications, patients who have searched for disease-related information may repeatedly receive similar content on app homepages or through notifications. This study aims to assess the influence of health-related content delivered through mobile applications on the anxiety and depression levels of caregivers of pediatric oncology patients. METHODS: A survey consisting of 16 questions was conducted among 91 caregivers of pediatric oncology patients at the Children's Hospital affiliated with Chongqing Medical University. The questionnaire was designed by oncologists and the Hospital Anxiety and Depression Scale was used to assess the caregivers' psychological states. RESULTS: The study found that 31.5% of caregivers exhibited borderline anxiety symptoms, while 20.2% displayed borderline depression symptoms. Caregivers who noticed changes in homepage recommendations reported higher levels of anxiety (p = .004) and depression (p = .034). Additionally, 50.6% occasionally felt anxious or uneasy due to personalized notifications and 19.1% frequently felt this way. Moreover, 53.9% of the caregivers reported a negative impact on their emotions or daily life. SIGNIFICANCE: Personalized push notifications related to disease information in mobile applications can impose a significant psychological burden on patients and their caregivers. Mobile application developers and healthcare providers must strengthen their support in the digital health domain to enhance the emotional well-being of cancer patients and their caregivers.

Baicalein upregulates macrophage TREM2 expression via TrKB-CREB1 pathway to attenuate acute inflammatory injury in acute-on-chronic liver failure.

OBJECTIVE: Acute-on-chronic liver failure (ACLF) is a syndrome characterized by a high short-term mortality rate, and effective interventions are still lacking. This study aims to investigate whether the small molecule baicalein can mitigate ACLF and elucidate the molecular mechanisms. METHODS: The ACLF mouse model was induced through chronic liver injury using carbon tetrachloride, followed by acute inflammation induction with lipopolysaccharide (LPS). Baicalein was administered through intraperitoneal injection to explore its therapeutic effects. In vitro experiments utilized the iBMDM macrophage cell line to investigate the underlying mechanisms. Peripheral blood was collected from clinical ACLF patients for validation. RESULTS: In the LPS-induced ACLF mouse model, baicalein demonstrated a significant reduction in acute inflammation and liver damage, as evidenced by histopathological evaluation, liver function analysis, and inflammatory marker measurements. Transcriptomic analysis, coupled with molecular biology experiments, uncovered that baicalein exerts its effects in ACLF by activating the TrKB-CREB1 signaling axis to upregulate the surface expression of the TREM2 receptor on macrophages. This promotes M2 macrophage polarization and activates efferocytosis, thereby inhibiting inflammation and alleviating liver damage. Furthermore, we observed a substantial negative correlation between postoperative peripheral blood plasma soluble TREM2 (sTREM2) levels and inflammation, as well as adverse outcomes in clinical ACLF patients. CONCLUSION: Baicalein plays a protective role in ACLF by enhancing the surface expression of the TREM2 receptor on macrophages, leading to the suppression of inflammation, mitigation of liver damage, and a reduction in mortality. Additionally, plasma sTREM2 emerges as a critical indicator for predicting adverse outcomes in ACLF patients.

No causal relationship between glucose and inflammatory bowel disease: a bidirectional two-sample mendelian randomization study.

BACKGROUND: Association between glucose and inflammatory bowel disease (IBD) was found in previous observational studies and in cohort studies. However, it is not clear whether these associations reflect causality. Thus, this study investigated whether there is such a causal relation between elevated glucose and IBD, Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We performed a two-sample Mendelian Randomization (MR) with the independent genetic instruments identified from the largest available genome-wide association study (GWAS) for IBD (5,673 cases; 213,119 controls) and its main subtypes, CD and UC. Summarized data for glucose which included 200,622 cases and glycemic traits including HbA1c and type 2 diabetes(T2DM) were obtained from different GWAS studies. Primary and secondary analyses were conducted by preferentially using the radial inverse-variance weighted (IVW) approach. A number of other meta-analysis approach and sensitivity analyses were carried out to assess the robustness of the results. RESULTS: We did not find a causal effect of genetically predicted glucose on IBD as a whole (OR 0.858; 95% CI 0.649-1.135; P = 0.286). In subtype analyses glucose was also suggestively not associated with Crohn's disease (OR 0.22; 95% CI 0.04-1.00; P = 0.05) and ulcerative colitis (OR 0.940; 95% CI 0.628-1.407; P = 0.762). In the other direction, IBD and its subtypes were not related to glucose and glycemic traits. CONCLUSIONS: This MR study is not providing any evidence for a causal relationship between genetically predicted elevated glucose and IBD as well as it's subtypes UC and CD. Regarding the other direction, no causal associations could be found. Future studies with robust genetic instruments are needed to confirm this conclusion.

Finotonlimab with chemotherapy in recurrent or metastatic head and neck cancer: a randomized phase 3 trial.

Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402 .

Insights into the panorama of multiple DNA viruses in municipal wastewater and recycled sludge in Tianjin, China.

Environmental viruses in wastewater and sludge are widely recognized for their roles in waterborne diseases. However, previous studies mainly focused on RNA viruses, and little is known about the diversity of DNA viral communities and their driving factors in municipal wastewater treatment environments. Herein, we conducted a pilot study to explore DNA virus profiles in municipal wastewater and recycled sludge by metagenomics method, and track their temporal changes in northern China. Results showed that 467 viral species were co-shared among all the samples. We identified six families of human viruses with a prevalence of 0.1%, which were rare but relatively stable in wastewater and sludge for six months. Adenoviridae, Parvoviridae, and Herpersviridae were the most dominant human viral families in municipal wastewater and recycled sludge. A time series of samples revealed that the dynamic changes of human DNA viruses were stable based on qPCR results, particularly for high-risk fecal-oral transmission viruses of adenovirus, bocavirus, polyomavirus, human gamma herpesvirus, human papillomavirus, and hepatitis B virus. Concentrations of Adenovirus (5.39-7.48 log10 copies/L) and bocavirus (4.36-7.48 log10 copies/L) were observed to be the highest in these samples compared to other viruses. Our findings demonstrated the DNA viruses' high prevalence and persistence in municipal wastewater treatment environments, highlighting the value of enhancing public health responses based on wastewater-based epidemiology.

CD276-dependent efferocytosis by tumor-associated macrophages promotes immune evasion in bladder cancer.

Interplay between innate and adaptive immune cells is important for the antitumor immune response. However, the tumor microenvironment may turn immune suppressive, and tumor associated macrophages are playing a role in this transition. Here, we show that CD276, expressed on tumor-associated macrophages (TAM), play a role in diminishing the immune response against tumors. Using a model of tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in BLCA male mice we show that genetic ablation of CD276 in TAMs blocks efferocytosis and enhances the expression of the major histocompatibility complex class II (MHCII) of TAMs. This in turn increases CD4 + and cytotoxic CD8 + T cell infiltration of the tumor. Combined single cell RNA sequencing and functional experiments reveal that CD276 activates the lysosomal signaling pathway and the transcription factor JUN to regulate the expression of AXL and MerTK, resulting in enhanced efferocytosis in TAMs. Proving the principle, we show that simultaneous blockade of CD276 and PD-1 restrain tumor growth better than any of the components as a single intervention. Taken together, our study supports a role for CD276 in efferocytosis by TAMs, which is potentially targetable for combination immune 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.

Serum high mobility group box 1 as a potential biomarker for the progression of kidney disease in patients with type 2 diabetes.

Background: As a damage-associated molecular pattern protein, high mobility group box 1 (HMGB1) is associated with kidney and systemic inflammation. The predictive and therapeutic value of HMGB1 as a biomarker has been confirmed in various diseases. However, its value in diabetic kidney disease (DKD) remains unclear. Therefore, this study aimed to investigate the correlation between serum and urine HMGB1 levels and DKD progression. Methods: We recruited 196 patients with type 2 diabetes mellitus (T2DM), including 109 with DKD and 87 T2DM patients without DKD. Additionally, 60 healthy participants without T2DM were also recruited as controls. Serum and urine samples were collected for HMGB1 analysis. Simultaneously, tumor necrosis factor receptor superfamily member 1A (TNFR-1) in serum and kidney injury molecule (KIM-1) in urine samples were evaluated for comparison. Results: Serum and urine HMGB1 levels were significantly higher in patients with DKD than in patients with T2DM and healthy controls. Additionally, serum HMGB1 levels significantly and positively correlated with serum TNFR-1 (R 2 = 0.567, p<0.001) and urine KIM-1 levels (R 2 = 0.440, p<0.001), and urine HMGB1 has a similar correlation. In the population with T2DM, the risk of DKD progression increased with an increase in serum HMGB1 levels. Multivariate logistic regression analysis showed that elevated serum HMGB1 level was an independent risk factor for renal function progression in patients with DKD, and regression analysis did not change in the model corrected for multiple variables. The restricted cubic spline depicted a nonlinear relationship between serum HMGB1 and renal function progression in patients with DKD (p-nonlinear=0.007, p<0.001), and this positive effect remained consistent across subgroups. Conclusion: Serum HMGB1 was significantly correlated with DKD and disease severity. When the HMGB1 level was ≥27 ng/ml, the risk of renal progression increased sharply, indicating that serum HMGB1 can be used as a potential biomarker for the diagnosis of DKD progression.

Upfront surgery versus definitive radiotherapy: competing risk analyses for cancer-specific and noncancer mortality in oropharyngeal cancer.

PURPOSE: The optimal treatment strategy for oropharyngeal cancer (OPC) is undetermined. We aim to compare the survival outcomes of OPC patients treated with upfront surgery versus definitive radiotherapy (RT). METHODS: A total of 8057 cases were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine-Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. RESULTS: In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 1.31; 95% confidence interval [CI], 1.05-1.64; P = 0.017) and noncancer mortality (adjusted SHR, 1.59; 95% CI 1.13-2.25; P = 0.008). In the HPV-positive cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted SHR, 1.51; 95% CI 1.23-1.85; P < 0.001) and noncancer mortality (adjusted SHR, 1.53; 95% CI 1.11-2.12; P = 0.009). CONCLUSION: Upfront surgery is a superior treatment modality compared with definitive RT in terms of lowering cancer-specific and noncancer mortality in OPC patients, regardless of HPV status. Further prospective clinical trials are needed to confirm our findings.

Comprehensive evaluation of chemical constituents and antioxidant activity between crude and processed Polygalae radix based on UPLC-Q-TOF-MS/MS combined with multivariate statistical analysis.

Polygalae radix (PR) is a famous herbal medicine obtained by drying the root of Polygala tenuifolia Willd., one of the traditional Chinese medicines (TCM) that can be used for healthy food. There are three main processed methods of PR, including removing the xylem of roots (Polygalae Cortex, PC), frying PC with licorice (LP), and frying PC with honey (HP). While processing is believed to enhance efficacy and reduce toxicity, it is crucial to understand the differences in chemical composition and biological activities between crude and processed PR. This study used ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) combined with multivariate statistical analysis to analyze the chemical profiles and differences between the crude and processed products. Total polyphenol contents (TPC), total flavonoid contents (TFC), total saponin contents (TSC) and antioxidant activity of the processed and crude PR were also investigated. A total of 131 chemical compounds, including 42 saponins, 44 oligosaccharide esters, 25 xanthones, 2 organic acids, 3 Carbohydrates, and 15 components detected in auxiliary materials, were detected in all samples. Notably, PC exhibited significant changes among the three processed products, with the content of 62 compounds being higher. Processing of licorice (LP) and honey (HP) decreased the content of several compounds due to temperature and moisture influences. Comprehensive comparison of the antioxidant capacity of crude and processed PR showed that the antioxidant capacity of PC was higher than that of PR, HP, and LP. Our results can provide a scientific basis for further developing and applying P. tenuifolia resources.

Cutaneous Mycobacterium Abscessus Infection Following Plastic Surgery: Three Case Reports.

Aim: Mycobacterium abscessus is ubiquitous in the environment and seldom causes infections in immunocompetent individuals. However, skin and soft tissue infections caused by M. abscessus have been reported in recent years. Additionally, the cutaneous infections or outbreaks post cosmetic surgery caused by M. abscessus have been increasing due to the popularity of plastic surgery. The main modes of transmission are through contaminated saline, disinfectants, or surgery equipment, as well as close contact between patients. This article describes three patients who were admitted to our hospital between November 2019 and October 2020. They presented with long-term non-healing wounds caused by M. abscessus infection after undergoing plastic surgery. Symptoms presented by the three patients included swelling, ulceration, secretion, and pain. After identification of M. abscessus with Ziehl-Neelsen staining and MALDI-TOF MS system, the patients were treated with surgical debridement and clarithromycin. Conclusion: It is important to note that a long-term wound that does not heal, especially after plastic surgery, should raise suspicion for M. abscessus infection. The infection mechanism in these three patients may have been due to exposure to surgical equipment that was not properly sterilized or due to poor sterile technique by the plastic surgeon. To prevent such infections, it is important to ensure proper sterilization of surgical equipment and saline.

Unraveling the link: environmental tobacco smoke exposure and its impact on infertility among American women (18-50 years).

Purpose: The detrimental effects of environmental tobacco smoke (ETS) on women's reproductive health have been widely recognized. However, the detailed association between exposure to environmental tobacco smoke and the incidence of infertility remains under-explored. This investigation focuses on exploring this potential connection. Methods: For this analysis, we extracted data from the US National Health and Nutrition Examination Survey (NHANES) database, covering the years 2013 to 2018, focusing on individuals with recorded serum cotinine levels and infertility information. ETS exposure and fertility status were analyzed as independent and dependent variables, respectively. We applied weighted multivariate logistic regression method to evaluate the impact of ETS on infertility, including subgroup analyses for more detailed insights. Results: The study encompassed 3,343 participants. Logistic regression analysis revealed a notable positive correlation between ETS exposure and infertility, with an odds ratio (OR) of 1.64 (95% Confidence Interval [CI]: 1.14-2.36). We observed a non-linear relationship between ETS exposure and infertility risk. Notably, infertility risk increased by 64% in serum cotinine levels above 0.136 compared to that in serum cotinine levels below 0.011. Further, subgroup analysis and interaction tests showed consistent results across different segments, underscoring the robustness of the ETS-infertility link. Conclusion: Our findings suggest that environmental tobacco smoke exposure may be a contributing factor to infertility. These results reinforce the recommendation for women in their reproductive years to avoid ETS exposure, especially when planning for pregnancy.

Water-soluble intracellular extract of Desmodesmus sp. YT enhanced the antioxidant capacity of human skin fibroblast to protect the skin from UV damage.

BACKGROUND: The oxidative stress induced by ultraviolet (UV) radiation is a pivotal factor in skin aging and can even contribute to the development of skin cancer. AIM: This study explored the antioxidant effect and mechanism of water-soluble intracellular extract (WIE) of Desmodesmus sp.YT (YT), aiming to develop a natural antioxidant suitable for incorporation into cosmetics. METHODS: The study evaluated the scavenging capacity of YT-WIE against free radicals and assessed its impact on human skin fibroblasts (HSF) cell viability and UV resistance using Cell Counting Kit-8 (CCK-8). Transcriptome sequencing was employed to elucidate the mechanism of action, while RT-qPCR and western blot were used to validate the expression of key genes. RESULTS: YT-WIE displayed robust antioxidant activity, demonstrating potent scavenging abilities against 2,2-diphenyl-1-picrylhydrazyl (DPPH; IC50 = 0.55 mg mL-1), 2,2'-Azino-bis (3 ethylbenzothiazoline-6-sulfonic acid; ABTS; IC50 = 3.11 mg mL-1), Hydroxyl (·OH; IC50 = 2.21 mg mL-1), and Superoxide anion (O2 •-; IC50 = 0.98 mg mL-1). Furthermore, compared to the control group, the YT-WIE group exhibited an 89.30% enhancement in HSF viability and a 44.63% increase in survival rate post-UV irradiation. Significant upregulation of antioxidant genes (GCLC, GCLM, TXNRD1, HMOX1, NQO1) was observed with YT-WIE treatment at 400 µg mL-1, with fold increases ranging from 1.13 to 5.85 times. CONCLUSION: YT-WIE demonstrated considerable potential as an antioxidant, shielding human cells from undue oxidative stress triggered by external stimuli such as UV radiation. This suggests its promising application in cosmetics antioxidants.

The use of multicomponent reactions in the development of bis-boronic acids for the detection of ß-sialic acid.

Sialic acid (SA) is a naturally occurring monosaccharide found in glycoproteins and glycolipids. Changes in the expression of SA are associated with several diseases; thus, the detection of SA is of great significance for biological research, cancer diagnosis, and treatment. Boronic acid analogs have emerged as a promising tool for detecting sugars such as SA due to its reversible covalent bonding ability. In this study, 11 bis-boronic acid compounds and 2 mono-boronic acid compounds were synthesized via a highly efficient Ugi-4CR strategy. The synthesized compounds were subjected to affinity fluorescence binding experiments to evaluate their binding capability to SA. Compound A1 was shown to have a promising binding constant of 2602 ± 100 M-1 at pH = 6.0. Density Functional Theory (DFT) calculations examining the binding modes between A1 and SA indicated that the position of the boronic acid functional group was strongly correlated with its interaction with SA's α-hydroxy acid unit. The DFT calculations were consistent with the observations from the fluorescence experiments, demonstrating that the number and relative positions of the boronic acid functional groups are critical factors in enhancing the binding affinity to SA. DFT calculations of both S and R configuration of A1 indicated that the effect of the S/R configuration of A1 on its binding with ß-sialic acid was insignificant as the Ugi-4CR generated racemic products. A fluorine atom was incorporated into the R2 substituent of A1 as an electron-withdrawing group to produce A5, which possessed a significantly higher capability to bind to SA (Keq = 7015 ± 5 M-1 at pH = 6.0). Finally, A1 and A5 were shown to possess exceptional binding selectivity toward ß-sialic acid under pH of 6.0 and 6.5 while preferring to bind with glucose, fructose, and galactose under pH of 7.0 and 7.5.

Clinical and dosimetric predictors of radiation-induced rhinosinusitis following VMAT for nasopharyngeal carcinoma: A retrospective study.

Background: We aimed to investigate the clinical and dosimetric factors associated with radiation-induced rhinosinusitis, and further elucidate the optimal dose-volume constraints for nasopharyngeal cancer patients who underwent volumetric-modulated arc therapy (VMAT). Methods: A retrospective review of 196 nasopharyngeal carcinoma (NPC) patients who underwent definitive VMAT between August 2018 and May 2021 was conducted. Both clinical and dose-volume histogram (DVH) data of NPC patients without rhinosinusitis at baseline were selected for analysis. Results: The cumulative incidence of post-RT rhinosinusitis at the 3-, 6-, 9-, and 12-months, and >1 year were 29.6 %, 41.3 %, 42.9 %, and 45.4 %, and 47.4 %, respectively. Nasal irrigation was negatively associated with post-RT rhinosinusitis (p < 0.001). Higher cumulative incidences of maxillary and ethmoid sinusitis were associated with V70 > 1.16 % and >1.00 %, respectively (p = 0.027 and p = 0.002). Sphenoid sinusitis was more frequent when Dmax(maxillary sinus) exceeded 69.2Gy (p = 0.005). Conclusions: Regular nasal irrigation may reduce the development of rhinosinusitis. Dose-volume constraints of V70 and Dmax to the maxillary sinus are suggested for VMAT planning. Patients exceeding these thresholds should be closely monitored and potentially offered preventative interventions within 3-6 months post-RT.

Predictors of Myelosuppression for Patients with Head and Neck Squamous Cell Carcinoma After Induction Chemotherapy.

Background: Induction chemotherapy (ICT) has become an initial treatment for head and neck squamous cell carcinoma (HNSCC). However, myelosuppression, an unavoidable side effect of ICT, significantly impacts follow-up treatment and prognosis. The main objective of this study is to identify the risk factors and predictors of myelosuppression and its different severity after ICT for ICT. Methods: We retrospectively reviewed medical records of 102 patients with hypopharyngeal cancer or oropharyngeal cancer who received initial ICT from 2013 to 2022. Univariate and multivariate logistic regression analyses were performed to identify risk factors for myelosuppression. Receiver-operating characteristic (ROC) curves were generated using the results of multiple logistic regression analysis to identify data with the highest sensitivity and lowest false-negative rate. Results: Pretreatment lymphocyte count (PLC) and the pretreatment platelet count (PPC) were identified as independent risk factors of myelosuppression (P < .05). Pretreatment hemoglobin count (PHC) was an independent risk factor for predicting myelosuppression in patients with grades III to IV disease. Patients with myelosuppression after ICT are more sensitive to chemotherapy. Conclusions: The PLC and PPC predicted myelosuppression in patients with HNSCC-administered ICT, and the PHC predicted grades III to IV myelosuppression. Myelosuppressed patients were more chemosensitive after ICT.