Genetically predicted inflammatory proteins and the risk of atrial fibrillation: a bidirectional Mendelian randomization study.

Purpose: The causal associations between inflammatory factors and atrial fibrillation (AF) remained unclear. We aimed to investigate whether genetically predicted inflammatory proteins are related to the risk of AF, and vice versa. Methods: A bidirectional two-sample Mendelian randomization study was performed. The genetic variation of 91 inflammatory proteins were derived from genome-wide association study (GWAS) data of European ancestry (n = 14,824). Summary statistics for AF were obtained from a published meta-analysis study (n = 1,030,836) and the FinnGen study (n = 261,395). Results: Genetically predicted fibroblast growth factor 5 (FGF5) was significantly positively associated with risk of AF [[odds ratio (OR): 1.07; 95% CI: 1.04-1.10; P < 0.01], and CD40l receptor was significantly negatively associated with risk of AF (OR: 0.95; 95% CI: 0.92-0.98; P = 0.02) in the meta-analysis study. In the FinnGen study, similar results were observed in FGF5 (OR: 1.11; 95% CI: 1.06-1.16; P < 0.01) and CD40l receptor (OR: 0.93; 95% CI: 0.89-0.97; P = 0.03) for AF. In the FinnGen study, TNF-beta was significantly positively associated with risk of AF (OR: 1.05; 95% CI: 1.02-1.09; P = 0.03) and leukemia inhibitory factor receptor was significantly negatively associated with risk of AF (OR: 0.86; 95% CI: 0.80-0.91; P = 0.001). The causal effect of AF on inflammatory proteins was not observed. Conclusion: Our study suggested that FGF5 and CD40l receptor have a potential causal association with AF, and targeting these factors may help in the treatment of AF.

Investigating Temperature-Dependent Microscopic Deformation in Tough and Self-Healing Hydrogel Using Time-Resolved USAXS.

Tough and self-healing hydrogels are typically sensitive to loading rates or temperatures due to the dynamic nature of noncovalent bonds. Understanding the structure evolution under varying loading conditions can provide valuable insights for developing new tough soft materials. In this study, polyampholyte (PA) hydrogel with a hierarchical structure is used as a model system. The evolution of the microscopic structure during loading is investigated under varied loading temperatures. By combining ultra-small angle X-ray scattering (USAXS) and Mooney-Rivlin analysis, it is elucidated that the deformation of bicontinuous hard/soft phase networks is closely correlated with the relaxation dynamics or strength of noncovalent bonds. At high loading temperatures, the gel is soft and ductile, and large affine deformation of the phase-separated networks is observed, correlated with the fast relaxation dynamics of noncovalent bonds. At low loading temperatures, the gel is stiff, and nonaffine deformation occurs from the onset of loading due to the substantial breaking of noncovalent bonds and limited chain mobility as well as weak adaptation of phase deformation to external stretch. This work provides an in-depth understanding of the relationship between structure and performance of tough and self-healing hydrogels.

Discovery of Novel (+)-Nootkatone-Based Amine Derivatives as Potential Insecticide Candidates.

To discover novel natural product-based insecticides, a series of (+)-nootkatone-based amine derivatives 3a-t were prepared and evaluated for their insecticidal activities against Mythimna separata Walker, Myzus persicae Sulzer, and Plutella xylostella Linnaeus. Insecticidal assays showed that most of the title (+)-nootkatone derivatives exhibited stronger insecticidal activities against three insect pests than the precursor (+)-nootkatone after the introduction of amine groups on the parent (+)-nootkatone. Compounds 3a, 3d, 3h, 3m, 3n, 3p, and 3r displayed more promising growth inhibitory (GI) effect against M. separata than the commercially available botanical insecticide toosendanin. Compound 3o exhibited the most potent aphicidal activity with an LD50 value of 0.011 µg/larvae, which was 2.09-fold higher than the positive control rotenone. Additionally, compounds 3g and 3n showed more promising larvicidal activity against P. xylostella with LC50 values of 260 and 230 mg/L, respectively, superior to that of rotenone (460 mg/L). Moreover, derivatives 3g and 3n exhibited better control efficacy toward P. xylostella than rotenone under greenhouse conditions. Preliminary mechanistic studies revealed that derivative 3n could inhibit the activity of glutathione S-transferase (GST) in P. xylostella and thus exerted larvicidal activity, and molecular docking further demonstrated that 3n could interact well with some amino acid residues of GST. Finally, the toxicity assay suggested that derivatives 3g and 3n were relatively less toxic to nontarget organisms. These findings will provide insights into the development of (+)-nootkatone derivatives as green pesticides.

Involvement of lncRNAs in the regulation of aerobic glycolysis in hepatocellular carcinoma: Main functions, regulatory mechanisms and potential therapeutic implications (Review).

Even under aerobic conditions, tumor cells can reprogram their metabolism to preferentially metabolize glucose into lactic acid. This abnormal metabolic pattern, known as the 'Warburg' effect or aerobic glycolysis, promotes cancer progression. Long non­coding RNAs (lncRNAs) are RNAs that are >200 nucleotides in length and do not have protein­coding capabilities. However, these RNAs play a key role in tumor development. There is increasing evidence to indicate that lncRNAs regulate glucose metabolism in tumor cells by affecting metabolic enzymes and some signaling pathways, thereby regulating the occurrence and progression of hepatocellular carcinoma (HCC). Therefore, it is crucial to understand which lncRNAs play a regulatory role in HCC glycolysis and to determine the related molecular mechanisms. The present review summarized and discussed the functions of lncRNAs, focusing on the regulatory mechanisms of lncRNAs in the process of glycolysis in HCC. In addition, the present review suggests the importance of lncRNAs as future therapeutic targets for antitumor cell metabolism.

Targeting the adenosine signaling pathway in macrophages for cancer immunotherapy.

One of the ways in which macrophages support tumorigenic growth is by producing adenosine, which acts to dampen antitumor immune responses and is generated by both tumor and immune cells in the tumor microenvironment (TME). Two cell surface expressed molecules, CD73 and CD39, boost catalytic adenosine triphosphate, leading to further increased adenosine synthesis, under hypoxic circumstances in the TME. There are four receptors (A1, A2A, A2B, and A3) expressed on macrophages that allow adenosine to perform its immunomodulatory effect. Researchers have shown that adenosine signaling is a key factor in tumor progression and an attractive therapeutic target for treating cancer. Several antagonistic adenosine-targeting biological therapies that decrease the suppressive action of tumor-associated macrophages have been produced and explored to transform this result from basic research into a therapeutic advantage. Here, we'll review the newest findings from studies of pharmacological compounds that target adenosine receptors, and their potential therapeutic value based on blocking the suppressive action of macrophages in tumors.

A case of neonatal tsutsugamushi disease diagnosed with the aid of rickettsial macrogenomic detection.

BACKGROUND: Tsutsugamushi, also known as bush typhus, is a naturally occurring disease caused by Orientia tsutsugamushi. We reported a case of vertical mother-to-newborn transmission of Orientia tsutsugamushi infection in a newborn from Yunnan (China). CASE PRESENTATION: Decreased fetal movements were observed at 39 weeks of gestation. After birth, the newborn (female) had recurrent fever, shortness of breath, and bruising around the mouth and extremities. At 5 h 58 min of age, the newborn was admitted for fever, shortness of breath and generalized rash. The liver was palpable 3 cm below the costal margin, and the limbs showed pitting edema. There was subcutaneous bleeding. Investigations suggested heavy infection, myocardial damage, decreased platelets. Treatment with cefotaxime and ampicillin failed. The mother was hospitalized at 29 weeks of gestation with a fever for 4 consecutive days, and an ulcerated crust was found in the popliteal fossa. Due to this pregnancy history, A diagnosis of Orientia tsutsugamushi infection was suspected in our index case and confirmed by macrogenomic testing and she was treated with vancomycin and meropenem, and later azithromycin for 1 week. The newborn was discharged in good general condition, gradually normalizing body temperature, and decreasing rash and jaundice. There were no abnormalities on subsequent blood macrogenomic tests for the baby. And one month later she showed good mental health, sleep, and food intake and no fever, rash, or jaundice. CONCLUSION: Determining the cause of symptoms is the key to treating diseases, especially the rare diseases that can be misdiagnosed. SUITABLE FOR PEOPLE WITH: Infectious Diseases; Neonatology; Obstetrics.

Topochemical-like bandgap regulation engineering: A bismuth thiooxide nanocatalyst for breast cancer phototherapy.

The physical property tuning of nanomaterials is of great importance in energy, medicine, environment, catalysis, and other fields. Topochemical synthesis of nanomaterials can achieve precise control of material properties. Here, we synthesized a kind of element-doped bismuth-based nanomaterial (BOS) by topochemical-like synthesis and used it for the phototherapy of tumors. In this study, we employed bismuth fluoride nanoflowers as a template and fabricated element-doped bismuth oxide nanoflowers by reduction conditions. The product is consistent with the precursor in crystal structure and nanomorphology, realizing topochemical-like synthesis under mild conditions. BOS can generate reactive oxygen species, consume glutathione, and perform photothermal conversion under 730 nm light irradiation. In vitro and in vivo studies demonstrate that BOS could suppress tumor growth by inducing apoptosis and ferroptosis through phototherapy. Therefore, this study offers a general regulation method for tuning the physical properties of nanomaterials by using a topochemical-like synthesis strategy.

Dye-augmented bandgap engineering of a degradable cascade nanoreactor for tumor immune microenvironment-enhanced dynamic phototherapy of breast cancer.

Non-invasive precision tumor dynamic phototherapy has broad application prospects. Traditional semiconductor materials have low photocatalytic activity and low reactive oxygen species (ROS) production rate due to their wide band gap, resulting in unsatisfactory phototherapy efficacy for tumor treatment. Employing the dye-sensitization mechanism can significantly enhance the catalytic activity of the materials. We develop a multifunctional nanoplatform (BZP) by leveraging the benefits of bismuth-based semiconductor nanomaterials. BZP possesses robust ROS generation and remarkable near-infrared photothermal conversion capabilities for improving tumor immune microenvironment and achieving superior phototherapy sensitization. BZP produces highly cytotoxic ROS species via the photocatalytic process and cascade reaction, amplifying the photocatalytic therapy effect. Moreover, the simultaneous photothermal effect during the photocatalytic process facilitates the improvement of therapeutic efficacy. Additionally, BZP-mediated phototherapy can trigger the programmed death of tumor cells, stimulate dendritic cell maturation and T cell activation, modulate the tumor immune microenvironment, and augment the therapeutic effect. Hence, this study demonstrates a promising research paradigm for tumor immune microenvironment-improved phototherapy. STATEMENT OF SIGNIFICANCE: Through the utilization of dye sensitization and rare earth doping techniques, we have successfully developed a biodegradable bismuth-based semiconductor nanocatalyst (BZP). Upon optical excitation, the near-infrared dye incorporated within BZP promptly generates free electrons, which, under the influence of the Fermi energy level, undergo transfer to BiF3 within BZP, thereby facilitating the effective separation of electron-hole pairs and augmenting the catalytic capability for reactive oxygen species (ROS) generation. Furthermore, a cascade reaction mechanism generates highly cytotoxic ROS, which synergistically depletes intracellular glutathione, thereby intensifying oxidative stress. Ultimately, this dual activation strategy, combining oxidative and thermal damage, holds significant potential for tumor immunotherapy.

Er:YAG laser settings for debonding zirconia restorations: An in vitro study.

This in vitro study aimed to determine the optimal frequency and energy settings for debonding zirconia restorations using an erbium-doped yttrium aluminum garnet (Er:YAG) laser. A total of 200 zirconia specimens (5 mm × 5 mm × 1.5 mm) were fabricated from two types of materials: (1) 3 mol% yttria oxide stabilized tetragonal zirconia polycrystalline (3Y-TZP) and (2) 5 mol% yttria oxide stabilized tetragonal zirconia polycrystalline (5Y-TZP). The zirconia specimens were bonded to dentin using resin cement (RelyX Ultimate, 3 M) and divided into 20 groups based on their laser treatments (n = 5). Er:YAG laser treatment was applied at various frequencies (10 Hz and 20 Hz) and energies (80 mJ, 100 mJ, 120 mJ, 140 mJ, 160 mJ, 180 mJ, 200 mJ, 220 mJ, 240 mJ, and 260 mJ). The time required to debond the specimens and the temperature changes that dentin underwent during the laser treatment were recorded. The surface morphologies of the debonded dentin and zirconia specimens were observed using scanning electron microscopy (SEM). Additional zirconia specimens were fabricated for 4-point flexural strength testing and surface roughness measurements. Statistical analyses were conducted using three-way analysis of variance (ANOVA) and Student-Newman-Keuls (SNK)-q tests (α = 0.05). The debonding time of each specimen varied between 4.8 and 160.4 s, with an average value of 59.2 s. The dentin temperature change for each specimen ranged from 2.3 to 3.6 °C, with an average value of 2.7 °C. The debonding time was significantly influenced by the zirconia material type and laser energy, but it was not affected by the laser frequency. Among the specimens, those made of 3Y-TZP needed significantly more time for debonding than 5Y-TZP. The optimal energies were 220 mJ for 3Y-TZP and 200 mJ for 5Y-TZP. The laser frequency, laser energy, and type of zirconia material had no effect on the dentin temperature change. Additionally, no surface alternations were observed on the dentin or zirconia materials after laser treatment. The surface roughness and flexural strength of the zirconia materials remained unchanged after laser treatment. In summary, Er:YAG laser treatment effectively and safely removes zirconia restorations without impacting their mechanical properties, with a safe temperature change of less than 5.6 °C. The optimum frequency and energy settings for debonding 3Y-TZP and 5Y-TZP restorations were found to be 10/20 Hz and 220 mJ and 10/20 Hz and 200 mJ, respectively.

Spatiotemporal modulation of nitric oxide and Notch signaling by hemodynamic-responsive Trpv4 is essential for ventricle regeneration.

Zebrafish have a remarkable ability to regenerate injured hearts. Altered hemodynamic forces after larval ventricle ablation activate the endocardial Klf2a-Notch signaling cascade to direct zebrafish cardiac regeneration. However, how the heart perceives blood flow changes and initiates signaling pathways promoting regeneration is not fully understood. The present study demonstrated that the mechanosensitive channel Trpv4 sensed the altered hemodynamic forces in injured hearts and its expression was regulated by blood flow. In addition to mediating the endocardial Klf2a-Notch signal cascade around the atrioventricular canal (AVC), we discovered that Trpv4 regulated nitric oxide (NO) signaling in the bulbus arteriosus (BA). Further experiments indicated that Notch signaling primarily acted at the early stage of regeneration, and the major role of NO signaling was at the late stage and through TGF-ß pathway. Overall, our findings revealed that mechanosensitive channels perceived the changes in hemodynamics after ventricle injury, and provide novel insights into the temporal and spatial coordination of multiple signaling pathways regulating heart regeneration.

Dietary Achievable Dose of Protocatechuic Acid, a Metabolite of Flavonoids, Inhibits High-Fat Diet-Induced Obesity in Mice.

SCOPE: Protocatechuic acid (PCA), a gut microbiota metabolite of flavonoids, inhibits dietary obesity and increases uncoupling protein 1 (UCP1), a critical regulator responsible for adipose thermogenesis; however, these effects are achieved at dietary unachievable (pharmacological) dose. It evaluates whether dietary achievable dose of PCA inhibits adiposity by activating adipose thermogenesis. METHODS AND RESULTS: Six-week-old male C57BL/6J mice are fed a high-fat diet (HFD) alone (control) or supplemented with 0.003% PCA w/w for 16 weeks. PCA consumption does not affect food intake but appreciably reduces body weight gain, improves insulin sensitivity, and attenuates hepatic steatosis. These effects are associated with no significant changes in the abundance of UCP1 in adipose tissues. Instead, PCA consumption increases the abundance and enzymatic activity of carnitine palmitoyltransferase 1 (the first rate-limiting enzyme in fatty acid oxidation) in the livers, inguinal white, and brown adipose tissues. Surprisingly, PCA at physiologically achievable dose does not affect the abundance and enzymatic activity of carnitine acyltransferase-1 expression and the capacity of fatty acid oxidation in 3T3-L1-derived white or brown adipocytes and human hepatoma HepG2 cells. CONCLUSIONS: Dietary achievable dose of PCA attenuates HFD-induced adiposity, which is likely achieved by increasing fatty acid oxidation other than activating adipose thermogenesis.

Establishment and study of a rat internal haemorrhoid model.

To establish a relatively stable internal haemorrhoid model in rats. A total of 48 SPF SD rats were selected and randomly divided into a blank group of 16 and a model group of 32. The model was created by croton oil-mixed liquid stimulation combined with standing and swimming experiments, and the modelling times were 1 week and 2 weeks, respectively. By observing the symptoms and signs of rats, pathological morphology and immunohistochemical staining of anorectal tissue, anorectal laser speckle blood-flow imaging and defecation contrast, etc., the effect of different modelling times was evaluated. The stability of the model was evaluated after feeding for 2 weeks. Both model-formation times caused rats to produce local symptoms of tissue bulging in the haemorrhoid area. Microscopy showed that the rectal submucosal interstitial blood vessels were dilated, and inflammatory cell infiltration and other manifestations were observed. Laser speckle blood-flow imaging revealed increased anorectal blood perfusion and capillary dilatation, and defecography showed a longitudinal and continuous rectal mucosa. After 2 weeks of normal feeding, lifting of the haemorrhoidal tissue was still present. The effect of modelling for 1 week was most in line with the clinical manifestations of internal haemorrhoids. The 1-week modelling scheme in this study can effectively establish a rat internal haemorrhoid model that closely approximates clinical internal haemorrhoid symptoms and pathological manifestations. The operation is simple, the success rate is high, and the model has certain stability. This model can be used as an important basis for studying various treatment methods for internal haemorrhoids.

Role of hierarchy structure on the mechanical adaptation of self-healing hydrogels under cyclic stretching.

Soft materials with mechanical adaptability have substantial potential for various applications in tissue engineering. Gaining a deep understanding of the structural evolution and adaptation dynamics of soft materials subjected to cyclic stretching gives insight into developing mechanically adaptive materials. Here, we investigate the effect of hierarchy structure on the mechanical adaptation of self-healing hydrogels under cyclic stretching training. A polyampholyte hydrogel, composed of hierarchical structures including ionic bonds, transient and permanent polymer networks, and bicontinuous hard/soft-phase networks, is adopted as a model. Conditions for effective training, mild overtraining, and fatal overtraining are demonstrated in soft materials. We further reveal that mesoscale hard/soft-phase networks dominate the long-term memory effect of training and play a crucial role in the asymmetric dynamics of compliance changes and the symmetric dynamics of hydrogel shape evolution. Our findings provide insights into the design of hierarchical structures for adaptive soft materials.

Association Between Physical Activity and Arterial Stiffness in Patients with Type 2 Diabetes in Ningbo, China: A Cross-Sectional Study.

Aim: The study aimed to investigate the association between physical activity and arterial stiffness in patients with type 2 diabetes mellitus (T2DM) in Ningbo, China. Methods: A cross-sectional study was conducted using the Metabolic Management Center (MMC) dataset of The First Affiliated Hospital of Ningbo University from 1st March 2018 to 28th February 2023. 4444 adults with T2DM were included in the study. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ)-Short and was categorized into high, moderate, and low. Arterial stiffness was defined as brachial-ankle pulse wave velocity (baPWV) ≥1800cm/s or common carotid artery intima-media thickness (CCA IMT) ≥1mm. Multiple logistic regression analyses were performed to identify the association between physical activity and arterial stiffness. Results: 6.5%, 47.0%, and 46.5% of patients with T2DM had high, moderate, and low physical activity, respectively. 18.8% and 17.5% of patients had arterial stiffness based on baPWV and CCA IMT, respectively. The odds of arterial stiffness (based on baPWV) were lower in patients having moderate to high physical activity (OR 0.82, 95% CI 0.68 to 0.98 and OR 0.58, 95% CI 0.39 to 0.87, respectively). The odds of arterial stiffness (based on CCA IMT) were found to be lower in patients having high physical activity (OR 0.49, 95% CI 0.33 to 0.74). Conclusion: Higher physical activity was found to be associated with lower arterial stiffness in patients with T2DM in Ningbo, China. This was a cross-sectional study, and there is a need to conduct longitudinal studies on this topic.

Identification of Genes Associated with Decreasing Abundance of Monocytes in Long-Term Peritoneal Dialysis Patients.

Purpose: Chronic kidney disease (CKD) will become an end-stage renal disease (ESRD) at stage 5. Peritoneal dialysis (PD) is required for renal replacement therapy. This study aims to identify monocytes-related genes in peritoneal cells from long-term PD (LPD) patients and short-term PD (SPD) patients. Methods: Bulk RNA-seq data (GSE125498 dataset) and ScRNA-seq data (GSE130888) were downloaded to identify differentially expressed genes, monocytes-related genes, and monocytes marker genes in LPD patients. Immune infiltration was analyzed in the GSE125498 dataset. Core genes associated with monocytes changes were screened out, followed by functional analysis and expression validation using RT-PCR. Results: Monocytes are the most abundant immune cell in PD. The number of monocytes was remarkably decreased in LPD compared with SPD. A total of 16 up-regulated core genes negatively correlated with the abundance of monocytes were obtained in LPD. The expression of 16 core genes was lower in monocyte clusters than that in other cell clusters. In addition, LCK, CD3G, CD3E, CD3D, and LAT were involved in the signaling pathways of Th1 and Th2 cell differentiation, T cell receptor signaling pathway, and Th17 cell differentiation. CD2 was involved in hematopoietic cell lineage signaling pathway. Conclusion: Identification of monocytes related-genes and related signaling pathways could be helpful in understanding the molecular mechanism of monocytes changes during PD.

miR-146b-5p downregulates IRAK1 and ADAM19 to suppress trophoblast proliferation, invasion, and migration in miscarriage†.

A large proportion of miscarriages are classified as unexplained miscarriages since no cause is identified. No reliable biomarkers or treatments are available for these pregnancy losses. While our transcriptomic sequencing has revealed substantial upregulation of miR-146b-5p in unexplained miscarriage villous tissues, its role and associated molecular processes have yet to be fully characterized. Our work revealed that relative to samples from normal pregnancy, miR-146b-5p was significantly elevated in villous tissues from unexplained miscarriage patients and displayed promising diagnostic potential. Moreover, miR-146b-5p agomir contributed to higher rates of embryonic resorption in ICR mice. When overexpressed in HTR-8/SVneo cells, miR-146b-5p attenuated the proliferative, invasive, and migratory activity of these cells while suppressing the expression of MMP9 and immune inflammation-associated cytokines, including IL1B, IL11, CXCL1, CXCL8, and CXCL12. Conversely, inhibition of its expression enhanced proliferation, migration, and invasion abilities. Mechanistically, IL-1 receptor-associated kinase-1 and a disintegrin and metalloproteinase 19 were identified as miR-146b-5p targets regulating trophoblast function, and silencing IL-1 receptor-associated kinase-1 had similar effects as miR-146b-5p overexpression, while IL-1 receptor-associated kinase-1 overexpression could partially reverse the inhibitory impact of this microRNA on trophoblasts. miR-146b-5p may inhibit trophoblast proliferation, migration, invasion, and implantation-associated inflammation by downregulating IL-1 receptor-associated kinase-1 and a disintegrin and metalloproteinase 19, participating in the pathogenesis of miscarriage and providing a critical biomarker and a promising therapeutic target for unexplained miscarriage.

The quality of life in nasopharyngeal carcinoma radiotherapy: A longitudinal study.

Objective: This article aims to longitudinally compare nasopharyngeal carcinoma (NPC) patients' quality of life (QoL) during radiotherapy (RT) and identify QoL correlates. Methods: This study included 98 patients, with 85 completing full follow-up. Data were collected at baseline (T1), midpoint of RT (T2), and RT completion (T3), between October 2021 and November 2022. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). RIOM severity was evaluated by the toxicity criteria of Radiation Therapy Oncology Group (RTOG). The nutritional status was evaluated using the Nutritional Risk Screening 2002 (NRS 2002), body mass index (BMI), and the Patient-Generated Subjective Global Assessment (PG-SGA). The generalized estimating equation described the QoL evolution and correlated it with RIOM, nutritional status, and other influential factors. Results: Significant deterioration was observed in various subscales of EORTC QLQ-C30 during RT, including global health status (GHS), physical function, role function, emotional function, fatigue, nausea/vomiting, pain, insomnia, appetite loss, and constipation (all P â€‹< â€‹0.05). Substantial deterioration was also observed in RIOM, nutritional status, and part of hematological indexes (all P â€‹< â€‹0.05). The decline of QoL was associated with gender, age, education level, chemotherapy regimen, Karnofsky performance status (KPS) score, RIOM severity, NRS 2002 score, PG-SGA score, and lymphocyte level (all P â€‹< â€‹0.05). Conclusions: QoL declined during RT and were associated with certain factors. Healthcare professionals should focus on alleviating treatment-related complications and identifying individuals at high risk of malnutrition early to improve outcomes for patients with NPC.

Light-Elicited and Oxygen-Saved Iridium Nanocapsule for Oxidative Damage Intensified Oncotherapy.

Regulating redox homeostasis in tumor cells and exploiting oxidative stress to damage tumors is an efficacious strategy for cancer therapy. However, the strengths of organic nanomaterials within this strategy are often ignored. In this work, a light-triggered reactive oxygen species (ROS) damaging nanoamplifier (IrP-T) was developed for enhanced photodynamic therapy (PDT). The IrP-T was fabricated with an amphiphilic iridium complex and a MTH1 inhibitor (TH287). Under green light stimulation, IrP-T catalyzed the oxygen in cells to generate ROS for realizing oxidative damage; meanwhile, TH287 increased the accumulation of 8-oxo-dGTP, further strengthening oxidative stress and inducing cell death. IrP-T could maximize the use of a small amount of oxygen, thus further boosting the efficacy of PDT in hypoxic tumors. The construction of nanocapsules provided a valuable therapeutic strategy for oxidative damage and synergizing PDT.

Integrating machine learning and bioinformatics analysis to m6A regulator-mediated methylation modification models for predicting glioblastoma patients' prognosis and immunotherapy response.

BACKGROUND: Epigenetic regulations of immune responses are essential for cancer development and growth. As a critical step, comprehensive and rigorous explorations of m6A methylation are important to determine its prognostic significance, tumor microenvironment (TME) infiltration characteristics and underlying relationship with glioblastoma (GBM). METHODS: To evaluate m6A modification patterns in GBM, we conducted unsupervised clustering to determine the expression levels of GBM-related m6A regulatory factors and performed differential analysis to obtain m6A-related genes. Consistent clustering was used to generate m6A regulators cluster A and B. Machine learning algorithms were implemented for identifying TME features and predicting the response of GBM patients receiving immunotherapy. RESULTS: It is found that the m6A regulatory factor significantly regulates the mutation of GBM and TME. Based on Europe, America, and China data, we established m6Ascore through the m6A model. The model accurately predicted the results of 1206 GBM patients from the discovery cohort. Additionally, a high m6A score was associated with poor prognoses. Significant TME features were found among the different m6A score groups, which demonstrated positive correlations with biological functions (i.e., EMT2) and immune checkpoints. CONCLUSIONS: m6A modification was important to characterize the tumorigenesis and TME infiltration in GBM. The m6Ascore provided GBM patients with valuable and accurate prognosis and prediction of clinical response to various treatment modalities, which could be useful to guide patient treatments.

A novel extraperitoneal approach exploration for the treatment of urachal mass: a retrospective observational single-center study.

BACKGROUND: To explore the extraperitoneal laparoscopic urachal mass excision technique and its safety and efficacy in treating urachal mass. METHODS: Baseline characteristics were collected from patients who underwent surgery to diagnose a urachal cyst or abscess in our hospital between January 2020 and August 2021. The full-length of the urachus and part of the top bladder wall were completely removed through the extraperitoneal approach. Patient outcomes were collected to evaluate surgical safety and efficacy, including operation time, intraoperative blood loss, drainage tube removal time, length of stay (LOS), and postoperative complications. RESULTS: All 20 surgeries were successfully performed laparoscopically, and no case was converted to open surgery. The mean body mass index of the patients was 24.6 ± 2.2. The mean patient age was 49.3 ± 8.7 years. The mean size of the cysts was 3.0 ± 0.4 cm. The mean operation time was 56.3 ± 12.0 min. The mean intraoperative blood loss was 28.0 ± 6.4 mL. The mean drainage tube removal time was 3.0 ± 0.5 days. The mean LOS was 5.2 ± 0.4 days. The mean follow-up was 13.4 ± 2.1 months. No postoperative complications were observed during the follow-up period. The short-term follow-up and small patient cohort limited our outcome evaluation. CONCLUSION: Our results indicated that the extraperitoneal laparoscopic approach was a safe and effective method to treat urachal mass. Given the limitations of the study, further multiple and larger sample-sized trials are required to confirm our findings.