Fatty acids and epigenetics in health and diseases.

Lipids are crucial for human health and reproduction and include diverse fatty acids (FAs), notably polyunsaturated FAs (PUFAs) and short-chain FAs (SCFAs) that are known for their health benefits. Bioactivities of PUFAs, including ω-6 and ω-3 FAs as well as SCFAs, have been widely studied in various tissues and diseases. Epigenetic regulation has been suggested as a significant mechanism affecting the progression of various diseases, including cancers and metabolic and inflammatory diseases. Epigenetics encompasses the reversible modulation of gene expression without altering the DNA sequence itself, mediated by mechanisms such as DNA methylation, histone acetylation, and chromatin remodeling. Bioactive FAs have been demonstrated to regulate gene expression via epigenetic modifications that are potentially important for modulating metabolic control and disease risk. This review paper discusses the evidence in support of bioactive FAs, including ω-6 and ω-3 FAs and SCFAs, eliciting various disease prevention via epigenetic regulation including methylation or acetylation.

Lung immune prognostic index is associated with clinical outcomes in recurrent or metastatic (R/M) nasopharyngeal carcinoma receiving immunotherapy: Results from the multicenter, single-arm, phase 2 study.

BACKGROUND: Immune-related biomarkers are linked to the outcomes of cancer immunotherapy. This study evaluates the baseline and longitudinal association between the lung immune prognostic index (LIPI) and immune checkpoint inhibitor outcomes in previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC) patients. METHODS: Data from 153 R/M NPC patients (median age = 49.00 years old) enrolled in a multicenter, single-arm, phase 2 study (NCT03848286) were analyzed. Pretreatment LIPI was classified into good and intermediate/poor (inter/poor) groups. Longitudinal LIPI variations were categorized into "Stable good", "Trend to increase", "Trend to decrease", and "Stable inter/poor". Primary and secondary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). RESULTS: Pretreatment LIPI was significantly associated with OS (inter/poor vs. good: HR = 2.54, 95 % CI: 1.60-4.04, P < 0.001), PFS [inter/poor vs. good: hazard ratio (HR) = 2.18, 95 % CI: 1.47-3.23, P < 0.001], and DCR [inter/poor vs. good: odd ratio (OR) = 0.26, 95 % CI: 0.12-0.58, P < 0.001)]. Patients with persistently inter/poor LIPI status showed worse OS (HR = 3.25, 95 % CI: 1.84-5.74, P < 0.001), PFS (HR = 2.96, 95 % CI: 1.85-4.74, P < 0.001), and ORR (OR = 0.21, 95 % CI: 0.08-0.56, P < 0.001) compared to the persistently good subgroup. CONCLUSION: Pretreatment LIPI and its longitudinal variations may serve as potential biomarkers for predicting immune checkpoint inhibitor outcomes in R/M NPC patients.

Associations between Patient-Generated Subjective Global Assessment criteria and all-cause mortality among cancer patients: Evidence from baseline and longitudinal analyses.

OBJECTIVES: The prognostic effects of the Patient-Generated Subjective Global Assessment (PG-SGA) criteria in cancer survivors have been observed but require validation in clinical practice. This study was designed to evaluate the prognostic effects of baseline and longitudinal changes in PG-SGA scores on all-cause mortality among Chinese cancer patients in a real-world setting. METHODS: Study patients were selected from one representative tertiary hospital in West China. Kaplan-Meier curves and Cox regression analyses were used to estimate the prognostic effect of baseline and dynamic changes in PG-SGA scores on the all-cause mortality of cancer patients. Receiver operating characteristic curves and a concordance index were used to evaluate the predictive accuracy of PG-SGA criteria. RESULTS: A total of 1415 cancer patients were included in this study, with a mean age of 46 years old. Cox regression analysis showed that baseline malnourished status was significantly associated with the survival of cancer patients (PG-SGA 4-8: hazard ratio [HR] = 1.46, 95% confidence interval [CI]: 1.09-1.96, P = 0.012; PG-SGA ≥9: HR = 1.78, 95% CI: 1.34-2.37, P < 0.001). Cancer patients with longitudinal increased PG-SGA scores (>2 points) were observed to have high risks for mortality (HR = 1.69, 95% CI: 1.04-2.74, P = 0.033). Compared with longitudinal changes in PG-SGA scores, baseline malnourished status showed higher predictive power in identifying the risk subgroup (concordance index: 0.646 vs. 0.586). Sensitivity analyses supported the main findings. CONCLUSIONS: This study highlights the prognostic value of baseline and dynamic changes in PG-SGA scores for cancer patients, which can help improve their outcomes.

A cross sectional study of role of technology in health for middle-aged and older adults in Singapore.

Telemedicine has gained popularity due to the increasing use of technology in our lives. However, no studies have explored the demographic factors affecting acceptability, desirability and adherence (ADA) to telemedicine in Singapore. Our study aims to evaluate the level of ADA of telemedicine services within demographic factors and to explore the association of potential demographic factors with the degree of acceptability, desirability and adherence of telemedicine among older adults in Singapore. A cross-sectional study was conducted with Singapore citizens or permanent residents aged 40-99 years, who were able to provide informed consent. Interviewers conducted door-to-door surveys in 67 Blocks of Housing & Development Board flats in Singapore, offering a self-administered electronic questionnaire available in four languages. Random sampling without replacement determined the order of blocks, floors and units visited. The questionnaire utilised Qtelemediab scoring and covered sociodemographic data, usage of telemedicine, as well as ADA towards telemedicine. A total of 324 valid responses were analysed. Increased age was associated with a significant decrease across all three domains of ADA namely acceptability (ß = - 0.02, 95%CI - 0.03; - 0.02, p-value = 0.002), desirability (ß = - 0.02, 95%CI - 0.02; - 0.02, p-value < 0.001) and adherence (ß = - 0.02, 95%CI - 0.03; - 0.0.02, p-value < 0.001). Additionally, lower education was associated with a decrease in all domains of ADA. Conversely, employment and increased household income were associated with higher ADA scores across all three domains. These associations were independent of gender, chronic health conditions and smoking history. Older participants with lower income and lesser education demonstrated lower levels of acceptability, desirability and adherence towards telemedicine. Our study highlights the importance of considering these factors in the implementation and promotion of telemedicine solutions.

Analysis of quality of life in patients after transgastric natural orifice transluminal endoscopic gallbladder-preserving surgery.

BACKGROUND: At present, laparoscopic cholecystectomy (LC) is the main surgical treatment for gallstones. But, after gallbladder removal, there are many complications. Therefore, it is hoped to remove stones while preserving the function of the gallbladder, and with the development of endoscopic technology, natural orifice transluminal endoscopic surgery came into being. AIM: To compare the quality of life, perioperative indicators, adverse events after LC and transgastric natural orifice transluminal endoscopic gallbladder-preserving surgery (EGPS) in patients with gallstones. METHODS: Patients who were admitted to The First Affiliated Hospital of Xinjiang Medical University from 2020 to 2022 were retrospectively collected. We adopted propensity score matching (1:1) to compare EGPS and LC patients. RESULTS: A total of 662 cases were collected, of which 589 cases underwent LC, and 73 cases underwent EGPS. Propensity score matching was performed, and 40 patients were included in each of the groups. In the EGPS group, except the gastrointestinal defecation (P = 0.603), the total score, physical well-being, mental well-being, and gastrointestinal digestion were statistically significant compared with the preoperative score after surgery (P < 0.05). In the LC group, except the mental well-being, the total score, physical well-being, gastrointestinal digestion, the gastrointestinal defecation was statistically significant compared with the preoperative score after surgery (P < 0.05). When comparing between groups, gastrointestinal defecation had significantly difference (P = 0.002) between the two groups, there was no statistically significant difference in the total postoperative score and the other three subscales. In the surgery duration, hospital stay and cost, LC group were lower than EGPS group. The recurrence factors of gallstones after EGPS were analyzed: and recurrence was not correlated with gender, age, body mass index, number of stones, and preoperative score. CONCLUSION: Whether EGPS or LC, it can improve the patient's symptoms, and the EGPS has less impact on the patient's defecation. It needed to, prospective, multicenter, long-term follow-up, large-sample related studies to prove.

Evaluation of a novel vaginal cells self-sampling device for human papillomavirus testing in cervical cancer screening: A clinical trial assessing reliability and acceptability.

Cervical cancer is a significant public health concern, particularly in low- and middle-income countries where resources for prevention and treatment are limited. Routine screening, such as the Papanicolaou test (Pap smears) and human papillomavirus (HPV) testing, plays a crucial role in the early detection and prevention of cervical cancer. However, the participation rate in cervical cancer screening programs remains below optimal levels due to various factors. This study aimed to evaluate the reliability and acceptability of the HygeiaTouch Self Sampling Kit for Women in collecting vaginal samples for HPV typing, comparing the results with samples collected by physicians. The study included 1210 women aged 21-65 from three medical centers in Taiwan. The findings indicated that the self-sampling kit was as effective as physician-collected specimens in terms of obtaining valid samples and identifying HPV. The agreement between the two methods was 88%, with a κ value of 0.75. Furthermore, the study assessed the mechanical characteristics of the self-sampling applicator through tensile, bending, and torque tests, and determined that it was safe for intravaginal use. Additionally, the study evaluated the safety and satisfaction of self-sampling and found a low rate of adverse events (0.7%) and high levels of satisfaction (over 90%) among participants. Overall, we demonstrated that the HygeiaTouch Self Sampling Kit for Women is a reliable and acceptable device for HPV testing and cervical screening, providing a convenient, safe, and effective alternative for women.

Long-term outcomes following hepatectomy in patients with lean non-alcoholic fatty liver disease-associated hepatocellular carcinoma versus overweight and obese counterparts: A multicenter analysis.

BACKGROUND & AIMS: With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) as a significant etiology for hepatocellular carcinoma (HCC), lean NAFLD-HCC has emerged as a specific distinct subtype. This study sought to investigate long-term outcomes following curative-intent hepatectomy for early-stage NAFLD-HCC among lean patients compared with overweight and obese individuals. METHODS: A multicenter retrospective analysis was used to assess early-stage NAFLD-HCC patients undergoing curative-intent hepatectomy between 2009 and 2022. Patients were stratified by preoperative body mass index (BMI) into the lean (<23.0 kg/m2), overweight (23.0-27.4 kg/m2) and obese (≥27.5 kg/m2) groups. Study endpoints were overall survival (OS) and recurrence-free survival (RFS), which were compared among groups. RESULTS: Among 309 patients with NAFLD-HCC, 66 (21.3 %), 176 (57.0 %), and 67 (21.7 %) were lean, overweight, and obese, respectively. The three groups were similar relative to most liver, tumor, and surgery-related variables. Compared with overweight patients (71.3 % and 55.6 %), the lean individuals had a worse 5-year OS and RFS (55.4 % and 35.1 %, P = 0.017 and 0.002, respectively), which were comparable to obese patients (48.5 % and 38.2 %, P = 0.939 and 0.442, respectively). After adjustment for confounding factors, multivariable Cox-regression analysis identified that lean bodyweight was independently associated with decreased OS (hazard ratio: 1.69; 95 % confidence interval: 1.06-2.71; P = 0.029) and RFS (hazard ratio: 1.72; 95 % confidence interval: 1.17-2.52; P = 0.006) following curative-intent hepatectomy for early-stage NAFLD-HCC. CONCLUSIONS: Compared with overweight patients, individuals with lean NAFLD-HCC had inferior long-term oncological survival after hepatectomy for early-stage NAFLD-HCC. These data highlight the need for examination of the distinct carcinogenic pathways of lean NAFLD-HCC and its potential consequences in HCC recurrence.

Combining [177Lu]Lu-DOTA-TOC PRRT with PARP inhibitors to enhance treatment efficacy in small cell lung cancer.

PURPOSE: Small cell lung cancer (SCLC) is a highly aggressive tumor with neuroendocrine origin. Although SCLC frequently express somatostatin receptor type 2 (SSTR2), a significant clinical benefit of SSTR2-targeted radionuclide therapies of SCLC was not observed so far. We hypothesize that combination treatment with a PARP inhibitor (PARPi) could lead to radiosensitization and increase the effectiveness of SSTR2-targeted therapy in SCLC. METHODS: SSTR2-ligand uptake of the SCLC cell lines H69 and H446 was evaluated in vitro using flow cytometry, and in vivo using SPECT imaging and cut-and-count biodistribution. Single-agent (Olaparib, Rucaparib, [177Lu]Lu-DOTA-TOC) and combination treatment responses were determined in vitro via cell viability, clonogenic survival and γH2AX DNA damage assays. In vivo, we treated athymic nude mice bearing H69 or H446 xenografts with Olaparib, Rucaparib, or [177Lu]Lu-DOTA-TOC alone or with combination treatment regimens to assess the impact on tumor growth and survival of the treated mice. RESULTS: H446 and H69 cells exhibited low SSTR2 expression, i.e. 60 to 90% lower uptake of SSTR2-ligands compared to AR42J cells. In vitro, combination treatment of [177Lu]Lu-DOTA-TOC with PARPi resulted in 2.9- to 67-fold increased potency relative to [177Lu]Lu-DOTA-TOC alone. We observed decreased clonogenic survival and higher amounts of persistent DNA damage compared to single-agent treatment for both Olaparib and Rucaparib. In vivo, tumor doubling times increased to 1.6-fold (H446) and 2.2-fold (H69) under combination treatment, and 1.0 to 1.1-fold (H446) and 1.1 to 1.7-fold (H69) in monotherapies compared to untreated animals. Concurrently, median survival was higher in the combination treatment groups in both models compared to monotherapy and untreated mice. Fractionating the PRRT dose did not lead to further improvement of therapeutic outcome. CONCLUSION: The addition of PARPi can markedly improve the potency of SSTR2-targeted PRRT in SCLC models in SSTR2 low-expressing tumors. Further evaluation in humans seems justified based on the results as novel treatment options for SCLC are urgently needed.

Joint association of physical activity and dietary quality with survival among US cancer survivors: a population-based cohort study.

BACKGROUND: Limited studies have explored the joint effect of physical activity (PA) and dietary quality (DQ) on the mortality outcomes of the cancer population. The authors aim to investigate the separate and joint prognostic effect of PA and DQ on the survival of US cancer survivors. METHODS: Data of cancer survivors ( n =3007, representing 22 million cancer survivors) were from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. PA was assessed using the self-reported Global Physical Activity Questionnaire (GPAQ) and DQ was evaluated through the Health Eating Index-2015 (HEI-2015). Kaplan-Meier (KM) curves and the Cox proportional hazard model were used to evaluate the associations between separate and joint prognostic effects of PA and DQ with mortality outcomes among cancer survivors. RESULTS: In the joint analyses, cancer survivors with sufficiently active PA (≥600 MET-min/week) and qualified DQ (≥60) presented reduced risks of all-cause mortality (HR 0.45, 95% CI: 0.35-0.59) as compared with each lifestyle intervention separately. Meanwhile, the joint effects of either insufficiently or sufficiently active PA (>0 MET-min/week) and qualified DQ (≥60) were associated with lower risks for cancer (HR 0.60, 95% CI: 0.40-0.90) and noncancer mortality (HR 0.43, 95% CI: 0.32-0.59). CONCLUSIONS: Our study highlights the combination of active PA and qualified DQ was strongly associated with reduced mortality risk of cancer survivors. Our findings might help to refine the lifestyle intervention recommendations for this population.

Correlation between Angiotensin Inhibitor Administration and Longer Survival in Patients Who Underwent Curative Resection for Pancreatic Cancer.

PURPOSE: The microenvironment of pancreatic ductal adenocarcinoma (PDAC) with extensive desmoplastic stroma contributes to aggressive cancer behavior. Angiotensin system inhibitors (ASIs) reduce stromal fibrosis and are a promising therapeutic strategy. The purpose of this study was to examine how ASIs affected the oncological results of patients who had their PDAC removed. MATERIALS AND METHODS: A retrospective assessment was conducted on the clinicopathological and survival data of patients who received curative resection for PDAC at Severance Hospital between January 2012 and December 2019. RESULTS: A total of 410 participants (228 male and 182 female), with a median follow-up period of 12.8 months, were included in this study. Patients were divided into three groups, based on ASI use and history of hypertension: group 1, normotensive and never used ASI (n=210, 51.2%); group 2, ASI non-users with hypertension (n=50, 12.2%); and group 3, ASI users with hypertension (n=150, 36.6%). The three groups did not differ significantly in terms of age, sex, kind of operation, T and N stages, or adjuvant and neoadjuvant therapy. Moreover, there was no discernible difference in disease-free survival between those who used ASI and those who did not (p=0.636). The 5-year overall survival (OS) rates in groups 1, 2, and 3 were 52.6%, 32.3%, and 38.0%, respectively. However, the OS rate of ASI users was remarkably higher than that of non-users (p=0.016). CONCLUSION: In patients with resected PDAC, ASI is linked to longer survival rates. Furthermore, for individuals with hypertension, ASI in conjunction with conventional chemotherapy may be an easy and successful treatment option.

Human ß-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506.

BACKGROUND: Colorectal cancer has a low 5-year survival rate and high mortality. Human ß-defensin-1 (hBD-1) may play an integral function in the innate immune system, contributing to the recognition and destruction of cancer cells. Long non-coding RNAs (lncRNAs) are involved in the process of cell differentiation and growth. AIM: To investigate the effect of hBD-1 on the mammalian target of rapamycin (mTOR) pathway and autophagy in human colon cancer SW620 cells. METHODS: CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration. Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation. Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway. Additionally, p-mTOR (Ser2448), Beclin1, and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis. RESULTS: hBD-1 inhibited the proliferative ability of SW620 cells, as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1. hBD-1 decreased the expression of p-mTOR (Ser2448) protein and increased the expression of Beclin1 and LC3II/I protein. Furthermore, bioinformatics analysis identified seven lncRNAs (2 upregulated and 5 downregulated) related to the mTOR pathway. The lncRNA TCONS_00014506 was ultimately selected. Following the inhibition of the lncRNA TCONS_00014506, exposure to hBD-1 inhibited p-mTOR (Ser2448) and promoted Beclin1 and LC3II/I protein expression. CONCLUSION: hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.

Synthesis of bioactive evodiamine and rutaecarpine analogues under ball milling conditions.

Mechanochemical reactions achieved by processes such as milling and grinding are promising alternatives to traditional solution-based chemistry. This approach not only eliminates the need for large amounts of solvents, thereby reducing waste generation, but also finds applications in chemical and materials synthesis. The focus of this study is on the synthesis of quinazolinone derivatives by ball milling, in particular evodiamine and rutaecarpine analogues. These compounds are of interest due to their diverse bioactivities, including potential anticancer properties. The study examines the reactions carried out under ball milling conditions, emphasizing their efficiency in terms of shorter reaction times and reduced environmental impact compared to conventional methods. The ball milling reaction of evodiamine and rutaecarpine analogues resulted in yields of 63-78% and 22-61%, respectively. In addition, these compounds were tested for their cytotoxic activity, and evodiamine exhibited an IC50 of 0.75 ± 0.04 µg mL-1 against the Ca9-22 cell line. At its core, this research represents a new means to synthesise these compounds, providing a more environmentally friendly and sustainable alternative to traditional approaches.

Steric Effects on the Photovoltaic Performance of Panchromatic Ruthenium Sensitizers for Dye-Sensitized Solar Cells.

Three new heteroleptic Ru complexes, CYC-B22, CYC-B23C, and CYC-B23T, were prepared as sensitizers for coadsorbent-free, panchromatic, and efficient dye-sensitized solar cells. They are simultaneously functionalized with highly conjugated anchoring and ancillary ligands to explore the electronic and steric effects on their photovoltaic characteristics. The coadsorbent-free device based on CYC-B22 achieved the best power conversion efficiency (PCE) of 8.63% and a panchromatic response extending to 850 nm. The two stereoisomers, CYC-B23C and CYC-B23T coordinated with an unsymmetrical anchoring ligand, display similar absorption properties and the same driving forces for electron injection as well as dye regeneration. Nevertheless, the devices show not only the remarkably distinct PCE (6.64% vs 8.38%) but also discernible stability. The molecular simulation for the two stereoisomers adsorbed on TiO2 clarifies the distinguishable distances (16.9 Å vs 19.0 Å) between the sulfur atoms in the NCS ligands and the surface of the TiO2, dominating the charge recombination dynamics and iodine binding and therefore the PCE and stability of the devices. This study on the steric effects caused by the highly conjugated and unsymmetrical anchoring ligand on the adsorption geometry and photovoltaic performance of the dyes paves a new way for advancing the molecular design of polypyridyl metal complex sensitizers.

Miro1 improves the exogenous engraftment efficiency and therapeutic potential of mitochondria transfer using Wharton's jelly mesenchymal stem cells.

Mitochondria are important for maintaining cellular energy metabolism and regulating cellular senescence. Mitochondrial DNA (mtDNA) encodes subunits of the OXPHOS complexes which are essential for cellular respiration and energy production. Meanwhile, mtDNA variants have been associated with the pathogenesis of neurodegenerative diseases, including MELAS, for which no effective treatment has been developed. To alleviate the pathological conditions involved in mitochondrial disorders, mitochondria transfer therapy has shown promise. Wharton's jelly mesenchymal stem cells (WJMSCs) have been identified as suitable mitochondria donors for mitochondria-defective cells, wherein mitochondrial functions can be rescued. Miro1 participates in mitochondria trafficking by anchoring mitochondria to microtubules. In this study, we identified Miro1 over-expression as a factor that could help to enhance the efficiency of mitochondrial delivery. More specifically, we reveal that Miro1 over-expressed WJMSCs significantly improved intercellular communications, cell proliferation rates, and mitochondrial membrane potential, while restoring mitochondrial bioenergetics in mitochondria-defective fibroblasts. Furthermore, Miro1 over-expressed WJMSCs decreased rates of induced apoptosis and ROS production in MELAS fibroblasts; although, Miro1 over-expression did not rescue mtDNA mutation ratios nor mitochondrial biogenesis. This study presents a potentially novel therapeutic strategy for treating mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), and other diseases associated with dysfunctional mitochondria, while the pathophysiological relevance of our results should be further verified by animal models and clinical studies.

An Infant-Type Hemispheric Glioma With SOX5::ALK: A Novel Fusion.

Infant-type hemispheric glioma (IHG) is a rare pediatric brain tumor with variable response to chemotherapy and radiotherapy. Molecular insights into IHG can be useful in identifying potentially active targeted therapy. A male fetus was found to have congenital hydrocephalus at the gestational age of 37 weeks. Fetal MRI showed a 2.6 × 2.0-cm tumor located at the frontal horn of the left lateral ventricle, involving the left basal nuclei and thalamus. Tumor biopsy at the age of 2 days revealed an IHG consisting of spindle tumor cells with strong expression of GFAP and ALK. Targeted RNA sequencing detected a novel fusion gene of SOX5::ALK. After initial chemotherapy with cyclophosphamide, carboplatin, and etoposide for 2 cycles, the tumor size progressed markedly and the patient underwent a subtotal resection of brain tumor followed by treatment with lorlatinib, an ALK tyrosine kinase inhibitor with central nervous system (CNS) activity. After 3 months of treatment, reduction of tumor size was observed. After 14 months of treatment, partial response was achieved, and the infant had normal growth and development. In conclusion, we identified a case of congenital IHG with a novel SOX5::ALK fusion that had progressed after chemotherapy and showed partial response and clinical benefit after treatment with the CNS-active ALK inhibitor lorlatinib.

Consistency in human papillomavirus type detection between self-collected vaginal specimens and physician-sampled cervical specimens.

With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.

Robinetin Alleviates Metabolic Failure in Liver through Suppression of p300-CD38 Axis.

Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression. The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300-CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.

Association between time from diagnosis to treatment and survival of patients with nasopharyngeal carcinoma: A population-based cohort study.

BACKGROUND: Treatment delays have frequently been observed in cancer patients. Whether the treatment delays would impair the survival of patients with nasopharyngeal carcinoma (NPC) is still unclear. METHODS: The data were derived from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Patients were divided into groups of timely treatment (<1 month), intermediate delay (1 and 2 months), and long delay (3-6 months). The influence of different treatment delay intervals on long-term survival was evaluated by multivariate Cox regression analysis. RESULTS: In total, 2,048 patients with NPC were included in our study. There were 551 patients in the early stage (I, II stage: 26.9 %) and 1,497 patients in the advanced stage (III, IV stage: 73.1 %). No significant difference in overall survival (OS) or cancer-specific survival (CSS) was observed among the groups with various treatment delay intervals (p = 0.48 in OS and p = 0.43 in CSS, respectively). However, upon adjusting for covariates, a significantly improved OS probability emerged in patients with intermediate treatment delays compared to those who received timely interventions in both the entire study population (adjustedHazard Ratio (aHR)=0.86, 95 % CI: 0.74-0.99, p = 0.043) and the subgroup with advanced stage (aHR=0.85, 95 % CI: 0.72-1.00, p = 0.049). Regarding the CSS probability, similar associations were also observed in the entire study population (aHR=0.84, 95 % CI: 0.71-0.98, p = 0.030) as well as the advanced-stage patients (aHR=0.83, 95 % CI: 0.70-0.99, p =  0.038). CONCLUSIONS: Our results revealed that treatment delays are not associated with worse survival of NPC patients. Tumor-specific characteristics and subsequent treatment modalities play more pivotal roles in the prognosis of NPC.

D-A-D organic fluorescent probes for NIR-II fluorescence imaging and efficient photothermal therapy of breast cancer.

Near-infrared second region (NIR-II) fluorescent probes are used in the diagnosis of early cancer due to their high tissue penetration. However, there are still few reports on organic small molecule fluorescent probes with NIR-II fluorescence imaging (NIR-II FI) combined with efficient photothermal therapy (PTT). In this study, planar cyclopentadithiophene (CPDT) was incorporated into the twisted structural skeleton (D-A-D), and the strong acceptor TTQ molecule (A) and the donor triphenylamine (D) were introduced to synthesize an organic small molecule (TCT) with enhanced NIR-II fluorescence emission performance. To improve the hydrophilicity of TCT molecules, we used the nanoprecipitation method to coat DSPE-mPEG2000 on the TCT molecules and obtained nanoparticles (TCT-NPs) with a strong absorption band, good water dispersibility, and NIR-II FI ability, which realized NIR-II FI-guided PTT for breast cancer tumors. Due to their effective near-infrared absorption, TCT-NPs exhibit high photothermal conversion efficiency (η = 40.1%) under 660 nm laser irradiation, making them a photothermal therapeutic agent with good performance. Therefore, TCT-NPs have the potential to diagnose, eliminate, and monitor the diffusion of cancer.

Ultrasensitive and Rapid Detection of Procalcitonin via Waveguide-Enhanced Nanogold-Linked Immunosorbent Assay for Early Sepsis Diagnosis.

Sepsis, a life-threatening inflammatory response, demands economical, accurate, and rapid detection of biomarkers during the critical "golden hour" to reduce the patient mortality rate. Here, we demonstrate a cost-effective waveguide-enhanced nanogold-linked immunosorbent assay (WENLISA) based on nanoplasmonic waveguide biosensors for the rapid and sensitive detection of procalcitonin (PCT), a sepsis-related inflammatory biomarker. To enhance the limit of detection (LOD), we employed sandwich assays using immobilized capture antibodies and detection antibodies conjugated to gold nanoparticles to bind the target analyte, leading to a significant evanescent wave redistribution and strong nanoplasmonic absorption near the waveguide surface. Experimentally, we detected PCT for a wide linear response range of 0.1 pg/mL to 1 ng/mL with a record-low LOD of 48.7 fg/mL (3.74 fM) in 8 min. Furthermore, WENLISA has successfully identified PCT levels in the blood plasma of patients with sepsis and healthy individuals, offering a promising technology for early sepsis diagnosis.