Diurnal and eating-associated microbial patterns revealed via high-frequency saliva sampling.

The oral microbiome is linked to oral and systemic health, but its fluctuation under frequent daily activities remains elusive. Here, we sampled saliva at 10- to 60-min intervals to track the high-resolution microbiome dynamics during the course of human activities. This dense time series data showed that eating activity markedly perturbed the salivary microbiota, with tongue-specific Campylobacter concisus and Oribacterium sinus and dental plaque-specific Lautropia mirabilis, Rothia aeria, and Neisseria oralis increased after every meal in a temporal order. The observation was reproducible in multiple subjects and across an 11-mo period. The microbiome composition showed significant diurnal oscillation patterns at different taxonomy levels with Prevotella/Alloprevotella increased at night and Bergeyella HMT 206/Haemophilus slowly increased during the daytime. We also identified microbial co-occurring patterns in saliva that are associated with the intricate biogeography of the oral microbiome. Microbial source tracking analysis showed that the contributions of distinct oral niches to the salivary microbiome were dynamically affected by daily activities, reflecting the role of saliva in exchanging microbes with other oral sites. Collectively, our study provides insights into the temporal microbiome variation in saliva and highlights the need to consider daily activities and diurnal factors in design of oral microbiome studies.

Proteome Landscapes of Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

Liver cancer is among the top leading causes of cancer mortality worldwide. Particularly, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA) have been extensively investigated from the aspect of tumor biology. However, a comprehensive and systematic understanding of the molecular characteristics of HCC and CCA remains absent. Here, we characterized the proteome landscapes of HCC and CCA using the data-independent acquisition (DIA) mass spectrometry (MS) method. By comparing the quantitative proteomes of HCC and CCA, we found several differences between the two cancer types. In particular, we found an abnormal lipid metabolism in HCC and activated extracellular matrix-related pathways in CCA. We next developed a three-protein classifier to distinguish CCA from HCC, achieving an area under the curve (AUC) of 0.92, and an accuracy of 90% in an independent validation cohort of 51 patients. The distinct molecular characteristics of HCC and CCA presented in this study provide new insights into the tumor biology of these two major important primary liver cancers. Our findings may help develop more efficient diagnostic approaches and new targeted drug treatments.

Capillary blood self-collection for high-throughput proteomics.

In this study, we sought to compare protein concentrations obtained from a high-throughput proteomics platform (Olink) on samples collected using capillary blood self-collection (with the Tasso+ device) versus standard venipuncture (control). Blood collection was performed on 20 volunteers, including one sample obtained via venipuncture and two via capillary blood using the Tasso+ device. Tasso+ samples were stored at 2°C-8°C for 24-hs (Tasso-24) or 48-h (Tasso-48) prior to processing to simulate shipping times from a study participant's home. Proteomics were analyzed using Olink (384 Inflammatory Panel). Tasso+ blood collection was successful in 37/40 attempts. Of 230 proteins included in our analysis, Pearson correlations (r) and mean coefficient of variation (CV) between Tasso-24 or Tasso-48 versus venipuncture were variable. In the Tasso-24 analysis, 34 proteins (14.8%) had both a correlation r > 0.5 and CV < 0.20. In the Tasso-48 analysis, 68 proteins (29.6%) had a correlation r > 0.5 and CV < 0.20. Combining the Tasso-24 and Tasso-48 analyses, 26 (11.3%) proteins met these thresholds. We concluded that protein concentrations from Tasso+ samples processed 24-48 h after collection demonstrated wide technical variability and variable correlation with a venipuncture gold-standard. Use of home capillary blood self-collection for large-scale proteomics should be limited to select proteins with good agreement with venipuncture.

Efficient computation of Faith's phylogenetic diversity with applications in characterizing microbiomes.

The number of publicly available microbiome samples is continually growing. As data set size increases, bottlenecks arise in standard analytical pipelines. Faith's phylogenetic diversity (Faith's PD) is a highly utilized phylogenetic alpha diversity metric that has thus far failed to effectively scale to trees with millions of vertices. Stacked Faith's phylogenetic diversity (SFPhD) enables calculation of this widely adopted diversity metric at a much larger scale by implementing a computationally efficient algorithm. The algorithm reduces the amount of computational resources required, resulting in more accessible software with a reduced carbon footprint, as compared to previous approaches. The new algorithm produces identical results to the previous method. We further demonstrate that the phylogenetic aspect of Faith's PD provides increased power in detecting diversity differences between younger and older populations in the FINRISK study's metagenomic data.

Decreased postpartum exercise capacity after a diagnosis of pre-eclampsia: Implications for CVD risk prediction.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes) and heart failure. Exercise capacity is a known predictor of heart failure in patients with normal resting cardiac filling pressures. In this prospective observational cohort study, we sought to identify predictors of reduced postpartum exercise capacity in participants with normotensive vs. preeclamptic pregnancies. METHODS: Preeclampsia (PreE) and normotensive subjects were enrolled to undergo bedside echocardiography within 48 hours of delivery, and rest/exercise echocardiography 12 weeks postpartum. RESULTS: Recruited subjects (n=68) were grouped according to their blood pressure as: a) normotensive pregnancy n=15; b) PreE with normotensive postpartum (PreE-Resolved, n=36); c) PreE with persistent postpartum HTN (PreE-HTN, n=17). At enrollment, a significantly higher percentage of subjects in the PreE-HTN group were Black. Compared to normotensive and PreE-Resolved subjects, those with PreE-HTN demonstrated higher resting systolic blood pressure (SBP, 112 [normotensive] vs 112 [PreE-Resolved] vs 134 [PreE-HTN], p<0.001) and diastolic blood pressure (DBP, 70.0 vs 72.5 vs 85.0, p<0.001), and significantly less postpartum weight loss (9.6% vs 13.6% vs 3.8%, p<0.001). Following Bruce protocol stress testing, PreE-HTN subjects demonstrated achieved significantly lower exercise duration (10.4 vs 10.2 vs 7.9 minutes, p = 0.001). Subjects with PreE-HTN also demonstrated evidence of exercise-induced diastolic dysfunction as assessed by peak exercise lateral e' (18.0 vs 18.0 vs 13.5, p=0.045) and peak exercise tricuspid regurgitation velocity (TR Vm, 2.4 vs 3.0 vs 3.1, p = 0.045). Exercise duration was negatively associated with gravidity (R=-0.27, p=0.029) and postpartum LV mass index (R=-0.45, p<0.001), resting average E/e' (R=-0.51, p<0.001), BMI (R=-0.6, p<0.001) and resting SBP (R=-0.51, p<0.001). CONCLUSIONS: Postpartum exercise stress testing capacity is related to readily available clinical markers including pregnancy factors, echocardiographic parameters and unresolved cardiometabolic risk factors.

Challenges in benchmarking metagenomic profilers.

Accurate microbial identification and abundance estimation are crucial for metagenomics analysis. Various methods for classification of metagenomic data and estimation of taxonomic profiles, broadly referred to as metagenomic profilers, have been developed. Nevertheless, benchmarking of metagenomic profilers remains challenging because some tools are designed to report relative sequence abundance while others report relative taxonomic abundance. Here we show how misleading conclusions can be drawn by neglecting this distinction between relative abundance types when benchmarking metagenomic profilers. Moreover, we show compelling evidence that interchanging sequence abundance and taxonomic abundance will influence both per-sample summary statistics and cross-sample comparisons. We suggest that the microbiome research community pay attention to potentially misleading biological conclusions arising from this issue when benchmarking metagenomic profilers, by carefully considering the type of abundance data that were analyzed and interpreted and clearly stating the strategy used for metagenomic profiling.

Pathological response to neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma in Eastern versus Western countries: meta-analysis.

OBJECTIVE: Locally advanced oesophageal squamous cell carcinoma can be treated with neoadjuvant chemoradiotherapy or chemotherapy followed by oesophagectomy. Discrepancies in pathological response rates have been reported between studies from Eastern versus Western countries. The aim of this study was to compare the pathological response to neoadjuvant chemoradiotherapy in Eastern versus Western countries. METHODS: Databases were searched until November 2022 for studies reporting pCR rates after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma. Multi-level meta-analyses were performed to pool pCR rates separately for cohorts from studies performed in centres in the Sinosphere (East) or in Europe and the Anglosphere (West). RESULTS: For neoadjuvant chemoradiotherapy, 51 Eastern cohorts (5636 patients) and 20 Western cohorts (3039 patients) were included. Studies from Eastern countries included more men, younger patients, more proximal tumours, and more cT4 and cN+ disease. Patients in the West were more often treated with high-dose radiotherapy, whereas patients in the East were more often treated with a platinum + fluoropyrimidine regimen. The pooled pCR rate after neoadjuvant chemoradiotherapy was 31.7% (95% c.i. 29.5% to 34.1%) in Eastern cohorts versus 40.4% (95% c.i. 35.0% to 45.9%) in Western cohorts (fixed-effect P = 0.003). For cohorts with similar cTNM stages, pooled pCR rates for the East and the West were 32.5% and 41.9% respectively (fixed-effect P = 0.003). CONCLUSION: The pathological response to neoadjuvant chemoradiotherapy is less favourable in patients treated in Eastern countries compared with Western countries. Despite efforts to investigate accounting factors, the discrepancy in pCR rate cannot be entirely explained by differences in patient, tumour, or treatment characteristics.

Prospective study of urinary incontinence recovery following endoscopic enucleation of the prostate.

OBJECTIVE: To investigate the clinical trajectories and identify risk factors linked to post-enucleation urinary incontinence (UI). PATIENTS AND METHODS: In this prospective study (April 2020 to March 2022) at a single institution, 316 consecutive patients receiving endoscopic enucleation due to benign prostatic enlargement were included. Patient information and perioperative details were collected. Follow-ups, from 1 to 6 months, assessed postoperative UI using International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and a four-item pad questionnaire, classified per International Continence Society definitions. Logistic regression analysed predictors at 1 week, while generalised estimating equation assessed risk factors from 1 to 3 months postoperatively. RESULTS: Patients with a median prostate volume of 57 mL underwent enucleation, with 22.5% experiencing postoperative UI at 1 week, 5.6% at 3 months, decreasing to 1.9% at 6 months. Multivariable analysis identified age (>80 years), specimen weight (>70 g), en bloc with anteroposterior dissection, and anal tone (Digital Rectal Examination Scoring System score <3) as potential factors influencing UI. Subgroup analysis revealed that specimen weight was associated with both continuous and stress UI. Anal tone was related to both other types and stress UI, while overactive bladder symptoms were associated with urge UI. CONCLUSION: In summary, our study elucidates transient risk factors contributing to temporary post-enucleation UI after prostatectomy. Informed decisions and personalised interventions can effectively alleviate concerns regarding postoperative UI.

Boron Neutron Capture Therapy Enhanced by Boronate Ester Polymer Micelles: Synthesis, Stability, and Tumor Inhibition Studies.

Boron neutron capture therapy (BNCT) targets invasive, radioresistant cancers but requires a selective and high B-10 loading boron drug. This manuscript investigates boron-rich poly(ethylene glycol)-block-(poly(4-vinylphenyl boronate ester)) polymer micelles synthesized via atom transfer radical polymerization for their potential application in BNCT. Transmission electron microscopy (TEM) revealed spherical micelles with a uniform size of 43 ± 10 nm, ideal for drug delivery. Additionally, probe sonication proved effective in maintaining the micelles' size and morphology postlyophilization and reconstitution. In vitro studies with B16-F10 melanoma cells demonstrated a 38-fold increase in boron accumulation compared to the borophenylalanine drug for BNCT. In vivo studies in a B16-F10 tumor-bearing mouse model confirmed enhanced tumor selectivity and accumulation, with a tumor-to-blood (T/B) ratio of 2.5, surpassing BPA's T/B ratio of 1.8. As a result, mice treated with these micelles experienced a significant delay in tumor growth, highlighting their potential for BNCT and warranting further research.

A Biomimetic Fibrous Composite Scaffold with Nanotopography-Regulated Mineralization for Bone Defect Repair.

The effective regeneration of large bone defects via bone tissue engineering is challenging due to the difficulty in creating an osteogenic microenvironment. Inspired by the fibrillar architecture of the natural extracellular matrix, we developed a nanoscale bioengineering strategy to produce bone fibril-like composite scaffolds with enhanced osteogenic capability. To activate the surface for biofunctionalization, self-adaptive ridge-like nanolamellae were constructed on poly(ε-caprolactone) (PCL) electrospinning scaffolds via surface-directed epitaxial crystallization. This unique nanotopography with a markedly increased specific surface area offered abundant nucleation sites for Ca2+ recruitment, leading to a 5-fold greater deposition weight of hydroxyapatite than that of the pristine PCL scaffold under stimulated physiological conditions. Bone marrow mesenchymal stem cells (BMSCs) cultured on bone fibril-like scaffolds exhibited enhanced adhesion, proliferation, and osteogenic differentiation in vitro. In a rat calvarial defect model, the bone fibril-like scaffold significantly accelerated bone regeneration, as evidenced by micro-CT, histological histological and immunofluorescence staining. This work provides the way for recapitulating the osteogenic microenvironment in tissue-engineered scaffolds for bone repair.

Asymmetric (3 + 3) and (4 + 2) Annulation Reactions of 2,3-Dioxopyrrolidines with 3-Alkylidene Oxindoles to Construct Diverse Chiral Heterocyclic Frameworks.

Two substrate-controlled regiodivergent annulation protocols for 2,3-dioxopyrrolidines with 3-alkylidene oxindoles have been developed, which furnished a series of fused dihydropyrrolidone derivatives in high yields with excellent stereoselectivities. Plausible mechanistic pathways for both annulation reactions are proposed that [3 + 3] annulation reaction involves vinylogous Michael addition followed by intramolecular aldol cyclization, while [4 + 2] annulation reaction occurs through a vinylogous Michael addition and a subsequent intramolecular oxa-Michael cyclization.

Predictive Dosimetry and Outcomes of Hepatocellular Carcinoma Treated by Yttrium-90 Resin Microsphere Radioembolization: A Retrospective Analysis Using Technetium-99m Macroaggregated Albumin SPECT/CT and Planning Software.

PURPOSE: To characterize estimated mean absorbed tumor dose (ADT), objective response (OR), and estimated target dose of hepatocellular carcinoma (HCC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. MATERIALS AND METHODS: In this retrospective, single-center study, multicompartment dosimetry of index tumors receiving 90Y radioembolization between October 2015 and June 2022 was performed using a commercial software package and pretreatment technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT)/computed tomography (CT). In total, 101 patients with HCC underwent 102 treatments of 127 index tumors. Patients underwent imaging every 2-3 months after treatment to determine best response per modified Response Evaluation Criteria in Solid Tumors (mRECIST). Best response was defined as the greatest response category per mRECIST and categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and progression-free survival using ADT. RESULTS: The median follow-up period was 148 days (interquartile range [IQR], 92-273 days). The median ADT of OR was 141.9 Gy (IQR, 89.4-215.8 Gy) compared with the median ADT of NR treatments of 70.8 Gy (IQR, 42.0-135.3 Gy; P < .001). Only ADT was predictive of response (hazard ratio = 2.79 [95% confidence interval {CI}: 1.44-5.40]; P = .003). At 6 months, an ADT of 157 Gy predicted 90.0% (95% CI: 41.3%-98.3%) probability of OR. At 1 year, an ADT of 157 Gy predicted 91.6% (95% CI: 78.3%-100%) probability of progression-free survival. Partition modeling and delivered activity were predictive of progression (P = .021 and P = .003, respectively). CONCLUSIONS: For HCC treated with resin microspheres, tumors receiving higher ADT exhibited higher rates of OR. An ADT of 157 Gy predicted 90.0% OR at 6 months.

Seed-borne bacterial synthetic community resists seed pathogenic fungi and promotes plant growth.

AIMS: In this study, the control effects of synthetic microbial communities composed of peanut seed bacteria against seed aflatoxin contamination caused by Aspergillus flavus and root rot by Fusarium oxysporum were evaluated. METHODS AND RESULTS: Potentially conserved microbial synthetic communities (C), growth-promoting synthetic communities (S), and combined synthetic communities (CS) of peanut seeds were constructed after 16S rRNA Illumina sequencing, strain isolation, and measurement of plant growth promotion indicators. Three synthetic communities showed resistance to root rot and CS had the best effect after inoculating into peanut seedlings. This was achieved by increased defense enzyme activity and activated salicylic acid (SA)-related, systematically induced resistance in peanuts. In addition, CS also inhibited the reproduction of A. flavus on peanut seeds and the production of aflatoxin. These effects are related to bacterial degradation of toxins and destruction of mycelia. CONCLUSIONS: Inoculation with a synthetic community composed of seed bacteria can help host peanuts resist the invasion of seeds by A. flavus and seedlings by F. oxysporum and promote the growth of peanut seedlings.

The effect of environmental regulation and green subsidies on agricultural low-carbon production behavior: A survey of new agricultural management entities in Guangdong Province.

Agricultural low-carbon production emerges as a pivotal function for achieving sustainable green development. However, there remains insufficient empirical evidence regarding the effect of environmental regulations and green subsidies upon the low-carbon production behavior of new agricultural entities. In this study, a questionnaire survey was administered to 268 respondents representing new agricultural entities in Guangdong Province, P.R.C. Subsequently, a structural equation model had been employed for validation analysis. This study's findings demonstrate that in general, environmental regulations positively and significantly affect the behavior of agricultural low-carbon production. Conversely, the influence of green subsidies is not statistically significant. In addition, differences are observed across different sectors, with environmental regulations significantly affecting low-carbon production behavior in the plantation sector, but not in the livestock sector. Conversely, green subsidies significantly impact low-carbon production behavior in the livestock sector, but not in the plantation sector. These findings highlight the promotional role of government-enforced environmental regulations and green subsidies in fostering low-carbon agricultural practices. Therefore, new agricultural entities should strive to augment green production technology capacities to realize sustainable green development.

The consumption of animal products is associated with plasma levels of alpha-aminoadipic acid (2-AAA).

BACKGROUND AND AIMS: The cardiometabolic disease-associated metabolite, alpha-aminoadipic acid (2-AAA) is formed from the breakdown of the essential dietary amino acid lysine. However, it was not known whether elevated plasma levels of 2-AAA are related to dietary nutrient intake. We aimed to determine whether diet is a determinant of circulating 2-AAA in healthy individuals, and whether 2-AAA is altered in response to dietary modification. METHODS AND RESULTS: We investigated the association between 2-AAA and dietary nutrient intake in a cross-sectional study of healthy individuals (N = 254). We then performed a randomized cross-over dietary intervention trial to investigate the effect of lysine supplementation (1 week) on 2-AAA in healthy individuals (N = 40). We further assessed the effect of a vegetarian diet on 2-AAA in a short-term (4-day) dietary intervention trial in healthy omnivorous women (N = 35). We found that self-reported dietary intake of animal products, including meat, poultry, and seafood, was associated with higher plasma 2-AAA cross-sectionally (P < 0.0001). Supplementary dietary lysine (5g/day) caused no significant increase in plasma 2-AAA; however, plasma 2-AAA was altered by general dietary modification. Further, plasma 2-AAA was significantly reduced by a short-term vegetarian diet (P = 0.003). CONCLUSION: We identified associations between plasma 2-AAA and consumption of animal products, which were validated in a vegetarian dietary intervention trial, but not in a trial designed to specifically increase the 2-AAA amino acid precursor lysine. Further studies are warranted to investigate whether implementation of a vegetarian diet improves cardiometabolic risk in individuals with elevated 2-AAA.

Successful treatment with efgartigimod as an add-on therapy in acute attack of anti-AQP4 antibody-positive NMOSD: a case report.

BACKGROUND: Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune demyelinating disease characterized by recurrent myelitis and optic neuritis. It is associated with high rates of relapse and disability. The main treatment strategies for acute attacks include intravenous methylprednisolone pulse (IVMP) treatment and rescue treatment with plasma exchange (PLEX). Recently, the blockade of neonatal Fc receptor (FcRn)-IgG interaction has gained momentum as a therapeutic strategy. Efgartigimod, the first approved FcRn inhibitor for treating generalized myasthenia gravis, has shown impressive safety, efficacy, and tolerability, and is being regarded as "PLEX in a bottle". CASE DESCRIPTION: We report a 65-year-old female patient who was diagnosed with anti-AQP4 antibody positive NMOSD. Add-on treatment with efgartigimod to IVMP and intravenous immunoglobulin (IVIG) at the second acute relapse showed favorable results. CONCLUSION: This case suggests that efgartigimod is a potentially effective add-on therapy in acute attacks of AQP4-IgG-positive NMOSD.

Elevated Pulmonary Arterial Compliance Is Associated with Survival in Pulmonary Hypertension: Results from a Novel Network Medicine Analysis.

Rationale: Predictors of adverse outcome in pulmonary hypertension (PH) are well established; however, data that inform survival are lacking. Objectives: We aim to identify clinical markers and therapeutic targets that inform the survival in PH. Methods: We included data from patients with elevated mean pulmonary artery pressure (mPAP) diagnosed by right heart catheterization in the U.S. Veterans Affairs system (October 1, 2006-September 30, 2018). Network medicine framework was used to subgroup patients when considering an N of 79 variables per patient. The results informed outcome analyses in the discovery cohort and a sex-balanced validation right heart catheterization cohort from Vanderbilt University (September 24, 1998-December 20, 2013). Measurements and Main Results: From an N of 4,737 complete case patients with mPAP of 19-24 mm Hg, there were 21 distinct subgroups (network modules) (all-cause mortality range = 15.9-61.2% per module). Pulmonary arterial compliance (PAC) drove patient assignment to modules characterized by increased survival. When modeled continuously in patients with mPAP ⩾19 mm Hg (N = 37,744; age, 67.2 yr [range = 61.7-73.8 yr]; 96.7% male; median follow-up time, 1,236 d [range = 570-1,971 d]), the adjusted all-cause mortality hazard ratio was <1.0 beginning at PAC ⩾3.0 ml/mm Hg and decreased progressively to ∼7 ml/mm Hg. A protective association between PAC ⩾3.0 ml/mm Hg and mortality was also observed in the validation cohort (N = 1,514; age, 60.2 yr [range = 49.2-69.1 yr]; 48.0% male; median follow-up time, 2,485 d [range = 671-3,580 d]). The association was strongest in patients with precapillary PH at the time of catheterization, in whom 41% (95% confidence interval, 0.55-0.62; P < 0.001) and 49% (95% confidence interval, 0.38-0.69; P < 0.001) improvements in survival were observed for PAC ⩾3.0 versus <3.0 ml/mm Hg in the discovery and validation cohorts, respectively. Conclusions: These data identify elevated PAC as an important parameter associated with survival in PH. Prospective studies are warranted that consider PAC ⩾3.0 ml/mm Hg as a therapeutic target to achieve through proven interventions.

Short-term OS as a surrogate endpoint for 5-year OS in nasopharyngeal carcinoma in non-endemic area.

PURPOSE: To address this evidence gap and validate short-term OS at less than 5 years as a reliable surrogate endpoint for 5-year OS. METHODS: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on non-metastatic NPC patients diagnosed between 2010 and 2015. Patients were categorized into radiotherapy and chemoradiotherapy groups. RESULTS: This retrospective study examined 2,047 non-metastatic NPC patients. Among them, 217 received radiotherapy, and 1,830 received chemoradiotherapy. Our analysis results indicated that the 4-year OS may serve as a reliable surrogate endpoint for patients with AJCC clinical stage I (80 vs. 78%, P = 0.250), regardless of the treatment received. Specifically, in the radiotherapy group, patients with stage I, T0-T1, and N0 NPC showed similar OS rates at 4 and 5 years (83 vs. 82%, P = 1.000; 78 vs. 76%, P = 0.250; 78 vs. 77%, P = 0.500, respectively). Similarly, patients with stage II-IV, T2-T4, and N1-3 NPC showed no significant difference in OS rates between 3 and 5 years (57 vs. 51%, P = 0.063; 52 vs. 46%, P = 0.250; 54 vs. 46%, P = 0.125, respectively) in the radiotherapy group. In the chemoradiotherapy group, only the 3-year OS rate did not significantly differ from that at 5 years in stage I patients (79vs. 72%, P = 0.063). CONCLUSIONS: Our study suggests that short-term surrogate endpoints may be valuable for evaluating 5-year OS outcomes in NPC patients in non-endemic areas.

Marine Prostanoids with Cytotoxic Activity from Octocoral Clavularia spp.

Octocoral of the genus Clavularia is a kind of marine invertebrate possessing abundant cytotoxic secondary metabolites, such as prostanoids and dolabellanes. In our continuous natural product study of C. spp., two previously undescribed prostanoids [clavulone I-15-one (1) and 12-O-deacetylclavulone I (2)] and eleven known analogs (3-13) were identified. The structures of these new compounds were elucidated based on analysis of their 1D and 2D NMR, HRESIMS, and IR data. Additionally, all tested prostanoids (1 and 3-13) showed potent cytotoxic activities against the human oral cancer cell line (Ca9-22). The major compound 3 showed cytotoxic activity against the Ca9-22 cells with the IC50 value of 2.11 ± 0.03 µg/mL, which echoes the cytotoxic effect of the coral extract. In addition, in silico tools were used to predict the possible effects of isolated compounds on human tumor cell lines and nitric oxide production, as well as the pharmacological potentials.

Multi-omics analysis of immune-related microbiome and prognostic model in head and neck squamous cell carcinoma.

OBJECTIVES: The aim of our study is to explore the transcriptional and microbial characteristics of head and neck cancer's immune phenotypes using a multi-omics approach. MATERIALS AND METHODS: Employing TCGA data, we analyzed head and neck squamous cell carcinoma (HNSCC) immune cells with CIBERSORT and identified differentially expressed genes using DESeq2. Microbial profiles, obtained from the TCMA database, were analyzed using LEfSe algorithm to identify differential microbes in immune cell infiltration (ICI) subgroups. Random Forest algorithm and deep neural network (DNN) were employed to select microbial features and developed a prognosis model. RESULTS: We categorized HNSCC into three immune subtypes, finding ICI-2 with the worst prognosis and distinct microbial diversity. Our immune-related microbiome (IRM) model outperformed the TNM staging model in predicting survival, linking higher IRM model scores with poorer prognosis, and demonstrating clinical utility over TNM staging. Patients categorized as low-risk by the IRM model showed higher sensitivity to cisplatin and sorafenib treatments. CONCLUSIONS: This study offers a comprehensive exploration of the ICI landscape in HNSCC. We provide a detailed scenario of immune regulation in HNSCC and report a correlation between differing ICI patterns, intratumor microbiome, and prognosis. This research aids in identifying prime candidates for optimizing treatment strategies in HNSCC. CLINICAL RELEVANCE: This study revealed the microbial signatures associated with immunophenotyping of HNSCC and further found the microbial signatures associated with prognosis. The prognostic model based on IRM microbes is helpful for early prediction of patient prognosis and assisting clinical decision-making.