Insights into the oral microbiota in human systemic cancers.

The oral cavity stands as one of the pivotal interfaces facilitating the intricate interaction between the human body and the external environment. The impact of diverse oral microorganisms on the emergence and progression of various systemic cancers, typified by oral cancer, has garnered increasing attention. The potential pathogenicity of oral bacteria, notably the anaerobic Porphyromonas gingivalis and Fusobacterium nucleatum, has been extensively studied and exhibits obvious correlation with different carcinoma types. Furthermore, oral fungi and viruses are closely linked to oropharyngeal carcinoma. Multiple potential mechanisms of oral microbiota-induced carcinogenesis have been investigated, including heightened inflammatory responses, suppression of the host immune system, influence on the tumor microenvironment, anti-apoptotic activity, and promotion of malignant transformation. The disturbance of microbial equilibrium and the migration of oral microbiota play a pivotal role in facilitating oncogenic functions. This review aims to comprehensively outline the pathogenic mechanisms by which oral microbiota participate in carcinogenesis. Additionally, this review delves into their potential applications in cancer prevention, screening, and treatment. It proves to be a valuable resource for researchers investigating the intricate connection between oral microbiota and systemic cancers.

Causal relationships between modifiable risk factors and polycystic ovary syndrome: a comprehensive Mendelian randomization study.

Background: Polycystic Ovary Syndrome (PCOS) is a heritable condition with an as yet unclear etiology. Various factors, such as genetics, lifestyle, environment, inflammation, insulin resistance, hyperandrogenism, iron metabolism, and gut microbiota, have been proposed as potential contributors to PCOS. Nevertheless, a systematic assessment of modifiable risk factors and their causal effects on PCOS is lacking. This study aims to establish a comprehensive profile of modifiable risk factors for PCOS by utilizing a two-sample Mendelian Randomization (MR) framework. Methods: After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Results: We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL, phospholipids in very large HDL, triglycerides in very large HDL, the genus Oscillibacter, the genus Alistipes, the genus Ruminiclostridium 9, the class Mollicutes, and the phylum Tenericutes, showed a significant effect on heightening genetic susceptibility of PCOS. In contrast, factors including fasting insulin interaction with body mass index, sex hormone-binding globulin, iron, ferritin, SDF1a, college or university degree, years of schooling, household income, the genus Enterorhabdus, the family Bifidobacteriaceae, the order Bifidobacteriales, the class Actinobacteria, and the phylum Actinobacteria were determined to reduce risk of PCOS. Conclusion: This study innovatively employs the MR method to assess causal relationships between 400 modifiable risk factors and the susceptibility of PCOS risk. It supports causal links between factors like smoking, BMI, and various blood lipid levels and PCOS. These findings offer novel insights into potential strategies for the management and treatment of PCOS.

Hierarchical Porous N-Doped Carbon Particles Derived from ZIF-8 as Highly Efficient H2S Selective Oxidation Catalysts.

In the selective oxidation of H2S, the catalytic activity over N-doped carbon-based catalysts is significantly influenced by the accessibility of active sites and the mass transfer rates of reactant molecules (e.g., H2S and O2) as well as generated sulfur monomers. Therefore, it is crucial for enhancing the initial performance via the controlled synthesis of carbon-based catalysts with highly exposed active sites and unique porous structures. Herein, we reported on an efficient strategy to synthesize nanosized N-doped carbon particles with hierarchical porous structures by directly pyrolyzing an oversaturated NaCl-encapsulated ZIF-8 precursor mixture. The introduction of NaCl not only serves as a pollution-free template to promote the formation of graphitic carbon layers but also acts as an intercalating agent to guide the derivation of hierarchical porous structures, as well as enhances the amount of active nitrogen species in the catalysts. As a result, the as-prepared H-NC800 catalyst shows excellent H2S selective oxidation performance (sulfur formation rate is 794 gsulfur·kgcat-1·h-1), good stability (>80 h), and antiwater vapor properties. The characterization results and DFT calculations indicate the crucial role of pyridinic N in the adsorbing and activating reactant molecules (H2S, O2). Furthermore, nanoscale N-doped carbon particles accelerated the rapid transport of generated sulfur monomers under a hierarchical porous structure. This investigation introduces a distinctive strategy for synthesizing ZIF-8-derived N-doped carbon nanosized with a hierarchical porous structure, while its efficient and stable H2S selective oxidation performance highlights significant potential for practical implementation in the industrial desulfurization process.

LEVA: Using Large Language Models to Enhance Visual Analytics.

Visual analytics supports data analysis tasks within complex domain problems. However, due to the richness of data types, visual designs, and interaction designs, users need to recall and process a significant amount of information when they visually analyze data. These challenges emphasize the need for more intelligent visual analytics methods. Large language models have demonstrated the ability to interpret various forms of textual data, offering the potential to facilitate intelligent support for visual analytics. We propose LEVA, a framework that uses large language models to enhance users' VA workflows at multiple stages: onboarding, exploration, and summarization. To support onboarding, we use large language models to interpret visualization designs and view relationships based on system specifications. For exploration, we use large language models to recommend insights based on the analysis of system status and data to facilitate mixed-initiative exploration. For summarization, we present a selective reporting strategy to retrace analysis history through a stream visualization and generate insight reports with the help of large language models. We demonstrate how LEVA can be integrated into existing visual analytics systems. Two usage scenarios and a user study suggest that LEVA effectively aids users in conducting visual analytics.

Evaluation of Profile Control and Oil Displacement Effect of Starch Gel and Nano-MoS2 Combination System in High-Temperature Heterogeneous Reservoir.

The Henan Oilfield's medium-permeability blocks face challenges such as high temperatures and severe heterogeneity, making conventional flooding systems less effective. The starch gel system is an efficient approach for deep profile control in high-temperature reservoirs, while the nano-MoS2 system is a promising enhanced oil recovery (EOR) technology for high-temperature low-permeability reservoirs. Combining these two may achieve the dual effects of profile control and oil displacement, significantly enhancing oil recovery in high-temperature heterogeneous reservoirs. The basic performance evaluation of the combination system was carried out under reservoir temperature. Displacement experiments were conducted in target blocks under different permeabilities and extreme disparity core flooding to evaluate the combination system's oil displacement effect. Additionally, the displacement effects and mechanisms of the starch gel and nano-MoS2 combination system in heterogeneous reservoirs were evaluated by simulating interlayer and intralayer heterogeneity models. The results show that the single nano-MoS2 system's efficiency decreases with increased core permeability, and its effectiveness is limited in triple and quintuple disparity parallel experiments. After injecting the starch gel-nano-MoS2 combination system, the enhanced oil recovery effect was significant. The interlayer and intralayer heterogeneous models demonstrated that the primary water flooding mainly affected the high-permeability layers, while the starch gel effectively blocked the dominant channels, forcing the nano-MoS2 oil displacement system towards unswept areas. This coordination significantly enhanced oil displacement, with the combination system improving recovery by 15.33 and 12.20 percentage points, respectively. This research indicates that the starch gel and nano-MoS2 combination flooding technique holds promise for enhancing oil recovery in high-temperature heterogeneous reservoirs of Henan Oilfield, providing foundational support for field applications.

OldVisOnline: Curating a Dataset of Historical Visualizations.

With the increasing adoption of digitization, more and more historical visualizations created hundreds of years ago are accessible in digital libraries online. It provides a unique opportunity for visualization and history research. Meanwhile, there is no large-scale digital collection dedicated to historical visualizations. The visualizations are scattered in various collections, which hinders retrieval. In this study, we curate the first large-scale dataset dedicated to historical visualizations. Our dataset comprises 13K historical visualization images with corresponding processed metadata from seven digital libraries. In curating the dataset, we propose a workflow to scrape and process heterogeneous metadata. We develop a semi-automatic labeling approach to distinguish visualizations from other artifacts. Our dataset can be accessed with OldVisOnline, a system we have built to browse and label historical visualizations. We discuss our vision of usage scenarios and research opportunities with our dataset, such as textual criticism for historical visualizations. Drawing upon our experience, we summarize recommendations for future efforts to improve our dataset.

From bacteria to biomedicine: Developing therapies exploiting NAD+ metabolism.

Nicotinamide adenine dinucleotide (NAD+) serves as a critical cofactor in cellular metabolism and redox reactions. Bacterial pathways rely on NAD+ participation, where its stability and concentration govern essential homeostasis and functions. This review delves into the role and metabolic regulation of NAD+ in bacteria, highlighting its influence on physiology and virulence. Notably, we explore enzymes linked to NAD+ metabolism as antibacterial drug targets and vaccine candidates. Moreover, we scrutinize NAD+'s medical potential, offering insights for its application in biomedicine. This comprehensive assessment informs future research directions in the dynamic realm of NAD+ and its biomedical significance.

A tumor microenvironment-associated circRNA predictor for tumor relapse and chemotherapy vulnerability in nasopharyngeal carcinoma.

Accurate risk stratification for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is crucial for prognosis and treatment decisions. Here, we develop a tumor microenvironment-associated circular RNA (circRNA) signature that can stratify LA-NPC patients with different risks of relapse and vulnerability to induction chemotherapy (IC). Relapsed-related circRNAs are identified by comparing expression profiles between patients with and without relapse, followed by quantitative validation in the training cohort (n = 170). A nine-circRNA signature is constructed to classify patients into high-risk and low-risk groups. Low-risk patients have significantly favorable clinical survivals, which is validated in the internal (n = 170) and external (n = 150) cohorts. They are characterized by an immune-active microenvironment and can derive benefits from IC. Meanwhile, high-risk patients characterized with pro-relapse and DNA repair-associated features, are vulnerable to chemoresistance. Overall, the circRNA-based classifier serves as a reliable prognostic tool and might guide chemotherapy decisions for patients with LA-NPC.

Combatting resistance: Understanding multi-drug resistant pathogens in intensive care units.

The escalating misuse and excessive utilization of antibiotics have led to the widespread dissemination of drug-resistant bacteria, posing a significant global healthcare crisis. Of particular concern is the increasing prevalence of multi-drug resistant (MDR) opportunistic pathogens in Intensive Care Units (ICUs), which presents a severe threat to public health and contributes to substantial morbidity and mortality. Among them, MDR ESKAPE pathogens account for the vast majority of these opportunistic pathogens. This comprehensive review provides a meticulous analysis of the current prevalence landscape of MDR opportunistic pathogens in ICUs, especially in ESKAPE pathogens, illuminating their resistance mechanisms against commonly employed first-line antibiotics, including polymyxins, carbapenems, and tigecycline. Furthermore, this review explores innovative strategies aimed at preventing and controlling the emergence and spread of resistance. By emphasizing the urgent need for robust measures to combat nosocomial infections caused by MDR opportunistic pathogens in ICUs, this study serves as an invaluable reference for future investigations in the field of antibiotic resistance.

Steroidal constituents from Solanum nigrum.

Three previously undescribed steroidal constituents including two sterols (1-2) and one pregnane-type steroidal glycoside (6), along with nineteen known ones (3-5, 7-22), were isolated from the 80% alcohol extraction of Solanum nigrum L. Their structures and the absolute configurations were established by analysis of the extensive spectroscopic data (1H/13 NMR, 1H1H COSY, HSQC, HMBC, and NOESY), and/or by comparisons of the experimental electronic circular dichroism (ECD) spectra with those calculated ones by TDDFT method. Further, a MTT assay was applied to demonstrate that compounds 1-4, 6-12, 18, and 22 exhibited significant cytotoxic activities against SW480 cells, and compounds 1-4, 6-14, and 16-22 showed significant cytotoxic activities against Hep3B cells.

A molecular understanding of citrate adsorption on calcium oxalate polyhydrates.

Calcium oxalate precipitation is a common pathological calcification in the human body, whereby crystallite morphology is influenced by the chelating properties of biological ions such as citrate. It has been suggested that citrate could steer oxalate formation towards its dihydrated form and away from the monohydrated form, which was identified as a major cause for disease. To assess the influence of the citrate ion on the resulting calcium oxalate, surface energies were calculated at the dispersion-corrected density functional level of theory for both monohydrated and dihydrated calcium oxalate. Different adsorption geometries were considered by varying the attacking angle of citrate as well as by considering the citrate ion on top of an adsorbed water layer or penetrating the water layer. The obtained results were compared to ab initio molecular dynamics simulations and experimental scanning electron microscope images. A strong preference for citrate adsorption on calcium oxalate dihydrate was observed, suggesting medical applications for the treatment of such pathological calcifications.

Visual Explanation for Open-domain Question Answering with BERT.

Open-domain question answering (OpenQA) is an essential but challenging task in natural language processing that aims to answer questions in natural language formats on the basis of large-scale unstructured passages. Recent research has taken the performance of benchmark datasets to new heights, especially when these datasets are combined with techniques for machine reading comprehension based on Transformer models. However, as identified through our ongoing collaboration with domain experts and our review of literature, three key challenges limit their further improvement: (i) complex data with multiple long texts, (ii) complex model architecture with multiple modules, and (iii) semantically complex decision process. In this paper, we present VEQA, a visual analytics system that helps experts understand the decision reasons of OpenQA and provides insights into model improvement. The system summarizes the data flow within and between modules in the OpenQA model as the decision process takes place at the summary, instance and candidate levels. Specifically, it guides users through a summary visualization of dataset and module response to explore individual instances with a ranking visualization that incorporates context. Furthermore, VEQA supports fine-grained exploration of the decision flow within a single module through a comparative tree visualization. We demonstrate the effectiveness of VEQA in promoting interpretability and providing insights into model enhancement through a case study and expert evaluation.

Chemotherapy-Induced Senescence Reprogramming Promotes Nasopharyngeal Carcinoma Metastasis by circRNA-Mediated PKR Activation.

Senescence is associated with tumor metastasis and chemotherapy resistance, yet the mechanisms remain elusive. Here, it is identified that nasopharyngeal carcinoma (NPC) patients who developed distant metastasis are characterized by senescence phenotypes, in which circWDR37 is a key regulator. CircWDR37 deficiency limits cisplatin or gemcitabine-induced senescent NPC cells from proliferation, migration, and invasion. Mechanistically, circWDR37 binds to and dimerizes double-stranded RNA-activated protein kinase R (PKR) to initiate PKR autophosphorylation and activation. Independent of its kinase activity, phosphorylated PKR induces I-kappaB kinase beta (IKKß) phosphorylation, binds to and releases RELA from NF-κB inhibitor alpha (IκBα) to trigger nuclear factor kappa B (NF-κB) activation, thereby stimulating cyclin D1 (CCND1) and senescence-associated secretory phenotype component gene transcription in a circWDR37-dependent manner. Low circWDR37 levels correlate with chemotherapy response and favorable survival in NPC patients treated with gemcitabine or cisplatin induction chemotherapy. This study uncovers a new mechanism of circWDR37 activated PKR in senescence-driven metastasis and provides appealing therapeutic targets in NPC.

Non-coding RNA-mediated high expression of SFXN3 as a prognostic biomarker associated with paclitaxel resistance and immunosuppressive microenvironment in head and neck cancer.

Chemoresistance is the leading cause of poor prognosis in head and neck squamous cell carcinoma (HNSC); however, promising biomarkers to identify patients for stratified chemotherapy are lacking. Sideroflexin 3 (SFXN3) is an important mitochondrial serine transporter during one-carbon metabolism, which is involved in the proliferation of cancer cells. However, the specific role of SFXN3 in HNSC remains unknown. In this study, we performed expression and survival analysis for SFXN3 in pan-cancer using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) and found that SFXN3 served as a potential oncogene in HNSC. Notably, SFXN3 expression was found to be positively associated with enriched tumor-infiltrating macrophages, other immune suppressive cells, and immune checkpoint expression and resistance to paclitaxel. Gene, clinical, and immune variables included in the univariate and multivariate analyses showed that SFXN3 expression was an independent risk factor. Moreover, the LINC01270/hsa-miR-29c-3p/SFXN3 axis was identified as the most likely upstream non-coding RNA-related pathway of SFXN3 in HNSC using bioinformatic analysis, expression analysis, correlation analysis, and survival analysis. Taken together, our findings demonstrated that a non-coding RNA-mediated high expression of SFXN3 is a prognostic biomarker and is associated with the immunosuppressive microenvironment in HNSC.

CircIPO7 Promotes Nasopharyngeal Carcinoma Metastasis and Cisplatin Chemoresistance by Facilitating YBX1 Nuclear Localization.

PURPOSE: Cisplatin-based chemotherapy effectively improves the distant-metastasis control in nasopharyngeal carcinoma (NPC), but approximately 30% of patients develop treatment failure due to chemoresistance. However, the underlying mechanisms remain poorly understood. EXPERIMENTAL DESIGN: Circular RNA (circRNA) sequencing data were used to identify metastasis-specific circRNAs and the expression of circIPO7 was validated in NPC tissues as well as NPC cell lines by qRT-PCR. The whole transcriptional profile upon circIPO7 knockdown was applied to explore the biological function and regulatory mechanism, which were further confirmed by in vitro and in vivo metastasis/chemosensitivity assays. We also evaluated the value of circIPO7 expression in predicting NPC metastasis and cisplatin chemoresistance by analyzing a cohort of 183 NPC patients. RESULTS: In this study, circIPO7, a novel circRNA, is found to be specifically overexpressed in NPC patients with distant metastasis. Knockdown of circIPO7 in NPC cells suppresses their metastasis and increases sensitivity to cisplatin treatment in vitro and in vivo. Mechanistically, circIPO7 binds to Y-box binding protein-1 (YBX1) protein in the cytoplasm and facilitates its phosphorylation at serine 102 (p-YBX1S102) by the kinase AKT, which further promotes YBX1 nuclear translocation and activates FGFR1, TNC, and NTRK1 transcription. Clinically, higher circIPO7 expression indicates unfavorable distant metastasis-free survival in NPC patients given cisplatin-based chemotherapy. CONCLUSIONS: Altogether, this study identifies oncogenic circIPO7 as a prognostic marker after cisplatin-based chemotherapy and as a potential therapeutic target for overcoming metastasis and chemoresistance in NPC.

Ultrasound-Assisted Extraction of Anthocyanins from Malus 'Royalty' Fruits: Optimization, Separation, and Antitumor Activity.

Red Malus 'Royalty' fruits are rich in anthocyanins. This study aimed to obtain the optimal parameters for the extraction and separation of anthocyanins from Malus 'Royalty' fruits and to evaluate the inhibitory effect of the enriched anthocyanin fraction on gastric cancer cells. Ultrasonic-assisted extraction was used for the extraction of the anthocyanins of Malus 'Royalty' fruit, and the extraction results showed that the optimum parameters were an extraction temperature of 20 °C, a solid-liquid ratio of 1:6 (g/mL), ethanol and formic acid contents of 70% and 0.4%, respectively, an extraction time of 40 min, and an ultrasonic power of 300 W. The optimum extraction parameters to achieve the highest anthocyanin yield by a single-factor experiment coupled with response surface methodology were identified. The separation results showed that the AB-8 macroporous resin was a better purifying material, with 60% ethanol as an adsorbent, and the adsorption-desorption equilibrium times were 6 h and 1 h, respectively. Cyanidin-3-galactoside was the main body composition separation of anthocyanins by a high-performance liquid chromatography-diode array detector. The antitumor activity results showed that the anthocyanins of Malus 'Royalty' fruits have a significant inhibitory effect on the gastric cancer cell line BGC-803. The in vitro cell viability test of CCK-8 showed that the inhibitory effect on tumor cells was more significant with the increased anthocyanin concentration, with a half maximal inhibitory concentration (IC50) value of 105.5 µg/mL. The cell morphology was observed by an inverted microscope, and it was found that the backbone of BGC-803 treated with a high concentration of anthocyanins was disintegrated and the nucleoplasm was concentrated. The mechanism of apoptosis was analyzed by Western blotting, and the results showed that with increasing anthocyanin concentration in the medium, the expression levels of the proapoptotic proteins Bax and Bak increased, and the expression levels of the antiapoptotic proteins Bcl-2 and Bcl-xL decreased, which coordinated the regulation of cell apoptosis. This research suggests that the enriched anthocyanin fraction from Malus 'Royalty' fruits have potential antitumor and adjuvant therapeutic effects on gastric cancer.

How the Color Fades From Malus halliana Flowers: Transcriptome Sequencing and DNA Methylation Analysis.

The flower color of many horticultural plants fades from red to white during the development stages, affecting ornamental value. We selected Malus halliana, a popular ornamental species, and analyzed the mechanisms of flower color fading using RNA sequencing. Forty-seven genes related to anthocyanin biosynthesis and two genes related to anthocyanin transport were identified; the expression of most of these genes declined dramatically with flower color fading, consistent with the change in the anthocyanin content. A number of transcription factors that might participate in anthocyanin biosynthesis were selected and analyzed. A phylogenetic tree was used to identify the key transcription factor. Using this approach, we identified MhMYB10 as directly regulating anthocyanin biosynthesis. MhMYB10 expression was strongly downregulated during flower development and was significantly positively related to the expression of anthocyanin biosynthetic genes and anthocyanin content in diverse varieties of Malus. To analyze the methylation level during flower development, the MhMYB10 promoter sequence was divided into 12 regions. The methylation levels of the R2 and R8 increased significantly as flower color faded and were inversely related to MhMYB10 expression and anthocyanin content. Therefore, we deduce that the increasing methylation activities of these two regions repressed MhMYB10 expression.

Ice Nucleation of Confined Monolayer Water Conforms to Classical Nucleation Theory.

We confirmed that monolayer water confined by parallel graphene sheets spontaneously crystallizes from a structurally and dynamically heterogeneous liquid phase under moderate supercooling via direct molecular dynamics simulation. Square-lattice-like geometric order is observed at the early stage of nucleation and is preserved during the entire nucleus growth process. The diffusion coefficient and free energy profile in the cluster space extracted from a Bayesian trajectory analysis agree well with the classical nucleation theory (CNT) prediction and yield thermodynamic quantities exhibiting linear temperature dependence. The effectiveness of maximum cluster size as the descriptor of ice nucleation dynamics in the CNT framework can be attributed to the dynamical time scale decoupling and strong structural pattern dependence of density fluctuation in the liquid phase.