Associations between polychlorinated biphenyls and cancer risk among type 2 diabetes: The modifying effects of lifestyle.

A growing percentage of diabetes-related deaths has been attributed to cancer, with environmental factors playing important contributions. Thus, we studied the potential relationship between endocrine disruptors polychlorinated biphenyls (PCBs) and cancer risk in diabetes. We aimed to evaluate the association between serum seven indicator-PCB (PCB-28/52/101/118/138/153/180) levels and incident cancer, and further explore the possible modifying role of lifestyle. A total of 2806 type 2 diabetes mellitus (T2DM) cases were included from the Dongfeng-Tongji cohort at the baseline in 2008 and tracked until December 2018, and 320 incident cancers were identified during about 10-year follow-up. Cox proportional hazards models and competing risk regression models were used to reveal associations of baseline concentrations of PCBs with total cancer and specific cancer, respectively. Lifestyle score was determined by body mass index, waist circumference, physical activity, smoking, alcohol drinking, and diet. Each interquartile range (IQR) increment of non-dioxin-like PCBs (NDL-PCBs) generated an 8%-30% increase in cancer incidence. Individuals in the highest quartile for PCB-52, PCB-101, PCB-138, and lowly chlorinated PCBs had 1.44- to 1.68-fold higher cancer risk compared to those in the lowest quartile. Restricted cubic spline analyses and the quantile g-computation model showed similar results. Significant interactions were found between PCBs and fasting blood glucose or simplified insulin resistance assessment indicators. NDL-PCBs were positively and significantly associated with gastrointestinal cancer and respiratory cancer, especially with liver cancer, colorectal cancer, and lung cancer. Higher PCBs showed a significant increase in total cancer risk among participants with an unhealthy lifestyle, however, no associations were observed in those with a relatively healthy lifestyle (Pinteraction < 0.05). Our findings indicated an increased cancer risk associated with NDL-PCBs, highlighted the role of a healthy lifestyle in potentially reducing adverse impact, and provided preliminary data for environmental and public health interventions to alleviate the risk of cancer among diabetes.

[Predictive Model for O3 in Shanghai Based on the KZ Filtering Technique and LSTM].

In this study, a Kolmogorov-Zurbenko （KZ） filter was proposed to decompose the original ozone （O3） sequence to improve the accuracy of ozone long-term series prediction and select relevant meteorological features. Furthermore, the enhanced maximal minimal redundancy （mRMR） feature selection technique was combined with the support vector regression （SVR） approach to select the most illuminating meteorological features. Subsequently, from May to August 2023, during high ozone concentration periods, a long short-term memory network （LSTM） was utilized to assess and predict high ozone concentration periods at the monitoring stations of Jingan （urban area）, Pudong-Chuansha （suburban area）, and Dianshan Lake （suburban area） in Shanghai. The results showed that pressure, temperature, humidity, boundary layer height, and wind direction were the best combinations of O3 baseline and short-term components, as chosen by feature screening. The R2 values for Jingan Station, Pudong-Chuansha Station, and Dianshan Lake Station were 0.86, 0.83, and 0.85, respectively. The RMSE values were 18.26, 18.74, and 20.02 µg·m-3, respectively. These findings suggest that decomposing the original O3 sequence improved the prediction accuracy of ozone concentrations. Additionally, as indicated by the R2 and RMSE values found for every monitoring station, feature screening preserved the model's predictive performance.

An innovative strategy harnessing self-activating CAR-NK cells to mitigate TGF-ß1-driven immune suppression.

The dysfunction of natural killer (NK) cells, mediated by transforming growth factor ß1 (TGFß1) within the tumor microenvironment, impedes antitumor therapy and contributes to poor clinical outcomes. Our study introduces self-activating chimeric antigen receptor (CAR)-NK cells that block TGFß1 signaling by releasing a specifically designed peptide, P6, which targets mesothelin in pancreatic tumors. P6 originates from the interaction sites between TGFß1 and TGFß receptor 1 and effectively disrupts TGFß1's inhibitory signaling in NK cells. Our analysis demonstrates that P6 treatment interrupts the SMAD2/3 pathway in NK cells, mitigating TGFß1-mediated suppression of NK cell activity, thereby enhancing their metabolic function and cytotoxic response against pancreatic tumors. These CAR-NK cells exhibit potent antitumor capabilities, as evidenced in spheroid cultures with cancer-associated fibroblasts and in vivo mouse models. Our approach marks a substantial advancement in overcoming TGFß1-mediated immune evasion, offering a promising avenue for revolutionizing cancer immunotherapy.

The effects of optimized microstructured surfaces on bond strength and durability of NPJ-printed zirconia.

OBJECTIVES: This study was to investigate the effects of optimized microstructured surfaces on bond strength and bond durability of the latest nanoparticle jetting (NPJ)-printed zirconia. METHODS: Zirconia microstructured surfaces with different geometries and void volume were analyzed through three-dimensional finite element analysis for surface micromorphology optimization. Zirconia disks and cylinders were additively manufactured by an NPJ 3D printer (N = 128). They were randomly divided into four groups based on surface micromorphology optimization and airborne-particle abrasion (APA) treatment before they were bonded using 10-methacryloloxydecyl dihydrogen phosphate (MDP) containing resin cement (Clearfil SA luting cement). The shear bond strengths (SBSs) were tested before and after 10,000 thermocycles and were analyzed by one-way ANOVA analysis. Failure modes were determined by optical microscopy. Zirconia surfaces were analyzed with X-ray diffraction, scanning electron microscopy, and three-dimensional interference microscopy. RESULTS: The optimized microstructured surface was characterized by circular microstructures with 60 % void volume, about 20 µm of depths, about 10 µm of undercuts, and consistent beam widths. The optimized microstructured surface combined with APA treatment and MDP-containing resin cement possessed the highest SBSs both before and after thermocycling aging (P＜0.05). The greater reductions of zirconia bond strengths occurred when the zirconia were not treated with APA (P＜0.05). SIGNIFICANCE: The optimized microstructured zirconia surface with circular microstructures and 60 % void volume fabricated by the latest NPJ printing technology could greatly enhance the zirconia bond strength and durability in combination with APA treatment and application of MDP-containing resin cement, which might be promising for adhesively bonded indirect restorations of NPJ-printed zirconia.

Association between phthalates exposure and all-cause mortality among diabetic cases: A prospective study.

The aim of this study was to explore the association between phthalates (PAEs) exposure and all-cause mortality among diabetic cases, and potential molecular mechanisms of the effect. We followed 2806 diabetes cases from 2008 to the end of 2018 based on the Dongfeng-Tongji study, of which 446 cases died. We measured serum levels of six PAEs (DMP, DEP, DiBP, DnBP, BBP, and DEHP). Cox models were used to investigate the associations between PAEs and all-cause mortality. Genes related to PAEs are obtained from the Comparative Toxicogenomics Database. We constructed polygenic scores for sex hormone-binding globulin (SHBG) and testosterone, and functional SNPs for IL-6, PPARG, and GPX1 from genotyping data, and further analyzed the environment-gene interactions. The positive associations of PAEs (DMP, DiBP, DnBP, DEHP) with mortality were only observed in males but not in females. Comparing with the extreme quartile 1, the HRs (95% CI) for quartile 4 were 1.63 (0.17, 2.26) for DMP, 1.82 (1.29, 2.56) for DiBP, 1.68 (1.18, 2.40) for DnBP, 1.66 (1.17, 2.36) for DEHP. Enrichment analysis showed that PAEs-related genes were mainly associated with hormones and IL-6-related pathways. Genetic variants of SHBG, testosterone, and IL-6 modified the association between PAEs mixture and all-cause mortality. PAEs exposure are associated with all-cause mortality among diabetic cases, and PAE exposure increases the risk of all-cause mortality only in males. Effects on the hormonal system and IL6-related pathways may be potential mechanisms.

Antifungal Activity of Phloroglucinol Derivatives against Botrytis cinerea and Monilinia fructicola.

Naturally derived compounds show promise as treatments for microbial infections. Polyphenols, abundantly found in various plants, fruits, and vegetables, are noted for their physiological benefits including antimicrobial effects. This study introduced a new set of acylated phloroglucinol derivatives, synthesized and tested for their antifungal activity in vitro against seven different pathogenic fungi. The standout compound, 3-methyl-1-(2,4,6-trihydroxyphenyl) butan-1-one (2b), exhibited remarkable fungicidal strength, with EC50 values of 1.39 µg/mL against Botrytis cinerea and 1.18 µg/mL against Monilinia fructicola, outperforming previously screened phenolic compounds. When tested in vivo, 2b demonstrated effective antifungal properties, with cure rates of 76.26% for brown rot and 83.35% for gray mold at a concentration of 200 µg/mL, rivaling the commercial fungicide Pyrimethanil in its efficacy against B. cinerea. Preliminary research suggests that 2b's antifungal mechanism may involve the disruption of spore germination, damage to the fungal cell membrane, and leakage of cellular contents. These results indicate that compound 2b has excellent fungicidal properties against B. cinerea and holds potential as a treatment for gray mold.

Comparison of structural characteristics and anti-tumor activity of two alkali extracted peach gum arabinogalactan.

Two polysaccharides, PGP-90 and PGP-100 (molecular weights of 7.59 × 102 kDa and 10.48 × 102 kDa, respectively), were isolated from Peach gum using alkaline electrolyte water as an extraction solution. Structural characterization showed that PGP-90 and PGP-100 are AG-II arabinogalactans with ß-D-(1 â†’ 6)-Galp as the main chain and 1 â†’ 3 Araf and 1 â†’ 5 Araf branched chains at O-3 and O-4 positions. Animal experiments showed that PGP-90 and PGP-100 significantly improved immune function, enhance the proliferative capacity of lymphocytes and phagocytosis of peritoneal macrophages, and regulated the ratio of lymphocyte subpopulations in S180 tumor-bearing mice. Meanwhile, PGP-90 and PGP-100 promoted the secretion of cytokines (TNF-α, IFN-γ, and IL-2) by activated macrophages and blocked apoptosis at the G1 phase, resulting in tumor suppression rates of 40.80 % and 46.30 % (100 mg/kg), respectively, with PGP-100 demonstrating stronger in vivo anti-tumor activity. The above experimental results indicate that Peach gum polysaccharides have the potential to be functional anti-tumor agents.

Genetic predisposition to impaired beta-cell function modifies the association between serum pyrethroid levels and the risk of type 2 diabetes: A gene-environment interaction study.

Previous studies suggested that pyrethroid exposure was associated with elevated type 2 diabetes (T2D) risk, while it remains uncertain whether genetic predisposition modifies this association. A nested case-control study within the prospective Dongfeng-Tongji cohort comprised 1832 T2D cases, age- (±5 years) and sex-matched controls with qualified genotyping data. Serum pyrethroids were measured by gas chromatography-tandem mass spectrometry. Overall diabetes-related genetic risk score (GRS) or pathway-specific GRS, including unweighted GRSs (uGRS) and weighted GRSs (wGRS), was developed by genetic variants identified in Asian populations. Higher overall diabetes-related GRS and GRS specific to the pathway of impaired beta cell function (Beta-cell GRS) were associated with a higher incident T2D risk. Beta-cell uGRS significantly modified the association of serum permethrin (Pinteraction=0.04) and deltamethrin (Pinteraction=0.01) with T2D. Specifically, for each doubling increase in serum deltamethrin, the odds ratios (ORs) (95 % confidence intervals [CIs]) for T2D were 1.23 (0.98-1.56) and 0.91 (0.77-1.07) in the highest and lowest Beta-cell uGRS group, as well as 1.23 (1.02-1.47) and 0.95 (0.78-1.15) for Beta-cell wGRS group, respectively. When considering jointly, those with the highest deltamethrin levels and highest Beta-cell GRS had a substantially higher T2D risk, compared with the reference group (OR for uGRS: 3.79 [95 % CI: 2.03-7.07], Pinteraction=0.03 and 3.23 [95 % CI: 1.78-5.87], Pinteraction=0.05 for wGRS). Our findings suggested that genetic susceptibility to impaired beta-cell function should be considered for T2D prevention targeting pyrethroid exposure, particularly deltamethrin.

Structural characteristics and anti-tumor activity of alcohol-precipitated polysaccharides from Cordyceps militaris under different ethanol concentrations.

Six Cordyceps militaris polysaccharides (named CMP-1, CMP-2, CMP-3, CMP-4, CMP-9, and CMP-A) were obtained by fractional alcohol precipitation. The experimental results showed that the six Cordyceps militaris polysaccharides had similar chemical composition and spectral features, and different molecular weights, monosaccharide compositions and anti-tumor activities. Purification of CMP-9 yielded the small molecule polysaccharide LMW-CMP (3.06 kDa). Structural experiments showed that LMW-CMP is an α-glucan with (1 â†’ 4)-α-D-Glcp as the main chain and a glucose branched chain attached at the O-6 position. The results of cell experiments showed that LMW-CMP could effectively inhibit the growth and proliferation of HepG2 cells, activate the downstream NF-κB signaling pathway through the MAPK pathway to induce apoptosis of HepG2 cells, and block apoptosis at the G1 phase. Animal experiments showed that LMW-CMP inhibited the proliferation of tumor cells in H22 tumor-bearing mice by improving the state of immune organs, increasing the activity of immune cells and cytokine levels in the body, and regulating the distribution of lymphocyte subpopulations, with a tumor inhibition rate of 45.70 % (200 mg/kg).

Prenylated Flavonoids Isolated from the Root of Sophora flavescens as Potent Antifungal Agents against Botrytis cinerea.

Sophora flavescens, a traditional Chinese herb, produces a wide range of secondary metabolites with a broad spectrum of biological activities. In this study, we isolated six isopentenyl flavonoids (1-6) from the roots of S. flavescens and evaluated their activities against phytopathogenic fungi. In vitro activities showed that kurarinone and sophoraflavanone G displayed broad spectrum and superior activities, among which sophoraflavanone G displayed excellent activity against tested fungi, with EC50 values ranging from 4.76 to 13.94 µg/mL. Notably, kurarinone was easily purified and showed potential activity against Rhizoctonia solani, Botrytis cinerea, and Fusarium graminearum with EC50 values of 16.12, 16.55, and 16.99 µg/mL, respectively. Consequently, we initially investigated the mechanism of kurarinone against B. cinerea. It was found that kurarinone disrupted cell wall components, impaired cell membrane integrity, increased cell membrane permeability, and affected cellular energy metabolism, thereby exerting its effect against B. cinerea. Therefore, kurarinone is expected to be a potential candidate for the development of plant fungicides.

Design, synthesis and antimicrobial activity of novel berberine derivatives.

BACKGROUND: The threats to the safety of humans and the environment and the resistance of agricultural chemicals to plant pathogenic fungi and bacteria highlight an urgent need to find safe and efficient alternatives to chemical fungicides and bactericides. In this study, a series of Berberine (BBR) derivatives were designed, synthesized and evaluated for in vitro and in vivo antimicrobial activity against plant pathogenic fungi and bacteria. RESULTS: Bioassay results indicated that compounds A11, A14, A20, A21, A22, A25, A26, E1, E2, E3, Z1 and Z2 showed high inhibitory activity against Sclerotinia sclerotiorum and Botrytis cinerea. Especially, A25 showed a broad spectrum and the highest antifungal activity among these compounds. Its EC50 value against Botrytis cinerea was 1.34 µg mL-1. Compound E6 possessed high inhibitory activity against Xanthomonas oryzae and Xanthomonas Campestris, with MIC90 values of 3.12 µg mL-1 and 1.56 µg mL-1. A Topomer CoMFA model was generated for 3D-QSAR studies based on anti-B. cinerea effects, with high predictive accuracy, showed that the addition of an appropriate substituent group at the para-position of benzyl of BBR derivatives could effectively improve the anti-B. cinerea activity. In addition, compound A25 could significantly inhibit the spore germination of Botrytis cinerea at low concentration, and compound F4 exhibited remarkable curative and protective efficiencies on rice bacterial leaf blight. CONCLUSION: This study indicates that the BBR derivatives are hopeful for further exploration as the lead compound with novel antimicrobial agents. © 2024 Society of Chemical Industry.

Generalized Quantum Fluctuation Theorem for Energy Exchange.

The nonequilibrium fluctuation relation is a cornerstone of quantum thermodynamics. It is widely believed that the system-bath heat exchange obeys the famous Jarzynski-Wójcik fluctuation theorem. However, this theorem is established in the Born-Markovian approximation under the weak-coupling condition. Via studying the energy exchange between a harmonic oscillator and its coupled bath in the non-Markovian dynamics, we establish a generalized quantum fluctuation theorem for energy exchange being valid for arbitrary coupling strength. The Jarzynski-Wójcik fluctuation theorem is recovered in the weak-coupling limit. We also find the average energy exchange exhibits rich nonequilibrium characteristics when different numbers of system-bath bound states are formed, which suggests a useful way to control the quantum heat. Deepening our understanding of the fluctuation relation in quantum thermodynamics, our result lays the foundation to design high-efficiency quantum heat engines.

Three-Dimensional Integrated Synaptic Devices Based on a Silver-Cluster Conduction Mechanism with High Thermostability.

During the operation of synaptic devices based on traditional conductive filament (CF) models, the formation and dissolution of CFs are usually uncertain. Moreover, when the device is operated for a long time, the CFs may dissolve due to both the Joule heat generated by the device itself and the thermal coupling between the devices. These problems seriously reduce the reliability and stability of the synaptic device. Here, an artificial synapse device based on polyimide-molybdenum disulfide quantum dot (MoS2 QD) nanocomposites is presented. Research has shown that MoS2 QDs doped into the active layer can effectively induce the reduction of Ag ions into Ag atoms, leading to the formation of Ag clusters and thereby achieving control over the growth of the CFs. Therefore, the device is capable of stably realizing various basic synaptic functions. Moreover, the long-term potentiation/long-term depression (LTP/LTD) of this device shows good linearity. In addition, due to the change in the shape of the CFs, the highly integrated devices with a three-dimensional (3D) stacked structure can operate normally even in a high-temperature environment of 110 °C. Finally, the synaptic characteristics of the devices on learning and inference tests show that their recognition rates are approximately 90.75% (room temperature) and 90.63% (110 °C).

Effect of Cotesia ruficrus Parasitization on Diversity and Community Composition of Intestinal Bacteria in Spodoptera frugiperda.

Parasitoids have the potential to alter the gut microbiota of their host insects post-parasitization, thereby influencing the host's physiological functions and creating a more favorable environment for the survival of the parasitoid's progeny. Cotesia ruficrus is a native enemy of the important invasive fall armyworm (FAW) pest, Spodoptera frugiperda, in China, exhibiting significant pest control capabilities. To investigate the impact of C. ruficrus on the gut bacteria of FAW caterpillars following parasitism, we used 16S rRNA sequencing technology to analyze the diversity and richness of gut bacteria in both long-term laboratory and short-term laboratory FAW caterpillars. The results revealed Enterococcus as the predominant bacteria across all treatments, while no significant differences were observed in the diversity and richness of gut bacteria between non-parasitized and parasitized long-term laboratory FAW caterpillars. Similarly, while the diversity of gut bacteria in non-parasitized and parasitized short-term laboratory FAWs showed no significant variance, a marked discrepancy in richness was noted. Moreover, the richness of gut bacteria in short-term laboratory FAW caterpillars surpassed that of their long-term laboratory counterparts. In addition, it was found that Corynebacterium existed only in the intestinal tract of FAW caterpillars that were parasitized by C. ruficrus. These results substantiate that C. ruficrus parasitization can alter the gut microbiota of FAW caterpillars, providing valuable insights into the interplay between gut microbiota and the dynamics of parasitoid-host interactions.

S-adenosyl-L-methionine supplementation alleviates aortic dissection by decreasing inflammatory infiltration.

Methionine, an indispensable amino acid crucial for dietary balance, intricately governs metabolic pathways. Disruption in its equilibrium has the potential to heighten homocysteine levels in both plasma and tissues, posing a conceivable risk of inducing inflammation and detriment to the integrity of vascular endothelial cells. The intricate interplay between methionine metabolism, with a specific focus on S-adenosyl-L-methionine (SAM), and the onset of thoracic aortic dissection (TAD) remains enigmatic despite acknowledging the pivotal role of inflammation in this vascular condition. In an established murine model induced by ß-aminopropionitrile monofumarate (BAPN), we delved into the repercussions of supplementing with S-adenosyl-L-methionine (SAM) on the progression of TAD. Our observations uncovered a noteworthy improvement in aortic dissection and rupture rates, accompanied by a marked reduction in mortality upon SAM supplementation. Notably, SAM supplementation exhibited a considerable protective effect against BAPN-induced degradation of elastin and the extracellular matrix. Furthermore, SAM supplementation demonstrated a robust inhibitory influence on the infiltration of immune cells, particularly neutrophils and macrophages. It also manifested a notable reduction in the inflammatory polarization of macrophages, evident through diminished accumulation of MHC-IIhigh macrophages and reduced expression of inflammatory cytokines such as IL1ß and TNFα in macrophages. Simultaneously, SAM supplementation exerted a suppressive effect on the activation of CD4 + and CD8 + T cells within the aorta. This was evidenced by an elevated proportion of CD44- CD62L + naïve T cells and a concurrent decrease in CD44 + CD62L- effector T cells. In summary, our findings strongly suggest that the supplementation of SAM exhibits remarkable efficacy in alleviating BAPN-induced aortic inflammation, consequently impeding the progression of thoracic aortic dissection.

LncRNA DANCR promotes macrophage lipid accumulation through modulation of membrane cholesterol transporters.

The progression of atherosclerosis (AS), the pathological foundation of coronary artery disease (CAD), is featured by massive lipid deposition in the vessel wall. LncRNAs are implicated in lipid disorder and AS, whereas the specific role of lncRNA DANCR in atherogenesis remains unknown. Here, we demonstrated that DANCR promotes macrophage lipid accumulation by regulating the expression of membrane cholesterol transport proteins. qPCR showed that compared to control groups, CAD patients and atherosclerotic mice had higher DANCR levels. Treating human THP-1 macrophages and mouse RAW264.7 macrophages with ox-LDL significantly upregulated the expression levels of DANCR. Oil Red O staining showed that the silence of DANCR robustly reduced, while overexpression of DANCR significantly increased the numbers and size of lipid droplets in ox-LDL-treated THP-1 macrophages. In contrast, the opposite phenomena were observed in DANCR overexpressing cells. The expression of ABCA1, ABCG1, SR-BI, and NBD-cholesterol efflux was increased obviously by DANCR inhibition and decreased by DANCR overexpression, respectively. Furthermore, transfection with DANCR siRNA induced a robust decrease in the levels of CD36, SR-A, and Dil-ox-LDL uptake, while DANCR overexpression amplified the expression of CD36, SR-A and the uptake of Dil-ox-LDL in lipid-laden macrophages. Lastly, we found that the effects of DANCR on macrophage lipid accumulation and the expression of membrane cholesterol transport proteins were not likely related to miR-33a. The present study unraveled the adverse role of DANCR in foam cell formation and its relationship with cholesterol transport proteins. However, the competing endogenous RNA network underlying these phenomena warrants further exploration.

Flavokawain C inhibits glucose metabolism and tumor angiogenesis in nasopharyngeal carcinoma by targeting the HSP90B1/STAT3/HK2 signaling axis.

OBJECTIVE: Over the past decade, heat shock protein 90 (HSP90) inhibitors have emerged as promising anticancer drugs in solid and hematological malignancies. Flavokawain C (FKC) is a naturally occurring chalcone that has been found to exert considerable anti-tumor efficacy by targeting multiple molecular pathways. However, the efficacy of FKC has not been studied in nasopharyngeal carcinoma (NPC). Metabolic abnormalities and uncontrolled angiogenesis are two important features of malignant tumors, and the occurrence of these two events may involve the regulation of HSP90B1. Therefore, this study aimed to explore the effects of FKC on NPC proliferation, glycolysis, and angiogenesis by regulating HSP90B1 and the underlying molecular regulatory mechanisms. METHODS: HSP90B1 expression was analyzed in NPC tissues and its relationship with patient's prognosis was further identified. Afterward, the effects of HSP90B1 on proliferation, apoptosis, glycolysis, and angiogenesis in NPC were studied by loss-of-function assays. Next, the interaction of FKC, HSP90B1, and epidermal growth factor receptor (EGFR) was evaluated. Then, in vitro experiments were designed to analyze the effect of FKC treatment on NPC cells. Finally, in vivo experiments were allowed to investigate whether FKC treatment regulates proliferation, glycolysis, and angiogenesis of NPC cells by HSP90B1/EGFR pathway. RESULTS: HSP90B1 was highly expressed in NPC tissues and was identified as a poor prognostic factor in NPC. At the same time, knockdown of HSP90B1 can inhibit the proliferation of NPC cells, trigger apoptosis, and reduce glycolysis and angiogenesis. Mechanistically, FKC affects downstream EGFR phosphorylation by regulating HSP90B1, thereby regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. FKC treatment inhibited the proliferation, glycolysis, and angiogenesis of NPC cells, which was reversed by introducing overexpression of HSP90B1. In addition, FKC can affect NPC tumor growth and metastasis in vivo by regulating the HSP90B1/EGFR pathway. CONCLUSION: Collectively, FKC inhibits glucose metabolism and tumor angiogenesis in NPC by targeting the HSP90B1/EGFR/PI3K/Akt/mTOR signaling axis.

Selenochemical modification of low molecular weight polysaccharides from Grifola frondosa and the mechanism of their inhibitory effects on gastric cancer cells.

An important micronutrient involved in immune response and antitumor is selenium. LMW-GFP, a polysaccharide extracted from Grifola frondosa seed bodies, has a relatively weak antitumor effect on BGC-823 and MFC cells in vitro, whereas selenium binding to LMW-GFP can significantly increase the in vitro antitumor activity of LMW-GFP. In this study, Se-LMW-GFP was prepared by the HNO3-Na2SeO3 method, and the structures of LMW-GFP and Se-LMW-GFP were characterized by UV-visible spectroscopy of absorption, FTIR spectroscopy, and electron scanning microscopy, and these structural analyses showed that selenium was successfully complexed to LMW-GFP. The selenium content of Se-LMW-GFP was measured to be 2.08 % ± 0.08 % by ICP-MS. The anti-tumor activity of LMW-GFP before and after selenium modification was compared by cellular experiments, and the findings indicated that the anti-tumor activity of Se-LMW-GFP was considerably improved over that of LMW-GFP, and inhibited the proliferation of BGC-823 cells and MFC cells through a combination of the Fas/FasL-mediated exogenous death receptor pathway as well as the endogenous mitochondrial pathway. Our results suggest that Se-LMW-GFP not only has great potential for natural health food and anti-gastric cancer drug development but is also a good selenium supplement.

Pediatric Benign Paroxysmal Positional Vertigo: Degree of Nystagmus and Concurrent Dizziness Differs from Adult BPPV.

Background: Benign paroxysmal positional vertigo (BPPV) is characterized by brief, intense episodes of vertigo triggered by abrupt changes in head position. It is generally accepted as being most common in adults, while it is regarded as rare in children. It is necessary to compare the disease between pediatric and adult patients for a better understanding of the disease's characteristics and its natural history. This study aimed to identify the clinical characteristics of BPPV in children and compare them with those of adult BPPV patients. Methods: All children ≤ 18 years old who were diagnosed with BPPV were selected by searching the electronic database of our hospital. Clinical features were identified by medical record review. For adult patients, we collected data from patients > 19 years of age. Results: A total of 30 pediatric (13.65 ± 4.15 years old) and 264 adult patients (60.86 ± 13.74 years old) were included in the study. Among pediatric patients, the lateral canals were involved in 80% and the posterior canals in 16.67%. In adult patients, the lateral and posterior canals were involved similarly (p = 0.007). The degree of nystagmus in pediatric patients was 6.82 ± 12.09, while in adults it was 15.58 ± 20.90 (p < 0.001). The concurrent dizziness disorder was higher in the pediatric group and recurrence was higher in the adult group. In the regression analysis, it was found that adult patients had a stronger nystagmus with a value of 6.206 deg/sec, and the risk of concurrent dizziness disorder was found to be 5.413 times higher in the pediatric group (p < 0.05). Conclusions: BPPV occurs in pediatric patients with lower prevalence, but it cannot be overlooked. In the pediatric group, a relatively high proportion of patients demonstrated lateral canal involvement, weaker nystagmus, and additional dizziness disorder.

Gut microbiota deficiency aggravates arsenic-induced toxicity by affecting bioaccumulation and biotransformation in C57BL/6J mice.

Gut microbiome can influence the arsenic metabolism in mammals. Confusingly, gut microbiome was found to both mitigate and exacerbate arsenic toxicity. In this study, the role of gut microbiota in arsenic bioaccumulation, biotransformation, and organ toxicity in C57BL/6J mice was investigated. Gut microbiota deficiency model was established by antibiotics (Ab) cocktail AVNM. Conventional and gut microbiota deficiency mice were exposed to NaAsO2 for 4 weeks. Comparing with Ab-treated mice, the total arsenic (tAs) in the tissues was significantly reduced in conventional mice, which was opposed to the results of those in feces. Interestingly, dimethyl arsenite (DMA) was the most abundant metabolite in the feces of Ab-treated mice, while arsenic acid (AsV) had the highest proportion in the feces of conventional mice with approximately 16-fold than that in Ab-treated mice, indicating the critical role of gut microbiota in metabolizing arsenious acid (AsIII) to AsV. Additionally, the liver and kidney in Ab-treated mice showed more severe pathological changes and apoptosis. The significant increased level of ionized calcium-binding adapter molecule 1 (IBA-1) was also found in the brains of Ab-treated mice. Our results indicated that gut microbiota protected the host from arsenic-induced toxicity in liver, kidney, and brain by reducing the arsenic accumulation.