Angelica sinensis polysaccharide ameliorates nonalcoholic fatty liver disease via restoring estrogen-related receptor α expression in liver.

Angelica sinensis polysaccharide (ASP) showed increasingly recognized hepatoprotective effects and lipid regulation. Because polysaccharides are typically degraded into fragments or short-chain fatty acids in the gut, rather than being absorbed in their intact form, it is worth pondering why ASP can regulate hepatic lipid metabolism and protect the liver from damage caused by lipid accumulation. In vivo and in vitro nonalcoholic fatty liver disease (NAFLD) models with lipid accumulation were established to investigate the effect and potential mechanisms of ASP on hepatic fat accumulation. Our results showed that ASP remodeled the composition and abundance of the gut microbiota in high-fat diet-fed mice and increased their levels of propionate (0.92 ± 0.30 × 107 vs. 2.13 ± 0.52 × 107 ) and butyrate (1.83 ± 1.31 × 107 vs. 6.39 ± 1.44 × 107 ). Sodium propionate significantly increased the expression of estrogen-related receptor α (ERRα) in liver cells (400 mM sodium propionate for 2.19-fold increase) and alleviated the progress of NAFLD in methionine-choline-deficient diet model. Taken together, our study demonstrated that ASP can regulate hepatic lipid metabolism via propionate/ERRα pathway and ultimately relieving NAFLD. Our findings demonstrate that ASP can be used as a health care product or food supplement to prevent NAFLD.

Effects of species mixtures on soil water storage in the semiarid hilly gully region.

Mixed-species plantations are promoted to restore degraded ecosystems and improve soil quality worldwide. However, differences of soil water conditions between pure and mixed plantations are still controversial and how species mixtures affect soil water storage (SWS) was not well quantified. In this study, vegetation characteristics, soil properties and SWS were continuously monitored and quantified in three pure plantations (Armeniaca sibirica (AS), Robinia pseudoacacia (RP) and Hippophae rhamnoides (HR)) and their corresponding mixed plantations (Pinus tabuliformis-Armeniaca sibirica (PT-AS), Robinia pseudoacacia-Pinus tabuliformis-Armeniaca sibirica (RP-PT-AS), Platycladus orientalis-Hippophae rhamnoides plantation (PO-HR), Populus simonii-Hippophae rhamnoides (PS-HR)). The results found that SWS of 0-500 cm in RP (333.60 ± 75.91 mm) and AS (479.52 ± 37.50 mm) pure plantations were higher than those in their corresponding mixed plantations (p > 0.05). SWS in the HR pure plantation (375.81 ± 81.64 mm) was lower than that in its mixed plantation (p > 0.05). It is suggested that the effect of species mixing on SWS was species specific. Additionally, soil properties exerted more contributions (38.05-67.24 %) to SWS than vegetation characteristics (26.80-35.36 %) and slope topography (5.96-29.91 %) at different soil depths and the whole 0-500 cm soil profile. Furthermore, by excluding the effects of soil properties and topographic factors, plant density and height were particularly important to SWS (with standard coefficients 0.787 and 0.690 respectively). The results implied that not all the mixed plantations exhibits the better soil water conditions than the compared pure plantations, which was tightly related to species selected for mixing. Our study provides scientific support for revegetation technique improvement (structural adjustment and species optimization) in this region.

Characterization and Control of Dendrobium officinale Bud Blight Disease.

Dendrobium officinale is an important traditional Chinese medicine (TCM). A disease causing bud blight in D. officinale appeared in 2021 in Yueqing city, Zhejiang Province, China. In this paper, 127 isolates were obtained from 61 plants. The isolates were grouped into 13 groups based on collected areas and morphological observations. Four loci (ITS, LSU, tub2 and rpb2) of 13 representative isolates were sequenced and the isolates were identified by constructing phylogenetic trees with the multi-locus sequence analysis (MLSA) method. We found the disease to be associated with three strains: Ectophoma multirostrata, Alternaria arborescens and Stagonosporopsis pogostemonis, with isolates frequencies of 71.6%, 21.3% and 7.1%, respectively. All three strains are pathogenic to D. officinale. A. arborescens and S. pogostemonis isolated from D. officinale were reported for the first time. Iprodione (50%), 33.5% oxine-copper and Meitian (containing 75 g/L pydiflumetofen and 125 g/L difenoconazole) were chosen to control the dominant pathogen E. multirostrata, with an EC50 value of 2.10, 1.78 and 0.09 mg/L, respectively. All three fungicides exhibited an effective inhibition of activities to the growth of the dominant pathogen E. multirostrata on potato dextrose agar (PDA) plates, with Meitian showing the strongest inhibitory effect. We further found that Meitian can effectively control D. officinale bud blight disease in pot trial.

Muscle Health Patterns and Brain MRI Indices: A Cluster Analysis.

Background and Objectives: The interplay between muscle and brain lacks a holistic approach to assess the combined effect of multiple factors. This study utilizes clustering analysis to identify muscle health patterns and their relationships with various brain magnetic resonance imaging (MRI) indices. Research Design and Methods: Two hundred and seventy-five cognitively intact participants who completed brain MRI from the Health, Aging, and Body Composition Study were enrolled. Muscle health-related markers that showed significant relationship with total gray matter volume entered the cluster analysis. Subsequently, macrostructural and microstructural MRI indices were examined with analysis of variance and multiple linear regression analysis to determine significant associations with muscle health clusters. The muscle health cluster included 6 variables: age, skeletal muscle mass index, gait speed, handgrip strength, change of total body fat, and serum leptin level. Clustering method produced 3 clusters which had characteristics of obese, leptin-resistant, and sarcopenia, respectively. Results: Brain MRI indices that revealed significant associations with the clusters included gray matter volume (GMV) in cerebellum (p < .001), superior frontal gyrus (p = .019), inferior frontal gyrus (p = .003), posterior cingulum (p = .021), vermis (p = .045), and gray matter density (GMD) in gyrus rectus (p < .001) and temporal pole (p < .001). The leptin-resistant group had most degree of reduction in GMV, whereas the sarcopenia group had most degree of reduction in GMD. Discussion and Implications: The leptin-resistant and sarcopenia populations had higher risk of neuroimaging alterations. Clinicians should raise awareness on the brain MRI findings in clinical settings. Because these patients mostly had central nervous system conditions or other critical illnesses, the risk of sarcopenia as a comorbidity will substantially affect the prognosis and medical care.

Inverse Association between Serum Selenium Level and Severity of Liver Fibrosis: A Cross-Sectional Study.

Selenium has been well recognized for its important role in human health. Prior studies showed that low serum selenium was associated with various diseases, including cardiovascular disease, cancer, infertility, and cognitive decline. Recent studies demonstrated an association between selenium deficiency and liver cirrhosis. In our study, we aimed to explore the association between serum selenium levels and severity of liver fibrosis. In total, 5641 participants at an age of 12 and above, from the 2017-2018 United States National Health and Nutrition Examination Survey, were enrolled. The severity of liver fibrosis was determined by liver ultrasound transient elastography. There was a significant linear decrease in liver stiffness measurement (LSM) values in male groups with increased serum selenium levels. The beta coefficient (ß) = -1.045 in male groups. A significantly negative association was also observed in the group of age ≥ 60. In addition, those in the highest quartile of serum selenium had lower LSM values (ß = -0.416). This is the first study using LSM to demonstrate the correlation between selenium deficiency and severity of liver cirrhosis. Our findings suggest that a high plasma selenium concentration is negatively correlated with the severity of liver cirrhosis and there are gender and age differences.

Fusarium spp. Associated with Dendrobium officinale Dieback Disease in China.

A rare plant species of the Orchidaceae family, Dendrobium officinale is considered among the top ten Chinese medicinal herbs for its polysaccharide. Since 2021, when the dieback disease of D. officinale was first reported in Yueqing City, Zhejiang Province, China, Fusarium isolates (number = 152) were obtained from 70 plants in commercial greenhouses. The disease incidence ranged from 40% to 60% in the surveyed areas. Multilocus sequence analysis (MLSA) coupled with morphological characterization revealed that the collected isolates belonged to five species (sp.), viz., Fusarium concentricum, F. fujikuroi, F. nirenbergiae, F. curvatum, and F. stilboides, with isolation frequencies of 34.6%, 22.3%, 18.4%, 13.8%, and 10.5%, respectively. Notably, at least two Fusarium species were simultaneously isolated and identified from the infected plants. Finally, the pathogenicity test results demonstrated that such species were responsible for the dieback disease of D. officinale. However, F. concentricum and F. fujikuroi were more invasive compared to the other species in this study. To the best of the authors' knowledge, this study was the first report of F. concentricum, F. curvatum, F. fujikuroi, F. nirenbergiae, and F. stilboides causing the dieback disease of D. officinale in China and worldwide. This work provides valuable data about the diversity and pathogenicity of Fusarium populations, which will help in formulating effective strategies and policies for better control of the dieback disease.

Sarc-frailty: towards an integrated view of ageing.

OBJECTIVES: Sarcopenia and frailty have both been related to adverse events in ageing, but have long been studied in parallel. The purpose of this study was to provide a better depiction of ageing by taking the advantages of both entities. STUDY DESIGN: 2532 participants were enrolled from the National Health and Nutrition Examination Survey 1999-2002. A new diagnostic entity, sarc-frailty, was established by merging the diagnostic elements of both sarcopenia and frailty. MAIN OUTCOME MEASURES: Cox proportional hazard models, Kaplan-Meier curve, and receiver operating characteristic (ROC) curve analysis were utilized to compare the hazard ratios and predictive power in relation to mortality of sarcopenia, frailty, and sarc-frailty. Two different classification strategies, categorical and scoring, were used as alternative assessment methods. RESULTS: The median follow-up duration was 67.49 months, and no participants were lost to follow-up. ROC analysis revealed the highest area under curves (AUC) in sarc-frailty by both categorical and scoring classification (AUC = 0.660, p value <0.001 and AUC = 0.697, p value <0.001, respectively), indicating the best predictive ability in relation to mortality. Kaplan-Meier analysis also demonstrated the shortest overall survival for sarc-frailty with both classifications (p value both <0.001). In addition, hazard ratios (HRs) of sarc-frailty with both classifications were higher than their counterparts for sarcopenia and frailty (HR = 12.599, 95 % CI = 7.780 to 20.403, p < 0.001 by categorical method, and HR = 20.121, 95 % CI = 8.101 to 49.973, p < 0.001 by scoring classification). Moreover, the scoring classification revealed a more delicate hierarchical structure of mortality levels than the categorical classification. CONCLUSIONS: Sarc-frailty had a better predictive ability in relation to mortality. Considering that ageing well is a holistic health-care issue, our new entity, along with the scoring method, provides clinicians with more effective tools in geriatric assessment.

Detrimental health relationship between blood lead and cadmium and the red blood cell folate level.

Increasing studies have demonstrated the association between heavy metal pollution and micronutrients, especially folate. However, the relationship between cadmium and folate remains rarely discussed. In this study, we aim to explore the potential correlation between cadmium and folate in human population and highlight the possible mechanism of cadmium impacting human health. We utilized the National Health and Nutrition Examination Survey (NHANES) 2017-2018 data with 5690 participants in this study. Multivariable linear regression models were adopted to investigate the serum lead and cadmium levels and RBC folate concentration. A significant reverse relationship was found between serum lead and cadmium and RBC folate. A negative relationship between serum lead and cadmium levels and the levels of RBC folate in the U.S. adult population was found in this study. Nevertheless, due to the general limitations of the NHANES data, as a cross-sectional study, a further prospective investigation is needed to discover the causality of lead and cadmium in folate status and to determine whether the folate supplement has a beneficial influence against heavy metal toxicities.

Moderate Sun Exposure Is the Complementor in Insufficient Vitamin D Consumers.

Background and Aims: Vitamin (Vit) D plays a vital role in human health, and the prevalence of Vit D deficiency worldwide has been a rising concern. This study investigates the serum 25-hydroxy-Vit D [25(OH)D] status in healthy US civilians and identifies how the two main sources, sun exposure and dietary Vit D intake, determine the final 25(OH)D levels in individuals. Methods: A total of 2,360 of participants from The National Health and Nutrition Examination Survey (NHANES) 2009-2014 were analyzed. We divided the levels of sun exposure and dietary Vit D intake of all subjects into 10 strata and gave a score ranging from 1 to 10 points, respectively. Scores 1-5 in sun exposure and dietary intake were considered as relatively low exposure groups, whereas scores 6-10 were considered as relatively high exposure groups. Serum Vit D inadequacy was defined as <50 nmol/L. Linear and logistic regression analyses were used to examine the associations between sources of Vit D and serum 25(OH)D levels. Results: In relatively low Vit D intake groups (Vit D intake score 1-5), relatively high sun exposure (sun exposure score >5) resulted in higher serum 25(OH)D levels (average 57 nmol/L) compared with relatively low sun exposure (sun exposure score <5) (average 50 nmol/L), whereas this difference became negligible in high intake groups (Vit D intake score 6-10). Moreover, the greatest slope occurred in the low Vit D intake curve (decile 3 of Vit D intake), which shows increased sun exposure time causing the greatest degree of change in serum 25(OH)D level in this group. Conclusion: Sun exposure can significantly make up for deficiencies in subjects who consume insufficient dietary Vit D. Compared with the extra cost and time for building habits of Vit D supplementation, moderate sun exposure appears to be a simple and costless means for the public to start in daily practice.

Electroacupuncture in the Contralesional Hemisphere Improves Neurological Function Involving GABA in Ischemia-Reperfusion Injury Rats.

This study investigated the effect and mechanism of electroacupuncture (EA) on the contralesional hemisphere in rats with ischemic stroke. EA of 2 Hz was applied on the contralesionally Luoque (BL8) and Tongtian (BL7) acupoints of the scalp to investigate the neurological status and mechanism in ischemia-reperfusion injury rats. The differences in the neurological deficit score and Rotarod test time between days 3 and 15 after reperfusion were significantly lower in the sham group (0.00 (-1.00, 0.00) and 3.53 (-0.39, 7.48) second, respectively) than in the EA group (-4.00 (-4.00, -3.00) and 44.80 (41.69, 54.13) second, respectively, both p < 0.001). The ratio of infarction volume was 0.19 ± 0.04 in the sham group greater than 0.07 ± 0.04 in the EA group (p < 0.001). On day 15, in the cerebral cortex of the lesioned hemisphere, the gamma-aminobutyric acid (GABA)-A/actin ratio in the normal group (1.11 ± 0.36) was higher than that in the sham group (0.38 ± 0.07, p < 0.05) and similar to that in the EA group (0.69 ± 0.18, p > 0.05); the difference between the EA and sham groups was significant (p < 0.05). EA of 2 Hz on the BL8 and BL7 acupoints on the contralesional scalp can improve motor function and also can reduce infarction volume, and this effect of EA, and that GABA-A, plays at least a partial role in ischemia-reperfusion injury rats.

Discovery of Novel Azetidine Amides as Potent Small-Molecule STAT3 Inhibitors.

We optimized our previously reported proline-based STAT3 inhibitors into an exciting new series of (R)-azetidine-2-carboxamide analogues that have sub-micromolar potencies. 5a, 5o, and 8i have STAT3-inhibitory potencies (IC50) of 0.55, 0.38, and 0.34 µM, respectively, compared to potencies greater than 18 µM against STAT1 or STAT5 activity. Further modifications derived analogues, including 7e, 7f, 7g, and 9k, that addressed cell membrane permeability and other physicochemical issues. Isothermal titration calorimetry analysis confirmed high-affinity binding to STAT3, with KD of 880 nM (7g) and 960 nM (9k). 7g and 9k inhibited constitutive STAT3 phosphorylation and DNA-binding activity in human breast cancer, MDA-MB-231 or MDA-MB-468 cells. Furthermore, treatment of breast cancer cells with 7e, 7f, 7g, or 9k inhibited viable cells, with an EC50 of 0.9-1.9 µM, cell growth, and colony survival, and induced apoptosis while having relatively weaker effects on normal breast epithelial, MCF-10A or breast cancer, MCF-7 cells that do not harbor constitutively active STAT3.

Beneficial relevance of vitamin D concentration and urine flow rate.

BACKGROUND & AIMS: Micturition dysfunction is a problem in the general population that progresses with aging in both males and females. In the past few decades, the relationship between voiding symptoms and body biochemical status has been a subject of research in several disciplines. Micronutrition is considered to affect different aspects of urinary flow, including neuroregulation, detrusor muscle function, and the structures around the bladder outlet such as the pelvic floor and prostate. Therefore, the objective of our study was to determine the correlation between urine flow rate (UFR) and 25-hydroxyvitamin D (25(OH)D) in the general healthy population. METHODS: Our study involved 3981 adult participants over age 20 from the U.S. National Health and Nutrition Examination Survey datasets (2011-2012). The associations between UFR and serum 25(OH)D concentration were analyzed through multivariate regression models. RESULTS: There was a significant positive association of serum 25(OH)D concentration with UFR (25(OH)D2+25(OH)D3: ß coefficient: 0.003; 95% CI: 0.002, 0.004; p < 0.001, 25(OH)D3; p = 0.003; epi-25(OH)D3, p = 0.020) in an unadjusted model. The substantial associations were still observed in the gender and age subgroups. In analysis of age subgroup, the association of serum 25(OH)D concentration with urine flow rate was significant in fully adjusted model (age<60: 25(OH)D2+25(OH)D3: ß coefficient: 0.004, p < 0.001; 25(OH)D3: p = <0.001, epi-25(OH)D3: p = 0.007; Age≥60: 25(OH)D2+25(OH)D3: ß coefficient: 0.004, p = 0.002; 25(OH)D3: p = 0.001, epi-25(OH)D3: p = 0.001). In gender subgroup analysis, the ß coefficient of 25(OH)D2+25(OH)D3 in male is 0.004 (p < 0.001), and in female is 0.004 (p < 0.001) in fully adjusted model. The higher quartiles of UFR tended to have higher 25(OH)D3 levels with statistically significant in quartile-based analysis. CONCLUSIONS: UFR was associated with increased level of total vitamin D and bioactive form vitamin D3. Vitamin D supplements may be a simple and effective way of improving of bladder function.

Clinical Relevance of Serum Selenium Levels and Abdominal Aortic Calcification.

Selenium (Se) is an essential micronutrient with antioxidative properties, but previous studies have shown that extremely high circulating Se concentrations are associated with a higher prevalence of cardiovascular diseases (CVDs). To date, it remains unknown whether this association has connections with arterial calcification. A total of 982 participants with both serum Se concentration and abdominal aortic calcification (AAC) score data were enrolled from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), a cross-sectional study of a noninstitutionalized population in the USA. Serum Se levels were determined by inductively coupled plasma-dynamic reaction cell-mass spectrometry. AAC was obtained from dual-energy X-ray absorptiometry and quantified by the Kauppila score system. Severe AAC was defined as Kauppila score ≥ 5. Among all participants, the mean serum Se level was 132.89 µg/L. The average AAC score was 1.51, and 11.7% had severe AAC. Compared with those in the lowest quartile of Se (< 121.1 µg/L), the highest quartile subgroup (> 143.1 µg/L) was associated with a higher mean AAC score (ß-coefficient 0.88; 95% CI 0.28, 1.47; p = 0.004) and greater odds of having severe AAC (odds ratio 2.19; 95% CI 1.10, 4.36; p = 0.026) after adjusting for demographic, biochemical, and clinical characteristics. The concentrations of other circulating trace elements showed no statistically significant association with the AAC score. High serum Se levels were independently associated with an increased mean AAC score and aggravated AAC severity among noninstitutionalized US adults. Serum Se might adversely affect the cardiovascular system when the serum Se concentration exceeds 143 µg/L.

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3.

Chemoresistance is a major cause of cancer progression and the mortality of cancer patients. Developing a safe strategy for enhancing chemosensitivity is a challenge for biomedical science. Recent studies have suggested that vitamin D supplementation may decrease the risk of many cancers. However, the role of vitamin D in chemotherapy remains unknown. We found that vitamin D sensitised oral cancer cells to cisplatin and partially reversed cisplatin resistance. Using RNA-seq, we discovered that lipocalin 2 (LCN2) is an important mediator. Cisplatin enhanced the expression of LCN2 by decreasing methylation at the promoter, whereas vitamin D enhanced methylation and thereby inhibited the expression of LCN2. Overexpression of LCN2 increased cell survival and cisplatin resistance both in vitro and in vivo. High LCN2 expression was positively associated with differentiation, lymph node metastasis, and T staging and predicted a poor prognosis in oral squamous cell carcinoma (OSCC) patients. LCN2 was also associated with post-chemotherapy recurrence. Moreover, we found that LCN2 promoted the activation of NF-κB by binding to ribosomal protein S3 (RPS3) and enhanced the interaction between RPS3 and p65. Our study reveals that vitamin D can enhance cisplatin chemotherapy and suggests that vitamin D should be supplied during chemotherapy; however, more follow-up clinical studies are needed.

Serum Phosphorus as a Risk Factor of Metabolic Syndrome in the Elderly in Taiwan: A Large-Population Cohort Study.

BACKGROUND: The impact of serum phosphorus concentration on metabolic syndrome were limited. Therefore, this study aimed to explore the association between the serum phosphorus and incident metabolic syndrome in the elderly in Taiwan. METHODS: We included 1491 participants who had health check-ups in the Tri-Service General Hospital for the period 2007 to 2015 and divided them based on age to assess the incidence of metabolic syndrome. We performed the COX regression model to explore the impact of serum phosphorus for metabolic syndrome, diabetes mellitus, and hypertension by an age-specific group. RESULTS: Our result showed that higher serum phosphorus concentration was noted in the elderly in the baseline characteristics. In the group older than 60 years, serum phosphorus concentration was correlated with the incidence of metabolic syndrome (hazard ratios (HR) = 1.39, 95% CI 1.11-1.74) and diabetes mellitus (HR = 1.49, 95% CI 1.15-1.92) after adjustment. We further found the relationship between serum phosphorus and incidence of the components of metabolic syndrome, including higher waist circumference, high-density lipoprotein (HDL), serum triglyceride, and fast glucose. CONCLUSIONS: Our study might provide an epidemiological evidence that serum phosphorus was related with the incidence of metabolic syndrome in the elderly in Taiwan.

Health Disparities of Employees in Taiwan with Major Cancer Diagnosis from 2004 to 2015: A Nation- and Population-Based Analysis.

Background: Health disparities related to environmental exposure exist in different industries. Cancer is currently a leading cause of morbidity and mortality worldwide. Much remains unknown about the types of work and industries that face the greatest cancer risks. In this study, we aimed to provide the overall and specific cancer incidences among all workers from 2004 to 2015. We also aimed to show the all-cause mortality for all employees with a first-ever cancer diagnosis. Methods: All workers in Taiwan in the labor insurance database in 2004-2015 were linked to the national health insurance databases. The annual overall and specific cancer incidences in 2004-2015 were calculated and stratified by industry and gender. Age-standardized incidence rates were also calculated. Results: A total of 332,575 workers (46.5% male) who had a first-ever cancer diagnosis from 2004-2015 were identified from 16,720,631 employees who provided 1,564,593 person-years of observation. The fishing, wholesale, construction, and building industries were identified as high-risk industries, with at least 5% of employees within them receiving a first-ever cancer diagnosis. Temporal trends of cancer incidences showed a range from 235.5 to 294.4 per 100,000 with an overall upward trend and an increase of 1.3-fold from 2004 to 2015. There were significant increases over that time for breast cancer (25%); colon cancer (8%); lung, bronchial, and tracheal cancers (11%); and oral cancer (1.7%). However, the incidence rates of cervical cancer and liver and intrahepatic cholangiocarcinoma decreased by 11.2% and 8.3%, respectively. Among the 332,575 workers with a first-ever cancer diagnosis, there were 110,692 deaths and a mortality rate of 70.75 per 1000 person-years. Conclusions: The overall incidence of cancer increased over the 10-year study period, probably due to the aging of the working population. High-risk industries are concentrated in the labor-intensive blue-collar class, which is related to aging and socioeconomic status intergradation.

A Novel 3D in Vitro Tumor Model Based on Silk Fibroin/Chitosan Scaffolds To Mimic the Tumor Microenvironment.

Drug development involves various evaluation processes to ascertain drug effects and rigorous analysis of biological indicators during in vitro preclinical studies. Two-dimensional (2D) cell cultures are commonly used in numerous in vitro studies, which are poor facsimiles of the in vivo conditions. Recently, three-dimensional (3D) tumor models mimicking the tumor microenvironment and reducing the use of experimental animals have been developed generating great interest to appraise tumor response to treatment strategies in cancer therapy. In this study, silk fibroin (SF) protein and chitosan (CS), two natural biomaterials, were chosen to construct the scaffolds of 3D cell models. Human non-small cell lung cancer A549 cells in the SF/CS scaffolds were found to have a great tendency to gather and form tumor spheres. A549 cell spheres in the 3D scaffolds showed biological and morphological characteristics much closer to the in vivo tumors. Besides, the cells in 3D models displayed better invasion ability and drug resistance than 2D models. Additionally, differences in drug-resistant and immune-related protein levels were found, which indicated that 3D models might resemble the real-life situation. These findings suggested that these 3D tumor models composed of SF/CS are promising to provide a valuable biomaterial platform in the evaluation of anticancer drugs.

The chemical states and atomic structure evolution of ultralow-energy high-dose Boron implanted Si(110) via laser annealing.

Further scale down the dimension of silicon-based integrated circuit is a crucial trend in semiconductor fabrication. One of the most critical issues in the nano-device fabrication is to confirm the atomic structure evolution of the ultrathin shallow junction. In this report, UV Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray absorption near edge structure (XANES) and reflective second harmonic generation (RSHG) are utilized to monitor the pulse laser induced atomic structure evolution of ultralow-energy high-dose Boron implanted Si(110) at room and cold substrate temperature. A peak feature around 480 cm-1 resolved in UV Raman spectra indicates the formation of Si-B bond after the laser irradiation. The red shift of binding energy of Si element (~99 eV) in XPS and the evolution of absorption peak (~196.2 eV) in XANES reveal that the changes in the chemical states of ultra shallow junction strongly correlate to the activation process of Boron implantation, which is confirmed by RSHG measurement. The substrate temperature effect in the recrystallization of Boron implanted region is also realized by cross-section high-resolution TEM (HRTEM). The phenomena of Si-B bond formation and ultra-shallow junction recrystallization can be traced and applied to improve the reliability of Si ultra shallow junction in the future.

Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin.

Physicochemical properties, including particle size, zeta potential, and drug release behavior, affect targeting efficiency, cellular uptake, and antitumor effect of nanocarriers in a formulated drug-delivery system. In this study, a novel stepwise pH-responsive nanodrug delivery system was developed to efficiently deliver and significantly promote the therapeutic effect of doxorubicin (DOX). The system comprised dimethylmaleic acid-chitosan-urocanic acid and elicited stepwise responses to extracellular and intracellular pH. The nanoparticles (NPs), which possessed negative surface charge under physiological conditions and an appropriate nanosize, exhibited advantageous stability during blood circulation and enhanced accumulation in tumor sites via enhanced permeability and retention effect. The tumor cellular uptake of DOX-loaded NPs was significantly promoted by the first-step pH response, wherein surface charge reversion of NPs from negative to positive was triggered by the slightly acidic tumor extracellular environment. After internalization into tumor cells, the second-step pH response in endo/lysosome acidic environment elicited the on-demand intracellular release of DOX from NPs, thereby increasing cytotoxicity against tumor cells. Furthermore, stepwise pH-responsive NPs showed enhanced antiproliferation effect and reduced systemic side effect in vivo. Hence, the stepwise pH-responsive NPs provide a promising strategy for efficient delivery of antitumor agents.

Associations among integrated psychoneuroimmunological factors and metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) has been reported to cause considerable psychoneuroimmunology (PNI) disturbances such as, psychological distress, autonomic nervous imbalance, and impaired immune function. Associations among these psychoneuroimmunology (PNI) factors and their integrated effects with MetS and risk components of MetS necessitate further exploration. OBJECTIVE: This study investigated associations among psychoneuroimmunological factors, their integrated effects with MetS and risk components of MetS. METHODS: This was a cross-sectional study. Participants were recruited from two health management centers at a medical center in Northern Taiwan. Demographics and data on psychological distress (e.g., perceived stress and depression) were collected using self-reported questionnaires. Heart rate variability (HRV) and C-reactive protein values (CRP) were measured to evaluate participants' autonomic nervous function and immune reaction. The risk components of MetS (e.g., elevated blood pressure, impaired fasting glucose, dyslipidemia, and abdominal obesity) were identified according to the Taiwan-specific definition of MetS and were determined based on participants' health examination profiles. RESULTS: A total of 345 participants with complete data were included for data analysis. Compared with healthy controls, participants with MetS exhibited higher depression scores (11.2±8.5 vs. 8.7±7.0), higher CRP values (2.1±2.5 vs. 0.7±1.0), and lower HRV (total power: 758.7±774.9 vs. 1064.4±1075.0). However, perceived stress in participants with MetS did not significantly differ from that of their healthy counterparts (p>0.05). Univariate analyses indicated that associations among psychoneuroimmunological factors and MetS risk components were statistically heterogeneous: a) perceived stress and depression were significantly associated only with high blood glucose (p<0.05); b) CRP was significantly associated with all MetS risk components (p<0.05); and c) HRV was significantly associated with high triglycerides and high fasting blood glucose (p<0.05). Multivariate analysis indicated that the integrated effects of depression, CRP, and HRV were significantly associated with MetS (p<0.01) after controlling for age and education level. CONCLUSIONS: Higher depression scores, higher CRP values, and lower HRV are independently and additively associated with MetS and risk components of MetS. Accordingly, a multidisciplinary approach to alleviating psychological distress, immune dysfunction, and autonomic nervous imbalance is recommended for promoting well-being in people with subclinical metabolic abnormalities or MetS to minimize downstream health consequences.