Three amphioxus reference genomes reveal gene and chromosome evolution of chordates.

The slow-evolving invertebrate amphioxus has an irreplaceable role in advancing our understanding of the vertebrate origin and innovations. Here we resolve the nearly complete chromosomal genomes of three amphioxus species, one of which best recapitulates the 17 chordate ancestor linkage groups. We reconstruct the fusions, retention, or rearrangements between descendants of whole-genome duplications, which gave rise to the extant microchromosomes likely existed in the vertebrate ancestor. Similar to vertebrates, the amphioxus genome gradually establishes its three-dimensional chromatin architecture at the onset of zygotic activation and forms two topologically associated domains at the Hox gene cluster. We find that all three amphioxus species have ZW sex chromosomes with little sequence differentiation, and their putative sex-determining regions are nonhomologous to each other. Our results illuminate the unappreciated interspecific diversity and developmental dynamics of amphioxus genomes and provide high-quality references for understanding the mechanisms of chordate functional genome evolution.

Downregulated BMP-Smad1/5/8 signaling causes emphysema via dysfunction of alveolar type II epithelial cells.

Bone morphogenetic protein (BMP)-Smad1/5/8 signaling plays a crucial regulatory role in lung development and adult lung homeostasis. However, it remains elusive whether BMP-Smad1/5/8 signaling is involved in the pathogenesis of emphysema. In this study, we downregulated BMP-Smad1/5/8 signaling by overexpressing its antagonist Noggin in adult mouse alveolar type II epithelial cells (AT2s), resulting in an emphysematous phenotype mimicking the typical pathological features of human emphysema, including distal airspace enlargement, pulmonary inflammation, extracellular matrix remodeling, and impaired lung function. Dysregulation of BMP-Smad1/5/8 signaling in AT2s leads to inflammatory destruction dominated by macrophage infiltration, associated with reduced secretion of surfactant proteins and inhibition of AT2 proliferation and differentiation. Reactivation of BMP-Smad1/5/8 signaling by genetics or chemotherapy significantly attenuated the morphology and pathophysiology of emphysema and improved the lung function in Noggin-overexpressing lungs. We also found that BMP-Smad1/5/8 signaling was downregulated in cigarette smoke-induced emphysema, and that enhancing its activity in AT2s prevented or even reversed emphysema in the mouse model. Our data suggest that BMP-Smad1/5/8 signaling, located at the top of the signaling cascade that regulates lung homeostasis, represents a key molecular regulator of alveolar stem cell secretory and regenerative function, and could serve as a potential target for future prevention and treatment of pulmonary emphysema. © 2023 The Pathological Society of Great Britain and Ireland.

Systematic review of epidemiological and toxicological evidence on health effects of fluoride in drinking water.

INTRODUCTION: Fluoride is a naturally occurring substance that is also added to drinking water, dental hygiene products, and food supplements for preventing dental caries. Concerns have been raised about several other potential health risks of fluoride. OBJECTIVE: To conduct a robust synthesis of evidence regarding human health risks due to exposure to fluoride in drinking water, and to develop a point of departure (POD) for setting a health-based value (HBV) for fluoride in drinking water. METHODS: A systematic review of evidence published since recent reviews of human, animal, and in vitro data was carried out. Bradford Hill considerations were used to weigh the evidence for causality. Several key studies were considered for deriving PODs. RESULTS: The current review identified 89 human studies, 199 animal studies, and 10 major in vitro reviews. The weight of evidence on 39 health endpoints was presented. In addition to dental fluorosis, evidence was considered strong for reduction in IQ scores in children, moderate for thyroid dysfunction, weak for kidney dysfunction, and limited for sex hormone disruptions. CONCLUSION: The current review identified moderate dental fluorosis and reduction in IQ scores in children as the most relevant endpoints for establishing an HBV for fluoride in drinking water. PODs were derived for these two endpoints, although there is still some uncertainty in the causal weight of evidence for causality for reducing IQ scores in children and considerable uncertainty in the derivation of its POD. Given our evaluation of the overall weight of evidence, moderate dental fluorosis is suggested as the key endpoint until more evidence is accumulated on possible reduction of IQ scores effects. A POD of 1.56 mg fluoride/L for moderate dental fluorosis may be preferred as a starting point for setting an HBV for fluoride in drinking water to protect against moderate and severe dental fluorosis. Although outside the scope of the current review, precautionary concerns for potential neurodevelopmental cognitive effects may warrant special consideration in the derivation of the HBV for fluoride in drinking water.

Using a new human milk fortifier to optimize human milk feeding among very preterm and/or very low birth weight infants: a multicenter study in China.

BACKGROUND: Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. METHODS: VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. RESULTS: Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (ß = 0.6, 95%CI:0.1, 1.0; P = 0.01). CONCLUSIONS: The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04283799).

Assessing the role of dental insurance in oral health care disparities in Canadian adults.

Background: This study examines the association of dental insurance with oral health care access and utilization in Canada while accounting for income and sociodemographic factors. It contributes to a baseline of oral health care disparities before the implementation of the Canadian Dental Care Plan (CDCP). Data and methods: This retrospective study of Canadians aged 18 to 64 years is based on data from the 2022 Canadian Community Health Survey. Multivariable logistic regression was employed to evaluate the association of dental insurance with the recency and frequency of dental visits, as well as avoidance of dental care because of cost. Results: Overall, 65.7% of Canadians reported visiting a dental professional in the previous year: 74.6% of those with private insurance, 62.8% with public insurance, and 49.8% uninsured. Cost-related avoidance of dental care was 16.0%, 20.9%, and 47.4% for the privately insured, publicly insured, and uninsured, respectively. After adjustment, adults with private (odds ratio [OR]=2.54; 95% confidence interval [CI]: 2.32 to 2.78) and public (OR=2.17; 95% CI: 1.75 to 2.68) insurance were more likely to have visited a dental professional in the last year compared with those without insurance. Similarly, both private (OR=0.22; 95% CI: 0.20 to 0.25) and public (OR=0.22; 95% CI: 0.17 to 0.29) insurance holders showed a significantly lower likelihood of avoiding dental visits because of cost when compared with uninsured individuals. Interpretation: This study showed the significant association of dental insurance with access to oral health care in Canada, contributing to setting a critical benchmark for assessments of the CDCP's effectiveness in addressing oral health disparities.

Nitrogen Fertilization Increases Soil Microbial Biomass and Alters Microbial Composition Especially Under Low Soil Water Availability.

Soil microbial biomass and composition are affected by resource supply and water availability. However, the response of soil microbial communities to nitrogen fertilization under different water availability conditions is unclear. Therefore, this study conducted a 6-year pot experiment comprising five watering regimes (40%, 50%, 60%, 80%, and 100% of field capacity (FC)) and three nitrogen fertilization levels (NH4NO3 solution; 0 [N0], 20 [N1], and 40 [N2] g N m-2 year-1) to investigate soil microbial biomass, composition, and properties. The results indicated that soil microbial biomass and composition were more strongly affected by nitrogen fertilization compared with water regime. Nitrogen fertilization increased soil microbial biomass and altered soil microbial community composition, especially under low soil water availability. Soil microbial biomass was positively linearly associated with soil water regimes under N0, whereas it responded polynomially to soil water regimes under N1 and N2. The maximal soil microbial biomass was observed at FC80 for N1 and FC60 for N2. Furthermore, the biomass of soil microbial groups with high nitrogen and carbon acquisition ability as well as the enzyme activities of carbon and nitrogen cycling (ß-1,4-glucosidase and ß-1,4-N-acetyl-glucosaminidase, respectively) were stimulated by nitrogen fertilization. Soil microbial biomass was affected directly by nitrogen fertilization and indirectly by nitrogen and water regimes, via altering soil pH, dissolved inorganic nitrogen (NH4+-N and NO3--N) concentration, and soil organic carbon concentration. This study provides new insights into the effect of interaction between soil nitrogen and water availabilities on soil microbial biomass, composition, and its underlying mechanism.

Construction of g-C3N4/CdS/BiVO4 ternary nanocomposite with enhanced visible-light-driven photocatalytic activity toward methylene blue dye degradation in the aqueous phase.

Herein, the ternary CdS/BiVO4/g-C3N4 (CBG) hybrid semiconductor photocatalyst was prepared via a hydrothermal technique. The synthesized photocatalysts were thoroughly characterized using powder XRD, XPS, FTIR, SEM, TEM, and UV-DRS to investigate the microstructural, morphological attributes, and optical properties. The photocatalytic activity of the ternary CBG hybrid semiconductor was assessed through the photodegradation of Methylene Blue (MB) aqueous dye under visible light. The outcomes exhibited that the CBG hybrid semiconductor showed excellent photocatalytic activity (about 94.5% after 120 min) compared to the results obtained with the pristine materials or the other composite (CdS/BiVO4). The enhancement of photocatalytic activity can be due to the construction of heterojunctions among g-C3N4, CdS, and BiVO4, which improves charge transfer efficiency and hence favors the degradation of organic dyes. Moreover, the as-prepared photocatalyst showed excellent stability after five cycles, indicating good stability and reusability. Subsequently, a possible photocatalytic mechanism was proposed based on the experimental results. The current investigation provides a promising strategy to promote photocatalytic activity to eliminate waterborne contaminants.

The variation of antenatal corticosteroids administration for the singleton preterm birth in China, 2017 to 2018.

BACKGROUND: The administration of antenatal corticosteroids (ACS) to women who are at risk of preterm birth has been proven to reduce not only the mortality, but also the major morbidities of the preterm infants. The rate of ACS and the risk factors associated with ACS use in Chinese population is unclear. This study aimed to investigate the rate of ACS use and the associated perinatal factors in the tertiary maternal centers of China. METHODS: Data for this retrospective observational study came from a clinical database of preterm infants established by REIN-EPIQ trial. All infants born at < 34 weeks of gestation and admitted to 18 tertiary maternal centers in China from 2017 to 2018 were enrolled. Any dose of dexamethasone was given prior to preterm delivery was recorded and the associated perinatal factors were analyzed. RESULTS: The rate of ACS exposure in this population was 71.2% (range 20.2 - 92%) and the ACS use in these 18 maternal centers varied from 20.2 to 92.0% in this period. ACS exposure was higher among women with preeclampsia, caesarean section delivery, antibiotic treatment and who delivered infants with lower gestational age and small for gestational age. ACS use was highest in the 28-31 weeks gestational age group, and lowest in the under 26 weeks of gestational age group (x2 = 65.478, P < 0.001). ACS exposure was associated with lower odds of bronchopulmonary dysplasia or death (OR, 0.778; 95% CI 0.661 to 0.916) and invasive respiration requirement (OR, 0.668; 95% CI 0.585 to 0.762) in this population. CONCLUSION: The ACS exposure was variable among maternity hospitals and quality improvement of ACS administration is warranted.

Photoaging and release profile of acrylonitrile butadiene styrene microplastics under simulated solar radiation in water.

Microplastics (MPs) pollution has become a major environmental problem and poses a risk to a variety of organisms. In this study, the photoaging behavior of acrylonitrile butadiene styrene microplastics (ABS-MP) in aqueous environment was investigated under simulated solar irradiation. Results showed that the long chains of ABS-MP broke under the light irradiation, and its thermal stability was reduced. ABS-MP was oxidized during photoaging and produced a large number of oxygen-containing functional groups. Structure destruction of ABS-MP decreased the formation of environmentally persistent free radicals (EPFRs) and further photoirradiation generated secondary EPFRs. Nuclear magnetic resonance (NMR) analysis of the aged leachates confirmed that ABS-MP was oxidized and some small molecular fragments were dropped during photoaging. Meanwhile, C-Br bond broke of additive tetrabromobisphenol A (TBBPA) resulting in more bromine released into water and Sb(III) of additive Sb2O3 was oxidized to Sb(V) during photoaging. These findings illustrate the necessity of considering the aging of MPs in natural environment, expand the understanding of the potential harm and fate of MPs in aqueous environment, which is important for the management of MPs.

NT5DC2 promotes leiomyosarcoma tumour cell growth via stabilizing unpalmitoylated TEAD4 and generating a positive feedback loop.

5'-Nucleotidase Domain Containing 2 (NT5DC2) is a novel oncoprotein, the regulatory effects of which have not been well characterized. This study aimed to investigate the expression profile and functional regulation of NT5DC2 and its potential interplay with TEAD4 in leiomyosarcoma (LMS). Bioinformatic analysis was conducted using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) program. LMS cell lines SK-LMS-1 and SK-UT-1 were used for both in vitro and in vivo analysis. Results showed that NT5DC2 is aberrantly upregulated in LMS. Its overexpression was associated with unfavourable survival. Deletion of NT5DC2 significantly reduced the expression of cyclin B1, cyclin A2, cyclin E1 and CDK1 and increased G1 phase arrest in LMS cell lines, and suppressed their proliferation both in vitro and in vivo. NT5DC2 interacted with unpalmitoylated TEAD4, and this association reduced TEAD4 degradation via the ubiquitin-proteasome pathway. TRIM27 is a novel E3 ubiquitin ligase that induces K27/48-linked ubiquitination of unpalmitoylated TEAD4 at Lys278. TEAD4 inhibition significantly suppressed LMS cell growth both in vitro and in vivo. Dual-luciferase assay demonstrated that TEAD4 could bind to the NT5DC2 promoter and activate its transcription. Based on these findings, we infer that the NT5DC2-TEAD4 positive feedback loop plays an important role in LMS development and might serve as a potential therapeutic target.

Electron-transfer-dominated non-radical activation of peroxydisulfate for efficient removal of chlorophenol contaminants by one-pot synthesized nitrogen and sulfur codoped mesoporous carbon.

Synergistic adsorption and oxidative degradation (via persulfate activation) on metal-free carbonaceous materials are expected to be environmentally friendly and highly efficient approach toward contaminants removal. Herein, nitrogen and sulfur codoped mesoporous carbon (NSDMC) were firstly synthesized via co-carbonization of calcium citrate and thiourea without any templates. NSDMC samples exhibit remarkably enhanced adsorption capacity and oxidative degradation (by activating PDS) for chlorophenols elimination. Increased SBET and introduced N-containing functional groups are beneficial for chlorophenols adsorption, PDS accessibility and successive activation. Doped sulfur species (especially for thiophenic S) can enhance the electron-transport performance of NSDMC, further promoting PDS activation and chlorophenols degradation. It can be ascribed to the synergistic effect of N and S codoping. NSDMC-30 (containing 5.83 at.% nitrogen and 2.15 at.% sulfur, and possessing SBET of 1935.9 m2 g-1) exhibits the optimal adsorption and catalytic oxidation capability for 4-CP removal. Degradation rate constant of NSDMC-30 is 0.125 min-1, which is 3.0 times and 7.8 times higher than nitrogen-doped MC and pristine MC, respectively. Radicals quenching experiments and EPR tests demonstrate that non-radical pathways play dominant role for PDS activation and chlorophenols degradation. Based on the influences of catalyst loading, initial 4-CP concentration, and PDS dosage on degradation kinetics of 4-CP, the pre-adsorption is unveiled to be the critical step determining oxidation rate of chlorophenols. More importantly, the results of in-situ Raman and electrochemical tests show that the surface-confined and activated PDS complex (carbon-PDS*) and continuous electron transfer from co-adsorbed 4-CP are mainly responsible for the oxidative degradation of chlorophenols. The intermediate products and TOC removal indicate that chlorophenols can be efficiently degraded and mineralized by as-synthesized NSDMC via activating PDS. Besides, the present NSDMC/PDS system is also applicable for purification of actual polluted water samples. This work provides in-depth knowledge of carbon-driven nonradical process for PDS activation and contaminants remediation.

Systematic screening identifies a 2-gene signature as a high-potential prognostic marker of undifferentiated pleomorphic sarcoma/myxofibrosarcoma.

The Cancer Genome Atlas (TCGA) Research Network confirmed that undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) share a high level of genomic similarities and fall into a single spectrum of tumour. However, no molecular prognostic biomarkers have been identified in UPS/MFS. In this study, by extracting data from TCGA-Sarcoma (SARC), we explored relapse-related genes, their prognostic value and possible mechanisms of the dysregulations. After systematic screening, ITGA10 and PPP2R2B were included to construct a 2-gene signature. The 2-gene signature had an AUC value of 0.83 and had an independent prognostic value in relapse-free survival (RFS) (HR: 2.966, 95%CI: 1.995-4.410 P < .001), and disease-specific survival (DSS) (HR: 2.283, 95%CI: 1.358-3.835, P = .002), as a continuous variable. Gene-level copy number alterations (CNAs) were irrelevant to their dysregulation. Two CpG sites (cg15585341 and cg04126335) around the promoter of ITGA10 showed strong negative correlations with ITGA10 expression (Pearson's r < -0.6). Transcript preference was observed in PPP2R2B expression. The methylation of some CpG sites in two gene body regions showed at least moderate positive correlations (Pearson's r > .4) with PPP2R2B expression. Besides, the 2-gene signature showed a moderate negative correlation with CD4 + T cell infiltration. High-level CD4 + T cell infiltration and neutrophil infiltration were associated with significantly better RFS. Based on these findings, we infer that the 2-gene signature might be a potential prognostic marker in patients with UPS/MFS. Considering the potential benefits of immunotherapy for UPS/MFS patients, it is imperative to explore the predictive value of this signature in immunotherapeutic responses in the future.

Population pharmacokinetic study of caffeine citrate in Chinese premature infants with apnea.

WHAT IS KNOWN AND OBJECTIVES: Caffeine citrate is a commonly used methylxanthine for pharmacologic treatment of apnea of prematurity. The aim of this study was to develop and verify a population pharmacokinetic (PPK) model, which can provide a reference for individualized caffeine citrate treatment of apnea in Chinese premature infants. METHODS: A total of 88 serum concentration measurements from 46 preterm patients (median gestational age 29 weeks) were retrospectively collected and the relevant clinical data of patients were recorded. The PPK analysis was performed by non-linear mixed-effect modelling method using NONMEM. Allometric scaling was applied in the PPK analysis, and the final model was evaluated by graphic and statistical methods, including goodness-of-fit plots, normalized prediction distribution errors plots and bootstrap procedures. RESULTS: A one-compartment model with first-order elimination was successfully fitted to the data. The typical scaled values for the parameters clearance and volume of distribution (V) were 0.268 L/h and 109 L per 70 kg, respectively. The weight at the time of blood collection (CW) and post-natal age were identified as important predictors for pharmacokinetic parameters of caffeine. The evaluation process showed good stability and predictability of the final PPK model. WHAT IS NEW AND CONCLUSION: This is a complete PPK study of caffeine citrate in Chinese premature infants with apnea, which complements caffeine pharmacokinetic data of the premature from China. A final PPK model was developed which may serve as a beneficial tool for the use of caffeine citrate in the treatment of apnea in Chinese preterm infants.

Impact of low-level mercury exposure on intelligence quotient in children via rice consumption.

Wanshan is a city in southwest China that has several inactive mercury (Hg) mines. The local population are exposed to methylmercury (MeHg) due to the consumption of Hg contaminated rice. The relationship between Hg exposure and the cognitive functions of local children is unknown. This study investigated the relationship between hair Hg concentrations and the intelligence quotient (IQ) of 314 children aged 8-10 years, recruited from three local primary schools in Wanshan area in 2018 and 2019. IQ was evaluated using Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV). The average THg concentration in children's hair samples was 1.53 µg g-1 (range: 0.21-12.6 µg g-1), and 65.6% exceeded the United States Environment Protection Agency (USEPA) recommended value of 1 µg g-1. Results of logistic regression analysis showed that children with hair Hg ≥ 1 µg g-1 were 1.58 times more likely to have an IQ score <80, which is the clinical cut-off for borderline intellectual disability (R2 = 0.20, p = 0.03). Increasing of 1 µg g-1 hair Hg resulted in 1 point of IQ loss in Wanshan children, which was.much higher than that via fish consumption. The economical cost due to Hg exposure was estimated to be $69.8 million (9.43% of total GDP) in the Wanshan area in 2018.

A Highly Sensitive and Selective ppb-Level Acetone Sensor Based on a Pt-Doped 3D Porous SnO2 Hierarchical Structure.

In view of the low sensitivity, high operating temperature and poor selectivity of acetone measurements, in this paper much effort has been paid to improve the performance of acetone sensors from three aspects: increasing the surface area of the material, improving the surface activity and enhancing gas diffusion. A hierarchical flower-like Pt-doped (1 wt %) 3D porous SnO2 (3DPS) material was synthesized by a one-step hydrothermal method. The micropores of the material were constructed by subsequent annealing. The results of the experiments show that the 3DPS-based sensor's response is strongly dependent on temperature, exhibiting a mountain-like response curve. The maximum sensor sensitivity (Ra/Rg) was found to be as high as 505.7 at a heating temperature of 153 °C and with an exposure to 100 ppm acetone. Additionally, at 153 °C, the sensor still had a response of 2.1 when exposed to 50 ppb acetone gas. The 3DPS-based sensor also has an excellent selectivity for acetone detection. The high sensitivity can be explained by the increase in the specific surface area brought about by the hierarchical flower-like structure, the enhanced surface activity of the noble metal nanoparticles, and the rapid diffusion of free-gas and adsorbed gas molecules caused by the multiple channels of the microporous structure.

Highly Selective, ppb-Level Xylene Gas Detection by Sn2+-Doped NiO Flower-Like Microspheres Prepared by a One-Step Hydrothermal Method.

Detecting xylene gas is an important means of avoiding human harm from gas poisoning. A precise measurement demands that the gas sensor used must have high sensitivity, high selectivity, and low working temperature. To meet these requirements, in this study, Sn2+-doped NiO flower-like microspheres (SNM) with different amounts of Sn2+ synthesized by a one-step hydrothermal process were investigated. The responses of gas sensors based on different Sn2+-doped NiO materials for various targeting gases were fully characterized. It was found that all of the synthesized materials exhibited the best gas response at a working temperature of 180 degrees, which was much lower than the previously reported working temperature range of 300-500 degrees. When exposed to 10 ppm xylene, the 8 at% Sn2+-doped NiO sensor (mol ratio) exhibited the highest response, with a value of 30 (Rg/Ra). More significantly, the detection limit of the 8 at% Sn2+-doped NiO sensor for xylene is down in the ppb level. The Sn2+-doped NiO material also exhibits excellent selectivity for other gases with long-term stability and repeatability. The significant improvement in the response to xylene can theoretically be attributed to a decrease in the intrinsic hole carrier concentration, higher amounts of adsorbed oxygen and active sites.

[Applications of marine-derived chitosan and alginates in biomedicine].

Marine-derived biopolymers are excellent raw materials for biomedical products due to their abundant resources, good biocompatibility, low cost and other unique functions. Marine-derived biomaterials become a major branch of biomedical industry and possess promising development prospects since the industry is in line with the trend of "green industry and low-carbon economy". Chitosan and alginates are the most commonly commercialized marine-derived biomaterials and have exhibited great potential in biomedical applications such as wound dressing, dental materials, antibacterial treatment, drug delivery and tissue engineering. This review focuses on the properties and applications of chitosan and alginates in biomedicine.

2-Aminoimidazole facilitates efficient gene delivery in a low molecular weight poly(amidoamine) dendrimer.

Functional groups have shown great potential in gene delivery. However, a number of the reported functional groups can only overcome one certain physiological barrier, resulting in limited transfection efficiencies. Based on the structure-activity relationships of both imidazolyl and guanidyl, we designed a novel multifunctional group, 2-aminoimidazole (AM), for gene delivery. On modifying with the AM group, the transfection efficiency of low molecular weight poly(amidoamine) (G2) was 200 times greater than the parent dendrimer in vitro. In contrast, the transfection efficiency of G2 showed a decreasing trend when it was grafted with imidazole. Assays revealed that the AM group played multiple roles in gene delivery, including condensing DNA into monodisperse nanoparticles of 80-90 nm in diameter, achieving nearly ten times higher cellular-uptake efficacy, and enhancing the abilities of endosome/lysosome escape and nuclear localization. What's more, AM showed low toxicity. These results demonstrate that the AM group could be a promising tool in non-viral gene delivery.

[Effects of cultivated Cordyceps sinensis on proliferation and apoptosis of human leukemia K562 cells].

The present study was designed to investigate the effect of cultivated Cordyceps sinensis (CCS) on leukemia-derived K562 cells, and further explore the underlying mechanisms. After routine culture of K562 cells, MTT assay was used to detect the effect of CCS on survivel of human leukemia cell lines K562;DAPI staining was used to observe the morphological changes of the nucleus and AO/EB staining was used to observe cell apoptosis. JC-1 staining was employed to detect the changes in mitochondrial membrane potential. Flow cytometry (FCM) was used to detect cell cycle distribution, and Western blot analysis was used to detect the expression levels of Bax, Bcl-2, caspase 3, caspase 8, cyclin D1, CDK2, and CDK4 in K562 cells. The results showed that CCS (0.345-5.524 g·L⁻¹) substantially suppressed proliferation of K562 cells and induced G1/S phase arrest in a dose-dependent manner. DAPI and AO/EB staining indicated that cell apoptosis was significantly induced by CCS treatment, accompanied by decreased mitochondrial membrane potential demonstrated by JC-1 staining. Western blot results showed that CCS significantly increased the expression of Bax and, meanwhile, decreased the expression levels of Bcl-2, cyclin D1, CDK2, CDK4, caspase 3 and caspase 8. Collectively, our data demonstrated that CCS dose-dependently suppressed cell proliferation and induced cell apoptosis in K562 cells, and the mechanism might be associated with inducing cell cycle arrest, regulating Bcl-2/Bax ratio and activating the mitochondrial apoptosis pathway.

Prognostic value of total tumor volume in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.

BACKGROUND: Few studies have evaluated the prognostic value of total tumor volume (TTV), which reflects both the primary tumor volume and nodal tumor volume, in NPC. Furthermore, the relationship between TTV and survival remains unknown. The purpose of this study was to evaluate the prognostic value of TTV in patients with NPC treated with intensity-modulated radiation therapy (IMRT). METHODS: TTV was retrospectively assessed in 455 patients with newly diagnosed, non-metastatic NPC. All patients were treated using IMRT; 91.1% (288/316) of patients with stage III-IVb also received cisplatin-based chemotherapy. Receiver operating characteristic (ROC) curves were used to identify the optimal TTV cut-off point and examine the prognostic value of combined TTV with current clinical stage. RESULTS: Mean TTV was 11.1 cm3 (range, 0.3-27.9 cm3) in stage I, 22.5 cm3 (1.3-92.4 cm3) in stage II, 40.6 cm3 in stage III (3.2-129.2 cm3), and 77.5 cm3 in stage IVa-b (7.1-284.1 cm3). For all patients, the 4-year estimated FFS, OS, DMFS, and LRRFS rates for patients with a TTV ≤ 28 vs. > 28 cm3 were 93 vs. 71.4% (P < 0.001), 95.1 vs. 75.4% (P < 0.001), 94.5 vs. 79.4% (P < 0.001), and 96.2 vs. 88% (P = 0.001). TTV was an independent prognostic factor for FFS, OS, DMFS and LRRFS in all patients. In stage III-IVb, 4-year estimated FFS, OS, DMFS, and LRRFS for a TTV ≤28 vs. >28 cm3 were 88.9 vs. 70.5% (P = 0.001), 96.2 vs. 72.7% (P < 0.001), 91.2 vs. 78.3% (P = 0.008), and 93.8 vs. 87.6% (P = 0.063). TTV was an independent prognostic factor for FFS, OS and DMFS in stage III-IVb. Receiver operating characteristic (ROC) curve analysis curves revealed adding TTV to clinical stage had superior prognostic value for treatment failure compared to clinical stage alone (P = 0.016). CONCLUSIONS: TTV is an important prognosticator for treatment outcome and significantly improves the prognostic value of the current staging system for patients with NPC treated with IMRT.