TCP transcription factor StAST1 represses potato tuberization by regulating tuberigen complex activity.

Potato (Solanum tuberosum L.) is cultivated worldwide for its underground tubers, which provide an important part of human nutrition and serve as a model system for belowground storage organ formation. Similar to flowering, stolon-expressed FLOWERING LOCUS T-like (FT-like) protein SELF-PRUNING 6A (StSP6A) plays an instrumental role in tuberization by binding to the bZIP transcription factors StABI5-like 1 (StABL1) and StFD-like 1 (StFDL1), causing transcriptional reprogramming at the stolon subapical apices. However, the molecular mechanism regulating the widely conserved FT-bZIP interactions remains largely unexplored. Here, we identified a TCP transcription factor StAST1 (StABL1 and StSP6A-associated TCP protein 1) binding to both StSP6A and StABL1. StAST1 is specifically expressed in the vascular tissue of leaves and developing stolons. Silencing of StAST1 leads to accelerated tuberization and a shortened life cycle. Molecular dissection reveals that the interaction of StAST1 with StSP6A and StABL1 attenuates the formation of the alternative tuberigen activation complex (aTAC). We also observed StAST1 directly activates the expression of potato GA 20-oxidase gene (StGA20ox1) to regulate GA responses. These results demonstrate StAST1 functions as a tuberization repressor by regulating plant hormone levels; our findings also suggest a mechanism by which the widely conserved FT-FD genetic module is fine-tuned.

Integrative bioinformatics approach yields a novel gene expression risk model for prognosis and progression prediction in prostate cancer.

Prostate cancer (PCa), a prevalent malignancy among elderly males, exhibits a notable rate of advancement, even when subjected to conventional androgen deprivation therapy or chemotherapy. An effective progression prediction model would prove invaluable in identifying patients with a higher progression risk. Using bioinformatics strategies, we integrated diverse data sets of PCa to construct a novel risk model predicated on gene expression and progression-free survival (PFS). The accuracy of the model was assessed through validation using an independent data set. Eight genes were discerned as independent prognostic factors and included in the prediction model. Patients assigned to the high-risk cohort demonstrated a diminished PFS, and the areas under the curve of our model in the validation set for 1-year, 3-year, and 5-year PFS were 0.9325, 0.9041 and 0.9070, respectively. Additionally, through the application of single-cell RNA sequencing to two castration-related prostate cancer (CRPC) samples and two hormone-related prostate cancer (HSPC) samples, we discovered that luminal cells within CRPC exhibited an elevated risk score. Subsequent molecular biology experiments corroborated our findings, illustrating heightened SYK expression levels within tumour tissues and its contribution to cancer cell migration. We found that the knockdown of SYK could inhibit migration in PCa cells. Our progression-related risk model demonstrated the potential prognostic value of SYK and indicated its potential as a target for future diagnosis and treatment strategies in PCa management.

StMLP1, as a Kunitz trypsin inhibitor, enhances potato resistance and specifically expresses in vascular bundles during Ralstonia solanacearum infection.

Miraculin-like proteins (MLPs), members of the Kunitz trypsin inhibitor (KTI) family that are present in various plants, have been discovered to have a role in defending plants against pathogens. In this study, we identified a gene StMLP1 in potato that belongs to the KTI family. We found that the expression of StMLP1 gradually increases during Ralstonia solanacearum (R. solanacearum) infection. We characterized the promoter of StMLP1 as an inducible promoter that can be triggered by R. solanacearum and as a tissue-specific promoter with specificity for vascular bundle expression. Our findings demonstrate that StMLP1 exhibits trypsin inhibitor activity, and that its signal peptide is essential for proper localization and function. Overexpression of StMLP1 in potato can enhance the resistance to R. solanacearum. Inhibiting the expression of StMLP1 during infection accelerated the infection by R. solanacearum to a certain extent. In addition, the RNA-seq results of the overexpression-StMLP1 lines indicated that StMLP1 was involved in potato immunity. All these findings in our study reveal that StMLP1 functions as a positive regulator that is induced and specifically expressed in vascular bundles in response to R. solanacearum infection.

Feasibility Trial Exploring Immune-Related Biomarkers Pertaining to Rapid Immune Surveillance and Cytokine Changes after Consuming a Nutraceutical Supplement Containing Colostrum- and Egg-Based Low-Molecular-Weight Peptides.

Immune protection associated with consuming colostrum-based peptides is effective against bacterial and viral insults. The goal for this study was to document acute changes to immune surveillance and cytokine levels after consuming a single dose of a nutraceutical blend in the absence of an immune challenge. A double-blind, randomized, placebo-controlled, cross-over pilot study involved healthy participants attending two clinic visits. Blood draws were performed pre-consumption and at 1, 2, and 24 h after consuming a blend of bovine colostrum- and hen's egg-based low-molecular-weight peptides (CELMPs) versus a placebo. Immunophenotyping was performed by flow cytometry, and serum cytokines were measured by multiplex cytokine arrays. Consumption of CELMPs triggered increased immune surveillance after 1 h, involving monocytes (p < 0.1), natural killer (NK) cells (p < 0.1), and natural killer T (NKT) cells (p < 0.05). The number of NKT cells expressing the CD25 immunoregulatory marker increased at 1 and 2 h (p < 0.1). Increased serum levels of monocyte chemoattractant protein-1 (MCP-1) was observed at 2 and 24 h (24 h: p < 0.05). Selective reduction in pro-inflammatory cytokines was seen at 1, 2, and 24 h, where the 2-h reduction was highly significant for IL-6, IFN-γ, and IL-13. The rapid, transient increase in immune surveillance, in conjunction with the reduced levels of inflammatory markers, suggests that the CELMP blend of natural peptides provides immune benefits of use in preventive medicine. Further studies are warranted in chronic inflammatory conditions.

Bidirectional relationship between late-onset epilepsy (LOE) and dementia: A systematic review and meta-analysis of cohort studies.

OBJECTIVE: To explore the bidirectional relationship of late-onset epilepsy (LOE) with dementia and Alzheimer's disease (AD). METHODS: Using the common electronic databases, including PubMed, Cochrane Library databases and EMBASE, we systematically reviewed published cohort studies that assessed the risk of LOE in individuals comorbid with dementia or AD, and those with dementia or AD comorbid with LOE that had been published up to 31 March 2023. The data extraction process was carried out independently by two authors. The summary adjusted relative ratio (aRR) was calculated by employing Rev Man 5.3 for the inclusion of studies. To investigate the origins of heterogeneity, we conducted both subgroup and sensitivity analyses. In the presence of heterogeneity, a random-effects model was employed. To evaluate potential publication bias, we utilized the funnel plot and conducted Begg's and Egger's tests. RESULTS: We included 20 eligible studies in the final analysis after a rigorous screening process. Pooled results indicated that LOE was association with an increased risk of all-cause dementia (aRR: 1.34, 95% confidence interval [CI]: 1.13-1.59) and AD (aRR: 2.49, 95% CI: 1.16-5.32). In addition, the pooled effect size for LOE associated with baseline AD and all-cause dementia were 3.51 (95% CI: 3.47-3.56) and 2.53 (95% CI: 2.39-2.67), respectively. Both sensitivity and subgroup analyses showed that these positive correlations persisted. According to the results of the Egger's and Begg's tests, as well as visual inspection of funnel plots, none of the studies appeared to be biased by publication. CONCLUSION: The findings suggested that LOE is a potential risk factor for dementia and AD, and vice versa, dementia and AD are both potential risk indicators for LOE. Since there is substantial heterogeneity among the cohorts analyzed and more cohort studies should be conducted to confirm the correlations found in the current study.

Modulation of JA signalling reveals the influence of StJAZ1-like on tuber initiation and tuber bulking in potato.

Phytohormones and their interactions play critical roles in Solanum tuberosum (potato) tuberization. The stimulatory role of jasmonic acid (JA) in tuber development is well established because of its significant promotion of tuber initiation and tuber bulking. However, the dynamics and potential function of JA signalling in potato tuberization remain largely unknown. The present study investigated the role of the JAZ1 subtype, a suppressor of JA signalling, in potato tuberization. Using 35S:StJAZ1-like-GUS as a reporter, we showed that JA signalling was attenuated from the bud end to the stem end shortly after tuber initiation. Overexpression of StJAZ1-like suppressed tuber initiation by restricting the competence for tuber formation in stolon tips, as demonstrated by grafting an untransformed potato cultivar to the stock of StJAZ1-like-overexpressing transgenic potato plants (StJAZ1-like ox). In addition, transcriptional profiling analysis revealed that StJAZ1-like modulates the expression of genes associated with transcriptional regulators, cell cycle, cytoskeleton and phytohormones. Furthermore, we showed that StJAZ1-like is destabilised upon treatment with abcisic acid (ABA), and the attenuated tuberization phenotype in StJAZ1-like ox plants can be partially rescued by ABA treatment. Altogether, these results revealed that StJAZ1-like-mediated JA signalling plays an essential role in potato tuberization.

In Situ Separable Nanovaccines with Stealthy Bioadhesive Capability for Durable Cancer Immunotherapy.

Because of tumor heterogeneity and the immunosuppressive tumor microenvironment, most cancer vaccines typically do not elicit robust antitumor immunological responses in clinical trials. In this paper, we report findings about a bioadhesive nanoparticle (BNP)-based separable cancer vaccine, FeSHK@B-ovalbumin (OVA), to target multi-epitope antigens and exert effective cancer immunotherapy. After the FeSHK@B-OVA "nanorocket" initiates the "satellite-rocket separation" procedure in the acidic tumor microenvironment, the FeSHK@B "launch vehicle" can amplify intracellular oxidative stress persistently. This procedure allows for bioadhesiveness-mediated prolonged drug retention within the tumor tissue and triggers the immunogenic death of tumor cells that transforms the primary tumors into antigen depots, which acts synergistically with the OVA "satellite" to trigger robust antigen-specific antitumor immunity. The cooperation of these two immunostimulants not only efficiently inhibits the primary tumor growth and provokes durable antigen-specific immune activation in vivo but also activates a long-term and robust immune memory effect to resist tumor rechallenge and metastasis. These results highlight the enormous potential of FeSHK@B-OVA to serve as an excellent therapeutic and prophylactic cancer nanovaccine. By leveraging the antigen depots in situ and the synergistic effect among multi-epitope antigens, such a nanovaccine strategy with stealthy bioadhesion may offer a straightforward and efficient approach to developing various cancer vaccines for different types of tumors.

Transcription factor StABI5-like 1 binding to the FLOWERING LOCUS T homologs promotes early maturity in potato.

Potato (Solanum tuberosum L.) maturity involves several important traits, including the onset of tuberization, flowering, leaf senescence, and the length of the plant life cycle. The timing of flowering and tuberization in potato is mediated by seasonal fluctuations in photoperiod and is thought to be separately controlled by the FLOWERING LOCUS T-like (FT-like) genes SELF-PRUNING 3D (StSP3D) and SELF-PRUNING 6A (StSP6A). However, the biological relationship between these morphological transitions that occur almost synchronously remains unknown. Here, we show that StABI5-like 1 (StABL1), a transcription factor central to abscisic acid (ABA) signaling, is a binding partner of StSP3D and StSP6A, forming an alternative florigen activation complex and alternative tuberigen activation complex in a 14-3-3-dependent manner. Overexpression of StABL1 results in the early initiation of flowering and tuberization as well as a short life cycle. Using genome-wide chromatin immunoprecipitation sequencing and RNA-sequencing, we demonstrate that AGAMOUS-like and GA 2-oxidase 1 genes are regulated by StABL1. Phytohormone profiling indicates an altered gibberellic acid (GA) metabolism and that StABL1-overexpressing plants are insensitive to the inhibitory effect of GA with respect to tuberization. Collectively, our results suggest that StABL1 functions with FT-like genes to promote flowering and tuberization and consequently life cycle length in potato, providing insight into the pleiotropic functioning of the FT gene.

ScAREB4 promotes potato constitutive and acclimated freezing tolerance associated with enhancing trehalose synthesis and oxidative stress tolerance.

Cold is a major environmental factor that restrains potato production. Abscisic acid (ABA) can enhance freezing tolerance in many plant species, but powerful evidence of the ABA-mediated signalling pathway related to freezing tolerance is still in deficiency. In the present study, cold acclimation capacity of the potato genotypes was enhanced alongside with improved endogenous content of ABA. Further exogenous application of ABA and its inhibitor (NDGA) could enhance and reduce potato freezing tolerance, respectively. Moreover, expression pattern of downstream genes in ABA signalling pathway was analysed and only ScAREB4 was identified with specifically upregulate in S. commersonii (CMM5) after cold and ABA treatments. Transgenic assay with overexpression of ScAREB4 showed that ScAREB4 promoted freezing tolerance. Global transcriptome profiling indicated that overexpression of ScAREB4 induced expression of TPS9 (trehalose-6-phosphate synthase) and GSTU8 (glutathione transferase), in accordance with improved TPS activity, trehalose content, higher GST activity and accumulated dramatically less H2 O2 in the ScAREB4 overexpressed transgenic lines. Taken together, the current results indicate that increased endogenous content of ABA is related to freezing tolerance in potato. Moreover, ScAREB4 functions as a downstream transcription factor of ABA signalling to promote cold tolerance, which is associated with increased trehalose content and antioxidant capacity.

Protein phosphatase StTOPP6 negatively regulates potato bacterial wilt resistance by modulating MAPK signaling.

Potato (Solanum tuberosum) is an important crop globally and is grown across many regions in China, where it ranks fourth in the list of staple foods. However, its production and quality are severely affected by bacterial wilt caused by Ralstonia solanacearum. In this study, we identified StTOPP6, which belongs to the type one protein phosphatase (TOPP) family, and found that transient knock down of StTOPP6 in potato increased resistance against R. solanacearum. RNA-seq analysis showed that knock down of StTOPP6 activated immune responses, and this defense activation partly depended on the mitogen-activated protein kinase (MAPK) signal pathway. StTOPP6 inhibited the expression of StMAPK3, while overexpression of StMAPK3 enhanced resistance to R. solanacearum, supporting the negative role of StTOPP6 in plant immunity. Consistent with the results of knock down of StTOPP6, overexpressing the phosphatase-dead mutation StTOPP6m also attenuated infection and up-regulated MAPK3, showing that StTOPP6 activity is required for disease. Furthermore, we found that StTOPP6 affected the StMAPK3-mediated downstream defense pathway, eventually suppressing the accumulation of reactive oxygen species (ROS). Consistent with these findings, plants with knock down of StTOPP6, overexpression of StTOPP6m, and overexpression of StMAPK3 all displayed ROS accumulation and enhanced resistance to R. solanacearum. Taken together, the findings of our study demonstrate that StTOPP6 negatively regulates resistance to bacterial wilt by affecting the MAPK3-mediated pathway.

Exploration of meaning, motivation, and preparedness to care amongst the one-child policy generation in China.

OBJECTIVES: In China there is a cultural expectation (Xiao, -filial piety) that offspring should provide care for their parents. However, the sustainability of this is threatened by the impact of the One-Child Policy (OCP) (1979-2015), which has resulted in a diminution in numbers of children available to care, rapid urbanisation and increase in the number of women in employment. In this context, the objective was to explore the motivations, meaning, and preparedness for future caregiving of offspring affected by the OCP. DESIGN AND METHODS: We adopted a constructivist position using a hermeneutic phenomenology approach and interviewed eight current and prospective caregivers aged 20-35 years about future caregiving responsibilities. Data were obtained through in-depth interviews, analysed using reflective Thematic Analysis. RESULTS AND CONCLUSION(S): Three prominent themes: (i) Caregiving beliefs, (ii) Caregiving conditions and (iii) Contextual factors were identified under an overarching theme "Competing pressures-meanings, motivation and preparedness". Despite the inherent stress, participants envisaged providing or organising care in the future to fulfil Xiao, and most viewed long-term care settings as unviable. Ultimately, the findings suggested that the actual performance of caregiving would not always measure up to ideal expectations, resulting in 'filial discrepancy' that is, a gap between societal expectations for caregiving to older relatives and actual caregiving performance. This could adversely impact the caregivers and quality of care provided. The findings highlighted the urgent need to develop culturally attuned services, including education and training for family caregivers, health and social care professionals.

Differential Activities of the Botanical Extract PBI-05204 and Oleandrin on Innate Immune Functions under Viral Challenge Versus Inflammatory Culture Conditions.

The Nerium oleander extract PBI 05204 (PBI) and its cardiac glycoside constituent oleandrin have direct anti-viral properties. Their effect on the immune system, however, is largely unknown. We used an in vitro model of human peripheral blood mononuclear cells to document effects under three different culture conditions: normal, challenged with the viral mimetic polyinosinic:polycytidylic acid Poly I:C, and inflamed by lipopolysaccharide (LPS). Cells were evaluated for immune activation marks CD69, CD25, and CD107a, and culture supernatants were tested for cytokines. Both PBI and oleandrin directly activated Natural Killer (NK) cells and monocytes and triggered increased production of cytokines. Under viral mimetic challenge, PBI and oleandrin enhanced the Poly I:C-mediated immune activation of monocytes and NK cells and enhanced production of IFN-γ. Under inflammatory conditions, many cytokines were controlled at similar levels as in cultures treated with PBI and oleandrin without inflammation. PBI triggered higher levels of some cytokines than oleandrin. Both products increased T cell cytotoxic attack on malignant target cells, strongest by PBI. The results show that PBI and oleandrin directly activate innate immune cells, enhance anti-viral immune responses through NK cell activation and IFN-γ levels, and modulate immune responses under inflamed conditions. The potential clinical impact of these activities is discussed.

The changes and causes of asthenopia after ICL implantation.

OBJECTIVE: To detect the presence of asthenopia after implantation of Implantable Collamer Lens (ICL). METHOD: Design: prospective observational case series. Patients with myopia and/or astigmatism who underwent ICL surgeries and completed 3-month follow-up were enrolled. Asthenopia scores, amplitude of accommodation (AA), positive/negative relative accommodation (PRA/NRA), accommodative facility (AF), the ratio of accommodative convergence and accommodation (AC/A), Schirmer test, noninvasive breakup time (NBUT), and HOA were examined before surgeries and at 1 week, 1 month and 3 months postoperatively then statistically analyzed. RESULTS: Symptoms of asthenopia were significantly decreased at 1 week after ICL surgeries than those before surgeries, but increased gradually as time went by, eventually recovered at 3 months postoperatively. AA, AF, AC/A decreased 1 week postoperatively, returned to the baseline at 1 month and were improved at 3 months after surgeries. NBUT at 1 week, 1 month and 3 months after surgeries were significantly decreased and was the lowest at 1 week postoperatively. PRA, NRA, Schiermer values and HOA had no significant change. Correlation analysis showed that the lower AF and NBUT after ICL surgeries, the more severe the asthenopia symptoms. CONCLUSION: The symptoms of asthenopia aggravated transiently after ICL implantation surgeries, but improved gradually with time. AF and NBUT were important factors affecting the changes of asthenopia.

The Role of Surveillance Inspections in Reducing False-Positives of SARS-CoV-2 Omicron Variants during the COVID-19 Epidemic.

Objective: This study aims to assess the effectiveness of surveillance inspections conducted by the provincial health committee in Quanzhou city during a COVID-19 outbreak in reducing false-positive results in SARS-CoV-2 RT-PCR assays. Method: The team conducted on-site inspections of laboratories that participated in mass screening, recording any violations of rules. Results: The positive cases in five rounds of mass screening were 23, 173, and 4 in Licheng District, Fengze District, and Luojang District, respectively. The false-positive rates in the five rounds of mass screening were 0.0099%, 0.0063%, 0.0018%, 0.0006%, and 0%, respectively. The study also recorded that the number of violations in the seven selected laboratories was 36, 68, 69, 42, 60, 54 and 47. The corresponding false-positive rates were 0.0012%, 0.0060%, 0.0082%, 0.0032%, 0.0060%, 0.0027%, and 0.0021%, respectively. The study found a positive correlation between false-positive rates and the number of violations (r = 0.905, P=0.005), and an inverse correlation between false-positive rates and the frequency of surveillance inspections (r = -0.950, P < 0.001). Conclusion: Daily surveillance inspection in laboratories can remind laboratories to strictly comply with standard procedures, focus on laboratory quality control, and reduce the occurrence of false-positive cases in SARS-CoV-2 nucleic acid tests to some extent. This study recommends that government decision-making departments establish policies and arrange experts to conduct daily surveillance inspections to improve laboratory quality control.

[COL4A5 genotypes and clinical characteristics of children with Alport syndrome]. / 儿童Alport综合征COL4A5åŸºå› åž‹åŠä¸´åºŠç‰¹ç‚¹åˆ†æž.

OBJECTIVES: To investigate the genotypes of the pathogenic gene COL4A5 and the characteristics of clinical phenotypes in children with Alport syndrome (AS). METHODS: A retrospective analysis was performed for the genetic testing results and clinical data of 19 AS children with COL4A5 gene mutations. RESULTS: Among the 19 children with AS caused by COL4A5 gene mutations, 1 (5%) carried a new mutation of the COL4A5 gene, i.e., c.3372A>G(p.P1124=) and presented with AS coexisting with IgA vasculitis nephritis; 3 children (16%) had large fragment deletion of the COL4A5 gene, among whom 2 children (case 7 had a new mutation site of loss51-53) had gross hematuria and albuminuria at the onset, and 1 child (case 13 had a new mutation site of loss3-53) only had microscopic hematuria, while the other 15 children (79%) had common clinical phenotypes of AS, among whom 7 carried new mutations of the COL4A5 gene. Among all 19 children, 3 children (16%) who carried COL4A5 gene mutations also had COL4A4 gene mutations, and 1 child (5%) had COL4A3 gene mutations. Among these children with double gene mutations, 2 had gross hematuria and proteinuria at the onset. CONCLUSIONS: This study expands the genotype and phenotype spectrums of the pathogenic gene COL4A5 for AS. Children with large fragment deletion of the COL4A5 gene or double gene mutations of COL4A5 with COL4A3 or COL4A4 tend to have more serious clinical manifestations.

Heritability of tea drinking and its relationship with cigarette smoking in the Chinese male adult twins.

The aims of this study are to estimate the contributions of genetic factors to the variation of tea drinking and cigarette smoking, to examine the roles of genetic factors in their correlation and further to investigate underlying causation between them. We included 11 625 male twin pairs from the Chinese National Twin Registry (CNTR). Bivariate genetic modelling was fitted to explore the genetic influences on tea drinking, cigarette smoking and their correlation. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was further used to explore the causal relationship between them. We found that genetic factors explained 17% and 23% of the variation in tea drinking and cigarette smoking, respectively. A low phenotypic association between them was reported (rph = 0.21, 95% confidence interval [CI]: [0.19, 0.24]), which was partly attributed to common genetic factors (rA = 0.45, 95% CI [0.19, 1.00]). In the ICE FALCON analysis with current smoking as the exposure, tea drinking was associated with his own (ßself = 0.39, 95% CI [0.23, 0.55]) and his co-twin's smoking status (ßco-twin = 0.25, 95% CI [0.10, 0.41]). Their association attenuated with borderline significance conditioning on his own smoking status (p = 0.045), indicating a suggestive causal effect of smoking status on tea drinking. On the contrary, when we used tea drinking as the predictor, we found familial confounding between them only. In conclusion, both tea drinking and cigarette smoking were influenced by genetic factors, and their correlation was partly explained by common genetic factors. In addition, our finding suggests that familial confounders account for the relationship between tea drinking and cigarette smoking. And current smoking might have a causal effect on weekly tea drinking, but not vice versa.

Discovery of novel sulphonamide hybrids that inhibit LSD1 against bladder cancer cells.

Aim:A series of sulphonamide hybrids were designed, synthesised, and identified as potential lysine-specific demethylase 1 (LSD1) inhibitors.Materials and methods: Bladder cancer cell lines were cultured to evaluate the antiproliferative activity. Inhibitory evaluation of sulphonamide hybrids against LSD1 were performed.Conclusion: sulphonamide derivative L8 exhibited the antiproliferative activity against HTB5, HTB3, HT1376, and HTB1 cells with IC50 values of 1.87, 0.18, 0.09, and 0.93 µM, respectively. Compound L8 as a selective and reversible LSD1 inhibitor could inhibit LSD1 with the IC50 value of 60 nM. It effectively inhibited LSD1 by increasing the expression levels of H3K4me1, H3K4me2, and H3K9me2 in HT1376 cells. To the best of our knowledge, this was the first report which showed that sulphonamide-quinoline-dithiocarbamate hybrids potently inhibited LSD1 in bladder cancer cells. Our studies give the potential application of the sulphonamide-based scaffold for developing LSD1 inhibitors to treat bladder cancer.

Bioadhesive Nanoparticles for Local Drug Delivery.

Local drug delivery is an effective strategy for achieving direct and instant therapeutic effects. Current clinical treatments have fallen short and are limited by traditional technologies. Bioadhesive nanoparticles (NPs), however, may be a promising carrier for optimized local drug delivery, offering prolonged drug retention time and steadily maintained therapeutic concentrations. In addition, the possibility of clinical applications of this platform are abundant, as most polymers used for bioadhesion are both biodegradable and biocompatible. This review highlights the major advances in the investigations of polymer-based bioadhesive nanoparticles and their innumerable applications in local drug delivery.

Sex-linked genetic diversity and differentiation in a globally distributed avian species complex.

Sex chromosomes often bear distinct patterns of genetic variation due to unique patterns of inheritance and demography. The processes of mutation, recombination, genetic drift and selection also influence rates of evolution on sex chromosomes differently than autosomes. Measuring such differences provides information about how these processes shape genomic variation and their roles in the origin of species. To test hypotheses and predictions about patterns of autosomal and sex-linked genomic diversity and differentiation, we measured population genetic statistics within and between populations and subspecies of the barn swallow (Hirundo rustica) and performed explicit comparisons between autosomal and Z-linked genomic regions. We first tested for evidence of low Z-linked genetic diversity and high Z-linked population differentiation relative to autosomes, then for evidence that the Z chromosome bears greater ancestry information due to faster lineage sorting. Finally, we investigated geographical clines across hybrid zones for evidence that the Z chromosome is resistant to introgression due to selection against hybrids. We found evidence that the barn swallow mating system, demographic history and linked selection each contribute to low Z-linked diversity and high Z-linked differentiation. While incomplete lineage sorting is rampant across the genome, our results indicate faster sorting of ancestral polymorphism on the Z. Finally, hybrid zone analyses indicate barriers to introgression on the Z chromosome, suggesting that sex-linked traits are important in reproductive isolation, especially in migratory divide regions. Our study highlights how selection, gene flow and demography shape sex-linked genetic diversity and underlines the relevance of the Z chromosome in speciation.

Anticancer evaluation of a novel dithiocarbamate hybrid as the tubulin polymerization inhibitor.

Novel quinoline-dithiocarbamate hybrids were synthesized and designed by the molecular hybridization strategy. All these derivatives were evaluated for their antiproliferative activity against three selected cancer cell lines (MGC-803, HepG-2 and PC-3). Among them, compound 10c displayed the best antiproliferative activity against PC-3 cells with an IC50 value of 0.43 µM. Celluar mechanisms investigated that compound 10c could inhibit the migration against PC-3 cells by regulation the expression levels of E-cadherin and N-cadherin. Compound 10c induced morphological changes of PC-3 cells and regulated apoptosis-related proteins (Bcl-2, Bax and Cleaved-Parp). In addition, compound 10c inhibited tubulin polymerization in vitro with an IC50 value of 4.02 µM. Importantly, compound 10c inhibited the growth of PC-3 cells in vivo with the low toxicity toward mice. These results suggested that compound 10c might be an antitumor agent with potential for treating prostate cancer.