Search

Background: Panax notoginseng saponins (PNS) are commonly used first-line drugs for treating cerebral thrombosis and stroke in China. However, the synchronized and targeted delivery of active ingredients in traditional Chinese medicine (TCM) poses a significant challenge for modern TCM formulations. Methods: Bovine serum albumin (BSA) was modified using 2-methacryloyloxyethyl phosphorylcholine (MPC), an analog of acetylcholine, and subsequently adsorbed the major PNS onto the modified albumin to produce MPC-BSA@PNS nanoparticles (NPs). This novel delivery system facilitated efficient and synchronized transport of PNS across the blood–brain barrier (BBB) through active transport mediated by nicotinic acetylcholine receptors. Results: In vitro experiments demonstrated that the transport rates of R1, Rg1, Rb1, and Rd across the BBB were relatively synchronous in MPC-BSA@PNS NPs compared to those in the PNS solution. Additionally, animal experiments revealed that the brain-targeting efficiencies of R1 + Rg1 + Rb1 in MPC-BSA@PNS NPs were 2.02 and 7.73 times higher than those in BSA@PNS NPs and the free PNS group, respectively. Conclusions: This study presents a simple and feasible approach for achieving the targeted delivery of complex active ingredient clusters in TCM. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis (MPS) is a lysosomal storage disease caused by genetic defects that result in deficiency of one specific enzyme activity, consequently impairing the stepwise degradation of glycosaminoglycans (GAGs). Except for MPS II, the other types of MPS have autosomal recessive inheritance in which two copies of an abnormal allele must be present in order for the disease to develop. In this study, we present the status of variant alleles and biochemistry results found in infants suspected of having MPS I, II, IVA, and VI. A total of 324 suspected infants, including 12 for MPS I, 223 for MPS II, 72 for MPS IVA, and 17 for MPS VI, who were referred for MPS confirmation from newborn screening centers in Taiwan, were enrolled. In all of these infants, one specific enzyme activity in dried blood spot filter paper was lower than the cut-off value in the first blood sample, as well asin a second follow-up sample. The confirmatory methods used in this study included Sanger sequencing, next-generation sequencing, leukocyte enzyme fluorometric assay, and GAG-derived disaccharides in urine using tandem mass spectrometry assays. The results showed that five, nine, and six infants had MPS I, II, and IVA, respectively, and all of them were asymptomatic. Thus, a laboratory diagnosis is extremely important to confirm the diagnosis of MPS. The other infants with identified nucleotide variations and reductions in leukocyte enzyme activities were categorized as being highly suspected cases requiring long-term and intensive follow-up examinations. In summary, the final confirmation of MPS depends on the most powerful biomarkers found in urine, i.e., the quantification of GAG-derived disaccharides including dermatan sulfate, heparan sulfate, and keratan sulfate, and analysis of genetic variants can help predict outcomes and guide treatment. [ABSTRACT FROM AUTHOR]

Key message: MADS-box genes family may play important roles in the flower sex determination in Excoecaria agallocha. A total of 73 MADS-box genes were identified in E. agallocha. De novo transcriptome assembly analysis suggested that AP1/FUL, AP3/PI, AGL104, and SOC1 plays potential roles in E. agallocha flower sex determination. Context: Excoecaria agallocha is a dioecious species containing both male and female individuals producing unisexual flowers. The underlying mechanisms regulating inflorescence differentiation in these species remains poorly understood. Aims: Flower development influences reproduction and breeding in E.agallocha, which contributes to ecological restoration in the intertidal zone. Methods: We performed de novo transcriptome assembly analysis on male and female flowers and leaves from E. agallocha. Results: We identified a total of 73 MADS-box genes in the E. agallocha genome, which we grouped into five distinct classes (MIKCc, Mα, Mβ, Mγ, MIKC*) after phylogenetic comparisons with J. curcas homologs. We analyzed expression profiles and suggested AP1/FUL, AP3/PI, AGL104, and SOC1 as candidate regulators of sex determination. In addition, several EaMADS genes were significantly upregulated in flowers compared to leaves. Conclusion: Our study represents the first detailed, comprehensive evaluation of the regulation of MADS-box genes associated with sex determination in E. agallocha. The assembled transcriptomic profiles increase the genetic information available for this species and constitute an important contribution to functional studies of inflorescence genes. In turn, this will help exploring the molecular mechanisms underlying the evolution of E. agallocha. [ABSTRACT FROM AUTHOR]

Background: Mucopolysaccharidosis II (MPS II) is an X-linked disorder resulting from a deficiency in lysosomal enzyme iduronate-2-sulfatase (IDS), which causes the accumulation of glycosaminoglycans (GAGs) in the lysosomes of many tissues and organs, leading to progressive cellular dysfunction. An MPS II newborn screening program has been available in Taiwan since 2015. The aim of the current study was to collect and analyze the long-term follow-up data of the screen-positive subjects in this program. Methods: From August 2015 to April 2022, 548,624 newborns were screened for MPS II by dried blood spots using tandem mass spectrometry, of which 202 suspected infants were referred to our hospital for confirmation. The diagnosis of MPS II was confirmed by IDS enzyme activity assay in leukocytes, quantitative determination of urinary GAGs by mass spectrometry, and identification of the IDS gene variant. Results: Among the 202 referred infants, 10 (5%) with seven IDS gene variants were diagnosed with confirmed MPS II (Group 1), 151 (75%) with nine IDS gene variants were classified as having suspected MPS II or pseudodeficiency (Group 2), and 41 (20%) with five IDS gene variants were classified as not having MPS II (Group 3). Long-term follow-up every 6 months was arranged for the infants in Group 1 and Group 2. Intravenous enzyme replacement therapy (ERT) was started in four patients at 1, 0.5, 0.4, and 0.5 years of age, respectively. Three patients also received hematopoietic stem cell transplantation (HSCT) at 1.5, 0.9, and 0.6 years of age, respectively. After ERT and/or HSCT, IDS enzyme activity and the quantity of urinary GAGs significantly improved in all of these patients compared with the baseline data. Conclusions: Because of the progressive nature of MPS II, early diagnosis via a newborn screening program and timely initiation of ERT and/or HSCT before the occurrence of irreversible organ damage may lead to better clinical outcomes. The findings of the current study could serve as baseline data for the analysis of the long-term effects of ERT and HSCT in these patients. [ABSTRACT FROM AUTHOR]

Key message: MADS-box genes family may play important roles in the flower sex determination in Excoecaria agallocha. A total of 73 MADS-box genes were identified in E. agallocha. De novo transcriptome assembly analysis suggested that AP1/FUL, AP3/PI, AGL104, and SOC1 plays potential roles in E. agallocha flower sex determination. Context: Excoecaria agallocha is a dioecious species containing both male and female individuals producing unisexual flowers. The underlying mechanisms regulating inflorescence differentiation in these species remains poorly understood. Aims: Flower development influences reproduction and breeding in E.agallocha, which contributes to ecological restoration in the intertidal zone. Methods: We performed de novo transcriptome assembly analysis on male and female flowers and leaves from E. agallocha. Results: We identified a total of 73 MADS-box genes in the E. agallocha genome, which we grouped into five distinct classes (MIKCc, Mα, Mβ, Mγ, MIKC*) after phylogenetic comparisons with J. curcas homologs. We analyzed expression profiles and suggested AP1/FUL, AP3/PI, AGL104, and SOC1 as candidate regulators of sex determination. In addition, several EaMADS genes were significantly upregulated in flowers compared to leaves. Conclusion: Our study represents the first detailed, comprehensive evaluation of the regulation of MADS-box genes associated with sex determination in E. agallocha. The assembled transcriptomic profiles increase the genetic information available for this species and constitute an important contribution to functional studies of inflorescence genes. In turn, this will help exploring the molecular mechanisms underlying the evolution of E. agallocha. [ABSTRACT FROM AUTHOR]

Background: Chronic cough is a common complaint which affects a large number of patients worldwide. Increased cough sensitivity is a very important cause of chronic persistent cough. However, there are limited clinical diagnosis and treatment for increased cough sensitivity. Transient receptor potential vanilloid-1 (TRPVl) is a member of the transient receptor potential (TRP) family of channels which is very closely associated with respiratory diseases. However, the mechanism through which TRPV1 that influences downstream events is still poorly understood. Results: Capsaicin induced increase in cough sensitivity by upregulating the protein level of TRPV1, leading to the secretions of Substance P and neurokinin A which stimulated neurogenic inflammation. However, sinomenine, a component of traditional Chinese medicine, significantly attenuated the capsaicin-induced cough by inhibiting the expression of TRPV1 in guinea pigs. In addition, capsaicin increased the expression of SOX5 which mediated the transcriptional upregulation of TRPV1. However, pretreatment with sinomenine reduced the expression of SOX5. Conclusion: These results indicate that capsaicin induced increase in cough sensitivity by activating neurogenic inflammation, while sinomenine attenuated the increase in cough sensitivity by inhibiting the expressions of SOX5 and TRPV1 in guinea pigs. This finding may provide a novel target for the treatment of aggravated cough sensitivity. [ABSTRACT FROM AUTHOR]

A novel moderately halophilic bacterial strain, designated YIM 93176T, was isolated from a saltern in Korea and subjected to a polyphasic taxonomic study. This isolate YIM 93176T was observed to grow in the presence of 0–22% (w/v) NaCl and at pH 6.0–10.0 and 10–45 °C; optimum growth was observed with 5–10% (w/v) NaCl and at pH 7.0–9.0 and 28–37 °C. Based on 16S rRNA gene sequences analysis, the nearest relatives were Lentibacillus alimentarius M2024T (96.5% similarity), followed by Virgibacillus carmonensis LMG 20964T (96.0%) and the other type strains of the family Bacillaceae, but phylogenetic analysis indicated that strain YIM 93176T belonged to the cluster comprising type species of the genus Lentibacillus. Genome sequencing of strain YIM 93176T revealed a genome size of 3.2 Mb and a DNA G + C content of 40.5 mol%. The major fatty acids were anteiso-C15:0 (40.7%) and iso-C15:0 (26.4%), while the predominant respiratory quinone was menaquinone 7. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. These genotypic and chemotaxonomic characteristics supported affiliation of strain YIM 93176T to the genus Lentibacillus. In addition, phenotypic characteristics could distinguish strain YIM 93176T from its closely related species in genus Lentibacillus. Based on the cumulative evidences from the polyphasic taxonomic study, strain YIM 93176T represents a novel species of the genus Lentibacillus, for which name Lentibacillus saliphilus sp. nov. (type strain YIM 93176T = CCTCC AB 208139T = DSM 21375T) is proposed. [ABSTRACT FROM AUTHOR]

Objective: To test the effect of Banxia Xiexin Decoction (半夏泻心汤, BXD) on the contraction and relaxation of gastric smooth muscle (SM) in diabetic gastroparesis (DGP) model rats, and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro. Methods: Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table: control group, model group, high-, medium- and low-dose BXD groups (9.2, 4.6 and 1.8 g/(kg·d), respectively), and domperidone group (10 mg/(kg·d)), 10 rats per group. DGP model was established initially by a single intraperitoneal injection of streptozotocin (STZ), and was confirmed by recording gastric emptying, intestinal transport velocity and gastric myoelectric activity of rats after 2 months. Each group was treated with a corresponding drug for 4 weeks. The mRNA and protein expressions of phospholipase C (PLC), inositol triphosphate (IP3), neuronal nitric oxide synthase (nNOS), and cyclic guanosine monophosphate (cGMP) dependent protein kinase G (PKG) were detected by reverse transcription-polymerase chain reaction and Western blot, respectively, while nitric oxide (NO) and cGMP expressions were detected by enzyme-linked immunosorbent assay. Gastric tissues were obtained from rats for primary cell culture preparation. Gastric SM cells were treated with 0.8 µmol/L of STZ or STZ plus 1,000, 500 and 200 µg/mL of BXD or STZ plus 2.5 µmol/mL of domperidone for 24, 48, 72 or 96 h, respectively. The length of gastric SM cells and intracellular Ca2+ concentration ([Ca2+]i) before and after BXD treatment was measured. Results: Compared with the model group, high- and medium-dose BXD and domperidone significantly increased the expressions of PLC, IP3, NO, nNOS, cGMP and PKG in rat's gastric tissue (P<0.01). Gastric SM cells treated with BXD showed a time- and dose-dependent increase in cell viability (P<0.01). The treatment with high- and medium-dose BXD and domperidone inhibited the increase in gastric SM cells length and increased [Ca2+]i compared with the model cells (P<0.01). Conclusions: Treatment with high- and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats. The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP3-Ca2+/NO-cGMP-PKG signal pathway. [ABSTRACT FROM AUTHOR]

The pathogenesis of inflammatory bowel disease (IBD) remains unclear, and it is currently believed that an imbalance in regulatory T (Treg) cells/T helper 17 cells (Th17 cells) is related to the occurrence and development of IBD. Recently, the JAK2 inhibitor AG490 has been used in animal models such as rheumatoid arthritis and bronchial asthma models and shown to exert immunoregulatory functions that improve disorder in the Treg/Th17 cell balance. This study aimed to evaluate the effect of AG490 on the intestinal inflammatory process in an IBD rat model. A dextran sulfate sodium (DSS)‐induced IBD rat model was established, and disease activity index (DAI) scores were calculated. The histopathological damage score was determined by haematoxylin‐eosin (H&E) staining. Treg/Th17 cells in the spleen were detected by flow cytometry. The levels of interleukin (IL)‐10, IL‐6 and IL‐17A were detected by enzyme‐linked immunosorbent assay (ELISA). AG490 attenuated DSS‐induced IBD injury by regulating the Treg/Th17 balance and related cytokine secretion to reduce the DAI and colonic tissue damage. Thus, AG490 may be a new method for effective treatment of IBD. [ABSTRACT FROM AUTHOR]

In this paper, we propose an integrated approach for human detection in surveillance video. In our approach, the moving object is extracted by background subtraction; and the background model is updated by the first-order recurrence filter. Then, two complementary features are extracted for moving object classification. They are contour-based description: Fourier descriptor and region-based description: histogram of oriented gradient. As the binary classifier (support vector machine) is able to provide the posterior probability, we effectively integrate two types of features to achieve better performance. Experimental results show that the proposed approach is effective and outperforms some existing technique. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) X protein (HBx) has been implicated in HBV-associated carcinogenesis through activation of IκB kinase (IKK)/nuclear factor kappa B (NF-κB) signaling pathway. Besides activating NF-κB in the cytoplasm, IKKα was found in the nucleus to regulate gene expression epigenetically in response to various stimuli. However, it is unknown whether nuclear IKKα plays a role in HBx-associated tumor progression. Moreover, the molecular mechanism underlying IKKα nuclear transport also remains to be elucidated. Here, we disclosed HBx as a new inducer of IKKα nuclear transport in hepatoma cells. HBx induced IKKα nuclear transport in an Akt-dependent manner. HBx-activated Akt promoted IKKα nuclear translocation via phosphorylating its threonine-23 (Thr23). In addition, IKKα ubiquitination enhanced by HBx and Akt also contributed to the IKKα accumulation in the nucleus, indicating the involvement of ubiquitination in Akt-increased IKKα nuclear transport in response to HBx. Furthermore, inhibition of IKKα nuclear translocation by mutation of its nuclear localization signal and Thr23 diminished IKKα-dependent cell migration. Taken together, our findings shed light on the molecular mechanism of IKKα nuclear translocation and provide a potential role of nuclear IKKα in HBx-mediated hepatocellular carcinoma (HCC) progression. J. Cell. Physiol. 227: 1446-1454, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Although expansion of higher education in East Asia has had a positive impact on Asian societies, it has created a number of challenges relating to accountability. [ABSTRACT FROM AUTHOR]

The complete chloroplast genome of Ilex asprella, a species of Aquifoliaceae is reported for the first time in this study. The complete chloroplast genome of I. asprella is 157,856 bp in length with a typical quadripartite structure, consisting of a large single-copy region (LSC, 87,258 bp), a single-copy region (SSC, 18,441 bp) and a pair of inverted repeats (IRs, 26,082 bp). There are 114 genes annotated, including 85 unique protein-coding genes, four unique ribosomal RNA genes, and 30 transfer RNA genes. To investigate the evolution status of T. concolor, as well as Scrophulariaceae, we build a phylogenetic tree with I. asprella and other eight species based on their complete chloroplast genomes. According to the phylogenetic topologies, I. asprella was closely related to I. wilsonii. [ABSTRACT FROM AUTHOR]

Torenia benthamiana Hance is an endemic plant species distributed in southern China. In this study, we report and characterize the complete plastid genome sequence of T. benthamiana in order to provide genomic resources helpful for promoting its conservation and garden utilization. The complete plastome is 153,526 bp in length and contains the typical quadripartite structure of angiosperm plastome, including two inverted repeat (IR) regions of 24,638 bp, a large single-copy (LSC) region of 85,417 bp, and a small single-copy (SSC) region of 18,833 bp. The plastome contains 114 genes, consisting of 80 unique protein-coding genes, 30 unique tRNA gene, and 4 unique rRNA genes. The overall A/T content in the plastome of T. benthamiana is 62.40%. The complete plastome sequence of T. benthamiana will provide a useful resource for the conservation and garden utilization of this species as well as for the phylogenetic studies of Linderniaceae. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases (LSDs) caused by an inherited gene defect. MPS patients can remain undetected unless the initial signs or symptoms have been identified. Newborn screening (NBS) programs for MPSs have been implemented in Taiwan since 2015, and more than 48.5% of confirmed cases of MPS have since been referred from these NBS programs. The purpose of this study was to report the current status of NBS for MPSs in Taiwan and update the gold standard criteria required to make a confirmative diagnosis of MPS, which requires the presence of the following three laboratory findings: (1) elevation of individual urinary glycosaminoglycan (GAG)-derived disaccharides detected by MS/MS-based assay; (2) deficient activity of a particular leukocyte enzyme by fluorometric assay; and (3) verification of heterogeneous or homogeneous variants by Sanger sequencing or next generation sequencing. Up to 30 April 2021, 599,962 newborn babies have been screened through the NBS programs for MPS type I, II, VI, and IVA, and a total of 255 infants have been referred to MacKay Memorial Hospital for a confirmatory diagnosis. Of these infants, four cases were confirmed to have MPS I, nine cases MPS II, and three cases MPS IVA, with prevalence rates of 0.67, 2.92, and 4.13 per 100,000 live births, respectively. Intensive long-term regular physical and laboratory examinations for asymptomatic infants with confirmed MPS or with highly suspected MPS can enhance the ability to administer ERT in a timely fashion. [ABSTRACT FROM AUTHOR]

Background: Mucopolysaccharidoses (MPS) are lysosomal storage diseases in which mutations of genes encoding for lysosomal enzymes cause defects in the degradation of glycosaminoglycans (GAGs). The accumulation of GAGs in lysosomes results in cellular dysfunction and clinical abnormalities. The early initiation of enzyme replacement therapy (ERT) can slow or prevent the development of severe clinical manifestations. MPS I and II newborn screening has been available in Taiwan since August 2015. Infants who failed the recheck at recall were referred to MacKay Memorial Hospital for a detailed confirmatory diagnosis.Methods: From August 2015 to November 2017, 294,196 and 153,032 infants were screened using tandem mass spectrometry for MPS I and MPS II, respectively. Of these infants, 84 suspected cases (eight for MPS I; 76 for MPS II) were referred for confirmation. Urinary first-line biochemistry examinations were performed first, including urinary GAG quantification, two-dimensional electrophoresis, and tandem mass spectrometry assay for predominant disaccharides derived from GAGs. If the results were positive, a confirmative diagnosis was made according to the results of leukocyte enzymatic assay and molecular DNA analysis. Leukocyte pellets were isolated from EDTA blood and used for fluorescent α-iduronidase (IDUA) or iduronate-2-sulfatase (IDS) enzymatic assay. DNA sequencing analysis was also performed.Results: Normal IDS and IDUA enzyme activities were found in most of the referred cases except for four who were strongly suspected of having MPS I and three who were strongly suspected of having MPS II. Of these infants, three with novel mutations of the IDS gene (c.817C > T, c.1025A > G, and c.311A > T) and four with two missense mutations of the IDUA gene (C.300-3C > G, c.1874A > C; c.1037 T > G, c.1091C > T) showed significant deficiencies in IDS and IDUA enzyme activities (< 5% of mean normal activity), respectively. Urinary dermatan sulfate and heparan sulfate quantitative analyses by tandem mass spectrometry also demonstrated significant elevations. The prevalence rates of MPS I and MPS II in Taiwan were 1.35 and 1.96 per 100,000 live births, respectively.Conclusions: The early initiation of ERT for MPS can result in better clinical outcomes. An early confirmatory diagnosis increases the probability of receiving appropriate medical care such as ERT quickly enough to avoid irreversible manifestations. All high risk infants identified in this study so far remain asymptomatic and are presumed to be affected with the attenuated disease variants. [ABSTRACT FROM AUTHOR]