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To investigate the fibrin(ogen)olytic character of FIIa isolated fromAgkistrodon acutusvenomin vitroandin vivo.125I-labeled human plasma clot lysis was measuredin vitroand rabbit carotid artery thrombosis was as anin vivomodel.In vitro, urokinase (UK) at 25,35,40,45,60 kU/L and FIIa at 0.08,0.23,0.4,0.5, and 0.7 g/L resulted an equivalent clot lysis (20%, 40%, 50%, 60%, and 80%). UK at 25-60 kU/L induced 27.3%±3.6%, 35.2%±2.3%, 39.3%±2.4%, 44.2%±4.6%, and 51.1%±1.2% fibrinogen degradation. But FIIaat 0.08–0.7 g/L induced 95.4%±0.3%,>95.6%,>95.6%,>95.6%,>95.6% fibrinogen degradation respectively.In vivo, UK 40 kU/kg and FIIa 1.0 mg/kg reduced the weight of residual thrombus to 9.0±2.5 mg and 7.8±3.5 mg compared with negative control group (30.0±5.4 mg). But the fibrinogen degradation rate after UK 40 kU/kg and FIIa 1.0 mg/kg treatment was 24.4%±6.2% and 4.1%±7.8%, respectively (P<0.05,n=6). The order of the lysis speed after UK 125 kU/L treatment was platelet poor plasma (PPP) clots>the whole blood clots>platelet rich plasma (PRP) clots. The sequence for FIIa 0.4 g/L was PRP>PPP>whole blood clots.At the same percentage of clot lysis, FIIa degraded more fibrinogen than UK didin vitrobut less fibrinogen than UK didin vivo.The order of the lysis speed was PPP>whole blood clots>PRP clots for UK and PRP>PPP>whole blood clots for FIIa. [ABSTRACT FROM AUTHOR]

Abstract Background Blueberry fruit exhibit atypical climacteric ripening with a non-auto-catalytic increase in ethylene coincident with initiation of ripening. Further, application of ethephon, an ethylene-releasing plant growth regulator, accelerates ripening by increasing the proportion of ripe (blue) fruit as compared to the control treatment. To investigate the mechanistic role of ethylene in regulating blueberry ripening, we performed transcriptome analysis on fruit treated with ethephon, an ethylene-releasing plant growth regulator. Results RNA-Sequencing was performed on two sets of rabbiteye blueberry (‘Powderblue’) fruit: (1) fruit from divergent developmental stages; and (2) fruit treated with ethephon, an ethylene-releasing compound. Differentially expressed genes (DEGs) from divergent developmental stages clustered into nine groups, among which cluster 1 displayed reduction in expression during ripening initiation and was enriched with photosynthesis related genes, while cluster 7 displayed increased expression during ripening and was enriched with aromatic-amino acid family catabolism genes, suggesting stimulation of anthocyanin biosynthesis. More DEGs were apparent at 1 day after ethephon treatment suggesting its early influence during ripening initiation. Overall, a higher number of genes were downregulated in response to ethylene. Many of these overlapped with cluster 1 genes, indicating that ethylene-mediated downregulation of photosynthesis is an important developmental event during the ripening transition. Analyses of DEGs in response to ethylene also indicated interplay among phytohormones. Ethylene positively regulated abscisic acid (ABA), negatively regulated jasmonates (JAs), and influenced auxin (IAA) metabolism and signaling genes. Phytohormone quantification supported these effects of ethylene, indicating coordination of blueberry fruit ripening by ethylene. Conclusion This study provides insights into the role of ethylene in blueberry fruit ripening. Ethylene initiates blueberry ripening by downregulating photosynthesis-related genes. Also, ethylene regulates phytohormone-metabolism and signaling related genes, increases ABA, and decreases JA concentrations. Together, these results indicate that interplay among multiple phytohormones regulates the progression of ripening, and that ethylene is an important coordinator of such interactions during blueberry fruit ripening.

Abstract This review paper explores approaches to sustaining the enduring connection between communities and heritage places in conservation planning. Amidst global overtourism, the gradual outmigration and sudden displacement of local communities from heritage places disrupt not only physical ties between people and places but also shared traditions, memories and emotional bonds. These intangible qualities constitute the social dimension of heritage and are pivotal to its cultural significance. However, existing conservation approaches to safeguarding this social dimension often rely on the continued presence of local communities, which may yield limited effectiveness in restoring people–place bonds amidst challenges posed by overtourism and displacement. This review unpacks the term ‘social value’ within the framework of value-based assessment and progresses towards a dynamic conception of ‘sense of place’. In response to the changing social composition of ‘local communities’ at heritage places, this review examines approaches for conserving the social dimension of heritage, aiming to sustain the enduring continuity of people–place bonding. It proposes a broader definition of ‘sense of place’ that transcends the preconceived notion of stakeholder groups as a geographically defined community and suggests leveraging digital social platforms to re-establish these bonds. The review concludes by advocating for the ‘glocal community’ approach, acknowledging the personal emotional connections that individuals form with a heritage place regardless of their places of residence. This approach has the potential to complement existing methods, such as value-based assessment and the living heritage approach, which are commonly practised in contemporary conservation efforts.

Mixed fermentation with Saccharomyces cerevisiae and Pichia kudriavzevii has been shown to enhance wine aroma, yet the underlying mechanisms remain unclear. Monoculture of S. cerevisiae, monoculture of P. kudriavzevii, and mixed culture of S. cerevisiae and P. kudriavzevii were conducted, and the study analyzed and compared the biomass, flavor profile, and transcriptome responses of the three groups. Both yeast species exhibited growth inhibition in mixed culture, especially P. kudriavzevii. Significant differences were observed in three organic acids and the foremost 20 volatile compounds. Mixed fermentation enhanced esters (e.g., ethyl butyrate, isoamyl acetate) and volatile acids (e.g., hexanoic acid), but decreased isobutanol, phenylethyl alcohol, and quinic acid. Transcriptomic analysis revealed 294 and 332 differentially expressed genes (DEGs) in S. cerevisiae and P. kudriavzevii, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation results indicated that DEGs in mixed fermentation were concentrated in carbohydrate metabolism and amino acid metabolism. Our integrated analysis suggested that genes such as TDH2, TDH3, and ENO2 were pivotal for ester biosynthesis. Moreover, ADH1, ADH2, HPA3, ALD6, and ARO8 were associated with quinic acid synthesis. Furthermore, ILV2, ILV5, ALD6, and others were central to the production of isobutanol and phenylethyl alcohol.

Delayed wound healing in skin burn injuries is common owing to inhibition of proliferation caused by excessive inflammation, necrosis, autophagy, and oxidative stress. Gold nanoclusters modified with lipoic acid (AuNCs) exhibited antioxidant and anti-inflammatory effects in a murine burn healing model. However, the impact of the AuNCs on dermal cell proliferation and granulation tissue formation remains unclear. We therefore examined their effects on dermal cell proliferation, the cell cycle, and the signaling pathways involved. AuNCs were combined with a silk fibroin scaffold and tested in a mouse burn model and human dermal fibroblasts in vitro. Combined with the silk fibroin scaffold, 50 nmol/L of AuNCs activated fibroblast differentiation, collagen deposition, and angiogenesis, increasing granulation-tissue formation, reducing tissue necrosis and systemic inflammatory response, and improving wound healing in the model. The AuNCs increased PI3K/Akt signaling pathway phosphorylation in human dermal fibroblasts, upregulating protein expression of cyclin A, B, and CDK1, which participate in the G2/M cell cycle phase, ultimately promoting fibroblast proliferation. These findings support the beneficial effects of AuNCs on burn wound healing. We suggested that AuNCs on a silk fibroin scaffold or other vector is a potential clinical strategy for burn wound treatment.

We present the measurements of the temperature dependence of the internal quality factor (Qi) of a microwave resonator, well below the superconducting transition temperature. The device is a quarter-wavelength niobium (Tc = 9.2 K) coplanar waveguide resonator. The measured |S21| parameter shows typically the skewed Lorentzian distributions, from which the fitted quality factor monotonically decreases with the temperature increasing from 30 mK to 900 mK. It is observed that for the lower temperature range (i.e., at T < 700 mK) the temperature dependence of the fitted Qi deviates significantly from the predictions of the usual Mattis—Bardeen theory. The measured 3 dB internal quality factor Q′i also verifies such an anomalous temperature dependence. Physically, this phenomenon could be attributed dominantly to the effects of the two-level systems in the device, rather than the usual temperature-dependent complex conductance. [ABSTRACT FROM AUTHOR]

Camelina sativa (L.) Crantz, a member of the Brassicaceae, has potential as a biofuel feedstock which is attributable to the production of fatty acids in its seeds, its fast growth cycle, and low input requirements. While a genome assembly is available for camelina, it was generated from short sequence reads and is thus highly fragmented in nature. Using long read sequences, we generated a chromosome-scale, highly contiguous genome assembly (644,491,969 bp) for the spring biotype cultivar ‘Suneson’ with an N50 contig length of 12,031,512 bp and a scaffold N50 length of 32,184,682 bp. Annotation of protein-coding genes revealed 91,877 genes that encode 133,355 gene models. We identified a total of 4,467 genes that were significantly up-regulated under cold stress which were enriched in gene ontology terms associated with “response to cold” and “response to abiotic stress”. Coexpression analyses revealed multiple coexpression modules that were enriched in genes differentially expressed following cold stress that had putative functions involved in stress adaptation, specifically within the plastid. With access to a highly contiguous genome assembly, comparative analyses with Arabidopsis thaliana revealed 23,625 A. thaliana genes syntenic with 45,453 Suneson genes. Of these, 24,960 Suneson genes were syntenic to 8,320 A. thaliana genes reflecting a 3 camelina homeolog to 1 Arabidopsis gene relationship and retention of all three homeologs. Some of the retained triplicated homeologs showed conserved gene expression patterns under control and cold-stressed conditions whereas other triplicated homeologs displayed diverged expression patterns revealing sub- and neo-functionalization of the homeologs at the transcription level. Access to the chromosome-scale assembly of Suneson will enable both basic and applied research efforts in the improvement of camelina as a sustainable biofuel feedstock.

This study involved direct doping of In2O3 into silicon carbide (SiC) powder, resulting in 8.0 at% In-doped SiC powder. Subsequently, heating at 500 °C was performed to form a target, followed by the utilization of electron beam (e-beam) technology to deposit the In-doped SiC thin films with the thickness of approximately 189.8 nm. The first breakthrough of this research was the successful deposition of using e-beam technology. The second breakthrough involved utilizing various tools to analyze the physical and electrical properties of In-doped SiC thin films. Hall effect measurement was used to measure the resistivity, mobility, and carrier concentration and confirm its n-type semiconductor nature. The uniform dispersion of In ions in SiC was as confirmed by electron microscopy energy-dispersive spectroscopy and secondary ion mass spectrometry analyses. The Tauc Plot method was employed to determine the Eg values of pure SiC and In-doped SiC thin films. Semiconductor parameter analyzer was used to measure the conductivity and the I-V characteristics of devices in In-doped SiC thin films. Furthermore, the third finding demonstrated that In2O3-doped SiC thin films exhibited remarkable current density. X-ray photoelectron spectroscopy and Gaussian-resolved spectra further confirmed a significant relationship between conductivity and oxygen vacancy concentration. Lastly, depositing these In-doped SiC thin films onto p-type silicon substrates etched with buffered oxide etchant resulted in the formation of heterojunction p-n junction. This junction exhibited the rectifying characteristics of a diode, with sample current values in the vicinity of 102 mA, breakdown voltage at approximately −5.23 V, and open-circuit voltage around 1.56 V. This underscores the potential of In-doped SiC thin films for various semiconductor devices.

Introduction: Circulating tumor cells (CTCs) have the characteristics of cancer stem cells and play an important role in the recurrence and metastasis of tumors. CD44 is a surface marker molecule for gastric cancer stem cells (GCSCs) and can be used to identify and isolate GCSCs. Here, we investigated the effect of CD44 protein expression, circulating tumor cells, and CD44-positive CTCs on the prognosis of gastric cancer (GC).Material and methods: Blood samples from 58 GC patients being treated at the First Affiliated Hospital of Anhui Medical University from August 2015 to October 2016 were obtained before surgery. The cancer tissues from 58 GC patients after surgery and the same amount of adjacent normal tissues 5 cm away from the center of the cancer tissues were collected as controls. Immunohistochemistry was used to detect CD44 expression in cancer tissues and adjacent normal tissues. Immunomagnetically negative enrichment combined with im-FISH was used to detect CTCs and CD44-positive CTCs in gastric cancer patients.Results: Circulating tumor cells were detected in 44 of 58 patients, and CD44 protein was positive in 34 cases of GC. The presence of CTCs and CD44 is significantly associated with depth of tumor infiltration, lymph node metastasis, TNM stage, and recurrence (p < 0.01). Twenty-nine of 44 CTC-positive patients had CD44-positive CTCs. The patients with CD44-positive CTCs were more likely to develop recurrence than patients with CD44-negative CTCs (p < 0.01). Furthermore, 28 of 29 patients with CD44-positive CTCs developed recurrent disease, and the mean time to recurrence was shorter than that in patients with CD44-negative CTCs (16.030 ±5.268 and 21.800 ±4.601 months; p < 0.01). The Cox proportional hazards model indicated that the presence of CD44-positive CTCs and TNM stage were independent predictors of recurrence for GC (p = 0.044 and 0.035).Conclusions: The detection of stem cell characteristics of GC CTCs can provide more prognostic information than simply detecting GC CTCs and GC CD44 expression. [ABSTRACT FROM AUTHOR]

Abstract Wars and conflict have existed since the beginning of time. Most battlefield conservation work is done for battlefields that lie in the borders of the nations that were involved, thus fostering citizens’ personal ties with the site and their national identities. However, some areas of the world suffer from conservation neglect because of the distance and separation between the battlefield’s location and the country to which it is relevant, thus creating a dislocated appreciation of heritage described by Price (J Confl Archaeol 1:181–196, 2005) as ‘orphan heritage’. This paper questions the extent to which post-colonial nations are willing to protect and conserve World War II battlefields on their soil. It examines two battlefields in Asia—the Gin Drinkers’ Line in Hong Kong, China, and the Green Ridge battlefield in Kampar, Malaysia—that have been the subject of campaigns to recognise their transnational heritage value. Both battles involved multinational Allied forces led by the British against Japanese troops. A combination of political and economic factors has influenced how the two battlefields are understood and appreciated by citizens and local governments in the host nations. The paper delineates how these two Asian battlegrounds, which are relatively unknown to the general public, have been brought to the public’s attention and by whom as well as how the local governments have handled the demand to safeguard the battlefields. We argue that the global nature of WWII makes its commemoration geographically challenging and politically contentious. The WWII battlefields in Asia attest to the historical authenticity of past conflicts and thus should be conserved as neutrally as possible. The successful protection of battlefields in Malaysia and Hong Kong thus far can be largely attributed to grassroots initiatives, pressure from stakeholder countries, such as the UK, and academic research whereby the significance of the battleground is made known to people in Hong Kong and Malaysia. With public support, responsible government leadership and a shared understanding of their importance as transnational heritage, WWII battlefields can help calm bitter resentment and promote reconciliation.

Background/purpose: SraP is a serine-rich repeat protein (SRRP) from Staphylococcus aureus that binds to sialylated receptors to promote bacterial adhesion to and invasion into host epithelial cells, mediated by the l-lectin module of its ligand-binding region. Methods: The sequence encoding the L-lectin module of SraP was inserted into pET28a plasmid, and the recombinant protein was purified by His label affinity chromatography. A monoclonal antibody (mAb) against the l-lectin module was obtained and confirmed by enzyme-linked immunosorbent assay and western blotting. The effect of the mAb on S. aureus adhesion and invasion was assessed in A549 cells and mice subjected to S. aureus challenge. Results: We successfully obtained a mAb against the l-lectin module of SraP. Pre-incubation with the mAb dramatically inhibited the bacteria's ability to adhere to and invade A549 cells. Moreover, mice administered mAb through tail vein injection had significantly fewer bacteria in the blood. Conclusion: The anti-SraPL-Lectin mAb significantly reduced the adherence and invasion of S. aureus to host cells. This study lays the foundation for the future development of the l-lectin module of SraP as a target for the prevention and treatment of S. aureus infection. Our findings suggest that specific subdomains of SRRPs may represent potential antibacterial drug targets for intervention.

Nerve damage caused by accumulated oxidative stress is one of the characteristics and main mechanisms of Alzheimer’s disease (AD). Previous studies have shown that phosphatidylserine (PS) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) plays a significant role in preventing and mitigating the progression of AD. However, whether DHA-PS and EPA-PS can directly protect primary hippocampal neurons against oxidative damage has not been studied. Here, the neuroprotective functions of DHA-PS and EPA-PS against H2O2/t-BHP-induced oxidative damage and the possible mechanisms were evaluated in primary hippocampal neurons. It was found that DHA-PS and EPA-PS could significantly improve cell morphology and promote the restoration of neural network structure. Further studies showed that both of them significantly alleviated oxidative stress-mediated mitochondrial dysfunction. EPA-PS significantly inhibited the phosphorylation of ERK, thus playing an anti-apoptotic role, and EPA-PS significantly increased the protein expressions of p-TrkB and p-CREB, thus playing a neuroprotective role. In addition, EPA-PS, rather than DHA-PS could enhance synaptic plasticity by increasing the expression of SYN, and both could significantly reduce the expression levels of p-GSK3β and p-Tau. These results provide a scientific basis for the use of DHA/EPA-enriched phospholipids in the treatment of neurodegenerative diseases, and also provide a reference for the development of related functional foods.

Background: Due to globalization, the frequency to stay in other countries has increased, resulting in more chances to nursing staff to communicate with foreign patients in English. However, English is not the native language in many countries, including Taiwan. Many nurses cannot communicate with foreign patients efficiently. Aim: This study aimed to identify the clinical English Communication Abilities of nurses and their willingness and requirements to improve, negative communication situations, and their influential factors. Methods: A questionnaire to conduct a descriptive, exploratory, cross-sectional survey was applied to 273 clinical nurses at a teaching hospital in Taiwan. Results: Most nurses stated that their English Communication Abilities was insufficient to cope with clinical requirements and were willing to improve this ability. In negative communication situations, the major problems included the nurses felt that they had to spend more time, were more stressed, and were not able to perform at a professional level when interacting with foreign patients, which would reduce interaction with patients. The factors that impact these problems include frequency of self-study and clinical English communicative abilities. English handout containing hygiene instructions was considered the most useful resource to facilitate clinical English conversation. Conclusions: Inadequate English Communication Abilities results in more time spent when communicating with foreign patients. Nurses who have better English Communication Abilities or have set hours for studying English may reduce the frequency of negative situations while communicating in English. Periodical advanced study of English might reduce the negative situation of nurse–patient communicated in English. To provide high-quality international medical service, the hospital managers have to offer appropriate assist strategies to improve nurses' clinical English communication abilities.

Liver cancer is one of the most lethal cancers in the world, mainly owing to the lack of effective means for early monitoring and treatment. Accordingly, there is considerable research interest in various clinically applicable methods for addressing these unmet needs. At present, the most commonly used biomarker for the early diagnosis of liver cancer is alpha-fetoprotein (AFP), but AFP is sensitive to interference from other factors and cannot really be used as the basis for determining liver cancer. Treatment options in addition to liver surgery (resection, transplantation) include radiation therapy, chemotherapy, and targeted therapy. However, even more expensive targeted drug therapies have a limited impact on the clinical outcome of liver cancer. One of the big reasons is the rapid emergence of drug resistance. Therefore, in addition to finding effective biomarkers for early diagnosis, an important focus of current discussions is on how to effectively adjust and select drug strategies and guidelines for the treatment of liver cancer patients. In this review, we bring this thought process to the drug resistance problem faced by different treatment strategies, approaching it from the perspective of gene expression and molecular biology and the possibility of finding effective solutions.

Background: Renal cell carcinoma with rhabdoid features (RCC-RF) is an aggressive histologic variant in the adults and is usually unresponsive to standard chemotherapy. Methods: Expression of SMARCB1/INI1 was examined in primary RCC-RF (n = 5). Stable INI1 with/without prostaglandin E2 receptor 1 (EP1) knockdown cell lines were created in the ACHN and 786-O RCC cell lines and measured for epidermal growth factor receptor (EGFR)-related signaling pathways. Chemosensitivity to targeted drugs in vitro was tested after knocking down of INI1 in both cell lines. The outcome of co-targeting of INI1 and EP1 in RCC was examined using a tumorigenicity assay. Results: Expression of INI1 was markedly reduced at both transcriptional and translational levels in primary RCC-RF. Immunohistochemical expression of INI1 protein was lost in the nuclei of rhabdoid cells compared with conventional RCC (n = 8). Using two cell lines with different genetic background, we showed that knocking down of INI1 activates the EGFR signaling with up-regulated AKT and ERK pathways and sensitizes cancer cells to Erlotinib treatment in vitro. However, cell-line dependent effects were also demonstrated with reference to impact of INI1 or EP1 on cell growth, migration and response to Gefitinib or Everolimus treatment in vitro. Conclusion: Inactivation of INI1 may play a role in the pathogenesis of RCC-RF. Erlotinib is recommended in the management of patients with INI1-related RCC.

Background: In our preliminary screening, expression of miR-338-5p was found to be higher in primary colorectal cancer (CRC) with metastasis. The autophagy related gene- phosphatidylinositol 3-kinase, catalytic subunit type 3 (PIK3C3) appeared to be targeted by miR-338-5p. Here, we provide solid evidence in support of PIK3C3 involved in miR-338-5p related metastasis of CRC in vitro and in vivo. Methods: The potential clinical relevance of miR-338-5p and its target gene was analysed on benign colorectal polyps and primary CRCs by QPCR. Mouse spleen xenograft experiment was performed to examine the importance of miR-338-5p for metastasis. Findings: PIK3C3 was one of target genes of miR-338-5p. In primary CRCs, expression of miR-338-5p is positively related to tumour staging, distant metastasis and poor patient survival. Patients with higher ratios of miR-338-5p/PIK3C3 also had significantly poor overall survival, supporting their significance in the progression of CRC. Over-expression of miR-338-5p promotes CRC metastasis to the liver and lung in vivo, in which PIK3C3 was down-regulated in the metastatic tumours. In contrast, overexpression of PIK3C3 in miR-338-5p stable cells inhibited the growth of metastatic tumours. Both migration and invasion of CRC in vitro induced by miR-338-5p are mediated by suppression of PIK3C3. Using forward and reverse approaches, autophagy was proved to involve in CRC migration and invasion induced by miR-338-5p. Interpretation: MiR-338-5p induces migration, invasion and metastasis of CRC in part through PIK3C3-related autophagy pathway. The miR-338-5p/PIK3C3 ratio may become a prognostic biomarker for CRC patients. Fund: NCKU Hospital, Taiwan, Ministry of Science and Technology, Taiwan. Keywords: miR-338-5p, PIK3C3, Autophagy and colorectal cancer

In this study, 24 h quantitative precipitation forecasts (QPFs) in Taiwan at the ranges of day 1 (0–24 h), day 2 (24–48 h), and day 3 (48–72 h) by a cloud-resolving model are examined using categorical statistics, targeted mainly for the most-rainy 24 h from 10 typhoon cases between 2010 and 2015, following two earlier studies that evaluated the overall performance for all the typhoons that hit Taiwan from 2010 to 2012 and through 2015. In the selected examples with a peak amount of 322 to 1110 mm, the QPFs by the model (with a grid size of 2.5 km) are shown to be of very high quality for two typhoons (Soulik and Soudelor), and fairly good quality for three cases (Fanapi, Megi, and Fung-Wong) up to day 3 and for four others (Saola, Kong-Rey, Nanmadol, and Tembin) within day 2, respectively. The results are more variable for the one remaining case of Matmo, also impressive on day 1 but degraded at longer ranges. Overall, the quality of the QPFs ranges from excellent to satisfactory for all the typhoons studied as the threat score can achieve 0.2 at thresholds fairly close to the observed peak amount in some typhoons, or at least about half of it in most others. Since the majority of the typhoons produced the greatest rainfall amounts over the mountains in Taiwan due to the topographic effect, in agreement with many previous studies, the QPF skills by the model, often extending into high thresholds, as demonstrated, suggest that heavy rainfall from typhoons in Taiwan is generally of high predictability if and when the model has an adequate resolution.

Electro-Wetting-On-Dielectric (EWOD) based digital operations have demonstrated outstanding potential in actuating and manipulating liquid droplets. Here, we adapted the EWOD for extracting femtogram quantities of cell-free DNA (cf-DNA) from 1 μL of KSOM mouse embryo culture medium. Our group extracted the femtogram quantity of cf-DNA from 1 μL of mouse embryo culture medium in our previous work. Here, we initially explain a modification from our previous extraction protocol, which improves the extraction percentage to 36.74%. Though the modified extraction protocol improves the extraction percentage from our previously reported work, the quantity is still in the femtogram range. The cf-DNA in femtogram quantity is in subcritical/subthreshold concentration for any further analysis, such as sequencing. To the best of our knowledge, we need a minimum of picogram/nanogram DNA quantities for further analysis. We demonstrated a ground-breaking mechanism of this subcritical concentration of cf-DNA amplification to the nanogram range and performed DNA sequencing. Basic Local Alignment Search Tool (BLAST) is used as a sequence similarity search program to confirm the identity percentage between query and subject. More than 97% of nucleotide identities between query and subject sequences have been obtained from the sequencing result. Hence, we can use the methodology to amplify the subcritical concentration of extracted DNA for further analytics. Moreover, as we extract the cf-DNA from the embryo culture medium, the natural growth of the embryo has not been disrupted. This entire mechanism will pave a new path towards the lab-on-a-chip (LOC) concept.

Abstract While industrial manufacturing is giving way to the creative economy in the 21st century, Shanghai—similar to many major cities around the world—is keen to bolster a stronger economy and increase its competitiveness by encouraging the development of cultural and creative industries. Over the past decade, the Shanghai municipal government has made a concerted effort to exploit the heritage assets of the city’s industrial past to reform its economic structure. There has been a deliberate attempt to establish a stronger correlation between industrial heritage conservation and creative industry cluster development. The aim of this research is to investigate the process of converting former industrial sites into loci of creativity. In doing so, we can determine the main actors, how different stakeholder groups came into play and the evolution of the subtle interplay between the designation of heritage architecture and that of creative industry cluster. Drawing on qualitative research methods, this paper presents a detailed analysis of three case studies in Shanghai: M50 Creative Park, 1933 Shanghai and the Cool Docks. The results reveal the changing positions of three major stakeholder groups. Whereas the private sector and the general public have developed increasing interests in the embedded economic and cultural values of the former industrial structures, local government has consciously reduced its presence and influence in valorising industrial heritage. Thus, the growing public awareness of cultural heritage protection and the increasing interest in the economic contribution of cultural and creative industries are intrinsic to Shanghai’s reindustrialisation in the 21st century.

In the context of tourism planning and promotion, there is wide acknowledgement that conceptualisations of tourism identity cannot be grounded merely in physical place, but should also encompass a wide range of factors including, for instance, cultural relations, tourist activities, and social networking. There are opportunities in late modern society for relating the identity of a city’s tourism with digitally-presented tourists’ perceptions and activities through social media studies. This research explores multiple research approaches to delineate the digital identity of Suzhou’s tourist destinations, as presented in online user-generated contents. It is hoped that this social media study can provide supplementary information for tourism bureaus and agencies to make informed judgements on effecting pertinent improvements to optimise existing tourism resources and create more enticing environments for tourists. The research follows a case study approach and conducts an empirical study on Suzhou, a Chinese historic city. The analysis of the results show that the social media study is potentially useful in identifying the key characteristics of particular tourist destinations from visitors’ perspectives that may also be helpful for the evaluation of tourists’ experiences.

Background and Objectives: Overactive bladder (OAB) is a serious urination-related symptom of unknown pathogenesis that affects one’s everyday activities. The objective of this study was to examine how OAB prevalence, symptom severity, and degree of distress caused by OAB symptoms evolved throughout the course of pregnancy. Materials and Methods: A total of 659 pregnant women were recruited from 2015 to 2020, and were evaluated through the International Consultation on Incontinence Questionnaire-Overactive Bladder (ICIQ-OAB) on OAB symptoms, administered in the early, middle, and late stages of pregnancy. Results: Generalized estimating equation analysis revealed that the odds of OAB occurring in the middle and late stages of pregnancy were 1.90 and 2.33 times higher, respectively, than in early pregnancy. The corresponding odds for OAB-wet were 1.63 and 2.07 higher, respectively, and the odds of OAB-dry occurring during late pregnancy were 0.80 higher than during early pregnancy. Symptoms were more severe by 0.07 and 0.21 points (on a 4-point scale) in the middle and late stages of pregnancy, respectively, than in early pregnancy; distress was greater by 0.13 and 0.27 points (on a 10-point scale) in the middle and late stages of pregnancy, respectively, than in early pregnancy. The prevalence of OAB, OAB-dry, and OAB-wet was significantly higher in early pregnancy than pre-pregnancy. Conclusions: The prevalence of OAB and OAB-wet increased over the course of pregnancy, but the prevalence of OAB-dry decreased. Furthermore, symptom severity and degree of distress increased over time.

Impaired wound healing is an ongoing issue that cancer patients undergoing chemotherapy or radiotherapy face. Our previous study regarding lung-cancer-associated pleural fluid (LCPF) demonstrated its propensity to promote endothelial proliferation, migration, and angiogenesis, which are crucial features during cutaneous wound healing. Therefore, the current study aimed to investigate the effect of pleural fluid on cutaneous wound closure in vitro and in vivo using HaCaT keratinocytes and a full-thickness skin wound model, respectively. Both heart-failure-associated pleural fluid (HFPF) and LCPF were sequentially centrifuged and filtered to obtain a cell-free status. Treatment with HFPF and LCPF homogeneously induced HaCaT proliferation with cell cycle progression, migration, and MMP2 upregulation. Western blotting revealed increased PI3K/Akt phosphorylation and VEGFR2/VEGFA expression in HaCaT cells. When treated with the PI3K inhibitor, LCPF-induced keratinocyte proliferation was attenuated with decreased pS6 levels. By applying the VEGFR2 inhibitor, LCPF-induced keratinocyte proliferation was ameliorated by pS6 and MMP2 downregulation. The effect of LCPF-induced cell junction rearrangement was disrupted by co-treatment with a VEGFR2 inhibitor. Compared with a 0.9% saline dressing, LCPF significantly accelerated wound closure and re-epithelization when used as a dressing material in a full-thickness wound model. Histological analysis revealed increased neo-epidermis thickness and dermis collagen synthesis in the LCPF-treated group. Furthermore, LCPF treatment activated basal keratinocytes at the wound edge with the upregulation of Ki-67, VEGFA, and MMP2. Our preliminaries provided the benefit of wet dressing with pleural fluid to improve cutaneous wound closure through enhanced re-epithelization and disclosed future autologous application in cancer wound treatment.

In this study, 24 h quantitative precipitation forecasts (QPFs) by a cloud-resolving model (with a grid spacing of 2.5 km) on days 1–3 for 29 typhoons in six seasons of 2010–2015 in Taiwan were examined using categorical scores and rain gauge data. The study represents an update from a previous study for 2010–2012, in order to produce more stable and robust statistics toward the high thresholds (typically with fewer sample points), which is our main focus of interest. This is important to better understand the model’s ability to predict such high-impact typhoon rainfall events. The overall threat scores (TS, defined as the fraction among all verification points that are correctly predicted to reach a given threshold to all points that are either observed or predicted to reach that threshold, or both) were 0.28 and 0.18 on day 1 (0–24 h) QPFs, 0.25 and 0.16 on day 2 (24–48 h) QPFs, and 0.15 and 0.08 on day 3 (48–72 h) QPFs at 350 mm and 500 mm, respectively, showing improvements over 5 km models. Moreover, as found previously, a strong dependence of higher TSs for larger rainfall events also existed, and the corresponding TSs at 350 and 500 mm for the top 5% of events were 0.39 and 0.25 on day 1, 0.38 and 0.21 on day 2, and 0.25 and 0.12 on day 3. Thus, for the top typhoon rainfall events that have the highest potential for hazards, the model exhibits an even higher ability for QPFs based on categorical scores. Furthermore, it is shown that the model has little tendency to overpredict or underpredict rainfall for all groups of events with different rainfall magnitude across all thresholds, except for some tendency to under-forecast for the largest event group on day 3. Some issues associated with categorical statistics to be aware of are also demonstrated and discussed.

Currently, there are several therapeutic approaches available for wound injury management. However, a better understanding of the underlying mechanisms of how biomaterials affect cell behavior is needed to develop potential repair strategies. Bacterial cellulose (BC) is a bacteria-produced biopolymer with several advantageous qualities for skin tissue engineering. The aim here was to investigate BC-based scaffold on epithelial regeneration and wound healing by examining its effects on the expression of scavenger receptor-A (SR-A) and underlying macrophage behavior. Full-thickness skin wounds were generated on Sprague-Dawley rats and the healing of these wounds, with and without BC scaffolds, was examined over 14 days using Masson’s trichome staining. BC scaffolds displayed excellent in vitro biocompatibility, maintained the stemness function of cells and promoted keratinocyte differentiation of cells, which are vital in maintaining and restoring the injured epidermis. BC scaffolds also exhibited positive in vivo effects on the wound microenvironment, including improved skin extracellular matrix deposition and controlled excessive inflammation by reduction of SR-A expression. Furthermore, BC scaffold significantly enhanced epithelialization by stimulating the balance of M1/M2 macrophage re-programming for beneficial tissue repair relative to that of collagen material. These findings suggest that BC-based materials are promising products for skin injury repair.

Background: During ablative fractional resurfacing (AFR) laser therapy, thermal damage to the skin is inevitable, resulting in inflammatory responses and small wounds. Corticosteroids are known for their anti-inflammatory effect. However, inappropriate application of corticosteroids carries the risk of delayed wound healing. Therefore, we aimed to find the optimal administration route, timing, and duration of medium potency corticosteroid treatment to prevent AFR laser-induced inflammatory responses and to minimize the risk of delayed wound healing. Methods: We determined the anti-inflammatory efficacy of corticosteroids by skin erythema and tissue biopsies on C57BL/6 mice. Wound healing was evaluated by crust area and epithelial gap. Finally, Masson’s trichrome stain and α-SMA immunohistochemistry stain were used to analyze scar contracture. Results: Our results demonstrated that one dose of medium-potency topical corticosteroid applied immediately after AFR laser treatment could prevent erythema effectively with minimal disruption to wound healing. Notably, when more than one dose was administered, wound healing was delayed and scar contracture was aggravated by the application of medium-potency topical corticosteroids in a dosage-dependent manner. Conclusion: Our findings suggested that single-dose medium-potency topical corticosteroids could potentially improve AFR laser-induced acute inflammatory responses in clinical applications.

Blueberry fruit are perishable after harvesting due to fruit softening, water loss and susceptibility to pathogens. Light, especially blue light, increases the accumulation of anthocyanins and reduces postharvest decay in some fruits, but the effect of blue light on postharvest fruit quality attributes in blueberries is unknown. In this study, we evaluated the effect of blue light on fruit quality, anthocyanin accumulation and disease development during postharvest cold storage (2 °C–4 °C) in two experiments with southern highbush blueberry ‘Star’ and rabbiteye blueberry ‘Alapaha’. Overall, diurnal blue light did not affect postharvest fruit quality attributes, such as visual defects, fruit compression, skin puncture, total soluble solid content and titratable acidity, in the two cultivars compared with their respective controls (diurnal white light or continuous darkness). Further, there was no effect of blue light on fruit color and anthocyanin accumulation. Fruit disease incidence in ‘Star’ ranged from 19.0% to 27.3% after 21 days and in ‘Alapaha’ from 44.9% to 56.2% after 24 days in postharvest storage, followed by 4 days at room temperature, but blue light had no consistent effect on postharvest disease incidence for either cultivar. Disease progression following artificial inoculations with Alternaria tenuissima and Colletotrichum acutatum in ‘Star’ was not influenced by light treatment prior to inoculation and during fruit storage. In a separate experiment, we tested the effect of blue light on color development in ‘Farthing’, a southern highbush blueberry cultivar with fruit prone to non-uniform ripening, whereby the stem-end remains green as the rest of the fruit turns blue. Although green stem-end spots turned blue over time, there was no statistically significant effect of the blue light treatment. Overall, these data indicate that blue light does not affect fruit quality attributes or disease development in ripe blueberry fruit during postharvest storage in the conditions investigated here.

Droplet microfluidics has appealed to many interests for its capability to epitomize cells in a microscale environment and it is also a forceful technique for high-throughput single-cell epitomization. A dielectrophoretic microfluidic system imitates the oviduct of mammals with a microchannel to achieve fertilization in vitro (IVF) of an imprinting control-region (ICR) mouse. We applied a microfluidic chip and a positive dielectrophoretic (p-DEP) force to capture and to screen the sperm for the purpose of manipulating the oocyte. The p-DEP responses of the oocyte and sperm were exhibited under applied bias conditions (waveform AC 10 Vpp, 1 MHz) for trapping 1 min. The insemination concentration of sperm nearby the oocyte was increased to enhance the probability of natural fertilization through the p-DEP force trapping. A simulation tool (CFDRC-ACE+) was used to simulate and to analyze the distribution of the electric field. The DEP microfluidic devices were fabricated using poly (dimethylsiloxane) (PDMS) and ITO (indium tin oxide)-glass with electrodes. We discuss the requirement of sperm in a DEP microfluidic chip at varied concentrations to enhance the future rate of fertilization in vitro for an oligozoospermia patient. The result indicates that the rate of fertility in our device is 17.2 ± 7.5% (n = 30) at about 3000 sperms, compatible with traditional droplet-based IVF, which is 14.2 ± 7.5% (n = 28).

Due to risks from potential exposures to ionizing radiation (IR), improved radiological countermeasures are required, as well as rapid high-throughput biodosimetry. Genotypic variation in the general population contributes to differences in radiosensitivity that may affect biodosimetry accuracy. Previous studies utilized radiosensitive mutant mouse models (Parp1−/− and Atm−/−) to determine the effects of genotypic deficiency on radiation signatures. Here, we extend this approach by examining changes in the urinary metabolome in a hematopoietic (HP) resistant mouse model (p53−/−) after IR exposure. As p53 is a primary regulator in radiation response and apoptosis, limited hematopoietic stem cell apoptosis leads to reduced mortality at doses of ~8–10 Gy but increased mortality at higher doses (>15 Gy) due to mitotic catastrophe in gastrointestinal (GI) crypt cells. Urine was collected from mice (wild-type (WT), p53+/−, and p53−/−) pre-irradiation and at 4 and 24 h after total body irradiation (TBI) (WT: 8 and 10 Gy; p53−/−: 10 Gy) for metabolic phenotyping using an ultra-performance liquid chromatography mass spectrometry (UPLC-MS) platform. Minimal differences were detected between unirradiated WT, p53+/−, and p53−/− mice. While similar perturbations were observed for metabolites involved in tryptophan, vitamin B6, and histamine pathways, glycine conjugation, and redox metabolism for WT and p53−/− mice after TBI, an overall dampened response was observed in p53-deficient mice. Despite comparable metabolite patterns between genotypes, differentiation was achieved through receiver operating characteristic curve analysis with high specificity and sensitivity for carnitine, N1-acetylspermidine, and creatine. These studies highlight that both attenuated and dampened metabolic responses due to genetic variability in the general population need to be addressed in biodosimetry frameworks.

Skin substitutes with existing vascularization are in great demand for the repair of full-thickness skin defects. In the present study, we hypothesized that a pre-vascularized skin substitute can potentially promote wound healing. Novel three-dimensional (3D) skin substitutes were prepared by seeding a mixture of human endothelial progenitor cells (EPCs) and fibroblasts into a human plasma/calcium chloride formed gel scaffold, and seeding keratinocytes onto the surface of the plasma gel. The capacity of the EPCs to differentiate into a vascular-like tubular structure was evaluated using immunohistochemistry analysis and WST-8 assay. Experimental studies in mouse full-thickness skin wound models showed that the pre-vascularized gel scaffold significantly accelerated wound healing 7 days after surgery, and resembled normal skin structures after 14 days post-surgery. Histological analysis revealed that pre-vascularized gel scaffolds were well integrated in the host skin, resulting in the vascularization of both the epidermis and dermis in the wound area. Moreover, mechanical strength analysis demonstrated that the healed wound following the implantation of the pre-vascularized gel scaffolds exhibited good tensile strength. Taken together, this novel pre-vascularized human plasma gel scaffold has great potential in skin tissue engineering.

Background To treat skin color disorders, such as vitiligo or burns, melanocytes are transplanted for tissue regeneration. However, melanocyte distribution in the human body varies with age and location, making it difficult to select the optimal donor skin to achieve a desired color match. Determining the correlations with the desired skin color measurement based on CIELAB color, epidermal melanocyte numbers, and melanin content of individual melanocytes is critical for clinical application. Method Fifteen foreskin samples from Asian young adults were analyzed for skin color, melanocyte ratio (melanocyte proportion in the epidermis), and melanin concentration. Furthermore, an equation was developed based on CIELAB color with melanocyte ratio, melanin concentration, and the product of melanocyte ratio and melanin concentration. The equation was validated by seeding different ratios of keratinocytes and melanocytes in tissue-engineered skin substitutes, and the degree of fitness in expected skin color was confirmed. Results Linear regression analysis revealed a significant strong negative correlation (r = − 0.847, R2 = 0.717) between CIELAB L* value and the product of the epidermal melanocyte ratio and cell-based melanin concentration. Furthermore, the results showed that an optimal skin color match was achieved by the formula. Discussion We found that L* value was correlated with the value obtained from multiplying the epidermal melanocyte ratio (R) and melanin content (M) and that this correlation was more significant than either L* vs M or L* vs R. This suggests that more accurate prediction of skin color can be achieved by considering both R and M. Therefore, precise skin color match in treating vitiligo or burn patients would be potentially achievable based on extensive collection of skin data from people of Asian descent.

Microfluidic biochip techniques are prominently replacing conventional biochemical analyzers by the integration of all functions necessary for biochemical analysis using microfluidics. The microfluidics of droplets offer exquisite control over the size of microliter samples to satisfy the requirements of embryo culture, which might involve a size ranging from picoliter to nanoliter. Polydimethylsiloxane (PDMS) is the mainstream material for the fabrication of microfluidic devices due to its excellent biocompatibility and simplicity of fabrication. Herein, we developed a microfluidic biomedical chip on a PDMS substrate that integrated four key functions—generation of a droplet of an emulsion, sorting, expansion and restoration, which were employed in a mouse embryo system to assess reproductive medicine. The main channel of the designed chip had width of 1200 μm and height of 500 μm. The designed microfluidic chips possessed six sections—cleaved into three inlets and three outlets—to study the key functions with five-day embryo culture. The control part of the experiment was conducted with polystyrene (PS) beads (100 μm), the same size as the murine embryos, for the purpose of testing. The outcomes of our work illustrate that the rate of success of the static droplet culture group (87.5%) is only slightly less than that of a conventional group (95%). It clearly demonstrates that a droplet-based microfluidic system can produce a droplet in a volume range from picoliter to nanoliter.

We design and fabricate two types of superconducting niobium coplanar waveguide microwave resonators with different coupling capacitors on high purity Si substrates. Their microwave transmissions are measured at 20 mK. It is found that these two types of resonators possess significantly different loaded quality factors; one is 5.6 × 103 and the other is 4.0 × 104. The measured data are fitted well by classical ABCD matrix approach and consequently the coupling capacitances are determined. It is found that the transmission peak deviates from the standard Lorentizian with a frequency broadening. [ABSTRACT FROM AUTHOR]

A filter-based wide-range programmable sinusoidal wave synthesizer for electrochemical impedance spectroscopy measurement is proposed. The adopted filter is implemented with switched-capacitor circuits, so its corner frequency is accurate and adjustable by changing its switching frequency. The proposed sine wave synthesizer is implemented by using a 0.35 μm 2P4M 3.3 V mixed-signal polycide process. According to the measured results, the output frequency of the proposed synthesizer is 40 mHz-40 kHz . The measured total harmonic distortion is 0.073% at 10 Hz and 0.075% at 10 kHz, both of which are better than that of a typical function generator.