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A new estuarine moray eel, Uropterygius hades sp. nov., is described based on 14 specimens from Japan, Taiwan, the Philippines, southern Indonesia, and Fiji. It is a small-bodied, slender, uniformly dark-brown moray separated from congeners within the U. concolor species complex. The new species can be distinguished from congeners by the anteriorly positioned small eyes (5.0–7.2% of head length), absence of branchial pores, and extended inner rows of teeth which reach the posterior end of the jaws. Uropterygius hades sp. nov. represents a rare species of moray eel that inhabits turbid estuarine environments, preferring soft, muddy substrates, and burrowing and hiding among rocks or in fallen mangrove leaves. Additionally, Uropterygius mactanensis Huang, Balisco, Evacitas & Liao, another species recently separated from the U. concolor species complex, is reported for the first time from Iriomote Island in the Ryukyu Archipelago based on two specimens; this new record expands the geographic range of U. mactanensis from the central Philippines to southern Japan.

Abstract Human malignant pleural mesothelioma (hMPM) is an aggressive, rare disease with a poor prognosis. Histologically, MPM is categorized into epithelioid, biphasic, and sarcomatoid subtypes, with the epithelioid subtype generally displaying a better response to treatment. Conversely, effective therapies for the non-epithelioid subtypes are limited. This study aimed to investigate the potential role of FK228, a histone deacetylase inhibitor, in the suppression of hMPM tumor growth. We conducted a comprehensive analysis of the histological and molecular characteristics of two MPM cell lines, CRL-5820 (epithelioid) and CRL-5946 (non-epithelioid). CRL-5946 cells and non-epithelioid patient-derived xenografted mice exhibited heightened growth rates compared to those with epithelioid MPM. Both CRL-5946 cells and non-epithelioid mice displayed a poor response to cisplatin. However, FK228 markedly inhibited the growth of both epithelioid and non-epithelioid tumor cells in vitro and in vivo. Cell cycle analysis revealed FK228-induced G1/S and mitotic arrest in MPM cells. Caspase inhibitor experiments demonstrated that FK228-triggered apoptosis occurred via a caspase-dependent pathway in CRL-5946 but not in CRL-5820 cells. Additionally, a cytokine array analysis showed that FK228 reduced the release of growth factors, including platelet-derived and vascular endothelial growth factors, specifically in CRL-5946 cells. These results indicate that FK228 exhibits therapeutic potential in MPM by inducing cytotoxicity and modulating the tumor microenvironment, potentially benefiting both epithelioid and non-epithelioid subtypes.

Abstract A morphology-based barcoding library of market teleost fishes (Teleostei) in Cebu is built based on cytochrome c oxidase subunit I (COI) sequences and voucher specimens which aimed to establish a reliable reference of frequently traded fishes in the province, a biodiversity hotspot at the center of the Philippine archipelago. A total of 1721 specimens were collected from 18 fish markets and landing sites around the province, in which 538 specimens were sequenced belonging to 393 species from 229 genera, 86 families, and 37 orders. Most speciose families are coral reef or reef-related shallow-water species. Twelve species from 11 families are newly recorded in the Philippine waters, among which 7 species are deep-sea inhabitants, while 3 species have expanded their distribution range. Only 20 taxa could not be identified to the species level due to the difficulty in morphological examinations, absence of matched reference sequences in online databases, and/or problematic species awaiting further studies. This first comprehensive DNA barcoding survey of Cebu fishes can facilitate further taxonomic research as well as the conservation and management of fisheries in the Philippines.

Among genetically engineered mouse models of breast cancer, MMTV-PyVT is a mouse strain in which the oncogenic polyoma virus middle T antigen is driven by the mouse mammary tumor virus promoter. The aim of the present study was to perform morphologic and genetic analyses of mammary tumors arising from MMTV-PyVT mice. To this end, mammary tumors were obtained at 6, 9, 12, and 16 weeks of age for histology and whole-mount analyses. We conducted whole-exome sequencing to identify constitutional and tumor-specific mutations, and genetic variants were identified using the GRCm38/mm10 mouse reference genome. Using hematoxylin and eosin analysis and whole-mount carmine alum staining, we demonstrated the progressive proliferation and invasion of mammary tumors. Frameshift insertions/deletions (indels) were noted in the Muc4. Mammary tumors showed small indels and nonsynonymous single-nucleotide variants but no somatic structural alterations or copy number variations. In summary, we validated MMTV-PyVT transgenic mice as a multistage model for mammary carcinoma development and progression. Our characterization may be used as a reference for guidance in future research.

Rhinogobius formosanus Oshima, 1919 has long been considered an amphidromous goby. However, a landlocked population recently found in the Jingualiao Creek upstream of the Feitsui Reservoir in Taipei suggests that R. formosanus may complete its life in the river. This study aims to verify the habitat use of the landlocked population of R. formosanus collected from the Feitsui Reservoir and an amphidromous population collected in Malian Creek using otolith Sr:Ca ratio analysis. The hypothesis that early life history varies between the landlocked and migratory gobies was also tested. Genetic analyses show that the Feitsui Reservoir and Malian Creek populations are not genetically different. Rhinogobius formosanus from Malian Creek showed high-to-low otolith Sr:Ca ratios suggesting that these specimens spent a planktonic larval stage in the sea followed by a freshwater life at later stages. In contrast, R. formosanus from the Feitsui Reservoir showed constant lower otolith Sr:Ca ratios, implying a landlocked life history of fish in the creek upstream of the reservoir. In addition, the analysis of growth increments showed a longer pelagic larval duration for the fish in the Malian Creek (58.8 days) than those in the Feitsui Reservoir (38.8). Variation of pelagic larval duration in two genetically homogenous populations implies acclimatization to the reservoir by the landlocked gobies. This study shows that R. formosanus, like some other congeners, is capable of adapting to a freshwater landlocked environment in its early developmental stage and supports the hypothesis that landlocked populations may have a shorter pelagic larval duration.

BackgroundThis study aimed to elucidate the influence of dementia etiologies on the degree of caregiver burden and determine which factors predict a high caregiving burden.MethodsThis 18-month retrospective cohort study enrolled 630 patients and their caregivers from the Dementia Center of Changhua Christian Hospital. The care team performed face-to-face interviews every 6 months, for 18 months from when a diagnosis of dementia was made. The primary outcome was the change in Zarit Burden Interview (ZBI) scores. Generalized estimating equations were used for the longitudinal data analysis.ResultsParticipants with Lewy body disease (LBD) had a significantly higher caregiving burden compared with those with Alzheimer's disease (AD) (β = 3.83 ± 1.47, Wald = 6.79, p = 0.009) after adjusting for patient and caregiver features. Caregivers of mixed-type dementia and frontotemporal dementia (FTD) experienced a greater burden than caregivers of AD, at 6- and 18-month follow-up. Patients with more severe dementia, neuropsychiatric symptoms, being cared for by more than two caregivers, or utilizing social resources were associated with higher ZBI scores; the depressive mood of caregiver also predicted higher ZBI scores.ConclusionThis longitudinal study demonstrated that caregiver burden was influenced by the underlying dementia etiology of patients. The dementia care team should provide personalized education and transfer patients and caregivers to appropriate resources, especially for high-risk populations.

It is both important and required to quickly and accurately detect chemical warfare agents, such as the highly toxic nerve agent sarin. Surface-enhanced Raman scattering (SERS) has received considerable attention due to its rapid results, high sensitivity, non-destructive data acquisition, and unique spectroscopic fingerprint. In this work, we successfully prepared SERS cotton swabs (CSs) for the detection of the sarin simulant agent dimethyl methyl phosphonate (DMMP) by anchoring N1-(3-trimethoxysilylpropyl) diethylenetriamine (ATS)/silver nanoparticle (AgNP) nanocomposites on CSs using ATS as the stabilizer and coupling agent. Simultaneously, the binding mode and reaction mechanics between the AgNP, ATS, and CS were confirmed by XPS. The modified CSs exhibited good uniformity, stability, and adsorption capability for SERS measurements, enabling the adsorption and detection of DMMP residue from an irregular surface via a simple swabbing process, with a detection limit of 1 g/L. The relative standard deviations (RSDs) of RSD710 = 5.6% had high reproducibility. In this research, the fabrication method could easily be extended to other cellulose compounds, such as natural fibers and paper. Furthermore, the versatile SERS CSs can be used for the on-site detection of DMMP, particularly in civil and defense applications, to guarantee food security and the health of the population.

Abstract Background Metastasis is a leading cause of breast cancer mortality. The induction of epithelial-to-mesenchymal transition (EMT) and complex oncogenic signaling is a vital step in the evolution of highly metastatic and therapeutically-intractable breast cancer; necessitating novel target discovery or development of therapeutics that target metastatic breast cells (MBCs). Methods To achieve this, this study employs a combination of in silico bioinformatics analyses, protein and transcript analyses, drug sensitivity assays, functional assays and animal studies. Results The present study identified CDH11 as an inductor and/or facilitator of metastatic signaling, and biomarker of poor prognosis in MBCs. Furthermore, we showed that in the presence of CDH11-rich cancer-associated fibroblasts (CAFs), MCF7 and MDA-MB-231 MBC cell lines acquired enhanced metastatic phenotype with increased CDH11, β-catenin, vimentin, and fibronectin (FN) expression. We also demonstrated, for the first time to the best of our knowledge that exposure to anti-CDH11 antibody suppresses metastasis, reduces CDH11, FN and β-catenin expression, and abrogate the cancer stem cell (CSC)-like traits of MBC cells. Interestingly, ectopic expression of miR-335 suppressed CDH11, β-catenin and vimentin expression, in concert with attenuated metastatic and CSC potentials of the MBC cells; conversely, inhibition of miR-335 resulted in increased metastatic potential. Finally, corroborating the in silica and in vitro findings, in vivo assays showed that the administration of anti-CDH11 antibody or miR-335 mimic suppressed tumorigenesis and inhibited cancer metastasis. Conclusions These findings validate our hypotheses that miR-335 mediates anti-CDH11 antibody therapy response and that an enhanced miR-335/CDH11 ratio elicits marked suppression of the MBC CSC-like and metastatic phenotypes, thus revealing a therapeutically-exploitable inverse correlation between CDH11-enhanced CSC-like and metastatic phenotype and miR-335 expression in MBCs. Thus, we highlight the therapeutic promise of humanized anti-CDH11 antibodies or miR-335-mimic, making a case for their clinical application as efficacious therapeutic option in patients with MBC.

Abstract Background Lung cancer often ranks one of the most prevalent malignancies in the world. One of the most challenging aspects of treating late-stage lung cancer patients is the development of drug resistance, from both conventional chemo- and targeted therapeutic agents. Tumor-associated microphages (TAMs) have been shown to promote the survival and distant metastasis of lung cancer cells. Methods This study investigated the TAMs - modulating potential of cisplatin-resistant non-small cell lung cancer (NSCLC) cell lines, A549R and H460R by using bioinformatics approach, immunoblotting, immunofluorescence staining, migration, invasion, colony, lung sphere formation and xenograft tumorigenecity assays. Results In this study, we first demonstrated the elevated expression of oncogenic and stemenss markers such as Src, Notch1, macrophage inhibitory factor (MIF) and CD155 in trained cisplatin (CDDP)-resistant A549 and H460 cells (A549R and H460R cells). When co-cultured with TAMs, A549R and H460R cells promoted the M2-polarization in TAMs. In addition, A549R and H460R cells showed an increased self-renewal ability as they formed tumor spheres at higher frequency comparing to their parental counterparts. The increased MIF secretion by the A549R and H460R cells could be suppressed by a multiple kinase inhibitor, dasatinib, which resulted in the decreased of oncogenic network of Src, CD155 and MIF expression. Similarly, dasatinib treatment reduced the M2 polarization in TAMs and suppressed self-renewal ability of the A549R and H460R cells. Conclusion In summary, cisplatin resistant lung cancer cells not only showed an increased self-renewal ability but also promoted M2 polarization of TAMs via the secretion of MIF. These findings were linked to the increased Src-associated signaling as dasatinib treatment significantly reversed these phenomena. Thus, kinase inhibitors such as dasatinib may be of potential for treating cisplatin-resistant lung cancer by targeting both tumor and the tumor microenvironment. Graphical abstract

Rhinogobius gigas is an amphidromous fish endemic to eastern Taiwan. Fishes with the diadromous behavior are expected to have a broader distribution range and higher genetic homogeneity despite that some amphidromous fishes with limited distribution are observed and R. gigas is an additional exception with a limited distribution range. Rhinogobius gigas has been documented to be retained inshore near the river plume with a short pelagic larval duration of 30-40 days, which may account for the endemism of this species. The short marine larval stage of R. gigas may imply a population genetic structure and the aim of the present study is to test whether the population genetic structure is present in R. gigas. To test the population genetic structure, fragments of mitochondrial displacement loop and cytochrome c oxidase subunit I were sequenced to provide molecular inference for genetic structure among populations. Sixty-nine haplotypes were identified among 191 R. gigas from 10 populations of eastern Taiwan and the mean haplotype and nucleotide diversities for all samples were 0.956 and 0.0024, respectively, implying a bottleneck followed by a recent population expansion further supported by Fu's Fs (-26.6; p < 0.001) and Tajima's D (-1.5; p = 0.037) values. The phylogenetic analysis revealed lack of genetic structure and the bush-like median joining network without commonly shared haplotypes supports the same scenario. The genetic homogeneity is probably due to the amphidromous life history providing the opportunity for passive larval transportation among the rivers through coastal currents in eastern Taiwan. The endemism to eastern Taiwan may be a consequence of complicated interactions among short pelagic larval duration, interspecific competition and coastal currents.

Abstract Background Lung cancer is the leading cause of cancer death worldwide. Recently, epigenetic dysregulation has been known to promote tumor progression and therefore may be a therapeutic target for anticancer therapy. JARID1B, a member of histone demethylases, has been found to be related to tumorigenesis in certain kinds of cancers. However, its biological roles in non-small cell lung cancer (NSCLC) remain largely unclear. Methods We firstly examined the expression of JARID1B in surgical specimens and six NSCLC cell lines. Then, we evaluated the relationship between JARID1B expression and clinicopathologic parameters in 72 NSCLC patients, thereby established its prognostic importance. We subsequently studied the functional roles of JARID1B in tumorigenesis to verify its clinicopathologic significance. Results Our results showed that JARID1B was overexpressed in NSCLC cells and JARID1B overexpression was associated with tumor size, lymph node metastasis, advanced stages, and poor overall survival in NSCLC patients. JARID1B overexpression resulted in increased cell proliferation and formation of tumorspheres and correlated positively with the expression of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) markers, while the c-Met signaling pathway was actively involved. It also correlated with the strength of resistance to cisplatin and doxorubicin. On the contrary, downregulation of JARID1B expression by applying shRNA or JARID1B inhibitor PBIT reversed these phenomena. Conclusions JARID1B worsens prognosis of NSCLC patients by promotion of tumor aggressiveness through multiple biological facets which were associated with activation of the c-Met signaling, and can be a novel prognostic biomarker and therapeutic target for NSCLC.

DNA barcoding based on a fragment of the cytochrome c oxidase subunit I (COI) gene is widely applied in species identification and biodiversity studies. The aim of this study was to establish a comprehensive barcoding database of coastal ray-finned fishes in Vietnam. A total of 3,638 specimens were collected from fish landing sites in northern, central and southern Vietnam. Seven hundred and sixty-five COI sequences of ray-finned fishes were generated, belonging to 458 species, 273 genera, 113 families and 43 orders. A total of 59 species were newly recorded in Vietnam and sequences of six species were new to the Genbank and BOLD online databases. Only 32 species cannot be annotated to species level because difficulty in morphological identifications and their Kimura-2-Parameter (K2P) genetic distances to most similar sequences were more than 2%. Moreover, intra-specific genetic distances in some species are also higher than 2%, implying the existence of putative cryptic species. The mean K2P genetic distances within species, genera, families, orders and classes were 0.34%, 12.14%, 17.39%, 21.42%, and 24.80, respectively. Species compositions are quite different with only 16 common species among northern, central and southern Vietnam. This may attribute to multiple habitats and environmental factors across the 3,260 km Vietnamese coastline. Our results confirmed that DNA barcoding is an efficient and reliable tool for coastal fish identification in Vietnam, and also established a reliable DNA barcode reference library for these fishes. DNA barcodes will contribute to future efforts to achieve better monitoring, conservation, and management of fisheries in Vietnam.

The epicardial adipose tissue (EAT), mainly composed of brown adipose tissue, is a metabolically active tissue releasing various bioactive factors with a critical role in metabolic diseases. The EAT is often irradiated during radiotherapy in patients with esophageal cancer due to its proximity to the target region. We aimed to evaluate the effect of radiation to the EAT on survival outcomes in patients with esophageal cancer receiving neoadjuvant chemoradiotherapy followed by esophagectomy. We analyzed data on 36 patients with esophageal cancer treated with trimodal therapy between 2012 and 2017. The median follow-up period was 22.0 months. The 3-year overall survival and progression-free survival rates were 39.7% and 32.5%, respectively. Multivariate analysis revealed that higher EAT-REI was independently associated with worse overall survival (hazard ratio: 1.002, p = 0.028) and progression-free survival (hazard ratio: 1.002, p = 0.03). The cutoff value with the highest accuracy for avoiding mortality was EAT-REI = 68.8 cGy/mL (area under the curve, 0.78, p = 0.006). The 3-year overall survival rate in patients with EAT-REI ≥68.8 and p = 0.003). The EAT should be considered an organ at risk during radiotherapy in patients with esophageal cancer. EAT-REI might serve as a biomarker of survival outcomes in these patients.

The relationships between pelagic larval duration (PLD) and geographic distribution patterns or population genetic structures of fishes remain obscure and highly variable among species. To further understand the early life history of the tidepool snake moray Uropterygius micropterus and the potential relationship between PLD and population genetic structure of this species, otolith microstructure and population genetics based on concatenated mtDNA sequence (cytochrome b and cytochrome oxidase subunit I, 1,336 bp) were analyzed for 195 specimens collected from eight locations around the southern Ryukyu Islands, Taiwan, and the central Philippines. Eels with longer PLD and lower otolith growth rates were observed at relatively higher latitudes with lower water temperatures (54.6 ± 7.7 days and 1.28 ± 0.16 µm day−1 on Ishigaki Island, Japan, vs. 43.9 ± 4.9 days and 1.60 ± 0.19 µm day−1 on Badian, the Philippines), suggesting that leptocephali grew faster and had shortened pelagic periods in warmer waters. Meanwhile, the eels along the southwest coast of Taiwan had relatively longer PLD (57.9 ± 10.5 days), which might be associated with the more complex ocean current systems compared to their counterparts collected along the east coast of Taiwan (52.6 ± 8.0 days). However, the southwestern and eastern Taiwan groups had similar otolith growth rates (1.33 ± 0.19 µm day−1 vs. 1.36 ± 0.16 µm day−1). Despite the intergroup variation in PLD, genetic analysis revealed fluent gene flow among the tidepool snake morays in the study regions, implying that intraspecies PLD variation had a weak effect on genetic structure. The leptocephalus stage might have ensured the widespread gene flow among the study areas and leptocephalus growth was likely influenced by regional water temperature.

Background: Limited data are available on the management of esophageal perforations in elderly patients. The aim of this study is to analyze the characteristics and treatments of esophageal perforations in elderly patients. Methods: Data on patients with esophageal perforations and older than 65 years of age were retrospectively reviewed from January 2001 to November 2012. Surgery-related and caustic-induced perforations were excluded in this study. Disease-related parameters, such as sex, bacteriology, locations, time to treatment, treatment types, and outcomes, were analyzed. A new method, cervical esophageal ligation and T-tube diversion following repair of esophageal perforations, was introduced. Results: A total of 61 patients, 24 females and 37 males, were eligible for this study. Heterogeneous presentations were noted following diagnosis of esophageal perforations. Esophagoscopy was the most frequently used method for diagnosis of esophageal perforations. Different sites of perforations would induce heterogeneous complications, among which thoracic perforations were most lethal. In this study, disease-related mortality rate was 13.1% (8 patients). Thoracic and abdominal perforations (p 48 hours (p = 0.002) were two significant factors responsible for mortality of patients esophageal perforations. The suggested new diversion method can be used as a salvage treatment option for complicated perforations. Conclusion: Early diagnosis and prompt treatments are the important determinants to reduce mortalities of elderly patients with esophageal perforations. Cervical esophageal ligation combined with T-tube diversion can be considered as a salvage method for complicated perforations.

Current standard chemotherapy for late stage ovarian cancer is found unsuccessful due to relapse after completing the regimens. After completing platinum-based chemotherapy, 70% of patients develop relapse and resistance. Recent evidence proves ovarian cancer stem cells as the source of resistance. Therefore, treatment strategy to target both cancer stem cells and normal stem cells is essential. In this study, we developed a novel chalcone derivative as novel drug candidate for ovarian cancer treatment. We found that methoxyphenyl chalcone was effective to eliminate ovarian cancer cells when given either as monotherapy or in combination with cisplatin. We found that cell viability of ovarian cancer cells was decreased through apoptosis induction. Dephosphorylation of Bcl2-associated agonist of cell death protein was increased after methoxyphenyl chalcone treatment that led to activation of caspases. Interestingly, this drug also worked as a G2/M checkpoint modulator with alternative ways of DNA damage signal–evoking potential that might work to increase response after cisplatin treatment. In addition, methoxyphenyl chalcone was able to suppress autophagic flux and stemness regulator in ovarian spheroids that decreased their survival. Therefore, combination of methoxyphenyl chalcone and cisplatin showed synergistic effects. Taken together, we believe that our novel compound is a promising novel therapeutic agent for effective clinical treatment of ovarian cancer.

In this study, we describe a nested PCR-DGGE strategy to detect Legionella communities from river water samples. The nearly full-length 16S rRNA gene was amplified using bacterial primer in the first step. After, the amplicons were employed as DNA templates in the second PCR using Legionella specific primer. The third round of gene amplification was conducted to gain PCR fragments apposite for DGGE analysis. Then the total numbers of amplified genes were observed in DGGE bands of products gained with primers specific for the diversity of Legionella species. The DGGE patterns are thus potential for a high-throughput preliminary determination of aquatic environmental Legionella species before sequencing. Comparative DNA sequence analysis of excised DGGE unique band patterns showed the identity of the Legionella community members, including a reference profile with two pathogenic species of Legionella strains. In addition, only members of Legionella pneumophila and uncultured Legionella sp. were detected. Development of three step nested PCR-DGGE tactic is seen as a useful method for studying the diversity of Legionella community. The method is rapid and provided sequence information for phylogenetic analysis.

The purpose of the technical note is to introduce the complex coil assisted coil embolization method in the treatment of intracranial small aneurysm, in order to enhance the safety of the procedure. The first microcatheter was navigated into the aneurysm sac and the ultrasoft coil was used as the embolization coil. If the embolizations coil could not stay within the aneurysm sac smoothly, such as coil herniation into parent artery during the delivery process. The second microcatheter would be navigated to the aneurysm level in the parent artery. Another complex coil was delivered within the parent artery via the second microcatheter to provide the neck bridge effect in order to enhance the stability of embolization coil. Besides, the protection coil will not disturb the parent artery flow. While the embolization coil was put into the aneurysm sac smoothly under the help of complex protective coil, the protective coil was then withdrawn gently. We use the most magnified view, dual-plane approach simultaneously to observe the stability of embolization coil. The embolization coil would be detached without any evidence of coil motion or vibration. The new method could provide the physiological protective method, without leaving any protective device such as stent within the parent artery.

There are few encounters with massive thyromegaly and intrathoracic extension as a result of the general usage of iodized salt and bread, which was an early therapeutic intervention for thyroid disorders. However, cervical goiter enlargement over time may extend into the thoracic space, causing respiratory distress, dysphagia, and vascular compression. Hence, even though it may be asymptomatic, there is potential for sudden enlargement (secondary to hemorrhage), cystic degeneration, or malignant change that can be life threatening and may require surgery. Patients who underwent surgery with curative intent for intrathoracic goiter from January 1970 to July 2002 were included in this retrospective study at the thoracic surgical division of Taipei Veteran General Hospital in Taipei, Taiwan. Data were compared between patients ≥65 years of age (elderly group) and patients

Multi-drug resistance (MDR), an unfavorable factor compromising treatment efficacy of anticancer drugs, involves upregulated ATP binding cassette (ABC) transporters and activated Sonic hedgehog (Shh) signaling. By preparing human breast cancer MCF-7 cells resistant to doxorubicin (DOX), we examined the effect and mechanism of norcantharidin (NCTD), a small-molecule synthetic compound, on reversing multidrug resistance. The DOX-prepared MCF-7R cells also possessed resistance to vinorelbine, characteristic of MDR. At suboptimal concentration, NCTD significantly inhibited the viability of DOX-sensitive (MCF-7S) and DOX-resistant (MCF-7R) cells and reversed the resistance to DOX and vinorelbine. NCTD increased the intracellular accumulation of DOX in MCF-7R cells and suppressed the upregulated the mdr-1 mRNA, P-gp and BCRP protein expression, but not the MRP-1. The role of P-gp was strengthened by partial reversal of the DOX and vinorelbine resistance by cyclosporine A. NCTD treatment suppressed the upregulation of Shh expression and nuclear translocation of Gli-1, a hallmark of Shh signaling activation in the resistant clone. Furthermore, the Shh ligand upregulated the expression of P-gp and attenuated the growth inhibitory effect of NCTD. The knockdown of mdr-1 mRNA had not altered the expression of Shh and Smoothened in both MCF-7S and MCF-7R cells. This indicates that the role of Shh signaling in MDR might be upstream to mdr-1/P-gp, and similar effect was shown in breast cancer MDA-MB-231 and BT-474 cells. This study demonstrated that NCTD may overcome multidrug resistance through inhibiting Shh signaling and expression of its downstream mdr-1/P-gp expression in human breast cancer cells.

Collecting basic biological information of a species is crucial for developing effective conservation strategies and ensuring its sustainable management. Dongsha Atoll is considered a vital, possibly the primary, nursery ground for the endangered sicklefin lemon shark (Negaprion acutidens) in the South China Sea. In this study, we employed acoustic telemetry to investigate the habitat utilization and preferences of N. acutidens at different life stages in Dongsha Atoll. A total of 44 sharks, including 16 juveniles, 14 small sharks, 11 sub-adults, and three adults, were tagged and tracked for 1-848 days. Results of this preliminary assessment revealed that: (1) juvenile and small sharks commonly utilize the shallow seagrass flats around Dongsha Island, with juveniles spending a significant amount of time in the embedded lagoon; (2) sharks of all sizes utilize the lagoon mouth area, especially small and sub-adult sharks; (3) adult sharks exhibit a broader activity range within the atoll and are unlikely to enter the embedded lagoon. We hypothesize that the embedded shallow lagoon of Dongsha Island serves as a shelter area for newborns and juveniles, while the lagoon mouth may function as an important hunting ground for small and sub-adult sharks. Adult sharks may have the broadest home range around the atoll and close to Dongsha Island during the breeding season. This study underscores the importance of considering habitat shifts and changes in home range size throughout the ontogeny of N. acutidens when planning effective spatial management strategies. [ABSTRACT FROM AUTHOR]