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A direct strategy to achieve specific treatments and reduce side effects is through cell type‐specific drug delivery. Exosomes (Exos) can be modified with folic acid (FA) to prepare drug delivery systems targeting tumor cells that highly express FA receptors. This study aimed to produce an exo drug delivery system with FA decoration and temozolomide (TMZ) loading to improve the sustained TMZ release and targeting. We used DSPE‐PEG2000‐FA to modify exos derived from astrocyte U‐87 to prepare FA‐modified exos (Astro‐exo‐FA). TMZ was encapsulated into Astro‐exo‐FA or Astro‐exo through electroporation to produce TMZ@Astro‐exo and TMZ@Astro‐exo‐FA. In vitro drug release was examined using the dialysis bag method. Through cell experiments in vitro and mouse glioma models in vivo, the effect of TMZ@Astro‐exo‐FA on U‐87 cells was determined. Exo properties were not affected by FA modification and TMZ loading. The drug release rate of TMZ@Astro‐exo‐FA was slower. TMZ@Astro‐exo‐FA uptake by U‐87 cells was higher compared to TMZ@Astro‐exo, indicating that TMZ@Astro‐exo‐FA has a stronger targeting toward U‐87 cells. TMZ@Astro‐exo‐FA remarkably reduced U‐87 cell proliferation, migration, and invasion compared with TMZ@Astro‐exo and free TMZ. Treatment with TMZ@Astro‐exo‐FA reduced the side effects of TMZ (minimal change in body weight), prolonged survival, and inhibited tumor growth in mouse glioma models, and its efficacy was stronger than that of TMZ@Astro‐exo and free TMZ. TMZ@Astro‐exo‐FA could enhance the effect of TMZ against glioma, providing novel ideas for drug targeting delivery and exploring exos as drug carriers against glioma.

A flood risk assessment of urban areas in Kaohsiung city along the Dianbao River was performed based on flood hazards and social vulnerability. In terms of hazard analysis, a rainfall-runoff model (HEC-HMS) was adopted to simulate discharges in the watershed, and the simulated discharges were utilized as inputs for the inundation model (FLO-2D). Comparisons between the observed and simulated discharges at the Wulilin Bridge flow station during Typhoon Kongrey (2013) and Typhoon Megi (2016) were used for the HEC-HMS model calibration and validation, respectively. The observed water levels at the Changrun Bridge station during Typhoon Kongrey and Typhoon Megi were utilized for the FLO-2D model calibration and validation, respectively. The results indicated that the simulated discharges and water levels reasonably reproduced the observations. The validated model was then applied to predict the inundation depths and extents under 50-, 100-, and 200-year rainfall return periods to form hazard maps. For social vulnerability, the fuzzy Delphi method and the analytic hierarchy process were employed to select the main factors affecting social vulnerability and to yield the weight of each social vulnerability factor. Subsequently, a social vulnerability map was built. A risk map was developed that compiled both flood hazards and social vulnerability levels. Based on the risk map, flood mitigation strategies with structural and nonstructural measures were proposed for consideration by decision-makers.

In this paper, the long-lasting impact of the winter North Atlantic Oscillation (NAO) on Arctic sea ice is investigated using reanalysis data, with focus on the Barents–Kara (BK) sea where the air-sea-ice response is closely associated with the interdecadal shift in the northern action center of the NAO. A significant negative correlation between the winter NAO and the late autumn BK sea ice has been dominant since the early 2000s, which is in sharp contrast to the extremely weak correlation before the late 20th century. When the northern center of the NAO retreats westward, a prevailing low-level southerly wind anomaly creates significant positive air temperature anomalies over the BK sea, and the induced ocean current strengthens the northward transport of warm sea water, resulting in a positive BK upper-layer ocean temperature anomaly and a negative sea ice anomaly until early spring. Entering summer, the preexisting less-than-normal sea ice causes the amount of solar shortwave radiation absorbed by the upper-layer sea water to significantly increase and thereby continues to warm up the upper layer of sea water and reduce the sea ice. The warmed sea water enables the negative sea ice anomaly to last until late autumn owing to its relatively large specific heat capacity. Thus, the NAO in the previous winter exerts a long-lasting impact on the BK sea ice.

Background The chloroacetamide herbicides pretilachlor is an emerging pollutant. Due to the large amount of use, its presence in the environment threatens human health. However, the molecular mechanism of pretilachlor degradation remains unknown. Results Now, Rhodococcus sp. B2 was isolated from rice field and shown to degrade pretilachlor. The maximum pretilachlor degradation efficiency (86.1%) was observed at a culture time of 5 d, an initial substrate concentration 50 mg/L, pH 6.98, and 30.1 °C. One novel metabolite N -hydroxyethyl-2-chloro- N -(2, 6-diethyl-phenyl)-acetamide was identified by gas chromatography-mass spectrometry (GC–MS). Draft genome comparison demonstrated that a 32,147-bp DNA fragment, harboring gene cluster ( EthRABCD B2 ), was absent from the mutant strain TB2 which could not degrade pretilachlor. The Eth gene cluster, encodes an AraC/XylS family transcriptional regulator (EthR B2 ), a ferredoxin reductase (EthA B2 ), a cytochrome P450 monooxygenase (EthB B2 ), a ferredoxin (EthC B2 ) and a 10-kDa protein of unknown function (EthD B2 ). Complementation with EthABCD B2 and EthABD B2 , but not EthABC B2 in strain TB2 restored its ability to degrade chloroacetamide herbicides. Subsequently, codon optimization of EthABCD B2 was performed, after which the optimized components were separately expressed in Escherichia coli , and purified using Ni-affinity chromatography. A mixture of EthABCD B2 or EthABD B2 but not EthABC B2 catalyzed the N- dealkoxymethylation of alachlor, acetochlor, butachlor, and propisochlor and O -dealkylation of pretilachlor, revealing that EthD B2 acted as a ferredoxin in strain B2. EthABD B2 displayed maximal activity at 30 °C and pH 7.5. Conclusions This is the first report of a P450 family oxygenase catalyzing the O -dealkylation and N- dealkoxymethylation of pretilachlor and propisochlor, respectively. And the results of the present study provide a microbial resource for the remediation of chloroacetamide herbicides-contaminated sites.

In this work, we extend the quasiparticle model to include the chemical potential dependence of the coupling constant g and consider the density-dependent bag constant B m in order to satisfy the asymptotic freedom feature. By satisfying the absolutely stable condition at zero temperature, we draw the stability region of the strange quark matter (SQM) and describe the recently discovered pulsars PSR J0952-0607, PSR J2215+5135, PSR J0740+6620, 4U 1702-429, and HESS J1731-347 as quark stars (QSs) within the extended quasiparticle model. In particular, our results indicate that the polytropic index γ of the quark star matter becomes anisotropic with different magnetic field orientation distributions, and γ decreases with the increment of the maximum star mass of QSs at zero temperature or under the density-dependent magnetic fields within quasiparticle model.

Meningiomas are the most frequently diagnosed primary intracranial tumors in adults. Surgical resection is preferred if the meningioma is accessible; for those that are not suitable for surgical resection, radiotherapy should be considered to improve local tumor control. However, recurrent meningiomas are challenging to treat, as the recurrent tumor might be located in the previously irradiated area. Boron Neutron Capture Therapy (BNCT) is a highly selective radiotherapy modality in which the cytotoxic effect focuses mainly on cells with increased uptake of boron-containing drugs. In this article, we describe four patients with recurrent meningiomas treated with BNCT in Taiwan. The mean boron-containing drug tumor-to-normal tissue uptake ratio was 4.125, and the tumor mean dose was 29.414 GyE, received via BNCT. The treatment response showed two stable diseases, one partial response, and one complete response. We also introduce and support the effectiveness and safety of BNCT as an alternative salvage treatment for recurrent meningiomas.

In this study, we investigate temperature fluctuations in hot QCD matter using a three-flavor Polyakov loop-extended Nambu–Jona-Lasinio (PNJL) model. The high-order cumulant ratios Rn2 (n>2) exhibit non-monotonic variations across the chiral phase transition, characterized by slight fluctuations in the chiral crossover region and significant oscillations around the critical point. In contrast, distinct peak and dip structures are observed in the cumulant ratios at low-baryon chemical potential. These structures gradually weaken and eventually vanish at high chemical potential as they compete with the sharpening of the chiral phase transition, particularly near the critical point and the first-order phase transition. Our results indicate that these non-monotonic peak and dip structures in high-order cumulant ratios are associated with the deconfinement phase transition. This study quantitatively analyzes temperature fluctuation behavior across different phase transition regions, and the findings are expected to be observed and validated in heavy-ion collision experiments through measurements of event-by-event mean transverse momentum fluctuations.

Taiwan is frequently affected by typhoons, which cause storm surges and wave impacts that damage sea dikes, resulting in overflow and subsequent flooding. Therefore, it is essential to analyze the damage to sea dikes caused by storm surges and wave impacts, leading to overflow, for effective coastal protection. This study employs the ADCIRC model coupled with the SWAN model to simulate storm surges and waves around Taiwan and develops a sea dike failure model that incorporates mechanisms for impact damage, run-up damage, and overflow calculation. To ensure model accuracy, three historical typhoon events were used for calibration and validation of the ADCIRC+SWAN model. The results show that the ADCIRC coupled with SWAN model can effectively simulate storm surges and waves during typhoons. Typhoon Soulik (2013) was simulated to examine a breach in the Tamsui Youchekou sea dike in northern Taiwan, and an uncertainty analysis was conducted using the Monte Carlo method and Bayesian theorem. The results indicate that when the compressive strength of the sea dike is reduced to 5% of its original strength, impact and run-up damage occur, leading to overflow. In the case of impact damage, the overflow volume due to the breach falls within a 95% confidence interval of 0.16 × 106 m3 to 130 × 106 m3. For run-up damage, the 95% confidence interval for the overflow volume ranges from 0.16 × 106 m3 to 639 × 106 m3. The ADCIRC+SWAN model is used to simulate storm surge and waves, incorporating impact damage and run-up damage mechanisms to represent concrete sea dike failure. This approach effectively models dike failure and calculates the resulting overflow.

Background: Boron neutron capture therapy (BNCT) is a radiotherapeutic approach that can destroy cancer cells while sparing the surrounding normal cells. Currently, boronophenylalanine (BPA) is the most common boron delivery agent used in BNCT for treating recurrent cancers of the head and neck, gliomas, and melanomas. On the other hand, valproic acid (VPA) is one of the representative class I histone deacetylase inhibitors (HDACi), which is a promising sensitizer for cancer therapies. In this study, we aimed to verify whether VPA could induce an enhanced effect in destroying melanoma cells in concurrence with BNCT and to explore the underlying mechanism of VPA-BNCT action in killing these cells. Materials and Methods: Murine melanoma B16-F10 cells were pre-treated with VPA and irradiated with neutron during BPA-BNCT. We explored the clonogenic assay and the expression of phosphorylated H2AX (γH2AX) for cell survival and DNA double-strand breaks (DSBs), respectively. We also examined the expression levels of DNA damage responses-associated proteins and performed a cell cycle analysis. Results: Our data indicated that the combination treatment of VPA and BNCT could significantly inhibit the growth of melanoma cells. Furthermore, VPA-BNCT treatment could exacerbate and perturb DNA DSBs in B16-F10 cells. In addition, pre-treatment of VPA abolished the G2/M arrest checkpoint caused by BNCT. Conclusion: Our results demonstrate that VPA has the potential to serve as a radiosensitizer of BPA-mediated BNCT for melanoma. These findings could improve BNCT treatments for melanoma.

Taiwan faces intense rainfall during typhoon seasons, leading to rapid increases in water level in rivers. Accurate flood forecasting in rivers is essential for protecting lives and property. The objective of this study is to develop a river flood forecasting model combining multiple additive regression trees (MART) and ensemble Kalman filtering (EnKF). MART, a machine learning technique, predicts water levels for internal boundary conditions, correcting a one-dimensional (1D) unsteady flow model. EnKF further refines these predictions, enabling precise real-time forecasts of water levels in the Danshui River system for up to three hours lead time. The model was calibrated and validated using observed data from four historical typhoons to evaluate its accuracy. For the present time at three water level stations in the Danshui River system, the root mean square error (RMSE) ranged from 0.088 to 0.343 m, while the coefficient of determination (R2) ranged from 0.954 to 0.999. The validated model (module 1) was divided into two additional modules: module 2, which combined the ensemble unsteady flow model with inner boundary correction and MART, and module 3, which featured an ensemble 1D unsteady flow model without inner boundary correction. These modules were employed to forecast water levels at three stations from the present time to 3 h lead time during Typhoon Muifa in 2022. The study revealed that the Tu-Ti-Kung-Pi station was less affected by inner boundaries due to significant tidal influences. Consequently, excluding the upstream and downstream boundaries, Tu-Ti-Kung-Pi station showed a superior RMSE trend from present time to 3 h lead time across all three modules. Conversely, the Taipei Bridge and Bailing Bridge stations began using inner boundary forecast values for correction from 1 h to 3 h lead times. This increased the uncertainty of the inner boundary, resulting in higher RMSE values for these locations in modules 1 and 2 compared to module 3.