Search Results (72)

Background: Fluorescent gold nanoclusters conjugated with α-lipoic acid (FANCs) have shown great promise for drug development. In a previous study, FANCs did not show any acute or subacute toxicity under 0.6–20 μM/100 μL/25 g body weight in male and female ICR mice. However, the chronic toxicity of FANCs has not been studied. Aim of study: This study used oral administration of FANCs to determine the long-term safety profile and adverse effects in ICR mice. Methods: In vivo chronic toxicity was examined via oral administration of FANCs to male and female ICR mice. The daily food consumption, body weight, hematological profile, serum biochemical profile, organ coefficient, histopathological changes, and survival rate of the mice were calculated. Results: FANCs did not result in mortality due to chronic toxicity in both male and female mice. The animal behavior, body weight, hematological profile, serum biochemical profile, and organ coefficient showed no treatment-related malignant changes. This indicates that FANCs do not cause liver, renal, or other organ damage. Conclusions: These results indicate that the no-observed-adverse-effect level (NOAEL) is 20 μM/100 μL/25 g for 6 months of treatment in male and female ICR mice. Full article

Background/Objectives: Crohn’s disease (CD) is a progressive condition, and early treatment with infliximab combined with an immunosuppressant within six months has been shown to improve clinical outcomes. However, the impact of early ustekinumab (UST) use in biologic-naïve CD patients remains unclear. This study aims to address this gap by evaluating the clinical outcomes of early UST intervention in such patients. Methods: In this retrospective cohort study, we included biologic-naïve CD patients treated with UST, with a clinical follow-up period of at least six months from October 2020 to January 2024 across four medical centers. Patients who received UST within six months of CD diagnosis were categorized into the Early-UST group, while those who were initially treated with conventional therapies and subsequently received UST after six months were assigned to the control group. The primary endpoint was the improvement of clinical outcomes at six months. Results: A total of 60 biologic-naïve CD patients were enrolled. Baseline characteristics were comparable between the two groups. At six months, the Early-UST group (n = 24) demonstrated significantly lower Crohn’s Disease Activity Index (CDAI) scores (73.03 vs. 112.42, p = 0.038), lower Harvey–Bradshaw Index (HBI) scores (1.46 ± 1.69 vs. 2.72 ± 2.17, p = 0.020), higher rates of clinical remission (91.7% vs. 63.9%, p = 0.017), and higher rates of steroid-free clinical remission (79.2% vs. 50.0%, p = 0.031) compared to the control group (n = 36). At one year, the early-UST group continued to exhibit lower CDAI scores (39.94 vs. 91.48, p = 0.005). Conclusions: Initiating ustekinumab within six months of CD diagnosis is associated with improved clinical outcomes and enhanced quality of life in biologic-naïve Crohn’s disease patients. Full article

Chronic kidney disease (CKD) is a progressive condition linked to sarcopenia, a syndrome characterized by loss of skeletal muscle mass and strength, affecting a quarter of CKD patients globally. Sarcopenia has multiple paths through which it can worsen morbidity and mortality as well as decrease the quality of life in CKD, including systemic inflammation, hormonal imbalances, metabolic changes, and dysbiosis of gut microbiota. There is a regional variation in the criteria set for diagnosis, with two main groups being the European Working Group on Sarcopenia in Older People and the Asian Working Group for Sarcopenia. Management regimes such as nutritional optimization, vitamin D, exercise, correction of metabolic acidosis, and modulation of gut microbiota constitute effective intervention strategies. Emerging therapeutic options include anabolic agents, myostatin inhibitors, and anti-inflammatory treatment options. Future advances such as genomics, proteomics, and personalized medicine will open up new avenues for addressing the complex pathophysiology of sarcopenia. Hence, a comprehensive multidisciplinary approach focused on the specific needs of each patient will be vital in reducing the effects of sarcopenia and improving the situation of people with CKD. Full article

This study investigates Mg isotopes (δ²⁶Mg) in vent fluids from Milos, Aegean Sea, to evaluate phase separation and secondary mineral formation. The δ²⁶Mg vary significantly in Milos, exceeding 0.66‰, allowing for the classification of the fluids into three sub-groups based on chemical characteristics: seawater-like, cave fluids, and submarine-brines. The seawater-like fluids exhibit large δ²⁶Mg variation, −0.64 to −1.18‰, and mostly follow a Rayleigh fractionation trend, with a fractionation factor α = 1.00020 ± 0.00011. The cave fluids are highly acidic, have low Cl, are vapor-rich, and display heavy δ²⁶Mg compositions (−0.52 to −0.63‰). The submarine-brines are characterized by high Cl, high non-volatile metals, and light δ²⁶Mg (−0.65 to −1.00‰). The latter two fluid types represent vapors and brines, respectively, which underwent phase separation at depth in Milos. These δ²⁶Mg values were combined with major/trace elements, as well as Li and B isotopes, to explore possible controlling mechanisms. We report for the first time a shallow submarine hydrothermal system that has a vapor component enriched in heavy δ²⁶Mg, but with no detectable isotopic changes in the brines. It is evident that δ²⁶Mg in vent fluids is unique for separating effects of water/rock interaction and secondary mineral and phase separation at shallow-water systems. Full article

This study investigates water–rock interactions of Taiwan hot springs by analyzing rare earth elements (REEs) concentrations and strontium (Sr) isotopes. REEs were separated from samples using RE resin, and their concentrations were measured by HR-ICPMS. Strontium was isolated using Sr^SPEC resin, and the strontium isotopic ratio was determined by MC-ICPMS. The ΣREE in the hot springs ranges from 3.17 ng/L to 29.7 µg/L, with the highest levels found in the Tatun Volcano Group, followed by springs from sedimentary and metamorphic regions. The primary factors controlling REE compositions are lithology and pH. REE patterns of hot springs can be categorized into five types, indicating that the hot springs were affected by various mechanisms. The most distinct hot spring samples are from Tatun Volcano, Ginshan, and Kuantzuling. The ⁸⁷Sr/⁸⁶Sr ratios range from 0.70468 to 0.71730, with the most radiogenic samples originating from metamorphic regions, reflecting the nature of the parent rock interacting with the hot spring water. Seawater intrusion and preferential weathering of carbonate also have minor effects on Sr isotope composition. The findings indicate that the types of surrounding rocks and the pH values of the hot springs significantly influence REE patterns and Sr isotope compositions in Taiwan’s hot springs. Full article

Type 2 diabetes mellitus (T2DM) is often associated with chronic inflammation exacerbated by hyperglycemia and dyslipidemia. Mung beans have a longstanding reputation in traditional medicine for their purported ability to lower blood glucose levels, prompting interest in their pharmacological properties. This study aimed to explore the impact of mung bean water (MBW) on carbohydrate and lipid metabolism in a T2DM rat model induced by nicotinamide/streptozotocin. Normal and DM rats were supplemented with a stock solution of MBW as drinking water ad libitum daily for 8 weeks. MBW supplementation led to significant reductions in plasma total cholesterol, HDL-C, and VLDL-C + LDL-C levels, and decreased malondialdehyde levels in plasma and liver samples, indicating reduced oxidative stress. MBW supplementation lowered plasma glucose levels and upregulated hepatic hexokinase activity, suggesting enhanced glucose utilization. Additionally, MBW decreased hepatic glucose-6-phosphate dehydrogenase and glutathione peroxidase activities, while hepatic levels of glutathione and glutathione disulfide remained unchanged. These findings underscore the potential of MBW to improve plasma glucose and lipid metabolism in DM rats, likely mediated by antioxidant effects and the modulation of hepatic enzyme activities. Further exploration of bioactive components of MBW and its mechanisms could unveil new therapeutic avenues for managing diabetes and its metabolic complications. Full article

Uremic toxins cause bone disorders in patients with chronic kidney disease (CKD). These disorders are characterized by low turnover osteodystrophy and impaired bone formation in the early stages of CKD. Evidence indicates that the aryl hydrocarbon receptor (AhR) mediates signals that suppress early osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). However, whether the AhR mediates the effects of indoxyl sulfate (IS), a uremic toxin, on BMSC osteogenesis remains unclear. We investigated whether IS affects osteogenesis through the AhR/Hes1 pathway. Expression levels of osteogenesis genes (Runx2, Bmp2, Alp, and Oc), AhR, and Hes1 were measured in mouse BMSCs (D1 cells). At concentrations of 2–50 μM, IS significantly reduced mineralization, particularly in the early stages of BMSC osteogenesis. Furthermore, IS significantly downregulated the expression of Runx2, Bmp2, Oc, and Alp. Notably, this downregulation could be prevented using an AhR antagonist and through Ahr knockdown. Mechanistically, IS induced the expression of Hes1 through AhR signaling, thereby suppressing the transcription of Runx2 and Bmp2. Our findings suggest that IS inhibits early osteogenesis of BMSCs through the AhR/Hes1 pathway, thus suppressing the transcription of Runx2 and Bmp2. Our findings may guide new therapeutic strategies against CKD-related bone disorders. Full article

Groundwater is a vital resource in the Chuoshui River alluvial plain (CSAP), a key agricultural area in Taiwan. Understanding groundwater recharge is crucial for sustainable water management amidst changing climatic conditions and increasing water demand. This study investigates the major ion composition, solute Sr concentrations, and ⁸⁷Sr/⁸⁶Sr ratios in groundwater and stream water from the Choushui River (CSR) to trace groundwater recharge sources. The Piper diagram reveals that most groundwater samples are of the freshwater Ca–HCO₃ type, aligning with the total dissolved solids (TDS) classification. TDS and major ion compositions indicate that groundwater near Baguashan Terrace (BGT) and Douliu Hill (DLH) primarily derives from stream water and rainwater. Na⁺ and Cl⁻ enrichment in some aquifers of BGT and DLH is attributed to the dissolution of paleo-sea salt and mixing with paleo-seawater from sedimentary porewater. Elevated dissolved Sr concentrations and lower ⁸⁷Sr/⁸⁶Sr ratios in these aquifers further support the intrusion of paleo-seawater. Groundwater in the proximal fan shows high TDS due to intensive weathering, complicating the use of TDS as a tracer. Sr isotopic compositions and solute Sr²⁺ concentrations effectively distinguish recharge sources, revealing that the CSR mainstream primarily recharges the proximal fan and BGT region, while CSR tributaries and rainwater mainly recharge the DLH region. This study concludes that Sr isotopic compositions and solute Sr²⁺ concentrations are more reliable than TDS and major ion compositions in identifying groundwater recharge sources, enhancing our understanding of groundwater origins and the processes affecting water quality. Full article

Nuclear fission reactions can release massive amounts of energy accompanied by neutrons and γ photons, which create a mixed radiation field and enable a series of reactions in nuclear reactors. This study demonstrates a one-pot/one-step approach to synthesizing radioactive gold nanoparticles (RGNP) without using radioactive precursors and reducing agents. Trivalent gold ions are reduced into gold nanoparticles (8.6–146 nm), and a particular portion of ¹⁹⁷Au atoms is simultaneously converted to ¹⁹⁸Au atoms, rendering the nanoparticles radioactive. We suggest that harnessing nuclear energy to gold nanoparticles is feasible in the interests of advancing nanotechnology for cancer therapy. A combination of RGNP applied through convection-enhanced delivery (CED) and temozolomide (TMZ) through oral administration demonstrates the synergistic effect in treating glioblastoma-bearing mice. The mean survival for RGNP/TMZ treatment was 68.9 ± 9.7 days compared to that for standalone RGNP (38.4 ± 2.2 days) or TMZ (42.8 ± 2.5 days) therapies. Based on the verification of bioluminescence images, positron emission tomography, and immunohistochemistry inspection, the combination treatment can inhibit the proliferation of glioblastoma, highlighting the niche of concurrent chemoradiotherapy (CCRT) attributed to RGNP and TMZ. Full article

Gallium nitride (GaN) possesses remarkable characteristics such as a wide bandgap, high critical electric field, robust antiradiation properties, and a high saturation velocity for high-power devices. These attributes position GaN as a pivotal material for the development of power devices. Among the various GaN-based devices, vertical GaN MOSFETs stand out for their numerous advantages over their silicon MOSFET counterparts. These advantages encompass high-power device applications. This review provides a concise overview of their significance and explores their distinctive architectures. Additionally, it delves into the advantages of vertical GaN MOSFETs and highlights their recent advancements. In conclusion, the review addresses methods to enhance the breakdown voltage of vertical GaN devices. This comprehensive perspective underscores the pivotal role of vertical GaN MOSFETs in the realm of power electronics and their continual progress. Full article

Oral cancer poses a major health challenge in Taiwan, consistently ranking among the highest globally in both incidence and cancer-related mortality. Transoral robotic surgery (TORS) has potential advantages over open surgery, but its long-term oncologic outcomes are not well established. In this study, we sought to elucidate the role of TORS in improving treatment outcomes among oral cancer patients. A case–control study with propensity score matching was conducted in a single teaching hospital in Taiwan. It included 72 oral cancer patients in each group to analyze and compare survival outcomes between the surgical approaches. The TORS group demonstrated a higher negative resection margin rate, a lower mortality risk and better overall survival than the open-surgery group. Multivariate Cox regression analysis confirmed TORS’s association with a reduced risk of death. Kaplan–Meier survival analysis and log-rank tests indicated significantly better survival outcomes for the TORS group across all cancer stages. Moreover, the TORS group exhibited improved overall survival rates for stage III and IV patients compared to the conventional open-surgery group. In conclusion, this study suggests that TORS may offer better overall survival rates and potential advantages over conventional surgery for oral cancer treatment. Full article

The snowball Earth (SBE) describes a state of the Earth’s climate with global or near-global ice cover. The cap dolostone at the base of the Ediacaran successions serves as useful archives for studying environmental change during the Marinoan Snowball Earth deglaciation in Neoproterozoic. The characteristic compositions in dolomite provide critical information on continental weathering and coastal water mixing after glacial retreat. However, valid methods for pristine dolomite separation remain challenging. In this study, four selected cap dolostone samples from the base of the Ediacaran Lantian Formation were used for establishing a new 3-step leaching method, to remove the secondary calcite and other impurities before determination of δ²⁶Mg and ⁸⁷Sr/⁸⁶Sr in dolomite. Non-destructive Raman, X-ray diffractometer (XRD) and scanning electron microscopy (SEM) were used to examine the distribution of dolomite and minor calcite/silicate in each sample. Micro-drill powders before each extraction procedure were examined in weight loss and mineralogical compositions, as well as the chemicals in the leaching solutions. Potential diagenetic artifacts were evaluated using Sr/Ca, Mn/Sr, ⁸⁷Sr/⁸⁶Sr and δ²⁶Mg in solutions. By applying a simple two-end member mixing between the seawater and the silicate sources (R² = 0.48, n = 23), the down-core variations of δ²⁶Mg and ⁸⁷Sr/⁸⁶Sr in cap dolostone can be used to gain a better understand of the temporal weathering intensity changes, as well as the coastal oceanic mixing processes, after the Marinoan deglaciation. Full article

Osteoarthritis (OA) is a prevalent form of arthritis that affects over 32.5 million adults worldwide, causing significant cartilage damage and disability. Unfortunately, there are currently no effective treatments for OA, highlighting the need for novel therapeutic approaches. Thrombomodulin (TM), a glycoprotein expressed by chondrocytes and other cell types, has an unknown role in OA. Here, we investigated the function of TM in chondrocytes and OA using various methods, including recombinant TM (rTM), transgenic mice lacking the TM lectin-like domain (TM^LeD/LeD), and a microRNA (miRNA) antagomir that increased TM expression. Results showed that chondrocyte-expressed TM and soluble TM [sTM, like recombinant TM domain 1 to 3 (rTMD123)] enhanced cell growth and migration, blocked interleukin-1β (IL-1β)-mediated signaling and protected against knee function and bone integrity loss in an anterior cruciate ligament transection (ACLT)-induced mouse model of OA. Conversely, TM^LeD/LeD mice exhibited accelerated knee function loss, while treatment with rTMD123 protected against cartilage loss even one-week post-surgery. The administration of an miRNA antagomir (miR-up-TM) also increased TM expression and protected against cartilage damage in the OA model. These findings suggested that chondrocyte TM plays a crucial role in counteracting OA, and miR-up-TM may represent a promising therapeutic approach to protect against cartilage-related disorders. Full article

In this work, we demonstrated the thermal analysis of different flip-chip bonding designs for high power GaN HEMT developed for power electronics applications, such as power converters or photonic driver applications, with large gate periphery and chip size, as well as an Au metal heat-spreading layer deposited on top of a planarized dielectric/passivation layer above the active region. The Au bump patterns can be designed with high flexibility to provide more efficient heat dissipation from the large GaN HEMT chips to an AlN package substrate heat sink with no constraint in the alignment between the HEMT cells and the thermal conduction bumps. Steady-state thermal simulations were conducted to study the channel temperatures of GaN HEMTs with various Au bump patterns at different levels of current and voltage loadings, and the results were compared with the conventional face-up GaN die bonding on an AlN package substrate. The simulations were started from a single finger isolated HEMT cell and then extended to multiple fingers HEMT cells (total gate width > 40 mm) to investigate the “thermal cross-talk” effect from neighboring devices. Thermal analysis of the GaN HEMT under pulse operation was also performed to better reflect the actual conditions in power conversion or pulsed laser driver applications. Our analysis provides a combinational assessment of power GaN HEMT dies under a working condition (e.g., 1MHz, 25% duty cycle) with different flip chip packaging schemes. The analysis indicated that the channel temperature rise (∆T) of a HEMT cell in operation can be reduced by 44~46% by changing from face-up die bonding to a flip-chip bonding scheme with an optimized bump pattern design. Full article

Graphene quantum dots (GQDs), nanomaterials derived from graphene and carbon dots, are highly stable, soluble, and have exceptional optical properties. Further, they have low toxicity and are excellent vehicles for carrying drugs or fluorescein dyes. Specific forms of GQDs can induce apoptosis and could be used to treat cancers. In this study, three forms of GQDs (GQD (nitrogen:carbon = 1:3), ortho-GQD, and meta-GQD) were screened and tested for their potential to inhibit breast cancer cell (MCF-7, BT-474, MDA-MB-231, and T-47D) growth. All three GQDs decreased cell viability after 72 h of treatment and specifically affected breast cancer cell proliferation. An assay for the expression of apoptotic proteins revealed that p21 and p27 were up-regulated (1.41-fold and 4.75-fold) after treatment. In particular, ortho-GQD-treated cells showed G2/M phase arrest. The GQDs specifically induced apoptosis in estrogen receptor-positive breast cancer cell lines. These results indicate that these GQDs induce apoptosis and G2/M cell cycle arrest in specific breast cancer subtypes and could potentially be used for treating breast cancers. Full article