The surface sediments off Southwestern Taiwan were collected during three different cruises in May 2009, November 2009, and March 2010, respectively. The concentrations of chlorophyll-a and ...phaeopigment, as well as benthic foraminifera species, were analyzed.The results show that the concentration of chlorophyll-a decreases with the distance from the shore, and the concentration of chlorophyll-a also decreases with increasing water depth. The concentration of phaeopigment seems to have no significant relationship with the water depth. The relationships between the concentrations of benthic foraminifera, chlorophyll-a, and phaeopigment are also not significant. Because samples were collected from different water depths on the continental shelf, slope and in a canyon, the oceangraphic setting therefore may be one of the main factors which influences the distribution pattern of benthic foraminifera.According to the EOF analysis, the water depth in sampling sites plays a very important role in terms of the distribution of living benthic foraminifera in this study. The distribution do not show significant difference between collecting seasons. Finally, the concentrations of the chlorophyll-a and phaeopigment decrease drastically in a downcore record. Quinqueloculina spp., an epifaunal foraminifer, shows a significant peak concentration in the depth of 5-6 cm downcore. Bioturbation probably was responsible for this change.
Cancer metastasis is a common cause of failure in cancer therapy. However, over 60% of oral cancer patients present with advanced stage disease, and the five‐year survival rates of these patients ...decrease from 72.6% to 20% as the stage becomes more advanced. In order to manage oral cancer, identification of metastasis biomarker and mechanism is critical. In this study, we use a pair of oral squamous cell carcinoma lines, OC3, and invasive OC3‐I5 as a model system to examine invasive mechanism and to identify potential therapeutic targets. We used two‐dimensional differential gel electrophoresis (2D‐DIGE) and matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF/TOF MS) to examine the global protein expression changes between OC3 and invasive OC3‐I5. A proteomic study reveals that invasive properties alter the expression of 101 proteins in OC3‐I5 cells comparing to OC3 cells. Further studies have used RNA interference technique to monitor the influence of progesterone receptor membrane component 1 (PGRMC1) protein in invasion and evaluate their potency in regulating invasion and the mechanism it involved. The results demonstrated that expression of epithelial‐mesenchymal transition (EMT) markers including Twist, p‐Src, Snail1, SIP1, JAM‐A, vimentin and vinculin was increased in OC3‐I5 compared to OC3 cells, whereas E‐cadherin expression was decreased in the OC3‐I5 cells. Moreover, in mouse model, PGRMC1 is shown to affect not only migration and invasion but also metastasis in vivo. Taken together, the proteomic approach allows us to identify numerous proteins, including PGRMC1, involved in invasion mechanism. Our results provide useful diagnostic markers and therapeutic candidates for the treatment of oral cancer invasion.
Background
Lenvatinib and atezolizumab plus bevacizumab(A + B) have been used for unresectable hepatocellular carcinoma (HCC) as first‐line therapy. Real‐world studies comparison of efficacy and ...safety in these two regimens are limited, we therefore conduct this study to investigate these issues.
Methods
We retrospectively reviewed patients received lenvatinib (n = 46) and A + B (n = 46) as first‐line systemic therapy for unresectable HCC in a tertiary medical center. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Inverse probability weighting (IPW) was performed for baseline clinical features balance.
Results
A total of 92 patients with median age of 63.8 year‐old, 78.3% male, 85.9% viral hepatitis infected, 67.4% BCLC stage C were enrolled. The median treatment and follow‐up duration were 4.7 months and 9.4 months, respectively. There was no significant difference in ORR (26.1% vs. 41.3%, p = 0.1226), PFS (5.9 vs. 5.3 months, p = 0.4066), and OS (not reached vs. not reached, p = 0.7128) between the lenvatinib and A + B groups. After IPW, the results of survival and response rate were also compared. Subgroup analysis suggested that using lenvatinib was not inferior to A + B in regards of PFS, including those with elder, Child‐Pugh class B, beyond up‐to‐seven, or portal vein invasion VP4 patients. Among the lenvatinib treated patients, multivariate analysis showed patients elder than 65‐year‐old was an independent predictor associated with shorter PFS (adjust HR: 2.0850.914–4.753, p = 0.0213). The incidence rates of adverse events were similar between two groups (76 vs. 63%, p = 0.1740). Both of two regimens had similarly few impact on liver function by comparison of baseline, third month, and sixth month albumin‐bilirubin index and Child‐Pugh score.
Conclusions
The efficacy and safety of lenvatinib are similar to A + B as a first‐line systemic therapy for unresectable HCC.
This study provides real‐world experience of lenvatinib and A + B as firstline treatment for unresectable HCC. The data showed that compared survival, response rate, and adverse events between two regimens.
The phosphor‐converted light‐emitting diode (PC‐LED) has become an indispensable solid‐state lighting and display technologies in the modern society. Nevertheless, the use of scarce rare‐earth ...elements and the thermal quenching (TQ) behavior are still two most crucial issues yet to be solved. Here, this work successfully demonstrates a highly efficient and thermally stable green emissive MnI2(XanPO) crystals showing a notable photoluminescence quantum yield (PLQY) of 94% and a super TQ resistance from 4 to 623 K. This unprecedented superior thermal stability is attributed to the low electron–phonon coupling and the unique rigid crystal structure of MnI2(XanPO) over the whole temperature range based on the temperature‐dependent photoluminescence (PL) and single crystal X‐ray diffraction (SCXRD) analyses. Considering these appealing properties, green PC‐LEDs with a power efficacy of 102.5 lm W−1, an external quantum efficiency (EQE) of 22.7% and a peak luminance up to 7750 000 cd m−2 are fabricated by integrating MnI2(XanPO) with commercial blue LEDs. Moreover, the applicability of MnI2(XanPO) in both micro‐LEDs and organic light‐emitting diodes (OLEDs) is also demonstrated. In a nutshell, this study uncovers a candidate of highly luminescent and TQ resistant manganese halide suitable for a variety of emission applications.
A highly efficient and thermally stable manganese halide crystal, MnI2(XanPO) is demonstrated. The low electron–phono coupling along with rigid crystal structure contributes to excellent photoluminescent quantum yield of 94% with unprecedented near zero thermal quenching from 4 to 623 K. The crystals find their applications in light emitting diodes and micro light emitting diodes with excellent external quantum efficiency (EQE) up to 22.7% and power efficacy as high as 102.5 lm W−1.
HLA‐G is considered as an immune checkpoint protein and a tumor‐associated antigen. In the previous work, it is reported that CAR‐NK targeting of HLA‐G can be used to treat certain solid tumors. ...However, the frequent co‐expression of PD‐L1 and HLA‐G) and up‐regulation of PD‐L1 after adoptive immunotherapy may decrease the effectiveness of HLA‐G‐CAR. Therefore, simultaneous targeting of HLA‐G and PD‐L1 by multi‐specific CAR could represent an appropriate solution. Furthermore, gamma‐delta T (γδT) cells exhibit MHC‐independent cytotoxicity against tumor cells and possess allogeneic potential. The utilization of nanobodies offers flexibility for CAR engineering and the ability to recognize novel epitopes. In this study, Vδ2 γδT cells are used as effector cells and electroporated with an mRNA‐driven, nanobody‐based HLA‐G‐CAR with a secreted PD‐L1/CD3ε Bispecific T‐cell engager (BiTE) construct (Nb‐CAR.BiTE). Both in vivo and in vitro experiments reveal that the Nb‐CAR.BiTE‐γδT cells could effectively eliminate PD‐L1 and/or HLA‐G‐positive solid tumors. The secreted PD‐L1/CD3ε Nb‐BiTE can not only redirect Nb‐CAR‐γδT but also recruit un‐transduced bystander T cells against tumor cells expressing PD‐L1, thereby enhancing the activity of Nb‐CAR‐γδT therapy. Furthermore, evidence is provided that Nb‐CAR.BiTE redirectes γδT into tumor‐implanted tissues and that the secreted Nb‐BiTE is restricted to the tumor site without apparent toxicity.
Elevated PD‐L1 in solid tumors increases the risk of immune escape from HLA‐G‐CAR cell therapy. The bicistronic mRNA construct that drives PD‐L1 Nb‐BiTE and HLA‐G Nb‐CAR in γδT cells via electroporation is designed to address this issue. This Nb‐CAR.BiTE‐γδT therapy can overcome HLA‐G and PD‐L1 dilemma and even kill tumor cells with inadequate antigen expression, resulting in potent anti‐tumor activity without apparent toxicity.
The subject of this study was to investigate the species composition and spatial distribution pastern of iving (Rose Bengal stained) benthic foraminifera in sediment surface samples (0-1 cm) off the ...Southwestern Taiwan and Dongsha Atoll. The main objectives of this study was to document the living benthic foraminiferal assemblages off the Southwestern Taiwan and Dongsha Atoll and to examine their distribution in relation to environmental parameters.Four benthic foraminiferal biofacies were recognized within the substrate type in Dongsha Atoll: A1 (Fine-grained) is represented by Pseudomassilina spp. - Quinqueloculina parkeri, A2 (Fine-grained) is represented by Hauerina spp. - Pseudomassilina spp., B1 (Coarse-grained) is characterised by Calcarina spp. - Quinqueloculina spp., B2 (Coarse-grained) is characterised by Amphistegina spp. - Quinqueloculina spp.Sediment surface samples off the Southwestern Taiwan during May 2009 led to the identification of four assemblages. Assemblage A is characterised by Ammonia spp. - Bolivina spp., Assemblage B between is characterized by Asterorotalia spp. - Globobulimina spp., Assemblage C is represented by Cibicides spp. - Nummulites spp., Assemblage D is represented by Ammonia spp. - Cibicides spp.Sediment surface samples off the Southwestern Taiwan during Nov. 2009 led to the identification of three assemblages. Assemblage A is dominated by Ammonia spp. - Cibicides spp., Assemblage B is characterised by Ammonia spp. - Bolivina spp., Assemblage C is characterised by Asterorotalia spp. - Bolivina spp.Stained benthic foraminifera form Dongsha Atoll correlated with current wave, collected site, coarse fraction and TOC contents. Living benthic foraminifera off the Southwestern Taiwan seems not to be related with TOC contents and coarse fraction, the assemblages were found to be more related to tidal energy and lateral transport.
Gut microbiota is very important for energy metabolism and regulation, which in turn affect the health and physiological functions of the host, and provide energy required for exercise. ...Supplementation with probiotics may be one of the ways to change the gut microbiota. In recent years, many studies have shown that probiotic supplementation can effectively improve sports performance. In this study, we screened Lactobacillus plantarum (PL-02), a probiotic of human-origin, from the intestines of 2008 Olympic women's 48 kg weightlifting gold medalist and explored the role of PL-02 in improved exercise endurance performance, reduced fatigue biochemical parameters, and changes in body composition. Male Institute of Cancer Research (ICR) mice were assigned to 0, 2.05 × 10
, 4.10 × 10
and 1.03 × 10
CFU/kg/day groups and were fed by oral gavage once daily for 4 weeks. The results showed that 4 weeks of PL-02 supplementation could significantly increase muscle mass, muscle strength and endurance performance, and hepatic and muscular glycogen storage. Furthermore, PL-02 could significantly decrease lactate, blood urea nitrogen (BUN), ammonia, and creatine kinase (CK) levels after exercise (p < 0.05). We believe that PL-02 can be used as a supplement to improve exercise performance and for its anti-fatigue effect.
The shell weight and abundance of planktonic foraminifera, together with seawater parameters, collected from area off the Southern Taiwan were analyzed in this study. Plankton tows were conducted ...between April 2006 and December 2011 at water depths of 50, 100, 150, and 200 m. In addition, five sediment trap moorings and one box core were sampled at the same area. Globigerinoides sacculifer was picked for counting numbers and measuring weight from towed samples and core sediments. For seawater samples, dissolved inorganic carbon was analyzed. The age model of sediment core was determined based on the excess lead-210.The seasonal variation of planktonic foraminifera abundance is not obvious in the Gao-ping submarine canyon regime. The shell abundance decreases as the depth increases. Furthermore, the relationship between shell abundance and lunar cycle can be observed from the sediment trap moorings. Shell abundance reaches its maximum before full moon. The sea surface is dominated with larger shells at night than daytime. Shell abundance and size are closely related with the optima growth environmental parameters than anything else.The foraminiferal shell weight is not so different between winter, summer, and autumn. But in spring the shell weight is the lightest among all. Based on the foraminiferal shell weight and the corresponding seawater carbonate ion concentration obtained from this study, it is not easy to explain the relationship between both. Shell weight in downcore record was lighter after A.D. 1890, which probably was caused by the acidification of seawater resulted from the increase of CO2 in the atmosphere.
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To ensure a long-term quantum computational advantage, the quantum hardware should be upgraded to withstand the competition of continuously improved classical algorithms and ...hardwares. Here, we demonstrate a superconducting quantum computing systems Zuchongzhi 2.1, which has 66 qubits in a two-dimensional array in a tunable coupler architecture. The readout fidelity of Zuchongzhi 2.1 is considerably improved to an average of 97.74%. The more powerful quantum processor enables us to achieve larger-scale random quantum circuit sampling, with a system scale of up to 60 qubits and 24 cycles, and fidelity of FXEB=(3.66±0.345)×10-4. The achieved sampling task is about 6 orders of magnitude more difficult than that of Sycamore Nature 574, 505 (2019) in the classic simulation, and 3 orders of magnitude more difficult than the sampling task on Zuchongzhi 2.0 arXiv:2106.14734 (2021). The time consumption of classically simulating random circuit sampling experiment using state-of-the-art classical algorithm and supercomputer is extended to tens of thousands of years (about 4.8×104 years), while Zuchongzhi 2.1 only takes about 4.2 h, thereby significantly enhancing the quantum computational advantage.
IMPORTANCE: The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with ...eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. OBJECTIVE: To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. MAIN OUTCOMES AND MEASURES: Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. RESULTS: The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10−17). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z=8.58; P < .00001) for CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease. CONCLUSIONS AND RELEVANCE: This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.
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