With the emergence of large-language models (LLM) and generative AI, which require an enormous amount of model parameters, the required memory bandwidth and capacity for high-end systems is on an ...unprecedented increase. To meet this need, we present an extended version of the high-bandwidth memory-3 (HBM3 DRAM), HBM3E, which achieves a 1280GB/s bandwidth with a cube density of 48GB. New design schemes and features, such as all-around power-through-silicon via (TSV), a 6-phase read-data-strobe (RDQS) scheme, a byte-mapping swap scheme, and a voltage-drift compensator for write data strobe (WDQS), are implemented to achieve extended bandwidth and capacity with enhanced reliability. The overall architecture and specifications, such as bump map footprint, the number of channel and I/Os, and the operation voltage, are identical to the latest HBM3 1, 2; therefore, backward compatibility is provided, avoiding system modification.
AIM To evaluate the efficacy and safety of HL tablet extracted from magnolia officinalis for treating patients with nonalcoholic fatty liver disease(NAFLD).METHODS Seventy-four patients with NAFLD ...diagnosed by ultrasonography were randomly assigned to 3 groups given high dose(400 mg) HL tablet, low dose(133.4 mg) HL tablet and placebo, respectively, daily for 12 wk. The primary endpoint was post-treatment change of hepatic fat content(HFC) measured by magnetic resonance spectroscopy. Secondary endpoints included changes of serum aspartate aminotransferase, alanine aminotransferase(ALT), cholesterol, triglyceride, free fatty acid, homeostasis model assessment-estimated insulin resistance, and body mass index(BMI).RESULTS The mean HFC of the high dose HL group, but not of the low dose group, declined significantly after 12 wk of treatment(high dose vs placebo, P = 0.033; low dose vs placebo, P = 0.386). The mean changes of HFC from baseline at week 12 were-1.7% ± 3.1% in the high dose group(P = 0.018),-1.21% ± 4.97% in the low dose group(P = 0.254) and 0.61% ± 3.87% in the placebo group(relative changes compared to baseline, high dose were:-12.1% ± 23.5%, low dose:-3.2% ± 32.0%, and placebo: 7.6% ± 44.0%). Serum ALT levels also tended to decrease in the groups receiving HL tablet while other factors were unaffected. There were no moderate or severe treatment-related safety issues during the study.CONCLUSION HL tablet is effective in reducing HFC without any negative lipid profiles, BMI changes and adverse effects.
Synthetic MRI is a technique that synthesizes contrast‐weighted images from multicontrast MRI data. There have been advances in synthetic MRI since the technique was introduced. Although a number of ...synthetic MRI methods have been developed for quantifying one or more relaxometric parameters and for generating multiple contrast‐weighted images, this review focuses on several methods that quantify all three relaxometric parameters (T1, T2, and proton density) and produce multiple contrast‐weighted images. Acquisition, quantification, and image synthesis techniques are discussed for each method. We discuss the image quality and diagnostic accuracy of synthetic MRI methods and their clinical applications in neuroradiology. Based on this analysis, we highlight areas that need to be addressed for synthetic MRI to be widely implemented in the clinic.
Level of Evidence
5
Technical Efficacy Stage
1
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Graft-versus-host disease (GvHD) is a severe complication of hematopoietic stem cell transplantation driven by activated allogeneic T cells. Here, we identify a distinct subset of T cell ...factor-1 (TCF1)
+
CD8
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T cells in mouse allogeneic and xenogeneic transplant models of acute GvHD. These TCF1
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cells exhibit distinct characteristics compared to TCF1
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cells, including lower expression of inhibitory receptors and higher expression of costimulatory molecules. Notably, the TCF1
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subset displays exclusive proliferative potential and could differentiate into TCF1
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effector cells upon antigenic stimulation. Pathway analyses support the role of TCF1
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and TCF1
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subsets as resource cells and effector cells, respectively. Furthermore, the TCF1
+
CD8
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T cell subset is primarily present in the spleen and exhibits a resident phenotype. These findings provide insight into the differentiation of allogeneic and xenogeneic CD8
+
T cells and have implications for the development of immunotherapeutic strategies targeting acute GvHD.
A novel series of 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides was designed, synthesized and evaluated for their biological activities on glucose-stimulated insulin secretion (GSIS). The cytotoxicity ...of all 41 novel compounds was screened to assess their pharmacological safety in pancreatic β-cells. A two-step optimization process was carried out to establish the structure-activity relationship for this class and subsequently we identified the most active analogue 26. Further modification study of 26 evidenced the necessity of N-hydrogens in the core architecture. Protein expression analysis suggested that 26 increases insulin secretion via the activation of the upstream effector of pancreatic and duodenal homeobox 1 (PDX-1), which is an important factor promoting GSIS. Moreover, the administration of 26 effectively augmented glucose uptake in C2C12 myotube cells via the suppression of Mitsugumin 53 (MG53), an insulin receptor substrate 1 (IRS-1) ubiquitination E3 ligase.
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•Novel 41 compounds of 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides were designed, synthesized, and biologically evaluated.•Compound 26 showed the highest GSI value.•Western blotting assay suggested 26 increase GSIS by regulating PDX-1 activity in INS-1 cells.•26 could augment glucose uptake in C2C12 myotube cells through suppressing MG53 expression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tamoxifen (Tam) has long been a top treatment option for breast cancer patients, but the challenge of eliminating cancer recurrence remains. Here, we identify a signalling pathway involving ELOVL2, ...ELOVL2-AS1, and miR-1233-3p, which contributes to drug resistance in Tam-resistant (TamR) breast cancer. ELOVL2-AS1, a long noncoding RNA, was significantly upregulated by its antisense gene, ELOVL2, which is known to be downregulated in TamR cells. Additionally, ELOVL2-AS1 underwent the most hypermethylation in MCF-7/TamR cells. Furthermore, patients with breast cancer who developed TamR during chemotherapy had significantly lower expression of ELOVL2-AS1 compared to those who responded to Tam. Ectopic downregulation of ELOVL2-AS1 by siRNA both stimulated cancer cell growth and deteriorated TamR. We also found that ELOVL2-AS1 sponges miR-1233-3p, which has pro-proliferative activity and elevates TamR, leading to the activation of potential target genes, such as MYEF2, NDST1, and PIK3R1. These findings suggest that ELOVL2-AS1, in association with ELOVL2, may contribute to the suppression of drug resistance by sponging miR-1233-3p in breast cancer.
•Surface shielding of inorganic photocatalyst by hydrophobic organic photocatalyst.•Restrict the self-oxidation of photogenerated H2O2, and maximize the H2O2 production.•A potential strategy for ...sustainable H2O2 production from natural resources (sun, water, and air).•The atomistic simulation studies substantiate the hydrophobicity induced H2O2 production.•A facile yet effective approach for solar H2O2 production over inorganic/organic heterojunction.
Photocatalytic H2O2 production is one of the most promising methods because it is a safe and sustainable technique. However, the inactiveness of inorganic photocatalysts (TiO2) under visible light irradiation and severe photodecomposition of H2O2 on their surfaces result in low performance for solar H2O2 production. Here, we report for the first time, a hydrophobic organic/inorganic (polymer/TiO2) heterojunction photocatalyst, which not only can utilize visible light, but also suppress H2O2 decomposition. In the absence of a hole scavenger, the photogenerated H2O2 concentration of the poly(9,9-dioctylfluorene-alt-benzothiadiazole) (PFBT)/TiO2 heterojunction photocatalyst (67 µM) was >70 times higher than that of pristine PFBT polymer. Further, improvement of polymer hydrophobicity by fluorine substitution results in enhanced photogenerated H2O2 concentration (110.4 µM) on (Poly(9,9-dioctyl fluorine-alt-difluorobenzothiadiazole) (PF2FBT)/TiO2). The atomistic simulation studies substantiate that the low adsorption energy of H2O2 on the heterojunction and the surface shielding of TiO2 induced by the hydrophobicity of the fluorinated polymers significantly improve H2O2 production.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The side effect and inefficiency of paclitaxel (PTX) in clinic have became the major problem in field of cancer chemotherapy. The local drug delivery constructed by injectable hydrogel has been ...suggested as the alternative due to its superior properties such as tumor selectivity, minimally invasive administration and sustained drug release behavior. Polysaccharides have been commonly used as a gelling agent to construct injectable hydrogel due to its wide resources, biocompatibility and bioactive functions. Here, we reported an injectable drug carrier with enhanced therapeutic effect based on Pinus koraiensis polysaccharide (PKP). The interaction, morphology and mechanical properties were studied. Interestingly, gels exhibited excellent injectable property including rapid recovery time, excellent thixotropy ability and good rheological property after injection, and these special properties make them more suitable to be constructed as an injectable drug carrier. In addition, the biocompatibility of gel was demonstrated in terms of hemolysis analysis. PTX-loaded gel showed excellent tumor inhibition effect against 4T1 and MCF-7 breast cancer cell lines in vitro, and exhibited the significant tumor growth suppression and reduced systemic toxicity in vivo. The successful construction of PTX-loaded gel demonstrates that PKP can be used as a promising carrier in local drug delivery.
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•An injectable hydrogel based on natural polysaccharide PKP was prepared.•In vitro cellular assays showed an excellent tumor cell inhibition of PTX-loaded gel.•In vivo antitumor activity proved the efficacy of PTX-loaded gel for tumor treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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