Scripps Korea Antibody Institute

This paper reports a repeatable spectral artifact observed in 4-phase (I/Q) BLE backscatter transmitters operating with single-sideband modulation. Despite nominal 90° Hilbert phasing, a dominant third-order spur appears near the image sideband. We show that this artifact originates from the four-step phase staircase combined with the short periodicity of the {2,3}-tick fractional-divider dwell pattern used for BLE subcarrier generation. While the fundamental tone is mapped to the desired sideband, the third harmonic is deterministically placed on the opposite sideband. To mitigate this effect without disturbing BLE timing or CPFSK modulation, a frame-dithered 2/3-dwell mapping technique is proposed. It preserves the exact per-bit dwell budgets while breaking frame-to-frame phase coherence. Measurement results demonstrate a reduction of the third-order spur from −61.8/−63.5 dBm to −66.9/−66.6 dBm and corresponding improvements in SFDR to 15.7/15.5 dBc and IRR to 15.5 dB, with negligible impact on the fundamental tone.

Chimeric antigen receptor-T cell (CAR-T) therapy shows promise for treating hematologic malignancies but faces limitations including insufficient CAR-T cell activation. We developed a novel tetramer CAR-T (tCAR-T) system targeting CD19, which is overexpressed in hematologic malignancies. We created a tetrameric antibody scaffold by linking anti-CD19 scFv to traptavidin, then engineered T cells expressing CD8 hinge, CD8 transmembrane, costimulatory domains (4-1BB, CD3ζ), and YFP, followed by biotinylation using biotin ligase. The tCAR-T system was assembled via biotin-avidin interaction. This tetrameric arrangement significantly enhanced antibody avidity, promoting stronger antigen engagement and demonstrating potent cytotoxicity against CD19+ B-cell lymphoblast lines including Raji, Nalm-6, and Ramos. Notably, tCAR-T exhibited superior antitumor activity compared to Kymriah, with enhanced cytokine release and improved target cell elimination. This innovative approach improves cancer treatment efficacy through enhanced binding avidity and modular targeting flexibility, demonstrating that tCAR-T can overcome limitations of conventional CAR-T therapy and highlighting its potential to improve therapeutic outcomes for cancer patients.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition requiring accurate and non-invasive imaging for diagnosis and monitoring. Current clinical methods, including Disease Activity Index (DAI) scoring, have limitations due to their subjectivity and inability to detect mild or early inflammation. This study introduces a novel 89Zr-labeled IL-23p19 monoclonal antibody ([89Zr]Zr-IL-23p19) for targeted immuno-PET imaging in a dextran sulfate sodium-induced murine IBD model. Radiolabeling of IL-23p19 antibody with [89Zr]Zr yielded a stable tracer with high radiochemical purity. PET/MR imaging showed focal accumulation of [89Zr]Zr-IL-23p19 in inflamed colonic regions, aligning closely with histological inflammation and IL-23p19 expression. In contrast, the previous metabolic tracer [18F]FSPG demonstrated diffuse uptake without clear localization to inflamed tissues. Quantitative PET analysis indicated a significant correlation between [89Zr]Zr-IL-23p19 uptake and DAI scores, whereas [18F]FSPG exhibited weak correlations. These results highlight [89Zr]Zr-IL-23p19 immuno-PET imaging as a sensitive, specific, and non-invasive biomarker with strong potential for clinical translation in diagnosing and monitoring chronic intestinal inflammation in patients with IBD.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-29881-8.

This paper presents a fully integrated digital pulse-width-modulation three-level DC-DC buck converter. An internal switching frequency of 100 MHz is selected to minimize the value of passive components, and the package bond-wire based inductor is selected. In the integrated voltage regulator, a three-level structure is used to reduce the output voltage ripple, and Digital pulse width modulation (DPWM) is employed to achieve efficient current and voltage control. This digitally configured control scheme is robust against external environmental factors, such as process, voltage, and temperature variations, and also achieves a fast load transient time. The proposed circuit is fabricated using a 130-nm BCDMOS process, and it can regulate the 5-V input voltage to the output voltage range of 3.3–3.7 V. The three-level buck converter with an active area of 1.035 mm2 shows a power conversion efficiency of 72.4% under the load current of 200 mA.

Physical debilitation and other health risks such as cardiovascular disease and osteoporosis often accompany decreased estrogen production in postmenopausal women. Phytoestrogens, natural compounds that functionally mimic estrogens, have emerged as a potential treatment method for hormonal dysregulation during menopause. Among these, chaga (Inonotus obliquus) extract has gained attention for its various health benefits, including anti-cancer and antioxidant properties. The aim of this study was to investigate the bone metabolic efficacy of lactic acid bacteria derived from I. obliquusin ovariectomized C57BL/6J female mice. The results demonstrated the estrogenic activity of probiotics derived from I. obliquus and its potential to alleviate osteoporosis symptoms by improving bone microstructure and density. Furthermore, probiotics derived from I. obliquus favored biochemical markers associated with a reduction in bone resorption. Additionally, effects on brain neurotransmitters and serum estradiol levels suggested its regulatory role in estrogen mimicry. These findings underscore the therapeutic potential of probiotics derived from I. obliquus in managing menopausal symptoms and thus warrant potential human investigation in improving bone health in postmenopausal women.

In this paper, for the wireless network, wearable device, and Internet of Things (IoT) markets, a delay-locked loop (DLL) is used to implement accurate multiplication for a reference clock and the frequency of various applications through an edge combiner (EC). A simpler structure is more sensitive to process, voltage, and temperature (PVT), so DLL complements itself quickly in the feedback system and improves the stability of the final output. The proposed DLL-based multiplier can prevent harmonic lock generation using a first phase canceller (FPC), thus compensating for faster lock time. The circuit is built with a 55 nm CMOS process and has a chip area of 0.0225 mm2. The proposed design achieves a total power consumption of 0.48 mW at the 30.72 MHz operating clock frequency, and the clock duty can also operate stably from 15 to 75%.

As the wireless communication market grows rapidly worldwide, efficient communication technologies and methods of communication devices are needed. In particular, a method of minimizing total power consumption is adopted by constructing a PLL capable of covering all different bands. In addition, the Type-2 CP-PLL structure is adopted, and it is configured with a fractional PLL to cover the dual band with a final output of 2620–4470 MHz. This study used a 1V supply voltage and a 55nm CMOS process.

A better understanding of the metabolic phenotype of stem-like cancer cells could provide targets to help overcome chemoresistance. In this study, we hypothesized that colon cancer cells with the stem cell feature of CD133 expression have increased proton leakage that influences glucose metabolism and offers protection against reactive oxygen species (ROS)-inducing treatment. In HT29 colon cancer cells, 18 F-fluorodeoxyglucose (FDG) uptake was increased by CD133 selection and decreased by CD133 silencing. In CD133(+) cells, greater 18 F-FDG uptake was accompanied by increased oxygen consumption rate (OCR) and reduced mitochondrial membrane potential and mitochondrial ROS, indicating increased proton leakage. The uncoupling protein inhibitor genipin reversed the increased 18 F-FDG uptake and greater OCR of CD133(+) cells. The ROS-inducing drug, piperlongumine, suppressed CD133(-) cell survival by stimulating mitochondrial ROS generation but was unable to influence CD133(+) cells when used alone. However, cotreatment of CD133(+) cells with genipin and piperlongumine efficiently stimulated mitochondrial ROS for an enhanced antitumor effect with substantially reduced CD133 expression. These results demonstrate that mitochondrial uncoupling is a metabolic feature of CD133(+) colon cancer cells that provides protection against piperlongumine therapy by suppressing mitochondrial ROS generation. Hence, combining genipin with ROS-inducing treatment may be an effective strategy to reverse the metabolic feature and eliminate stem-like colon cancer cells.

G protein-coupled receptors (GPCRs) play crucial roles in numerous physiological and pathological processes. Mutations in GPCRs that result in loss of function or alterations in signaling can lead to inherited or acquired diseases. Herein, studying prokineticin receptor 2 (PROKR2), we initially identify distinct interactomes for wild-type (WT) versus a mutant (P290S) PROKR2 that causes hypogonadotropic hypogonadism. We then find that both the WT and mutant PROKR2 are targeted for endoplasmic reticulum (ER)-associated degradation, but the mutant is degraded to a greater extent. Further analysis revealed that both forms can also leave the ER to reach the Golgi. However, whereas most of the WT is further transported to the cell surface, most of the mutant is retrieved to the ER. Thus, the post-ER itinerary plays an important role in distinguishing the ultimate fate of the WT versus the mutant. We have further discovered that this post-ER itinerary reduces ER stress induced by the mutant PROKR2. Moreover, we extend the core findings to another model GPCR. Our findings advance the understanding of disease pathogenesis induced by a mutation at a key residue that is conserved across many GPCRs and thus contributes to a fundamental understanding of the diverse mechanisms used by cellular quality control to accommodate misfolded proteins.

This paper presents an active rectifier design with a gate charge recycling technique. Gate switching increases the switching losses of the active rectifier, therefore, as a way to reduce switching losses, the gate charge recycling technique is proposed. The output power of 15 W is achieved to enable rapid charging using the three standards for wireless charging mode, magnetic induction (WPC and PMA), and magnetic resonance (A4WP). Power-sharing is used to lower the amount of power consumed by each standard mode core. In WPC, and PMA mode zero current sensing (ZCS) technique has been used while in the A4WP mode, the digitally controlled delay adjustment (DCDA) technique has been employed. By using a gate charge recycling block, the efficiency has been considerably improved due to the lower power consumption. It aims to increase the overall efficiency by reusing switching loss using the gate charge recycling block, and it has effectiveness by allowing three standard modes to operate with one single chip. The proposed design combines charge-recycling with zero current sensing techniques to improve power efficiency. The layout size is <inline-formula> <tex-math notation="LaTeX">$4.75~\mu \text{m}^{2}$ </tex-math></inline-formula>. The achieved efficiency is 98.6 &#x0025; in the magnetic induction method (WPC/PMA) at 15 W, and 94.86 &#x0025; in the magnetic resonance method (A4WP) with an output power level of 15 W. The chip is fabricated in the BCD <inline-formula> <tex-math notation="LaTeX">$0.18~\mu \text{m}$ </tex-math></inline-formula> CMOS process.