PHGDH: a novel therapeutic target in cancer.

Serine is a key contributor to the generation of one-carbon units for DNA synthesis during cellular proliferation. In addition, it plays a crucial role in the production of antioxidants that prevent abnormal proliferation and stress in cancer cells. In recent studies, the relationship between cancer metabolism and the serine biosynthesis pathway has been highlighted. In this context, 3-phosphoglycerate dehydrogenase (PHGDH) is notable as a key enzyme that functions as the primary rate-limiting enzyme in the serine biosynthesis pathway, facilitating the conversion of 3-phosphoglycerate to 3-phosphohydroxypyruvate. Elevated PHGDH activity in diverse cancer cells is mediated through genetic amplification, posttranslational modification, increased transcription, and allosteric regulation. Ultimately, these characteristics allow PHGDH to not only influence the growth and progression of cancer but also play an important role in metastasis and drug resistance. Consequently, PHGDH has emerged as a crucial focal point in cancer research. In this review, the structural aspects of PHGDH and its involvement in one-carbon metabolism are investigated, and PHGDH is proposed as a potential therapeutic target in diverse cancers. By elucidating how PHGDH expression promotes cancer growth, the goal of this review is to provide insight into innovative treatment strategies. This paper aims to reveal how PHGDH inhibitors can overcome resistance mechanisms, contributing to the development of effective cancer treatments.

Gene signature from cutaneous autoimmune diseases provides potential immunotherapy-relevant biomarkers in melanoma.

Immune checkpoint inhibitors (ICIs) are promising agents for treating melanoma. Given that autoimmune skin diseases exhibit hyper immune reaction, investigation of immune cells from autoimmune skin disease is crucial to validate the effectiveness of ICIs in melanoma treatment. We employed multipanel markers to predict the response to immune checkpoint inhibitors by characterizing the gene expression signatures of skin immune cells in systemic lupus erythematosus (SLE), atopic dermatitis (AD), and psoriasis (PS). By analyzing single-cell RNA sequencing data from each dataset, T cell gene signatures from autoimmune skin diseases exhibit a complex immune response in tumors that responded to immunotherapy. Based on that CD86 and CD80 provide essential costimulatory signals for T cell activation, we observed that interaction of CD86 signaling has been enhanced in the T cells of patients with SLE, AD, and PS. Our analysis revealed a common increase in CD86 signals from dendritic cells (DCs) to T cells in patients with SLE, AD, and PS, confirming that dendritic cells produce pro-inflammatory cytokines to activate T cells. Thus, we hypothesize that T cell gene signatures from autoimmune skin diseases exhibit a pro-inflammatory response and have the potential to predict cancer immunotherapy. Our study demonstrated that T cell gene signatures derived from inflammatory skin diseases, particularly SLE and PS, hold promise as potential biomarkers for predicting the response to immune checkpoint blockade therapy in patients with melanoma. Our data provide an understanding of the immune-related characteristics and differential gene expression patterns in autoimmune skin diseases, which may represent promising targets for melanoma immunotherapy.

A Wireless Power and Data Transfer IC for Neural Prostheses Using a Single Inductive Link With Frequency-Splitting Characteristic.

This paper presents a frequency-splitting-based wireless power and data transfer IC that simultaneously delivers power and forward data over a single inductive link. For data transmission, frequency-shift keying (FSK) is utilized because the FSK modulation scheme supports continuous wireless power transmission without disruption of the carrier amplitude. Moreover, the link that manifests the frequency-splitting characteristic due to a close distance between coupled coils provides wide bandwidth for data delivery without degrading the quality factors of the coils. It results in large power delivery, high data rate, and high power transfer efficiency. The presented IC fabricated in a 180-nm BCD process simultaneously achieves up-to-115-mW wireless power delivery to the load and 2.5-Mb/s downlink data rate over the single inductive link. The measured overall power efficiency from the DC power supply at the transmitter module to the load at the receiver module reaches 56.7 % at its maximum, and the bit error rate is lower than 10 -6 at 2.5 Mb/s. As a result, the figure of merit (FoM) for data transmission is enhanced by 2 times, and the FoM for power delivery is improved by 38.7 times compared to prior state-of-the-arts using a single inductive link.