Pharmacology and Toxicology

Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injury

1. Yaying Zhu
2. Chengxiang Deng
3. Bo Chen
4. Jia He
5. Yanan Liu
6. Cheng Peng
7. Zhao Shan

• Curated by eLife

  eLife Assessment

  This study addresses an important question in liver biology: how zonal hepatocytes balance survival and proliferation following injury; using spatial transcriptomics, mechanistic perturbations, and functional assays, the authors propose that a mid-zone Atf4-Chop axis to Btg2 program temporarily suppresses proliferation to promote survival during APAP-induced hepatotoxicity. The idea that distinct intrahepatic zones mount tailored stress responses is conceptually significant and has implications for regeneration and toxicology. The dataset is rich and the methodology modern, but several conclusions rely on assumptions about zonation under injury, limited injury models, and incomplete functional validation of the Atf4-Chop-Btg2 axis. With targeted revisions and additional experiments, the work has the potential to provide strong mechanistic insights into liver zonation and injury responses.

Reviewed by eLife

Mechanism of SK2 channel gating and its modulation by the bee toxin apamin and small molecules

1. Samantha J Cassell
2. Weiyan Li
3. Simon Krautwald
4. Maryam Khoshouei
5. Yan Tony Lee
6. Joyce Hou
7. Wendy Guan
8. Stefan Peukert
9. Wilhelm Weihofen
10. Jonathan R Whicher

• Curated by eLife

  eLife Assessment

  In this important manuscript, Cassell and colleagues set out on a mechanistic and pharmacological exploration of an engineered chimeric small conductance calcium-activated potassium channel 2 (SK2). They show compelling evidence that the SK2 channel possesses a unique extracellular structure that modulates the conductivity of the selectivity filter, and that this structure is the target for the SK2 inhibitor apamin. The interpretations are sound and the writing is clear, and the manuscript was strengthened during review by providing more detailed information for the electrophysiological experiments and the structural analyses attempted, in addition to relating dilation of the filter to mechanisms of inactivation in other potassium channels. This high-quality study will be of interest to membrane protein structural biologists, ion channel biophysicists, and chemical biologists, and will help to inform future drug development targeting SK channels.

Reviewed by eLife

Interleukin-4 induces CD11c+ microglia leading to amelioration of neuropathic pain in mice

1. Keita Kohno
2. Ryoji Shirasaka
3. Keita Hirose
4. Takahiro Masuda
5. Makoto Tsuda

• Curated by eLife

  eLife Assessment

  This study is important as it highlighted how IL-4 regulates the reactive state of a specific microglial population by increasing the proportion of CD11c+ microglial cells and ultimately suppressing neuropathic pain. The study employs a combination of behavioral assays, pharmacogenetic manipulation of microglial populations, and characterization of microglial markers to address these questions. It provided convincing evidence for the proposed mechanism of IL-4-mediated microglial regulation in neuropathic pain.

Reviewed by eLife

Transgenerational effects of perinatal cannabis exposure on female reproductive parameters in mice

1. Mingxin Shi
2. Yeongseok Oh
3. Debra A Mitchell
4. James A MacLean
5. Ryan J McLaughlin
6. Kanako Hayashi

Reviewed by preLights

A novel bispecific antibody CVL006 superior to AK112 for dual targeting of PD-L1 and VEGF in cancer therapy

1. Chunyan Wang
2. Hao Huang
3. Zeng Song
4. Zhongyuan Li
5. Jinwen Huang
6. Liang Cao
7. Ziai Wu
8. Junfang Pan
9. XiaoBing Chen
10. Xiaokun Shen

Reviewed by PREreview

Target protein identification in live cells and organisms with a non-diffusive proximity tagging system

1. Yingjie Sun
2. Changheng Li
3. Xiaofei Deng
4. Wenjie Li
5. Xiaoyi Deng
6. Weiqi Ge
7. Miaoyuan Shi
8. Ying Guo
9. Yanxun V Yu
10. Hai-bing Zhou
11. Youngnam N Jin

• Curated by eLife

  eLife Assessment

  The study presents important findings that reveal SEPHS2 and VPS37C as new potential drug targets for dasatinib and hydroxychloroquine respectively in addition to confirming known targets of these drugs. The evidence provided is compelling as observed in the methods, data and analyses. This article will be of great interest to chemical biologists, biochemists, and scientists in drug discovery and diagnostics.

Reviewed by eLife

Visualization of endogenous G proteins on endosomes and other organelles

1. Wonjo Jang
2. Kanishka Senarath
3. Gavin Feinberg
4. Sumin Lu
5. Nevin A Lambert

• Curated by eLife

  eLife assessment

  This important study investigates the intracellular localization patterns of G proteins involved in GPCR signaling, presenting compelling evidence for their preference for plasma and lysosomal membranes over endosomal, endoplasmic reticulum, and Golgi membranes. This discovery has significant implications for understanding GPCR action and signaling from intracellular locations. This research will interest cell biologists studying protein trafficking and pharmacologists exploring localized signaling phenomena.

Reviewed by eLife

SntB triggers the antioxidant pathways to regulate development and aflatoxin biosynthesis in Aspergillus flavus

1. Dandan Wu
2. Chi Yang
3. Yanfang Yao
4. Dongmei Ma
5. Hong Lin
6. Ling Hao
7. Wenwen Xin
8. Kangfu Ye
9. Minghui Sun
10. Yule Hu
11. Yanling Yang
12. Zhenhong Zhuang

• Curated by eLife

  eLife assessment

  In this useful study, the authors investigate the regulatory mechanisms related to toxin production and pathogenicity in Aspergillus flavus. Their observations indicate that the SntB protein regulates morphogenesis, aflatoxin biosynthesis, and the oxidative stress response. The data supporting the conclusions are compelling and contribute significantly the advancing the understanding of SntB function.

Reviewed by eLife

Synthesis and biological assessment of chalcone and pyrazoline derivatives as novel inhibitor for ELF3-MED23 interaction

1. Soo-Yeon Hwang
2. Kyung-Hwa Jeon
3. Hwa-Jong Lee
4. Inhye Moon
5. Sehyun Jung
6. Seul-Ah Kim
7. Hyunji Jo
8. Seojeong Park
9. Misun Ahn
10. Soo-Yeon Kwak
11. Younghwa Na
12. Youngjoo Kwon

• Curated by eLife

  eLife assessment

  This valuable study characterized a new set of small molecules targeting the interaction between ELF3-MED23, with one of the reported compounds representing a promising novel therapeutic strategy, The evidence supporting the conclusions is convincing. This article will be of interest to medical and cell biologists working on cancer and, particularly, on HER2-overexpression cancers.

Reviewed by eLife

Noncaloric monosaccharides induce excessive sprouting angiogenesis in zebrafish via foxo1a-marcksl1a signal

1. Xiaoning Wang
2. Jinxiang Zhao
3. Jiehuan Xu
4. Bowen Li
5. Xia Liu
6. Gangcai Xie
7. Xuchu Duan
8. Dong Liu

• Curated by eLife

  eLife assessment

  This valuable study investigates the effect of noncaloric monosaccharides, sugar substitutes that are commonly used by diabetic patients, on angiogenesis in the zebrafish embryo. The authors show that noncaloric monosaccharides and glucose similarly induce excessive blood vessel formation due to the increased formation of tip cells by endothelial cells through the foxo1a-marcksl1a pathway. This solid study is of interest for the medical community in charge of the prevention and of the treatment of diabetes and other metabolic diseases.

Reviewed by eLife