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Received — 10 September 2026 ⏭

A complement C5-targeted GalNAc-conjugated siRNA with sustained efficacy in a non-human primate model of IgA nephropathy

✇Molecular Therapy
By: Xueyan Zhang · Xue Zhang · Qiuyu Yang · Bin Kang · Mo Dan · Chunlei Li · Yan Chen · Jianhua Gan · Xiaoye Su
13 August 2026 at 08:00
This study characterizes a GalNAc-C5 small interfering RNA with potent in vitro and in vivo activity. Single subcutaneous dosing sustains long-term C5 suppression in cynomolgus monkeys with IgA nephropathy, outperforming Nefecon in blocking glomerular complement deposition, supporting its standalone or combinational clinical application.

A helicase-fused Cas9 improves large-size fragment knockin

✇Molecular Therapy
By: Duowei Zhao · Xiangjie Zhao · Yuhang Gao · Sujie Yang · Xiaochen Guo · Caiyan Zhang · Chuanpei Li · Chengda Zhang · Huan Tian · Qianqian Xu · Zhi Yin · Zhonghua Liu · Jun Song
29 July 2026 at 08:00
By fusing MCM5, a subunit of the eukaryotic MCM2–7 helicase complex, to the N terminus of spCas9 (MCCas), the MCCas fusion protein enhances large-size fragment knockin via homologous recombination, reduces insertions and deletions (indels), and enables efficient large-size fragment insertions in human cells and rabbit embryos.

Integrative Pan-Cancer Characterization of lncRNA UPK1A-AS1 and Its Role in Hypoxia-Associated Sorafenib Resistance in Hepatocellular Carcinoma

✇Omics in Hepatocellular
By: Ze-Kai Li · Min-Rui Luo · Shu-Jie Fang · Yi-Da Wu · Quan-Hui Hu · Dong-Yan Zhang
1 September 2026 at 18:00

Anal Cell Pathol (Amst). 2026;2026(1):e1554526. doi: 10.1155/ancp/1554526.

ABSTRACT

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of tumor initiation and progression through transcriptional and posttranscriptional mechanisms. UPK1A antisense RNA 1 (UPK1A-AS1), a cancer-associated lncRNA, has been reported to participate in oncogenic processes; however, its overall landscape across human malignancies and its biological role in therapy resistance remain poorly understood. Given the increasing importance of identifying functional lncRNAs with prognostic and therapeutic potential, this study presents a comprehensive multiomics characterization of UPK1A-AS1 and its experimental validation in hepatocellular carcinoma (HCC). We integrated datasets from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), the cancer immunology data engine (CIDE), and the cBioPortal for cancer genomics (cBioPortal) to systematically assess its expression pattern, genomic alterations, clinical significance, and immunological associations. Our analyses revealed that UPK1A-AS1 is significantly upregulated in multiple tumor types, with copy-number amplification as the predominant genomic alteration driving its overexpression. Elevated UPK1A-AS1 expression was correlated with advanced disease stage, poor differentiation, immune exclusion, and unfavorable prognosis, supporting its potential as a cancer type-dependent biomarker. In parallel, functional studies demonstrated that hypoxia transcriptionally induces UPK1A-AS1 in HCC, where it promotes sorafenib resistance by suppressing apoptosis. Silencing UPK1A-AS1 restored apoptotic and enhanced sorafenib efficacy both in vitro and in vivo. Collectively, our findings suggest that UPK1A-AS1 is a hypoxia-inducible oncogenic lncRNA that plays dual roles in cancer, with cancer type-dependent associations with progression and immune modulation across malignancies and mechanistically mediating hypoxia-associated drug resistance in HCC.

PMID:42678131 | PMC:PMC13532061 | DOI:10.1155/ancp/1554526

Received — 27 May 2026 ⏭

Kaempferol functionally reprograms CD47 signaling to promote cytoprotection and attenuate oxeiptosis in severe acute pancreatitis

✇(Multiomics OR Omics) AND (Pancreatic)
By: Yu Tian · Yan Zhang · Qiang Gao · Peng Zhang · Lanlan You · Rongzhong Huang · An Zhang · E Wen
25 May 2026 at 18:00

Phytomedicine. 2026 May 15;157:158305. doi: 10.1016/j.phymed.2026.158305. Online ahead of print.

ABSTRACT

BACKGROUND: Severe acute pancreatitis (SAP) lacks targeted therapies, and massive loss of functional pancreatic acinar cells (PAC) drives mortality. Kaempferol (KA) possesses well-established anti-inflammatory and cytoprotective activities and is derived from herbal medicinal plants, but its direct molecular targets and mechanism of action in SAP remain undefined.

PURPOSE: To evaluate the protective effects of KA against SAP and to elucidate its molecular mechanism of specific action, with a focus on identifying the direct cellular target through which KA exerts its cytoprotective effects.

STUDY DESIGN: Gain‑/loss‑of‑function in vitro and PAC‑specific CD47 SAP mouse models, combined with multi‑omics screening and biophysical assays.

METHODS: CD47 manipulation (siRNA/overexpression) was performed in primary PACs and cell lines, combined with WT/CD47-/-/Mist1‑CD47‑iOE (PAC‑specific) mouse models. Network pharmacology, transcriptomics and proteomics were integrated to screen and validate KA's protective effects. Computational‑experimental approaches (molecular docking/dynamics, CETSA, SPR, co‑IP, pharmacological epistasis) characterized KA's allosteric modulation of CD47 signaling.

RESULTS: CD47 was upregulated in SAP; its knockout reduced PAC death via KEAP1/PGAM5/AIFM1-driven oxeiptosis. KA reduced PAC death across genotypes, afforded no extra benefit in CD47-KO, and was not overridden by CD47‑OE. Mechanistically, KA allosterically binds CD47 ectodomain, stabilizes the CD47‑ UBQLN1 complex, and redirects signaling from Gαi‑mediated death to Gβγ/ ERK/NRF2‑mediated survival. ERK inhibition attenuated KA's protection. KA's action was CD47‑dependent.

CONCLUSION: This study identifies anti-oxeiptosis as a novel pharmacological activity of KA in SAP. This is achieved through allosteric modulation of CD47, redirecting its signaling from death‑promoting to a protective axis via activating Gβγ/ERK/NRF2 to suppress oxeiptosis. These findings reveal the CD47‑oxeiptosis axis as a therapeutic target and position KA as a promising candidate for SAP therapy, adding a new mechanistic dimension to KA's known pharmacological profile.

PMID:42184499 | DOI:10.1016/j.phymed.2026.158305

CD300ld on pathologically activated neutrophils promotes tumor immune suppression by binding phosphatidylserine on CD8<sup>+</sup> T cells

✇Nature Cancer
By: Chaoxiong Wang · Peixuan Zheng · Anhui Wang · Xinrui Fan · Tianxiang Li · Jingjing Hong · Runze Wang · Chunyan Zhang · Chaogui Luo · Weiwei Yang · Dong Gao · Adili Salai · Min Luo · Zhigang Lu · Dianfan Li · Moubin Lin · Jiayin Peng · Guohui Li · Shuo Han · Yun Zhao
15 May 2026 at 08:00

Nature Cancer, Published online: 15 May 2026; doi:10.1038/s43018-026-01169-4

Zhao and colleagues show that CD300ld, upregulated in pathologically activated neutrophils, mediates contact-dependent suppression of cytotoxic CD8+ T cells by binding to phosphatidylserine, inhibiting antitumor immune responses.
Received — 8 April 2026 ⏭

ActionNex: A Virtual Outage Manager for Cloud

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zhenfeng Lin · Haoji Hu · Ming Hao · Xuchao Zhang · Ryan Zhang · Junhao Li · Ze Li · Oleg Kulygin · Chetan Bansal · Hatay Tuna · Murali Chintalapati · Sheila Jiang · Salman Zafar · Angie Anderson
7 April 2026 at 12:00
arXiv:2604.03512v1 Announce Type: new Abstract: Outage management in large-scale cloud operations remains heavily manual, requiring rapid triage, cross-team coordination, and experience-driven decisions under partial observability. We present \textbf{ActionNex}, a production-grade agentic system that supports end-to-end outage assistance, including real-time updates, knowledge distillation, and role- and stage-conditioned next-best action recommendations. ActionNex ingests multimodal operational signals (e.g., outage content, telemetry, and human communications) and compresses them into critical events that represent meaningful state transitions. It couples this perception layer with a hierarchical memory subsystem: long-term Key-Condition-Action (KCA) knowledge distilled from playbooks and historical executions, episodic memory of prior outages, and working memory of the live context. A reasoning agent aligns current critical events to preconditions, retrieves relevant memories, and generates actionable recommendations; executed human actions serve as an implicit feedback signal to enable continual self-evolution in a human-agent hybrid system. We evaluate ActionNex on eight real Azure outages (8M tokens, 4,000 critical events) using two complementary ground-truth action sets, achieving 71.4\% precision and 52.8-54.8\% recall. The system has been piloted in production and has received positive early feedback.
Received — 2 April 2026 ⏭

Correction: The multifunctional RNA helicase DDX39A drives glioblastoma progression by modulating WISP1 alternative splicing that induces an immunosuppressive macrophage polarization

✇Oncogene - Issue - nature.com science feeds
By: Yan Zhang · Zhiwei Xue · Naibin Zhang · Yuehua Zhu · YanZhao Wu · Meilin Lv · Zhihan Zhang · Feiyu Mu · Wenchen Xing · Ziyi Tang · Chunjie Wang · Zhiyi Xue · Wenjing Zhou · Xiaofei Liu · Xingang Li · Rolf Bjerkvig · Bin Huang · Mingzhi Han · Jian Wang · Donghai Wang
1 April 2026 at 08:00

Oncogene, Published online: 01 April 2026; doi:10.1038/s41388-026-03756-2

Correction: The multifunctional RNA helicase DDX39A drives glioblastoma progression by modulating WISP1 alternative splicing that induces an immunosuppressive macrophage polarization
Received — 11 March 2026 ⏭
Received — 25 February 2026 ⏭

HONEST-CAV: Hierarchical Optimization of Network Signals and Trajectories for Connected and Automated Vehicles with Multi-Agent Reinforcement Learning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Ziyan Zhang · Changxin Wan · Peng Hao · Kanok Boriboonsomsin · Matthew J. Barth · Yongkang Liu · Seyhan Ucar · Guoyuan Wu
24 February 2026 at 13:00
arXiv:2602.18740v1 Announce Type: cross Abstract: This study presents a hierarchical, network-level traffic flow control framework for mixed traffic consisting of Human-driven Vehicles (HVs), Connected and Automated Vehicles (CAVs). The framework jointly optimizes vehicle-level eco-driving behaviors and intersection-level traffic signal control to enhance overall network efficiency and decrease energy consumption. A decentralized Multi-Agent Reinforcement Learning (MARL) approach by Value Decomposition Network (VDN) manages cycle-based traffic signal control (TSC) at intersections, while an innovative Signal Phase and Timing (SPaT) prediction method integrates a Machine Learning-based Trajectory Planning Algorithm (MLTPA) to guide CAVs in executing Eco-Approach and Departure (EAD) maneuvers. The framework is evaluated across varying CAV proportions and powertrain types to assess its effects on mobility and energy performance. Experimental results conducted in a 4*4 real-world network demonstrate that the MARL-based TSC method outperforms the baseline model (i.e., Webster method) in speed, fuel consumption, and idling time. In addition, with MLTPA, HONEST-CAV benefits the traffic system further in energy consumption and idling time. With a 60% CAV proportion, vehicle average speed, fuel consumption, and idling time can be improved/saved by 7.67%, 10.23%, and 45.83% compared with the baseline. Furthermore, discussions on CAV proportions and powertrain types are conducted to quantify the performance of the proposed method with the impact of automation and electrification.

AI-driven Large-scale Electron Microscopy enables Whole-tissue Subcellular Digitization

✇cs.AI, q-bio.NC updates on arXiv.org
By: Li Xiao · Liqing Liu · Hongjun Wu · Jiayi Zhong · Xixia Li · Yan Zhang · Junjie Hu · Sun Fei · Ge Yang · Tao Xu
24 February 2026 at 13:00
arXiv:2511.02860v2 Announce Type: replace-cross Abstract: The distribution and interactions of cellular organelles play a critical role in mediating cellular physiology and pathology. Large-scale electron microscopy enables visualization of organelle distribution and interactions at the tissue level with nanometer resolution, but robust and efficient computational analysis tools are lacking. Here, we present a deep learning tool for universal large-scale 2D/3D electron microscopy analysis, DeepOrganelle. This new tool enables high-throughput, cell-resolved spatiotemporal mapping and digitization of organelle distribution and interactions. When applied to spermatogenesis across 12 stages and 22 differentiation status of the germ cells, DeepOrganelle uncovered previously unrecognized, stage-dependent dynamics of mitochondria-endoplasmic reticulum contact sites within one subphase of prophase I during meiosis. It also revealed coordinated organelle redistribution in Sertoli cells towards the blood-testis barrier, digitizing the remodeling dynamics of the tissue. This study demonstrates that DeepOrganelle provides a powerful framework that captures subcellular dynamics at the whole-tissue level.
Received — 17 February 2026 ⏭

KVCache Cache in the Wild: Characterizing and Optimizing KVCache Cache at a Large Cloud Provider

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jiahao Wang · Jinbo Han · Xingda Wei · Sijie Shen · Dingyan Zhang · Chenguang Fang · Rong Chen · Wenyuan Yu · Haibo Chen
17 February 2026 at 13:00
arXiv:2506.02634v5 Announce Type: replace-cross Abstract: Serving large language models (LLMs) is important for cloud providers, and caching intermediate results (KV\$) after processing each request substantially improves serving throughput and latency. However, there is limited understanding of how LLM serving benefits from KV\$ caching, where system design decisions like cache eviction policies are highly workload-dependent. In this paper, we present the first systematic characterization of the KV\$ workload patterns from one of the leading LLM service providers. We draw observations that were not covered by previous studies focusing on synthetic workloads, including: KV\$ reuses are skewed across requests, where reuses between single-turn requests are equally important as multi-turn requests; the reuse time and probability are diverse considering all requests, but for a specific request category, the pattern tends to be predictable; and the overall cache size required for an ideal cache hit ratio is moderate. Based on the characterization, we further propose a workload-aware cache eviction policy that improves the serving performance under real-world traces, especially with limited cache capacity.
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