yg Xu

[yg Xu @ygXu4]

@ashley50rd9 看

[秦仁杰 @qrjie]

第一个拍魔镜系列的导演简直是个天才，用同一个场景同时拍出了 NTR、多人、女同、露出、偷窥等等性癖... https://t.co/ytk38xhRG3

[yg Xu @ygXu4]

学习

[오창명 @changmyung1981]

HMGCS1: How Tumors Repair Immune Damage and Escape Killing

Cancer cells are not passive targets. When cytotoxic T cells or NK cells attack, they punch holes in the tumor membrane using perforin. A new Nature Communications study reveals that tumors actively repair this damage through a metabolic defense mechanism centered on HMGCS1-driven cholesterol synthesis.

Researchers screened 111 metabolic enzymes and identified HMGCS1, the first committed enzyme in the mevalonate/cholesterol pathway, as the strongest regulator of plasma membrane repair. Loss of HMGCS1 dramatically increased membrane damage following perforin-like injury and sensitized tumor cells to immune attack.

Mechanistically, HMGCS1 increases de novo cholesterol synthesis, which supports membrane repair through two complementary functions:

🔹 Structural role — supplies cholesterol as a building block for membrane reconstruction.

🔹 Signaling role — cholesterol directly binds the ESCRT repair protein CHMP4B, promoting its localization to damaged plasma membranes and accelerating repair.

Without HMGCS1:

• Cholesterol levels fall
• CHMP4B membrane recruitment decreases
• ESCRT-mediated repair fails
• Perforin pores persist
• Granzyme entry increases
• Tumor cell killing is enhanced
The translational implications are striking.
HMGCS1 depletion significantly improved:
✅ NK-cell therapy
✅ CAR-T therapy
✅ Anti-PD-1 immunotherapy
across multiple in vitro and in vivo lung cancer models. Tumors lacking HMGCS1 became markedly more sensitive to immune-mediated destruction.
The study also uncovered an upstream regulatory circuit. c-Jun activation—driven by inflammatory cytokines, hypoxia, and oncogenic mutations such as EGFR L858R, KRAS G12V, and BRAF V600E—induces HMGCS1 expression. This links oncogenic signaling directly to immune evasion through metabolic membrane repair.

Perhaps most clinically relevant, lung cancer patients who failed anti-PD-1 therapy showed:

• Higher HMGCS1 expression
• Increased cholesterol accumulation
• Greater plasma membrane CHMP4B localization
• Stronger c-Jun activation

These findings suggest that HMGCS1 may function both as a predictive biomarker and as a therapeutic target.
Rather than suppressing immune cells directly, tumors can survive by rapidly repairing immune-inflicted membrane damage. Blocking this repair system may expose a previously unrecognized vulnerability in immunotherapy-resistant cancers.
Reference

Zhang Y, Wang S, Luo T, et al. HMGCS1 drives cholesterol-dependent membrane repair and shields tumor cells from lymphocyte attack. Nature Communications. 2026. DOI: 10.1038/s41467-026-74022-y.

#CancerImmunology #HMGCS1 #CholesterolMetabolism #ESCRT #CHMP4B #CAR_T #NKCells #PD1 #TumorImmuneEvasion #NatureCommunications

[yg Xu @ygXu4]

张力！

[yg Xu @ygXu4]

@TBedchamber @BBBBTTTCC @SexytoBaby @SexytoDoll @SexytoGirl 这配音？很诡异你知道吗？

[yg Xu @ygXu4]

@LCA176232 一眼丁真鉴定为-败家子

[yg Xu @ygXu4]

青岛的冬天
昨天缩在沙发上玩手机，屋外狂风呼啸，仿佛要把小区内的老树连根拔起一般。与春天的清风，夏天的热风，秋天干燥的热风不同，冬天的凛风总是让人印象深刻，可能是我上班骑电瓶车的缘故吧！昨日小区垃圾站内的垃圾桶也欢快地跳起了舞，仿佛这凛风赋予了它生命一般。

[yg Xu @ygXu4]

@UB_ZorroDemonio 毫无违和感！

[yg Xu @ygXu4]

@willlia06663041 绝了，这些人在现实中是啥样的啊？难以理解！

[yg Xu @ygXu4]

@Vxujianing @bbcchinese 哈哈哈

[yg Xu @ygXu4]

@Stellar40626620 这是什么神仙搭配？我是碳基生物，我不理解😊

[yg Xu @ygXu4]

@miren_41319 小日本这么想再挨一次原子弹？是嫌大街上熟人不多是吧😁

[yg Xu @ygXu4]

@rayloy888 @SEcho93543499 @bbcchinese 是呀，孝死我了，有的人真实当狗当习惯了😁

[yg Xu @ygXu4]

@willlia06663041 那我想问一下，现��咱们国家为什么不用核弹炸小日本呢？炸小日本肯定能炸，但是为什么不炸呢？
如果当时杜鲁门同意麦克阿瑟的提议，用核弹炸北京，那么苏联的核弹也会到达华盛顿。
一个道理，当时的美利坚，他就不敢用核弹，还留了一手，不知道咋想的，就硬舔呗😄
毛主席和世界各国的博弈从不落下风！

[yg Xu @ygXu4]

@nvshangwei @nncat2008 @icy_rainy_day ？你一外国人在这里说什么呀？分裂狗？你要是在中国大陆，你就当众说一遍你这句话，行不行呀，外国猪🐷？

[yg Xu @ygXu4]

@mizuha77 @miren_41319 笑死我了

[我是梦嫣❤️ @mengyan1234567]

当一个人全身穿满偷来抢来的东西时，
她就成了……🤔