rate up to 90%, but below 36% in the case of advanced GC patients. [1a] An effective approach of early GC detection requires the combination of initial pre-selection of high-risk individuals and follow-up endoscopy examination, while its largescale application is facing challenges like low cost-efficiency (e.g., inefficient preselection by non-specific risk factors), poor patient compliance, and shortage of experienced endoscopists, etc. [2b] Therefore, it is pressing to develop a rapid and noninvasive method to discover biomarkers and diagnose early GC with an improved prognosis.Liquid biopsy allows the detection of oncotarget biomarkers through non-invasive techniques from biofluids (e.g., blood), holding promise for early screening of GC in clinics. [4] Various genetic (e.g., circulating tumor DNA (ctDNA)) [5] and protein (e.g., carcino embryonic antigen (CEA)) biomarkers in human blood have been discovered for GC diagnosis, but the applicable performance is limited by suboptimal accuracy (e.g., sensitivity of 13% for CEA), [6] high cost (€140 per test), [7] and lack of validation in early GC patients. [1b,8] Besides genes and proteins, metabolites serve as direct signatures of biochemical activity and are associated with gastric carcinogenesis. [9] Mass spectrometry (MS), particularly laser desorption/ionization (LDI) MS, is a powerful analytical tool capable of the simultaneous detection and spatial mapping of various metabolites. [10] However, it is offset in metabolic profiling with Gastric cancer (GC) is a multifactorial process, accompanied by alterations in metabolic pathways. Non-invasive metabolic profiling facilitates GC diagnosis at early stage leading to an improved prognostic outcome. Herein, mesoporous PdPtAu alloys are designed to characterize the metabolic profiles in human blood. The elemental composition is optimized with heterogeneous surface plasmonic resonance, offering preferred charge transfer for photoinduced desorption/ionization and enhanced photothermal conversion for thermally driven desorption. The surface structure of PdPtAu is further tuned with controlled mesopores, accommodating metabolites only, rather than large interfering compounds. Consequently, the optimized PdPtAu alloy yields direct metabolic fingerprints by laser desorption/ionization mass spectrometry in seconds, consuming 500 nL of native plasma. A distinct metabolic phenotype is revealed for early GC by sparse learning, resulting in precise GC diagnosis with an area under the curve of 0.942. It is envisioned that the plasmonic alloy will open up a new era of minimally invasive blood analysis to improve the surveillance of cancer patients in the clinical setting.

Liver metastasis is a leading cause of death in patients with colorectal cancer. We previously found that colorectal cancer tumor-initiating cells (TICs) expressing CD110, the thrombopoietin (TPO)-binding receptor, mediate liver metastasis. Here, we show that TPO promotes metastasis of CD110+ TICs to the liver by activating lysine degradation. Lysine catabolism generates acetyl-CoA, which is used in p300-dependent LRP6 acetylation. This triggers tyrosine phosphorylation of LRP6, ultimately activating Wnt signaling to promote self-renewal of CD110+ TICs. Lysine catabolism also generates glutamate, which modulates the redox status of CD110+ TICs to promote liver colonization and drug resistance. Mechanistically, TPO-mediated induction of c-myc orchestrates recruitment of chromatin modifiers to regulate metabolic gene expression. Our findings, therefore, establish TPO as a component of the physiological environment critical for metastasis of colorectal cancer to the liver.

Laparoscopic incisional and ventral hernia repair is a feasible and effective alternative to the open technique. It is associated with lower incidences of wound infection and shorter length of hospital stay. However, caution is required because it is associated with an increased risk of bowel injury compared with the open technique. Given the relatively short follow-up duration of trials included in the systematic review, trials with long-term follow-up are needed to compare the durability of laparoscopic and open repair.