A Dual Coverage Monitoring of the Bile Acids Profile in the Liver-Gut Axis throughout the Whole Inflammation-Cancer Transformation Progressive: Reveal Hepatocellular Carcinoma Pathogenesis.

Hepatocellular carcinoma (HCC) is the terminal phase of multiple chronic liver diseases, and evidence supports chronic uncontrollable inflammation being one of the potential mechanisms leading to HCC formation. The dysregulation of bile acid homeostasis in the enterohepatic circulation has become a hot research issue concerning revealing the pathogenesis of the inflammatory-cancerous transformation process. We reproduced the development of HCC through an N-nitrosodiethylamine (DEN)-induced rat model in 20 weeks. We achieved the monitoring of the bile acid profile in the plasma, liver, and intestine during the evolution of "hepatitis-cirrhosis-HCC" by using an ultra-performance liquid chromatography-tandem mass spectrometer for absolute quantification of bile acids. We observed differences in the level of primary and secondary bile acids both in plasma, liver, and intestine when compared to controls, particularly a sustained reduction of intestine taurine-conjugated bile acid level. Moreover, we identified chenodeoxycholic acid, lithocholic acid, ursodeoxycholic acid, and glycolithocholic acid in plasma as biomarkers for early diagnosis of HCC. We also identified bile acid-CoA:amino acid N-acyltransferase (BAAT) by gene set enrichment analysis, which dominates the final step in the synthesis of conjugated bile acids associated with the inflammatory-cancer transformation process. In conclusion, our study provided comprehensive bile acid metabolic fingerprinting in the liver-gut axis during the inflammation-cancer transformation process, laying the foundation for providing a new perspective for the diagnosis, prevention, and treatment of HCC.

An Integrated Mutually Oriented "Chemical Profiling-Pharmaceutical Effect" Strategy for Screening Discriminating Markers of Underlying Hepatoprotective Effects to Distinguish Garden-Cultivated from Mountain-Cultivated Ginseng.

Garden-cultivated Ginseng (GG) and mountain-cultivated Ginseng (MG) both belong to Panax Ginseng C. A. Meyer. However, the effective substances which can be used to distinguish GG from MG remain obscure. Therefore, the purpose of this study was to screen for discriminating markers that can assist in the correct identification of GG and MG. HPLC Q-TOF/MS and various chemometrics methods were used to analyze the chemical profiles of 13 batches of Ginseng and to explore the characteristic constituents of both GG and MG. The hepatocyte-protecting effects of GG and MG were investigated through a paclitaxel-induced liver injury model. Through a combination of correlation analysis and bioinformatic techniques, markers for differentiation between GG and MG were ascertained. A total of 40 and 41 compounds were identified in GG and MG, respectively, and 15 characteristic ingredients contributed significantly to the discrimination of GG from MG. Correlation analysis and network pharmacology were applied and ginsenosides Rg1, Re, Rb1, Rc, Rb2, and Rg3 were found to be discriminating markers of GG and MG. Six markers for the identification of GG and MG were screened out by a step-wise mutually oriented "chemical profiling-pharmaceutical effect" correlation strategy, which is of great significance for future quality assessment of Ginseng products.

Versatile photonic molecule switch in multimode microresonators.

Harnessing optical supermode interaction to construct artificial photonic molecules has uncovered a series of fundamental optical phenomena analogous to atomic physics. Previously, the distinct energy levels and interactions in such two-level systems were provided by coupled microresonators. The reconfigurability is limited, as they often require delicate external field stimuli or mechanically altering the geometric factors. These highly specific approaches also limit potential applications. Here, we propose a versatile on-chip photonic molecule in a multimode microring, utilizing a flexible regulation methodology to dynamically control the existence and interaction strength of spatial modes. The transition between single/multi-mode states enables the "switched-off/on" functionality of the photonic molecule, supporting wider generalized applications scenarios. In particular, "switched-on" state shows flexible and multidimensional mode splitting control in aspects of both coupling strength and phase difference, equivalent to the a.c. and d.c. Stark effect. "Switched-off" state allows for perfect low-loss single-mode transition (Qi ~ 10 million) under an ultra-compact bend size (FSR ~ 115 GHz) in a foundry-based silicon microring. It breaks the stereotyped image of the FSR-Q factor trade-off, enabling ultra-wideband and high-resolution millimeter-wave photonic operations. Our demonstration provides a flexible and portable solution for the integrated photonic molecule system, extending its research scope from fundamental physics to real-world applications such as nonlinear optical signal processing and sixth-generation wireless communication.

Waveguide-integrated twisted bilayer graphene photodetectors.

Graphene photodetectors have exhibited high bandwidth and capability of being integrated with silicon photonics (SiPh), holding promise for future optical communication devices. However, they usually suffer from a low photoresponsivity due to weak optical absorption. In this work, we have implemented SiPh-integrated twisted bilayer graphene (tBLG) detectors and reported a responsivity of 0.65 A W-1 for telecom wavelength 1,550 nm. The high responsivity enables a 3-dB bandwidth of >65 GHz and a high data stream rate of 50 Gbit s-1. Such high responsivity is attributed to the enhanced optical absorption, which is facilitated by van Hove singularities in the band structure of high-mobility tBLG with 4.1o twist angle. The uniform performance of the fabricated photodetector arrays demonstrates a fascinating prospect of large-area tBLG as a material candidate for heterogeneous integration with SiPh.

A convenient and efficient 4-(diethylamino)-butylamine-labeled polarity-response-homodispersed strategy for absolute quantification of carboxyl submetabolome: Monitoring the whole progressive course of hepatocellular carcinoma.

Recent studies have shown that dysregulation of carboxyl submetabolome homeostasis is closely related to the occurrence and development of hepatocellular carcinoma (HCC). However, it is still a challenge to quantify carboxyl metabolites with high efficiency by conventional methods due to their species diversity and nature differences. Moreover, there are few studies on carboxyl submetabolome profiling during the whole progression of HCC. In this study, a convenient and efficient workflow for absolute quantification of carboxyl submetabolome was established based on the 4-(diethylamino)-butylamine (DEABA)-labeled polarity-response-homodispersed strategy. After optimizing derivation conditions with response surface methodology (RSM), the reaction only needed 1 min at room temperature, which radically simplified the labeling process. Compared with nonderivatization, the gaps of polarities and responses of the analytes were narrowed by DEABA labeling, realizing the polarity-response-homodispersion. Then resolution and sensitivity in HPLC-MS/MS were improved significantly. Ultimately, the workflow was applied to monitor carboxyl metabolic profile in human plasma of the whole progressive course of hepatocellular carcinoma. Combined with analysis of variance (ANOVA), orthogonal partial least squares discrimination analysis (OPLS-DA), Bayesian linear discriminant analysis (BLDA) and other data mining methods, the biomarkers of "health-hepatitis-cirrhosis-HCC" were screened out, and the diagnostic model was established. Furthermore, the relevancy between carboxyl submetabolome disorders and the pathogenesis of HCC was investigated. The developed method has the characteristics of high sensitivity, high coverage and high practicability, which is suitable for the study of biomarkers of carboxyl submetabolome in the whole progression of HCC.