Rapid Self-Assembly Mini-Livers Protect Mice Against Severe Hepatectomy-Induced Liver Failure.

The construction of bioartificial livers, such as liver organoids, offers significant promise for disease modeling, drug development, and regenerative medicine. However, existing methods for generating liver organoids have limitations, including lengthy and complex processes (taking 6-8 weeks or longer), safety concerns associated with pluripotency, limited functionality of pluripotent stem cell-derived hepatocytes, and small, highly variable sizes (typically ≈50-500 µm in diameter). Prolonged culture also leads to the formation of necrotic cores, further restricting size and function. In this study, a straightforward and time-efficient approach is developed for creating rapid self-assembly mini-livers (RSALs) within 12 h. Additionally, primary hepatocytes are significantly expanded in vitro for use as seeding cells. RSALs exhibit consistent larger sizes (5.5 mm in diameter), improved cell viability (99%), and enhanced liver functionality. Notably, RSALs are functionally vascularized within 2 weeks post-transplantation into the mesentery of mice. These authentic hepatocyte-based RSALs effectively protect mice from 90%-hepatectomy-induced liver failure, demonstrating the potential of bioartificial liver-based therapy.

Bidirectional Charge Transfer at the Heme Iron in Reversible and Quasi-irreversible Cytochrome P450 Inhibition.

The coordination bonding between inhibitor ligands and heme iron plays a critical role in disrupting the essential catalytic functions of cytochrome P450 enzymes (P450s). Despite its intrinsic importance and consequential implications for human health, our current understanding of coordination bonding in P450 inhibition remains limited. To address this knowledge gap, we conducted a systematic theoretical analysis of the complexes between a ferric or a ferrous heme model and representative inhibitor ligands. Specifically, we evaluated the charge-transfer (CT) effect within these complexes by employing a series of theoretical methods based on density functional theory (DFT). Through a comprehensive analysis, we unveiled the relative significance of ligand-to-heme forward CT in the ferric and ferrous complexes of reversible inhibitors. In contrast, backward CT dominates over forward CT in the ferrous heme complexes of quasi-irreversible inhibitors. Further analysis using the compact frontier orbital method underscores the elevated electron-accepting abilities of quasi-irreversible inhibitors for π backdonation, which greatly amplifies their binding affinity for the ferrous heme. This study sheds light on the intricate mechanisms underlying P450 inhibition and provides valuable insights for future inhibitor design and development.

Palm-Sized Laser Spectrometer with High Robustness and Sensitivity for Trace Gas Detection Using a Novel Double-Layer Toroidal Cell.

A palm-sized laser spectrometer has been developed for detecting trace gases based on tunable diode laser absorption spectroscopy in combination with a novel double-layer toroidal cell. With the benefit of a homemade electronic system and compact optical design, the physical dimensions of the sensor are minimized to 24 × 15× 16 cm3. A toroidal absorption cell, with 84 reflections in 2 layers for an effective optical path length of 8.35 m, was used to enhance the absorption signals of gaseous species. A homemade electronic system was designed for implementing a distributed feedback (DFB) diode laser controller, an analog lock-in amplifier, data acquisition, and communication. Calibration-free scanned wavelength modulation spectroscopy was employed to determine the concentration of the gas and reduce the random fluctuations from electronical noise and mechanical vibration. The measurement of CH4 in ambient air was demonstrated using a DFB laser at 1.653 µm. The rise time and fall time for renewing the gas mixture are approximately 16 and 14 s, respectively. Vibration and temperature tests have been carried out for verifying the performance of the spectrometer, and standard deviations of 0.38 ppm and 0.11 ppm for 20 ppm CH4 at different vibration frequencies and temperatures, respectively, have been determined. According to the Allan deviation analysis, the minimum detection limit for CH4 can reach 22 ppb at an integration time of 57.8 s. The continuous measurement of atmospheric CH4 for 2 days validated the feasibility and robustness of our laser spectrometer, providing a promising laser spectral sensor for deploying in unmanned aerial vehicles or mobile robots.

A portable low-power integrated current and temperature laser controller for high-sensitivity gas sensor applications.

A low-noise, low power, high modulation-bandwidth design integrated laser current and temperature driver with excellent long-term stability is described. The current driver circuit is based on the Hall-Libbrecht design. A high sensitivity and a stable driver current were obtained using a differential amplifier and an integral amplifier. The set-point voltage for the current driver came from an ultra-compact, ultra-low temperature coefficient voltage reference chip or the digital to analog convertor output of a microcontroller or a modulation signal. An integral temperature chip, referred to as ADN8834, was used to drive the thermoelectric cooler controller of the distributed feedback (DFB) laser. The internal amplifier acquired the feedback current of the temperature sensor. The proportional-integral-derivative parameters such as proportion, integration, and derivative were set by external resistors. The short- and long-term stability and linearity of the developed laser driver were tested using a DFB laser with a central wavelength of 6991 cm-1. The laser driver was validated for high-sensitivity gas sensing of CO2 and C2H2 via a laser absorption spectroscopy experiment. The limits of detection were less than 11.5 ppm and 0.124 ppm for CO2 and C2H2, respectively. Direct absorption measurements and the 1-f and 2-f demodulation signals confirmed the capabilities of the proposed laser driver system in high-sensitivity gas sensing applications. The driver unit can readily be accommodated into many portable laser sensing devices for industrial applications.