Liver bioprinting within a novel support medium with functionalized spheroids, hepatic vein structures, and enhanced post-transplantation vascularization.

Cell-laden bioprinting is a promising biofabrication strategy for regenerating bioactive transplants to address organ donor shortages. However, there has been little success in reproducing transplantable artificial organs with multiple distinctive cell types and physiologically relevant architecture. In this study, an omnidirectional printing embedded network (OPEN) is presented as a support medium for embedded 3D printing. The medium is state-of-the-art due to its one-step preparation, fast removal, and versatile ink compatibility. To test the feasibility of OPEN, exceptional primary mouse hepatocytes (PMHs) and endothelial cell line-C166, were used to print hepatospheroid-encapsulated-artificial livers (HEALs) with vein structures following predesigned anatomy-based printing paths in OPEN. PMHs self-organized into hepatocyte spheroids within the ink matrix, whereas the entire cross-linked structure remained intact for a minimum of ten days of cultivation. Cultivated HEALs maintained mature hepatic functions and marker gene expression at a higher level than conventional 2D and 3D conditions in vitro. HEALs with C166-laden vein structures promoted endogenous neovascularization in vivo compared with hepatospheroid-only liver prints within two weeks of transplantation. Collectively, the proposed platform enables the manufacture of bioactive tissues or organs resembling anatomical architecture, and has broad implications for liver function replacement in clinical applications.

Carbon Fiber Film with Multi-Hollow Channels to Expedite Oxygen Electrocatalytic Reaction Kinetics for Flexible Zn-Air Battery.

The high oxygen electrocatalytic overpotential of flexible cathodes due to sluggish reaction kinetics result in low energy conversion efficiency of wearable zinc-air batteries (ZABs). Herein, lignin, as a 3D flexible carbon-rich macromolecule, is employed for partial replacement of polyacrylonitrile and constructing flexible freestanding air electrodes (FFAEs) with large amount of mesopores and multi-hollow channels via electrospinning combined with annealing strategy. The presence of lignin with disordered structure decreases the graphitization of carbon fibers, increases the structural defects, and optimizes the pore structure, facilitating the enhancement of electron-transfer kinetics. This unique structure effectively improves the accessibility of graphitic-N/pyridinic-N with oxygen reduction reaction (ORR) activity and pyridinic-N with oxygen evolution reaction (OER) activity for FFAEs, accelerating the mass transfer process of oxygen-active species. The resulting N-doped hollow carbon fiber films (NHCFs) exhibit superior bifunctional ORR/OER performance with a low potential difference of only 0.60 V. The rechargeable ZABs with NHCFs as metal-free cathodes possess a long-term cycling stability. Furthermore, the NHCFs can be used as FFAEs for flexible ZABs which have a high specific capacity and good cycling stability under different bending states. This work paves the way to design and produce highly active metal-free bifunctional FFAEs for electrochemical energy devices.

Development and validation of a novel model to predict liver-related mortality in patients with idiosyncratic drug-induced liver injury.

BACKGROUND: Early identification of patients with high mortality risk is critical for optimizing the clinical management of drug-induced liver injury (DILI). We aimed to develop and validate a new prognostic model to predict death within 6 months in DILI patients. METHODS: This multicenter study retrospectively reviewed the medical records of DILI patients admitted to three hospitals. A DILI mortality predictive score was developed using multivariate logistic regression and was validated with area under the receiver operating characteristic curve (AUC). A high-mortality-risk subgroup was identified according to the score. RESULTS: Three independent DILI cohorts, including one derivation cohort (n = 741) and two validation cohorts (n = 650, n = 617) were recruited. The DILI mortality predictive (DMP) score was calculated using parameters at disease onset as follows: 1.913 × international normalized ratio + 0.060 × total bilirubin (mg/dL) + 0.439 × aspartate aminotransferase/alanine aminotransferase - 1.579 × albumin (g/dL) - 0.006 × platelet count (109/L) + 9.662. The predictive performance for 6-month mortality of DMP score was desirable, with an AUC of 0.941 (95% CI: 0.922-0.957), 0.931 (0.908-0.949) and 0.960 (0.942-0.974) in the derivation, validation cohorts 1 and 2, respectively. DILI patients with a DMP score ≥ 8.5 were stratified into high-risk group, whose mortality rates were 23-, 36-, and 45-fold higher than those of other patients in the three cohorts. CONCLUSIONS: The novel model based on common laboratory findings can accurately predict mortality within 6 months in DILI patients, which should serve as an effective guidance for management of DILI in clinical practice.

Case Report: Life-threatening hypercalcemia associated with MMR-deficient endometrial carcinoma secreting parathyroid hormone.

Ectopic secretion of parathyroid hormone (PTH) is a rare cause of hypercalcemia in malignancy patients. A 56-year-old woman with life-threatening hypercalcemia was caused by poorly-differentiated endometrial carcinoma secreting PTH with concomitant nodular goiter mimic parathyroid tumors. The elevated level of PTH and calcium decreased immediately after cytoreductive surgery (CRS). The pathology confirmed mismatch repair (MMR)-deficient endometrial carcinoma with PTH expression. The patient received four-course chemotherapy and one-course immunotherapy after CRS. The disease progression led to multiple organ failure and death about five months after CRS. To our knowledge, this is the first case of hypercalcemia caused by MMR-deficient endometrial carcinoma with ectopic PTH secreting and the first report of malignancy associated hypercalcemia complicated with nodular goiter.

Mass Production of Sulfur-Tuned Single-Atom Catalysts for Zn-Air Batteries.

Single-atom catalysts (SACs) show great potential for rechargeable Zn-air batteries (ZABs); however, scalable production of SACs from sustainable resources is difficult owing to poor control of the local coordination environment. Herein, lignosulfonate, a by-product of the papermaking industry, is utilized as a multifunctional bioligand for the mass production of SACs with highly active MN4 S sites (M represents Fe, Cu, and Co) via strong metalnitrogen/sulfur coordination. This effectively adjusts the charge distribution and promotes the catalytic performance, leading to highly durable and excellent performance in oxygen reduction and evolution reactions for ZABs. This study paves the way for the industrial production of cost-effective SACs in a sustainable manner.

Cytomembrane-Inspired MXene Ink with Amphiphilic Surfactant for 3D Printed Microsupercapacitors.

Two-dimensional (2D) material-based hydrogels have been widely utilized as the ink for extrusion-based 3D printing in various electronics. However, the viscosity of the hydrogel ink is not high enough to maintain the self-supported structure without architectural deformation. It is also difficult to tune the microstructure of the printed devices using a low-viscosity hydrogel ink. Herein, by mimicking a phospholipid bilayer in a cytomembrane, the amphiphilic surfactant nonaethylene glycol monododecyl ether (C12E9) was incorporated into MXene hydrogel. The incorporation of C12E9 offers amphiphilicity to the MXene flakes and produces a 3D interlinked network of the MXene flakes. The 3D interlinked network offers a high-viscosity, homogenized flake distribution and enhanced printability to the ink. This ink facilitates the alignment of the MXene flakes during extrusion as well as the formation of the aligned micro- and sub-microsized porous structures, leading to the improved electrochemical performance of the printed microsupercapacitor. This study provides an example for the preparation of microelectronics with tunable microstructures.

Sex Differences in Clinical Characteristics and Prognosis in Primary Thrombotic Antiphospholipid Syndrome.

Objectives: This study aimed to investigate whether there are sex differences in clinical characteristics and prognosis in patients with primary thrombotic antiphospholipid syndrome (ptAPS). Methods: From January 2013 to July 2021, 154 consecutive patients diagnosed with ptAPS were prospectively recruited. Multivariable Cox regression was used to evaluate the association between gender and the composite endpoint including thromboembolic recurrence or all-cause death during follow-up. Results: Totally, 80 (52%) male and 74 (48%) female patients with ptAPS were included, and men had a higher percentage of smokers/ex-smokers [50 (62%) vs. 6 (8%), p < 0.001] and hyperhomocysteinemia [26 (32%) vs. 9 (12%), p = 0.003]. The baseline thromboembolic events were similar in two genders, except for limb ischemia [15 (19%) in men vs. 1 (1%) in women, p < 0.001]. During a median follow-up of 42 months, the composite endpoint occurred in 30 (38%) male and 15 (20%) female patients (p = 0.019). Male gender [HR 2.499, 95% CI (1.316, 4.743), p = 0.005] and warfarin administration [HR 0.482, 95% CI (0.257, 0.905), p = 0.023] remained independent risk factors for the composite endpoint. Male gender [HR 3.699, 95% CI (1.699, 8.246), p = 0.001] and isolated lupus anticoagulant positivity [HR 2.236, 95% CI (1.039, 4.811), p = 0.040] were independent risk factors for thromboembolic recurrence. Conclusion: There are sex disparities in the clinical characteristics in patients with ptAPS and the male gender is an independent risk factor for the poor prognosis. Male patients with isolated lupus anticoagulant (LA) positivity have the highest risk of thromboembolic recurrence.

A F-deficient and high-Mn ternary perovskite fluoride anode with a dominant conversion mechanism for advanced Li-ion batteries.

A F-deficient and high-Mn ternary perovskite fluoride anode (K1.00Ni0.06Co0.14Mn0.80F2.92, KNCMF-3#) has been explored for advanced Li-ion batteries (LIBs), showing a dominant conversion mechanism. Notably, the KNCMF-3#//LiFePO4 (LFP) LIBs furnish an ultra-high performance of 270.5-35.9 W h kg-1/0.63-11.6 kW kg-1/71% retention/5000 cycles/5 A g-1.

A conversion and pseudocapacitance-featuring cost-effective perovskite fluoride KCuF3 for advanced lithium-ion capacitors and lithium-dual-ion batteries.

A cost-effective perovskite fluoride KCuF3 material has been introduced as an advanced anode for lithium-ion capacitors (LICs) and lithium-dual-ion batteries (Li-DIBs), showing a conversion mechanism and pseudocapacitive kinetics for Li ion storage.

A vacancy-rich perovskite fluoride K0.79Ni0.25Co0.36Mn0.39F2.83@rGO anode for advanced Na-based dual-ion batteries.

A novel concept of Na-based dual-ion batteries (Na-DIBs) has been designed via a perovskite K0.79Ni0.25Co0.36Mn0.39F2.83@reduced graphene oxide (KNCMF@rGO) hetero-nanocrystal anode, showing surface conversion and insertion hybrid mechanisms. The KNCMF@rGO//graphite (KS6) DIBs deliver superior energy/power densities and cycling stability and have a significant impact on developing energy storage devices.

Vacant Manganese-Based Perovskite Fluorides@Reduced Graphene Oxides for Na-Ion Storage with Pseudocapacitive Conversion/Insertion Dual Mechanisms.

Na-ion capacitors (NICs) and Na-based dual-ion batteries (Na-DIBs) have been considered to be promising alternatives to traditional lithium-ion batteries (LIBs) because of the abundance and low cost of the Na-ion, but their energy density, power density and life cycle are limited. Herein, dual-vacancy (including K+ and F- vacancies) perovskite fluoride K0.86 MnF2.69 @reduced graphene oxide (rGO; recorded as Mn-G) as anode for NICs and Na-DIBs has been developed. The special conversion/intercalation dual Na-ion energy storage mechanism and pseudocapacitive dynamics are analyzed in detail. The Mn-G//AC NICs and Mn-G//KS6 Na-DIBs delivered a maximum energy density of 92.7 and 187.6 W h kg-1 , a maximum power density of 20.2 and 21.12 kW kg-1 , and long cycle performance of 61.3 and 68.4 % after 1000 cycles at 5 A g-1 , respectively. Moreover, Mn-G//AC NICs and Mn-G//KS6 Na-DIBs can work well over a wide range of temperatures (-20 to 40 °C). These results make it competitive in Na-ion storage applications with high energy/power density over a wide temperature range.

Pseudocapacitive trimetallic NiCoMn-111 perovskite fluorides for advanced Li-ion supercabatteries.

Exploring advanced electrochemical energy storage systems and clarifying their charge storage mechanisms are key scientific frontiers presenting a great challenge. Herein, we demonstrate a novel concept of Li-ion supercabatteries (i.e., Li-ion capacitors/batteries, LICBs), which were realized using a novel trimetallic Ni-Co-Mn perovskite fluoride (K0.97Ni0.31Co0.34Mn0.35F2.98, denoted as KNCMF-111 (8#)) anode and a high-performance activated carbon/LiFePO4 (AC/LFP) cathode, which makes the boundary between LICs and LIBs less distinctive. Thanks to the pseudocapacitive conversion mechanism of the KNCMF-111 (8#) anode with superior kinetics and the enhanced capacity of the capacitor/battery hybrid AC/LFP cathode, the designed KNCMF-111 (8#)//AC/LFP LICBs, integrating the synergistic superiority of pseudocapacitive, capacitive and faradaic characteristics, exhibit remarkable energy/power densities and a long cycle life, indicating a high-efficiency energy storage application. Overall, this work provides new insights into exploring advanced Li-ion supercabatteries and clarifying their charge storage mechanisms based on trimetallic Ni-Co-Mn perovskite fluoride electrode materials, which sheds light on the development of advanced electrochemical energy storage systems and in-depth understanding of their charge storage mechanisms.

Oxidation of Ryanodine Receptors Promotes Ca2+ Leakage and Contributes to Right Ventricular Dysfunction in Pulmonary Hypertension.

Right ventricular (RV) failure is a major cause of death in patients with pulmonary arterial hypertension, and the mechanism of RV failure remains unclear. While the malfunction of RyR2 (ryanodine receptor type 2) on sarcoplasmic reticulum (SR) and aberrant Ca2+ cycling in cardiomyocytes have been recognized in some cardiovascular diseases, their roles in RV failure secondary to pulmonary arterial hypertension require further investigation. In a monocrotaline-induced rat model of pulmonary arterial hypertension, the RV remodeling process was divided into normal, compensated, and decompensated stages according to the hemodynamic and morphological parameters. In both compensated and decompensated stages, significant diastolic SR Ca2+ leakage was detected along with reduced intracellular Ca2+ transient amplitude and SR Ca2+ contents in RV myocytes. RyR2 protein levels decreased progressively during the process, and the thiol oxidation proportions of RyR2 were higher in compensated and decompensated stages than in normal stage. Inhibition of RyR2 oxidation by dithiothreitol or repairing RyR2 directly by dantrolene could restore Ca2+ homeostasis in RV myocytes. Daily intraperitoneal injection of dantrolene delayed decompensation progression and significantly improved the survival rate of pulmonary hypertension rats in decompensated stage (79.3% versus 55.9%; P=0.026). Our findings suggest that diastolic SR Ca2+ leakage via oxidized RyR2 facilitates the development of RV failure. Dantrolene can inhibit diastolic SR Ca2+ leakage in RV cardiomyocytes, delay right cardiac dysfunction, and improve the survival of rats with pulmonary arterial hypertension.