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The need for basement membrane extract (BME) with undefined constituents, such as Matrigel, for intestinal stem cell (ISC) culture in traditional systems poses a significant barrier that must be overcome for the development of clinical-grade, scalable, ready-to-use ISCs. Here, we propose a functional polymer-based xenogeneic-free dish for the culture of intestinal stem cells (XF-DISC), ensuring substantially prolonged maintenance of ISCs derived from 3-dimensional human intestinal organoids (ISCs 3D-hIO ). XF-DISC enables remarkable expandability, exhibiting a 24-fold increase in cell numbers within 30 days, with long-term maintenance of ISCs 3D-hIO for more than 30 consecutive passages (>210 days). In addition, XF-DISC is fully compatible with a cell banking system. Notably, human pluripotent stem cell-derived ISCs 3D-hIO cultured on XF-DISC are successfully transplanted into intestinal injury and inflammation mouse models, leading to engraftment and regeneration of damaged mouse intestinal epithelium. As a reliable and scalable xenogeneic-free ISC 3D-hIO culture method, XF-DISC is highly promising for the development of regenerative ISC therapy for human intestinal diseases. Methods to culture intestinal stem cells (ISCs) are often limited by undefined culture conditions arising from the use of basement membrane extracts or feeder cell layers. Here, the authors propose a polymer-based xenogeneic-free dish to culture stem cells, ensuring extended maintenance of ISCs derived from 3D human intestinal organoids.

Gallium-based liquid metals (LMs) are promising materials for stretchable electronics due to their metallic conductivity and deformability. However, the fabrication of large-area stretchable integrated electronics using LMs on various polymers remains challenging due to their high surface tension, fluidity, and poor wettability. Current techniques, such as selective wetting and lift-off processes, face limitations related to substrate compatibility and Ga/metal alloying, hindering their applicability in integrated electronic systems. To address these challenges, we developed a high-resolution top-down etching-based photolithography combined with a universal cryogenic transfer method for transferring patterned LM particles (LMPs) in various polymer substrates. The cryogenic environment modifies the interfacial bonding between the LMPs and substrates, resulting in a universal transfer. The resulting liquid metal particle network embedded polymer (LNEP) exhibits high electrical conductivity (~1.71 × 10⁶ S/m), stability, and strain-insensitive performance across various polymers. This process is scalable to large-area fabrication, overcoming the limitations of existing LM patterning techniques. Leveraging this approach, we demonstrated the use of LNEP ranging from skin-conformal wearable sensors to hybrid stretchable circuits and implantable devices, demonstrating the universality of the method. This technique establishes a scalable pathway for stretchable electronics in advanced applications. Stretchable liquid-metal electronics is limited by high surface tension, fluidity, and poor wettability. Here, Lee et. al. presents a universal cryogenic transfer method for liquid metal particles, enabling high-throughput fabrication of wafer-scale stretchable integrated electronics with robust electrical performance.

Three-dimensional（3D） printing（3DP） is a rapid prototyping technology that has gained increasing recognition in many different fields. Inherent accuracy and low-cost property enable applicability of 3DP in many areas, such as manufacturing, aerospace,medical, and industrial design. Recently, 3DP has gained considerable attention in the medical field. The image data can be quickly turned into physical objects by using 3DP technology. These objects are being used across a variety of surgical specialties. The shortage of cadaver specimens is a major problem in medical education. However, this concern has been solved with the emergence of 3DP model. Custom-made items can be produced by using 3DP technology. This innovation allows 3DP use in preoperative planning and surgical training. Learning is difficult among medical students because of the complex anatomical structures of the liver. Thus, 3D visualization is a useful tool in anatomy teaching and hepatic surgical training. However,conventional models do not capture haptic qualities. 3DP can produce highly accurate and complex physical models. Many types of human or animal differentiated cells can be printed successfully with the development of 3D bio-printing technology. This progress represents a valuable breakthrough that exhibits many potential uses, such as research on drug metabolism or liver disease mechanism. This technology can also be used to solve shortage of organs for transplant in the future.

The root of Polygonum multiflorum Thunb （PM） has been used in China to treat a variety of diseases, such as constipation, early graying of the hair and hyperlipemia. Recent evidence shows that PM causes idiosyncratic drug-induced liver injury （IDILI） in humans. In this study, we investigated the molecular basis of PM-induced liver injury in a rat model of IDILI based on a non-hepatotoxic dose of LPS. SD rats were orally administered 3 potentially hepatotoxic compounds of PM： cis-stilbene glucoside （cis-SG, 50 mg/kg）, trans-SG （50 mg/kg） or emodin （5 mg/kg）, followed by injection of LPS （2.8 mg/kg, iv）. Serum and liver histology were evaluated 7 h after LPS injection. Among the 3 compounds tested, cis-SG, but not emodin or trans-SG, induced severe liver injury in rats when combined with LPS. The levels of AST and ALT in plasma and inflammatory cytokines in both plasma and liver tissues were markedly elevated. The liver tissues showed increased injury, hepatocyte apoptosis, and macrophage infiltration, and decreased cell proliferation. Microarray analysis revealed a negative correlation between peroxisome proliferator-activated receptor-y （PPAR-y） and LPS/cis-SG-induced liver injury. Immunohistochemical staining and RT-PCR results further confirmed that cis-SG significantly inhibited activation of the PPAR-~ pathway in the liver tissues of LPS/cis-SG-treated rats. Pre-treatment with a PPAR-y agonist pioglitazone （500 g/kg, ig） reversed LPS/ cis-SG-induced liver injury, which was associated with inhibiting the nuclear factor kappa B （NF-KB） pathway. These data demonstrate that c/s-stilbene glucoside induces immunological idiosyncratic hepatotoxicity through suppressing PPAR-γ in a rat model of IDILl.

Three-dimensional (3D) printing (3DP) is a rapid prototyping technology that has gained increasing recognition in many different fields. Inherent accuracy and low-cost property enable applicability of 3DP in many areas, such as manufacturing, aerospace, medical, and industrial design. Recently, 3DP has gained considerable attention in the medical field. The image data can be quickly turned into physical objects by using 3DP technology. These objects are being used across a variety of surgical specialties. The shortage of cadaver specimens is a major problem in medical education. However, this concern has been solved with the emergence of 3DP model. Custom-made items can be produced by using 3DP technology. This innovation allows 3DP use in preoperative planning and surgical training. Learning is difficult among medical students because of the complex anatomical structures of the liver. Thus, 3D visualization is a useful tool in anatomy teaching and hepatic surgical training. However, conventional models do not capture haptic qualities. 3DP can produce highly accurate and complex physical models. Many types of human or animal differentiated cells can be printed successfully with the development of 3D bio-printing technology. This progress represents a valuable breakthrough that exhibits many potential uses, such as research on drug metabolism or liver disease mechanism. This technology can also be used to solve shortage of organs for transplant in the future.

Planktonic bacteria are abundant in the Chukchi Borderland region. However, little is known about their di- versity and the roles of various bacteria in the ocean. Seawater samples were collected from two stations K2S and K4S where sea ice was melting obviously. The analysis of water samples with fluorescence in situ hybridization （FISH） showed that DMSP-degrading bacteria accounted for 13% of the total bacteria at the station K2S. No aerobic anoxygenic phototrophic （AAP） bacteria were detected in both samples. The bacterial communities were characterized by two 16S rRNA gene clone libraries. Sequences fell into four major lineages of the domain Bacteria, including Proteobacteria （Alpha, Beta and Gamma subclasses）, Bac- teroidetes, Actinobacteria and Firmicutes. No significant difference was found between the two clone li- braries. SAR11 and Rhodobacteraceae clades of Alphaproteobacteria and Pseudoalteromonas of Gammapro- teobacteria constituted three dominant fractions in the clone libraries. A total of 191 heterotrophic bacterial strains were isolated and 76% showed extracellular proteolytic activity. Phylogenetic analysis reveals that the isolates fell into Gammaproteobacteria, Bacteroidetes, Actinobacteria and Firmicutes. The most common genus in both the bacterial isolates and protease-producing bacteria was Pseudoalteromonas. UniFrac data showed suggestive differences in bacterial communities between the Chukchi Borderland and the northern Bering Sea.

Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor’s glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects. SGLT2 inhibitors, a class of type 2 diabetes medication, reduce cardiovascular events in patients beyond expectation from blood sugar control. Here the authors report a randomized controlled trial showing that SGLT2 inhibitors reduce inflammasome activation in peripheral macrophages, which may contribute to the cardiovascular protection.

Toward the development of surface-sensitive analytical techniques for biosensors and diagnostic biochip assays, a local integration of low-concentration target materials into the sensing region of interest is essential to improve the sensitivity and reliability of the devices. As a result, the dynamic process of sorting and accurate positioning the nanoparticulate biomolecules within pre-defined micro/nanostructures is critical, however, it remains a huge hurdle for the realization of practical surface-sensitive biosensors and biochips. A scalable, massive, and non-destructive trapping methodology based on dielectrophoretic forces is highly demanded for assembling nanoparticles and biosensing tools. Herein, we propose a vertical nanogap architecture with an electrode-insulator-electrode stack structure, facilitating the generation of strong dielectrophoretic forces at low voltages, to precisely capture and spatiotemporally manipulate nanoparticles and molecular assemblies, including lipid vesicles and amyloid-beta protofibrils/oligomers. Our vertical nanogap platform, allowing low-voltage nanoparticle captures on optical metasurface designs, provides new opportunities for constructing advanced surface-sensitive optoelectronic sensors. Label-free trapping of nanoparticles via dielectophoretic forces is traditionally done with electrodes in a horizontal gap layout. Here, the authors present a vertical nanogap architecture, which allows for precise capture and spatiotemporal manipulation of nanoparticles and molecular assemblies.

Preclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke. In a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules. Night-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.

Wearable and implantable devices require conductive, stretchable and biocompatible materials. However, obtaining composites that simultaneously fulfil these requirements is challenging due to a trade-off between conductivity and stretchability. Here, we report on Ag–Au nanocomposites composed of ultralong gold-coated silver nanowires in an elastomeric block-copolymer matrix. Owing to the high aspect ratio and percolation network of the Ag–Au nanowires, the nanocomposites exhibit an optimized conductivity of 41,850 S cm−1 (maximum of 72,600 S cm−1). Phase separation in the Ag–Au nanocomposite during the solvent-drying process generates a microstructure that yields an optimized stretchability of 266% (maximum of 840%). The thick gold sheath deposited on the silver nanowire surface prevents oxidation and silver ion leaching, making the composite biocompatible and highly conductive. Using the nanocomposite, we successfully fabricate wearable and implantable soft bioelectronic devices that can be conformally integrated with human skin and swine heart for continuous electrophysiological recording, and electrical and thermal stimulation.