Metal-Phosphonate-Organic Network as Ion Enrichment Layer for Sustainable Zinc Metal Electrode with High Rate Capability.

Zinc (Zn) metal batteries could be the technology of choice for sustainable battery chemistries owing to its better safety and cost advantage. However, their cycle life and Coulombic efficiency (CE) are strongly limited by the dendritic growth and side reactions of Zn anodes. Herein, we proposed an in situ construction of a metal-phosphonate-organic network (MPON) with three-dimensional interconnected networks on Zn metal, which can act as an ion enrichment layer for Zn anodes in Zn-metal batteries. This MPON with abundant porous structure and phosphate sites possesses ion enriching properties and high Zn2+ transference number (0.83), which is beneficial for enhancing Zn2+ migration and self-concentrating kinetics. Meanwhile, MPON offers hydrophobicity to effectively inhibit the water-induced Zn anode corrosion. As a result, the Zn electrode exhibits superior Zn/Zn2+ reversibility of over 4 months at 3 mA cm-2 and a high CE of 99.6%. Moreover, the Zn/NaV3O8 ·1.5H2O and Zn/MnO2 full cells using ultrathin Zn anodes (10 µm) exhibit high-capacity retention of 81% and 78% after 1400 and 1000 cycles, respectively. This work provides a unique promise to design high-performance anode for practical Zn-metal-based batteries.

Inhibition of colorectal cancer in Alzheimer's disease is mediated by gut microbiota via induction of inflammatory tolerance.

Epidemiological studies have revealed an inverse relationship between the incidence of Alzheimer's disease (AD) and various cancers, including colorectal cancer (CRC). We aimed to determine whether the incidence of CRC is reduced in AD-like mice and whether gut microbiota confers resistance to tumorigenesis through inducing inflammatory tolerance using 16S ribosomal RNA gene sequencing and fecal microbiota transplantation (FMT). AD-like mice experienced a significantly decreased incidence of CRC tumorigenesis induced by azoxymethane-dextran sodium sulfate as evidenced by suppressed intestinal inflammation compared with control mice. However, FMT from age-matched control mice reversed the inhibitory effects on the tumorigenesis of CRC and inflammatory response in AD-like mice. The key bacterial genera in gut microbiota, including Prevotella, were increased in both the AD-like mice and in patients with amnestic mild cognitive impairment (aMCI) but were decreased in patients with CRC. Pretreatment with low-dose Prevotella-derived lipopolysaccharides (LPS) induced inflammatory tolerance both in vivo and in vitro and inhibited CRC tumorigenesis in mice. Imbalanced gut microbiota increased intestinal barrier permeability, which facilitated LPS absorption from the gut into the blood, causing cognitive decline in AD-like mice and patients with aMCI. These data reveal that intestinal Prevotella-derived LPS exerts a resistant effect to CRC tumorigenesis via inducing inflammatory tolerance in the presence of AD. These findings provide biological evidence demonstrating the inverse relationship between the incidence of AD and CRC.

Flexible solid-liquid bi-continuous electrically and thermally conductive nanocomposite for electromagnetic interference shielding and heat dissipation.

In the era of 5 G, the rise in power density in miniaturized, flexible electronic devices has created an urgent need for thin, flexible, polymer-based electrically and thermally conductive nanocomposites to address challenges related to electromagnetic interference (EMI) and heat accumulation. However, the difficulties in establishing enduring and continuous transfer pathways for electrons and phonons using solid-rigid conductive fillers within insulative polymer matrices limit the development of such nanocomposites. Herein, we incorporate MXene-bridging-liquid metal (MBLM) solid-liquid bi-continuous electrical-thermal conductive networks within aramid nanofiber/polyvinyl alcohol (AP) matrices, resulting in the AP/MBLM nanocomposite with ultra-high electrical conductivity (3984 S/cm) and distinguished thermal conductivity of 13.17 W m-1 K-1. This nanocomposite exhibits excellent EMI shielding efficiency (SE) of 74.6 dB at a minimal thickness of 22 µm, and maintains high EMI shielding stability after enduring various harsh conditions. Meanwhile, the AP/MBLM nanocomposite also demonstrates promising heat dissipation behavior. This work expands the concept of creating thin films with high electrical and thermal conductivity.

Control nucleation for strong and tough crystalline hydrogels with high water content.

Hydrogels, provided that they integrate strength and toughness at desired high content of water, promise in load-bearing tissues such as articular cartilage, ligaments, tendons. Many developed strategies impart hydrogels with some mechanical properties akin to natural tissues, but compromise water content. Herein, a strategy deprotonation-complexation-reprotonation is proposed to prepare polyvinyl alcohol hydrogels with water content as high as ~80% and favorable mechanical properties, including tensile strength of 7.4 MPa, elongation of around 1350%, and fracture toughness of 12.4 kJ m-2. The key to water holding yet improved mechanical properties lies in controllable nucleation for refinement of crystalline morphology. With nearly constant water content, mechanical properties of as-prepared hydrogels are successfully tailored by tuning crystal nuclei density via deprotonation degree and their distribution uniformity via complexation temperature. This work provides a nucleation concept to design robust hydrogels with desired water content, holding implications for practical application in tissue engineering.

Cross-Species Insights into Trophoblast Invasion During Placentation Governed by Immune-Featured Trophoblast Cells.

Proper development of the placenta, the transient support organ forms after embryo implantation, is essential for a successful pregnancy. However, the regulation of trophoblast invasion, which is most important during placentation, remains largely unknown. Here, rats, mice, and pigs are used as biomedical models, used scRNA-seq to comparatively elucidate the regulatory mechanism of placental trophoblast invasion, and verified it using a human preeclampsia disease model combined with scStereo-seq. A dual-featured type of immune-featured trophoblast (iTrophoblast) is unexpectedly discovered. Interestingly, iTrophoblast only exists in invasive placentas and regulates trophoblast invasion during placentation. In a normally developing placenta, iTrophoblast gradually transforms from an immature state into a functional mature state as it develops. Whereas in the developmentally abnormal preeclamptic placenta, disordered iTrophoblast transformation leads to the accumulation of immature iTrophoblasts, thereby disrupting trophoblast invasion and ultimately leading to the progression of preeclampsia.

Superassembled Mesoporous Carbon-Fe2O3 Heterochannels for Photothermal-Enhanced Hyaluronidase Sensing.

Developing an activity detection platform for hyaluronidase (HAase) is crucial for diagnosing and treating cancer. However, traditional detection of HAase is based on changes in the flow rate caused by viscosity or requires complex modifications and processing, which limits the detection accuracy and sensitivity. Herein, hyaluronic acid (HA)-modified mesoporous-based heterochannels (mesoporous carbon-doped γ-Fe2O3 nanoparticles/anodized aluminum oxide, MC-γ-Fe2O3/AAO) featuring ordered 3D transport frameworks and a photothermal property were developed for high performance HAase detection. The HA molecules on the surface of the mesoporous layer provide abundant active sites for HAase detection. An improved ionic current was realized after enzymatic hydrolysis reactions between HA and HAase due to enhanced surface charges and more hydrophilicity, leading to highly sensitive and accurate HAase detection. Notably, the detection performance can be further upgraded with the assistance of the photothermal property of γ-Fe2O3. An amplified detection current signal was achieved owing to a synergistic effect between ion currents and photoresponsive currents. A wide linear detection range from 1 to 50 U/mL and a low detection limit of 0.348 U/mL were obtained, achieving a 2% improvement under illumination. Importantly, the heterochannels have also been successfully applied for HAase detection in fetal bovine serum samples, manifesting considerable application prospects. This work provides a new strategy in constructing photoresponsive nanochannels with a photothermal property for a highly efficient biosensing platform.

Development and validation of a nomogram of all-cause mortality in adult Americans with diabetes.

This study aimed to develop and validate a predictive model of all-cause mortality risk in American adults aged ≥ 18 years with diabetes. 7918 participants with diabetes were enrolled from the National Health and Nutrition Examination Survey (NHANES) 1999-2016 and followed for a median of 96 months. The primary study endpoint was the all-cause mortality. Predictors of all-cause mortality included age, Monocytes, Erythrocyte, creatinine, Nutrition Risk Index (NRI), neutrophils/lymphocytes (NLR), smoking habits, alcohol consumption, cardiovascular disease (CVD), urinary albumin excretion rate (UAE), and insulin use. The c-index was 0.790 (95% CI 0.779-0.801, P < 0.001) and 0.792 (95% CI: 0.776-0.808, P < 0.001) for the training and validation sets, respectively. The area under the ROC curve was 0.815, 0.814, 0.827 and 0.812, 0.818 and 0.829 for the training and validation sets at 3, 5, and 10 years of follow-up, respectively. Both calibration plots and DCA curves performed well. The model provides accurate predictions of the risk of death for American persons with diabetes and its scores can effectively determine the risk of death in outpatients, providing guidance for clinical decision-making and predicting prognosis for patients.

Implications of PD-L1 expression on the immune microenvironment in HER2-positive gastric cancer.

In the KEYNOTE-811 study, anti-HER2 and immunotherapy treatments resulted in longer survival in HER2-positive gastric cancer patients with CPS ≥ 1, whereas CPS < 1 patients lacked notable benefits. We studied this in a real-world cohort of 106 HER2-positive, CPS < 1 patients and found no survival differences between those treated with anti-HER2 therapy alone or with added immunotherapy. Thus, we investigate the tumor microenvironment variations in 160 HER2-positive patients, CPS ≥ 1 cases exhibited elevated spatial effective scores of immune cells, including CD4, CD8 subtypes, and NK cells, compared to CPS < 1. Furthermore, through single-cell sequencing in eight HER2-positive individuals, gene expressions revealed regulation of T-cell co-stimulation in CPS ≥ 1 and IL-1 binding in CPS < 1 cases. Notably, we discovered a CPS < 1 subtype marked by CXCR4+M2 macrophages, associated with poor prognosis, whose proportion and expression were reduced when benefiting from anti-HER2 therapy. These findings suggest CPS ≥ 1 patients, due to their immune microenvironment composition, may respond better to anti-PD-1/PD-L1 therapy.

Expressions of Type I-III Interferons in Sjögren's Syndrome and Non-Sjögren's Dry Eye.

INTRODUCTION: Systemic implications create a critical need for identification of dry eye patients with Sjögren syndrome (SS). Herein, we aimed to determine expressions of type I-III interferons (IFNs) in dry eye patients with or without underlying SS and their differential diagnosis. METHODS: A prospective, observational, case-control study was performed on 140 dry eye patients among which 78 patients were diagnosed with SS. Clinical evaluations included ELISA detections of serum type I IFN (IFN-α and IFN-ß, type II IFN (IFN-γ), and type III IFN (IFN-λ1/IL-29, IFN-λ2/IL-28, and IFN-λ3/IL-28B), as well as reporter cell assay for serum type I IFN activity. RESULTS: The serum levels of IFN-α and IFN-ß were notably higher in dry eye patients with SS than those without underlying SS (p < 0.0001). The functional assay for serum type I IFN activity showed the mean summed scores in dry eye patients with SS were remarkably increased compared to those without underlying SS (p < 0.0001). The serum levels of IFN-γ and IFN-λ1/IL-29 seemed higher in dry eye patients with SS than those without underlying SS (p < 0.0001). The serum levels of type I IFN (IFN-α combined with IFN-ß), type II IFN (IFN-γ level), and type III IFN (IFN-λ1/IL-29) used as a test to predict underlying SS among dry eye patients produced an area under the curve of 0.86, 0.73, and 0.94, respectively. CONCLUSION: Serum levels of type I-III IFNs, especially IFN-α, IFN-ß, and IFN-λ1/IL-29, may serve as a useful biomarker for identification of SS dry eye from non-SS dry eye.

A physical derivation of high-flux ion transport in biological channel via quantum ion coherence.

Biological ion channels usually conduct the high-flux transport of 107 ~ 108 ions·s-1; however, the underlying mechanism is still lacking. Here, by applying the KcsA potassium channel as a typical example, and performing multitimescale molecular dynamics simulations, we demonstrate that there is coherence of the K+ ions confined in biological channels, which determines transport. The coherent oscillation state of confined K+ ions with a nanosecond-level lifetime in the channel dominates each transport event, serving as the physical basis for the high flux of ~108 ions∙s-1. The coherent transfer of confined K+ ions only takes several picoseconds and has no perturbation effect on the ion coherence, acting as the directional key of transport. Such ion coherence is allowed by quantum mechanics. An increase in the coherence can significantly enhance the ion conductance. These findings provide a potential explanation from the perspective of coherence for the high-flux ion transport with ultralow energy consumption of biological channels.

Redo-TAVR for bioprosthetic valve degeneration with obvious neoplasm in a left cerebral infarction patient.

Key Clinical Message: In recent years, it is necessary to Redo-TAVR for the patients with bioprosthetic valve degeneration. This case report described a unique instance to successfully Redo-TAVR a patient with bioprosthetic valve degeneration, in addition, with left cerebral infarction and renal insufficiency. Abstract: Over time, more and more patients have bioprosthetic valve degeneration either used in SAVR or TAVR. In order to solve the produced problems due to the degenerated bioprosthetic valve, Redo-TAVR was increasingly popular due to its safe and efficiency especially for the high risk and complicated symptoms patients. In this case, the patient with left cerebral infarction and renal insufficiency has exhibited severe regurgitation and obvious neoplasm around the previous replaced aortic valve. For the patient with complicated symptoms, we did not image for this patient and only used CT to determine the position and angle for the Redo-TAVR on the base of metal stent for the previous replaced aortic valve. During the Redo-TAVR process, for fear of the obvious neoplasm slipping from the previous replaced aortic valve to embolism of important organs, before carrying out the Redo-TAVR, cerebral protection device, temporary pacemaker, and coronary artery protection device were utilized in order to avoid the damage for the important organs from the obvious neoplasm slipping from the previous replaced aortic valve. The surgery was successful and the patient recovered well. The patient's symptoms of chest tightness and suffocation have been greatly reduced.

CXCR4-Targeted 68 Ga-Pentixafor PET/CT Imaging in Inflammatory Bowel Disease.

PURPOSE: To investigate the role of CXCR4-targeted 68 Ga-pentixafor PET/CT imaging in inflammatory bowel disease (IBD). METHODS: Five IBD patients and 12 control subjects performing 68 Ga-pentixafor PET/CT examinations were included. 68 Ga-pentixafor PET/CT imaging and endoscopic findings were recorded and compared. The semiquantitative parameters of 68 Ga-pentixafor uptake by the lesion segments in IBD patients and the normal intestines in the control were investigated. RESULTS: Among these 5 IBD patients, endoscopy successfully examined a total of 26 intestinal segments, with 13 segments showing endoscopic lesions. 68 Ga-pentixafor PET/CT was positive in all endoscopy-proven lesions (13/13). Additionally, 68 Ga-pentixafor PET/CT revealed the lesions in small intestines and colons that cannot be reached by endoscopy due to severe stenosis, and mesenteric lymphadenitis accompanied IBD. The SUV max of the lesion segments in IBD patients was significantly higher than that of the normal intestines in the control group (median, 3.15 [range, 1.61-6.26] vs 1.67 [1.18-2.29], P < 0.001). Moreover, the SUV max ratios of the lesion segments/liver or blood pool were higher when compared with the control (2.20 [1.13-3.26] vs 0.85 [0.54-1.20]; 1.66 [0.94-2.95] vs 0.67 [0.52-1.04]; P ≤ 0.001). CONCLUSIONS: 68 Ga-pentixafor PET/CT can be a potentially valuable tool to assess the active intestinal lesions of IBD with high sensitivity. Moreover, this noninvasive approach does not require fasting or bowel preparation, offering good tolerance and safety.

Delivery of miRNAs Using Nanoparticles for the Treatment of Osteosarcoma.

Osteosarcoma is the predominant primary malignant bone tumor that poses a significant global health challenge. MicroRNAs (miRNAs) that regulate gene expression are associated with osteosarcoma pathogenesis. Thus, miRNAs are potential therapeutic targets for osteosarcoma. Nanoparticles, widely used for targeted drug delivery, facilitate miRNA-based osteosarcoma treatment. Numerous studies have focused on miRNA delivery using nanoparticles to inhibit the progress of osteosarcoma. Polymer-based, lipid-based, inorganic-based nanoparticles and extracellular vesicles were used to deliver miRNAs for the treatment of osteosarcoma. They can be modified to enhance drug loading and delivery capabilities. Also, miRNA delivery was combined with traditional therapies, for example chemotherapy, to treat osteosarcoma. Consequently, miRNA delivery offers promising therapeutic avenues for osteosarcoma, providing renewed hope for patients. This review emphasizes the studies utilizing nanoparticles for miRNA delivery in osteosarcoma treatment, then introduced and summarized the nanoparticles in detail. And it also discusses the prospects for clinical applications.

Akkermansia muciniphila alleviates abdominal aortic aneurysms via restoring CITED2 activated by EPAS1.

Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease that has been linked to gut microbiome dysbiosis. Therefore, this study aims to investigate the effects of Akkermansia muciniphila (Am) on AAA mice and the biomolecules involved. AAA mice were generated using angiotensin II (Ang II), and 16sRNA sequencing was used to identify an altered abundance of microbiota in the feces of AAA mice. Vascular smooth muscle cell (VSMC) markers and apoptosis, and macrophage infiltration in mouse aortic tissues were examined. The abundance of Am was reduced in AAA mouse feces, and endothelial PAS domain-containing protein 1 (EPAS1) was downregulated in AAA mice and VSMC induced with Ang II. Am delayed AAA progression in mice, which was blunted by knockdown of EPAS1. EPAS1 was bound to the Cbp/p300-interacting transactivator 2 (CITED2) promoter and promoted CITED2 transcription. CITED2 reduced VSMC apoptosis and delayed AAA progression. Moreover, EPAS1 inhibited macrophage inflammatory response by promoting CITED2 transcription. In conclusion, gut microbiome dysbiosis in AAA induces EPAS1-mediated dysregulation of CITED2 to promote macrophage inflammatory response and VSMC apoptosis.

Different viral effectors hijack TCP17, a key transcription factor for host Auxin synthesis, to promote viral infection.

Auxin is an important class of plant hormones that play an important role in plant growth development, biotic stress response, and viruses often suppress host plant auxin levels to promote infection. However, previous research on auxin-mediated disease resistance has focused mainly on signaling pathway, and the molecular mechanisms of how pathogenic proteins manipulate the biosynthetic pathway of auxin remain poorly understood. TCP is a class of plant-specific transcription factors, of which TCP17 is a member that binds to the promoter of YUCCAs, a key rate-limiting enzyme for auxin synthesis, and promotes the expression of YUCCAs, which is involved in auxin synthesis in plants. In this study, we reported that Tomato spotted wilt virus (TSWV) infection suppressed the expression of YUCCAs through its interaction with TCP17. Further studies revealed that the NSs protein encoded by TSWV disrupts the dimerization of TCP17, thereby inhibit its transcriptional activation ability and reducing the auxin content in plants. Consequently, this interference inhibits the auxin response signal and promotes the TSWV infection. Transgenic plants overexpressing TCP17 exhibit resistance against TSWV infection, whereas plants knocking out TCP17 were more susceptible to TSWV infection. Additionally, proteins encoded by other RNA viruses (BSMV, RSV and TBSV) can also interact with TCP17 and interfere with its dimerization. Notably, overexpression of TCP17 enhanced resistance against BSMV. This suggests that TCP17 plays a crucial role in plant defense against different types of plant viruses that use viral proteins to target this key component of auxin synthesis and promote infection.

Polyacrylic acid-reinforced organic-inorganic composite bone adhesives with enhanced mechanical properties and controlled degradability.

Bone adhesives, as alternatives to traditional bone fracture treatment methods, have great benefits in achieving effective fixation and healing of fractured bones. However, current available bone adhesives have limitations in terms of weak mechanical properties, low adhesion strength, and inappropriate degradability, hindering their clinical applications. The development of bone adhesives with strong mechanical properties, adhesion strength, and appropriate degradability remains a great challenge. In this study, polyacrylic acid was incorporated with tetracalcium phosphate and O-phospho-L-serine to form a new bone adhesive via coordination and ionic interactions to achieve exceptional mechanical properties, adhesion strength, and degradability. The bone adhesive could achieve an initial adhesion strength of approximately 3.26 MPa and 0.86 MPa on titanium alloys and bones after 15 min of curing, respectively, and it increased to 5.59 MPa and 2.73 MPa, after 24 h of incubation in water or simulated body fluid (SBF). The compressive strength of the adhesive increased from 10.06 MPa to 72.64 MPa over two weeks, which provided sufficient support for the fractured bone. Importantly, the adhesive started to degrade after 6 to 8 weeks of incubation in SBF, which is beneficial to cell ingrowth and the bone healing process. In addition, the bone adhesives exhibited favorable mineralization capability, biocompatibility, and osteogenic activity. In vivo experiments showed that it has a better bone-healing effect compared with the traditional polymethyl methacrylate bone cement. These results demonstrate that the bone adhesive has great potential in the treatment of bone fractures.

A smart roof that transforms raindrops into agricultural spraying.

We present a smart roof that makes fragmented droplets from the impact of raindrops on superhydrophobic meshes and utilizes the droplets for agricultural spraying. This facile method transforms raindrops or waterdrops into uniform microdroplets, which can both reduce crop lodging induced by heavy rainfall, and realize uniform spraying of pesticides.

Synthesis of benzothiazole compounds based on 2D graphene oxide membrane nanoreactors.

The nanoconfinement effect plays an important role in chemical reactions. Inspired by enzymes, this work presents a new way to conduct the rapid flow synthesis of benzothiazoles in the two-dimensional (2D) nanoconfined space created by a graphene oxide membrane. The conversion reaches 96.7% in a short reaction time of less than 23 s at 22 °C.

Achieving Super-Metallophobicity on Silicon-based Ceramics at High Temperature.

As a critical concept in physical chemistry, superwettability is widely concerned in both fundamental science and practical engineering in past few decades. Despite this, investigation on high temperature superwettability is still a void, which is significant both in scientific and industrial fields. Herein, a ceramic with specific high temperature non-wetting property, Si2N2O is proposed. Compared with other materials, Si2N2O is elucidated with better practical non-wetting property against various non-ferrous metals. Combining with micro-nanostructures, the metallophobicity is further improved (contact angle >150° and contact angle hysteresis ≈0°). The extraordinary metal repellency is defined as "super-metallophobicity", which is proved to be induced by distinctive thermodynamic and dynamic wetting behavior on the rough surface. The research of super-metallophobicity not only sheds light on superwettability at high temperature, but also offers worthy insights for future potential material design in a wide range of applications, such as metallurgy, 3D printing and semiconductor industry.

Light-Driven Ionic and Molecular Transport through Atomically Thin Single Nanopores in MoS2/WS2 Heterobilayers.

Nanofluidic ionic and molecular transport through atomically thin nanopore membranes attracts broad research interest from both scientific and industrial communities for environmental, healthcare, and energy-related technologies. To mimic the biological ion pumping functions, recently, light-induced and quantum effect-facilitated charge separation in heterogeneous 2D-material assemblies is proposed as the fourth type of driving force to achieve active and noninvasive transport of ionic species through synthetic membrane materials. However, to date, engineering versatile van der Waals heterostructures into 2D nanopore membranes remains largely unexplored. Herein, we fabricate single nanopores in heterobilayer transition metal dichalcogenide membranes with helium ion beam irradiation and demonstrate the light-driven ionic transport and molecular translocation phenomena through the atomically thin nanopores. Experimental and simulation results further elucidate the driving mechanism as the photoinduced near-pore electric potential difference due to type II band alignment of the semiconducting WS2 and MoS2 monolayers. The strength of the photoinduced localized electric field near the pore region can be approximately 1.5 times stronger than that of its counterpart under the conventional voltage-driven mode. Consequently, the light-driven mode offers better spatial resolution for single-molecule detection. Light-driven ionic and molecular transport through nanopores in van der Waals heterojunction membranes anticipates transformative working principles for next-generation biomolecular sequencing and gives rise to fascinating opportunities for light-to-chemical energy harvesting nanosystems.