Surface-Grafted Single-Atomic Pt-Nx Complex with a Precisely Regulating Coordination Sphere for Efficient Electron Acceptor-Inducing Interfacial Electron Transfer.

Based on the electron-withdrawing effect of the Pt(bpy)Cl2 molecule, a simple post-modification amide reaction was firstly used to graft it onto the surface of NH2-MIL-125, which formed a highly efficient electron acceptor that induced the conversion of the photoinduced charge migration pathway from internal BDC→TiOx migration to external BDC→PtNx migration, significantly improving the efficiency of photoinduced electron transfer and separation. Furthermore, precise control over the first coordination sphere of Pt single atoms was achieved using further post-modification with additional bipyridine to investigate the effect of Pt-Nx coordination numbers on reaction activity. The as-synthesized NML-PtN2 exhibited superior photocatalytic hydrogen evolution activity of 7.608 mmol g-1 h-1, a remarkable improvement of 225 and 2.26 times compared to pristine NH2-MIL-125 and NML-PtN4, respectively. In addition, the superior apparent quantum yield of 4.01% (390 nm) and turnover frequency of 190.3 h-1 (0.78 wt% Pt SA; 129 times compared to Pt nanoparticles/NML) revealed the high solar utilization efficiency and hydrogen evolution activity of the material. And macroscopic color changes caused by the transition of carrier migration paths was first observed. It holds profound significance for the design of MOF-Molecule catalysts with efficient charge carrier separation and precise regulation of single-atom coordination sphere.

Interaction Between Microbubbles and Microwave Ablation: A Phantom and Rabbit Model.

OBJECTIVES: This study aimed to explore the interactions between microbubbles and microwave ablation (MWA). METHODS: The study employed custom-made phantoms (in vitro) and white New Zealand rabbits (in vivo). MWA was performed with or without microbubbles in the phantoms (2 × 105 particles mL-1) and rabbit livers (intravenous injection of 0.05 mL/kg SonoVue). During the MWA, K-type thermocouple probes were used to monitor the MWA-induced temperature increase. Contrast-enhanced ultrasound imaging (CEUS) was used to monitor and analyze the microbubbles signal intensity. After MWA, the ablation-zone volumes were evaluated and compared between the groups with and without microbubbles. RESULTS: In both the phantom models and rabbits, microbubbles showed no significant influence on MWA, including the ablation range and MWA-induced temperature increase. In phantoms and rabbit livers filled with microbubbles, MWA caused the formation of a gradually expanding microbubble-defect region over the ablation time. An increase in the temperature caused microbubble destruction. CONCLUSIONS: Microbubbles had no significant influence on MWA. However, MWA induced the destruction of microbubbles in a temperature-dependent manner. Thus, the poor thermotolerance of microbubbles is a non-negligible barrier when using CEUS to monitor the ablation range during MWA in real-time.

Copper regulation of PtRhRuCu nanozyme targeted boosting peroxidase-like activity for ultrasensitive smartphone-assisted colorimetric sensing of glucose.

Point-of-care testing (POCT) is promising for biodetection in home healthcare due to advantages of simplicity, rapidity, low cost, portability, high sensitivity and accuracy, and object-oriented POCT platform can be developed by nanozyme-based biosensing. However, designing high-performance nanozymes with targeted regulated catalytic activity remains challenging. Herein, advanced PtRhRuCu quaternary alloy nanozymes (QANs) were rationally designed and successfully synthesized. Cu atoms induced mechanisms of hydrogen peroxide (H2O2) activation and d-band center regulation, achieving high enhancement of peroxide (POD)-like activity and inhibition of oxidase (OXD)-like activity. Inspired by this, a smartphone-assisted colorimetric platform integrated with test strips was established for glucose detection of soft drinks, with a detection limit of 0.021 mM and a recovery rate of 97.87 to 103.36 %. This work not only provides a novel path for tuning specific enzyme-like activities of metal nanozymes, but also shows the potential feasibility for rational design of POCT sensors in actual samples.

The relationship between ablation range and ablation energy in papillary thyroid microcarcinoma: a comparison between microwave ablation and laser ablation.

OBJECTIVES: To study the relationship between the ablation range and applied energy of laser ablation (LA) and microwave ablation (MWA) in papillary thyroid microcarcinoma (PTMC). METHODS: A total of 201 PTMC patients were treated with LA (n = 102) or MWA (n = 99) with single-applicator fixed ablation. The ablation range was determined by contrast-enhanced ultrasound. The ratios of ablation volume, longitudinal diameter, and orthogonal diameter to ablation energy (RAV/E, RAL/E, RAO/E) were analyzed and compared between MWA and LA. The effects of PTMC characteristics and Hashimoto's thyroiditis (HT) on ablation efficiency were evaluated by linear regression. RESULTS: The RAV/E was 0.72 (0.65-0.84) mm3/J for MWA and 0.48 (0.39-0.54) mm3/J for LA. HT was significantly correlated with RAV/E of LA (coefficient = - 0.367, p < 0.0001). RAL/E did not differ significantly between MWA and LA (MWA 0.026 mm/J, LA 0.025 mm/J; p = 0.957). However, MWA had a greater RAO/E than LA (MWA 0.014 mm/J, LA 0.012 mm/J; p < 0.0001). The plateau values of MWA and LA on the ablation orthogonal diameter were 10.7 mm and 8.69 mm, respectively. CONCLUSIONS: MWA showed a higher RAV/E than LA. More intuitively, MWA had a better ablation performance than LA on the orthogonal axis rather than the longitudinal axis. Theoretically, MWA and LA could achieve complete ablation of ≤ 6.70 mm and ≤ 4.69 mm PTMC separately by single-applicator fixed ablation considering a unilateral 2-mm safe margin. HT had a negative effect on LA but not on MWA. CLINICAL RELEVANCE STATEMENT: This study establishes strong connections between ablation energy and ablation range in papillary thyroid microcarcinoma (PTMC) in vivo, possibly contributing to the supplementation of the PTMC Ablation Consensus or Guidelines and providing a scientific basis for choosing clinical ablation parameters in PTMC. KEY POINTS: • Both microwave ablation (MWA) and laser ablation (LA) have excellent performance on the ablation longitudinal axis (easily exceeding 10 mm) for papillary thyroid microcarcinoma (PTMC). • MWA performed much better than LA on the ablation orthogonal axis. • MWA and LA are expected to achieve complete ablation of ≤ 6.70 mm and ≤ 4.69 mm PTMC separately by single-applicator fixed ablation considering a unilateral 2-mm safe margin.

A new insight into material basis of rhizoma Paridis saponins in alleviating pain.

ETHNOPHARMACOLOGICAL RELEVANCE: Paris polyphylla, as a traditional Chinese herbal medicine, was often used to relieve inflammation and pain. Rhizoma Paridis saponins (RPS) as the main active components of Paris polyphylla have excellent analgesic effects. AIM OF THE STUDY: Determine the analgesic material basis of RPS. MATERIALS AND METHODS: LC-MS/MS was used to analyze RPS, plasma after intravenous injection of RPS, and oral administration of RPS. H22 plantar pain model was established to explore the analgesic material basis of RPS. Moreover, correlation analysis, network pharmacology, RT-PCR and molecular docking were applied in this research. RESULTS: RPS had dose-dependently analgesic effects in acetic acid- and formalin-induced pain models. LC-MS/MS detection indicated that diosgenin as the metabolite of RPS mainly distributed in brain tissues. The addition of antibiotics increased the anti-tumor effect of RPS, but reduced its analgesic effect. Network pharmacology, RT-PCR and molecular docking showed that diosgenin exerted its analgesic effect through SRC and Rap1 signaling pathway. CONCLUSION: Diosgenin exhibited analgesic effects, while saponins had good anti-tumor effects in RPS. This discovery provided a better indication for the later application of RPS in anti-tumor and analgesic settings.

COVID-19 in Relation to Alzheimer's Disease: Mendelian Randomization Analyses Add to Multiple Lines of Evidence.

The potential link between COVID-19 and Alzheimer's disease (AD) has been an intriguing topic in the global pandemic. Whether the susceptibility and severity of COVID-19 affects the onset and progression of AD is of great concern. Clinical studies suggested an increased risk of AD occurrence or cognitive deficit after COVID-19. Basic research found that severe COVID-19 induced changes resembling AD. Evidence synthesis should always take into account diverse study designs, both traditional and novel. The recent study by Ding et al. aimed to investigate the association of COVID-19 with AD using a non-overlapping two-sample Mendelian randomization analysis.

Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon.

Most organs have tissue-resident immune cells. Human organoids lack these immune cells, which limits their utility in modeling many normal and disease processes. Here, we describe that pluripotent stem cell-derived human colonic organoids (HCOs) co-develop a diverse population of immune cells, including hemogenic endothelium (HE)-like cells and erythromyeloid progenitors that undergo stereotypical steps in differentiation, resulting in the generation of functional macrophages. HCO macrophages acquired a transcriptional signature resembling human fetal small and large intestine tissue-resident macrophages. HCO macrophages modulate cytokine secretion in response to pro- and anti-inflammatory signals and were able to phagocytose and mount a robust response to pathogenic bacteria. When transplanted into mice, HCO macrophages were maintained within the colonic organoid tissue, established a close association with the colonic epithelium, and were not displaced by the host bone-marrow-derived macrophages. These studies suggest that HE in HCOs gives rise to multipotent hematopoietic progenitors and functional tissue-resident macrophages.

Enteroendocrine Cells Protect the Stem Cell Niche by Regulating Crypt Metabolism in Response to Nutrients.

BACKGROUND & AIMS: The intestinal stem cell niche is exquisitely sensitive to changes in diet, with high-fat diet, caloric restriction, and fasting resulting in altered crypt metabolism and intestinal stem cell function. Unlike cells on the villus, cells in the crypt are not immediately exposed to the dynamically changing contents of the lumen. We hypothesized that enteroendocrine cells (EECs), which sense environmental cues and in response release hormones and metabolites, are essential for relaying the luminal and nutritional status of the animal to cells deep in the crypt. METHODS: We used the tamoxifen-inducible VillinCreERT2 mouse model to deplete EECs (Neurog3fl/fl) from adult intestinal epithelium and we generated human intestinal organoids from wild-type and NEUROGENIN 3 (NEUROG3)-null human pluripotent stem cells. We used indirect calorimetry, 1H-Nuclear Magnetic Resonance (NMR) metabolomics, mitochondrial live imaging, and the Seahorse bioanalyzer (Agilent Technologies) to assess metabolism. Intestinal stem cell activity was measured by proliferation and enteroid-forming capacity. Transcriptional changes were assessed using 10x Genomics single-cell sequencing. RESULTS: Loss of EECs resulted in increased energy expenditure in mice, an abundance of active mitochondria, and a shift of crypt metabolism to fatty acid oxidation. Crypts from mouse and human intestinal organoids lacking EECs displayed increased intestinal stem cell activity and failed to activate phosphorylation of downstream target S6 kinase ribosomal protein, a marker for activity of the master metabolic regulator mammalian target of rapamycin (mTOR). These phenotypes were similar to those observed when control mice were deprived of nutrients. CONCLUSIONS: EECs are essential regulators of crypt metabolism. Depletion of EECs recapitulated a fasting metabolic phenotype despite normal levels of ingested nutrients. These data suggest that EECs are required to relay nutritional information to the stem cell niche and are essential regulators of intestinal metabolism.

Prediction of gas production rate from shale gas reservoirs using a micro-macro analysis.

Shale gas has become one of the important contributors to the global energy supply. The declining pattern of the gas production rate with time from an unconventional gas reservoir is due to the depletion of shale gas stored in the nanovoids of the shale formation. However, there are only limited ways to predict the variation of the gas production rate with time from an unconventional gas reservoir. This is due to the multiple transport mechanisms of gas in nano-scale pores and changes in shale gas permeability with pressures in nano-scale pores, which is impacted by the pore structure of the shale. In this study, the permeability-pressure (K-p) relationship for different shales (Eagle Ford, Haynesville, Longmaxi and Opalinus) were determined using an equivalent anisotropic pore network model (PNM). This PNM has REV-scale shale gas flow in randomly generated nanovoids and their connection in the shale matrix, and the multiphase flow of shale gas including viscous flow, slip flow and Knudsen diffusion. These predicted K-p correlations were then used in a finite element model (FEM) to predict the variation of the gas production rate with time (flux-time curves) at the macroscale. The simulation results show that the flux-time curves can be simplified to two linear segments in logarithmic coordinates, which are influenced by the fracture length and initial gas pressure. The predicted results using the PNM-FEM were validated by comparing them with the reported field test data. The method described in this study can be used to upscale the gas transport process from micro- to macroscale, which can provide a predictive tool for the gas production in shales.

Chemically Induced Compatible Interface in Pyrolyzed Bacterial Cellulose/Graphene Sandwich for Electrochemical Energy Storage.

Herein, a three-step approach toward a multi-layered porous PBC/graphene sandwich has been developed, in which the chemical bonding interactions have been successfully enhanced via esterification between the layers of pyrolyzed bacterial cellulose (PBC) and graphene. Such a chemically induced compatible interface has been demonstrated to contribute significantly to the mass transfer efficiency when the PBC/graphene sandwich is deployed as electrode material for both supercapacitors and lithium-sulfur batteries. The high specific capacitance of the supercapacitors has been increased by three times, to 393 F g-1 at 0.1 A g-1. A high initial discharge specific capacity (~1100 mAhg-1) and high coulombic efficiency (99% after 300 cycles) of the rPG/S-based lithium-sulfur batteries have been achieved.

The value of ultrasound guided laser ablation in papillary thyroid recurrence carcinoma: A retrospective, single center study from China.

Objective: The efficacy and safety of ultrasound-guided percutaneous laser ablation (PLA) for treating recurrent papillary thyroid cancer nodules (RPTCNs). Methods: A retrospective study was conducted in 43 patients with single recurrent thyroid cancer which was diagnosed by fine needle aspiration biopsy (FNAB). The extent of ablation was assessed by contrast-enhanced ultrasound (CEUS) 24h after PLA. At baseline (before ablation), 6, and 12 months, and every 6 months thereafter, the following were recorded: nodule maximum diameter, volume reduction rate (VRR), complications, and side effects. Result: All 43 patients were successfully treated with PLA without serious complications. All patients underwent CEUS 24 hours after PLA treatment, and all achieved complete ablation. The success rate of single ablation was 100%. The average follow-up time was 23.47 ± 6.50 months, 12 ~ 36 months. At the last follow-up, 32 (74.4%) ablation lesions disappeared completely and 11 (25.6%) ablation lesions showed scar-like changes. No lymph node metastasis was found during follow-up. The maximum diameter and volume of nodules decreased from 5.1 ± 1.4 mm, 86.22 ± 20.46 mm3 before operation to 0.73 ± 1.1 mm, 1.02 ± 1.92 mm3 at the end of observation (P < 0.01). The average volume reduction rates (VRR) at 6, 12, 18, 24, 30 and 36 months after ablation were 11.92%, 60.64%, 82.26%, 90.96%, 93.7% and 97.79% respectively. No regrowth of treated nodule and distant metastases were detected. One patient (2.3%) had local recurrence and was treated with PLA again. Conclusion: Ultrasound-guided PLA appears to be effective and safe for treating unifocal RPTCNs in selected patients who are ineligible for surgery, which is suitable for clinical application and promotion.

Using Human Induced Pluripotent Stem Cell-Derived Organoids to Identify New Pathologies in Patients With PDX1 Mutations.

BACKGROUND & AIMS: Two patients with homozygous mutations in PDX1 presented with pancreatic agenesis, chronic diarrhea, and poor weight gain, the causes of which were not identified through routine clinical testing. We aimed to perform a deep analysis of the stomach and intestine using organoids derived from induced pluripotent stem cells from PDX1188delC/188delC patients. METHODS: Gastric fundic, antral, and duodenal organoids were generated using induced pluripotent stem cell lines from a PDX1188delC/188delC patient and an isogenic induced pluripotent stem cell line where the PDX1 point mutation was corrected. RESULTS: Patient-derived PDX1188delC/188delC antral organoids exhibited an intestinal phenotype, whereas intestinal organoids underwent gastric metaplasia with significant reduction in enteroendocrine cells. This prompted a re-examination of gastric and intestinal biopsy specimens from both PDX1188delC/188delC patients, which recapitulated the organoid phenotypes. Moreover, antral biopsy specimens also showed increased parietal cells and lacked G cells, suggesting loss of antral identity. All organoid pathologies were reversed upon CRISPR-mediated correction of the mutation. CONCLUSIONS: These patients will now be monitored for the progression of metaplasia and gastrointestinal complications that might be related to the reduced gastric and intestinal endocrine cells. This study demonstrates the utility of organoids in diagnosing uncovered pathologies.

Oxygen-rich ligands tailored for novel metal-organic gel electrocatalyst to promote two-electron selectivity electrocatalysis.

More extensive attention has been garnered about the H2O2 electroproduction via two-electron oxygen reduction reaction (2e- ORR). Aiming to develop a more active, more selective and more stable catalyst, herein we reported an unconventional raw metal-organic gels (MOGs) toward this process. This pioneering work, by ingeniously designing and altering the precursor ligands, achieving precisely controlling the number of oxygen groups (OGs). By elaborately comparing more than 70 samples, uncovered the significance that OGs could sufficiently promote the selectivity for H2O2 electrochemical synthesis through the two-electron pathway (realizing enhancement more than 20% in this work). The most potential Fe0.1Co0.9 MOG (H6L), performing an onset potential of 0.76 V (low overpotential), a high selectivity up to 93% ranging 0.15 V to 0.65 V (large voltage window) and 2.1 electron transfer number (implying the 2e- process dominate). This study, unlike other oxidation treatment, through the precise regulation of precursors, further confirmed the feasibility of oxygen-containing functional groups (OGs) tailoring strategy, providing a possibility for low-cost and efficient potential candidate of 2e- ORR.

Reinforced concrete inspired Si/rGO/cPAN hybrid electrode: highly improved lithium storage via Si electrode nanoarchitecture engineering.

Electrode nanoarchitecture engineering is a transformative way to improve the structural stability and build robust transport charge pathways for high-capacity silicon in lithium ion batteries (LIBs). However, the violent expansion of silicon during the lithiation/delithiation process is the chief reason for its limited industrialization. Here, we fabricated an integrated electrode structure using polyacrylonitrile (PAN) and graphene oxide (GO) inspired by reinforced concrete. Based on low-temperature annealing, cyclized PAN was assembled on the surface of silicon nanoparticles and tightly combined with reduced graphene oxide (rGO), which could construct stable and efficient transport channels for electrons and lithium ions and address the issues of electrode structure and interface stability. The resultant Si/rGO/cPAN (RC-Si) as the LIB anode exhibits exceptional combined performances including extraordinary mechanical properties, excellent cycling stability (∼1150 mA h g-1 at 2 A g-1 over 500 cycles), superior rate capability (∼600 mA h g-1 at 12 A g-1), and high areal capacity (∼5.6 mA h cm-2 at 0.5 mA cm-2). The novel electrode design concept is promising to promote the practical application of silicon anodes and open a new avenue to develop other high-capacity anodes for high-performance batteries.

A novel tissue-mimicking phantom for US/CT/MR-guided tumor puncture and thermal ablation.

AIM: This study aimed to develop a novel tumor-bearing tissue phantom model that can be used for US/CT/MR-guided tumor puncture and thermal ablation. METHODS: The phantom model comprised two parts: a normal tissue-mimicking phantom and a tumor-mimicking phantom. A normal tissue phantom was prepared based on a polyacrylamide gel mixed with thermochromic ink. Moreover, a spherical phantom containing contrast agents was constructed and embedded in the tissue phantom to mimic a tumor lesion. US/CT/MR imaging features and thermochromic property of the phantom model were characterized. Finally, the utility of the phantom model for imaging-guided microwave ablation training was examined. RESULTS: The tumor phantom containing contrast agents showed hyper-echogenicity, higher CT numbers, and lower T2 signal intensity compared with the normal tissue phantom in US/CT/MR images. Consequently, we could locate the position of the tumor in US/CT/MR imaging and perform an imaging-guided tumor puncture. When the temperature reached the threshold of 60 °C, the phantom exhibited a permanent color change from cream white to magenta. Based on this obvious color change, our phantom model could clearly map the thermal ablation region after thermotherapy. CONCLUSIONS: We developed a novel US/CT/MR-imageable tumor-bearing tissue model that can be used for imaging-guided tumor puncture and thermal ablation. Furthermore, it allows visual assessment of the ablation region by analyzing the obvious color change. Overall, this phantom model could be a good training tool in the field of thermal ablation.

A template oriented one-dimensional Schiff-base polymer: towards flexible nitrogen-enriched carbonaceous electrodes with ultrahigh electrochemical capacity.

Lithium-ion capacitors (LICs) have attracted much attention considering their efficient combination of high energy density and high-power density. However, to meet the increasing requirements of energy storage devices and the flexible portable electronic equipment, it is still challenging to develop flexible LIC anodes with high specific capacity and excellent rate capability. Herein, we propose a delicate bottom-up strategy to integrate unique Schiff-base-type polymers into desirable one-dimensional (1D) polymeric structures. A secondary-polymerization-induced template-oriented synthesis approach realizes the 1D integration of Schiff-base porous organic polymers with appealing characteristics of a high nitrogen-doping level and developed pore channels, and a further thermalization yields flexible nitrogen-enriched carbon nanofibers with high specific capacity and fast ion transport. Remarkably, when used as the flexible anode in LICs, the NPCNF//AC LIC demonstrates a high energy density of 154 W h kg-1 at 500 W kg-1 and a high power density of 12.5 kW kg-1 at 104 W h kg-1. This work may provide a new scenario for synthesizing 1D Schiff-base-type polymer derived nitrogen-enriched carbonaceous materials towards promising free-standing anodes in LICs.