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Water electrolysis is an advanced energy conversion technology to produce hydrogen as a clean and sustainable chemical fuel, which potentially stores the abundant but intermittent renewable energy sources scalably. Since the overall water splitting is an uphill reaction in low efficiency, innovative breakthroughs are desirable to greatly improve the efficiency by rationally designing non-precious metal-based robust bifunctional catalysts for promoting both the cathodic hydrogen evolution and anodic oxygen evolution reactions. We report a hybrid catalyst constructed by iron and dinickel phosphides on nickel foams that drives both the hydrogen and oxygen evolution reactions well in base, and thus substantially expedites overall water splitting at 10 mA cm −2 with 1.42 V, which outperforms the integrated iridium (IV) oxide and platinum couple (1.57 V), and are among the best activities currently. Especially, it delivers 500 mA cm −2 at 1.72 V without decay even after the durability test for 40 h, providing great potential for large-scale applications. Water electrolysis provides a carbon-neutral means to generate hydrogen fuel from water, but the process typically requires expensive, rare metal catalysts. Here, the authors prepare hydrogen- and oxygen-evolving electrocatalysts from earth-abundant elements that outperform noble-metal counterparts.

Experiments have shown that graphene-supported Ni-single atom catalysts (Ni-SACs) provide a promising strategy for the electrochemical reduction of CO 2 to CO, but the nature of the Ni sites (Ni-N 2 C 2 , Ni-N 3 C 1 , Ni-N 4 ) in Ni-SACs has not been determined experimentally. Here, we apply the recently developed grand canonical potential kinetics (GCP-K) formulation of quantum mechanics to predict the kinetics as a function of applied potential (U) to determine faradic efficiency, turn over frequency, and Tafel slope for CO and H 2 production for all three sites. We predict an onset potential (at 10 mA cm −2 ) U onset  = −0.84 V (vs. RHE) for Ni-N 2 C 2 site and U onset  = −0.92 V for Ni-N 3 C 1 site in agreement with experiments, and U onset  = −1.03 V for Ni-N 4 . We predict that the highest current is for Ni-N 4 , leading to 700 mA cm −2 at U = −1.12 V. To help determine the actual sites in the experiments, we predict the XPS binding energy shift and CO vibrational frequency for each site. Single atom catalysts (SACs) are promising in electrocatalysis but challenging to characterize. Here, the authors apply a recently developed quantum mechanical grand canonical potential kinetics method to predict reaction mechanisms and rates for CO 2 reduction at different sites of graphene-supported Ni-SACs.

In the additive manufacturing (AM) process, dynamic fluctuations in process parameters often result in non-uniform grain sizes in the microstructures of fabricated components, which impairs their stability of mechanical performance. Consequently, the accurate identification of microstructures in AM titanium alloy components is essential for optimizing their mechanical reliability and prolonging their service life in engineering applications. An approach combining ultrasonic testing and deep learning is provided to address the demands for high efficiency and intelligent identification of diverse grain microstructures in AM titanium alloys. First, the Centroidal Voronoi Tessellations (CVT) algorithm was employed to construct three representative simulation models that replicate the characteristic grain microstructures of AM titanium alloys encompassing fine-grained, coarse-grained, and mixed-grained configurations. Subsequently, COMSOL Multiphysics software (v.6.3) was utilized to perform laser-induced ultrasonic Lamb wave (LIULW) testing simulations on the CVT-based microstructure models. Further, a comprehensive simulation dataset was established, including time-domain signals and their frequency-domain features of LIULW. This simulation dataset was then used to train a neural network with an improved architecture, aiming to enhance the discriminative capability for subtle differences in LIULW signals induced by varying grain sizes. Experimental validation results demonstrated that the proposed enhanced Lamb wave-DenseNet network achieved an overall recognition accuracy of 97.93% for the three distinct grain microstructure categories. Collectively, these findings confirm that the integrated method provides a robust theoretical framework and a practical technical solution for large-scale, engineering-level microstructure identification of AM titanium alloy components. This work not only bridges the gap between microstructural simulation and intelligent LIULW testing but also lays a foundation for quality control in high-volume AM of titanium alloy structural parts.

With the massive consumption of fossil fuels and its detrimental impact on the environment, methods of generating clean power are urgent. Hydrogen is an ideal carrier for renewable energy; however, hydrogen generation is inefficient because of the lack of robust catalysts that are substantially cheaper than platinum. Therefore, robust and durable earth-abundant and cost-effective catalysts are desirable for hydrogen generation from water splitting via hydrogen evolution reaction. Here we report an active and durable earth-abundant transition metal dichalcogenide-based hybrid catalyst that exhibits high hydrogen evolution activity approaching the state-of-the-art platinum catalysts, and superior to those of most transition metal dichalcogenides (molybdenum sulfide, cobalt diselenide and so on). Our material is fabricated by growing ternary molybdenum sulfoselenide particles on self-standing porous nickel diselenide foam. This advance provides a different pathway to design cheap, efficient and sizable hydrogen-evolving electrode by simultaneously tuning the number of catalytic edge sites, porosity, heteroatom doping and electrical conductivity. There is on-going research into efficient noble metal-free materials for electrocatalytic hydrogen evolution. Here, the authors prepare ternary molybdenum sulfoselenide particles supported on three-dimensional porous nickel selenide foam, and demonstrate the high efficiency of the hydrogen evolving composite.

High-temperature afterglow organic amorphous materials expand the operational temperature beyond traditional room-temperature phosphorescent materials, broadening their potential applications. However, achieving tunable high-temperature afterglow from a single luminescent molecule remains a formidable challenge. Here, we employ host-guest anchoring coupled with single-bond rotors to achieve effective phosphorescence and tunable afterglow at high temperature simultaneously. The material demonstrates a wavelength-tunable afterglow: during heating (298 K to 473 K), the chromaticity coordinate shifts from (0.24, 0.47) to (0.18, 0.20) and the lifetime from 836 ms to 6.34 ms. The theoretical investigations reveal that the excited-state conformation of phosphors undergoes a temperature-dependent transformation, inducing the wavelength-tunable high-temperature afterglow phenomenon. This work offers a strategy for designing tunable high-temperature afterglow-emitting amorphous polymers, advancing the development of organic phosphorescent materials capable of delivering tunable high-temperature afterglow emissions. ‘High temperature afterglow materials are of interest, though designing luminescent single molecules is a challenge. Here the authors use a host-guest system achieving phosphorescence and tuneable afterglow. ‘

Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors. In mouse CAR-T cells, IL-7 and CCL19 expression have been demonstrated to improve T cell infiltration and CAR-T cell survival in mouse tumors. Therefore, in the current study, we engineered human CAR-T cells to secrete human IL-7 and CCL19 (7 × 19) and found that these 7 × 19 CAR-T cells showed enhanced capacities of expansion and migration in vitro. Furthermore, 7 × 19 CAR-T cells showed superior tumor suppression ability compared to conventional CAR-T cells in xenografts of hepatocellular carcinoma (HCC) cell lines, primary HCC tissue samples and pancreatic carcinoma (PC) cell lines. We then initiated a phase 1 clinical trial in advanced HCC/PC/ovarian carcinoma (OC) patients with glypican-3 (GPC3) or mesothelin (MSLN) expression. In a patient with advanced HCC, anti-GPC3-7 × 19 CAR-T treatment resulted in complete tumor disappearance 30 days post intratumor injection. In a patient with advanced PC, anti-MSLN-7 × 19 CAR-T treatment resulted in almost complete tumor disappearance 240 days post-intravenous infusion. Our results demonstrated that the incorporation of 7 × 19 into CAR-T cells significantly enhanced the antitumor activity against human solid tumor. Trial registration: NCT03198546. Registered 26 June 2017, https://clinicaltrials.gov/ct2/show/NCT03198546?term=NCT03198546&draw=2&rank=1

Background Upregulation of an RNA-binding protein HuR has been implicated in glomerular diseases. Herein, we evaluated whether it is involved in renal tubular fibrosis. Methods HuR was firstly examined in human kidney biopsy tissue with tubular disease. Second, its expression and the effect of HuR inhibition with KH3 on tubular injury were further assessed in a mouse model induced by a unilateral renal ischemia/reperfusion (IR). KH3 (50 mg kg −1 ) was given daily via intraperitoneal injection from day 3 to 14 after IR. Last, one of HuR-targeted pathways was examined in cultured proximal tubular cells. Results HuR significantly increases at the site of tubular injury both in progressive CKD in patients and in IR-injured kidneys in mice, accompanied by upregulation of HuR targets that are involved in inflammation, profibrotic cytokines, oxidative stress, proliferation, apoptosis, tubular EMT process, matrix remodeling and fibrosis in renal tubulointerstitial fibrosis. KH3 treatment reduces the IR-induced tubular injury and fibrosis, accompanied by the remarkable amelioration in those involved pathways. A panel of mRNA array further revealed that 519 molecules in mouse kidney following IR injury changed their expression and 71.3% of them that are involved in 50 profibrotic pathways, were ameliorated when treated with KH3. In vitro, TGFβ1 induced tubular HuR cytoplasmic translocation and subsequent tubular EMT, which were abrogated by KH3 administration in cultured HK-2 cells. Conclusions These results suggest that excessive upregulation of HuR contributes to renal tubulointerstitial fibrosis by dysregulating genes involved in multiple profibrotic pathways and activating the TGFß1/HuR feedback circuit in tubular cells. Inhibition of HuR may have therapeutic potential for renal tubular fibrosis.

Background One goal of Anterior Cervical Discectomy and Fusion (ACDF) is to restore the loss of intervertebral disc height (IDH) results from the degenerative process. However, the effects of IDH on postoperative dysphagia after ACDF remain unclear. Methods Based on the results of a one-year telephone follow-up, A total of 217 consecutive patients after single-level ACDF were enrolled. They were divided into dysphagia and non-dysphagia groups. The age, BMI, operation time and blood loss of all patients were collected from the medical record system and compared between patients with and without dysphagia. Radiologically, IDH, spinous process distance (SP) of the operated segment, and C2-7 angle (C2-7 A) were measured preoperatively and postoperatively. The relationship between changes in these radiological parameters and the development of dysphagia was analyzed. Results Sixty-three (29%) cases exhibited postoperative dysphagia. The mean changes in IDH, SP, and C2-7 A were 2.84 mm, -1.54 mm, and 4.82 degrees, respectively. Changes in IDH ( P  = 0.001) and changes in C2-7 A ( P  = 0.000) showed significant differences between dysphagia and non-dysphagia patients. Increased IDH and increased C2-7 A ( P  = 0.037 and 0.003, respectively) significantly and independently influenced the incidence of postoperative dysphagia. When the change in IDH was ≥ 3 mm, the chance of developing postoperative dysphagia for this patient was significantly greater. No significant relationship was observed between the change in spinous process distance (SP) and the incidence of dysphagia. The age, BMI, operation time and blood loss did not significantly influence the incidence of postoperative dysphagia. Conclusion The change in IDH could be regarded as a predictive factor for postoperative dysphagia after single-level ACDF.

Background Intramedullary spinal cord metastasis (ISCM) of malignant tumors rarely happens. To the best of our knowledge, only five cases of ISCM from esophageal cancer have been reported in literature. We here report the sixth descripted case of ISCM from esophageal cancer. Case presentation A 68-year-old male presented with weakness of right limbs and localized neck pain two years after diagnosed esophageal squamous cell carcinoma. The gadolinium enhanced Magnetic resonance imaging (MRI) of cervical spine showed a mixed-intense intramedullary tumor with typical more intense thin rim of peripheral enhancement in C4-C5. The patient died fifteen days after diagnosis of irreversible respiratory and circulatory failures. An autopsy was refused by his family. Conclusions This case highlights the importance of gadolinium enhanced MRI for diagnosis in ISCM. We believe that early diagnosis and surgery for selected patients shows helpfulness to save their neurologic function and improve quality of life.

The antitumor effects of caudatin have been explored in multiple cancers, but the research on lung cancer has not been fully understood. We explored the effects of caudatin on non-small cell lung cancer (NSCLC) in vitro and in vivo. In the in vitro experiments, 0, 25, 50 and 100 μM of caudatin were selected to examine the effects on stemness and glycolysis. Subcutaneous tumour xenografts were constructed by injecting the nude mice (BALB/C) with 5 × 10 6 H1299 cells. In the in vivo experiments, all nude mice were divided into the caudatin group (50 mg/kg/day, n = 5) and the sham group (equal amount of DMSO, n = 5). The IC 50 of caudatin for H1299 and H520 cells was 44.68 μM and 69.37 μM, respectively. Compared with caudatin 0 μM group, cell apoptosis rate was increased about 10 times and cell stemness was decreased by 75-85% in caudatin 100 μM group. Glucose uptake (65-80% reduction), lactic acid production (75-80% reduction), ATP level (70-80% reduction) and the expression of HK2 and LDHA (75-85% reduction) were decreased in caudatin 100 μM group. The expression of Raf/MEK/ERK pathway related proteins was decreased to 20-25% by caudatin. Tumour weight (about 70% reduction) and the expression of stemness, glycolysis and Raf/MEK/ERK pathway related proteins (about 50-75% reduction) were suppressed by caudatin in vivo. We revealed that caudatin blocked stemness and glycolysis in NSCLC for the first time. More experiments about exact dosage of caudatin in vivo should be conducted.