Fibrotic immune microenvironment remodeling mediates superior anti-tumor efficacy of a nano-PD-L1 trap in hepatocellular carcinoma.

The local microenvironment where tumors develop can shape cancer progression and therapeutic outcome. Emerging evidence demonstrate that the efficacy of immune-checkpoint blockade (ICB) is undermined by fibrotic tumor microenvironment (TME). The majority of hepatocellular carcinoma (HCC) develops in liver fibrosis, in which the stromal and immune components may form a barricade against immunotherapy. Here, we report that nanodelivery of a programmed death-ligand 1 (PD-L1) trap gene exerts superior efficacy in treating fibrosis-associated HCC when compared with the conventional monoclonal antibody (mAb). In two fibrosis-associated HCC models induced by carbon tetrachloride and a high-fat, high-carbohydrate diet, the PD-L1 trap induced significantly larger tumor regression than mAb with no evidence of toxicity. Mechanistic studies revealed that PD-L1 trap, but not mAb, consistently reduced the M2 macrophage proportion in the fibrotic liver microenvironment and promoted cytotoxic interferon gamma (IFNγ)+tumor necrosis factor α (TNF-α)+CD8+T cell infiltration to the tumor. Moreover, PD-L1 trap treatment was associated with decreased tumor-infiltrating polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) accumulation, resulting in an inflamed TME with a high cytotoxic CD8+T cell/PMN-MDSC ratio conductive to anti-tumor immune response. Single-cell RNA sequencing analysis of two clinical cohorts demonstrated preferential PD-L1 expression in M2 macrophages in the fibrotic liver, thus supporting the translational potential of nano-PD-L1 trap for fibrotic HCC treatment.

Photocatalytic Formamide Synthesis via Coupling of Electrophilic and Nucleophilic Radicals over Atomically Dispersed Bi Sites.

Formamide (HCONH2) plays a pivotal role in the manufacture of a diverse array of chemicals, fertilizers, and pharmaceuticals. Photocatalysis holds great promise for green fabrication of carbon-nitrogen (C-N) compounds owing to its environmental friendliness and mild redox capability. However, the selective formation of the C-N bond presents a significant challenge in the photocatalytic synthesis of C-N compounds. This work developed a photocatalytic radical coupling method for the formamide synthesis from co-oxidation of ammonia (NH3) and methanol (CH3OH). An exceptional formamide yield rate of 5.47 ± 0.03 mmol·gcat-1·h-1 (911.87 ± 0.05 mmol·gBi-1·h-1) was achieved over atomically dispersed Bi sites (BiSAs) on TiO2. An accumulation of 45.0 mmol·gcat-1 (0.2 g·gcat-1) of formamide was achieved after long-term illumination, representing the highest level of photocatalytic C-N compounds synthesis. The critical C-N coupling for formamide formation originated from the "σ-σ" interaction between electrophilic ●CH2OH with nucleophilic ●NH2 radical. The  BiSAs sites facilitated the electron transfer between reactants and photocatalysts and enhanced the nucleophilic attack of â—NH2 radical at the â—CH2OH radical, thereby advancing the selective C-N bond formation. This work deepens the understanding of the C-N coupling mechanism and offers an alternative and intriguing photocatalytic approach for the efficient and sustainable production of C-N compounds.

Targeting PPAR-gamma counteracts tumour adaptation to immune-checkpoint blockade in hepatocellular carcinoma.

OBJECTIVE: Therapy-induced tumour microenvironment (TME) remodelling poses a major hurdle for cancer cure. As the majority of patients with hepatocellular carcinoma (HCC) exhibits primary or acquired resistance to antiprogrammed cell death (ligand)-1 (anti-PD-[L]1) therapies, we aimed to investigate the mechanisms underlying tumour adaptation to immune-checkpoint targeting. DESIGN: Two immunotherapy-resistant HCC models were generated by serial orthotopic implantation of HCC cells through anti-PD-L1-treated syngeneic, immunocompetent mice and interrogated by single-cell RNA sequencing (scRNA-seq), genomic and immune profiling. Key signalling pathway was investigated by lentiviral-mediated knockdown and pharmacological inhibition, and further verified by scRNA-seq analysis of HCC tumour biopsies from a phase II trial of pembrolizumab (NCT03419481). RESULTS: Anti-PD-L1-resistant tumours grew >10-fold larger than parental tumours in immunocompetent but not immunocompromised mice without overt genetic changes, which were accompanied by intratumoral accumulation of myeloid-derived suppressor cells (MDSC), cytotoxic to exhausted CD8+ T cell conversion and exclusion. Mechanistically, tumour cell-intrinsic upregulation of peroxisome proliferator-activated receptor-gamma (PPARγ) transcriptionally activated vascular endothelial growth factor-A (VEGF-A) production to drive MDSC expansion and CD8+ T cell dysfunction. A selective PPARγ antagonist triggered an immune suppressive-to-stimulatory TME conversion and resensitised tumours to anti-PD-L1 therapy in orthotopic and spontaneous HCC models. Importantly, 40% (6/15) of patients with HCC resistant to pembrolizumab exhibited tumorous PPARγ induction. Moreover, higher baseline PPARγ expression was associated with poorer survival of anti-PD-(L)1-treated patients in multiple cancer types. CONCLUSION: We uncover an adaptive transcriptional programme by which tumour cells evade immune-checkpoint targeting via PPARγ/VEGF-A-mediated TME immunosuppression, thus providing a strategy for counteracting immunotherapeutic resistance in HCC.

Functional characterization of GATA6 genetic variants associated with mild congenital heart defects.

Damaging GATA6 variants can cause moderate congenital heart defects. With the application of next-generation sequencing approaches, various novel GATA6 variants with unknown significance have been identified from a broad spectrum of congenital heart defects. However, functional assessment for distinct GATA6 variants from different severity of congenital heart defects, especially from mild defects, is lacking, which hinders our understanding of the genotype-phenotype correlations and underlying mechanisms. Here, we assessed the functional consequences of nine rare GATA6 variants, which had been implicated as the most significant variants associated with mild congenital heart defects using the largest case and control cohort. We examined the effects of these variants on subcellular localization, transcriptional activity, and protein interactions in 293T or AC16 cells and their ability to rescue heart malformation in gata6 zebrafish mutant. We found that two of these nine variants, Q120X and S424I, significantly decreased transcriptional activity. Additionally, Q120X altered subcellular localization. Consistent with the in vitro results, the in vivo results showed that Q120X and S424I lost their potency to rescue ventricular malformation in gata6 -/- embryos. The results indicated that Q120X and S424I are pathogenic in mild congenital heart defects. Further, the inconsistence of severely impaired Q120X function and mild CHDs phenotype suggested the complexity of the genotype-phenotype correlation between the GATA6 variant and heart phenotype, which may help to inform prenatal genetic counseling and pre-implantation genotyping for congenital heart defects.

Vacancy-Mediated Control of Local Electronic Structure for High-Efficiency Electrocatalytic Conversion of N2 to NH3.

Ambient electrocatalytic nitrogen (N2 ) reduction has gained significant recognition as a potential substitute for producing ammonia (NH3 ). However, N2 adsorption and *NN protonation for N2 activation reaction with the competing hydrogen evolution reaction remain a daunting challenge. Herein, a defect-rich TiO2 nanosheet electrocatalyst with PdCu alloy nanoparticles (PdCu/TiO2-x ) is designed to elucidate the reactivity and selectivity trends of N2 cleavage path for N2 -to-NH3 catalytic conversion. The introduction of oxygen vacancy (OV) not only acts as active sites but also effectively promotes the electron transfer from Pd-Cu sites to high-concentration Ti3+ sites, and thus lends to the N2 activation via electron donation of PdCu. OVs-mediated control effectively lowers the reaction barrier of *N2 H and *H adsorption and facilitates the first hydrogenation process of N2 activation. Consequently, PdCu/TiO2-x catalyst attains a high rate of NH3 evolution, reaching 5.0 mmol gcat. -1  h-1 . This work paves a pathway of defect-engineering metal-supported electrocatalysts for high-efficient ammonia electrosynthesis.

Electrochemical Synthesis of Copper Mesh-Supported Thermo-Catalysts.

Metallic substrates, widely studied in the context of monolithic catalysts, offer inherent advantages in heterogeneous catalysis due to their exceptional thermal conductivity and mechanical properties. However, synthesizing stable monolithic catalysts with metallic substrates in a well-controlled manner remains a significant challenge. Here, this work introduces a simple, cost-efficient method to fabricate robust Cu mesh-supported thermo-catalysts using a modified cycling chronopotentiometry approach, where the Cu mesh serves as a donor of Cu ions. In this method, the Cu mesh surface generates two distinct layers of CuO and Cu2 O. In this context, CuO acts as the active phase, accounting for the high CO oxidation activity of Cu mesh catalysts with T90 ≈ 120 °C. Additionally, these catalysts exhibit considerable potential in electrocatalysis, showcasing significant research and application value.

Capillary-force-assisted self-assembly of gold nanoparticles into highly ordered plasmonic thin films for ultrasensitive SERS.

In this study, a capillary device based on the surface plasmon-enhanced Raman scattering effect was prepared by a simple and easy method. First, the capillary was treated with APTES solution. Due to the electrostatic effect, gold nanoparticles could be easily and tightly assembled in the capillary inner wall. On this basis, the effects of changing the concentration of APTES, the concentration of colloids and the soaking time of the capillary in the colloids on the assembly of gold nanoparticles on the inner wall of the capillary were studied, and the SERS enhancement effect under different conditions was analyzed, and the optimal solution was successfully found. At the same time, the reason why the capillary substrate shows better SERS performance than the traditional planar substrate is deeply discussed. Since the nanoparticles can be attached to the upper and lower surfaces of the inner wall of the capillary, the utilization rate of nanoparticles and laser is improved, thereby achieving higher enhancement. For the detection of the probe molecule rhodamine 6G, it was proved that the substrate has good uniformity and the lowest detection limit can reach 10-10 M. Finally, the real-life pesticide thiram and the food additive aspartame were tested, and the detection limits could reach 10-6 M and 0.25 g L-1. It is confirmed that the prepared capillary shows excellent SERS performance and can be used for rapid detection in various fields.

Low-cost and flexible paper-based plasmonic nanostructure for a highly sensitive SERS substrate.

The application of a noble-metal-based plasmon-enhanced substrate to detect low-concentration analytes has attracted extensive attention. Most of the substrates used in recently reported researches are based on two-dimensional structures. Hence, we prepared a higher efficiency Raman activity substrate with a filter paper structure, which not only provides more plasmonic "hot spots," but also facilitates analyte extraction and detection due to the flexibility of the paper. The preparation of the plasmonic paper substrate adopted centrifugation to deposit the alloy nanoparticles onto the paper base. The optimal particle deposition condition was found by adjusting the centrifugal force and centrifugation time. Then, the surface-enhanced Raman spectroscopy (SERS) performance of the substrate was enhanced by altering the plasmon resonance peak on the surface of the nanoparticles. The enhancement factor of this paper-based substrate was 1.55×107, with high detection uniformity (10-6 M, rhodamine 6G) and a low detection limit (10-11 M, rhodamine 6G). Then, we applied the SERS substrate to pesticide detection; the detection limit of the thiram reached 10-6 M. As a result, the simple and cost-effective paper-based SERS substrate obtained in this way has high detection performance for pesticides and can be used for rapid detection in the field, which is beneficial to food safety and environmental safety.

Plaque enhancement predicts recurrence in acute ischemic stroke patients with large artery intracranial atherosclerosis.

BACKGROUND: The association between the degree of plaque enhancement and ischemic brain stroke recurrence remains unclear. We aimed to establish models to predict plaque enhancement and stroke recurrence. METHODS: Seventy-eight participants with acute ischemic brain stroke due to intracranial arterial stenosis were recruited and divided into high enhancement (HE) and non-HE groups. The relationship between imaging characteristics (degree of stenosis, minimal lumen area, intraplaque hemorrhage, and plaque burden) and the degree of plaque contrast enhancement was analyzed. Inflammatory cytokine expression was examined by flow cytometry. Independent predictors of stroke recurrence were investigated via multivariate Cox proportional hazards regression analysis. Nomogram was used to construct a prediction model. Harrell's concordance indices (c-indices) and calibration curves were used to assess the discrimination of the nomogram. A risk prediction nomogram for prognosis was constructed. RESULTS: Thirty-three participants were assigned to the HE group and 45 to the non-HE group. The degree of stenosis and plaque burden in the HE group was higher than that in the non-HE group (P<0.05). Multiple linear regression analysis showed the degree of stenosis was associated with HE (ß=0.513; P=0.000). After adjusting for confounding factors, age (HR=1.115; 95%CI=1.034-1.203, P=0.005) and HE plaques (HR=10.457; 95%CI=1.176-93.018; P=0.035) were independent risk factors of stroke recurrence, whereas cytokine levels were not statistically significant between two group. CONCLUSIONS: HE of intracranial atherosclerosis plaques is an independent factor for ischemic brain stroke recurrence.

Experimental Study on the Incipient Movement of Muddy Clay under Different Salinity Conditions.

In order to understand the incipient movement of muddy clay under different salinity conditions, three series of flume tests were performed on incipient movement of muddy clay, including tests on incipient movement of salt-free clay mud under salt water conditions (salt water-salt-free clay mud), incipient movement of salt clay mud under salt water conditions (salt water-salt clay mud), and incipient movement of salt clay mud under freshwater conditions (freshwater-salt clay mud), using a circulating flume, in which the salinity of the water body or cohesive sediment varies from 0 to 40%. Based on the particle image velocimetry system and digital image gray processing technology, the gray curves of water near the clay mud bed surface with the velocity were plotted to quantitatively differentiate the incipient velocity of the sediment for each test. The experimental results showed that the higher the salinity of the water body or cohesive sediments is, the more difficult it is to start moving. There is a logarithmic relationship between the incipient velocity of cohesive sediments and the salinity of the water or cohesive sediments. The incipient velocity increases sharply at a salinity of 0∼10% and slowly at a salinity of 10∼40%. At the same salinity, the incipient velocity of salt clay mud under freshwater conditions is the largest, followed by that of salt clay mud under salt water conditions, while that of salt-free clay mud under salt water conditions is the smallest. In addition, the flow turbulence characteristics were analyzed under the critical conditions of the onset of muddy clay. Ultimately, an empirical formula to calculate the critical incipient velocity of muddy clay is proposed by introducing the salinity. In this study, salinity is included as a reference variable, which expands the research scope of sediment initiation and provides a reference for the study of estuary dynamics.

Mapping of critical events in disease progression through binary classification: Application to amyotrophic lateral sclerosis.

BACKGROUND: The progression of many degenerative diseases is tracked periodically using scales evaluating functionality in daily activities. Although estimating the timing of critical events (i.e., disease tollgates) during degenerative disease progression is desirable, the necessary data may not be readily available in scale records. Further, analysis of disease progression poses data challenges, such as censoring and misclassification errors, which need to be addressed to provide meaningful research findings and inform patients. METHODS: We developed a novel binary classification approach to map scale scores into disease tollgates to describe disease progression leveraging standard/modified Kaplan-Meier analyses. The approach is demonstrated by estimating progression pathways in amyotrophic lateral sclerosis (ALS). Tollgate-based ALS Staging System (TASS) specifies the critical events (i.e., tollgates) in ALS progression. We first developed a binary classification predicting whether each TASS tollgate was passed given the itemized ALSFRS-R scores using 514 ALS patients' data from Mayo Clinic-Rochester. Then, we utilized the binary classification to translate/map the ALSFRS-R data of 3,264 patients from the PRO-ACT database into TASS. We derived the time trajectories of ALS progression through tollgates from the augmented PRO-ACT data using Kaplan-Meier analyses. The effects of misclassification errors, condition-dependent dropouts, and censored data in trajectory estimations were evaluated with Interval Censored Kaplan Meier Analysis and Multistate Model for Panel Data. RESULTS: The approach using Mayo Clinic data accurately estimated tollgate-passed states of patients given their itemized ALSFRS-R scores (AUCs > 0.90). The tollgate time trajectories derived from the augmented PRO-ACT dataset provide valuable insights; we predicted that the majority of the ALS patients would have modified arm function (67%) and require assistive devices for walking (53%) by the second year after ALS onset. By the third year, most (74%) ALS patients would occasionally use a wheelchair, while 48% of the ALS patients would be wheelchair-dependent by the fourth year. Assistive speech devices and feeding tubes were needed in 49% and 30% of the patients by the third year after ALS onset, respectively. The onset body region alters some tollgate passage time estimations by 1-2 years. CONCLUSIONS: The estimated tollgate-based time trajectories inform patients and clinicians about prospective assistive device needs and life changes. More research is needed to personalize these estimations according to prognostic factors. Further, the approach can be leveraged in the progression of other diseases.

Hanshiyi Formula, a medicine for Sars-CoV2 infection in China, reduced the proportion of mild and moderate COVID-19 patients turning to severe status: A cohort study.

We formulated a traditional Chinese medicine (TCM) prescription, Hanshiyi Formula (HSYF), which was approved and promoted by the Wuhan Municipal Health Commission for treating mild and moderate coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of HSYF on the progression to severe disease in mild and moderate COVID-19 patients. We conducted a retrospective cohort study of patients with mild and moderate COVID-19 in a quarantine station in Wuchang District, Wuhan. Using the real-time Internet information collection application and Centers for Disease Control for the Wuchang District, patient data were collected through patient self-reports and follow-ups. HSYF intervention was defined as the exposure. The primary outcome was the proportion of patients who progressed to a severe disease status, and a stratification analysis was performed. Univariate and multivariate regression analyses were performed to identify influencing factors that may affect the outcome. Further, we used propensity score matching (PSM) to assess the effect of HSYF intervention on the conversion of mild and moderate to a severe disease status. Totally, 721 mild and moderate COVID-19 patients were enrolled, including 430 HSYF users (exposed group) and 291 non-users (control group). No cases in the exposed group and 19 (6.5 %, P < 0.001) cases in the control group progressed to severe disease, and the difference between the two groups (exposed group-control group) was -6.5 % [95 % confidence interval (CI): (-8.87 %, -4.13 %)]. Univariate regression analysis revealed sex (male), age, fever, cough, and fatigue as risk factors for progression to severe disease. After PSM, none of the HSYF users and 7 (4.7 %, P = 0.022) non-users transitioned to severe disease, and the difference between the two groups (exposed group-control group) was -4.7 % [95 % CI: (-8.2 %, -1.2 %)]. Multivariate regression analysis revealed that sex (male) [OR: 3.145; 95 % CI: 1.036-9.545; P = 0.043] and age (> 48 years) [odds ratio (OR): 1.044; 95 % CI: 1.001-1.088; P = 0.044] were independent risk factors for conversion to severe disease. Therefore, HSYF can significantly reduce the progression to severe disease in patients with mild and moderate COVID-19, which may effectively prevent and treat the disease. However, further larger clinical studies are required to verify our results.

Efficacy of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in treatment of COVID-19: A randomized controlled trial.

BACKGROUND: With the global epidemic of coronavirus disease (COVID-19), China has made progress in the prevention and control of the epidemic, and traditional Chinese medicine (TCM) has played a key role in dealing with the disease's effects on the respiratory system. This randomized controlled clinical trial evaluated the clinical efficacy and prognosis of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in patients with COVID-19. METHODS: A total of 283 patients participated in this clinical trial, and participants were randomly assigned to receive either 1) Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules or 2) Linahua granules, both combined with western medicine, or 3) western medicine alone for 14 days. At the end of the trial, the improvement and resolution rates of clinical symptoms and the rate of patients who progressed to severe disease status were evaluated. RESULTS: After 14 days of treatment, there was no significant difference in the improvement rate of clinical symptoms among the three groups (P > 0.05). Huoxiang Zhengqi dropping pills combined with Lianhua Qingwen granules has advantages in the treatment of nausea, vomiting and limb soreness. During treatment, all participants were treated with western medicine, and there was a significant difference in the use of macrolides among the three groups (P < 0.05). Specifically, the utilization rate of antibiotics in the western medicine group was significantly greater than that of the other two groups. Among the 182 diagnosed patients who completed this clinical trial, 13 patients progressed to severe disease, including one case in the Huoxiang + Lianhua group (1.6 %), five cases in the Lianhua group (8.6 %), and seven cases in the western medicine group (11.1 %). There was no statistical differences in this rate among the three groups (P > 0.05). However, the proportion of patients who progressed to severe disease in the Huoxiang + Lianhua group was the lowest, suggesting that the combination of TCM with western medicine has a potential advantage in improving the prognosis of patients with COVID-19. CONCLUSION: The use of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules combined with western medicine may have clinical advantages for COVID-19 patients in improving clinical symptoms, reducing utilization rate of anti-infective drugs, and improving patient prognosis, which could pave the way for the use of complementary medicine in treating this infection.

Ambient Reductive Amination of Levulinic Acid to Pyrrolidones over Pt Nanocatalysts on Porous TiO2 Nanosheets.

Construction of N-substituted pyrrolidones from biomass-derived levulinic acid (LA) via reductive amination is a highly attractive route for biomass valorization. However, realizing this transformation using H2 as the hydrogen source under mild conditions is still very challenging. Herein, we designed porous TiO2 nanosheets-supported Pt nanoparticles (Pt/P-TiO2) as the heterogeneous catalyst. The prepared Pt/P-TiO2 was highly efficient for reductive amination of LA to produce various N-substituted pyrrolidones (34 examples) at ambient temperature and H2 pressure. Meanwhile, Pt/P-TiO2 showed good applicability for reductive amination of levulinic esters, 4-acetylbutyric acid, 2-acetylbenzoic acid, and 2-carboxybenzaldehyde. Systematic studies indicated that the strong acidity of P-TiO2 and the lower electron density of the Pt sites as well as the porous structure resulted in the excellent activity of Pt/P-TiO2.

Hierarchical quality-guided phase unwrapping algorithm.

A hierarchical quality-guided phase unwrapping algorithm in a shared memory environment is proposed. First, the wrapped phase is divided into regular blocks, and local wrap counts of every block are obtained by a quality-guided strategy. Then, the gradient of the block wrap counts of adjacent blocks and the quality of every block are defined by the boundary local wrap counts of every block. Each block's data can be regarded as an abstract phase point, and the quality-guided strategy can be used again to solve the block wrap counts of each block. Finally, the absolute wrap counts of each phase point are obtained by adding local wrap counts and corresponding block wrap counts, and then the final unwrapped phase is obtained. The performance of the proposed algorithm is verified through an unwrapping experiment performed on simulated data and the real interferometric synthetic aperture sonar wrapped phase in a shared memory environment. The results show that the proposed method greatly improves phase unwrapping efficiency while maintaining the correctness of unwrapped results.

Innate Lymphoid Cells: A Link between the Nervous System and Microbiota in Intestinal Networks.

Innate lymphoid cells (ILCs) are a novel family of innate immune cells that act as key coordinators of intestinal mucosal surface immune defense and are essential for maintaining intestinal homeostasis and barrier integrity by responding to locally produced effector cytokines or direct recognition of exogenous or endogenous danger patterns. ILCs are also involved in the pathogenesis of inflammatory bowel disease (IBD). Many studies have demonstrated the occurrence of crosstalk between ILCs and intestinal microbiota, and ILCs have recently been shown to be connected to the enteric nervous system (ENS). Thus, ILCs may act as a key link between the nervous system and microbiota in intestinal networks. In this review, we briefly summarize the role of the ILCs in the intestinal tract (particularly in the context of IBD) and discuss the relationship between ILCs and the microbiota/ENS.

Intestinal Immunomodulatory Cells (T Lymphocytes): A Bridge between Gut Microbiota and Diabetes.

Diabetes mellitus (DM) is one of the most familiar chronic diseases threatening human health. Recent studies have shown that the development of diabetes is closely related to an imbalance of the gut microbiota. Accordingly, there is increasing interest in how changes in the gut microbiota affect diabetes and its underlying mechanisms. Immunomodulatory cells play important roles in maintaining the normal functioning of the human immune system and in maintaining homeostasis. Intestinal immunomodulatory cells (IICs) are located in the intestinal mucosa and are regarded as an intermediary by which the gut microbiota affects physiological and pathological properties. Diabetes can be regulated by IICs, which act as a bridge linking the gut microbiota and DM. Understanding this bridge role of IICs may clarify the mechanisms by which the gut microbiota contributes to DM. Based on recent research, we summarize this process, thereby providing a basis for further studies of diabetes and other similar immune-related diseases.

A Correction Approach for the Inclined Array of Hydrophones in Synthetic Aperture Sonar.

A correction approach for the inclined array of hydrophones is proposed to prevent decline of the image quality in SAS. In this approach, the 2-way exact acoustic propagation path of the inclined array is transformed into the sum of a single root term and an offset term, where the single root term is the 2-way ideal propagation path and the offset term contains all errors cause by the inclined array. The correction for the offset term is separated into two steps: phase correction and delay correction. The phase correction is performed on the echo signal of each receiving hydrophone in the 2-D time domain by a phase multiplication and the delay correction is performed on the echo signal of each receiving hydrophone in the range frequency domain by a phase multiplication with a linear function of range frequency at the reference range. Finally, the effectiveness of the proposed approach is examined by the simulation experiments.

Involvement of VKORC1 in the inhibition of calcium oxalate crystal formation in HK-2 cells.

The vitamin K epoxide reductase complex subunit 1 (VKORC1), the rate-limiting enzyme for vitamin K recycling, is significantly down-regulated in the kidneys of urolithiasis patients. This study searched for direct evidence to define the inhibitory activity of VKORC1 against calcium oxalate (CaOx) crystal formation. In the experiment of VKORC1 overexpression, HK-2 cells were transfected with the pFLAG-CMV-7.1-VKORC1 plasmid as a pFLAG-CMV-7.1-VKORC1 transfection group or the pFLAG-CMV-7.1 plasmid as a pFLAG-CMV-7.1 control group. In the experiment of VKORC1 knockdown, HK-2 cells were transfected with the PGPU6/GFP/Neo-VKORC1shRNA-2 as a PGPU6/GFP/Neo-VKORC1shRNA-2 transfection group or the PGPU6/GFP/Neo-shRNA-NC plasmid as a PGPU6/GFP/Neo-shRNA-NC control group. The expression of VKORC1 in HK-2 cells was detected by real-time quantitative PCR and Western blotting. The CaOx crystal formation was observed under the laser-scanning confocal microscope. It was found that the expression levels of VKORC1 mRNA and protein were significantly higher in the pFLAG-CMV-7.1-VKORC1 transfection group than in the pFLAG-CMV-7.1 control group (P<0.01). The number of CaOx crystals in HK-2 cells incubated in fluorescently labeled CaOx monohydrate (COM) crystal medium for 48 h was 14±4 per field (100×) in the pFLAG-CMV-7.1-VKORC1 transfection group and 26±5 per field (100×) in the pFLAG-CMV-7.1 control group respectively under the laser-scanning confocal microscope. The amount of CaOx crystal aggregation and formation in the pFLAG-CMV-7.1-VKORC1 transfection group was significantly reduced as compared with the pFLAG-CMV-7.1 control group (P<0.05). The expression levels of VKORC1 mRNA and protein were significantly lower in the PGPU6/GFP/Neo-VKORC1shRNA-2 transfection group than in the PGPU6/GFP/Neo-shRNA-NC control group (P<0.05). The number of CaOx crystals in HK-2 cells incubated in fluorescently labeled COM crystal medium was 65±11 per field (100×) in the PGPU6/GFP/Neo-VKORC1shRNA-2 transfection group and 24±6 per field (100×) in the PGPU6/GFP/Neo-shRNA-NC control group respectively under the laser-scanning confocal microscope. The amount of CaOx crystal aggregation and formation in the PGPU6/GFP/Neo-VKORC1shRNA-2 transfection group was significantly increased as compared with the PGPU6/GFP/Neo-shRNA-NC control group (P<0.05). These findings suggested that the VKORC1 protein could inhibit CaOx salt crystallization, adhesion and aggregation. This research would help us to understand the mechanisms involving the interaction between crystallization and epithelial cells and the formation of CaOx.

Recent Progress on Durable Metal-N-C Catalysts for Proton Exchange Membrane Fuel Cells.

It is essential for the widespread application of proton exchange membrane fuel cells (PEMFCs) to investigate low-cost, extremely active, and long-lasting oxygen reduction catalysts. Initial performance of PGM-free metal-nitrogen-carbon (M-N-C) catalysts for oxygen reduction reaction (ORR) has advanced significantly, particularly for Fe-N-C-based catalysts. However, the insufficient stability of M-N-C catalysts still impedes their use in practical fuel cells. In this review, we focus on the understanding of the structure-stability relationship of M-N-C ORR catalysts and summarize valuable guidance for the rational design of durable M-N-C catalysts. In the first section of this review, we discuss the inherent degrading mechanisms of M-N-C catalysts, such as carbon corrosion, demetallation, H2 O2 attack, etc. As we gain a thorough comprehension of these deterioration mechanisms, we shift our attention to the investigation of strategies that can mitigate catalyst deterioration and increase its stability. These strategies include enhancing the anti-oxidation of carbon, fortifying M-N bonds, and maximizing the effectiveness of free radical scavengers. This review offers a prospective view on the enhancement of the stability of non-noble metal catalysts.