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Dendritic organic molecular gels are a promising class of three-dimensional network compounds. Here, we have synthesized a new type of dendritic organic molecular gel stationary phase (SiO

The spatial spread of genetic material is fundamental to analyses of invasive species, species dispersal, and disease surveillance. Using a quantitative environmental DNA methodology, we assessed spatial variation in Atlantic salmon ( Salmo salar) eDNA concentration, originating from four active salmon farms, along ∼55 km of narrow channels in British Columbia, Canada. We evaluated eDNA from 36 and 47 seawater samples collected at 2 and 8 m depths, respectively, at 0.3–3 km intervals along the channels. We fitted a Laplace dispersal kernel to eDNA data separately for 2 and 8 m depths. The model estimates that 95% of eDNA spread at 2 m depth was within 1.6 km upstream and 3.2 km downstream from farms relative to a prevailing current, and this was expanded at 8 m (1.8 km upstream; 3.7 km downstream). Our modeling results were robust to multiple sources of simulated uncertainty associated with sampling regime and variable eDNA shedding rates. Our results provide a benchmark for the spatial spread of biological material such as pathogens or eDNA from invasive or imperilled species in a coastal marine context. This work has implications for the interpretation of eDNA data for species surveillance and predicting disease spread.

During spawning migrations, adult Pacific salmon ( Onco rhynchus spp.) must undergo a suite of morphological and physiological changes to prepare for spawning. Modern genomics approaches can be used to conduct nonlethal assessments of physiology and infectious agent presence in migrating salmon. We investigated gene expression changes and shifts in the prevalence and load of 18 infectious agents in the gill tissue of adult sockeye salmon ( Oncorhynchus nerka) during the final 50 km of their freshwater migration. We found 77% of fish successfully migrated to spawning grounds. Fish exhibited a decrease in thermal stress gene expression following lake migration, consistent with the hypothesized benefits of thermal refugia during spawning migrations. We also found evidence of cooler water selection (∼1.5 °C) during lake migration for fish with higher infection burden, suggesting behavioural changes for fish suffering higher infection burdens and potential benefits of thermal refuges for reducing the negative impacts of infection for migrating salmon. Collectively, our findings provide further evidence that fish behaviourally regulate exposure to stressful conditions such as high temperature that may undermine survival.

Although infectious agents can act as strong population regulators, knowledge of their spatial distributions in wild Pacific salmon is limited, especially in the marine environment. Characterizing pathogen distributions during early marine residence, a period considered a survival bottleneck for Pacific salmon, may reveal where salmon populations are exposed to potentially detrimental pathogens. Using high-throughput qPCR, we determined the prevalence of 56 infectious agents in 5719 Chinook, 2032 Coho and 4062 Sockeye salmon, sampled between 2008 and 2018, in their first year of marine residence along coastal Western Canada. We identified high prevalence clusters, which often shifted geographically with season, for most of the 41 detected agents. A high density of infection clusters was found in the Salish Sea along the east coast of Vancouver Island, an important migration route and residence area for many salmon populations, some experiencing chronically poor marine survival. Maps for each infectious agent taxa showing clusters across all host species are provided. Our novel documentation of salmon pathogen distributions in the marine environment contributes to the ecological knowledge regarding some lesser known pathogens, identifies salmon populations potentially impacted by specific pathogens, and pinpoints priority locations for future research and remediation.

SHR6390 (dalpiciclib) is a selective and effective cyclin-dependent kinase (CDK) 4/6 inhibitor and an effective cancer therapeutic agent. On 31 December 2021, the new drug application was approved by National Medical Product Administration (NMPA). The metabolism, mass balance, and pharmacokinetics of SHR6390 in 6 healthy Chinese male subjects after a single oral dose of 150 mg [14C]SHR6390 (150 µCi) in this research. The Tmax of SHR6390 was 3.00 h. In plasma, the t1/2 of SHR6390 and its relative components was approximately 17.50 h. The radioactivity B/P (blood-to-plasma) AUC0-t ratio was 1.81, indicating the preferential distribution of drug-related substances in blood cells. At 312 h after administration, the average cumulative excretion of radioactivity was 94.63% of the dose, including 22.69% in urine and 71.93% in stool. Thirteen metabolites were identified. In plasma, because of the low level of radioactivity, only SHR6390 was detected in pooled AUC0-24 h plasma. Stool SHR6390 was the main component in urine and stool. Five metabolites were identified in urine, and 12 metabolites were identified in stool. Overall, faecal clearance is the main method of excretion.

Recent decades have seen an increased appreciation for the role infectious diseases can play in mass mortality events across a diversity of marine taxa. At the same time many Pacific salmon populations have declined in abundance as a result of reduced marine survival. However, few studies have explicitly considered the potential role pathogens could play in these declines. Using a multi-year dataset spanning 59 pathogen taxa in Chinook and Coho salmon sampled along the British Columbia coast, we carried out an exploratory analysis to quantify evidence for associations between pathogen prevalence and cohort survival and between pathogen load and body condition. While a variety of pathogens had moderate to strong negative correlations with body condition or survival for one host species in one season, we found that Tenacibaculum maritimum and Piscine orthoreovirus had consistently negative associations with body condition in both host species and seasons and were negatively associated with survival for Chinook salmon collected in the fall and winter. Our analyses, which offer the most comprehensive examination of associations between pathogen prevalence and Pacific salmon survival to date, suggest that pathogens in Pacific salmon warrant further attention, especially those whose distribution and abundance may be influenced by anthropogenic stressors.

Salmon are keystone species across the North Pacific, supporting ecosystems, commercial opportunities, and cultural identity. Nevertheless, many wild salmon stocks have experienced significant declines. Salmon restoration efforts focus on fresh and coastal waters, but little is known about the open ocean environment. Here we use high throughput RT-qPCR tools to provide the first report on the health, condition, and infection profile of coho, chum, pink, and sockeye salmon in the Gulf of Alaska during the 2019 winter. We found lower infectious agent number, diversity, and burden compared with coastal British Columbia in all species except coho, which exhibited elevated stock-specific infection profiles. We identified Loma sp. and Ichthyophonus hoferi as key pathogens, suggesting transmission in the open ocean. Reduced prey availability, potentially linked to change in ocean conditions due to an El Niño event, correlated with energetic deficits and immunosuppression in salmon. Immunosuppressed individuals showed higher relative infection burden and higher prevalence of opportunistic pathogens. We highlight the cumulative effects of infection and environmental stressors on overwintering salmon, establishing a baseline to document the impacts of a changing ocean on salmon.

The treatment of bone defects is an important problem in clinical practice. The rapid development of bone tissue engineering (BTE) may provide a new method for bone defect treatment. Metal ions have been widely studied in BTE and demonstrated a significant effect in promoting bone tissue growth. Different metal ions can be used to treat bone defects according to specific conditions, including promoting osteogenic activity, inhibiting osteoclast activity, promoting vascular growth, and exerting certain antibacterial effects. Multiple studies have confirmed that metal ions-modified composite scaffolds can effectively promote bone defect healing. By studying current extensive research on metal ions in the treatment of bone defects, this paper reviews the mechanism of metal ions in promoting bone tissue growth, analyzes the loading mode of metal ions, and lists some specific applications of metal ions in different types of bone defects. Finally, this paper summarizes the advantages and disadvantages of metal ions and analyzes the future research trend of metal ions in BTE. This article can provide some new strategies and methods for future research and applications of metal ions in the treatment of bone defects.

The air, oxygen, moisture, thermal, and illumination stability of Cs2TiBr6 are investigated.

Substantial, acute mortality was observed in wild-caught Chinook salmon (Oncorhynchus tshawytscha) of various ages and sizes, from sub-adults to returning adults, held in tanks during two holding studies carried out in August and September 2022 at the Bamfield Marine Sciences Centre (BMSC), in Bamfield, British Columbia, Canada. Within days of capture, a substantial number of fish began presenting lethargy, loss of balance, abnormal swimming behavior, and skin ulcers involving the caudal peduncle, fins, belly, trunk and mouth. Molecular testing revealed high levels ofTenacibaculum dicentrarchiin skin swabs and gills, without appreciable consistent detections of other infectious agents.T. dicentrarchiwas also isolated from the skin ulcers. Histological analysis confirmed the presence of ulcerative dermatitis and myositis, associated with mats of filamentous, rod-shaped bacteria. In two individuals, the infection became systemic, with a bacterial colony (identified asT. dicentrarchi) observed in the liver of one individual. In-situ hybridization againstT. dicentrarchiandT. maritimumconfirmed the presence of only the former agent in the gills and skin ulcers of the affected fish. This clinical report represents the first diagnosed case of tenacibaculosis in wild-caught (captive) Chinook salmon in British Columbia.CONFLICT OF INTERESTThe authors have no conflicts of interest to report.DATA AVAILABILITY STATEMENTThe data that support the findings of this study are available from the corresponding author upon reasonable request.

The early marine life of Pacific salmon is believed to be a critical period limiting population-level survival. Recent evidence suggests that some infectious agents are associated with survival but linkages with underlying physiological mechanisms are lacking. While challenge studies can demonstrate cause and effect relationships between infection and pathological change or mortality, in some cases pathological change may only manifest in the presence of environmental stressors; thus, it is important to gain context from field observations. Herein, we examined physiological correlates with infectious agent loads in Chinook salmon during their first ocean year. We measured physiology at the molecular (gene expression), metabolic (plasma chemistry) and cellular (histopathology) levels. Of 46 assayed infectious agents, 27 were detected, including viruses, bacteria and parasites. This exploratory study identified: Importantly, our study provides the first evidence that the molecular activation of viral disease response and the lesions observed during the development of the PRV-related disease jaundice/anemia in farmed Chinook salmon are also observed in wild juvenile Chinook salmon.

Aims: To investigate the potential pharmacokinetic interactions of rezvilutamide on metabolic cytochrome P450 enzymes. Methods: A single-centre open-label, single-arm, fixed-sequence clinical trial was conducted in 18 patients with prostate cancer to evaluate the pharmacokinetic effects of rezvilutamide on the probe drugs for CYP3A4(midazolam), CYP2C9(S-warfarin) and CYP2C19 (omeprazole). Results: After a single oral dose of probe drugs alone and coadministration of rezvilutamide: (1) the geometric mean Cmax of plasma midazolam was 87.129 ng/mL and 7.778 ng/mL, the geometric mean AUC0-t was 273.806 h*ng/mL and 13.630 h*ng/mL, the geometric mean AUC0-∞ was 283.096 h*ng/mL and 14.284 h*ng/mL, the mean t1/2 was 5.347 h and 2.907 h, and the geometric mean CL/F was 52.986 L/h and 1050.102 L/h, respectively; (2) the geometric mean Cmax of plasma S-warfarin was 594.166 ng/mL and 555.228 ng/mL, the geometric mean AUC0-t was 17119.082 h*ng/mL and 9712.186 h*ng/mL, the geometric mean AUC0-∞ was 19510.761 h*ng/mL and 10130.752 h*ng/mL, the mean t1/2 was 38.730 h and 27.794 h, and the geometric mean CL/F was 0.513 L/h and 0.987 L/h, respectively; (3) the geometric mean Cmax of plasma omeprazole was 691.371 ng/mL and 282.064 ng/mL, the geometric mean AUC0-t was 2725.853 h*ng/mL and 599.078 h*ng/mL, the geometric mean AUC0-∞ was 2946.118 h*ng/mL and 661.989 h*ng/mL, the mean t1/2 was 2.612 h and 1.081 h, and the geometric mean CL/F was 6.825 L/h and 30.334 L/h, respectively Conclusion: Coadministration of rezvilutamide with midazolam, S-warfarin and omeprazole may cause loss of activity for these medications. Therefore, appropriate mitigation strategies are recommended.

The evaluation of scientific research projects is a multi-expert decision-making problem under incomplete information environment. Whether evaluation results are reasonable or not depends on the expression of experts’ opinions, the reliability of experts and the aggregation method of experts’ opinions. From the perspective of expert reliability, this paper proposes a data-driven evidential reasoning method based on two-dimensional frames of discernment. In the proposed method, project evaluation information and experts’ characteristics information are used as two-dimensional evidence to represent decision information and decision quality information respectively, and belief distribution is used to express these two kinds of information. Experts’ characteristics information is used to measure the reliability of experts to modify project evaluation information given by experts. The discounted project evaluation information is aggregated by using evidential reasoning analysis algorithm to complete the evaluation of scientific research projects. In addition, a learning optimisation model is constructed to determine the relevant parameter values of the proposed method in a data-driven manner using historical evaluation data of projects. The empirical analysis of the National Nature Science Foundation of China verifies the validity and applicability of the proposed method.

Radiative cooling is an electricity-free method for solar cells to dissipate waste heat, which has drawn much attention in recent years. In this paper, a periodic pyramid-textured polydimethylsiloxane (PDMS) film is proposed for radiative cooling of encapsulated commercial silicon solar cells. Spectral tests show that the proposed pyramid-textured PDMS film emits like a blackbody and simultaneously has an average transmittance of >0.9 in the silicon absorption spectrum from 0.3 µm to 1.1 µm. Outdoor cooling tests demonstrate that the encapsulated commercial silicon solar cells with the proposed textured PDMS film can be cooled by over 2 °C. Due to its good optical and flexible properties, the textured PDMS film has great potential for applications in the photovoltaic industry.

The treatment of infected bone defects is an intractable problem in orthopedics. It comprises two critical parts, namely that of infection control and bone defect repair. According to these two core tasks during treatment, the ideal approach of simultaneously controlling infection and repairing bone defects is promising treatment strategy. Several engineered biomaterials and drug delivery systems with dual functions of anti-bacterial action and ostogenesis-promotion have been developed and demonstrated excellent therapeutic effects. Compared with the conventional treatment method, the dual-functional composite scaffold can provide one-stage treatment avoiding multiple surgeries, thereby remarkably simplifying the treatment process and reducing the treatment time, overcoming the disadvantages of conventional bone transplantation. In this review, the impaired bone repair ability and its specific mechanisms in the microenvironment of pathogen infection and excessive inflammation were analyzed, providing a theoretical basis for the treatment of infectious bone defects. Furthermore, we discussed the composite dual-functional scaffold composed of a combination of antibacterial and osteogenic material. Finally, a series of advanced drug delivery systems with antibacterial and bone-promoting capabilities were summarized and discussed. This review provides a comprehensive understanding for the microenvironment of infectious bone defects and leading-edge design strategies for the antibacterial and bone-promoting dual-function scaffold, thus providing clinically significant treatment methods for infectious bone defects.

Inorganic nitrate is an indispensable nutrient, which has been used in experimental studies on the prevention and treatment of several diseases. However, its short half-life limits inorganic nitrate’s clinical application. To increase nitrate’s usability and overcome the challenges of traditional combination drug discovery through large-scale high-throughput biological experiments, we developed our deep learning–based combination drug prediction system, which identified vitamin C as the drug of choice to be combined with nitrate. Employing microencapsulation technology, we used vitamin C, sodium nitrate, and chitosan 3000 as the core material to prepare a nitrate nanoparticle, which we named Nanonitrator. The long-circulating delivery of nitrate by Nanonitrator significantly increased the efficacy and effect duration of nitrate in two animal models of injury, without compromising safety. Moreover, Nanonitrator at the same dose could better maintain intracellular homeostasis than nitrate (with or without vitamin C), emphasizing its potential for clinical use. More importantly, our work provides a method for the incorporation of inorganic compounds into sustained-release nanoparticles.

Hydrogen sulfide (H

BACKGROUND: Second-line treatment options for small cell lung cancer (SCLC) are limited. Preclinical research shows that inhibition of poly (ADP-ribose) polymerase (PARP) could upregulate programmed death-ligand 1 (PD-L1), and thus render cancer cells more sensitive to immune checkpoint inhibitors. This study investigated the tolerability, safety, and preliminary antitumor activity of fuzuloparib (a PARP inhibitor) plus SHR-1316 (a PD-L1 inhibitor) for relapsed SCLC. METHODS: Patients with SCLC who failed previous first-line platinum-based therapy were enrolled in this two-stage phase Ib trial. In stage 1, 2 dose levels were designed: fuzuloparib 100 mg or 150 mg twice daily plus SHR-1316 600 mg every 2 weeks, with 6 patients in each dose level. Based on the tolerability during the first 28-day cycle and the preliminary antitumor activity in stage 1, a recommended phase II dose (RP2D) was determined and introduced in the stage 2 expansion phase. The primary endpoints were safety and RP2D in stage 1 and objective response rate (ORR) in stage 2. RESULTS: A total of 23 patients were enrolled, with 16 receiving fuzuloparib 100 mg plus SHR-1316 and 7 receiving fuzuloparib 150 mg plus SHR-1316. At data cutoff on April 23, 2021, the median follow-up duration was 6.4 months (IQR, 3.0–9.7 months). All patients discontinued study treatment. One patient receiving fuzuloparib 150 mg plus SHR-1316 had clinically significant toxicities, and fuzuloparib 100 mg plus SHR-1316 was considered as the RP2D. In the RP2D cohort, the confirmed ORR was 6.3% (95% CI: 0.2–30.2%), and the disease control rate was 37.5% (95% CI: 15.2–64.6%). The median progression-free survival was 1.4 months (95% CI: 1.3–2.8 months), and the median overall survival was 5.6 months (95% CI: 3.0–16.7 months). Grade ≥3 treatment-related adverse events (TRAE) occurred in 8 patients (34.8%). No treatment-related death occurred, and no patients discontinued treatment due to TRAEs. CONCLUSIONS: Fuzuloparib combined with SHR-1316 failed to improve the outcomes in unselected patients with relapsed SCLC. Future studies with biomarker analysis are warranted to select patients most likely to benefit from this combination treatment. Fuzuloparib 100 and 150 mg plus SHR-1316 were both tolerable with no new signals observed.

To address the issues of not accurately identifying ice types and thickness in current fiber-optic ice sensors, in this paper, we design a novel fiber-optic ice sensor based on the reflected light intensity modulation method and total reflection principle. The performance of the fiber-optic ice sensor was simulated by ray tracing. The low-temperature icing tests validated the performance of the fiber-optic ice sensor. It is shown that the ice sensor can detect different ice types and the thickness from 0.5 to 5 mm at temperatures of −5 °C, −20 °C, and −40 °C. The maximum measurement error is 0.283 mm. The proposed ice sensor provides promising applications in aircraft and wind turbine icing detection.

Background Strategies to improve activity of immune checkpoint inhibitors for triple-negative breast cancer (TNBC) are needed. Preclinical studies showed that antiangiogenic agents and poly (ADP-ribose) polymerase (PARP) inhibitors might sensitize tumors to immunotherapy. Here, we investigated the tolerability, safety, and preliminary antitumor activity of camrelizumab, an anti-PD-1 antibody, in combination with apatinib, a vascular endothelial growth factor receptor-2 inhibitor, and fuzuloparib, a PARP inhibitor, in patients with recurrent or metastatic TNBC. Methods This phase Ib study included a dose-finding part and a dose-expansion part. In the dose-finding part, a 3 + 3 dose escalation scheme was introduced. Patients were given camrelizumab (200 mg every 2 weeks) plus apatinib (375 mg or 500 mg once daily) and fuzuloparib (starting dose 100 mg twice daily) every 28-day cycle. After evaluation of the tolerability and safety of the dosing regimens, a clinical recommended dose was determined for the dose-expansion part. The primary endpoint was dose-limiting toxicity (DLT). Results A total of 32 patients were enrolled. Three patients received camrelizumab 200 mg + apatinib 375 mg + fuzuloparib 100 mg, and 29 received camrelizumab 200 mg + apatinib 500 mg + fuzuloparib 100 mg (clinical recommended dose). No DLTs were observed in either group. The most common grade ≥ 3 treatment-related adverse events were decreased white blood cell count (20.7%), hypertension (13.8%), decreased neutrophil count (10.3%), and increased aspartate aminotransferase (10.3%). Two patients discontinued study treatment due to immune-mediated hepatitis (n = 1) and anemia, decreased platelet count, decreased white blood cell count, increased alanine aminotransferase, increased aspartate aminotransferase, and increased γ-glutamyltransferase (n = 1). One patient died of unknown cause. Two (6.9% [95% CI, 0.9–22.8]) of 29 patients with camrelizumab 200 mg + apatinib 500 mg + fuzuloparib 100 mg had objective response. The disease control rate was 62.1% (95% CI, 42.3–79.3). The median progression-free survival was 5.2 months (95% CI, 3.6–7.3), and the 12-month overall survival rate was 64.2% (95% CI, 19.0–88.8). Conclusions Combination of camrelizumab plus apatinib and fuzuloparib showed manageable safety profile and preliminary antitumor activity in patients with recurrent or metastatic TNBC. Trial registration ClinicalTrials.gov NCT03945604 (May 10, 2019).

The purpose of this study was to determine the pharmacokinetic characteristics and safety of dalpiciclib at 100-, 125-, and 150-mg doses after process modification in healthy Chinese volunteers. This single-center, randomized, open-label, three-dose, phase I clinical study was conducted in healthy Chinese adults. Thirty-six volunteers were randomized to three groups, including groups administered 100, 125, and 150 mg of dalpiciclib, and each group contained an equal number of males and females. A single oral dose of dalpiciclib was administered to each group, and plasma concentrations were measured by a validated liquid chromatography-tandem mass spectrometry method. The oral formulation of dalpiciclib was well absorbed, the plasma concentration reached the maximum concentration (C

The large incidence of bone defects in clinical practice increases not only the demand for advanced bone transplantation techniques but also the development of bone substitute materials. A variety of emerging bone tissue engineering materials with osteogenic induction ability are promising strategies for the design of bone substitutes. MicroRNAs (miRNAs) are a class of non-coding RNAs that regulate intracellular protein expression by targeting the non-coding region of mRNA3′-UTR to play an important role in osteogenic differentiation. Several miRNA preparations have been used to promote the osteogenic differentiation of stem cells. Therefore, multiple functional bone tissue engineering materials using miRNA as an osteogenic factor have been developed and confirmed to have critical efficacy in promoting bone repair. In this review, osteogenic intracellular signaling pathways mediated by miRNAs are introduced in detail to provide a clear understanding for future clinical treatment. We summarized the biomaterials loaded with exogenous cells engineered by miRNAs and biomaterials directly carrying miRNAs acting on endogenous stem cells and discussed their advantages and disadvantages, providing a feasible method for promoting bone regeneration. Finally, we summarized the current research deficiencies and future research directions of the miRNA-functionalized scaffold. This review provides a summary of a variety of advanced miRNA delivery system design strategies that enhance bone regeneration.

In some salmonid populations, multiple smolt age classes co-emigrate owing to variation in the duration of freshwater residence. While it is assumed that smolts prolong freshwater residence to maximize survival, infectious agent profiles and host gene expression (GE) have not been compared between concurrently migrating age classes. We coupled molecular assays of gill samples from nonlethally biopsied Chilko Lake sockeye salmon smolts with acoustic telemetry to study variation in infectious agent profiles and GE between age classes and survival groups. Although neither infectious agent profiles or GE were associated with survival, age-2 smolts exhibited higher mortality in the first 14 km of the downstream migration. There were measurable differences between the age classes in GE and the prevalence and load of “Candidatus Branchiomonas cysticola”, a bacterium commonly found in British Columbia salmonids. Relative to age-1 smolts, age-2 smolts displayed elevated GE related to inflammation and a molecular-based mortality-related signature. Although not associated with migration failure in this study, these patterns of GE are suggestive of mortality and could have implications for smolt survival.

Owing to the complexity and uncertainty of scientific research projects, government-funded institutions often invite multiple peer experts to evaluate the projects. How to aggregate the evaluation opinions of multiple peer experts is an important issue. With consideration of the experts' knowledge background and historical evaluation performance, this paper proposes an evidential reasoning approach under two-dimensional frames of discernment to aggregate the evaluation opinions of multiple experts. Firstly, two-dimensional frames of discernment are constructed. The I-dimensional frame of discernment describes experts' evaluation opinions, and the II-dimensional frame of discernment describes experts' knowledge background and historical evaluation performance. Experts' evaluation opinions and characteristic information are transformed into pieces of evidence, which could be expressed by their respective belief distributions. Secondly, the II-dimensional evidence information is used to generate the evidence correction factor to reflect experts' reliabilities. Finally, the experts' evaluation opinions are corrected using the evidence correction factors. Thus, the corrected experts' evaluation opinions contain the experts' characteristic information. In addition, the evidential reasoning approach is used to aggregate the evaluation opinions of multiple experts to complete the selection of the scientific research projects. An illustrative example on aggregating the evaluation opinions of the National Natural Science Foundation of China is provided to demonstrate the applicability and validity of the proposed method. Experimental results show that the proposed method can enhance the description of uncertainty in experts' evaluation opinions, reflect the qualities of the experts' evaluation opinions, and make the aggregation results of multiple experts' evaluation opinions more reasonable and accurate.

This trial (NCT04013048) investigated the metabolite profiles, mass balance and pharmacokinetics of fuzuloparib, a novel poly (ADP-ribose) polymerase inhibitor, in subjects with advanced solid cancers.A single dose of 150 mg [The maximum concentrations (CFuzuloparib was widely metabolized and excreted completely through urine and faeces in subjects with advanced solid cancer. Unchanged fuzuloparib was indicated to be the primary drug-related compound in circulation. [

Hebei Province, located in the North China Plain (NCP) and encircling Beijing and Tianjin, has been suffering from severe air pollution. The monthly average fine particulate matter (PM

In the last decade, perovskite solar cells have made a quantum leap in performance with the efficiency increasing from 3.8% to 25%. However, commercial perovskite solar cells have faced a major impediment due to toxicity and stability issues. Therefore, lead-free inorganic perovskites have been investigated in order to find substitute perovskites which can provide a high efficiency similar to lead-based perovskites. In recent studies, as a kind of lead-free inorganic perovskite material, Cs4CuSb2Cl12 has been demonstrated to possess impressive photoelectric properties and excellent environmental stability. Moreover, Cs4CuSb2Cl12 nanocrystals have smaller effective photo-generated carrier masses than bulk Cs4CuSb2Cl12, which provides excellent carrier mobility. To date, there have been no reports about Cs4CuSb2Cl12 nanocrystals used for making solar cells. To explore the potential of Cs4CuSb2Cl12 nanocrystal solar cells, we propose a lead-free perovskite solar cell with the configuration of FTO/ETL/Cs4CuSb2Cl12 nanocrystals/HTL/Au using a solar cell capacitance simulator. Moreover, we numerically investigate the factors that affect the performance of the Cs4CuSb2Cl12 nanocrystal solar cell with the aim of enhancing its performance. By selecting the appropriate hole transport material, electron transport material, thickness of the absorber layer, doping densities, defect density in the absorber, interface defect densities, and working temperature point, we predict that the Cs4CuSb2Cl12 nanocrystal solar cell with the FTO/TiO2/Cs4CuSb2Cl12 nanocrystals/Cu2O/Au structure can attain a power conversion efficiency of 23.07% at 300 K. Our analysis indicates that Cs4CuSb2Cl12 nanocrystals have great potential as an absorbing layer towards highly efficient lead-free all-inorganic perovskite solar cells.

Elastic, fracture and deformation behavior of B2 FeAl intermetallics modified by ternary additions as well as Al/Fe vacancy defects and anti-sites have been investigated based on density functional theory (DFT). Formation enthalpy indicates that ternary additions Sc, Y, Mo and W have a preference for Al site. While Fe site is more easily replaced by ternary Cu and Zn. Moreover, vacancy and antisite defects can be stable in FeAl. Pugh criteria ([Formula: see text] ratio), Poisson’s ratio [Formula: see text] and Cauchy pressure show that Sc, Y, Mo, W and Al vacancy (Al anti-site by Fe atom) can effectively improve the ductility of FeAl. Dislocation emission and micro-cracks propagation show that the improved ductility is due to the promoted dislocation emission but suppressed micro-cracks propagation. Bonding analyses reveal that the improved ductility is mainly own to the weakened the covalent interactions and strengthened the metallic interactions.

Objectives: Hepatic ischemia-reperfusion injury (HIRI) is of common occurrence during liver surgery and liver transplantation and may cause hepatic impairment, resulting in acute liver dysfunction. Nitrate plays an important physiological regulatory role in the human body. Whether dietary nitrate could prevent HIRI is, however, unknown.Methods: A HIRI mouse model was established in that the blood supply to the median lobe and left lateral lobe was blocked for 60 min through the portal vein and related structures using an atraumatic clip. Sodium nitrate (4 mM) was administrated in advance through drinking water to compare the influence of sodium nitrate and normal water on HIRI.Results: Liver necrosis and injury aggravated after HIRI. The group treated with sodium nitrate showed the lowest activities of plasma aminotransferase and lactate dehydrogenase and improved outcomes in histological investigation and TUNEL assay. Mechanistically, sodium nitrate intake increased plasma and liver nitric oxide levels, upregulated nuclear factor erythroid 2-related factor 2 (NRF2)–related molecules to reduce malondialdehyde level, and increased the activities of antioxidant enzymes to modulate hepatic oxidative stress.Conclusions: Dietary inorganic nitrate could prevent HIRI, possibly by activating the NRF2 pathway and modulating oxidative stress. Our study provides a novel therapeutic compound that could potentially prevent HIRI during liver transplantation or hepatic surgery.

It is well known that liquid Al wetting on a SiC substrate is an important process, especially when manufacturing Al/SiC composite materials. Many researchers have attempted to investigate ...