Surufatinib combined with transarterial embolization versus surufatinib monotherapy in patients with liver metastatic neuroendocrine tumors: Study protocol for a prospective, randomized, controlled trial.

BACKGROUND: More than half of neuroendocrine tumor (NET) patients will experience liver metastasis, and interventional therapy represented by transarterial embolization (TAE) is the main local treatment method. Surufatinib is recommended as a standard systemic treatment for advanced NETs. The efficacy and safety of surufatinib combined with TAE in the treatment of liver metastasis are undetermined. This study was conducted to compare the clinical outcome of surufatinib combined with TAE versus surufatinib monotherapy in liver metastatic NETs. METHODS: This is a prospective, multicenter, open-label, and randomized controlled trial. Patients diagnosed with liver metastatic NETs will be enrolled. Participants are randomly assigned in a 1:1 ratio to either the experimental group or the control group. Patients will be treated with surufatinib plus TAE in the experimental group, while patients in the control group will receive surufatinib monotherapy. The primary endpoint is progression-free survival (PFS) assessed by a blinded independent image review committee (BIIRC). The secondary endpoints are investigator-assessed PFS, liver-specific objective response rate (ORR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of adverse events. DISCUSSION: This is the first prospective study to investigate the efficacy of surufatinib combined with TAE. We expect this trial to propose a new and effective treatment strategy for liver metastatic NETs.

Automatic in situ short-distance deposition of PLGA/PLLA composite nanofibrous membranes for personalized wound dressings.

Improving the mechanical properties of wound dressings and achieving personalized automatic real-time in situ deposition are important for accelerating wound management and repair. In this study, we report a self-designed automatic in situ deposition device based on solution blow spinning (SBS) to prepare poly(lactic-co-glycolic acid) (PLGA) and poly-L-lactic acid (PLLA) composite (PLGA/PLLA) nanofibrous membranes for wound dressing at a short distance. Polymer solution and in situ deposition conditions, including air pressure, spinning distance, solvent extrusion rate, and spinning rate, were optimized using orthogonal experiments and characterized via dynamic mechanical analysis. The microscopic morphology and physical properties of the prepared PLGA/PLLA composite nanofibrous membranes show that their strength, adhesion, water vapor transmission rate (WVTR), water retention, water absorption, degradation, and other properties were sufficient for wound-dressing applications. To investigate the possibility of a biomedical wound-dressing material, tannic acid (TA) was incorporated into the PLGA/PLLA composite nanofibrous membranes. The resultant PLGA/PLLA/TA composite nanofibrous membranes exhibited good biocompatibility and exceptional antibacterial properties against both Escherichia coli and Staphylococcus aureus. A pilot animal study illustrated the potential of this in situ deposition of PLGA/PLLA/TA composite nanofibrous membranes across multiple applications in wound healing/repair by reducing wound scar tissue formation and fibroblast overactivation.

Emerging role of exosome-shuttled noncoding RNAs in gastrointestinal cancers: From intercellular crosstalk to clinical utility.

Gastrointestinal cancer remains a significant global health burden. The pursuit of advancing the comprehension of tumorigenesis, along with the identification of reliable biomarkers and the development of precise therapeutic strategies, represents imperative objectives in this field. Exosomes, small membranous vesicles released by most cells, commonly carry functional biomolecules, including noncoding RNAs (ncRNAs), which are specifically sorted and encapsulated by exosomes. Exosome-mediated communication involves the release of exosomes from tumor or stromal cells and the uptake by nearby or remote recipient cells. The bioactive cargoes contained within these exosomes exert profound effects on the recipient cells, resulting in significant modifications in the tumor microenvironment (TME) and distinct alterations in gastrointestinal tumor behaviors. Due to the feasibility of isolating exosomes from various bodily fluids, exosomal ncRNAs have shown great potential as liquid biopsy-based indicators for different gastrointestinal cancers, using blood, ascites, saliva, or bile samples. Moreover, exosomes are increasingly recognized as natural delivery vehicles for ncRNA-based therapeutic interventions. In this review, we elucidate the processes of ncRNA-enriched exosome biogenesis and uptake, examine the regulatory and functional roles of exosomal ncRNA-mediated intercellular crosstalk in gastrointestinal TME and tumor behaviors, and explore their potential clinical utility in diagnostics, prognostics, and therapeutics.

Oceanic repeaters boost the global climatic impact of the Tibetan Plateau.

The topography of the Tibetan Plateau (TP) has shaped the paleoclimatic evolution of the Asian monsoon. However, the influence of the TP on the global climate, beyond the domain of the Asian monsoon, remains unclear. Here we show that the Pacific and Atlantic Oceans act as efficient repeaters that boost the global climatic impact of the TP. The simulations demonstrate that oceanic repeaters enable TP heating to induce a wide-ranging climate response across the globe. A 1 °C TP warming can result in a 0.73 °C temperature increase over North America. Oceanic repeaters exert their influence by enhancing the air-sea interaction-mediated horizontal heat and moisture transport, as well as relevant atmospheric circulation pathways including westerlies, stationary waves, and zonal-vertical cells. Air-sea interactions were further tied to local feedbacks, mainly the decreased air-sea latent heat flux from the weakening air-sea humidity difference and the increased shortwave radiation from sinking motion-induced cloud reduction over the North Pacific and Atlantic Oceans. Our findings highlight the crucial influence of TP heating variation on the current climate under a quasi-fixed topography, in contrast to topography change previously studied in paleoclimate evolution. Therefore, TP heating should be considered in research on global climate change.

Investigation of In Vitro Cytocompatibility of Zinc-Containing Coatings Developed on Medical Magnesium Alloys.

In a neutral solution, we investigated the effects of Na2[ZnEDTA] concentrations at 0, 6, 12, 18, and 24 g/L on surface morphology, chemical composition, degradation resistance, and in vitro cytocompatibility of micro-arc oxidation (MAO) coatings developed on WE43 (Mg-Y-Nd-Zr) magnesium alloys. The results show that the enhanced Na2[ZnEDTA] concentration increased the Zn amount but slightly decreased the degradation resistance of MAO-treated coatings. Among the zinc-containing MAO samples, the fabricated sample in the base solution added 6 g/L Na2[ZnEDTA] exhibits the smallest corrosion current density (6.84 × 10-7 A·cm-2), while the sample developed in the solution added 24 g/L Na2[ZnEDTA] and contains the highest Zn content (3.64 wt.%) but exhibits the largest corrosion current density (1.39 × 10-6 A·cm-2). Compared to untreated WE43 magnesium alloys, zinc-containing MAO samples promote initial cell adhesion and spreading and reveal enhanced cell viability. Coating degradation resistance plays a more important role in osseogenic ability than Zn content. Among the untreated WE43 magnesium alloys and the treated MAO samples, the sample developed in the base solution with 6 g/L Na2[ZnEDTA] reveals the highest ALP expression at 14 d. Our results indicate that the MAO samples formed in the solution with Na2[ZnEDTA] promoted degradation resistance and osseogenesis differentiation of the WE43 magnesium alloys, suggesting potential clinic applications.

The emerging role of adopting protamine for reducing the risk of bleeding complications during the percutaneous coronary intervention: A meta-analysis.

BACKGROUND: The safety and the benefits of reducing the risk of bleeding complications via protamine administration during the percutaneous coronary intervention (PCI) remains unclear. This study aimed to systematically assessed the efficacy and safety of using protamine in PCI. METHOD: Potential academic studies were identified from PubMed, Cochrane Library, EMBASE, and Web of Science. The time range we retrieved from was that from the inception of electronic databases to March 31, 2022. Gray studies were identified from the references of included literature reports. Stata version 12.0 statistical software (StataCorp LP) was used to analyze the pooled data. RESULTS: A total of seven studies were involved in our study. The overall participants of the protamine group were 4983, whereas it was 1953 in the nonprotamine group. This meta-analysis indicated that protamine was preferable for PCI as its lower value of major bleeding (odds ratio [OR] = 0.489, 95% confidence interval [CI]: 0.362-0.661, p < .001) and minor bleeding (OR = 0.281, 95% CI: 0.123-0.643, p = .003). Additionally, the protamine did not tend to be related a higher incidence of mortality (p = .143), myocardial infarction (p = .990), and stent thrombosis (p = .698). CONCLUSIONS: Based on available evidence, use of protamine may reduce the risk of bleeding complications without increasing the risk of mortality, myocardial infarction, and stent thrombosis. Given the relevant possible biases in our study, adequately powered and better-designed studies with long-term follow-up are required to reach a firmer conclusion.

Pulmonary adverse events associated with hypertension in non-small cell lung cancer patients receiving PD-1/PD-L1 inhibitors.

Introduction: Non-small cell lung cancer patients have gained therapeutic benefits from immune checkpoint inhibitors, although immune-related adverse events (irAEs) could be inevitable. Whether irAEs are associated with chronic diseases is still unclear, our study aims to clarify the distinct adverse events in NSCLC patients with concomitant hypertension. Methods: Adverse event cases were searched and collected in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from January 2015 to December 2021. We performed disproportionality analysis to detect safety signals by calculating reporting odds ratios (ROR) and corresponding 95% confidence intervals (95% CIs), information component (IC), and the lower bound of the information component 95% credibility interval (IC025). Results: Among 17,163 NSCLC patients under treatment with single-agent anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1) inhibitor (nivolumab, pembrolizumab, cemiplimab, durvalumab, atezolizumab, and avelumab), 497 patients had hypertension while 16,666 patients had no hypertension. 4,283 pulmonary AEs were reported, including 166 patients with hypertension and 4,117 patients without hypertension. Compared with patients without hypertension, patients with hypertension were positively associated with increased reporting of interstitial lung disease (ROR = 3.62, 95%CI 2.68-4.89, IC = 1.54, IC025 = 0.57) among patients receiving anti-PD-1 treatment. The median duration of onset from the time of initiation of anti-PD-1 administration was 28 days (IQR, 12.00-84.25). Conclusion: Our pharmacovigilance analysis showed the profile of pulmonary toxicities in NSCLC patients with hypertension caused by anti-PD-1/PD-L1 inhibitors. Interstitial lung disease was the statistically significant reporting adverse event in patients with hypertension receiving anti-PD-1 treatment.

Personalized recommendation model of electronic commerce in new media era based on semantic emotion analysis.

Electronic commerce (E-commerce) through digital platforms relies on diverse user features to provide a better user experience. In particular, the user experience and connection between digital platforms are exploited through semantic emotions. This provides a personalized recommendation for different user categories across the E-commerce platforms. This manuscript introduces a Syntactic Data Inquiring Scheme (SDIS) to strengthen the semantic analysis. This scheme first identifies the emotional data based on user comments and repetition on the E-commerce platform. The identifiable and non-identifiable emotion data is classified using positive and repeated comments using the deep learning paradigm. This classification attunes the recommendation system for providing best-affordable user services through product selection, ease of access, promotions, etc. The proposed scheme strengthens the user relationship with the E-commerce platforms by improving the prioritization of user requirements. The user's interest and recommendation factors are classified and trained for further promotions/recommendations in the learning process. The recommendation data classified from the learning process is used to train and improve the user-platform relationship. The proposed scheme's performance is analyzed through appropriate experimental considerations. From the experimental analysis, as the session frequency increases, the proposed SDIS maximizes recommendation by 15.1%, the data analysis ratio by 9.41%, and reduces the modification rate by 17%.

Anthropogenic pollutants could enhance aridity in the vicinity of the Taklimakan Desert: A case study.

With the intensification of human activities, the mixture of anthropogenic pollutants and natural dust aerosols in the vicinity of the Taklimakan Desert (TD) has become a new uncertainty in the weather and climate system. In this study, using a Weather Research and Forecasting model version 4.0 with the Thompson aerosol-aware microphysics scheme, we investigated the impact of anthropogenic aerosols on clouds and precipitation in an atmospheric environment with abundant dust aerosols in the vicinity of the TD. Our findings indicate that anthropogenic aerosols can increase cloud droplet number concentrations in the vicinity of the TD, and the maximum percentage increase can reach 50 %. In addition, the effective radius of water clouds decreases significantly due to anthropogenic aerosols, which means that more numerous but smaller cloud droplets are formed with enhanced anthropogenic aerosol loading under a dusty background. Meanwhile, anthropogenic aerosols can decrease raindrops below 650 hPa, graupel and snow particles, causing less precipitation in the dusty atmosphere surrounding the TD. Furthermore, the anthropogenic aerosol-induced changes in daily precipitation accumulation are also large, with a regionally averaged maximum reduction of up to 4.2 %. Therefore, anthropogenic aerosols are an important factor that exacerbates aridity in the vicinity of the TD, and there is an urgent need to control anthropogenic pollutants around the TD.

Performance of high temperature phase-stable high entropy oxide (MgCuMnCoFe)O x in catalytic wet air oxidation of chloroquine phosphate.

With the continuous spread of COVID-19, the water pollution problems caused by the abuse of chloroquine phosphate (CQP) as an antiviral drug have attracted wide attention. The cubic Fm-3m spinel high entropy oxide (HEO)-(MgCuMnCoFe)O x was prepared by coprecipitation method as the catalytic wet air oxidation (CWAO) catalyst to treat CQP simulated wastewater. Through electron spin resonance (ESR) analysis, HEO will stimulate the production of superoxide radical (·O2 -) and hydroxyl radical (·OH) in the wet air oxidation (WAO) process, which accelerates the degradation and mineralization of CQP. Through response surface method (RSM) optimization, the optimal degradation conditions of CQP in CWAO were proposed: initial oxygen pressure of 15 bar, catalyst dosage of 1.4 g/L and temperature of 230 °C. The advantages of HEO in CWAO were analyzed by principal component analysis (PCA). The degradation mechanism of CQP in CWAO by (MgCuMnCoFe)O x were explored. This work provides a new idea for the rapid development of HEO in the field of environmental catalysis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10853-022-07271-z.

Feasibility of using different hydrothermal processes for sewage sludge management in China.

Due to its tremendous volume and severe environmental concern, sewage sludge (SS) management and treatment are significant in China. The recent prohibition (June 2021) of reusing SS as organic fertilizers makes it urgent to develop alternative processes. However, there is currently little research analyzing the applicability of using HP for sewage SS treatment in China. The significant difference in SS composition and the much less land supply in urban areas might invalidate most previous localized suggestions. In this paper, the development of emerging hydrothermal processes (HPs) for SS treatment will be reviewed, focusing on their decomposition mechanisms and the benefits of HPs compared with current SS treatment technologies. The SS volume, composition, and regulatory regime in China will also be evaluated. Those efforts could address the potential SS treatment capacity shortage and provide an opportunity to recover nutrients, organics and energy embedded in SS. The results show that HPs' high investment cost is mainly limited by the process scale, while their operating costs are comparable to incineration. Minimizing equipment erosion, ensuring process safety, and designing a more efficient heat recovery system are recommended for the future commercialization of HPs in China.

Monte Carlo study of the pseudogap and superconductivity emerging from quantum magnetic fluctuations.

The origin of the pseudogap behavior, found in many high-Tc superconductors, remains one of the greatest puzzles in condensed matter physics. One possible mechanism is fermionic incoherence, which near a quantum critical point allows pair formation but suppresses superconductivity. Employing quantum Monte Carlo simulations of a model of itinerant fermions coupled to ferromagnetic spin fluctuations, represented by a quantum rotor, we report numerical evidence of pseudogap behavior, emerging from pairing fluctuations in a quantum-critical non-Fermi liquid. Specifically, we observe enhanced pairing fluctuations and a partial gap opening in the fermionic spectrum. However, the system remains non-superconducting until reaching a much lower temperature. In the pseudogap regime the system displays a "gap-filling" rather than "gap-closing" behavior, similar to the one observed in cuprate superconductors. Our results present direct evidence of the pseudogap state, driven by superconducting fluctuations.

Environmental risks of disposable face masks during the pandemic of COVID-19: Challenges and management.

Since the COVID-19 outbreak in early 2020, face mask (FM) has been recognized as an effective measure to reduce the infection, increasing its consumption across the world. However, the large amount of at-home FM usage changed traditional medical waste management practices, lack of improper management. Currently, few studies estimate FM consumption at a global scale, not to say a comprehensive investigation on the environmental risks of FM from a life cycle perspective. Therefore, global FM consumption and its associated environmental risks are clarified in the present study. Our result shows that 449.5 billion FMs were consumed from January 2020 to March 2021, with an average of 59.4 FMs per person worldwide. This review also provides a basis to understand the environmental risk of randomly disposed of FM and highlights the urgent requirement for the attention of FMs waste management to prevent pollution in the near future.

Role of anthropogenic aerosols in affecting different-grade precipitation over eastern China: A case study.

Atmospheric aerosols play an important role in affecting clouds and precipitation by serving as condensation/ice nuclei. However, how to quantify the contribution of anthropogenic aerosols to the alteration of clouds and precipitation remains unknown. In this study, using a Weather Research and Forecasting-Chemistry (WRF-Chem) model, we quantified the impacts of anthropogenic aerosols on cloud water properties under different precipitation grades during a single rainfall event over eastern China. The results of this study show that anthropogenic aerosols have varying effects on hourly precipitation with heavy (greater than 1.04 mm/h), moderate (0.41-1.04 mm/h), and light (less than 0.41 mm/h) grades. Due to the presence of anthropogenic aerosols, heavy precipitation is intensified by 70.96%; however, moderate and light precipitation is further weakened by 24.87% and 86.43%, respectively. For heavy precipitation, the addition of anthropogenic aerosols induces an enhancement in upward motion, increases the cloud water path and effective radius through the aerosol-radiation interaction (ARI) effect, which is the main reason for the intensification of heavy-grade precipitation. In addition, the weakened upward motion and decreased ice water path caused by ARI and aerosol-cloud interaction (ACI) effects play common roles in reducing moderate and light precipitation. Studying anthropogenic aerosols' impacts on precipitation is of great importance for understanding the influence of anthropogenic pollution on the weather and climate and even for promoting precipitation forecasting and prediction.

Photocatalytic Hydrogen Evolution from Water Splitting Using Core-Shell Structured Cu/ZnS/COF Composites.

Hydrogen is considered to be a very efficient and clean fuel since it is a renewable and non-polluting gas with a high energy density; thus, it has drawn much attention as an alternative fuel, in order to alleviate the issue of global warming caused by the excess use of fossil fuels. In this work, a novel Cu/ZnS/COF composite photocatalyst with a core-shell structure was synthesized for photocatalytic hydrogen production via water splitting. The Cu/ZnS/COF microspheres formed by Cu/ZnS crystal aggregation were covered by a microporous thin-film COF with a porous network structure, where COF was also modified by the dual-effective redox sites of C=O and N=N. The photocatalytic hydrogen production results showed that the hydrogen production rate reached 278.4 µmol g-1 h-1, which may be attributed to its special structure, which has a large number of active sites, a more negative conduction band than the reduction of H+ to H2, and the ability to inhibit the recombination of electron-hole pairs. Finally, a possible mechanism was proposed to effectively explain the improved photocatalytic performance of the photocatalytic system. The present work provides a new concept, in order to construct a highly efficient hydrogen production catalyst and broaden the applications of ZnS-based materials.

Foresight regarding drug candidates acting on the succinate-GPR91 signalling pathway for non-alcoholic steatohepatitis (NASH) treatment.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is a liver manifestation of metabolic syndrome, with a histological spectrum from simple steatosis to non-alcoholic steatohepatitis (NASH). NASH can evolve into progressive liver fibrosis and eventually lead to liver cirrhosis. The pathological mechanism of NASH is multifactorial, involving a series of metabolic disorders and changes that trigger low-level inflammation in the liver and other organs. In the pathogenesis of NASH, the signal transduction pathway involving succinate and the succinate receptor (G-protein-coupled receptor 91, GPR91) regulates inflammatory cell activation and liver fibrosis. This review describes the mechanism of the succinate-GPR91 signalling pathway in NASH and summarizes the drugs that act on this pathway, with the aim of providing a new approach to NASH treatment.

A ratiometric electrochemical microsensor for monitoring chloride ions in vivo.

Chloride ion (Cl-), the most common anion in animal brain, has been verified to play a vital role in maintaining normal physiological processes. Thus, development of a reliable platform to determine Cl- is of great significance for brain research involving Cl-. In this work, a ratiometric electrochemical microsensor (REM) for the in vivo measurement of cerebral Cl- was designed. To prepare REM, uniform Ag nanoparticles (Ag NPs) with nano-level sizes were synthesized via an adsorption-reduction process, which served as selective recognition elements for Cl- determination, while methylene blue (MB) was absorbed and acted as an inner reference unit to avoid the environmental interference of complicated brain systems. As a result, this developed REM exhibited high sensitivity and selectivity, as well as good stability, reproducibility and anti-biofouling. This reliable approach was established to monitor Cl- in mouse brain.