Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

Effects of gentamicin on choline acetyltransferase expression in paraolivary nucleus neurons of guinea pigs

BACKGROUND： It is generally accepted that gentamicin can damage the cochlear nerve and acoustic nerve. In recent years, scholars have focused on neuronal changes and neurochemical information in the brainstem primary auditory center. OBJECTIVE： To explore morphological changes of choline acetyltransferase （ChAT）-positive neurons in the paraolivary nucleus （PON） of guinea pigs, and the effect on hearing following gentamicin injection. DESIGN, TIME AND SETTING： Randomized grouping and morphological observational study was performed at Animal Experimental Center of General Hospital of Shenyang Military Area Command of Chinese PLA from January to August 2007. MATERIALS： A total of 48 healthy guinea pigs were randomly divided into model （n = 40） and control （n = 8） groups. The model group was divided into five subgroups at five time points of 1 and 3 days, 1, 2, and 3 weeks. METHODS： Guinea pigs in the model group were intraperitoneally injected with gentamicin, and those in the control group were intraperitoneally injected with the same volume of saline. MAIN OUTCOME MEASURES： Auditory brainstem-evoked potential was used to record auditory threshold; distribution and morphological changes of ChAT-positive neurons in the PON were observed with immunohistochemistry; section area and gray value of ChAT-positive neurons were measured with Quantimet 570 image-analyzing system. RESULTS： ChAT-positive neurons were diffusedly distributed in the PON. The majority was composed of large, round cells, with positive neurites that could be clearly observed. Following gentamicin injection, the positive neurons displayed an irregular outline, and their neurites began to shorten and disappear. The gray value increased with prolonged gentamicin administration （P 〈 0.05）. In addition, the somatic cross-sectional area was enlarged in the model group at 1 and 3 days after injection （P 〈 0.05）, whereas cell number significantly decreased at ;three weeks after injection （P 〈 0.05）. Starting at 3-4 days, behavioral features and auditory degrees became gradually aggravated with prolonged gentamicin administration （P 〈 0.05）. CONCLUSION： Gentamicin damaged ChAT-positive neurons in the PON, and long-term gentamicin treatment aggravated hearing impairment.

A review of removal technology for antimony in aqueous solution

Antimony(Sb)and its compounds,toxic metalloid,have been classified as high-priority pollutants.Increasing Sb released into the water environment by natural processes and anthropogenic activities,which exposure threatens to human health and ecosystems.Therefore,it is of unquestionable importance to remove Sb from polluted water.Keeping in view the extreme importance of this issue,we summarize the source,chemistry,speciation,distribution,toxicity,and polluted situation of Sb about aqueous solution.Then,we provide the recent and common technology to remove Sb,which are based on adsorption,coagulation/flocculation,electrochemical technology,membrane technology,ion exchange,etc.In this review,we focus in detail on the adsorption method,researchers at present have been investigating to discover more advanced,cost-effective,eco-friendly,reusable adsorbents.However,to date the Sb-containing wastewater treatment technologies are not sufficiently developed and most of research have been tested only in controlled lab conditions.Few reports are available that include field studies and applications.We critically analyzed the salient features and removal mechanisms,evaluating benefits and limitations of these technologies,hoping to provide more references for further research.Finally,we considered the Fe-or Mn-based technologies was the most promising technique to remove Sb for field application.

Antimony smelting process generating solid wastes and dust:Characterization and leaching behaviors

A large amount of solid waste has been produced by the antimony smelting process in the＂World Capital of Antimony＂, Xikuangshan area in China. This study comprehensively investigated the physical and chemical characteristics of the various solid wastes, as well as the leaching behavior of the solid wastes, which included water-quenched slag,arsenic-alkali residue, desulfurized slag and blast furnace dust. These four types of waste were enriched in a variety of heavy metals and metalloids and more specifically with As and Sb levels up to 8.6 × 104 and 3.16 × 105mg/kg, respectively, in arsenic-alkali residue. For desulfurized slag and water-quenched slag, the leaching concentration of Sb significantly exceeded the acceptable limits during the leaching tests using the toxicity characteristic leaching procedure and the synthetic precipitation leaching procedure. In addition, As leaching in arsenic-alkali residue was extraordinarily hazardous, being three orders of magnitude higher than the regulatory level of As. According to the results of the extraction tests, all the tested wastes were classified as hazardous waste.

Advanced regeneration and fixed-bed study of ammonium and potassium removal from anaerobic digested wastewater by natural zeolite

Highly efficient regeneration of natural zeolite was developed in conjunction with the removal of high concentrations of ammonia and potassium from the reverse osmosis effluent of anaerobic-digested wastewater by fixed-bed ion exchange.The elution and uptake behavior of ammonium and potassium in the fixed bed were studied.Both batch desorption tests and on-column regeneration were conducted to develop an optimum regeneration condition compatible with the wastewater requirements.The effectiveness of ammonium elution increased with increasing alkaline concentration.The increase of salt dose significantly enhanced the ammonium maximum in the elution solution.Complete ammonium elution was achieved in 6 bed volumes（BV） when the alkaline and salt concentrations were respectively 0.1 mol/L and 18.6 g/L at a flow rate of 2.5-3.0 BV/hr.Due to the higher affinity of potassium with natural clinoptilolite,complete potassium elution was not achieved in all cases.

pH-dependent release characteristics of antimony and arsenic from typical antimony-bearing ores

The pH-dependent leaching of antimony（Sb） and arsenic（As） from three typical Sb-bearing ores（Banxi, Muli and Tongkeng Antimony Mine） in China was assessed using a pH-static leaching experiment. The pH changes of the leached solutions and pH-dependent leaching of Sb and As occurred in different ways. For the Banxi and Muli Sb ores, alkaline conditions were more favorable for the release of Sb compared to neutral and acidic conditions, but the reverse was true for the pH-dependent release of As. For the Tongkeng Sb ore, unlike the previous two Sb-bearing ores, acidic conditions were more favorable for Sb release than neutral and alkaline conditions.The ores with lower Sb and As contents released higher percentages of their Sb and As after 16 day leaching, suggesting that they are the largest potential sources of pollution. This work may provide key information on the geochemistry of Sb and As in the weathering zone.

Reactive oxygen species may play an essential role in driving biological evolution: The Cambrian Explosion as an example

The Cambrian Explosion is one of the most significant events in the history of life;essentially all easily fossilizable animal body plans first evolved during this event. Although many theories have been proposed to explain this event, its cause remains unresolved.Here, we propose that the elevated level of oxygen, in combination with the increased mobility and food intake of metazoans, led to increased cellular levels of reactive oxygen species（ROS）, which drove evolution by enhancing mutation rates and providing new regulatory mechanisms. Our hypothesis may provide a unified explanation for the Cambrian Explosion as it incorporates both environmental and developmental factors and is also consistent with ecological explanations for animal radiation. Future studies should focus on testing this hypothesis, and may lead to important insights into evolution.

The coupling of sand with ZVI/oxidants achieved proportional and highly efficient removal of arsenic

The coupling of zero-valent iron(ZVI)with common oxidants has recently achieved very rapid and highly efficient removal of Heavy metals from wastewater.However,the uniform activation of ZVI throughout the column and the proportional removal of target contaminants are urgently required for the prevention of premature filter clogging and the extension of the effective column operational time.In this study,we successfully achieved this objective by simply doping granular sand with ZVI at appropriate weight ratios.When pure ZVI packed column was spiked with oxidants,the majority of As trapping occurred between the column inlet and the first sampling point.In a packed column with a 1:20 mixture of ZVI and sand,the average As removal efficiency was 36(1st),13.1(2nd),18.5(3rd),19.2(4th)and 5.9%(5th outlet).The overall arsenic removal performance of the composite filling system of ZVI/sand was equally as efficient as that of the previous pure ZVI-packed system.Moreover,the leaching of Fe was significantly reduced with an increased sand ratio,resulting in clearer water with less turbidity.The results of X-ray photoelectron spectroscopy(XPS)demonstrated that more than 54%of the arsenic was reduced to As(III).X-ray diffraction(XRD)and scanning electron microscopy(SEM)confirmed the extensive corrosion of the ZVI surface,which resulted in various species of iron oxyhydroxides responsible for the highly efficient sequester of arsenic through reduction,adsorption,and coprecipitation.

Rapid and long-effective removal of broad-spectrum pollutants from aqueous system by ZVI/oxidants

Zero-valent iron(ZVI)technology has recently gained significant interest in the efficient sequestration of a wide variety of contaminants.However,surface passivation of ZVI because of its intrinsic passive layer would lead to the inferior reactivity of ZVI and its lower efficacy in contaminant removal.Therefore,to activate the ZVI surface cheaply,continuously,and efficiently is an important challenge that ZVI technology must overcome before its wide-scale application.To date,several physical and chemical approaches have been extensively applied to increase the reactivity of the ZVI surface toward the elimination of broad-spectrum pollutants.Nevertheless,these techniques have several limitations such as low efficacy,narrow working pH,eco-toxicity,and high installation cost.The objective of this mini-review paper is to identify the critical role of oxygen in determining the reactivity of ZVI toward contaminant removal.Subsequently,the effect of three typical oxidants(H2O2,KMnO4,and NaClO)on broad-spectrum contaminants removal by ZV1 has been documented and discussed.The reaction mechanism and sequestration efficacies of the ZVI/oxidant system were evaluated and reviewed.The technical basis of the ZVI/oxidant approach is based on the half-reaction of the cathodic reduction of the oxidants.The oxidants commonly used in the water treatment industry,i.e.,NaClO,O3,and H2O2,can be served as an ideal coupling electron receptor.With the combination of these oxidants,the surface corrosion of ZVI can be continuously driven.The ZVI/oxidants technology has been compared with other conventional technologies and conclusions have been drawn.