ELEMENTAL CONTENTS IN ORGANS AND TISSUES OF CHINESE ADULT MEN

Objective To provide basis of reference values for relevant parameters of Chinese Reference Man. Methods Eighteen kinds of major organ or tissue samples, including muscle, rib, liver, and so on, were obtained from 4 areas (Hebei, Shanxi, Jiangsu, and Sichuan provinces) with different dietary patterns in China in autopsy of 16 healthy adult men, who had just encountered sudden deaths. At the same time, whole blood samples were collected from 10 volunteers living in each of these areas. The concentrations of 56 elements in these samples were detected by using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES), and Graphite Furnace Atomic Absorption Spectrometry (GF-AAS) techniques. Based on obtained concentrations and reference values of these organ or tissue weights for Chinese Reference Man, the relative elemental burdens in these organs or tissues as well whole body were also estimated. Results The concentrations of 56 elements in 18 main organs or tissues were determined all together and their elemental organ or tissue and whole body burdens were estimated. Furthermore, the distributions of important elements for radiation protection in these organs or tissues were emphatically discussed. Conclusion By summing with past related results, the total results obtained from the series of research may provide more reliable and better representative basis of these reference values for Chinese Reference Man than before.

Recommendations on Strengthening the Development of Nuclear Medicine in China

This paper outlines briefly the role of nuclear medicine in life sciences and health care. Molecular imaging by using isotopic tracers can noninvasively visualize the chemistry or hidden process in the cells and tissues inside the body, obtaining "functional" images to provide early information of any disease and revealing the secrets of life. The vitality of nuclear medicine is its ability to translate bench into new clinical application that can benefits the patients. Although nuclear medicine community in China has made significant achievement with a great effort since 1950s, there are many obstacles to future development. Recommended measures are proposed here in an attempt to solve our existing problems.

Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line

Attrora-A kinase, a serine/threonine protein kinase, is a potential oncogene. Amplification and overexpression of Aurora-A have been found in several types of human tumors, including esophageal squamous cell carcinoma （ESCC）. It has been demonstrated that cells overexpressing Attrora-A are more resistant to cisplatin-induced apoptosis. However, the molecular mechanisms mediating these effects remain largely unknown. In this report, we showed that overexpression of Attrora-A through stable transfection of pEGFP-Aurora-A in human ESCC KYSE150 cells significantly promoted cell proliferation and inhibited cisplatin- or UV irradiation-induced apoptosis. Cleavages of caspase-3 and poly （ADPribose） polymerase （PARP） in Attrora-A overexpressing cells were substantially reduced after cisplatin or UV treatment. Furthermore, we found that silencing of endogenous Aurora-A kinase with siRNA substantially enhanced sensitivity to cisplatin- or UV-induced apoptosis in human ESCC EC9706 cells. In parallel, overexpression of Aurora-A potently upregulated the expression of Bcl-2. Moreover, the knockdown of Bcl-2 by siRNA abrogated the Aurora-A＇s effect on inhibiting apoptosis. Taken together, these data provide evidence that Aurora-A overexpression promoting cell proliferation and inhibiting apoptosis, suggesting a novel mechanism that is closely related to malignant phenotype and anti-cancer drugs resistance of ESCC cells.

Study of the External Dose Rate and Retained Body Activity of Patients with Hyperthyroidism Who Are Receiving Ⅰ-131 Therapy

Hyperthyroidism refers to a clinical state that results from inappropriately hight hyroid hormone levels in the tissues;.Ⅰ-131 therapy plays a critical role and provides a remarkable curative effect in targeting thyroid diseases. Thyroid cells can take up isotope I-131, which emits not only beta rays but also

Commensal microbiota in the digestive tract:a review of its roles in carcinogenesis and radiotherapy

The human microflora is a complex ecosystem composed of diverse microorganisms mainly distributed in the epidermal and mucosal habitats of the entire body,including the mouth,lung,intestines,skin,and vagina.These microbial communities are involved in many essential functions,such as metabolism,immunity,host nutrition,and diseases.Recent studies have focused on the microbiota associated with cancers,particularly the oral and intestinal microbiota.Radiotherapy,the most effective cytotoxic modality available for solid tumors,contributes to the treatment of cancer patients.Mounting evidence supports that the microbiota plays pivotal roles in the efficacy and prognosis of tumor radiotherapy.Here,we review current research on the microbiota and cancer development,and describe knowledge gaps in the study of radiotherapy and the microbiota.Better understanding of the effects of the microbiome in tumorigenesis and radiotherapy will shed light on future novel prevention and treatment strategies based on modulating the microbiome in cancer patients.

Semi-synthesis and Crystal Structure of Sophoridine N-oxide

Sophoridine N-oxide was synthesized and characterized by 1H-NMR,EI-MS,IR and elemental analysis,together with X-ray single-crystal diffraction analysis,and its crystal structure was reported for the first time.The crystal belongs to the orthorhombic system,space group P212121 with a = 8.321（2）,b = 15.650（3）,c = 24.352（5） ,V = 3171.1（11） 3,Z = 8,Dc = 1.258 g/cm3,λ（CuKα） = 1.54178,F（000） = 1440,the final R = 0.0351 and wR = 0.0970.The crystal structure shows Sophoridine N-oxide crystallizes with two host molecules of similar conformation and four water solvent molecules in the asymmetric unit.In the crystal structure,intermolecular O-H…O hydrogen bonds link the constituent molecules into a 2D layer structure,which further extends to a 3D supramolecular architecture via Van der Waals interactions and intermolecular O-H…O hydrogen bonds.

Regulation Effect of miR-34a Expression on Radiosensitivity of Lung Adenocarcinoma Cells by Targeting Bcl-2 and CDK4/6 Signaling Pathways

Objective: Radiotherapy has been widely used to treat lung cancer. However, non-small lung cancer cells are insensitive to radiation, diminishing their radiotherapy effects. Although the radiosensitivity of the non-small lung cancer cells was reported to be enhanced through regulating miR-34a, the regulation effects of miR-34a expression on radiosensitivity of lung adenocarcinoma cells through target genes CDK4, CDK6, CyclinD1, and Bcl-2/Bax have not been systematically investigated. Methods: In this study, we investigated the effect of miR-34a expression on the Bcl-2, CDK4, and CDK6 pathways in lung adenocarcinoma cells, to provide new insights into the sensitization treatment of lung cancer. We first studied the effect of miR-34a expression on H1299 and A549 cell activity. Then to investigate the mechanisms of radiosensitivity, we focused on apoptosis, cell cycle, and target genes. Results: We find that overexpression of miR-34a in lung adenocarcinoma cells inhibits cell activity, and improves radiosensitivity. Specifically, overexpression of miR-34a suppresses the expression of target genes CDK4, CDK6, CyclinD1, and Bcl-2/Bax, which leads to cell cycle arrest and promotes apoptosis of lung adenocarcinoma cells. Conclusions: Overall, our results demonstrate that the overexpression of miR-34a enhances the radiosensitivity of lung adenocarcinoma cells, indicating that miR-34a is a sensitizer for lung adenocarcinoma radiotherapy.

Mechanism of Visible Photoactivity of F-Doped TiO2

We calculate the electronic structure and optical properties of F-doped anatase TiO2. The results indicate that the band gap ofF-doped TiO2 increases slightly compared with the pure TiO2. However, it is interesting that the visible absorption of F-doped TiO2 located between 600 and 700 nm is observed, and it enhances gradually with the increasing F concentration. Furthermore, according to the results of densities of states and imaginary part of dielectric function ε2（ω）, we propose that the transition between Ti 3d and Ti 3d states may be responsible for the visible absorption, but not the band gap narrowing.

Anti-tumor Activities of Novel Estrogen Compound 17aα-D-Homo-Ethynylestradiol-3-Acetate

Objective： To study the anti-tumor activities of novel estrogen compound 17a α-D-homo-ethynylestradiol-3-acetate in vitro and in vivo. Methods： In vitro anti-tumor activity was assayed in adenoma cells A549 and human liver cancer cells Bel-7402 using MTT method, and half-inhibitory concentration （IC50） were observed. In vivo the pulmonary adenoma LA795 cells was selected and the conventional assay method of anti-tumor activity was employed. 5, 7.5, 10 mg/kg of 17a α-D-homo-ethynylestradiol-3-acetate was administered by i.p., and tumor-inhibitory rate, thymus and spleen indexes, bone marrow cells （BMC） were observed. Results： IC50 of 17a α-D-homo-ethynylestradiol-3-acetate in vitro for A549 and Bel-7402 cells were 12.28 μg/ml and 17.79 μg/ml, respectively. In vivo the highest tumor-inhibitory rates for LA795 was 60.0% （P〈0.01）. The drug had hardly any side-effect in spleen indexes, thymus indexes, and BMC compared with control mice. Nevertheless, compared with the positive control drug cyclophosphamide （CY）, thymus and spleen indexes, BMC showed obvious differences （P〈0.01）. Conclusion： 17a α-D-homo-ethynylestradiol-3-acetate has obvious anti-tumor activities in vitro and in vivo with low side-effect, thus worth further investigation.

A Novel Approach for Evaluation of Food Functions and Safety Applied in RR GM Soybeans

[Objective] This study aimed to evaluate tbe healthy risk of genetically modified （ GM ） soybeans by using a novel approach for functions and safety of food. [ Me^od] Different from traditional evaluation of substantial equivalence, three great innovations were performed in this study, involving in basic diet, evalu- ation approaches and principle, as well as the clarification of connotation differences between absolute and relative mass of organs. Hence a novel BDI-GS （Bendib Damage Index and General Score） evaluation approach was established and applied in comparative evaluation between RR GM and natural soybeans. Healthy male ICR mice during linear growth were selected; experimental mice were fed with 15% RR GM soybeans and 15% natural soybeans blending maize meal diets, and control mice were fed with single maize meal diet for 13 d; the mice were dissected after collecting blood samples and perfectly obtained nine organs or tissues to re- cord their masses and conduct statistical analyses. [Result] Plenty of matching information was obtained through simple design. The growth performance of treated mice was markedly of individual differences, some mice were thwarted due to regular intake of RR soybeans. Meanwhile, the functions and safety of RR soybeans were markedly lowered in overall nutritional and healthy effects than those of natural soybeans expressed in GS values, and presents some declines in nutrition and health of thymus, pancreas and spermary; especially, it can make thymus immune （P 〈0.05） in markedly lower level than that of natural soybeans. [ Conclusion] Therefore, major troubles and risks of RR soybeans intake are of personal risks in different degrees, in addition, it may increase sub-health and related chronic epi- demics risks, and herein it will presents certain safety issues. The creation of this novel evaluation system provides a simple and available evaluation approach for functions and potential risks revelation of food effects, and will yield far-reaching influences to safety evaluation and healthy development of GM foods, as well as public health.

Discovery of the radio-protecting effect of Ecliptae Herba,its constituents and targeting p53-mediated apoptosis in vitro and in vivo

Radiation protection drugs are often accompanied by toxicity,even amifostine,which has been the dominant radio-protecting drug for nearly 30 years.Furthermore,there is no therapeutic drug for radiation-induced intestinal injury(RⅢ).This paper intends to find a safe and effective radioprotecting ingredient from natural sources.The radio-protecting effect of Ecliptae Herba(EHE) was discovered preliminarily by antioxidant experiments and the mouse survival rate after137Cs irradiation.EHE components and blood substances in vivo were identified through UPLC-Q-TOF.The correlation network of “natural components in EHE-constituents migrating to blood-targets-pathways” was established to predict the active components and pathways.The binding force between potential active components and targets was studied by molecular docking,and the mechanism was further analyzed by Western blotting,cellular thermal shift assay(CETSA),and Ch IP.Additionally,the expression levels of Lgr5,Axin2,Ki67,lysozyme,caspase-3,caspase-8,8-OHd G,and p53 in the small intestine of mice were detected.It was found for the first time that EHE is active in radiation protection and that luteolin is the material basis of this protection.Luteolin is a promising candidate for RⅢ.Luteolin can inhibit the p53 signaling pathway and regulate the BAX/BCL2 ratio in the process of apoptosis.Luteolin could also regulate the expression of multitarget proteins related to the same cell cycle.

Enhanced catalysis of ultrasmall Au-MoS_2 clusters against reactive oxygen species for radiation protection

Ionizing radiation produces excessive reactive oxygen species （ROS） which impose detrimental effects on biological systems. Thus, it is important to explore clinically safe and efficacious radioprotection agents to scavenge ROS and reduce the risks of radiotherapy. Recently, emerging catalytic nanomaterials such as sulfide nanomaterials have shown capability of clearing ROS in vivo by unique electron transfers between atoms, but their catalytic activities are yet suboptimal. As such, there is an unmet need to improve cat- alytic properties for stronger antioxidant activities and radiation protection. Herein, we prepared ultra- small Au-MoS2 clusters （~2.Snm） and they showed enhanced catalytic properties via gold intercalation facilitating increased active sites and synergistic effects. Electrocatalysis results revealed that the catalytic activity of Au-MoS2 towards 1-1202 was superior to ultrasmall MoS2 without Au. As a result, we found that improving the electrocatalytic property of Au-MoS2 can effectively enhance corre- sponding antioxidant activities and radioprotection effects in vivo. In addition, Au-MoS2 also showed sig- nificant radioprotection in vitro and dramatically reduced the excess of radiation-induced adverse ROS. It also rescued radiation-induced DNA damages and protected the bone marrow hematopoietic system from ionizing radiation.

Author correction to‘Discovery of the radioprotecting effect of ecliptae herba,its constituents and targeting p53-mediated apoptosis in vitro and in vivo’[Acta Pharm Sin B 13(2023)1216-1230]

The authors regret that there is an error in the article Fig.4B due to the mistake of copying and pasting in the process of assembling figures and negligence in the proofreading.Although it does not affect the conclusion,it is an obvious error.The authors have now modified as below.The authors apologize for any inconvenience caused to the journal and readers.

Research progress on biodosimeters of ionizing radiation damage

Ionizing radiation can cause radiation injury to the human body under certain circumstances,such as unexpected radiation accidents and nuclear terrorist attacks.Methods that can accurately and rapidly measure the biological effects are necessary for rational triage and treatment of affected patients.In recent decades,significant researches attention has been focused on the development of accurate and efficient biodosimeters.In this review,we summarize recent developments in biological dosimeters,with a primary focus on cell-based and molecular markers,including comet assay,dicentric chromosome aberration,γ-H2AX,micronuclei,microRNA,lncRNA,and 8-Oxo-dG.

Study on urine biomarkers of radiation-induced injury guided by Caenorhabditis elegans as a model organism

Objective:Under the guidance of model organism Caenorhabditis elegans with fine olfactory system,small molecular metabolites sensitive to high dose radiation were screened as biomarkers of acute radiation-induced injury,and their metabolic pathways were elucidated by enrichment.Methods:Rats were irradiated with 12 Gyγ-rays to establish an acute radiation injury model,and their urine was fingerprinted using UPLC-Q/TOF-MS.Further,under the guidance of Caenorhabditis elegans as olfactory-sensitive model organism,the key differential metabolites in urine were found as biomarkers of radiation-induced injury.Results:After rats were irradiated,the radiation injury urine showed a difference from control(sham-irradiated)urine,which could be distinguished by Caenorhabditis elegans.Based on metabolomics analysis,a total of 21 key differential metabolites with P value<0.05 and fold change either>2 or<0.5 were identified,which can be used as sensitive and reliable biomarkers of radiation-induced injury.The pathways were further enriched,and it was found that disorders of five metabolic pathways,including citric acid cycle and amino acid metabolism,play an important role in radiation-induced injury.Conclusions:Due to radiation injury,the metabolites in urine will change significantly.The study on biomarkers guided by model organism Caenorhabditis elegans provides a new perspective to explain the details of metabolic disorders,and also provides experimental basis for the development of new biological dosimeters.

Status of hyperhomocysteinemia in China: results from the China Stroke High-risk Population Screening Program, 2018

A nationwide survey was conducted from October 2018 to September 2019 to assess the prevalence of hyperhomocysteinemia(Hhcy)and its influencing factors in China.A standardized questionnaire was used to collect information.Hhcy was defined as the level of serum homocysteine(HCY)≥15.0µmol/L.The H-type hypertension(HHYP)was defined as hypertension with an elevated serum HCY(≥15.0µmol/L).Finally,110551 residents≥40 years of age from 31 provinces in the mainland of China were included.Overall,the median serum HCY level was 10.9µmol/L(interquartile range 7.9–15.1).A total of 28633 participants(25.9%)were defined as Hhcy.The Hhcy prevalence ranged from 7.9%in Shanghai to 56.8%in Tianjin.The data showed that serum HCY levels were associated with age,male gender,cigarette smoking,hypertension,diabetes,ethnicity,endurance in exercise(inverse),and fruit and vegetable intake(inverse).In addition,15486 participants were defined as HHYP,and the rate was 14.0%.HHYP was an independent predictor of stroke with an adjusted odds ratio of 1.752(95%CI 1.338–2.105).The geographical distribution pattern of the Hhcy epidemic reflects dynamic differences,and national strategies should be carried out to further improve the care of patients with Hhcy across China.

Oxysophoridine Suppresses the Growth of Hepatocellular Carcinoma in Mice:In Vivo and cDNA Microarray Studies

Objective：To observe the in vivo effects of oxysophoridine on hepatocellular carcinoma in mice and to study the related mechanisms.Methods：C57BL mice were inoculated with mouse hepatoma H22 cells subcutaneously,then divided into 5 groups（14 per group）,and treated with oxysophoridine（50,100,or 150 mg/kg） or cisplatin（4 mg/kg） for 10 days.Inhibitory rate of tumor,body weight gain,and influence indices on internal organs（liver,spleen and thymus） were evaluated.The differentially expressed genes between the oxysophoridine-treated group,and the control group were analyzed using cDNA microarray and quantitative real-time PCR（qRT-PCR） experiments.Results：Compared with the tumor weight of the control group（2.75±0.66 g）,oxysophoridine significantly suppressed hepatocellular carcinoma growth in mice（P0.01）,with 0.82±0.36 g,0.57±0.22 g,and 1.22±0.67 g for the tumor weight in the low,moderate,and high dose treatment group, respectively.The moderate dose led to the highest inhibitory rate,79.3%.Observation of body weight gain and influence on three organs showed that compared with cisplatin,oxysophoridine produced fewer side effects in vivo.cDNA microarray and qRT-PCR showed that the most significant differentially expressed genes in the tumor samples of oxysophoridine-treated mice were mostly involved in regulating apoptosis,with the Tnfrsf11b （osteoprotegerin） gene being the most significantly affected.Conclusion：Oxysophoridine was a promising compound for developing drugs against hepatocellular carcinoma,and its anti-hepatoma effect was probably related to osteoprotegerin activation.

Highly efficient catalytic scavenging of oxygen free radicals with graphene-encapsulated metal nanoshields

Normal levels of oxygen free radicals play an important role in cellular signal transduction, redox homeostasis, regulatory pathways, and metabolic processes. However, radiolysis of water induced by high-energy radiation can produce excessive amounts of exogenous oxygen free radicals, which cause severe oxidative damages to all cellular components, disrupt cellular structures and signaling pathways, and eventually lead to death. Herein, we show that hybrid nanoshields based on single-layer graphene encapsulating metal nanoparticles exhibit high catalytic activity in scavenging oxygen superoxide （·O2^-）, hydroxyl （·OH）, and hydroperoxyl （HO2·） free radicals via electron transfer between the single-layer graphene and the metal core, thus achieving biocatalytic scavenging both in vitro and in vivo. The levels of the superoxide enzyme, DNA, and reactive oxygen species measured in vivo dearly show that the nanoshields can efficiently eliminate harmful oxygen free radicals at the cellular level, both in organs and circulating blood. Moreover, the nanoshields lead to an increase in the overall survival rate of gamma ray-irradiated mice to up to 90%, showing the great potential of these systems as protective agents against ionizing radiation.

Layered Double Hydroxide Modified by PEGylated Hyaluronic Acid as a Hybrid Nanocarrier for Targeted Drug Delivery

In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU)as electronegative model drug, a new type of organic-inorganic hybrid drug delivery system(LDH/HA-PEG/5-FU)was conceived and manufactured by the adsorption of PEGylated hyaluronic acid(HA-PEG)on the surface of layered double hydroxide(LDH, prepared via hydrothermal method)and the intercalation of 5-FU in the interlamination of LDH via ion exchange strategy. The drug loading amount of LDH/HA-PEG/5-FU achieved as high as 34.2%. LDH, LDH/5-FU and LDH/HA-PEG/5-FU were characterized by FT-IR, XRD, TGA, laser particle size analyzer and SEM. With the benefit of p Hdegradable feature of LDH and enzyme-degradable feature of HA, LDH/HA-PEG/5-FU showed p H-degradable and enzyme-degradable capacity in in vitro drug release. Moreover, the drug carrier LDH/HA-PEG contained biocompatible PEG and tumor-targeted HA, resulting in lower cytotoxicity and better endocytosis compared with LDH in vitro. It was suggested that the organic-inorganic hybrid drug delivery system, which was endowed with the properties of controlled release, low toxicity and tumor-targeting delivery for ameliorative cancer therapy, was advisable and might be applied further to fulfill other treatments.

Supramolecular co-assembly of self-adjuvanting nanofibrious peptide hydrogel enhances cancer vaccination by activating MyD88-dependent NF-κB signaling pathway without inflammation

Peptide vaccine targeting tumor-specific antigens is a promising cancer treatment regimen.However,peptide vaccines are commonly low-immunogenic,leading to suboptimal antitumor T-cell responses.Current peptide vaccination approaches are challenged by the variability of peptide physicochemical characters and vaccine formulations,flexibility,and the broad feasibility.Here,the supramolecular co-assembly of antigen epitope-conjugated peptides(ECPs)targeting CD8 or CD4 T-cell receptors was used to engineer a nanofibrious hydrogel vaccine platform.This approach provided precise and tunable loading of peptide antigens in nanofibers,which notably increased the antigen uptake,cross-presentation,and activation of dendritic cells(DCs).Immunization in mice indicated that the co-assembled peptide hydrogel did not induce local inflammation responses and elicited significantly promoted T-cell immunity by activating the MyD88-dependent NF-κB signaling pathway in DCs.Vaccination of mice using co-assembled peptide vaccine stimulated both enhanced CD8 and CD4 T cells against EG.7-OVA tumors without additional immunoadjuvants or delivery systems,and resulted in a more remarkable cancer immunotherapy efficacy,compared with free peptide vaccine or aluminum-adjuvanted peptide formulation.Altogether,peptide co-assembly demonstrated by three independent pairs of ECPs is a facile,customizable,and chemically defined approach for co-delivering peptide antigens in self-adjuvanting hydrogel vaccines that could induce stronger anticancer T-cell responses.