Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To investigate the present situation of radiation environment in Beijing and provide data support for monitoring and management of radiation environment in Beijing. Methods The γ radiation dose rate of environmental surface as well as the radioactive levels of aerosol, sediment, surface water, and soil samples were monitored in Beijing from 2015 to 2022. The radioactive levels of various environmental elements in this area were presented using statistical charts and statistical tables, and the related issues were discussed. Results The automatic monitoring and cumulative monitoring results of γ radiation dose rate were in the range of local natural background fluctuation. The radioactive levels of beryllium-7, lead-210, and polonium-210 in aerosols were low in summer and high in winter. The radioactive levels of total α, total β, and beryllium-7 in sediments were low in winter and high in summer. The activity concentration of radionuclide potassium-40 in aerosols and sediments did not change significantly with seasons. The total α and total β radioactivity levels of surface water fluctuated within the range of background. These values of reservoir water were within the limits specified in the Hygienic Standard for Drinking Water (GB 5749—2006). Natural radionuclides in soil were within the range of natural background fluctuation, and artificial radionuclides in soil were within the range of normal fluctuation over the years. Conclusion From 2015 to 2022, the environmental surface γ radiation dose rate as well as aerosol, sediment, surface water, and soil radioactivity levels in Beijing were generally low, all of which fluctuated within the environmental background.

Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules,and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers. Methods In this study,210 different structural types of VOCs were selected from the VOCMM penetration enhancer database,and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2),cholesterol(CHL),and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control,Nootkatone,and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments,with three rats in each group.The donor pool solutions were 3%gastrodin,3%gas-trodin+3%nootkatone,and 3%gastrodin+3%3-butylidenephthalide,respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12,μg/cm2). Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA,and hydrogen bonded to the head group of CER2.Among them,sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings,benzene rings,and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis,most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09 μg/cm2,and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5 503.00±1 080.00 μg/cm2,P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98 μg/cm2,P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2. Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers,and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.

Objective:To investigate prognostic factors for acral lentiginous melanoma (ALM) , and to construct a nomogram to verify the predictive value of these factors.Methods:Clinical data on 1 573 patients with ALM were collected from the Surveillance, Epidemiology, and End Results (SEER) database of National Cancer Institute in United States between 2004 and 2015. Data about patients′ age, gender, ulcer status, SEER staging, surgical protocols, T-, N- and M-staging, overall survival rates and disease-specific survival rates were extracted. Chi-square test was used to analyze the correlation of clinical characteristics with overall survival rates and melanoma-specific survival rates, and univariate and multivariate Cox proportional hazards regression models were used to investigate prognostic factors and establish predictive models.Results:Among the 1 537 patients with ALM, 714 were males, 823 were females, 818 were under 64 years of age, and 1 363 were Caucasian. Skin lesions occurred on the lower limbs and buttocks in 1 205 cases, and 974 cases had ulcers; according to the SEER staging, non-spread localized skin lesions were observed in 1 048 cases. There were significant differences in the mortality rate among patients of different ages at diagnosis, different gender, with different ulcer status, surgical status, and at different SEER stages, T-stages, N-stages and M-stages (all P < 0.001) . Univariate and multivariate Cox regression analysis showed that age ≥ 65 years, male, ulcers and distant lymph node metastasis in the SEER staging were associated with increased risk of death in the patients (all P < 0.05) , and the mortality rate was significantly higher in the patients with T2-, T3- or T4-stage ALM than in those with T1-stage ALM (all P < 0.05) , and higher in the patients with N1-, N2- and N3-stage ALM than in those with N0-stage ALM (all P < 0.05) . Conclusion:Age, gender, ulcer status, SEER stage, T-stage and N-stage are independent prognostic factors for overall survival rates and disease-specific survival rates of ALM.

Objective:To analyze locoregional recurrence (LRR) pattern of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, with and without adjuvant radiotherapy (RT). Methods:A total of 5442 eligible patients with breast cancer from 12 Chinese centers were included. The LRR sites and the effect of RT at different sites on recurrence in patients with and without RT were analyzed. The Kaplan-Meier method was used to calculate the cumulative LRR rate, and the difference was compared by the log-rank test.Results:With a median follow-up time of 63.8 months for the entire cohort, 395 patients developed LRR. The chest wall and supraclavicular fossa were the most common LRR sites, regardless of RT or molecular subtypes. The 5-year chest wall recurrence rates for patients with and without chest wall irradiation were 2.5% and 3.8%( P=0.003); the 5-year supraclavicular lymph nodal recurrence rates for patients with and without supraclavicular fossa irradiation were 1.3% and 4.1%( P<0.001); the 5-year axillary recurrence-free rates for patients with and without axillary irradiation were 0.8% and 1.5%( HR=0.31, 95% CI: 0.04-2.23, P=0.219); and the 5-year internal mammary nodal recurrence-free rates for patients with and without internal mammary nodal irradiation were 0.8% and 1.5%( HR=0.45, 95% CI: 0.11-1.90, P=0.268). Conclusions:The chest wall and supraclavicular fossa are the most common LRR sites of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, which is not affected by adjuvant RT or molecular subtypes. The chest wall and supraclavicular fossa irradiation significantly reduce the risk of recurrence in the corresponding area. However, axillary and internal mammary nodal irradiation has no impact on the risk of recurrence in the corresponding area.

Objective To investigate and evaluate the changes in total α and total β radioactivity levels in drinking water in Beijing, China, 2012—2021. Methods The test results of total α and total β radioactivity levels at 14 monitoring sites from 9 groundwater sources and 5 surface water sources in Beijing, 2012—2021 were collected. The radioactivity levels in the two types of water sources were compared. Statistical charts were used to show the monitoring situation at sampling sites in different regions during different periods, and related issues were explored. Results The total α and total β activity concentrations measured at monitoring sites from some water sources in Beijing, 2012—2021, were less than the total α and total β guideline values specified in the Standards for Drinking Water Quality (GB 5749—2006) (total α: 0.5 Bq/L, total β: 1.0 Bq/L). The mean total α activity concentration in the groundwater was significantly higher than that in the surface water. The total α and total β radioactivity levels in the reservoir D in the surface water were slightly higher than those in the other surface water. Conclusion In the past decade from 2012 to 2021, the total α and total β radioactivity levels in some water sources in Beijing were generally in a good condition and fluctuated within the range of environmental background values, without significant changes on the whole.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/β-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.
Adult ; Aged ; Animals ; Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition/genetics* ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism* ; Kinesins/metabolism* ; Liver Neoplasms/pathology* ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Neoplasm Staging ; Prognosis ; Protein Binding ; RNA, Small Interfering/metabolism* ; Survival Analysis ; Tumor Burden ; Wnt Signaling Pathway ; Xenograft Model Antitumor Assays ; beta Catenin/metabolism*

OBJECTIVE： To prepare pogostone transfersomes， and to evaluate its quality. METHODS： Film dispersion method was used to prepare pogostone transfersomes. Using the accumulative penetration volume （Qn） and accumulative penetration ratio （PR） of pogostone as evaluation indexes， the types of surfactant， formulation were screened in respects of the dosage of surfactant and the dosage of pogostone. The pogostone transfersomes were prepared with optimal formulation； the morphology， particle size distribution and Zeta potential were observed and the entrapment efficiency was measured. RESULTS： The optimal formulation was as follows as the sodium cholate was selected as surfactant； the dosage of sodium cholate was 0.25 g； the dosage of pogostone was 15 mg. The optimal pogostone transfersomes were ivory-white suspension； average particle size was （115.6±3.65） nm （RSD＝3.20％，n＝3）； PDI was 0.185±0.008 （RSD＝4.30％， n＝3）； Zeta potential was （－13.76±0.225） mV （RSD＝1.70％，n＝3）； entrapment efficiency of pogostone was （46.01±0.40）％ （RSD＝0.87％，n＝3）； Qn was （378.76±0.61）   μg/cm2 （RSD＝0.20％，n＝3）； PR was （89.02±0.96）％ （RSD＝1.10％，n＝3）. CONCLUSIONS： Prepared pogostone transfersomes are in line with quality requirements， which can provide reference for the further study of new dosage form of pogostone.

Objective To observe the effects ofTrametes robiniophila Murr and Isatidis Radix bidirectional fermentation products on the migration and invasion of human breast cancer MCF-7 cells and relevant factors; To discuss relevant mechanism of action.Methods Breast carcinoma cell line MCF-7 was used as research subject in this experiment. Control group, Isatidis Radix group,Trametes robiniophila Murr group, andTrametes robiniophila Murr and Isatidis Radix group were included in the experiment. The effects ofTrametes robiniophila Murr and Isatidis Radix bidirectional fermentation products on MCF-7 cell proliferation were measured by MTT method. Cell scratch assay, transwell assay and adhesion assay were used to measure the effects ofTrametes robiniophila Murrand Isatidis Radix bidirectional fermentation products on the migration, invasion and adhesion capability of MCF-7 cells, respectively. The effects ofTrametes robiniophila Murrand Isatidis Radix bidirectional fermentation products on the mRNA expression of MMP-9 and Vimentin were measured by RT-PCR.Results Compared with Isatidis Radix group andTrametes robiniophila Murrgroup, Trametes robiniophila Murr and Isatidis Radix bidirectional fermentation products could significantly inhibit the proliferation, migration, invasion and adhesion capability of MCF-7 cells (P<0.05). Similarly,Trametes robiniophila Murr and Isatidis Radix bidirectional fermentation products reduced the mRNA expression of MMP-9 and Vimentin (P<0.05).ConclusionTrametes robiniophila Murrand Isatidis Radix bidirectional fermentation products may down-regulate the expression of MMP-9 and Vimentin to inhibit the migration, invasion and adhesion capabilities of MCF-7 cells.

Objective To establish a high-throughput evaluation model for anaphylactic reactions; To screen and identify potential anaphylactogens from TCM monomeric compounds.MethodsCell model of stably expressed MrgX2 was established. Recombinate plasmid pmCherry-C1-MrgX2 was transfected to HEK293 to establish cell line for screening model. MrgX2 agonist and antagonist were used to identify the validation and stability of the cell line. A small library consisting of 180 compounds was profiled by using a cell-based calcium mobilization assay to find novel compounds targeting the MrgX2 receptor. EC50 test, IC50 test, specificity validation and cytotoxicity evaluation were carried out to detect the function of the positive agonist.ResultsThe EC50 of C48/80 to MrgX2 model was 2.7 μg/mL and the IC50 of 2-APB (evoked by 10 μg/mL C48/80) was 46.29 μmol/L. The first generation cell model of MrgX2 was similar to the 20th generation, and the Z factor of MrgX2 cell model was 0.78. In the primary screening for agonist, isoliensinine was identified as a novel agonist targeting receptor MrgX2 with an EC50 of 4.5 μmol/L and IC50 of39.47 μmol/L. Moreover, isoliensinine was validated to activate MrgX2 receptor specifically without cytotoxicity. Conclusion A high-throughput evaluation method for anaphylactic reactions can be established in vitro through calcium mobilization assay. A potential anaphylactogen isoliensinine is identified and validated.