Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

Objective To present and discuss beam characteristics of the first Mevion S250i gantry-mounted accelerator pencil beam scanning proton therapy system in China.Methods The output dose was measured using a parallel-plate ionization chamber.The integrated depth dose was measured with a large-radius Bragg peak ionization chamber,covering 19 energy levels ranging from 227 MeV to 28 MeV,to analyze the proton beam characteristics.The spots in the air were measured with Phoenix flat panel detector on the beam central axis,and the precision of the delivery position was verified by measuring the multi-spot beam map.The interleaf leakage and penumbra reduction of adaptive aperture were measured to characterize its performance.Results The proton system was calibrated for a maximum energy of 227 MeV,with a(10×10)cm2uniform field delivering 1 Gy dose at a depth of 5 cm underwater.The system effectively modulated the proton beam range to the patient's surface,maintaining a constant 80%-80%Bragg peak width of 8.6 mm at all energy levels.The spot size of the highest energy beam at the isocenter was about 4 mm in the air,and the spot delivery position error was less than 1 mm.The interleaf leakage rate of the adaptive aperture for the highest energy beam was below 1.5%,and the penumbra was significantly reduced.Conclusion Mevion S250i proton therapy system demonstrates unique design and beam characteristics,which is reflected in the Bragg peak shape,spot size variation with energy,and penumbra sharpening of adaptive aperture;and these differences should be considered in treatment planning system modeling and planning for precision treatment.

Background The serious air pollution of highway toll booths poses a high occupational exposure risk to toll collectors. It is urgent to develop purification methods suitable for airborne particles and microbial pathogens in highway toll booths. Objective To verify the purification effect of low temperature plasma air purifiers on airborne particles and microbes in highway toll booths. Methods Based on controlled-intervention design, we selected three toll booths in an expressway toll station as on-site experimental locations for 6 d (no-intervention period: the low-temperature plasma purifier was turned off in the first three days; intervention period: the purifier was turned on from 9:00 to 17:00 in the following three days). The indoor and outdoor PM_2.5 and PM₁₀ concentrations were continuously monitored during the study. At 9:00, 12:00, and 17:00 of every day during the experiment, indoor and outdoor air samples were collected to analyze the concentration of airborne culturable colonies with a plankton sampler. Airborne particle samples were collected in the outermost exit continuously from 9:00 to 17:00 every day during the experiment using a medium flow particulate sampler, and the species and relative abundance of fungi and bacteria contained in the samples were analyzed by gene sequencing. Independent-sample t test was used to compare the concentration of indoor PM_2.5, PM₁₀, and culturable colonies between the intervention period and the non-intervention period. α diversity analysis, β diversity analysis, and t test were used to compare the diversity and relative abundance of specific species of bacteria and fungi, as well as typical pathogenic bacteria and fungi in the samples between the non-intervention period and the intervention period to reflect the purification effect of low temperature plasma air purifier on airborne PM_2.5, PM₁₀, and microorganisms. Results During the intervention period, the mean indoor concentrations of PM_2.5, PM₁₀, and culturable colonies were lower than those of the no-intervention period (P<0.01 or P<0.001). The ratios of indoor to outdoor concentration (I/O) of PM_2.5 and PM₁₀ during the intervention period were significantly lower than those of the no-intervention period (P<0.001), except the I/O of culturable colonies. Compared with the average concentration at 9:00, the average cleaning rates at 12:00 and 17:00 for PM_2.5 were 49.0% and 46.1%, for PM₁₀ were 49.7% and 45.4%, for airborne culturable colonies were 50.8% and 49.9%, respectively. The β diversity analysis showed that there were significant differences in composition at the level of species of bacteria, and at the levels of genus and species of fungi between the intervention and the no-intervention periods. The relative abundances of 10 species of bacteria such as Lactobacillus and 7 species of fungi such as Torula in the intervention period were significantly lower than those in the non-intervention period, but the relative abundances of fungi such as unclassified_f_cladosporiaceae, trichomerium, and cercospora were higher (P<0.05). For typical pathogenic bacteria, the relative abundances of Lactobacillus and Clostridium_sensu_stricto_1 during the intervention period were 73.5% and 86.9% lower than those in the no-intervention period, and the relative abundance of Talaromyces was 53.5% lower (P<0.05). Conclusion Low temperature plasma air purifier has a good purification effect on indoor PM_2.5, PM₁₀, and culturable colonies in highway toll booths, and likely a limited effect on some fungi.

The essential oil from Curcuma longa L. (CLEO) was extracted by steam distillation. In this study, vasorelaxant activity and mechanism of CLEO was explored. Firstly, the experimental results of isolated rat thoracic aorta ring showed that the CLEO had vasorelaxant activity. By removing the endothelium of aorta ring and pre-incubating inhibitor of endothelial nitric oxide synthase (eNOS), it was found that the vasorelaxant activity of CLEO was endothelium-dependent and related to eNOS. By human umbilical vein endothelial cells (HUVECs) model, it was found that the CLEO could promote the production of nitric oxide (NO) in HUVECs, further indicating that the vasorelaxant activity of CLEO was related to eNOS. The results of Western blot showed that CLEO could up-regulate the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and eNOS. In summary, the CLEO has vasorelaxant activity, and its mechanism is related to activating the endothelial PI3K/Akt/eNOS pathway. All animal experiments in this paper were approved by the Committee of Laboratory Animal Welfare Ethics of Chengdu University of Traditional Chinese Medicine (approval No. 2020-04).

In this study, we have firstly investigated the feasibility of rhamnolipids as targeting ligands to develop drug delivery systems for active targeting of pancreatic cancer. Rhamnolipid-modified liposomes (RhaL-Lip) were prepared by a thin film hydration method, and were evaluated preliminarily for RhaL-Lip physicochemical properties, in vitro release characteristics, ex/in vivo targeting, and in vitro pharmacodynamics. RhaL-Lip exhibited excellent targeting ability of human pancreatic cancer (BxPC-3) cells and enhanced anti-tumor effects. On this basis, the natural structural analogue of rhamnolipid, Polyphyllin VII (PPVII), as the targeting material and active ingredient, we explored the targeting and anti-tumor activity of Polyphyllin VII modified liposomes (PPVII-Lip). The results showed that PPVII-Lip has a homogeneous particle size and has a more robust targeting ability for solid tumor in vivo, which can achieve more enrichment at the tumor site. Compared with gemcitabine, the first-line chemotherapy drug for pancreatic cancer, PPVII-Lip showed a stronger inhibitory effect. In conclusion, this targeted drug delivery strategy is expected to provide beneficial ideas for drug delivery studies in targeted therapy for pancreatic cancer. Animal experiments were conducted with approval from the Animal Ethics Committee of southwest university (approval number: IACUC-20210130-2).

Objective To detect the levels of serum collagen type Ⅰ alpha 1 chain(COL1A1)and collagen type Ⅰ alpha 2 chain(COL1A2)in patients with intracranial aneurysm(IA),and explore their correlations with aneurysm rupture.Methods A total of 110 IA patients admitted to our hospital were regarded as the IA group and another 100 volunteers who underwent physical examination in our hospital were regarded as the control group.The expression levels of serum COL1A1 and COL1A2 were detected by ELISA.The IA patients were divided into the ruptured group(n=66)and unruptured group(n=44)according to the presence or absence of aneurysm rupture,and the clinical data and expression levels of serum COL1A1 and COL1A2 were compared between the two groups.The expression levels of serum COL1A1 and COL1A2 in patients with different Hunt-Hess grades were compared.The risk factors of aneurysm rupture in patients with IA were analyzed by multivariate Logistic regression analysis.The predictive value of serum COL1A1 and COL1A2 for aneurysm rupture in patients with IA were evaluated by receiver operating characteristic(ROC)curve.The correlation of serum COL1A1 and COL1A2 with Hunt-Hess grade for patients in rupture group was analyzed by Spearman correlation analysis.Results The expression levels of serum COL1A1 and COL1A2 for patients in the IA group were significantly higher than those in the control group(P<0.05).The number of patients with hypertension,diabetes mellitus,hyperlipidemia,aneurysm diameter>10 mm,and the expression levels of serum COL1A1 and COL1A2 in the rupture group were significantly more/higher than those in the unruptured group(P<0.05).The expression levels of serum COL1A1 and COL1A2 in patients with Hunt-Hess grades from Ⅲ to Ⅳ were significantly higher than those in patients with grades from Ⅰ to Ⅱ(P<0.05).The expression levels of serum COL1A1 and COL1A2 for patients in the rupture group were positively correlated with Hunt-Hess grade(r=0.562,0.414,P<0.05).Multivariate Logistic regression analysis showed that hypertension,diabetes mellitus,aneurysm diameter>10 mm,and increased expression levels of COL1A1 and COL1A2 were risk factors for aneurysm rupture in IA patients(P<0.05).The area under the curve(AUC)of aneurysm rupture predicted by serum COL1A1 and COL1A2 together was significantly higher than that predicted by COL1A1 alone(Z=1.905,P=0.028)and COL1A2 alone(Z=1.754,P=0.040).Conclusion The increased expression levels of serum COL1A1 and COL1A2 are risk factors for aneurysm rupture in patients with IA,and their combined prediction of aneurysm rupture in IA patients has certain clinical value.

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

This study utilized a chiral liquid chromatography-mass spectrometry (LC-MS)-guided isolation strategy to accurately capture angular-type pyranocoumarins (APs) in Peucedani Radix (Chinese name: Qianhu). Sixteen APs were successfully purified from the ethyl acetate extract of Peucedani Radix through deploying various techniques such as silica gel, ODS, Sephadex LH-20, and achiral (chiral) semi-preparative liquid chromatography. After extensive structural measurements, such as ¹H and ¹³C NMR spectroscopy, their structures were identified as (3′S)-3′-(2-methyl-butyroyl)-4′-oxo-3′,4′-dihydroseselin (1A), (3′R)-3′-(2-methyl-butyroyl)-4′-oxo-3′,4′-dihydroseselin (1B), (3′S)-3′-isovaleryl-4′-oxo-lomatin (2A), (3′R)-3′-isovaleryl-4′-oxo-lomatin (2B), (3′S)-3′-angeloyloxy-4′-oxo-3′,4′-dihydroseselin (3A), (3′R)-3′-angeloyloxy-4′-oxo-3′,4′-dihydroseselin (3B), (3′S,4′S)-praeruptorin B (4A), (3′R,4′R)-praeruptorin B (4B), (3′S,4′S)-praeruptorin E (5A), (3′R,4′R)-praeruptorin E (5B), 3′-isovaleryl-4′-angeloyl-cis-khellactone (6), 3′-angeloyl-4′-(2-methyl-butyroyl)-cis-khellactone (7), (3′S,4′S)-praeruptorin A (8A), (3′R,4′R)-praeruptorin A (8B), (3′S,4′S)-khellactone (9A), and (3′R,4′R)-khellactone (9B), respectively. Thereof, compounds 1A and 1B were new compounds, while compound 2A represents a new configuration for a known planar structure. Compounds 2A and 2B were isolated for the first time from Peucedani Radix. Above all, chiral LC-MS-guided isolation strategy is advantageous at rapid capturing new compounds from herbal medicines, providing an effective means for the separation of novel structures, especially new enantiomers.

Antiviral drug research and development is an important research direction in the current and future biomedical field. The research and development of antiviral drugs not only requires the application of new strategies and new technologies, but also requires the complementary advantages and close cooperation of project teams. Based on the latest progress in this field and the author's drug research practice, this paper summarizes the underlying logic, innovative thinking and research paradigm of antiviral medicinal chemistry.

Objective To investigate the effect of ankyrin-repeat domain-containing protein 22(ANKRD22)on the proliferation,invasion,and migration of human hepatoma cells and its molecular mechanism.Methods The TCGA database was used to analyze the expression level of ANKRD22 in normal liver tissue and hepatocellular carcinoma tissue and its association with prognosis.Western Blot and qRT-PCR were used to measure the expression of ANKRD22 in human normal liver cells(L-02)and human hepatoma cells(Huh7,HepG2,MHCC-97H,SK-HEP-1,and SMMC-7721);CCK-8 assay,EdU,wound healing assay,and Transwell assay were used to observe the effect of ANKRD22 on the proliferation,invasion,and migration of hepatoma cells;Western Blot was used to investigate the association of ANKRD22 with cyclins and EMT-related proteins;KEGG and ssGSEA analyses were performed to investigate the mechanism of action of ANKRD22 in hepatoma cells,and related experiments were conducted for validation.The independent-samples t-test was used for comparison of continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results In the TCGA database,the expression level of ANKRD22 in hepatoma tissue was significantly higher than that in normal liver tissue(t=5.083,P<0.05),and the patients with a high expression level of ANKRD22 had longer overall survival and disease-related survival than those with a low expression level of ANKRD22(P<0.05).The expression level of ANKRD22 in various human hepatoma cell lines was higher than that in human normal liver cells(all P<0.05).Cell proliferation assay showed that the ANKRD22 overexpression group had significantly higher EdU positive rate and proliferation rate than the Vector group(t=19.60 and 6.72,both P<0.001),and compared with the si-NC group,the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower EdU positive rate and proliferation rate(all P<0.001).Compared with the Vector group,the overexpression group had significantly higher expression levels of Cyclin E1,Cyclin D1,CDK7,and CDK4(t=3.54,4.95,6.34,and 5.19,all P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001).The overexpression group had a significantly lower expression level of P27 than the Vector group(t=6.12,P<0.001),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had a significantly higher expression level than the si-NC group(both P<0.001).Invasion and migration experiments showed that compared with the Vector group,the ANKRD22 overexpression group had significantly higher migration rate and number of crossings through the membrane(migration group and invasion group)(t=5.01,25.60,and 3.67,all P<0.05),and compared with the si-NC group,thesi-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower migration rate and number of crossings through the membrane(migration group and invasion group)(all P<0.01).The overexpression group had significantly higher expression levels of N-cadherin,Vimentin,and Snail than the Vector group(t=12.13,8.85,and 13.97,all P<0.001),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001);the overexpression group had a significantly lower expression level of E-cadherin than the Vector group(t=4.98,P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had a significantly higher expression level than the si-NC group(both P<0.001).The KEGG enrichment analysis and the ssGSEA analysis showed that ANKRD22 was associated with the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma,and the overexpression group had significantly higher expression levels of p-AKT/AKT,p-PI3K/PI3K,and p-mTOR/mTOR than the Vector group(t=12.21,3.43,and 9.75,all P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001).Conclusion ANKRD22 is highly expressed in hepatoma cells and can promote the proliferation,invasion,and migration of hepatoma cells and the activation of the PI3K/AKT/mTOR signaling pathway.