Search

Objective Materials and Methods Results Conclusion In this study, our aim was to develop and validate the effectiveness of diverse radiomic models for distinguishing between gnathic fibrous dysplasia (FD) and ossifying fibroma (OF) before surgery.We enrolled 220 patients with confirmed FD or OF. We extracted radiomic features from nonenhanced CT images. Following dimensionality reduction and feature selection, we constructed radiomic models using logistic regression, support vector machine, random forest, light gradient boosting machine, and eXtreme gradient boosting. We then identified the best radiomic model using receiver operating characteristic (ROC) curve analysis. After combining radiomics features with clinical features, we developed a comprehensive model. ROC curve and decision curve analysis (DCA) demonstrated the models' robustness and clinical value.We extracted 1834 radiomic features from CT images, reduced them to eight valuable features, and achieved high predictive efficiency, with area under curves (AUC) exceeding 0.95 for all the models. Ultimately, our combined model, which integrates radiomic and clinical data, displayed superior discriminatory ability (AUC: training cohort 0.970; test cohort 0.967). DCA highlighted its optimal clinical efficacy.Our combined model effectively differentiates between FD and OF, offering a noninvasive and efficient approach to clinical decision‐making. [ABSTRACT FROM AUTHOR]

A series of pyrido[3,4- d ]pyrimidine derivatives were designed and synthesized. Compound 30 showed the most effective inhibitory effect on MGC-803 cells and induced apoptosis. [Display omitted] In order to find high-efficiency and low-toxic anti-tumor drugs, 29 pyrido[3,4- d ]pyrimidine compounds were designed, synthesized and evaluated by MTT assay in vitro. The results presented that most of the compounds had good antitumor activities, among which compound 30 had the best anti-tumor activity on MGC803 cells (IC 50 = 0.59 μM). Mechanistic studies exhibited that compound 30 inhibited migration of MGC803 and induced apoptosis. It was proved that compound 30 up-regulated expression of Bid and PARP, down-regulated expression of CycD1 by western blot experiments. This study indicated that compound 30 might be served as a lead agent for the treatment of human gastric cancers. [ABSTRACT FROM AUTHOR]

• 30 mg/L of combined SMX and TMP increased TN removal (∼70%) and achieved SND. • Abundant genera were more affected by legacy of antibiotics than rare genera. • Rare taxa were keystone taxa in network based on the full-scale classification. • Shared hosts of ARGs and hub ARGs were observed under legacy of antibiotics stress. • Antibiotics legacy effect was more obvious at higher levels of antibiotic stress. The effect of combined antibiotics exposure on nitrogen removal, microbial community assembly and proliferation of antibiotics resistance genes (ARGs) is a hotspot in activated sludge system. However, it is unclear that how the historical antibiotic stress affects the subsequent responses of microbes and ARGs to combined antibiotics. In this study, the effects of combined sulfamethoxazole (SMX) and trimethoprim (TMP) pollution on activated sludge under legacy of SMX or TMP stress with different doses (0.005-30 mg/L) were investigated to clarify antibiotic legacy effects. Nitrification activity was inhibited under higher level of combined exposure but a high total nitrogen removal (∼70%) occurred. Based on the full-scale classification, the legacy effect of past antibiotic stress had a marked effect on community composition of conditionally abundant taxa (CAT) and conditionally rare or abundant taxa (CRAT). Rare taxa (RT) were the keystone taxa in the microbial network, and the responses of hub genera were also affected by the legacy of antibiotic stress. Nitrifying bacteria and genes were inhibited by the antibiotics and aerobic denitrifying bacteria (Pseudomonas, Thaurea and Hydrogenophaga) were enriched under legacy of high dose, as were the key denitrifying genes (napA, nirK and norB). Furthermore, the occurrences and co-selection relationship of 94 ARGs were affected by legacy effect. While, some shared hosts (eg., Citrobacter) and hub ARGs (eg., mdtD, mdtE and acrD) were identified. Overall, antibiotic legacy could affect responses of activated sludge to combined antibiotic and the legacy effect was stronger at higher exposure levels. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Removal of size-fractionated ARGs and MGEs in secondary effluent were investigated. • VUV/PMS could effectively control PA- and CF-ARGs in secondary effluent from WWTPs. • FL-ARGs removal efficiency was lower and their regeneration was more obvious. • ·OH outnumbered SO 4 -· and they both contributed to size-fractionated ARGs removal. • Full-scale classification was applied to identify potential hosts of ARGs and MGEs. Antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in secondary effluent from wastewater treatment plants (WWTPs) have a size-fractionated character and conventional processes have difficulties in removing ARGs and MGEs. Therefore, this study aimed to explore the removal efficiency, removal mechanism and regeneration potential of size-fractionated ARGs and MGEs by vacuum ultraviolet (VUV)-activated peroxymonosulfate (PMS) and ascertain their potential hosts in secondary effluent. The proportion of particle-associated (PA)-ARGs and PA-MGEs was 85.07 %, followed by free-living (FL) fraction (14.91 %) and cell-free (CF) fraction (0.02 %). More than 95.00 %∼99.99 % of ARGs and MGEs in PA- and CF- fractions were removed by VUV/PMS, but the average removal efficiency of FL-ARGs and FL-MGEs was 66.15 %. Compared to the regeneration potential of PA- and CF-ARGs and MGEs (0.02 < C/C 0 < 5.27), the regeneration occurred mainly in FL-ARGs and FL-MGEs (0.08 < C/C 0 < 24.06). ·OH was the dominant radical (16.810 × 10-6 mol/L) in VUV/PMS for the removal of size-fractionated ARGs and MGEs from the secondary effluent, while SO 4 -· (4.478 × 10-6 mol/L) played a supporting role in the system based on the quenching experiment, electron paramagnetic resonance spectrometer and probe experiments. Based on full-scale classification, conditionally rare or abundant taxa (CRAT) were the core potential hosts in PA-, FL- and CF- fractions, while rare taxa (RT) and conditionally rare taxa (CRT) potential hosts were more diverse in the three fractions. This study suggests that VUV/PMS can effectively remove size-fractionated ARGs and MGEs from secondary effluent and thereby obviously reduce their dissemination risk to receiving water bodies, providing technical support for the engineering application of VUV/PMS in full-scale WWTPs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nitrification was more inhibited under gradient increasing exposure mode. • Responses of bacteria were less obvious than archaea to two exposure modes. • Bacteria and archaea have more co-occurrence under the two exposure modes. • AOA and Comammox were enriched under the two exposure modes, respectively. • Bacteria and archaea were both the potential hosts for 24 of 50 ARG subtypes. The responses of microbial communities and antibiotic resistance genes (ARGs) to azithromycin and copper combined pollution under gradient increasing (from 0.5 to 10 mg/L) and decreasing exposure (from 10 to 0.5 mg/L) modes were investigated. Nitrification was inhibited more obviously under gradient increasing exposure mode. Responses of archaeal community and function structure were more obvious than bacteria under both exposure modes. The dominant bacterial and archaeal compositions (Hyphomicrobium , Euryarchaeota , etc.) were affected by two exposure modes, except some rare archaea (Methanoregula and Methanosarcina). There were more positive correlations between bacteria and archaea, and Nitrospira was keystone genus. Ammonia-oxidizing archaea (0.37–3.06%) and complete ammonia oxidizers (Nitrospira_ENR4) were enriched, and Nitrososphaera_viennensis was closely related to denitrifying genes (napA/B , nosZ , etc.). 50 ARG subtypes were detected and specific ARG subtypes (aac , ImrA , etc.) proliferated in two exposure modes. Bacteria and archaea were common hosts for 24 ARGs and contributed to their shifts. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nitrification was inhibited in stress- and post-effects of combined pollution. • Response of abundant taxa was more obvious than rare taxa to combined pollution. • CRAT were keystone taxa in network based on the full-scale classification method. • AOA and aerobic denitrifying bacteria were enriched at high AZM concentration. • Nonpathogenic bacteria and functional genera were the main hosts of ARGs. This study aimed to investigate the short-term response of abundant-rare genera and antibiotic resistance genes (ARGs) to azithromycin (AZM, 0.05–40 mg/L) and copper (1 mg/L) combined pollution in activated sludge nitrification system at low temperature. Nitrification was as expected inhibited in stress- and post-effects periods under AZM concentration higher than 5 mg/L. Abundant and rare taxa presented dissimilar responses based on full-scale classification. Conditionally rare or abundant taxa (CRAT) were keystone taxa. Relative abundance of ammonia-oxidizing archaea increased, and three aerobic denitrifying bacteria (Brevundimonas , Comamonas and Trichococcus) were enriched (from 9.83% to 68.91% in total). Ammonia nitrogen assimilating into Org-N and denitrification may be nitrogen pathways based on predict analysis. 29 ARGs were found with more co-occurrence patterns and high concentration of AZM (greater than 5 mg/L) caused their proliferation. Importantly, expect for some abundant taxa, rare taxa, potential pathogens and nitrogen-removal functional genera were the main potential hosts of ARGs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Compare with AZM, nitrification was more inhibited by QSI. • AZM and QSI had more inhibitions on bacteria and archaea, respectively. • Functions differ little in bacteria/archaea and AZM had more impact on metabolism. • AZM had main impact on nitrifying bacteria and specific DNB were enriched. • Bacteria were main hosts for most ARGs and archaea carried multiple ARGs. Effects of antibiotics (azithromycin, AZM, 1–40 mg/L) and quorum sensing inhibitor (QSI, 2(5H)-furanone, 1–40 mg/L) combined pollution with environmental concentration of copper on bacterial/archaeal community and antibiotic resistance genes (ARGs) in activated sludge system were explored. QSI inhibited nitrification more obviously than AZM. AZM and QSI were synergistic inhibitions on bacterial diversity, and AZM inhibited bacterial compositions more than QSI. While, QSI had more impacts on archaeal diversity/compositions. Less interactions among bacteria and archaea communities with Aquimonas as keystone genus. Functional differences in bacteria/archaea communities were little, and AZM had more effects on metabolism. AZM mainly affected nitrifying bacteria (Candidatus Nitrospira nitrificans and Nitrosomonas). Specific denitrifying bacteria were enriched by AZM (Brevundimonas , 1.76–31.69%) and QSI (Comamonas , 0.61–9.61%), respectively. AZM enriched ARGs more easily than QSI and they were antagonistic to proliferation of ARGs. Bacteria were main hosts of ARGs (macrolide-lincosamide-streptogramin B, other/efflux, etc.) and archaea (Methanosphaerula , Methanolobus) carried multiple ARGs. [ABSTRACT FROM AUTHOR]

Histone deacetylase 6 (HDAC6) has emerged as a critical regulator of many cellular pathways in tumors due to its unique structure basis and abundant substrate types. Over the past few decades, the role played by HDAC6 inhibitors as anticancer agents has sparked great interest of biochemists worldwide. However, they were less reported for gastric cancer therapy. In this paper, with the help of bioisosteric replacement, in-house library screening, and lead optimization strategies, we designed, synthesized and verified a series of 1,3-diaryl-1,2,4-triazole-capped HDAC6 inhibitors with promising anti-gastric cancer activities. Amongst, compound 9r displayed the best inhibitory activity towards HDAC6 (IC 50 = 30.6 nM), with 128-fold selectivity over HDAC1. Further BLI and CETSA assay proved the high affinity of 9r to HDAC6. In addition, 9r could dose-dependently upregulate the levels of acetylated α-tubulin, without significant effect on acetylated histone H3 in MGC803 cells. Besides, 9r exhibited potent antiproliferative effect on MGC803 cells, and promoted apoptosis and suppressed the metastasis without obvious toxicity, suggesting 9r would serve as a potential lead compound for the development of novel therapeutic agents of gastric cancer. [Display omitted] ● A novel series of 1,3-diaryl-1,2,4-triazole-capped HDAC6 inhibitors were designed and synthesized by the strategies of bioisosteric replacement, in-house library screening, and lead optimization. ● Compound 9r exhibited the best potency to HDAC6 (IC 50 = 30.6 nM), with 128-fold selectivity over HDAC1. ● Compound 9r displayed promising anti-gastric cancer activity without obvious toxicity. [ABSTRACT FROM AUTHOR]