AI-based Virtual Screening of Traditional Chinese Medicine and the Discovery of Novel Inhibitors of TCTP.

BACKGROUND: Translationally controlled tumour protein (TCTP) is associated with tumor diseases, such as breast cancer, and its inhibitor can reduce the growth of tumor cells. Unfortunately, there is currently no effective medication available for treating TCTP-related breast cancer. OBJECTIVE: The objective of this study was to explore the inhibitor candidates among natural compounds for the treatment of breast cancer related to TCTP protein. METHODS: To explore the potential inhibitors of TCTP, we first screened out four potential inhibitors in the Traditional Chinese Medicine (TCM) for cancer based on AI virtual screening using the docking method, and then revealed the interaction mechanism of TCTP and four candidate inhibitors from TCM with molecular docking and molecular dynamics (MD) methods. RESULTS: Based on the conformational characteristics and the MD properties of the four leading compounds, we designed the new skeleton molecules with the AI method using MolAICal software. Our MD simulations have revealed that different small molecules bind to different sites of TCTP, but the flexible regions and the signaling pathways are almost the same, and the VDW and hydrophobic interactions are crucial in the interactions between TCTP and ligands. CONCLUSION: We have proposed the candidate inhibitor of TCTP. Our study has provided a potential new method for exploring inhibitors from Traditional Chinese Medicine (TCM).

Simultaneous nitrogen and phosphorus removal through an integrated partial-denitrification/anammox process in a single UAFB system.

With the aim of obtaining enhanced nitrogen removal and phosphate recovery in mainstream sewage, we examined an integrated partial-denitrification/anaerobic ammonia oxidation (PD/A) process over a period of 189 days to accomplish this goal. An up-flow anaerobic fixed-bed reactor (UAFB) used in the integrated PD/A process was started up with anammox sludge inoculated and the influent composition controlled. Results showed that the system achieved a phosphorus removal efficiency of 82% when the influent concentration reached 12.0 mg/L. Batch tests demonstrated that stable and efficient removal of chemical oxygen demand (COD), nitrogen, and phosphorus was achieved at a COD/NO3--N ratio of 3.5. Scanning electron microscope (SEM) and X-ray diffraction (XRD) analysis indicated that hydroxyapatite was the main crystal in the biofilm. Furthermore, substrate variation along the axial length of UAFB indicated that partial denitrification and anammox primarily took place near the reactor's bottom. According to a microbiological examination, 0.4% of the PD/A process's microorganisms were anaerobic ammonia oxidizing bacteria (AnAOB). Ca. Brocadia, Ca. Kuenenia, and Ca. Jettenia served as the principal AnAOB generals in the system. Thauera, Candidatus Accumulibacter, Pseudomonas, and Acinetobacter, which together accounted for 27% of the denitrifying and phosphorus-accumulating bacteria, were helpful in advanced nutrient removal. Therefore, the combined PD/A process can be a different option in the future for sewage treatment to achieve contemporaneous nutrient removal.

Stability and nutrients removal performance of a Phanerochaete chrysosporium-based aerobic granular sludge process by step-feeding and multi A/O conditions.

A Phanerochaete chrysosporium-based aerobic granular sludge (PC-AGS) was developed by inoculating fungal mycelial pellets into a lab-scale aerobic granular sequencing batch reactor (AGSBR). A strategy using step-anaerobic feeding coupled with multi A/O conditions was adopted. The results showed that the removal efficiencies for total phosphorus (TP) and total inorganic nitrogen (TIN) were 94.56 ± 2.92% and 75.20 ± 7.74%, respectively, under relatively low aeration time. Compared with original AGS, the content of extracellular proteins for PC-AGS obviously increased from 18.61 to 41.44 mg/g MLSS by the end of phase I. Moreover, the mature granules had a larger size and better stability during the 100 days operation. Furthermore, the analysis of microbial diversity detected many key functional groups in PC-AGS granules that were beneficial to nutrients removal. This work demonstrated that the addition of fungal pellets not only enhanced the removal performance, but also improved the stability of the AGS system.

Phosphorus recovery via the formation of hydroxyapatite crystals at various nitrogen loading rate in an anammox-based UAFB.

A strategy that integrates the anammox and hydroxyapatite crystallization in an up-flow anaerobic fixed-bed reactor (UAFB) was investigated to simultaneously remove nitrogen and recover phosphorus. During the 430 days of operation, 73.1 ±â€¯6.6% of influent phosphorus was removed with an efficient nitrogen removal efficiency of 87.8 ±â€¯1.7%. After long-term operation, numerous acicular and micron-sized crystals were observed on the matured biofilm, of which the phosphorus content was around 10.21% (wt%) and hydroxyapatite was the main form of crystals through SEM-EDS, FT-IR and XRD analysis. The variation of substrates along the axial length of UAFB showed that phosphate removal was positively correlated with anammox and pH. Moreover, three anammox bacteria including Candidatus Brocadia (19.73%), Candidatus Jettenia (0.49%) and Candidatus Kuenenia (0.85%) were detected at the bottom of UAFB, while Candidatus Jettenia (4.67%) was dominant at the top. Hence, the anammox-based biofilm system could be alternative for the recovery of phosphorus from nutrient-rich wastewater.

The influence of a stepwise pH increase on volatile fatty acids production and phosphorus release during Al-waste activated sludge fermentation.

In this study, the performance of volatile fatty acids (VFAs) production and phosphorus (P) release during Al-waste activated sludge (Al-WAS) anaerobic fermentation with stepwise pH increases from 8 to 11 was investigated via a long-term acclimation strategy. As results, VFAs concentration increased with increasing pH and the maximum yield of VFAs was 358.03 mg-COD/g VS at pH 11, which was much higher than at pH 8. P was also released during the process, and the P concentration increased gradually from 26 mg/L at pH 8 to 186 mg/L at pH 11, accounting for 35.8% of the total P in the Al-WAS. The P distribution results demonstrated the dissolution of non-apatite inorganic phosphorus (NAIP) and organic P in the sludge contributed to release P into the liquid at pH 8, 9, and 10, while inorganic P release originated from the dissolution of NAIP at pH 11.

Recovery of phosphorus via harvesting phosphorus-accumulating granular sludge in sequencing batch airlift reactor.

A novel approach was developed for phosphorus recovery from wastewater through thermal treatment of matured phosphorus-accumulating granular sludge cultivated in sequencing batch airlift reactor (SBAR) system. Results showed that SBAR system had stable performances, in which COD, total phosphorus (TP) and total nitrogen (TN) removal efficiencies were stabilized at 80%, 89% and 86%, respectively. The matured granules were gathered from SBAR reactor and heated at relatively low temperature (100°C, 200°C, 300°C). The total P content in thermal treated granular sludge was more than half of total nutrient. Furthermore, the phosphorus release rate for treated granules was negatively correlated with thermal treatment temperature. These results demonstrated that the granules harvested from SBAR system followed with thermal pre-treatment could probably be applied as excellent slow-release phosphorus fertilizer. Hence, low temperature treatment of phosphate-accumulating granules is efficient for phosphorus recovery from wastewater, which is likely to promote the application of granulation technology.

Interaction between phosphorus removal and hybrid granular sludge formation under low hydraulic selection pressure at alternating anaerobic/aerobic conditions.

The hybrid granular sludge (HGS) formation and its performances on phosphorus removal were investigated in a sequencing batch airlift reactor. Under conditions of low superficial air velocity (SAV = 0.68 cm s(-1)) and relatively long settling time (15-30 min), aerobic granules appeared and coexisted with bio-flocs after 120 days operation. At the stable phase, 54% of total suspended solid (m/m) was granular sludge with the two typical sizes (D(mean) = 1.77 ± 0.33 and 0.89 ± 0.11 mm) in the reactor, where the settling velocity was 98.7 ± 12.4 and 37.8 ± 0.9 m h(-1) for the big and small granules. With progressive extension of anaerobic time from 15 to 60 min before aerobic condition per cycle during the whole experiment, the HGS system can be maintained at a high total phosphorus removal efficiency (ca. 99%) since Day-270. The phosphorus content (wt %) in biomass was respectively 9.54 ± 0.29, 7.60 ± 0.48 and 6.15 ± 0.59 for the big granules, small granules and flocs.