Multiple-matrices metabolomics combined with serum pharmacochemistry for discovering the potential targets and active constituents of Qifu decoction against heart failure.

Qifu decoction (QFD) is an ancient traditional Chinese medicine (TCM) prescription for the treatment of heart failure. However, the mechanisms and active constituents of QFD are poorly understood. In this study, multi-matrices metabolomics (serum, urine, and myocardial mitochondria) based on ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOFMS), were employed for exploring the mechanisms of QFD against heart failure in rat model. Twenty-one, seventeen, and fifteen endogenous metabolite biomarkers associated with heart failure were identified from serum, urine, and myocardial mitochondria datasets, respectively. Fourteen, twelve, and ten of the identified serum, urine, and mitochondria biomarkers were significantly reversed by QFD, respectively. QFD-targeted pathways were involved in TCA cycle, branched chain amino acids metabolism, fatty acid ß-oxidation, sphingolipid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, tryptophan metabolism, purine metabolism. In addition, QFD-derived constituents in serum were fully analyzed by UHPLC-Q-TOFMS and SUS-plot, and 24 QFD-derived components were identified in serum. Then, the correlation analysis between the QFD-reversed serum biomarkers and QFD-derived constituents in serum was employed to dissect the active constituents of QFD. It was found that eight prototypical components and three metabolites were highly correlated with efficacy and could serve as the active constituents of QFD against heart failure. Finally, neoline and calycosin, which highly correlated with branched-chain amino acid metabolism and fatty acid ß-oxidation, were selected to validate in Na2S2O4-induced cell model. It was found that neoline and calycosin provided a significant protective effect against Na2S2O4-induced cell death in a low dose-dependent manner and increased the expressions of the pathway-related protein CPT1B and BCAT2 in the cell model. In conclusions, these findings provided light on the mechanisms and active constituents of QFD against heart failure. Neoline and calycosin could be selected as potential quality-markers of QFD against heart failure.

Gut microbiota-dependent modulation of pre-metastatic niches by Jianpi Yangzheng decoction in the prevention of lung metastasis of gastric cancer.

AIM OF THE STUDY: To evaluate the in vitro and in vivo anti-metastasis efficacy of Jianpi Yangzheng (JPYZ) decoction against gastric cancer (GC) and its potential mechanisms. MATERIALS AND METHODS: The distant metastasis of GC cells administered via tail vein injection was assessed using the pre-metastatic niche (PMN) model. 16S rRNA sequencing and GC-MS/MS were applied to determine the component of the gut microbiota and content of short-chain fatty acids (SCFAs) in feces of mice, respectively. The proportion of myeloid-derived suppressor cells (MDSCs) in the lung was evaluated by flow cytometry and immunofluorescence. Serum or tissue levels of inflammation factors including IL-6, IL-10 and TGF-ß were determined by ELISA or Western blot respectively. RESULTS: Injecting GC cells into the tail vein of mice led to the development of lung metastases and also resulted in alterations in the composition of gut microbiota and the levels of SCFAs produced. Nevertheless, JPYZ treatment robustly impeded the effect of GC cells administration. Mechanically, JPYZ treatment not only prevented the alteration in gut microbiota structure, but also restored the SCFAs content induced by GC cells administration. Specifically, JPYZ treatment recovered the relative abundance of genera Moryella, Helicobacter, Lachnoclostridium, Streptococcus, Tuzzerella, GCA-900066575, uncultured_Lachnospiraceae, Rikenellaceae_RC9_gut_group and uncultured_bacterium_Muribaculaceae to near the normal control levels. In addition, JPYZ abrogated MDSCs accumulation in the lung tissue and blocked inflammation factors overproduction in the serum and lung tissues, which subsequently impede the formation of the immunosuppressive microenvironment. Correlation analysis revealed that the prevalence of Rikenellaceae in the model group exhibited a positive correlation with MDSCs proportion and inflammation factor levels. Conversely, the scarcity of Muribaculaceae in the model group showed a negative correlation with these parameters. This suggests that JPYZ might exert an influence on the gut microbiota and their metabolites, such as SCFAs, potentially regulating the formation of the PMN and consequently impacting the outcome of GC metastasis. CONCLUSION: These findings suggest that GC cells facilitate metastasis by altering the gut microbiota composition, affecting the production of SCFAs, and recruiting MDSCs to create a pro-inflammatory pre-metastatic niche. JPYZ decoction counteracts this process by reshaping the gut microbiota structure, enhancing SCFA production, and inhibiting the formation of the pre-metastatic microenvironment, thereby exerting an anti-metastatic effect.

Large-scale sediment and phosphorus transport in the Three Gorges Reservoir based on a new reservoir operation method.

Change of hydrodynamic conditions is a key factor inducing sedimentation, water eutrophication and algal blooms in the Three Gorges Reservoir (TGR). How to mitigate sedimentation and phosphorus (P) retention by improving hydrodynamic conditions in the Three Gorges Reservoir area (TGRA) is an urgent issue in the study of sediment and water environment. In this study, a Hydrodynamic-Sediment-Water quality model for the whole TGRA is proposed considering sediment and P inputs from numerous tributaries, and a new reservoir operation method namely the tide-type operation method (TTOM) is used to investigate the large-scale sediment and P transport in the TGR based on the model. Results indicate that the TTOM can reduce sedimentation and total phosphorus (TP) retention in the TGR. Compared with the actual operation method (AOM), sediment outflow and sediment export ratio (Eratio) of the TGR increased about 17.13% and 1%-3% in 2015-2017, and sedimentation decreased about 3% under the TTOM. TP retention flux and retention rate (RE) decreased about 13.77% and 2%-4%. The flow velocity (V) and sediment carrying capacity (S*) increased about 40% in the local reach. Larger daily water level fluctuation at dam site is more conducive to reducing sedimentation and TP retention in the TGR. Sediment inputs from the Yangtze River, Jialing River, Wu River and other tributaries account for 59.27%, 11.21%, 3.81% and 25.70% of the total sediment inflow during 2015-2017, and TP inputs were 65.96%, 10.01%, 17.40% and 6.63%. In the paper, an innovative method is proposed to reduce sedimentation and P retention in the TGR under the given hydrodynamic conditions and related quantitative contribution driven by the proposed method is analyzed. The work is favorable for expanding the understanding of the hydrodynamic and nutrition flux changes in the TGR, and provides a new perspective for water environment protection and reasonable operation of large reservoirs.

Phenolamide extract of apricot bee pollen alleviates glucolipid metabolic disorders and modulates the gut microbiota and metabolites in high-fat diet-induced obese mice.

Obesity is a serious health problem, and it is important to discover natural active ingredients for alleviating it. In this study, we investigated the effect of phenolamide extract (PAE) from apricot bee pollen on obese mice fed a high-fat diet (HFD). The main compounds in PAE were identified by HPLC-ESI-QTOF-MS/MS, and HFD-fed mice were treated with PAE for 12 weeks. The results demonstrated that the content of phenolamides in PAE was 87.75 ± 5.37%, with tri-p-coumaroyl spermidine as the dominant compound. PAE intervention in HFD-fed mice effectively reduced weight gain and lipid accumulation in the liver and epididymal fat, increased glucose tolerance, reduced insulin resistance and improved lipid metabolism. In terms of the gut microbiota, PAE could reverse the increase in the Firmicutes/Bacteroidetes ratio in HFD-fed mice. In addition, PAE could increase beneficial bacteria such as Muribaculaceae and Parabacteroides, and reduce harmful bacteria such as Peptostreptococcaceae and Romboutsia. Metabolomic analysis revealed that PAE could regulate the levels of metabolites, including bile acids, phosphatidyl choline (PC), lysophosphatidylcholine (lysoPC), lysophosphatidylethanolamine (lysoPE) and tyrosine. This is the first study finding that PAE can regulate glucolipid metabolism and modulate the gut microbiota and metabolites in HFD-induced obese mice, and the results indicate that PAE can be used as a functional dietary supplement to alleviate HFD-induced obesity.

[Bioinformatics analysis of the molecular mechanism of Qibaipingfei Capsule in the regulation of chronic obstructive pulmonary disease related immune cells].

Objective To investigate the mechanism of the Qibaipingfei Capsule regulating chronic obstructive pulmonary (COPD) related immune cells by analyzing the single-cell transcriptome sequencing (scRNA-seq) data of COPD lung tissue and the pharmacology of Qibaipingfei Capsule. Methods The scRNA-seq data of COPD lung tissue downloaded from the gene expression omnibus (GEO) was used to obtain the COPD related immune cells and the differentially expressed RNA, and the primary active molecular and target genes of Qibaipingfei Capsule were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The "active molecules-immune cells-target genes" network was constructed by mapping the target genes of Qibaipingfei Capsules to the differentially expressed RNA of COPD related immune cells, and the Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the protein-protein interaction (PPI) were administrated to analyze the molecular mechanisms of target genes. Results Twelve active molecules including quercetin, kaempferol, and formononetin of Qibaipingfei Capsule targeted multiple COPD related immune cells like macrophages, alveolar macrophages, and T cells, and genes like PPARG, JUN, HMOX1, and HIF1A which were primarily collected in pathways such as interleukin 17 signaling pathway, nuclear factor-κB (NF-κB) signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway. Conclusions The Qibaipingfei Capsule may target multiple immune cells and intervene in inflammation and immune-related pathways to regulate the inflammation and immune response of COPD.

Effect of modified Jianpi Yangzheng on regulating content of PKM2 in gastric cancer cells-derived exosomes.

BACKGROUND: Modified Jianpi Yangzheng decoction (mJPYZ), as an empirical decoction of Traditional Chinese medicine has been shown significantly to prolong the survival of patients with advanced stage gastric cancer. Pyruvate kinase M2 (PKM2), has attracted attention for its important role on cellular aerobic glycolysis, however, few studies focus on PKM2 non-metabolic roles in tumor progression. PURPOSE: Our study aimed to investigate the potential role of gastric cancer exosomes containing PKM2 in regulating tumor-associated macrophages (TAM) and the mechanism of mJPYZ against gastric cancer. METHODS: Colony Formation Assay, flow cytometry and TUNEL staining were employed to estimate the effect of mJPYZ on gastric cancer in tumor-bearing mice and cells. Western blot analyzed apoptosis-related protein expression changes. Network pharmacology and bioinformatics predicted potential exosomes modulation of mJPYZ in gastric cancer. Exosomes were isolated and co-cultured with TAM. Diff-Quik Staining observed the TAM morphological changes when incubating with gastric cancer cells exosomes. Flow cytometry and immunofluorescence were performed to demonstrate whether exosomes PKM2 involved in TAM polarization. RESULTS: mJPYZ induced apoptosis of gastric cancer cells by targeting PKM2 and downregulating PI3K/Akt/mTOR axis in vivo and in vitro. Network pharmacology showed potential exosomes modulation of mJPYZ in gastric cancer. We extracted exosomes and found mJPYZ decreased the abundance of serum exosomes PKM2 in patients with advanced gastric cancer and xenograft tumor model. Additionally, we firstly detected and confirmed that PKM2 is a package protein of exosomes extracted from gastric cancer cells, and mJPYZ could diminish the content of exosomal PKM2 in gastric cancer cells. Importantly, mJPYZ reduced the delivery of exosomal PKM2 from tumor cells to macrophages, and alleviated exosomal PKM2-induced differentiation of M2-TAM in tumor microenvironment, eventually inhibited gastric cancer progression. CONCLUSION: Gastric cancer exosomes containing PKM2 could lead to M2 macrophages differentiation, thereby promoting gastric cancer progression. Our findings provide a rationale for potential application of mJPYZ in the treatment of gastric cancer via PKM2.

Metabolomics reveals that phenolamides are the main chemical components contributing to the anti-tyrosinase activity of bee pollen.

Bee pollen, which is known as a "full-nutrient food", has outstanding anti-tyrosinase activity. However, the chemical components contributing to this activity remain unknown. To comprehensively elucidate the chemical components of bee pollen inhibiting tyrosinase, we performed the anti-tyrosinase activity evaluation of bee pollen extract (BPE) of eight species, metabolomic analysis of chemical composition, multivariate statistical analysis and correlation analysis. The results revealed that the anti-tyrosinase activity of eight BPEs was significantly different (p < 0.05), with IC50 value ranging from 10.08 to 408.81 µg/mL. A total of 725 metabolites were detected from these BPEs, and 40 differential metabolites were identified, all of which were phenolamides. All these phenolamides were positively correlated with the anti-tyrosinase activity, among which 26 phenolamides (21 spermidine derivatives and five spermine derivatives) showed particularly high correlations (r > 0.7). This is the first report to reveal the main contributor to the anti-tyrosinase activity of bee pollen.

PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression.

Gastric cancer is the third leading cause of cancer death worldwide. Traditional Chinese medicine (TCM) is increasingly extensively applied as a complementary therapy for gastric cancer (GC) in China, which shows unique advantages in preventing gastric cancer metastasis. Previous study indicates modified Jian-pi-yang-zheng (mJPYZ) decoction inhibit the progression of gastric cancer by regulating tumor-associated macrophages (TAM). However, it is unclear whether mJPYZ can affect metabolic reprogramming of gastric cancer cells. Here, we showed that mJPYZ effectively attenuated GC cells proliferation, migration and invasion. Meantime, mJPYZ reduced the aerobic glycolysis level of GC cells in vivo and in vitro by regulating the expression and nuclear translocation of PKM2. Overexpression of PKM2 that could reverse the inhibitory effect of mJPYZ, migration and epithelial to mesenchymal transition (EMT). Our results showed PKM2/HIF-1α signaling was the key metabolic regulator of mJPYZ in GC cells. In summary, our present study suggested that abnormal PKM2 is required for maintaining the malignant phenotype of GC cells. The TCM decoction mJPYZ inhibited GC cells growth and EMT by reducing of glycolysis in PKM2 dependent manner. This evidence expanded our understanding of the anti-tumor mechanism of mJPYZ and further indicated mJPYZ a potential anti-tumor agent for GC patients. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Rutin (PubChem CID: 5280805); Lobetyolin (PubChem CID: 53486204); Calycosin-7-glucoside (PubChem CID: 71571502); Formononetin (PubChem CID: 5280378); Calycosin (PubChem CID: 5280448); Ononin (PubChem CID: 442813); P-Coumaric Acid (PubChem CID: 637542).

Qiyusanlong Formula Induces Autophagy in Non-Small-Cell Lung Cancer Cells and Xenografts through the mTOR Signaling Pathway.

OBJECTIVE: Qiyusanlong (QYSL) formula has been used in the clinic for more than 20 years and has been proved to have pronounced efficacy in the treatment of non-small-cell lung cancer (NSCLC). This work aims to evaluate the molecular mechanism of QYSL formula action on NSCLC, specifically in relation to autophagy induction. METHODS: In vitro, CCK-8 was used to detect the effect of QYSL serum on cell viability in A549 cells. In vivo, A549 cells were implanted subcutaneously in nude mice to establish a xenograft model. TUNEL staining was used to measure cell apoptosis and TEM to observe the autophagy-related morphological changes in vitro and in vivo. Western blotting, RT-qPCR, and immunofluorescence were used to measure autophagy-related proteins. In addition, rapamycin (an inhibitor of mTOR and inducer of autophagy) and MHY1485 (an activator of mTOR and inhibitor of autophagy) were used to determine whether QYSL-induced autophagy was regulated by the mTOR pathway. RESULTS: QYSL serum inhibited the cell viability of A549 cells in a concentration-dependent manner. In vivo, the QYSL formula inhibited xenograft growth. The QYSL formula promoted apoptosis in A549 cells and induced autophagosome formation in vitro and in vivo. In addition, the QYSL formula downregulated the expression of mTOR and p62, while it upregulated the expression of ATG-7 and Beclin-1 and increased the LC3-II/LC3-I ratio. QYSL serum inhibited p-mTOR in a similar manner to rapamycin while reducing the activating effects of MHY1485 on p-mTOR. CONCLUSION: The QYSL formula has anti-lung cancer effects and promotes autophagy through the mTOR signaling pathway.

The Gut Microbiota and Traditional Chinese Medicine: A New Clinical Frontier on Cancer.

Gut microbiota is a complex microecosystem, which is called the second genome of the human body. Herbal medicine can balance tumor-suppressing bacteria and tumor-promoting bacteria and exert its anti-cancer effect by regulating gut microbiota. Traditional Chinese medicine (TCM) has a history of thousands of years in prevention and treatment of diseases in China. In recent decades, TCM has been shown to have an obvious advantage in prolonging the survival time and improving the living quality of patients with cancer. Notably, gut microbiota has become a new pathway to understanding TCM. In this review, we will focus on gut microbiota and tumor progression, especially the diversity, functionality and metabolites of gut microbiota affected by TCM in various cancer. We will also discuss the potential mechanism of gut microbiota for exploring TCM in anti-cancer effect. This article aims to comprehensively review the anti-cancer research of TCM by regulating gut microbiota, and address future perspectives and challenges of gut microbiota in TCM intervention for cancer.

Genistein improves systemic metabolism and enhances cold resistance by promoting adipose tissue beiging.

Genistein, a naturally occurring phytoestrogen and a member of the large class of compounds known as isoflavones, exerts protective effects in several diseases. Recent studies indicate that genistein plays a critical role in controlling body weight, obesity-associated insulin resistance, and metabolic disorders, but its target organs in reversing obesity and related pathological conditions remain unclear. In this study, we showed that mice supplemented with 0.2% genistein in a high-fat diet for 12 weeks showed enhanced metabolic homeostasis, including reduced obesity, improved glucose uptake and insulin sensitivity, and alleviated hepatic steatosis. We also observed a beiging phenomenon in the white adipose tissue and reversal of brown adipose tissue whitening in these mice. These changes led to enhanced resistance to cold stress. Altogether, our data suggest that the improved metabolic profile in mice treated with genistein is likely a result of enhanced adipose tissue function.

Development of a novel denitrifying phosphorus removal and partial denitrification anammox (DPR + PDA) process for advanced nitrogen and phosphorus removal from domestic and nitrate wastewaters.

A novel energy-efficient DPR + PDA (denitrifying phosphorus removal and partial denitrification anammox) process for enhanced nitrogen and phosphorus removal was developed in the combined ABR-CSTR reactor. After 220 days operation, excellent total inorganic nitrogen (TIN) and phosphorus removal (97.57% and 95.66%, respectively) were obtained under external C/NO3--N of 0.7, with the effluent TIN and PO43--P concentrations of 3.51 mg/L and 0.28 mg/L, respectively. At the steady period, DPR contributed major TN removal (58.65%), while PDA mediated an increasingly considerable impact and finally achieved 37.07%, in which anammox accounted for a significant percentage. Batch tests demonstrated that efficient PD with nitrate-to-nitrite transformation ratio of 97.67% supplying stable nitrite for anammox, and phosphorus was mainly removed using nitrate as electron acceptor via DPR with the ideal phosphorus release/uptake rate (7.73/22.17 mgP/gVSS/h). Accumulibacter (6.24%) dominated high phosphorus removal performance, while Thauera (8.26%) and Candidatus Brocadia (2.57%) represented the superior nitrogen removal performance.

Modular characteristics and the mechanism of Chinese medicine's treatment of gastric cancer: a data mining and pharmacology-based identification.

BACKGROUND: Traditional Chinese medicine (TCM) is increasingly extensively being applied as a complementary and alternative therapy for gastric cancer (GC); however, there is a lack of large-scale evidence-based deep learning for the guidance of its clinical prescription. METHODS: The combinational search terms of "Gastric cancer and/or gastric malignancy" and "Traditional Chinese Medicine" were used to retrieve clinical study-based herbal prescriptions from public database over the past 3 decades [1990-2020]. Association rules mining (ARM) was used to analyze the prescription patterns of the herbs extracted from the eligible studies. Deep machine learning and computational prediction were conducted to explore candidate prescriptions with general applicability for GC. The action mechanism of the preferred prescription was investigated through network pharmacology, and further validated via in vivo and in vitro experiments. RESULTS: A total of 194 clinical study-based herbal prescriptions with good efficacy for GC were collected. TCM with focus on invigorating the Spleen and tonifying the vital-Qi is a promising adjuvant therapy for GC. The preferred prescription is composed of Atractylodis Macrocephalae Rhizoma, Astragali Radix, Pinelliae Rhizoma, Citri Reticulatae Pericarpium, Herba Hedyotidis Diffusae, Crataegi Fructus, and so on. We screened 74 bioactive compounds and 2,128 predictive targets of the preferred prescription from public databases. Eventually, 135 GC-related genes were identified as the targets of the preferred prescription. The compound-target network revealed that the crucial substances in the preferred prescription are quercetin, kaempferol, baicalein, and nobiletin. Experimentally, the preferred prescription was validated to modulate GC cell survival and inhibit tumor progression mainly via the hTERT/MDM2-p53 signaling pathway in vivo and in vitro. CONCLUSIONS: TCM aimed at invigorating the Spleen and tonifying the vital-Qi is a promising adjuvant therapy for GC, which offers a guidance for worldwide use of TCM in the treatment of GC.

A novel denitrifying phosphorus removal and partial nitrification, anammox (DPR-PNA) process for advanced nutrients removal from high-strength wastewater.

This study developed a novel DPR-PNA (denitrifying phosphorus removal, partial nitrification and anammox) process for sustaining high-strength wastewater treatment in a modified continuous flow reactor without external carbon source. After 259-days operation, a synchronous highly-efficient total inorganic nitrogen, PO43--P and CODcr removal efficiencies of 88.5%, 89.5% and 90.1% were obtained, respectively even influent nitrogen loading rate up to 3.2 kg m-3 d-1. Batch tests revealed that denitrifying phosphorus accumulating organisms (DPAOs) using NO3--N as electron acceptors significantly enriched (74% in total PAOs), which emerged remarkable positive impacts on deep-level nutrient removal as the key limiting factor. Furthermore, the NO2--N inhibitory threshold value (∼20.0 mg L-1) for DPAOs was identified, which demonstrated as an inhibitory component in excessive recycling NOx--N. From the molecular biology perspective, Dechloromonas-DPAOs group (18.59%) dominated the excellent dephosphatation performance, while Nitrosomonas-AOB (ammonia oxidizing bacteria) group (16.26%) and Candidatus_Brocadia-AnAOB (anammox bacteria) group (15.12%) were responsible for the desirable nitrogen loss process. Overall, the present work highlighted the novel DPR-PNA process for nutrients removal is a promising alternation for wastewater of high nitrogen but low carbon.

Effects of a Chinese Patent Medicine Gushen'antai Pills on Ongoing Pregnancy Rate of Hormone Therapy FET Cycles: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

In the past decade, the number of frozen-thawed embryo transfer (FET) has increased dramatically with the expansion of surgical indications and the improvement of freezing related technologies. How to improve the success rate and reduce the adverse effects of FET is our research priorities. This study aimed to investigate the safety and effectiveness of Gushen'antai pills (GSATP) by measuring the ongoing pregnancy rate (OPR) in patients from FET and hormone therapy (HT) cycle. From November 2019 to May 2020, 5 Chinese hospitals conducted a multi-center, randomized, double-blind, placebo-controlled study. In total, 271 HT FET cycles in patients were randomly divided (1:1 ratio) to receive GSATP (6 g, tid) or placebo (6g, tid) for 12 weeks of pregnancy. Patients, clinicians, and researchers were blinded to treatment allocation. The primary endpoint was the OPR at week 12 of pregnancy. The secondary endpoints were vaginal bleeding or brown discharge rate, implantation rate (IR), clinical pregnancy rate (CPR) and abortion rate (AR). Adverse events were recorded during the treatment period. The results showed that the OPR remained higher in the GSATP group when compared to placebo group (56.62% vs. 44.44%, p = 0.045). Vaginal bleeding or brown discharge rate was lower in the GSATP group than the placebo group (10% vs. 23.08%, p = 0.032), while the IR (35.16% vs. 27.64%, p = 0.070), CPR (58.82% vs. 48.15%, p = 0.078), incidence of total adverse events (8.09% vs. 3.22%, p = 0.051) and AR (3.75% vs. 7.69%, p = 0.504) were similar between GSATP and placebo groups. Subgroup analysis showed that there were significant differences in CPR (74.19% vs. 54.17%, p = 0.004) and OPR (72.04% vs. 51.04%, p = 0.003) between GSATP group and Placebo group when the patient was younger than 35 years old. This multi-center, randomized, double-blinded, placebo-controlled clinical study showed for the first evidence that GSATP may have potential to improve the OPR and decrease vaginal bleeding or brown discharge rate in HT FET cycle patients.

New insights on biological nutrient removal by coupling biofilm-based CANON and denitrifying phosphorus removal (CANDPR) process: Long-term stability assessment and microbial community evolution.

It was difficult to obtain a stable and efficient biological nutrient removal for high-strength wastewater treatment, the possibility of exploiting innovative CANDPR process, integrating biofilm-based completely autotrophic nitrogen removal over nitrite (CANON) with denitrifying phosphorus removal (DPR) was evaluated to resolve the difficulty. Results revealed that the excellent NH4+-N, PO43--P and COD removal efficiencies of 96%, 96% and 91%, were achieved respectively under a high nitrogen loading rate (0.79 kg·m-3·d-1) without adding organic matters during 320 days operation. Promoting NOx--N recirculation demonstrated as an efficient strategy for further nutrient depletion, facilitating the enhanced NO3--N removal to 100% with the considerably high P-uptake performance. Batch tests confirmed that denitrifying phosphorus accumulating organisms (DPAOs) using NO3--N as electron acceptors accounting for 68% in total PAOs. Dechloromonas was identified as dominating genus in DPR, while Nitrosomonas (1.31%), Candidatus_Kuenenia (5.53%) and Candidatus_Brocadia (1.77%) contributed to the desirable nitrogen removal, indicating that cooperative consortia of DPAOs, AOB and AnAOB were harvested during long-term operation. The CANDPR process was verified to be energy-saving and treatment-reliable for renovating of existing plants.

Feasibility of applying intermittent aeration and baffles for achieving granular nitritation in a continuous short-cut denitrifying phosphorus removal system.

It was difficult to obtain a stable and efficient short-cut denitrification and phosphorus removal process for domestic sewage treatment, therefore, the possibility of using granulation technology of nitritation sludge and intermittent aeration was evaluated to resolve the difficulty. Results showed that the nitrogen and phosphorus removal efficiencies of the system were 72% and 93%, respectively, under the condition of mode 3 (a period of 10 min with aeration 8 min and stop 2 min) with aeration energy consumption decreasing 20%. Microbial community revealed that Rhodocyclales was the dominant short-cut denitrifying phosphorus removing bacteria in the process, closely related to the performance of short-cut denitrifying phosphorus removal. Furthermore, Thauera and Denitratisoma belonging to the Rhodocyclales play a significant role of short-cut denitrifying phosphorus removal in the process. In addition, Aeromonas improved the performance of short-cut denitrifying phosphorus removal. Finally, nutrient removal efficiency was improved 8% in intermittent aeration mode 3 based on short-cut denitrifying phosphorus removal.

Modified Bu-zhong-yi-qi decoction synergies with 5 fluorouracile to inhibits gastric cancer progress via PD-1/PD- L1-dependent T cell immunization.

Gastric cancer remains the second most common tumor in China. Modified-Bu-zhong-yi-qi decoction (mBYD) as an adjuvant therapy for gastric cancer patients after chemotherapy could significantly prolong the survival time of patients. However, the potential anticancer mechanism for mBYD has not been well characterized. Here, we conducted a comprehensive study of mBYD on a gastric cancer xenograft model with MFC cells in 615 mice and patients. Our results showed that the survival times of the 5-FU + mBYD and mBYD groups were significantly longer than that of the control group. Moreover, the 5-FU + mBYD group had a longer survival time than the 5-FU group. Flow cytometry revealed that the value of CD4+/CD8+ in the mBYD group increased and that the proportions of CD8+PD-1+ T cells and PD-1+Treg cells were decreased when compared to the control group. Compared with the 5-FU group, CD8+PD-1+ T cells and Treg cells were both decreased when 5-FU was combined with mBYD. Further analysis showed that mBYD inhibited PD-L1 expression by the PI3K/AKT pathway in gastric cancer. An in vitro study also showed that mBYD directly promoted the proliferation, activation and cytotoxicity of T lymphocytes. Meanwhile, mBYD reduced the upregulation of CD8+PD-1+ T cells induced by chemotherapy in patients with gastric cancer. In conclusion, mBYD could modulate peripheral immunity and suppress the immune escape of tumors, which may be a promising therapy for gastric cancer.

The effect of Jianpi Yangzheng Xiaozheng Decoction and its components on gastric cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianpi Yangzheng Xiaozheng Decoction (JPYZXZ) is an empirical compound prescription based on the theory of traditional Chinese medicine. JPYZXZ, which is "Qi-invigorating, spleen-strengthening and stasis-removing," can improve the quality of life of gastric cancer patients and prolong their survival; however, the exact mechanism underlying the antitumor effects of this compound is still not clear. AIM OF THE STUDY: The aim of this study is to clearly define the effect of JPYZXZ and its components, Jianpi Yangzheng Decoction (JPYZ) and Xiao Zheng San Jie Decoction (XZSJ), on inhibiting the progression of gastric cancer. MATERIALS AND METHODS: The effect of JPYZXZ and its components on the motility of gastric cancer MGC-803 cells was measured by MTT, adhesion, transwell assays and wound-healing assays. JPYZXZ, JPYZ and XZSJ were administered to 615 mice with gastric cancer xenografts, and their effect on the inhibition of subcutaneous transplantation was analyzed. THP-1 monocyte cells were used to establish tumor-associated macrophage (TAM) models. The polarized state of the TAMs was detected by Flow Cytometry, ELISA and Immunohistochemistry. The mRNA and protein expression of tumor epithelial-mesenchymal transition (EMT) and TAM-related genes was determined by Real-time PCR and Western Blot, respectively. RESULTS: We determined that both JPYZXZ and its components inhibited the progress of gastric cancer in vitro, and JPYZXZ was clearly more effective than JPYZ or XZSJ. The in vivo results demonstrated that the JPYZXZ and XZSJ group exhibited a significant decrease in the tumor weight compared to the control group. Further analysis indicated that JPYZXZ was more active than JPYZ or XZSJ in inhibiting the gastric cancer EMT transformation both in vivo and in vitro. However, JPYZ was more effective compared with JPYZXZ for inducing the phenotypic change in macrophages from M2 to M1. CONCLUSIONS: Our results demonstrate that both JPYZXZ and its components prevent the progress of gastric cancer. JPYZXZ inhibits the gastric cancer EMT more effectively than JPYZ and XZSJ, but JPYZ primarily works to regulate the phenotypic change in macrophages from M2 to M1.

Lesson from Nature: Biomimetic Self-Assembling Phthalocyanines for High-Efficient Photothermal Therapy within the Biological Transparent Window.

Development of a facile but high-efficient small organic molecule-based photothermal therapy (PTT) in the in vivo transparent window (800-900 nm) has been regarded as a minimally invasive and most promising strategy for potential clinical cancer treatment. Phthalocyanine (Pc) molecules with remarkable photophysical and photochemical properties as well as high extinction coefficients in the near-infrared region are highly desirable for PTT, but as far satisfying single-component Pc-based PTT within the in vivo transparent window (800-900 nm) has very rarely been reported. Herein, inspired by the self-assembly algorithm of natural bacteriochlorophylls c, d, and e, biomimetic self-assembling tetrahexanoyl Pc Bio-ZnPc with outstanding light-harvesting capacity was demonstrated to exhibit excellent PTT efficacy evidenced by both in vitro and in vivo results, within the biological transparent window.