Machine learning approaches to predict the apparent rate constants for aqueous organic compounds by ferrate.

The apparent second-order rate constant with hexavalent ferrate (Fe(VI)) (kFe(VI)) is a key indicator to evaluate the removal efficiency of a molecule by Fe(VI) oxidation. kFe(VI) is often determined by experiment, but such measurements can hardly catch up with the rapid growth of organic compounds (OCs). To address this issue, in this study, a total of 437 experimental second-order kFe(VI) rate constants at a range of conditions (pH and temperature) were used to train four machine learning (ML) algorithms (lasso regression (LR), ridge regression (RR), extreme gradient boosting (XGBoost), and the light gradient boosting machine (LightGBM)). Using the Morgan fingerprint (MF)) of a range of organic compounds (OCs) as the input, the performance of the four algorithms was comprehensively compared with respect to the coefficient of determination (R2) and root-mean-square error (RMSE). It is shown that the RR, XGBoost, and LightGBM models displayed generally acceptable performance kFe(VI) (R2test > 0.7). In addition, the shapely additive explanation (SHAP) and feature importance methods were employed to interpret the XGBoost/LightGBM and RR models, respectively. The results showed that the XGBoost/LightGBM and RR models suggestd pH as the most important predictor and the tree-based models elucidate how electron-donating and electron-withdrawing groups influence the reactivity of the Fe(VI) species. In addition, the RR model share eight common features, including pH, with the two tree-based models. This work provides a fast and acceptable method for predicting kFe(VI) values and can help researchers better understand the degradation behavior of OCs by Fe(VI) oxidation from the perspective of molecular structure.

[Discussion on safety of Xanthii Fructus and consideration on its rational use].

Xanthii Fructus is a traditional Chinese medicine for the treatment of sinusitis and headache,rich in medicinal materials and is widely used for more than 1 800 years. Modern pharmacological studies have showed that Xanthii Fructus has anti-inflammatory,analgesic,anti-tumor,anti-bacterial,hypoglycemic,anti-allergic,immunomodulatory and other pharmacological effects,which can be commonly used in the treatment of diseases relating to immune abnormalities,such as rheumatoid arthritis,acute and chronic rhinitis,allergic rhinitis,and skin diseases,with a high medicinal value. Toxicological studies have shown that Xanthii Fructus poisoning can cause substantial damage to organs,such as the liver,kidney,and gastrointestinal tract,especially to liver. Because of the coexisting of its efficacy and toxicity,Xanthii Fructus often leads to a series of safety problems in the clinical application process. This study attempts to summarize its characteristics of adverse reactions,analyze the root cause of the toxicity of Xanthii Fructus from such aspects as processing,dose,course of treatment and eating by mistake,discuss the substance of its efficacy/toxicity from chemical compositions,and put forward exploratory thinking about how to promote its clinical rational application from the aspects such as strict processing,reasonable compatibility,medication information,contraindication,strict control of the dose,and course of treatment,so as to promote the safe and reasonable application of Xanthii Fructus.

Effect of Electroacupuncture on Gut Microbiota in Participants With Knee Osteoarthritis.

A close relationship between knee osteoarthritis (KOA) and gut microbiota has recently been described. Herein, we aim to investigate the effect of electroacupuncture (EA) on gut microbiota in participants with KOA. We conducted a study of 60 participants with KOA and 30 matched healthy controls (HCs). Sixty participants were allocated to either EA group (n=30) or sham acupuncture (SA) group (n=30). Five obligatory acupoints and three adjunct acupoints were punctured in the EA group. Eight non-acupoints that were separated from conventional acupoints or meridians were used for the SA group. Participants in both groups received 24 sessions within eight weeks. Fecal microbial analyses by 16S ribosomal RNA gene sequencing were carried out after collecting stools at T0 and T8 weeks (Four samples with changed defecation habits were excluded). The results showed that both Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score (P=0.043) and NRS score (P=0.002) decreased more in EA group than those in SA group. Moreover, EA could reverse more KOA-related bacteria including Bacteroides, [Eubacterium]_hallii_group, Agathobacter and Streptococcus. The number of significantly different genera between KOA patients and HCs were less after EA treatment than that after SA treatment. This meant that EA modified the composition of the gut microbiome, making it closer to healthy people, while not significantly affecting the microbial diversity. Two genera including Agathobacter (P=0.0163), Lachnoclostridium (P=0.0144) were statistically increased than baseline in EA group (paired Wilcoxon rank sum test). After EA treatment, Bacteroides (P=0.0394) was more abundant and Streptococcus (P=0.0306) was significantly reduced in patients who demonstrated adequate response than in those with inadequate response (Wilcoxon rank-sum test). Spearman correlation test between gut microbe and KOA clinical outcomes indicated that Bacteroides and Agathobacter was negatively correlated with NRS score, WOMAC total score, and WOMAC pain, stiffness and pain scores (P<0.001 or 0.05 or 0.01), while Streptococcus was positively correlated with them (P<0.05 or 0.01). Our study suggests that EA contributes to the improvement of KOA and gut microbiota could be a potential therapeutic target.

[Hypothalamic Transcription Profiles Associated with Twirling-reducing Needling in Rats with Stress-induced Prehypertension].

OBJECTIVE: To observe the effect of twirling-reducing needling on changes of profile of differentially-expressed genes in the hypothalamus in rats with stress-induced prehypertension (SI-PHT), so as to explore its mechanism under-lying improvement of prehypertension. METHODS: Wistar male rats were randomly divided into blank control group (n=12), model group (n=12) and acupuncture group (n=10). The SI-PHT model was established by planta-electric-shock stimulation (30 V, 5 s) plus noise stimulation (80-100 db, 50 ms), twice daily, continuously for 11 days. Manual acupuncture stimulation (twirling-reducing needling) was applied to bilateral "Taichong" (LR 3) and "Quchi" (LI 11) for about 1 min (60 cycles/min), followed by retaining the needles for 20 min during modeling preparation, once daily for 11 days. The systolic blood pressure (SBP) and behavior changes were recorded before intervention and on the 3rd, 5th, 7th, 9th and 11th day during modeling. The expression (Fold change,|FC| ≥ 1.5) profile of genes in the hypothalamus was analyzed using Affymetrix GeneChip Rat Gene 2.0 ST Array, followed by analyzing the differentially-expressed genes involving the related biological process,molecular function, and signaling pathways by using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), separately. RESULTS: After modeling, the systolic pressure levels were remarkably increased from the 3rd day to the 11th day in both model and acupuncture groups relatively to their respective baseline levels (P<0.01), and were significantly lower in the acupuncture group than in the model group (P<0.01) from the 5th day to the 11th day. Meanwhile, 93 genes were up-regulated and 153 down-regulated in the model group relative to the control group (P<0.05,|FC| ≥ 1.5), while in comparison with the model group, 59 genes were up-regulated and 86 down-regulated in the acupuncture group (P<0.05,|FC| ≥ 1.5). The expression levels of the 40 differen-tially-expressed genes (24 up-regulated and 16 down-regulated) in the model group were evidently reversed after acupuncture stimulation (P<0.05,|FC| ≥ 1.5). After acupuncture stimulation, the expression of acyl-CoA synthetase medium-chain family member 3 (Acsm 3) gene was down-regulated, and chorionic gonadotropin-alpha (Cgα), crystal (Cry) αB and thyroid stimulating hormone beta (Tshß) genes and the autoimmune thyroid disease (AITD) pathway were up-regulated (P<0.05,|FC| ≥ 1.5), suggesting an involvement of fatty acid biosynthetic processing, G-protein coupled receptor protein signaling, and hormone activity, etc. in acupuncture-induced blood-pressure lowering. CONCLUSIONS: Twirling-reducing needling of acupuncture can lower blood pressure in prehypertension rats, which may be related to its effects in regulating expression of Acsm 3, Cgα, CryαB, Tshß genes and in activating AITD pathway.

Effects on the tumor specific growth factor and tumor necrosis factor α in rats' precancerous lesion of primary hepatocellular carcinoma by direct moxibustion at Ganshu (BL 18) acupoint.

OBJECTIVE: To investigate the effect of direct moxibustion at Ganshu (BL18) on the serum concentrations of tumor specific growth factor (TSGF) and tumor necrosis factor α (TNF-α) in a rat model with precancerous lesion of primary hepatocellular carcinoma (HCC), so as to explore the mechanism of moxibustion underlying improvement of HCC. METHODS: Sixty male Wistar rats were randomly divided into control group (n=10), model group (n=20), prevention group 1 (n=15) and prevention group 2 (n=15). The normal rats were injected with physiological saline as blank control. At the same time, the rats of other three groups were injected with diethylnitrosamine to establish the HCC model. Direct moxibustion with grain-sized moxa was applied to bilateral Ganshu acupoint of the rats in the prevention group 1 (1 treatment course, 20 days) and prevention group 2 (2 treatment courses, 40 days), 5 doses for each acupoint, 0.5 mg/dose, once every other day. At each time point (before model establishment, the end of 1st course prevention, the end of 2nd course prevention and the end of model establishment), serum levels of TSGF and TNF-α were detected using enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, there was a remarkably increase of serum TSGF and TNF-α contents in the model group at the end of the experiment (P<0.05). At the end of the 1st course of direct moxibustion, the contents of serum TSGF and TNF-α of rats in the prevention group 1 were significantly increased compared with that of the model group (P<0.05). At the end of the 2nd course of direct moxibustion, serum TSGF and TNF-α levels of rats in the model group were higher than the normal group with significantly difference (P<0.05), and the levels of TSGF and TNF-α in the prevention group 2 were significantly reduced in comparison with the model group (P<0.05). CONCLUSION: It was possible that direct moxibustion could inhibit precancerous lesion and postpone hepatocarcinogenesis, and the therapeutic effect of two courses were better than one course.

[Effect of Electroacupuncture at "Yanglingquan" (GB 34) Acupoint on White Blood Cell Count and Gallbladder Wall Thickness in Rabbits with Acute Cholecystitis].

OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Yanglingquan"(GB 34) acupoint on white blood cell (WBC) count and gallbladder wall thickness in rabbits with acute cholecystitis, so as to explore the inherent correlation between the gallbladder and GB 34 acupoint according to the theory of Chinese medicine. METHODS: Thirty-two male rabbits were randomly and equally divided into control group, model group, EA "Yanglingquan"(GB 34) group (EA-GB 34) and EA "Yinlingquan"(SP 9) group (EA-SP 9). The acute cholecystitis model was induced by intra-gallbladder injection of escherichia coli liquid. EA stimulation was delivered once per day for consecutive 7 days. WBC count and gallbladder wall thickness were measured to assess the effects of EA treatment. HE staining was carried out to examine the pathological changes of the gallbladder tissue. RESULTS: Compared with the control group,WBC count and gallbladder wall thickness of the model group were significantly increased (P<0. 05), and those changes were reversed by EA intervention at either GB 34 or SP 9 acupoints (P<0. 05). As to WBC count, there was no significant difference between EA-GB 34 and EA-SP 9 groups (P>0. 05), whereas for reducing gallbladder wall thickness, EA stimulation at GB 34 acupoint resulted in a better effect than that of EA at SP 9 acupoint (P<0. 05). CONCLUSION: EA produces positive therapeutic benefits on acute cholecystitis in rabbits. It seems that stimulation at "Yan - glingquan" acupoint gives rise to a better effect than that of "Yinlingquan" acupoint in particular for the reduction of gallbladder wall thickhess.

[Effects of moxibustion at "Ganshu" (BL 18) on serum alpha-fatoprotein and liver livin levels in rats with precancerous lesion of primary hepatocellular carcinoma].

OBJECTIVE: To observe the effect of moxibustion at "Ganshu" (BL18) on levels of Livin (a novel member of the inhibitors of apoptosis family and plays crucial roles in apoptosis, cell proliferation, and cell cycle control) in the liver tissue in rats with precancerous lesion of primary hepatocellular carcinoma (HCC), so as to explore its mechanism underlying improvement of HCC. METHODS: Sixty male Wistar rats were randomly divided into control group (n = 10), model group (n = 20), moxibustion-20 d group (n = 15) and moxibustion-40 d group (n = 15). HCC model was established by intraperitoneal injection of diethylnitrosamine (DEN, 50 mg/kg), once every 3 days for 12 weeks. Moxibustion was applied to bilateral "Ganshu" (BL 18), once every other day for 10 times (moxibustion-20 d group) and 20 times (moxibustion-40 d group), respectively. Serum alpha-fetoprotein (AFP) content was detected with ELISA and Livin immunoactivity of the liver tissue detected using immunohistochemistry. RESULTS: After modeling, serum AFP content and liver Livin immunoactivity of the model group were significantly increased in comparison with the control group (P < 0.01). After moxibustion treatment, serum AFP content in the moxibustion-20 d group and liver Livin immunoactivity in both moxibustion-20 d and moxibustion-40 d groups were remarkably down-regulated in comparison with the model group (P < 0.05). No significant differences were found between the moxibustion-40 d group and the model group in serum AFP content (P > 0.05). CONCLUSION: Moxibustion can down-regulate liver Livin protein expression, which probably has a role in promoting hepatocellular apoptosis to inhibit precancerous lesion and to postpone hepatocarcinogenesis.