Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial.

BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .

Comparative study of the impact of dietary supplementation with different types of CpG oligodeoxynucleotides (CpG ODNs) on enhancing intestinal microbiota diversity, antioxidant capacity, and immune-related gene expression profiles in Pacific white shrimp (Litopenaeus vannamei).

The CpG oligodeoxynucleotides (CpG ODNs) reportedly possess the capacity to strengthen immunity in mammals. This experiment was conducted to evaluate the impact of dietary supplementation with 17 types of CpG ODNs on intestinal microbiota diversity, antioxidant capacity, and immune-related gene expression profiles of the shrimp Litopenaeus vannamei. Diets including 50 mg kg-1 CpG ODNs wrapped in egg whites were prepared and divided into 17 different groups, with 2 control groups (normal feed and feed with egg whites). These CpG ODNs supplemented diets and the control diets were fed to L. vannamei (5.15 ± 0.54 g) three times daily at 5%-8% shrimp body weight for three weeks. The results of consecutive detection of intestinal microbiota by 16S rDNA sequencing indicated that 11 of the 17 types of CpG ODNs significantly enhanced intestinal microbiota diversity, increased the populations of several probiotic bacteria, and activated possible mechanisms relevant to diseases. The immune-related genes expression and antioxidant capacity in hepatopancreas further demonstrated that the 11 types of CpG ODNs effectively improved the innate immunity of shrimp. Additionally, histology results showed that the CpG ODNs in the experiment did not damage the tissue structure of hepatopancreas. The results suggest that CpG ODNs could be used as a trace supplement to improve the intestinal health and immunity of shrimp.

Geranylated or prenylated flavonoids from Cajanus volubilis.

Five new flavonoid derivatives, cajavolubones A-E (1-5), along with six known analogues (6-11) were isolated from Cajanus volubilis, and their structures were elucidated by spectroscopic analysis and quantum chemical calculations. Cajavolubones A and B (1 and 2) were identified as two geranylated chalcones. Cajavolubone C (3) was a prenylated flavone, while cajavolubones D and E (4 and 5) were two prenylated isoflavanones. Compounds 3, 8, 9 and 11 displayed cytotoxicity against HCT-116 cancer cell line.

Improving flavor of summer Keemun black tea by solid-state fermentation using Cordyceps militaris revealed by LC/MS-based metabolomics and GC/MS analysis.

Cordyceps militaris (C. militaris) has been approved and widely used in healthy food. The present study aimed to improve the flavor of summer Keemun black tea (KBT) using C. militaris solid-state fermentation. Combined with sensory evaluation, the volatile and non-volatile components of solid-state fermentation of KBT (SSF-KBT) and KBT were analyzed. The results showed that after the solid-state fermentation, the contents of total polyphenol, total flavonoid, and total free amino acids were significantly reduced. Further non-targeted metabolomics analysis revealed that the contents of non-galloylated catechins and d-mannitol increased, while the galloylated catechins and flavonoid glycosides decreased as did the bitterness and astringency of KBT. Dihydro-ß-ionone and ß-ionone (OAV = 59321.97 and 8154.17) were the aroma-active compounds imparting woody and floral odors in SSF-KBT, respectively. Current study provides a new avenue to develop summer-autumn KBT.

Nitrative inactivation of thioredoxin-1 loses its protective effect in bleomycin-induced pulmonary fibrosis.

Pulmonary fibrosis is common in the development of inflammatory lung diseases with no effective clinical drug treatment currently. As an essential redox enzyme, thioredoxin (Trx) has been reported to be involved in pulmonary fibrosis, but the mechanism is to be revealed. Therefore, in bleomycin-indued pulmonary fibrosis model in C57 mice, Trx activity and nitrated Trx were examined.,p38-MAPK apoptosis pathway was determined in lung tissues. Additionally, before BLM administration, C57/BL6 mice were treated with aminoguanidine (AG, a peroxynitrite scavenger), recombinant human Trx-1 (rhTrx-1), or SIN-1 (a peroxynitrite donor) nitrated Trx-1 (N-Trx-1). In bleomycin (BLM)-induced pulmonary fibrosis model in C57/BL6 mice, we observed that nitrated Trx increased, while its activity decreased, with the increase of alveolar epithelial cells (AECs)apoptosis by p38-MAPK pathway. We demonstrated that AG or rhTrx-1, but not N-Trx-1 significantly reduced pulmonary fibrosis. Taken together, the results above revealed that blockade of Trx-1 nitration, or supplementation of exogenous rhTrx-1, might represent novel therapies to attenuate pulmonary fibrosis in idiopathic pulmonary fibrosis patients.

Two new catechins from Zijuan green tea enhance the fitness and lifespan of Caenorhabditis elegans via insulin-like signaling pathways.

Green tea polyphenols show positive effects on human health and longevity. However, knowledge of the antiaging properties of green tea is limited to the major catechin epigallocatechin gallate (EGCG). The search for new ingredients in tea with strong antiaging activity deserves further study. Here we isolated and identified two new catechins from Zijuan green tea, named zijuanin E (1) and zijuanin F (2). Their structures were identified by extensive high-resolution mass spectroscopy (HR-MS), nuclear magnetic resonance (NMR), ultraviolet-vis (UV), infrared (IR) and circular dichroism (CD) spectroscopic analyses, and their 13C NMR and CD data were calculated. We used the nematode Caenorhabditis elegans (C. elegans) to analyze the health benefits and longevity effects of 1 and 2. Compounds 1 and 2 (100 µM) remarkably prolonged the lifespan of C. elegans by 67.2% and 56.0%, respectively, delaying the age-related decline of phenotypes, enhancing stress resistance, and reducing ROS and lipid accumulation. Furthermore, 1 and 2 did not affect the lifespan of daf-16, daf-2, sir-2.1, and skn-1 mutant worms, suggesting that they might work via the insulin/IGF and SKN-1/Nrf2 signaling pathways. Meanwhile, 1 and 2 also exhibited strong antioxidant activity in vitro. Surface plasmon resonance (SPR) evidence suggests that zijuanins E and F have strong human serum albumin (HSA) binding ability. Together, zijuanins E and F represent a new valuable class of tea components that promote healthspan and could be developed as potential dietary therapies against aging.

Gut Microbiota Associated With Effectiveness And Responsiveness to Mindfulness-Based Cognitive Therapy in Improving Trait Anxiety.

Objective: Mindfulness-based interventions have been widely demonstrated to be effective in reducing stress, alleviating mood disorders, and improving quality of life; however, the underlying mechanisms remained to be fully understood. Along with the advanced research in the microbiota-gut-brain axis, this study aimed to explore the impact of gut microbiota on the effectiveness and responsiveness to mindfulness-based cognitive therapy (MBCT) among high trait anxiety populations. Design: A standard MBCT was performed among 21 young adults with high trait anxiety. A total of 29 healthy controls were matched for age and sex. The differences in gut microbiota between the two groups were compared. The changes in fecal microbiota and psychological indicators were also investigated before and after the intervention. Results: Compared with healthy controls, we found markedly decreased bacterial diversity and distinctive clusters among high trait anxiety populations, with significant overgrowth of bacteria such as Streptococcus, Blautia, and Romboutsia, and a decrease in genera such as Faecalibacterium, Coprococcus_3, and Lachnoclostridium. Moreover, MBCT attenuated trait anxiety and depression, improved mindfulness and resilience, and increased the similarity of gut microbiota to that of healthy controls. Notably, a high presence of intestinal Subdoligranulum pre-MBCT was associated with increased responsiveness to MBCT. Decreases in Subdoligranulum post-MBCT were indicative of ameliorated trait anxiety. The tryptophan metabolism pathways were significantly over-represented among high responders compared to low responders. Conclusion: The significantly increased diversity post-MBCT added evidence to gut-brain communication and highlighted the utility of mycobiota-focused strategies for promoting the effectiveness and responsiveness of the MBCT to improve trait anxiety. Clinical Trial Registration: chictr.org.cn, ChiCTR1900028389.

Differential efficacy of water lily cultivars in phytoremediation of eutrophic water contaminated with phosphorus and nitrogen.

Excessive inputs of phosphorus (P) and nitrogen (N) trigger eutrophication of the water bodies, which promotes the undesirable growth of algal bloom and deterioration of the water quality, and aquatic biodiversity. Macrophytes provide an environmentally benign and economically viable paradigm for the ecological restoration of eutrophic aquatic ecosystems. Water lily (Nymphaea) is largely used as ornamental plant for landscaping, and it has been documented that water lily possesses the potentiality in mitigating polluted aquatic environments. In the present study, water lily cultivars Nymphaea Texas Dawn (NTD), Nymphaea Colorado (NC), Nymphaea Madame Wilfron Gonnère (NMWG), and Nymphaea Sunshine Princess (NSP) were investigated for their potency in alleviating the eutrophication. The concentrations of total P and total N were significantly higher in the leaves of NC and NSP compared with NTD and NMWG. Therefore, NC and NSP were selected for subsequent studies to decipher their recuperation efficacy on eutrophic waters at different growth stages. NC and NSP significantly reduced the concentrations of eutrophication indicators i.e., total P, NH4+-N, and chemical oxygen demand in different gradients of the simulated eutrophic water in a growth-dependent manner. On the contrary, NC and NSP triggered a significant increase in the concentration of dissolved oxygen particularly at the seedling stage. Notably, the concentrations of total P (shoot and root) and total N (root) were relatively higher in NSP than NC. The study thus revealed a growth-dependent differential efficacy of NSP and NC in mitigating the different eutrophic waters.

Ginsenoside Rg1 promoted the wound healing in diabetic foot ulcers via miR-489-3p/Sirt1 axis.

PURPOSE: Diabetic foot ulcers (DFUs) are common complications of high severity for diabetes. Ginsenoside Rg1 (Rg1) has the potential for diabetes and cardiovascular diseases therapy. This research aimed at exploring the regulation of Rg1 on DFUs treatment and the underlying mechanism. METHODS: Human umbilical vein endothelial cells (HUVECs) incubated with high-glucose culture medium were established for induction of diabetes model. The MTT assay, Annexin V/PI assay and oxidative stress detection were carried out on high-glucose-induced HUVECs. Dual-luciferase reporter assay was performed to prove the interaction of miR-489-3p and Sirt1. DFUs model was established to determine the efficiency of Rg1 and miR-489-3p in wound closure of DFUs in vivo. RESULTS: Rg1 promoted cell proliferation, migration and angiogenesis, and reduced cell apoptosis in high-glucose-induced HUVECs. Knockdown of miR-489-3p alleviated the high-glucose-induced damage to HUVECs, while overexpression of miR-489-3p attenuated the protection effects of Rg1. Overexpression Sirt1 promoted wound healing in DFUs and Sirt1 was a direct target of miR-489-3p. In addition, animal experiments demonstrated that Rg1 promoted wound closure by regulating miR-489-3p/Sirt1 axis. CONCLUSIONS: Rg1 alleviated the DFUs by increasing Sirt1 expression via miR-489-3p downregulation and promoting activation of PI3K/AKT/eNOS signaling.

Effects of moxibustion on reproduction and metabolism of polycystic ovary syndrome: a protocol for meta-analysis and systematic review.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathy in women of reproductive age. Recently, moxibustion, as a complementary and alternative therapy, has been commonly used in assisted reproduction and improvement of metabolic abnormalities in patients with PCOS. Currently, intervention efficacy of the use of moxibustion in PCOS treatment still remains controversial due to lack of high-quality evidence. Consequently, this study protocol was designed to objectively review and evaluate the effectiveness and safety of moxibustion treatment for PCOS. METHODS AND ANALYSIS: Electronic searches will be carried out from inception to May 2021 in the online databases of The Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature, Chongqing VIP Chinese Science and Technology Periodical Database (VIP) and China National Knowledge Infrastructure. The Chinese Clinical Trial Registry Center and Clinical Trials will be used for searching ongoing trials. Randomised controlled trials and the first period in randomised cross-over trials involving any type of moxibustion for patients with PCOS will be included. Primary outcomes will be the ovulation rate, pregnancy rate and sex hormone levels, and secondary outcomes will be changes in clinical symptoms and metabolic indicators, total effective rate and the incidences of side effects and adverse events. Briefly, two reviewers will independently conduct study selection and data extraction, and the risk of bias will be assessed. Prior to the formal meta-analysis, the heterogeneity of included studies will be assessed. Review Manager Statistical Software (RevMan) V.5.3 will be used for data processing. Finally, the Grading of Recommendations Assessment, Development and Evaluation method will be applied to evaluate the quality of evidence. ETHICS AND DISSEMINATION: Ethical approval is not necessary since this study is designed as a systematic review. This study will be disseminated by a peer-review journal or conference presentation.

Discovery and Targeted Isolation of Phenylpropanoid-Substituted Ester-Catechins Using UPLC-Q/TOF-HRMS/MS-Based Molecular Networks: Implication of the Reaction Mechanism among Polyphenols during Green Tea Processing.

Tea is an important beverage source of dietary polyphenols and well known for containing phenolic structure diversity. A series of phenylpropanoid-substituted catechins, flavonols, flavan-3-hexoside, and proanthocyanidin are present in different herbs with various biological activities, inspiring our exploration of phenylpropanoid-substituted ester type of catechins (PSECs) due to the enrichment of galloylated catechins in tea. In this study, we used a guiding-screening-location-isolation integrated route including creating a hypothesized PSEC dataset, MS/MS data acquiring, construction of molecular networks, and traditional column chromatography and preliminarily identified 14 PSECs by MS/MS spectrum. Two of these PSECs were further purified and elucidated by NMR and CD spectra. Further MS detection in tea products and fresh leaves suggests that the production of the two new compounds was enhanced during tea processing. The synthesis mechanism was proposed to obtain these types of components for further investigation on their roles in human health protection. This study provides an example for the exploration of new functional ingredients from food sources guided by MS/MS data-based networking, and also new insights into the reaction mechanism to form new catechin conjugates among polyphenols in green tea.

Paeonol prevents migration and invasion, and promotes apoptosis of cervical cancer cells by inhibiting 5­lipoxygenase.

Cervical cancer is a common public health issue with high morbidity worldwide. Paeonol (Pae) has been recognized as a traditional Chinese medicine used for the treatment of various cancer types. However, whether Pae could exert a protective effect on cervical cancer remains to be investigated. The aim of the present study was to explore the role of Pae in cervical cancer cells and identify the potential mechanism. Cell Counting Kit­8 and colony­formation assays were conducted to test the proliferation of HeLa cells. Additionally, wound healing and transwell assays were used to detect the migratory and invasive abilities of cells. The plasmid that overexpressed 5­lipoxygenase (5­LO) or control vector was constructed and transfected into the cells. Subsequently, flow cytometry was used to monitor the apoptotic rate of cells. The expression levels of apoptosis­associated proteins and 5­LO were detected using western blot analysis. Reverse transcription­quantitative PCR analysis detected the expression of 5­LO. Pae inhibited the proliferation, invasion and migration of HeLa cells, promoted cell apoptosis and downregulated the expression of 5­LO. Overexpression of 5­LO, however, attenuated these effects. Thus, Pae could inhibit the proliferation, migration and invasion, as well as promote apoptosis of HeLa cells by regulating the expression of 5­LO.

Promotion of Zinc Tolerance, Acquisition and Translocation of Phosphorus in Mimosa pudica L. Mediated by Arbuscular Mycorrhizal Fungi.

Heavy metal contamination of soil is of increasing concern because of its potential risk to human health. In this study, two AMFs (Rhizophagus intraradices and Funneliformis mosseae) substantially increased the biomass of bashfulgrass in Zn-contaminated soil, even at Zn levels of up to 600 mg kg-1. Zn uptake in R. intraradices- and F. mosseae-mycorrhizal bashfulgrass was increased by 40-fold and 7-fold, respectively, when plants grown in Zn-contaminated (400 mg kg-1) soil. Elemental analysis showed that neither AMF had an effect on Zn concentration in plant tissues, including the roots and shoots. However, a significant increase of phosphorus (P) concentration was observed, suggesting the increased is from the improved use efficiency of soil nutrients by AMFs. Comparing the two AMFs, better growth performance with more biomass occurred with R. intraradices-inoculated bashfulgrass in Zn-contaminated soil. This is consistent with R. intraradices being more tolerant to Zn than F. mosseae, indicated by a higher colonization percentage in bashfulgrass roots. Taken together, our data indicate that AMFs possibly improve acquisition and translocation of P to promote increased biomass. Moreover, mycorrhiza did not enhance Zn accumulation in shoots and roots of bashfulgrass at the same Zn level. In the future, developing AMF (especially R. intraradices) inoculation of plants might be a desirable means of safe production of ornamental plants in metal-polluted soil.

Partial regression of foveoschisis following vitamin B6 supplementary therapy for gyrate atrophy in a Chinese girl.

BACKGROUND: To report a case of genetically confirmed gyrate atrophy (GA) of choroid and retina, who showed partial regression of foveoschisis following vitamin B6 supplementary therapy. CASE PRESENTATION: A 6-year-old Chinese girl complained about night blindness and progressive decreased vision in both eyes. Her best corrected visual acuity (BCVA) was 20/63 OD and 20/100 OS. Fundus examination showed bilateral multiple, sharply demarcated, scallop-shaped chorioretinal atrophy areas in the midperipheral and peripheral of the fundus. Spectral domain optical coherence tomography (SD-OCT) showed increased central macular thickness (CMT) with multiple intraretinal cystic spaces in the both eyes. There was no leakage or staining in the macular area in late phase of fluorescein angiography (FA). Blood tests confirmed hyperornithinemia and genetic analysis revealed two heterozygous mutations on ornithine aminotransferase (OAT) gene. Based on clinical presentation and genetic test, the patient was diagnosed as GA of the choroid and retina and further treated with vitamin B6 supplementary for three weeks. Her serum ornithine levels did not change but CMT on SD-OCT declined with partial regression of intraretinal cystic spaces. Then, the patient discontinued the drug because of severe muscle pain, and foveoschisis increased to initial level a month later. CONCLUSIONS: Foveoschisis is a rare complication of GA. Vitamin B6 supplementation may alleviate foveoschisis, but its effort for reducing serum ornithine level might be limited. Potential drug adverse effects should be noted in pediatric patients.

Prevalence, expenditures, and associated factors of purchasing non-prescribed Chinese herbal medicine in Taiwan.

BACKGROUND AND AIMS: Purchasing Chinese herbal medicine (CHM) without a physician's prescription may have adverse effects on health. However, the recent status of purchasing non-prescribed CHM and the associated factors are not completely understood. We aimed to report the prevalence of purchasing CHM and associated factors. METHODS: Using data from the 2017 Taiwan Survey of Family Income and Expenditure, we identified 16,528 individuals (householders) aged 18 years and older. Sociodemographic factors, expenditures on medical services and health behaviours were compared between people with and without a history of purchasing non-prescribed CHM by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in a multiple logistic regression analysis. RESULTS: The one-year prevalence of purchasing non-prescribed CHM was 74.8% in Taiwan. In addition to sociodemographics, marital status (OR 2.14, 95% CI 1.88-2.44), the use of traditional Chinese medicine (OR 3.62, 95% CI 3.30-3.97), the purchasing of non-prescribed biochemical medications (OR 3.09, 95% CI 2.75-3.48), the purchasing of health foods (OR 2.59, 95% CI 2.33-2.86), the use of folk therapy (OR 2.27, 95% CI 1.95-2.64), and a high level of expenditure on alcohol (OR 3.79, 95% CI 3.29-4.36) were strongly correlated with purchasing non-prescribed CHM. CONCLUSION: The one-year prevalence of purchasing non-prescribed CHM is very high in Taiwan and is correlated with sociodemographics, health behaviours, and the utilization of medical care. The interaction of non-prescribed CHM with physician-prescribed herbal medicine and biomedical medications requires more attention.

Triptolide Inhibits the Proliferation of HaCaT Cells Induced by IL22 via Upregulating miR-181b-5p.

BACKGROUND: Evidence has been shown that triptolide was effective in the treatment of psoriasis; however, the mechanisms remain poorly understood. Thus, this study aimed to investigate the role of triptolide on the proliferation and differentiation of HaCaT cells which are treated with IL22 to mimic abnormal proliferation/differentiation in keratinocyte of psoriasis. MATERIALS AND METHODS: HaCaT cells were transfected with miR-181b-5p antagomir for 24 h, and then exposed to 10 µM Triptolide for 24 h, following by 100 ng/mL of IL22 for 24 h. In addition, the proliferation and cell cycle distribution in HaCaT cells were assessed by immunofluorescence or flow cytometry assays, respectively. RESULTS: Triptolide obviously upregulated the level of miR-181b-5p in HaCaT cells. In addition, triptolide significantly inhibited IL22-induced proliferation of HaCaT cells via inducing cell cycle arrest. Moreover, IL22 markedly inhibited the differentiation of HaCaT cells, and this phenomenon was reversed by triptolide treatment. In contrast, the effects of triptolide on the proliferation and differentiation in IL22-stimulated HaCaT cells were notably reversed by miR-181b-5p antagomir. Moreover, dual-luciferase assay showed that E2F5 was the direct target of miR-181b-5p in HaCaT cells. Meanwhile, upregulation of miR-181b-5p obviously decreased the level of E2F5 in HaCaT cells. CONCLUSION: In this study, we found that triptolide could inhibit the proliferation and promote the differentiation in IL22-stimulated keratinocytes via upregulating miR-181b-5p. These data indicated that triptolide may be a potential agent for the treatment of psoriasis.

(±)-Meliviticines A and B: Rearranged prenylated acetophenone derivatives from Melicope viticina and their antimicrobial activity.

Two new prenylated acetophenone derivatives racemates, meliviticines A (1) and B (2) with unprecedented rearranged skeletons, were isolated from Melicope viticina. Subsequent chiral resolution led to the separation of two pairs of enantiomers, (±)-meliviticines A (1a/1b) and (±)-meliviticines B (2a/2b). Their structures including absolute configurations were elucidated by extensive spectroscopic data, electronic circular dichroism analysis, and X-ray crystallography. A plausible biosynthetic pathway of 1 and 2, involving ring cleavage and rearrangement of the prenylated acetophenone backbone was proposed. All the isolates showed moderate antimicrobial activities with MIC values of 25-50 µg/mL against several bacterial and fungal strains.

A review of bacteriophage therapy for pathogenic bacteria inactivation in the soil environment.

The emerging contamination of pathogenic bacteria in the soil has caused a serious threat to public health and environmental security. Therefore, effective methods to inactivate pathogenic bacteria and decrease the environmental risks are urgently required. As a century-old technique, bacteriophage (phage) therapy has a high efficiency in targeting and inactivating pathogenic bacteria in different environmental systems. This review provides an update on the status of bacteriophage therapy for the inactivation of pathogenic bacteria in the soil environment. Specifically, the applications of phage therapy in soil-plant and soil-groundwater systems are summarized. In addition, the impact of phage therapy on soil functioning is described, including soil function gene transmission, soil microbial community stability, and soil nutrient cycling. Soil factors, such as soil temperature, pH, clay mineral, water content, and nutrient components, influence the survival and activity of phages in the soil. Finally, the future research prospects of phage therapy in soil environments are described.

Theoretical explanation for the pharmaceutical incompatibility through the cooperativity effect of the drug-drug intermolecular interactions in the phenobarbital∙∙∙paracetamol∙∙∙H2O complex.

In order to reveal the essence of the pharmaceutical incompatibility, the cooperativity effects of the drug-drug intermolecular π∙∙∙π and H∙∙∙O H-bonding interactions involving hydration were evaluated in the phenobarbital∙∙∙paracetamol∙∙∙H2O complex at the M06-2X/6-311++G** and MP2/6-311++G** levels. The thermodynamic cooperativity effects were also investigated by the statistical thermodynamic method. The results show that the π∙∙∙π stacking ternary complexes with the moderate anti-cooperativity effects are dominant in controling the aggregation process of phenobarbital, paracetamol, and H2O, as is confirmed by the atoms-in-molecules (AIM) and reduced density gradient (RDG) analyses. Therefore, it can be inferred that the anti-cooperativity effect plays an important role in forming the pharmaceutical incompatibility, and thus a deduction on the formation process of the pharmaceutical incompatibility between phenobarbital and paracetamol, with the hydration effect, is given. Several valuable models that relate the features of molecular surface electrostatic potentials or their statistical parameters, such as the surface areas, average values ([Formula: see text]), variances ([Formula: see text], [Formula: see text] and [Formula: see text]), and product of [Formula: see text] and electrostatic balance parameter (ν) ([Formula: see text]ν), to the values of the cooperativity effects were predicted. The formation of the pharmaceutical incompatibility is a thermodynamic cooperativity process driven by the enthalpy change. Graphical abstract Anti-cooperativity effect plays an important role in forming the pharmaceutical incompatibility.

Cytotoxic arylalkenyl α,ß-unsaturated δ-lactones from Cryptocarya brachythyrsa.

Three new arylalkenyl α,ß-unsaturated δ-lactones, cryptobrachytones A-C (1-3), together with one known analogue kurzilactone (4), were isolated from the leaves and twigs of Cryptocarya brachythyrsa. Their structures were elucidated based on extensive spectroscopic data and electronic circular dichroism (ECD) analysis. All the isolates were evaluated in vitro for anti-proliferative activity against a panel of five human cancer cell lines and one human normal cell, respectively, and the results showed 1, 2 and 4 possessing significant selective cytotoxicity toward the human cancer cell lines with IC50 values from 5.41 to 15.43 µM. This is the first study for C. brachythyrsa.