Effects of Wetland Vegetation on Soil Microbial Composition:A Case Study in Tumen River Basin,Northeast China

Hydrology plays a dominant role in wetland plant distribution and microbial composition, but few studies explicitly attempted to relate the linkage between wetland vegetation and microbial community. The present study consisted of five wetland plant communities along three adjacent flood gradients zones(zone 1 dominated by Carex appendiculat, zone 2 dominated by Eleocharis ovate, and zone 3 dominated by Phragmites australis/Bidens pilosa/Calamagrostis angustifolia, which formed separate, monoculture patches). Gram negative and arbuscular mycorrhizal fungal phospholipid fatty acid(PLFA) are more abundant in the site with short flooding period(zone 3) than in the site with long flooding period(zone 1), and they are also different in the P. australis, B. spilosa and C. angustifolia of zone 3. Principle Component Analysis(PCA) showed that the flooding period could explain 92.4% of variance in microbial composition. Redundancy Analysis(RDA) showed that available nitrogen(AN), total nitrogen(TN) and soil organic matter(SOM) could explain the 79.5% of variance in microbial composition among E. ovata, P. australis, B. pilosa and C. angustifolia. Results demonstrated that flooding period was the main factor in driving the microbial composition and plant-derived resources could influence soil microbial composition in the seasonally flooded zones.

Photo-isomerization of Aromatic α-Hydroxy Hydrazone

Photo-isomerization of aromatic α-hydroxy hydrazone was reported. We investigated the structures of salicylaldehyde phenylhydrozone（SP） in the ground state using density functional theory（DFT） with the B3LYP functional and the 6-311＋G（d） basis set. All nine possible isomers of SP in the ground state consist of seven phenol forms and two ketone forms. Intrisic reaction coordinate（IRC） analysis discloses the existence of a cycle driven by the two proton transfer processes in the ground and excited states of SP, which suggests that no ketonic form could exist in the ground state. Further theoretical studies of the potential energy surfaces support a trans-cis conversion followed by a relaxation to the stable form of SP in the excited states.

Development of fluorine-substituted NH_(2)-biphenyl-diarylpyrimidines as highly potent non-nucleoside reverse transcriptase inhibitors:Boosting the safety and metabolic stability

Our recent studies for nonnucleoside reverse transcriptase inhibitors identified a highly potent compound JK-4b against WT HIV-1(EC_(50)=1.0 nmol/L),but the poor metabolic stability in human liver microsomes(t_(1/2)=14.6 min)and insufficient selectivity(SI=2059)with high cytotoxicity(CC_(50)=2.08μmol/L)remained major issues associated with JK-4b.The present efforts were devoted to the introduction of fluorine into the biphenyl ring of JK-4b,leading to the discovery of a novel series of fluorine-substituted NH_(2)-biphenyl-diarylpyrimidines with noticeable inhibitory activity toward WT HIV-1 strain(EC_(50)=1.8–349 nmol/L).The best compound 5t in this collection(EC_(50)=1.8 nmol/L,CC_(50)=117μmol/L)was 32-fold in selectivity(SI=66,443)compared to JK-4b and showed remarkable potency toward clinically multiple mutant strains,such as L100I,K103N,E138K,and Y181C.The metabolic stability of 5t was also significantly improved(t_(1/2)=74.52 min),approximately 5-fold higher than JK-4b in human liver microsomes(t_(1/2)=14.6 min).Also,5t possessed good stability in both human and monkey plasma.No significant in vitro inhibition effect toward CYP enzyme and hERG was observed.The single-dose acute toxicity test did not induce mice death or obvious pathological damage.These findings pave the way for further development of 5t as a drug candidate.

Structure-directed expansion of biphenyl-pyridone derivatives as potent non-nucleoside reverse transcriptase inhibitors with significantly improved potency and safety

Following our previous work on human immunodeficiency virus-1(HIV-1)non-nucleoside reverse transcriptase inhibitors(NNRTIs),a series of novel biphenyl-pyridone derivatives were synthesized and evaluated for their anti-HiV-1 activity to expand their structure-activity relationship.Some of them exhibited low nanomolar activity toward wild-type HiV-1 and clinically relevant single/double mutant strains.The most active compound B1 was 231-fold more potent(EC_(50)=17nmol/L)than the lead compound 2(EC_(50)=3.93μmol/L)against wild-type(WT)HIV-1.This compound was approximately 3.5-fold less cytotoxic(CC_(50)=100.58μmol/L)than compound 2(CC_(50)=28.24μmol/L),presenting a higher selectivity index(SI)value of 5923.Compared with 2,the antiviral potency of B1 was significantly increased against five single mutant strains(L1001,K103N,E138K,Y181C and Y188L)and two double mutant strains(F227L+V106A and K103N+Y181C).Especially,K103N,Y181C and K103N+Y181C were more sensitive to B1 than both 2 and doravirine.Besides,the enzymatic inhibitory activity of B1 against wild-type HIV-1 reverse transcriptase was approximately 32-fold higher(IC_(50)=100nmol/L)than 2(IC_(50)=3.21μmol/L).Molecular docking studies and dynamic simulations were conducted to explain their potent activity.Taken together,this research represents an important step toward the discovery of novel biphenylpyridone drug candidates for HIV therapy.

Structure-based design of novel heterocyclesubstituted ATDP analogs as non-nucleoside reverse transcriptase inhibitors with improved selectivity and solubility

Following on our recently developed biphenyl-ATDP non-nucleoside reverse transcriptase inhibitor ZLM-66(SI=2019.80,S=1.9μg/mL),a series of novel heterocycle-substituted ATDP derivatives with significantly improved selectivity and solubility were identified by replacement of the biphenyl moiety of ZLM-66 with heterocyclic group with lower lipophilicity.Evidently,the representative analog 7w in this series exhibited dramatically enhanced selectivity and solubility(SI=12,497.73,S=4472μg/mL)in comparison with ZLM-66(SI=2019.80,S=1.9μg/mL).This new NNRTI conferred low nanomolar inhibition of wild-type HIV-1 strain and tested mutant strains(K103N,L1001,Y181C,E138K,and K103N+Y181C).The analog also demonstrated favorable safety and pharmacokinetic profiles,as evidenced by its insensitivity to CYP and hERG,lack of mortality and pathological damage,and good oral bioavailability in rats(F=27.1%).Further development of 7w for HIV therapy will be facilitated by this valuable information.

Synthesis and biological evaluation of dihydrotriazine derivatives as potential antibacterial agents

A series of 1,4-dihydro-1,3,5-triazine derivatives were designed and synthesized and their antibacterial and antifungal activities were evaluated. Most of the synthesized compounds showed potent inhibition of several Gram-positive bacterial strains（including multidrug-resistant clinical isolates） and Gramnegative bacterial strains, with minimum inhibitory concentrations（MICs） in the range of 2.1–181.2 mmol/L. Compounds 7a and 7c presented the most potent inhibitory activities against Grampositive bacteria（e.g., Staphylococcus aureus 4220）, Gram-negative bacteria（e.g., Escherichia coli 1924）,and the fungus Candida albicans 7535, with MICs of 2.1 or 4.1 mmol/L. Especially, compound 7a was the most potent, with an MIC of 2.1 mmol/L against four multidrug-resistant, Gram-positive bacterial strains.The cytotoxic activity of the compound 7a, 7c and 7f was assessed in HepG2 cells, and the results suggest that 1,4-dihydro-1,3,5-triazine derivatives bearing a 6-benzyloxynaphthalen moiety are interesting scaffolds for the development of novel antibacterial agents.