Discovery of 1,3,4-oxadiazole derivatives as potential antitumor agents inhibiting the programmed cell death-1/programmed cell death-ligand 1 interaction.

Inhibition of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction by small-molecule inhibitors is emerging cancer immunotherapy. A series of novel 1,3,4-oxadiazole derivatives were designed, synthesized, and evaluated for their activities in vitro and vivo to find potent inhibitors of the PD-1/PD-L1 interaction. Among them, compoundⅡ-14exhibited outstanding biochemical activity, with an IC50of 0.0380 µM. Importantly, compound II-14, with a TGI value of 35.74 %, had more potent efficacy in a mouse tumor model compared to that in the control group. Surprisingly, when compound II-14 combined with 5-FU in a mouse tumor model having a TGI value of 64.59 %, which showed potential anti-tumor synergistic effects. Furthermore, immunohistochemistry analysis demonstrated thatcompound II-14 activated the immune microenvironment by promoting the infiltration of CD4+ T cells into tumor tissues. These results indicate that compound II-14 is a promising lead compound for further development of small-molecule PD-1/PD-L1 inhibitors for cancer therapy.

Effects of reclamation years on composition and diversity of soil bacterial communities in Northwest China.

The objective of this study was to evaluate bacterial community structure and diversity in soil aggregate fractions when salinized farmland was reclaimed after >27 years of abandonment and then farmed again for 1, 5, 10, and 15 years. Illumina MiSeq high-throughput sequencing was performed to characterize the soil bacterial communities in 5 aggregate size classes in each treatment. The results indicated that reclamation significantly increased macro-aggregation (>0.25 mm), as well as soil organic C, available N, and available P. The 10-year field had the largest proportion (93.9%) of soil in the macro-aggregate size classes (i.e., >0.25 mm) and the highest soil electrical conductivity. The 5 most dominant phyla in the soil samples were Proteobacteria, Actinobacteria, Gemmatimonadetes, Acidobacteria, and Bacteroidetes. The phylogenetic diversity, Chao1, and Shannon indices increased after the abandoned land was reclaimed for farming, reaching maximums in the 15-year field. Among aggregate size classes, the 1-0.25 mm aggregates generally had the highest phylogenetic diversity, Chao1, and Shannon indices. Soil organic C and soil electrical conductivity were the main environmental factors affecting the soil bacterial communities. The composition and structure of the bacterial communities also varied significantly depending on soil aggregate size and time since reclamation.

Duration of continuous cropping with straw return affects the composition and structure of soil bacterial communities in cotton fields.

Salinized land in the China's Xinjiang Region is being reclaimed for continuous cotton production. The specific objectives of this field study were (i) to compare bacterial composition and diversity in unfarmed (i.e., unreclaimed) and continuously (5, 10, 15, and 20 years) cropped soils and (ii) to explore correlations between soil properties and the bacterial communities identified by Illumina MiSeq sequencing. The results showed that bacterial species richness and diversity increased for 10-15 years and then declined when salinized land was reclaimed for cotton production. Proteobacteria and Firmicutes were the dominant phyla in unfarmed soil. Continuous cropping reduced the abundance of Firmicutes but increased that of Chloroflexi, Acidobacteria, and Actinobacteria. Cluster analyses showed that the greatest similarities in bacterial communities were between the 5- and 10-year treatments and between the 15- and 20-year treatments. Soil pH, electrical conductivity, alkali-hydrolyzable N, and available P were significantly correlated with bacterial community distribution. Overall, cotton production improved soil physicochemical properties and altered the structure and composition of soil bacterial communities compared with unfarmed soil. These positive effects began to decrease after 10-15 years of continuous cotton production.

Sustained-release pellets of nifedipine using microcrystals combined with MCC-based matrix.

The purpose of this study was to prepare sustained-release pellets of nifedipine (NSPs) based on MCC matrix. Wet-milling and extrusion-spheronization techniques were employed to prepare the microcrystals and pellets, respectively. The drug release mechanism and the influencing factors were investigated. After milled with HPMC (E5), the mean particle size of nifedipine in co-grinding mixture (CGM) was 5 µm, which is 15-fold smaller than that of raw material. DSC, X-ray powder diffraction and microscopic observation confirmed the microcrystals of drug were maintained in the CGM. With increased milling time and the content of HPMC, the dissolution rate was greatly enhanced compared with the raw material. The NSPs prepared by MCC and the CGM, which was obtained by cogrinding nifedipine with 5% HPMC solution for 210 min, exhibited sustained release pattern within 8 h. Nifedipine release from MCC-based NSPs followed the Korsmeyer model and closely related to the microstructure of pellet. High stability of NSPs was confirmed after 6 months of accelerated stability test. Using commercially available sustained product as reference, bioequivalence study in beagle dogs was executed and two formulations were bioequivalent. This sustained release pellet formulation of nifedipine was advantageous with convenient and easy scaled-up preparation process.

Improving Tuber Yield of Tiger Nut (Cyperus esculentus L.) through Nitrogen Fertilization in Sandy Farmland.

The cultivation of tiger nut (Cyperus esculentus L.) on marginal lands is a feasible and effective way to increase food production in Northern China. However, the specific influence of nitrogen fertilizer application on the growth dynamics, tuber expansion, overall yield, and nitrogen use efficiency (NUE) of tiger nuts cultivated on these sandy lands is yet to be fully elucidated. From 2021 to 2022, we conducted a study to determine the effect of N fertilizers on the leaf function morphology, canopy apparent photosynthesis (CAP), tuber yield, and NUE of tiger nut. The results indicate that the tuber yield and NUE are closely related to the specific leaf area (SLA), leaf area index (LAI), leaf nitrogen concentration per area (NA), CAP, and tuber expansion characteristics. Notably, significant enhancements in the SLA, LAI, NA, and CAP during the tuber expansion phase ranging from the 15th to the 45th day under the 300 kg N ha-1 treatment were observed, subsequently leading to increases in both the tuber yield and NUE. Moreover, a maximum average tuber filling rate was obtained under the N300 treatment. These improvements led to substantial increases in the tuber yield (32.1-35.5%), nitrogen agronomic efficiency (NAE, 2.1-5.3%), nitrogen partial factor productivity (NPP, 4.8-8.1%), and nitrogen recovery efficiency (NRE, 3.4-5.7%). Consequently, 300 kg N ha-1 of N fertilizers is the most effective dose for optimizing both the yield of tiger nut tubers and the NUE of tiger nut plants in marginal soils. Structural equation modeling reveals that N application affects the yield and NUE through its effects on leaf functional traits, the CAP, and the tuber filling characteristics. Modeling indicates that tuber expansion characteristics primarily impact the yield, while CAP predominantly governs the NUE. Above all, this study highlights the crucial role of N fertilizer in maximizing the tiger nut tuber yield potential on marginal lands, providing valuable insights into sustainable farming in dry areas.

Effects of maize and soybean intercropping on soil phosphorus bioavailability and microbial community structure in rhizosphere.

To investigate the effect of maize/soybean intercropping on rhizosphere soil microbial communities and phosphorus (P) bioavailability, we examined the changes of soil bioavailable P fractions and microbial community characteristics in the monoculture and intercropping systems based on high-throughput sequencing. The results showed that maize/soybean intercropping increased the contents of rhizosphere soil organic matter (SOM), available phosphorus (AP), microbial biomass phosphorus (MBP), and aboveground biomass. The increase of AP was mainly related to the increasing enzyme extracted phosphorus (Enzyme-P) and hydrochloric acid extracted phosphorus (HCl-P) contents. The dominant bacterial phyla under each treatment were Proteobacteria, Actinobacteria, Acidobacteria and Chloroflexi, while the dominant bacterial genera were Nocardioides, Solirubacter, Sphingomonas and Arthrobacter, with Proteobacteria and Sphingomonas having the highest relative abundance. The relative abundance of Proteobacteria and Sphingomonas in intercropping maize rhizosphere soil was significantly higher than that in monoculture, and that of Proteobacteria in intercropping soybean rhizosphere soil was significantly higher than monoculture. Soil properties and P fractions were closely related to the rhizosphere soil microbial composition. In all, maize/soybean intercropping could affect the rhizosphere soil P bioavailability by altering the structure of rhizosphere microbial communities.

Positive periodic solution for p-Laplacian neutral Rayleigh equation with singularity of attractive type.

In this paper, we consider a kind of p-Laplacian neutral Rayleigh equation with singularity of attractive type, [Formula: see text] By applications of an extension of Mawhin's continuation theorem, sufficient conditions for the existence of periodic solution are established.

Effect of reclamation of abandoned salinized farmland on soil bacterial communities in arid northwest China.

Understanding the impact of reclamation of abandoned salinized farmland on soil bacterial community is of great importance for maintaining soil health and sustainability in arid regions. In this study, we used field sampling and 454 pyrosequencing methods to investigate the effects of 5-year reclamation treatments on soil properties, bacterial community composition and diversity. The four reclamation treatments are: abandoned salinized farmland (CK), cropland (CL), grassland (GL) and woodland (WL). We have found soil properties are significantly altered by abandoned salinized farmland reclamation. In particular, the lowest soil pH and electrical conductivity (EC) values are observed in CL (P<0.05). The dominant phyla are Firmicutes, Proteobacteria, Chloroflexi, Actinobacteria and Acidobacteria in all treatments. At the genus levels, the relative abundance of Bacillus, Lactococcus, Streptococcus and Enterococcus in CK, GL and WL is significantly higher than in CL. Bacterial diversity indices (i.e. ACE, Chao and Shannon) dramatically increase after the reclamation, with the highest in CL. Similar patterns of bacterial communities have been observed in CK, GL and WL soils, but significantly different from CL. Regression analyses indicate that the relative abundance of these phyla are significantly correlated with soil Fe, pH and EC. Results from non-metric multidimensional scaling (NMDS) and redundancy analysis (RDA) indicate that soil Fe content, EC and pH are the most important factors in shaping soil bacterial communities. Overall, results indicate that abandoned salinized farmland reclaimed for CL significantly decrease soil pH and EC, and increase soil bacterial community diversity. Soil Fe concentration, EC and pH are the dominant environmental factors affecting soil bacterial community composition. The important role of Fe concentration in shaping bacterial community composition is a new discovery among the similar studies.

Roles of MSH2 and MSH6 in cadmium-induced G2/M checkpoint arrest in Arabidopsis roots.

DNA mismatch repair (MMR) proteins have been implicated in sensing and correcting DNA damage, and in governing cell cycle progression in the presence of structurally anomalous nucleotide lesions induced by different stresses in mammalian cells. Here, Arabidopsis seedlings were grown hydroponically on 0.5 × MS media containing cadmium (Cd) at 0-4.0 mg L-1 for 5 d. Flow cytometry results indicated that Cd stress induced a G2/M cell cycle arrest both in MLH1-, MSH2-, MSH6-deficient, and in WT roots, associated with marked changes of G2/M regulatory genes, including ATM, ATR, SOG1, BRCA1, WEE1, CYCD4; 1, MAD2, CDKA;1, CYCB1; 2 and CYCB1; 1. However, the Cd-induced G2/M phase arrest was markedly diminished in the MSH2- and MSH6-deficient roots, while a lack of MLH1 had no effect on Cd-induced G2 phase arrest relative to that in the wild type roots under the corresponding Cd stress. Expression of the above G2/M regulatory genes was altered in MLH1, MSH2 and MSH6-deficient roots in response to Cd treatment. Furthermore, Cd elicited endoreplication in MSH2- and MSH6-deficient roots, but not in MLH1-deficient Arabidopsis roots. Results suggest that MSH2 and MSH6 may act as direct sensors of Cd-mediated DNA damage. Taken together, we conclude that MSH2 and MSH6, but not MLH1, components of the MMR system are involved in the G2 phase arrest and endoreplication induced by Cd stress in Arabidopsis roots.

Study on a kind of ϕ-Laplacian Liénard equation with attractive and repulsive singularities.

In this paper, by application of the Manasevich-Mawhin continuation theorem, we investigate the existence of a positive periodic solution for a kind of ϕ-Laplacian singular Liénard equation with attractive and repulsive singularities.