T cell interactions with microglia in immune-inflammatory processes of ischemic stroke.

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke, which promotes neuronal death and inhibits nerve tissue regeneration. As the first immune cells to be activated after an ischemic stroke, microglia play an important immunomodulatory role in the progression of the condition. After an ischemic stroke, peripheral blood immune cells (mainly T cells) are recruited to the central nervous system by chemokines secreted by immune cells in the brain, where they interact with central nervous system cells (mainly microglia) to trigger a secondary neuroimmune response. This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke. We found that, during ischemic stroke, T cells and microglia demonstrate a more pronounced synergistic effect. Th1, Th17, and M1 microglia can co-secrete pro-inflammatory factors, such as interferon-γ, tumor necrosis factor-α, and interleukin-1ß, to promote neuroinflammation and exacerbate brain injury. Th2, Treg, and M2 microglia jointly secrete anti-inflammatory factors, such as interleukin-4, interleukin-10, and transforming growth factor-ß, to inhibit the progression of neuroinflammation, as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury. Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation, which in turn determines the prognosis of ischemic stroke patients. Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke. However, such studies have been relatively infrequent, and clinical experience is still insufficient. In summary, in ischemic stroke, T cell subsets and activated microglia act synergistically to regulate inflammatory progression, mainly by secreting inflammatory factors. In the future, a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells, along with the activation of M2-type microglia. These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.

Hua-Feng-Dan alleviates LPS-induced neuroinflammation by inhibiting the TLR4/Myd88/NF-κB pathway: Through Integrating Network Pharmacology and Experimental Validation.

BACKGROUND: Neuroinflammation is the pathological basis of many neurological diseases, including neurodegenerative diseases and stroke. Hua-Feng-Dan (HFD) is a well-established traditional Chinese medicine that has been used for centuries to treat stroke and various other brain-related ailments. OBJECTIVE: Our study aims to elucidate the molecular mechanism by which HFD mitigates neuroinflammation by combining network pharmacology and in vitro experiments. METHODS: TCMSP and SymMap databases were used to extract active compounds and their related targets. The neuroinflammation-related targets were obtained from the GeneCards database. The common targets of HFD and neuroinflammation were used to construct a protein-protein interaction (PPI) network. MCODE plug-in was used to find the hub module genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to dissect the hub module genes. The lipopolysaccharide (LPS)-induced BV2 microglial neuroinflammation model was utilized to assess the therapeutic effects of HFD on neuroin- flammation. Western blotting analysis was performed to examine the core target proteins in the TLR4/My- D88/NF-κB signaling pathway, potentially implicated in HFD's therapeutic effects on neuroinflammation. Hoechst 33342 staining and JC-1 staining were employed to evaluate neuronal apoptosis. RESULTS: Through network pharmacology, 73 active compounds were identified, with quercetin, beta-sitos- terol, luteolin, and (-)-Epigallocatechin-3-Gallate recognized as important compounds. Meanwhile, 115 com- mon targets of HFD and neuroinflammation were identified, and 61 targets were selected as the hub targets uti- lizing the MCODE algorithm. The results of in vitro experiments demonstrated that HFD significantly inhibit- ed microglial-mediated neuronal inflammation induced by LPS. Integrating the predictions from network phar- macology with the in vitro experiment results, it was determined that the mechanism of HFD in mitigating neu- roinflammation is closely related to the TLR4/MyD88/NF-κB pathway. Furthermore, HFD demonstrated the capacity to shield neurons from apoptosis by curbing the secretion of pro-inflammatory factors subsequent to microglial activation. CONCLUSION: The findings demonstrated that HFD had an inhibitory effect on LPS-induced neuroinflammation in microglia and elucidated its underlying mechanism. These findings will offer a theoretical foundation for the clinical utilization of HFD in treating neurodegenerative diseases associated with neuroinflammation.

Combined control of plant diseases by Bacillus subtilis SL44 and Enterobacter hormaechei Wu15.

Co-incubation of plant growth promoting rhizobacteria (PGPRs) have been proposed as a potential alternative to pesticides for controlling fungal pathogens in crops, but their synergism mechanisms are not yet fully understood. In this study, combined use of Bacillus subtilis SL44 and Enterobacter hormaechei Wu15 could decrease the density of Colletotrichum gloeosporioides and Rhizoctonia solani and enhance the growth of beneficial bacteria on the mycelial surface, thereby mitigating disease severity. Meanwhile, PGPR application led to a reorganization of the rhizosphere microbial community through modulating its metabolites, such as extracellular polymeric substances and chitinase. These metabolites demonstrated positive effects on attracting and enhancing conventional periphery bacteria, inhibiting fungal pathogens and promoting soil health effectively. The improvement in the microbial community structure altered the trophic mode of soil fungal communities, effectively decreasing the proportion of saprotrophic soil and reducing fungal plant diseases. Certain combinations of PGPR have the potential to serve as precise instruments for managing plant pathogens.

Preparation of pH-sensitive carboxymethyl chitosan nanoparticles loaded with ginsenoside Rb1 and evaluation of drug release in vitro.

Oral absorption of ginsenoside Rb1 (Rb1) is often hindered by the gastrointestinal tract. Carboxymethyl chitosan deoxycholic acid loaded with ginsenoside Rb1 nanoparticles (CMDA@Rb1-NPs), were prepared as a delivery system using a self-assembly technique with amphipathic deoxycholic acid grafted carboxymethyl chitosan as the carrier, which improved the stability and embedding rate of Rb1. In addition, the CMDA@Rb1-NPs was encapsulated with sodium alginate by ion crosslinking method with additional layer (CMDAlg@Rb1-NPs). Scanning electron microscopy showed that the nanoparticles were spherical, evenly distributed, smooth and without obvious adhesion. By evaluating drug loading, entrapment efficiency, the encapsulation efficiency of Rb1 increased from 60.07 % to 72.14 % after grafting deoxycholic acid improvement and optimization. In vitro release results showed that the cumulative release of Rb1 by CMDAlg-NPs showed a pH dependent effect, which was <10 % in simulated gastric juice with pH 1.2, completely released with pH 7.4 for about 48 h. In addition, Rb1 and CMDAlg@Rb1-NPs had inhibitory effects on A549 cells, and the inhibitory effect of CMDAlg@Rb1-NPs was better. Therefore, all results indicated that CMDA/Alg@Rb1 nanoparticles might be a novel drug delivery system to improve the stability and embedding rate of Rb1, and has the potential to be applied in oral pharmaceutical preparations.

Real-world evaluation of first-line treatment of extensive-stage small-cell lung cancer with atezolizumab plus platinum/etoposide: a focus on patients with brain metastasis.

PURPOSE: A previous real-world study conducted in China confirmed that first-line atezolizumab, in combination with etoposide/platinum (EP), leads to significantly longer progression-free survival (PFS) compared to EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC). The present study aimed to provide updated survival outcome data and evaluate the clinical efficacy of atezolizumab plus chemotherapy in ES-SCLC patients with brain metastasis (BM). METHODS: This retrospective study included 225 patients with ES-SCLC who were treated with EP alone (EP group) or a combination of EP + atezolizumab (atezolizumab group). Survival outcomes for the total study sample and patients in the BM subgroup were estimated using the Kaplan-Meier method. RESULTS: The atezolizumab group continued to demonstrate significantly longer PFS than the EP group (hazard ratio [HR], 0.68). The median overall survival (OS) was 26.2 months in the atezolizumab group vs. 14.8 months in the EP group (HR, 0.63). Additionally, among the BM patients in our study, the median PFS was found to be longer in the atezolizumab group (7.0 months) than in the EP group (4.1 months) (HR, 0.46). The OS of the BM patients did not differ significantly between the two treatment groups. CONCLUSIONS: The addition of atezolizumab to EP as a first-line treatment for ES-SCLC was found to improve survival outcomes. This treatment combination may also prolong PFS in patients with BM, regardless of the administration of cranial irradiation. However, among the BM patients in our study, there was no significant difference in OS between the two treatment groups.

Effect of microbial inoculum on composting efficiency in the composting process of spent mushroom substrate and chicken manure.

This work aimed to investigate the microbial mechanisms for the improvement of composting efficiency driven by the compound microbial inoculum (MI) (Bacillus subtilis SL-44, Enterobacter hormaechei Rs-189 and Trichoderma reesei) during co-composting of spent mushroom substrate (SMS) and chicken manure (CM). The treatments used in the study were as follows: 1) MI (inoculation with microbial inoculum), 2) CI (inoculation with commercial microbial inoculum), and 3) CK (without inoculation). The results demonstrated that MI increased the seed germination index (GI) by 25.11%, and contents of humus, humic acid (HA) and available phosphorus (AP) were correspondingly promoted by 12.47%, 25.93% and 37.16%, respectively. The inoculation of MI increased the temperature of the thermophilic stage by 3-7 °C and achieved a cellulose degradation rate of 52.87%. 16S rRNA gene analysis indicated that Actinobacteria (11.73-61.61%), Firmicutes (9.46-65.07%), Proteobacteria (2.86-32.17%) and Chloroflexi (0.51-10.92%) were the four major phyla during the inoculation composting. Bacterial metabolic functional analysis revealed that pathways involved in amino acid and glycan biosynthesis and metabolism were boosted in the thermophilic phase. There was a positive correlation between bacterial communities and temperature, humification and phosphorus fractions. The average dry weight, fresh weight and seedling root length in the seedling substrates adding MI compost were 1.13, 1.23 and 1.06 times higher than those of the CK, respectively. This study revealed that biological inoculation could improve the composting quality and efficiency, potentially benefiting the resource utilization of agricultural waste resources.

Bioreduction of hexavalent chromium via Bacillus subtilis SL-44 enhanced by humic acid: An effective strategy for detoxification and immobilization of chromium.

As an organic macromolecule, humic acid (HA) has been extensively used as the protectant for bacteria applied in Cr(VI) microbial remediation. However, the effect of the structural properties of HA on the reduction rate of bacteria and the respective contribution of bacteria and HA to soil Cr(VI) management remained uncertain. In this paper, the structural differences between two kinds of humic acid (AL-HA and MA-HA) were explored by means of spectroscopy and electrochemical characterization, and the potential influence of MA-HA on Cr(VI) reduction rate and physiological characteristics of bacteria (Bacillus subtilis, SL-44) also were analyzed. The results showed that the phenolic groups and carboxyl on the surface of HA are firstly complex with Cr(VI) ions, and the fluorescent component with more п-п conjugate structure in HA is the most sensitive species. Compared with single bacteria, the application of SL-44 and MA-HA complex (SL-MA) not only enhanced the reduction of 100 mg/L Cr(VI) to 39.8 % within 72 h and formation rate of intermediate Cr(V), but also reduced the electrochemical impedance. Moreover, the addition of 300 mg/L MA-HA also relieved the Cr(VI) toxicity and decreased the accumulation of glutathione to 94.51 % in bacterial extracellular polymeric substance, furthermore down-regulated the gene expression related to amino acid metabolism and polyhydroxybutyric acid (PHB) hydrolysis in SL-44. Finally, the application of SL-MA also enhanced the stability of chromium in soil and decreased its phytoavailability to 86.09 %, which further reduced chromium enrichment in cabbage organs. These findings provide new insights into Cr(VI) removal, which is also critical for evaluating the application potential of HA for enhancing Cr(VI) bio-reduction.

Insight into the microbial mechanisms for the improvement of spent mushroom substrate composting efficiency driven by phosphate-solubilizing Bacillus subtilis.

The objective of this study was to investigate the microbial mechanisms for the improvement of composting efficiency after Bacillus subtilis inoculation with soluble phosphorus function in the spent mushroom substrate (SMS) aerobic composting. The methods in this study, including redundant analysis (RDA), co-occurrence network analyze and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt 2) were carried out studying the dynamic changes of phosphorus (P) components, microbial interactions and metabolic characteristics in the SMS aerobic composting inoculated with phosphorus-solubilizing B. subtilis (PSB). An increase in germination index (GI) (up to 88.4%), total nitrogen (TN) (16.6 g kg-1), available P content (0.34 g kg-1) and total P (TP) content (3.20 g kg-1) and a decrease in total organic carbon (TOC), C/N and electrical conductivity (EC) in final composting stage indicated B. subtilis inoculation could further improve maturity quality of the composting product compared with CK. Other results also demonstrated that PSB inoculation increased the stability of compost, humification degree and bacterial diversity, contributing to P fractions transformation in the composting process. Co-occurrence analysis suggested that PSB strengthened microbial interactions. Metabolic function of bacterial community analysis showed pathways such as carbohydrate metabolism, and amino acid metabolism in the composting were increased by effects of PSB inoculation. In summary, this study reveals a useful basis for better regulating the P nutrient level of the SMS composting and reducing environmental risks by inoculating B. subtilis with P solubilizing function.

Isolation, purification, and identification of antifungal protein produced by Bacillus subtilis SL-44 and anti-fungal resistance in apple.

Apple anthracnose is a fruit fungal disease that is currently recognized as one of the most severe threats to apples worldwide. In this study, antifungal protein from Bacillus subtilis SL-44 was isolated, purified, identified, and applied for Colletotrichum gloeosporioides control. The antagonistic experiment showed that SL-44 had an excellent broad spectrum against plant pathogenic fungi. The optimal fermentation conditions were as follows: initial pH was 7, inoculum volume was 2%, and rotational speed was 180 r/min. The optimized yield of antifungal protein increased by 45.83% compared with that before. The crude protein was isolated and purified by (NH4)2SO4 precipitation, DEAE-Sepharose Fast Flow, and Sephadex G-100 column chromatography. LC-MS analyzed that antifungal protein was likely to be a novel protein with a molecular weight of 42 kDa. The mechanism revealed that the antifungal protein may disrupt the cell wall structure of C. gloeosporioides and function as its antifungal action. Additionally, antifungal protein significantly alleviated the size of the lesion to more than 70% in the apple infection protection test. In conclusion, antifungal protein has remarkable potential in developing fungicides for the biological control of apple anthracnose. HIGHLIGHTS: 1. B. subtilis SL-44 had broad-spectrum antagonism against plant pathogenic fungi. 2. The optimal fermentation conditions for extracting antifungal protein were optimized. 3. The antifungal protein is a novel protein with a molecular weight of 42 kDa. 4. The mechanism of antifungal protein may disrupt the cell wall structure of C. gloeosporioides.

Identification and characterization of siderophilic biocontrol strain SL-44 combined with whole genome.

Using rhizobacteria as biological fertilizer is gradually expanding in agriculture as excellent substitutes for chemical fertilizers. Bacillus subtilis SL-44 is a plant growth-promoting rhizobacteria screened from the severely salinized cotton rhizosphere soil in Xinjiang. Study showed that indole-3-acetic acid, organic acid production, nitrogen fixation, and other beneficial secondary metabolite secretion can be synthesized by stain SL-44. At the same time, fencyclin, lipopeptide, chitinase, and other antifungal substances were also detected from the secretion of Bacillus subtilis SL-44, which can effectively control plant diseases. Siderophore separated from SL-44 was verified by HPLC, and results showed it was likely bacillibactin. This study also verified that SL-44 has high antifungal activity against Rhizoctonia solani through in vitro antifungal experiments. The B. subtilis SL-44 whole genome was sequenced and annotated to further explore the biotechnological potential of SL-44. And a large number of genes involved in the synthesis of anti-oxidative stress, antibiotic, and toxins were found. Genome-wide analysis provides clear evidence to support the great potential of B. subtilis SL-44 strain to produce multiple bioantagonistic natural products and growth-promoting metabolites, which may facilitate further research into effective therapies for harmful diseases.

Preparation of pH-sensitive chitosan-deoxycholic acid-sodium alginate nanoparticles loaded with ginsenoside Rb1 and its controlled release mechanism.

Ginsenoside is a natural extract of the genus ginseng, which has tumor preventive and inhibiting effects. In this study, ginsenoside loaded nanoparticles were prepared by an ionic cross-linking method with sodium alginate to enable a sustained slow release effect of ginsenoside Rb1 in the intestinal fluid through an intelligent response. Chitosan grafted hydrophobic group deoxycholic acid was used to synthesize CS-DA, providing loading space for hydrophobic Rb1. Scanning electron microscopy (SEM) showed that the nanoparticles was spherical with smooth surfaces. The encapsulation rate of Rb1 enhanced with the increase of sodium alginate concentration and could reach to 76.62 ± 1.78 % when concentration was 3.6 mg/mL. It was found that the release process of CDA-NPs was most consistent with the primary kinetic model which is a diffusion-controlled release mechanism. CDA-NPs exhibited good pH sensitivity and controlled release properties in buffer solutions of different pH's at 1.2 and 6.8. The cumulative release of Rb1from CDA-NPs in simulated gastric fluid was <20 % within 2 h, while could release completely around 24 h in the simulated gastrointestinal fluid release system. It was demonstrated that CDA3.6-NPs can effectively control release and intelligently deliver ginsenoside Rb1, which is a promising alternative way for oral delivery.

Phosphate-solubilizing microorganisms regulate the release and transformation of phosphorus in biochar-based slow-release fertilizer.

Coupling phosphate-solubilizing microorganisms (PSM) can improve the availability of phosphorous (P) in biochar-based slow-release P fertilizers (BPF). However, the mechanism in release and transformation of P in BPF regulated by PSM is still unclear. Herein, the biocompatibility and the adhesion behaviors of BPF and PSM (Enterobacter hormaechei Rs-198) in soil were firstly studied, and a 90 days' laboratory-scale soil incubation experiment of BPF and Rs-198 was performed to study the transformation of P of BPF. The results show that BPF has a good biocompatibility for Rs-198 due to its low aromaticity, graphitization and free radicals' content (0.084 mg/g). Rs-198 are adhered to the surface of BPF in soil due to the high negative secondary energy minimum and low total interaction energy between Rs-198 and BPF. Available P in the incubation of BPF and Rs-198 (BR treatment) is significantly higher than that of the incubation of BPF (BF treatment) at initial 60 days. However, the content of available P in BR treatment is much lower compared with that in BF treatment on day 90, which is attributed to the entrapment of released P from BPF by Rs-198 and the formation of polyphosphate (polyP) rather than bound with soil mineral. Overall, this study presents new insights into the transformation of P in BPF regulated by PSM.

Whole genome analysis of Enterobacter cloacae Rs-2 and screening of genes related to plant-growth promotion.

The genus Enterobacter is widely recognized for its biotechnology potential in improving soil environment and crop growth promotion. To further explore these biotechnological potentials, we sequenced and analyzed the whole genome of Enterobacter cloacae Rs-2. The analysis showed that the total length of the Rs-2 genome was 6,965,070,514 bp, and GC content was 55.80%; the annotation results of GO and COG databases showed that the genome contains a variety of growth-promoting genes, such as iscU, glnA, glnB (nitrogen fixation); iucABCD (siderophore synthesis) and fepA, fcuA, fhuA, and pfeA, etc. (siderophore transport); ipdC (secreted IAA) and gcd, pqqBCDEF (dissolved phosphorus), etc. No pathogenic factors such as virulence genes were found. The application of Rs-2 as a soil inoculant in pot experiments showed great potential for growth promotion. This study proved the plant growth-promoting ability of Rs-2 at the molecular level through genetic screening and analysis, which provided guidance for the further improvement of the strain and laid a foundation for its application in agricultural production.

Role of SIRT3 in neurological diseases and rehabilitation training.

Sirtuin3 (SIRT3) is a deacetylase that plays an important role in normal physiological activities by regulating a variety of substrates. Considerable evidence has shown that the content and activity of SIRT3 are altered in neurological diseases. Furthermore, SIRT3 affects the occurrence and development of neurological diseases. In most cases, SIRT3 can inhibit clinical manifestations of neurological diseases by promoting autophagy, energy production, and stabilization of mitochondrial dynamics, and by inhibiting neuroinflammation, apoptosis, and oxidative stress (OS). However, SIRT3 may sometimes have the opposite effect. SIRT3 can promote the transfer of microglia. Microglia in some cases promote ischemic brain injury, and in some cases inhibit ischemic brain injury. Moreover, SIRT3 can promote the accumulation of ceramide, which can worsen the damage caused by cerebral ischemia-reperfusion (I/R). This review comprehensively summarizes the different roles and related mechanisms of SIRT3 in neurological diseases. Moreover, to provide more ideas for the prognosis of neurological diseases, we summarize several SIRT3-mediated rehabilitation training methods.

Valuation of Ecosystem Services for the Sustainable Development of Hani Terraces: A Rice-Fish-Duck Integrated Farming Model.

As a complementary and symbiotic agro-ecological cycle system, a nature-based integrated rice-fish-duck farming ecosystem was developed in the Honghe Hani Rice Terraces. The main research objective was to evaluate the ecosystem services based on case studies of the Hani integrated rice-fish-duck terraced farming system and determine its potential and its importance as an ecological asset. We developed a valuation model to assess the value of the integrated farming system based on the three aspects of provisioning, regulation and maintenance, and cultural services; we selected eight groups and 10 indictors to evaluate the ecosystem services of the integrated ecosystem in Honghe Hani Rice Terraces was 3.316 billion CNY, of which the provisioning service value was 1.76 billion CNY, the regulation and maintenance service value was 1.32 billion CNY, and the cultural services value was 230.85 million CNY. The evaluation will be useful as a theoretical reference for poverty alleviation policy makers in similar poverty-stricken areas, enabling them to better protect and promote this mode of farming and further promote the protection of the natural environment and cultural heritage alongside the sustainable development of natural resources and human well-being.

Effect of microbial agents on maturity, humification, and stability and the bacterial succession of spent mushroom substrate composting.

Two composting experiments were conducted to investigate the effects of commercial microbial agents on microbial succession and nutrient flow such as humification, maturation, and stability during the aerobic composting of the spent mushroom substrate (SMS). The cellulose degradation rate of T (added microbial agents at the initial stage) reached 41.8%, which was much significantly (p < 0.05) higher than that of CK (14.9%). The seed germination index (GI) in T (82.38%) was significantly (p < 0.05) higher than that in CK (74.74%) in the maturation phase. Moreover, the total organic carbon/total nitrogen ratio (C/N) and electrical conductivity (EC) value of T decreased to 10.5 and 2.37 mS/cm, respectively. Chemical detection and fluorescence excitation-emission region integration method (EEM-FRI) analysis showed that the microbial agents significantly accelerated the organic matter (OM) decomposition and promoted the quality of mature compost using SMS as a single raw material. The bacterial abundance of T was significantly richer than the CK due to the addition of microbial agents. The results could provide a comprehensive understanding of adding microbial agents into composting SMS and a scientific feasibility strategy to rational utilization of resources in the edible fungi industry, which was conducive to the waste management and sustainable development of the edible fungi industry.

De novo transcriptome sequencing of Capsicum frutescens. L and comprehensive analysis of salt stress alleviating mechanism by Bacillus atrophaeus WU-9.

Salt stress, as one of the most severe environmental stresses, can cause a series of changes in plants. However, the explanation of plant salt stress alleviating mechanism of plant growth-promoting rhizobacteria (PGPR) was hindered by the limited availability of transcriptomic information for salt stress-treated plants grown in a microorganism-controlled environment. Our previous reports have selected Bacillus atrophaeus WU-9 as PGPR significantly alleviating pepper (Capsicum frutescens. L) salt stress. In this work, the RNA-seq analysis of salt stress-treated and untreated plants, grown with and without WU-9 in a microorganism-controlled environment, was used to reveal the plant salt stress alleviating mechanisms of WU-9. Twelve sequencing libraries, prepared by treating with WU-9 and salt (150 mM NaCl for 36 h), were constructed by RNA-Seq technique. Non-inoculated seedlings mainly respond to salt stress through regulation of signal transduction, such as ethylene-activated signaling pathway, signaling and cell communication, etc. And ethylene signal participated in salt stress response in pepper through regulating defense responses, fruit ripening and senescence. WU-9 inoculation under salt stress mainly improves salt tolerance and plant growth by regulating salt stress-responding ethylene and auxin signal transduction, utilization of proline, photosynthesis, antioxidant enzyme activities and cell enlargement. Furthermore, 86 differentially expressed genes and 20 transcription factors were identified as associated with salt stress response and tolerance. Thus, this innovative transcriptomic study identified the salt stress response and alleviation in C. frutescens. L with PGPR inoculation. This result provided novel insights into the salinity alleviation in pepper regulated by PGPR.

Design, synthesis, and in vivo evaluation of GO-SWL-Ahx-K-SWL.

In order to acquire both expanded binding ability with the EphA2 receptor and superior drug delivery capacity, we designed and synthesized the modified GO-SWL-Ahx-K-SWL conjugate as a potential targeted therapeutic drug for non-small cell lung cancer (NSCLC). Various characterization methods have confirmed that the conjugate is consistent with the theoretical peptide. The cytotoxicity test results showed that the conjugate was slightly more toxic to A549 cells than in 3 T3 cells, and the toxicity increased in a concentration-dependent manner. Single photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging was performed to evaluate the conjugate binding to EphA2 receptor in vivo. The images showed obvious radioactive concentration in tumor tissues and significantly higher ratios of the tumor and muscle in the 125I-GO-SWL-Ahx-K-SWL group (10.78) than in the 125I-SWL-Ahx-K-SWL group (5.21) at all three time points (P < 0.01).

CELF1 promotes matrix metalloproteinases gene expression at transcriptional level in lens epithelial cells.

BACKGROUND: RNA binding proteins (RBPs)-mediated regulation plays important roles in many eye diseases, including the canonical RBP CELF1 in cataract. While the definite molecular regulatory mechanisms of CELF1 on cataract still remain elusive. METHODS: In this study, we overexpressed CELF1 in human cultured lens epithelial SRA01/04 cells and applied whole transcriptome sequencing (RNA-seq) method to analyze the global differences mediated by CELF1. We then analyzed public RNA-seq and CELF1-RNA interactome data to decipher the underlying mechanisms. RESULTS: The results showed that transcriptome profile was globally changed by CELF1 overexpression (CELF1-OE). Functional analysis revealed CELF1 specifically increased the expression of genes in extracellular matrix disassembly, extracellular matrix organization, and proteolysis, which could be classified into matrix metalloproteinases (MMPs) family. This finding was also validated by RT-qPCR and public mouse early embryonic lens data. Integrating analysis with public CELF1-RNA interactome data revealed that no obvious CELF1-binding peak was found on the transcripts of these genes, indicating an indirectly regulatory role of CELF1 in lens epithelial cells. CONCLUSIONS: Our study demonstrated that CELF1-OE promotes transcriptional level of MMP genes; and this regulation may be completed by other ways except for binding to RNA targets. These results suggest that CELF1-OE is implicated in the development of lens, which is associated with cataract and expands our understanding of CELF1 regulatory roles as an RNA binding protein.

Placental weight mediates association between prenatal exposure to cooking oil fumes and preterm birth.

Background: There are some reports on association between maternal prenatal cooking oil fume (COF) exposure and preterm birth (PTB), but its mechanism remains poorly understood. Therefore, this study aims to assess whether placental weight mediates their associations.Method: We enrolled 619 pregnant women delivering PTB newborns as cases and 1701 delivering full-term appropriate for gestational age newborns as controls. They were inquired with a self-reported questionnaire about prenatal COF exposure, socio-demographics and obstetric characteristics at Women and Children's Hospitals of Shenzhen and Foshan. After controlling for the potential confounders, a series of logistic and linear regressions were conducted to assess associations among COF exposure, placental weight and PTB, and the mediation of placental weight in the association between COF exposure and PTB.Results: Maternal prenatal COF exposure was significantly associated with PTB and the frequency of prenatal COF exposure was negatively associated with placental weight. Compared with mother who never cooked, those cooking occasionally, sometimes or often increased the risk of PTB, and similarly, those cooking between half to an hour was also showed a higher risk of PTB. Typical Chinese cooking methods including stir-frying, pan-frying and deep-frying were also associated with PTB. Different oil types mainly used, including peanut oil, corn oil and animal oil were associated with PTB as well. Mediation analysis illustrated that placental weight partially mediated 13.60% (95% CI = 10.62-33.20%) of the effects on the association between the frequency of maternal prenatal COF exposure and PTB.Conclusion: Maternal cooking during pregnancy and the frequency of prenatal COF exposure might increase the risk of PTB, in which placenta might play mediation role.