Exploring the regulatory mechanism of tRNA-derived fragments 36 in acute pancreatitis based on small RNA sequencing and experiments.

BACKGROUND: Acute pancreatitis (AP) is a disease featuring acute inflammation of the pancreas and histological destruction of acinar cells. Approximately 20% of AP patients progress to moderately severe or severe pancreatitis, with a case fatality rate of up to 30%. However, a single indicator that can serve as the gold standard for prognostic prediction has not been discovered. Therefore, gaining deeper insights into the underlying mechanism of AP progression and the evolution of the disease and exploring effective biomarkers are important for early diagnosis, progression evaluation, and precise treatment of AP. AIM: To determine the regulatory mechanisms of tRNA-derived fragments (tRFs) in AP based on small RNA sequencing and experiments. METHODS: Small RNA sequencing and functional enrichment analyses were performed to identify key tRFs and the potential mechanisms in AP. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to determine tRF expression. AP cell and mouse models were created to investigate the role of tRF36 in AP progression. Lipase, amylase, and cytokine levels were assayed to examine AP progression. Ferritin expression, reactive oxygen species, malondialdehyde, and ferric ion levels were assayed to evaluate cellular ferroptosis. RNA pull down assays and methylated RNA immunoprecipitation were performed to explore the molecular mechanisms. RESULTS: RT-qPCR results showed that tRF36 was significantly upregulated in the serum of AP patients, compared to healthy controls. Functional enrichment analysis indicated that target genes of tRF36 were involved in ferroptosis-related pathways, including the Hippo signaling pathway and ion transport. Moreover, the occurrence of pancreatic cell ferroptosis was detected in AP cells and mouse models. The results of interference experiments and AP cell models suggested that tRF-36 could promote AP progression through the regulation of ferroptosis. Furthermore, ferroptosis gene microarray, database prediction, and immunoprecipitation suggested that tRF-36 accelerated the progression of AP by recruiting insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) to the p53 mRNA m6A modification site by binding to IGF2BP3, which enhanced p53 mRNA stability and promoted the ferroptosis of pancreatic follicle cells. CONCLUSION: In conclusion, regulation of nuclear pre-mRNA domain-containing protein 1B promoted AP development by regulating the ferroptosis of pancreatic cells, thereby acting as a prospective therapeutic target for AP. In addition, this study provided a basis for understanding the regulatory mechanisms of tRFs in AP.

Combination of Bacillus and Low Fertigation Input Promoted the Growth and Productivity of Chinese Cabbage and Enriched Beneficial Rhizosphere Bacteria Lechevalieria.

Long-term overfertilization increases soil salinity and disease occurrence and reduces crop yield. Integrated application of microbial agents with low fertigation input might be a sustainable and cost-effective strategy. Herein, the promoting effects of Bacillus velezensis B006 on the growth of Chinese cabbage under different fertigation conditions in field trials were studied and the underlying mechanisms were revealed. In comparison with normal fertigation (water potential of -30 kPa and soluble N, P, K of 29.75, 8.26, 21.48 Kg hm-2) without B006 application, the combination of B. velezensis B006 and reduced fertigation input (-50 kPa and N, P, K of 11.75, 3.26, 6.48 Kg hm-2) promoted cabbage growth and root development, restrained the occurrence of soft rot disease, and improved the yield. High-performance liquid chromatography (HPLC) analyses indicated that B006 application promoted the production of indole-3-acetic acid and salicylic acid in cabbage roots, which are closely related to plant growth. Rhizosphere microbiota analyses indicated that the combination of low fertigation input and B006 application promoted the enrichment of Streptomyces, Lechevalieria, Promicromonospora, and Aeromicrobium and the abundance of Lechevalieria was positively correlated with the root length and vitality. This suggested that the integrated application of reduced fertigation and Bacillus is highly efficient to improve soil ecology and productivity and will benefit the sustainable development of crop cultivation in a cost-effective way.

The Co-Association of Enterobacteriaceae and Pseudomonas with Specific Resistant Cucumber against Fusarium Wilt Disease.

The root microbiota contributes to the plant's defense against stresses and pathogens. However, the co-association pattern of functional bacteria that improves plant resistance has not been interpreted clearly. Using Illumina high-throughput sequencing technology, the root bacterial community profiles of six cucumber cultivars with different resistance in response to the causative agent of cucumber Fusarium wilt (CFW), Fusarium oxysporum f. sp. cucumerinum (Foc), were analyzed. The principal coordinate analysis indicated that the interactions of the cultivars and pathogens drove the cucumber root bacterial communities (p = 0.001). The resistance-specific differential genera across the cultivars were identified, including Massilia in the resistant cultivars, unclassified Enterobacteriaceae in resistant CL11 and JY409, Pseudomonas in JY409, Cronobacter in moderately resistant ZN106, and unclassified Rhizobiaceae and Streptomyces in susceptible ZN6. The predominant root bacterium Massilia accounted for the relative abundance of up to 28.08-61.55%, but dramatically declined to 9.36% in Foc-inoculated susceptible ZN6. Pseudomonas ASV103 and ASV48 of Pseudomonadaceae and Cronobacter ASV162 of Enterobacteriaceae were consistently differential across the cultivars at the phylum, genus, and ASV levels. Using the culture-based method, antagonistic strains of Enterobacteriaceae with a high proportion of 51% were isolated. Furthermore, the bacterial complexes of Pantoea dispersa E318 + Pseudomonas koreensis Ps213 and Cronobacter spp. C1 + C7 reduced the disease index of CFW by 77.2% and 60.0% in the pot experiment, respectively. This study reveals the co-association of specific root bacteria with host plants and reveals insight into the suppressing mechanism of resistant cultivars against CFW disease by regulating the root microbiota.

Medicine-food herb: Angelica sinensis, a potential therapeutic hope for Alzheimer's disease and related complications.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, which has brought a huge burden to the world. The current therapeutic approach of one-molecule-one-target strategy fails to address the issues of AD because of multiple pathological features of AD. Traditionally, the herb of Angelica sinensis (AS) comes from the root of an umbrella plant Angelica sinensis (Oliv.) Diels. As a typical medicine-food herb, studies have shown that AS can alleviate AD and AD-complications by multiple targets through the various foundations of pharmaceutical material and dietary supply basis. Therefore, this review summarizes the pharmacological effects of AS for the treatment of AD and AD-complications for the first time. AS contains many effective components, such as ligustilide, z-ligustilide, n-butylidenephthalide, α-pinene, p-cymene, myrcene, ferulic acid, vanillic acid and coniferyl ferulate. It is found that AS, AS-active compounds and AS-compound recipes mainly treat AD through neuroprotective, anti-inflammation, and anti-oxidant effects, improving mitochondrial dysfunction, anti-neuronal apoptosis, regulating autophagy, regulating intestinal flora and enhancing the central cholinergic system, which shows the multi-component and multi-target effect of AS. The role of dietary supplement components in AS for AD intervention is summarized, including vitamin B12, folic acid, arginine, and oleic acid, which can improve the symptoms of AD. Besides, this review focuses on the safety and toxicity evaluation of AS, which provides a basis for its application. This review will provide further support for the research on AD and the application of medicine-food herb AS in a healthy lifestyle in the future.

Natural essential oils: A promising strategy for treating cardio-cerebrovascular diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential oils (EO) are volatile compounds obtained from different parts of natural plants, and have been used in national, traditional and folk medicine to treat various health problems all over the world. Records indicate that in history, herbal medicines rich in EO have been widely used for the treatment of CVDs in many countries, such as China. AIM OF THE STUDY: This review focused on the traditional application and modern pharmacological mechanisms of herbal medicine EO against CVDs in preclinical and clinical trials through multi-targets synergy. Besides, the EO and anti-CVDs drugs were compared, and the broad application of EO was explained from the properties of drugs and aromatic administration routes. MATERIALS AND METHODS: Information about EO and CVDs was collected from electronic databases such as Web of Science, ScienceDirect, PubMed, and China National Knowledge Infrastructure (CNKI). The obtained data sets were sequentially arranged for better understanding of EO' potential. RESULTS: The study showed that EO had significant application in CVDs at different countries or regions since ancient times. Aiming at the complex pathological mechanisms of CVDs, including intracellular calcium overload, oxidative stress, inflammation, vascular endothelial cell injury and dysfunction and dyslipidemia, we summarized the roles of EO on CVDs in preclinical and clinical through multi-targets intervention. Besides, EO had the dual properties of drug and excipients. And aromatherapy was one of the complementary therapies to improve CVDs. CONCLUSIONS: This paper reviewed the EO on traditional treatment, preclinical mechanism and clinical application of CVDs. As important sources of traditional medicines, EO' remarkable efficacy had been confirmed in comprehensive literature reports, which showed that EO had great medicinal potential.

Peripheral blood biological markers for early screening in children with autism spectrum disorder / 中国学校卫生

Objective@#To investigate the specifity of amyloid precursor protein(APP), brain derived neurotrophic factor (BDNF)and gamma aminobutyric acid(GABA) in peripheral blood in children with autism spectrum disorder, so as to explore the biomarkers for early screening of ASD and its relationship with the severity of ASD.@*Methods@#A total of 41 children diagnosed with autism from January to December 2019 were enrolled in the ASD group. Meanwhile, 41 healthy children with normal growth and development who were examined in the same period were selected as control group. And the sera total sAPP, sAPP α, sAPP β, BDNF and GABA of all participants were tested by sensitive enzyme linked immunosorbent assay method, and were compared between the two groups.@*Results@#The serum sAPP level in ASD group(2 132.98±333.28 ng/mL) was higher than control group(1 734.76 ±357.97 ng/mL),the serum sAPP α level(335.11±33.87 pg/mL) was higher than control group(274.84±32.12 pg/mL) and the serum GABA level(4.17±0.95 μmol/L)was lower than control group(6.35±0.84 μmol/L). GABA level (4.17±0.95 μmol/L) was lower than that of control group (6.35±0.84 μmol/L), the differences were statistically significant ( t =3.92, 4.25, -7.27, P < 0.05 ). In addition, the serum GABA level in children with severe ASD (3.48±0.77 μmol/L)was lower than children with mild to moderate (4.94±0.98 μmol/L).The difference was significant ( t =-3.31, P <0.05). ROC curve showed that total sAPP( AUC = 0.77 ,95% CI =0.66-0.87), sAPP α( AUC =0.77,95%CI=0.67-0.87), and GABA ( AUC =0.95,95% CI =0.90-0.93)had diagnostic efficacy for ASD( P <0.05), among which the AUC of GABA was the largest (0.95)and its sensitivity(85.65%) and specificity(80.76%) were the highest. The results of binary Logistic regression showed that the abnormal expression of sAPPα ( OR =1.04,95% CI = 1.00- 1.07) and GABA( OR =0.02,95% CI =0.00-0.32) were associated with risk for ASD( P <0.05).@*Conclusion@#Considering the specific change of total sAPP, sAPPα andGABA in peripheral blood in ASD children, total sAPP, sAPP α and GABA can be considered as promising biomarkers in the early diagnosis of ASD, among which GABA has the highest sensitivity and specificity.

A novel technology to reduce astringency of tea polyphenols extract and its mechanism.

Objective: Tea polyphenols are natural extracts used widely throughout the world. However, the severe astringency of tea polyphenols has reduced patient compliance. Based on the analysis of the formation mechanism of astringency, this paper hopes to propose a new method to control the astringency of tea polyphenols and improve patient compliance without changing its effect. Methods: Artificial saliva was used to prepare the tea polyphenols solution with different pH, using ß-casein to imitate salivary protein, and preparing 1.2 mg/mL ß-casein solution. A fluorescence quenching test was used to study the interaction between tea polyphenols and ß-casein, combined with the stability test results of the compound, we can choose the pH with weak binding but good stability as the best pH for masking astringency. The taste-masking tablets were prepared under the best pH conditions, and the Xinnaojian Original Tablets were prepared according to the conventional preparation method. The disintegration time limit and solubility were tested respectively. The astringency of Xinnaojian original tablets and taste-masking tablets was evaluated by visual analogue scale (VAS). Results: The result of the fluorescence quenching test prompted that the combination force was the weakest when the pH was 4.9. Further synchronous fluorescence analysis showed that an increase in pH resulted in a decrease of the binding sites between tea polyphenols and ß-casein, and this decrease was closely related to changes in tryptophan residues in ß-casein. Both original and taste-masking Xinnaojian Tablets were prepared. Volunteers' VAS scores illustrated that the astringency improved significantly with the masking tablets (P < 0.05). Conclusion: This pH-adjusting masking treatment had little effect on the recovery of polyphenols from the tablets or the dissolution of the tablets. This study provides a novel and feasible astringency masking technology for tea polyphenols and its preparation.

Combining chemical and genetic approaches to increase drought resistance in plants.

Drought stress is a major threat to crop production, but effective methods to mitigate the adverse effects of drought are not available. Here, we report that adding fluorine atoms in the benzyl ring of the abscisic acid (ABA) receptor agonist AM1 optimizes its binding to ABA receptors by increasing the number of hydrogen bonds between the compound and the surrounding amino acid residues in the receptor ligand-binding pocket. The new chemicals, known as AMFs, have long-lasting effects in promoting stomatal closure and inducing the expression of stress-responsive genes. Application of AMFs or transgenic overexpression of the receptor PYL2 in Arabidopsis and soybean plants confers increased drought resistance. The greatest increase in drought resistance is achieved when AMFs are applied to the PYL2-overexpression transgenic plants. Our results demonstrate that the combining of potent chemicals with transgenic overexpression of an ABA receptor is very effective in helping plants combat drought stress.