The application of varying amount of green manure combined with nitrogen fertilizer altered the soil bacterial community and rice yield in karst paddy areas.

Long-term application of green manure (GM) and nitrogen (N) fertilizers markedly improved soil fertility and boosted rice yield in ecologically fragile karst paddy fields. However, the precise response mechanisms of the soil bacterial community to varying amounts of green manure alone and in combination with N fertilizer in such environments remain poorly elucidated. In this study, we investigated the soil bacterial communities, keystone taxa, and their relationship with soil environmental variables across eight fertilization treatments. These treatments included group without N addition (N0M0, no N fertilizer and no GM; N0M22.5, 22.5 t/ha GM; N0M45, 45 t/ha GM, N0M67.5, 67.5 t/ha GM) and group with N addition (NM0, N fertilizer and no GM; NM22.5, N fertilizer and 22.5 t/ha GM; NM45, N fertilizer and 45 t/ha GM; NM67.5, N fertilizer and 67.5 t/ha GM). The results revealed that increasing green manure input significantly boosted rice yield by 15.51-22.08% and 21.84-35% in both the group without and with N addition, respectively, compared to N0M0 treatment. Moreover, with escalating green manure input, soil TN, AN, AK, and AP showed an increasing trend in the group without N addition. However, following the addition of N fertilizer, TN and AN content initially rose, followed by a decline due to the enhanced nutrient availability for rice. Furthermore, the application of a large amount of N fertilizer decreased the C: N ratio in the soil, resulting in significant changes in both the soil microbial community and its function. Particularly noteworthy was the transition of keystone taxa from their original roles as N-fixing and carbon-degrading groups (oligotrophs) to roles in carbon degradation (copiotrophs), nitrification, and denitrification. This shift in soil community and function might serve as a primary factor contributing to enhanced nutrient utilization efficiency in rice, thus significantly promoting rice yield.

Pathological mechanisms of amyotrophic lateral Sclerosis.

Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system, the cause of which remains unexplained despite several years of research. Thus, the journey to understanding or treating amyotrophic lateral sclerosis is still a long one. According to current research, amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways. The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis. Here, we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis, as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis. In addition, we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis. Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.

Research on the interaction of "tourism development-land use-landscape pattern" since the 1990s in a small karst basin, China.

The rapid rise of tourism in the karst regions has promoted the development of the local economy by relying on the unique landforms and landscapes. However, tourism development is often accompanied by land use changes and has an impact on the ecological environment. Exploring the coupling relationship between "tourism development-land use-landscape pattern" is very important for ecologically fragile karst areas. Taking the Yulong River Basin as an example, this research applied 3S technology, spatial analysis based on POIs, and regression analysis to the following: (1) identifying the process and effects of land use change, (2) determining the spatial pattern of tourism land and its correlation with land use change, (3) determining the characteristics and impacts of landscape pattern evolution. As the results suggested: (1) The significant expansion of construction land occupies a large amount of farmland, there is a balanced relationship between farmland and forest land for mutual conversion. (2) The aggregation of tourist land is affected by the trend of tourist behavior and the distribution of scenic spots. There is a significant moderate positive correlation between tourism land and construction land. (3) With the land use change, landscape heterogeneity has improved, but landscape fragmentation is serious and landscape connectivity is reduced. This research provides new evidences for the effect of the rapid development of tourism on land use change and ecological environment and as a reference to future orderly and moderate land development and ecological sustainability in karst regions.

Network pharmacology identify intersection genes of quercetin and Alzheimer's disease as potential therapeutic targets.

Background: Currently, there are no efficient therapies for Alzheimer's disease (AD) among the elderly, although it is the most common etiology of dementia among the elderly. Quercetin, which has a variety of therapeutic properties, may pave the way for novel approaches to AD treatment. In the AD patients' frontal cortex, current study aims to identify the potential mechanisms of quercetin's pharmacological targets. Materials and methods: The pharmacological targets of quercetin have been studied from DrugBank and SwissTarget. In order to distinguish AD-associated genes targeted by quercetin (Q-ADGs), we utilized an integrated intersection of gene expressions of the frontal cortex in combination with transcriptome analysis. To detect cortex-related Q-ADGs and immune-related Q-ADGs, a drug screening database and the immune infiltration analysis was utilized. The Q-ADGs were then linked with the AD severity scores (MMSE scores) to find severity-associated Q-ADGs. In addition, the miRNA-seq datasets were examined to identify severity-associated Q-ADG-miRNAs. Twelve genes, more frequently related to AD by previous studies among all the genes identified in the present study, were subjected to the verification of qRT-PCR in AD cell model. Results: In the frontal lobe of AD, 207 Q-ADGs were discovered and found that axonogenesis, glial differentiation, and other biological processes had been enriched. There were 155 immune-related Q-ADGs (e.g., COX2, NOS2, HMGB1) and 65 cortex-related Q-ADGs (e.g., FOXO1, CXCL16, NOTCH3). Sixteen Q-ADGs (e.g., STAT3, RORA, BCL6) and 28 miRNAs (e.g., miR-142-5p, miR-17-5p) were found to be related to MMSE scores. In the qRT-PCR results, six out of twelve genes were significantly regulated by quercetin. DYRK1A, FOXO1, NOS2, NGF, NQO1, and RORA genes were novel target of quercetin in AD. DYRK1A, NOS2, and NQO1 genes targeted by quercetin have benefits in the treatment of AD. However, FOXO1, NGF, and RORA genes targeted by quercetin might have a negative impact on AD. Conclusion: The role of quercetin in AD appears to be multifaceted, and it can affect patients' frontal cortex in a variety of pathways, such as axonogenesis, immune infiltration, and glial cell differentiation. DYRK1A, NOS2, and NQO1 might be potential novel effective drug targets for quercetin in AD.

Melatonin Induces Autophagy in Amyotrophic Lateral Sclerosis Mice via Upregulation of SIRT1.

Amyotrophic lateral sclerosis (ALS) is the neurodegenerative disease that leads to the motor dysfunction damaged by both upper and lower motor neurons. The etiology and pathogenesis of ALS hasn't completely been understood yet up to now, the current study suggests that autophagy plays an important role in the development of ALS. Meanwhile, melatonin is found to inhibit the progression of ALS. To this end, this study aimed to investigate the potential relation between melatonin and autophagy in ALS. The in vivo model of ALS was established to investigate the effects of melatonin in ALS. The mRNA expressions were performed to detect by RT-qPCR, and the protein levels were tested by western blot and immunofluorescence histochemistry staining. The inflammatory cytokine was applied to detect by ELISA. The results showed that melatonin dose-dependently reversed the ALS-induced survival time shortened, weight loss and rotating rod latency decrease. The expressions of both SIRT1 and Beclin-1 as well as the ratio of LC3II/LC3I were significantly upregulated in the ALS mice, while melatonin reversed the upregulation of both SIRT1 and Beclin-1 expression and LC3II/LC3I ratio in a dose-dependent manner. In contrast, melatonin dose-dependently significantly restored the ALS-induced downregulation of p62. Furthermore, SIRT1 silencing notably reduced the effect of melatonin on Beclin-1, LC3II/LC3I, and p62. Melatonin induced autophagy in the ALS mice via the upregulation of SIRT1. Thus, melatonin might act as a new agent for the treatment of ALS.

Identification of Molecular Correlations Between DHRS4 and Progressive Neurodegeneration in Amyotrophic Lateral Sclerosis By Gene Co-Expression Network Analysis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, and its candidate biomarkers have not yet been fully elucidated in previous studies. Therefore, with the present study, we aim to define and verify effective biomarkers of ALS by bioinformatics. Here, we employed differentially expressed gene (DEG) analysis, weighted gene co-expression network analysis (WGCNA), enrichment analysis, immune infiltration analysis, and protein-protein interaction (PPI) to identify biomarkers of ALS. To validate the biomarkers, we isolated the lumbar spinal cord from mice and characterized them using Western blotting and immunofluorescence. The results showed that Dhrs4 expression in the spinal cord was upregulated with the progression of SOD1G93A mice, and the upregulation of DHRS4 and its synergistic DHRS3 might be primarily associated with the activation of the complement cascade in the immune system (C1QA, C1QB, C1QC, C3, and ITGB2), which might be a novel mechanism that induces spinal neurodegeneration in ALS. We propose that DHRS4 and its synergistic DHRS3 are promising molecular markers for detecting ALS progression.

The pathogenesis of amyotrophic lateral sclerosis: Mitochondrial dysfunction, protein misfolding and epigenetics.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with multiple complex mechanisms involved. Among them, mitochondrial dysfunction plays an important role in ALS. Multiple studies have shown that mitochondria are closely associated with reactive oxygen species production and oxidative stress and exhibit different functional states in different genetic backgrounds. In this review we explored the roles of Ca2+, autophagy, mitochondrial quality control in the regulation of mitochondrial homeostasis and their relationship with ALS. In addition, we also summarized and analyzed the roles of protein misfolding and abnormal aggregation in the pathogenesis of ALS. Moreover, we also discussed how epigenetic mechanisms such as DNA methylation and protein post-translational modification affect initiation and progression of ALS. Nevertheless, existing events still cannot fully explain the pathogenesis of ALS at present, more studies are required to explore pathological mechanisms of ALS.

Phosphoinositide-3-kinase regulatory subunit 4 participates in the occurrence and development of amyotrophic lateral sclerosis by regulating autophagy.

The development of amyotrophic lateral sclerosis (ALS) may be related to the abnormal alterations of multiple proteins. Our previous study revealed that the expression of phosphoinositide-3-kinase regulatory subunit 4 (PIK3R4) was decreased in ALS. However, the role of PIK3R4 in ALS pathogenesis remains unknown. This study was the first to find that transfection of PC12 cells with small interfering RNA against the PIK3R4 gene significantly decreased the expression levels of PIK3R4 and the autophagy-related proteins p62 and LC3. Additionally, in vivo experiments revealed that the PIK3R4 protein was extensively expressed in the anterior horn, posterior horn, central canal, and areas surrounding the central canal in cervical, thoracic, and lumbar segments of the spinal cord in adult mice. PIK3R4 protein was mainly expressed in the neurons within the spinal lumbar segments. PIK3R4 and p62 expression levels were significantly decreased at both the pre-onset and onset stages of ALS disease in Tg(SOD1*G93A)1Gur mice compared with control mice, but these proteins were markedly increased at the progression stage. LC3 protein expression did not change during progression of ALS. These findings suggest that PIK3R4 likely participates in the prevention of ALS progression. This study was approved by the Ethics Committee for Animal Care and Use of Jiangxi Provincial People's Hospital, Affiliated People's Hospital of Nanchang University (approval No. 2020025) on March 26, 2020.

Response of soil microbial communities and rice yield to nitrogen reduction with green manure application in karst paddy areas.

Fertilizer application practices are one of the major challenges facing agroecology. The agrobenefits of combined application of green manure and chemical fertilizers, and the potential of green manure to replace chemical fertilizers are now well documented. However, little is known about the impact of fertilization practices on microbial communities and tice yield. In this study, the diversity of bacterial and fungal communities, symbiotic networks and their relationship with soil function were analyzed in five fertilization treatments (N: 100% nitrogen fertilizer alone; M: green manure alone; MN60: green manure couple with 60% nitrogen fertilizer, MN80: green manure couple with 80% nitrogen fertilizer; and MN100: green manure couple with 100% nitrogen fertilizer). First, early rice yield was significantly higher by 12.6% in MN100 treatment in 2021 compared with N. Secondly, soil bacterial diversity showed an increasing trend with increasing N fertilizer application after green manure input, however, the opposite was true for fungal diversity. Microbial interaction analysis showed that different fertilizer applications changed soil microbial network complexity and fertilizer-induced changes in soil microbial interactions were closely related to soil environmental changes. Random forest models further predicted the importance of soil environment, microorganisms and rice yield. Overall, nitrogen fertilizer green manure altered rice yield due to its effects on soil environment and microbial communities. In the case of combined green manure and N fertilizer application, bacteria and fungi showed different responses to fertilization method, and the full amount of N fertilizer in combination with green manure reduced the complexity of soil microbial network. In contrast, for more ecologically sensitive karst areas, we recommend fertilization practices with reduced N by 20-40% for rice production. Graphical Abstract.

Identification of an immune-related gene prognostic index for predicting prognosis, immunotherapeutic efficacy, and candidate drugs in amyotrophic lateral sclerosis.

Rationale and objectives: Considering the great insufficiency in the survival prediction and therapy of amyotrophic lateral sclerosis (ALS), it is fundamental to determine an accurate survival prediction for both the clinical practices and the design of treatment trials. Therefore, there is a need for more accurate biomarkers that can be used to identify the subtype of ALS which carries a high risk of progression to guide further treatment. Methods: The transcriptome profiles and clinical parameters of a total of 561 ALS patients in this study were analyzed retrospectively by analysis of four public microarray datasets. Based on the results from a series of analyses using bioinformatics and machine learning, immune signatures are able to be used to predict overall survival (OS) and immunotherapeutic response in ALS patients. Apart from other comprehensive analyses, the decision tree and the nomogram, based on the immune signatures, were applied to guide individual risk stratification. In addition, molecular docking methodology was employed to screen potential small molecular to which the immune signatures might response. Results: Immune was determined as a major risk factor contributing to OS among various biomarkers of ALS patients. As compared with traditional clinical features, the immune-related gene prognostic index (IRGPI) had a significantly higher capacity for survival prediction. The determination of risk stratification and assessment was optimized by integrating the decision tree and the nomogram. Moreover, the IRGPI may be used to guide preventative immunotherapy for patients at high risks for mortality. The administration of 2MIU IL2 injection in the short-term was likely to be beneficial for the prolongment of survival time, whose dosage should be reduced to 1MIU if the long-term therapy was required. Besides, a useful clinical application for the IRGPI was to screen potential compounds by the structure-based molecular docking methodology. Conclusion: Ultimately, the immune-derived signatures in ALS patients were favorable biomarkers for the prediction of survival probabilities and immunotherapeutic responses, and the promotion of drug development.

Potential Common Genetic Risks of Sporadic Parkinson's Disease and Amyotrophic Lateral Sclerosis in the Han Population of Mainland China.

Sporadic Parkinson's disease (sPD) and sporadic amyotrophic lateral sclerosis (sALS) are neurodegenerative diseases characterized by progressive and selective neuron death, with some genetic similarities. In order to investigate the genetic risk factors common to both sPD and sALS, we carried out a screen of risk alleles for sALS and related loci in 530 sPD patients and 530 controls from the Han population of Mainland China (HPMC). We selected 27 single-nucleotide polymorphisms in 10 candidate genes associated with sALS, and we performed allelotyping and genotyping to determine their frequencies in the study population as well as bioinformatics analysis to assess their functional significance in these diseases. The minor alleles of rs17115303 in DAB adaptor protein 1 (DAB1) gene and rs6030462 in protein tyrosine phosphatase receptor type T (PTPRT) gene were correlated with increased risk of both sPD and sALS. Polymorphisms of rs17115303 and rs6030462 were associated with alterations in transcription factor binding sites, secondary structures, long non-coding RNA interactions, and nervous system regulatory networks; these changes involved biological processes associated with neural cell development, differentiation, neurogenesis, migration, axonogenesis, cell adhesion, and metabolism of phosphate-containing compounds. Thus, variants of DAB1 gene (rs17115303) and PTPRT gene (rs6030462) are risk factors common to sPD and sALS in the HPMC. These findings provide insight into the molecular pathogenesis of both diseases and can serve as a basis for the development of targeted therapies.