CRISPR/Cas9: implication for modeling and therapy of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a deadly neurological disease with a complicated and variable pathophysiology yet to be fully understood. There is currently no effective treatment available to either slow or terminate it. However, recent advances in ALS genomics have linked genes to phenotypes, encouraging the creation of novel therapeutic approaches and giving researchers more tools to create efficient animal models. Genetically engineered rodent models replicating ALS disease pathology have a high predictive value for translational research. This review addresses the history of the evolution of gene editing tools, the most recent ALS disease models, and the application of CRISPR/Cas9 against ALS disease

Strain improvement of Trichoderma harzianum for enhanced biocontrol capacity: Strategies and prospects

In the control of plant diseases, biocontrol has the advantages of being efficient and safe for human health and the environment. The filamentous fungus Trichoderma harzianum and its closely related species can inhibit the growth of many phytopathogenic fungi, and have been developed as commercial biocontrol agents for decades. In this review, we summarize studies on T. harzianum species complex from the perspective of strain improvement. To elevate the biocontrol ability, the production of extracellular proteins and compounds with antimicrobial or plant immunity-eliciting activities need to be enhanced. In addition, resistance to various environmental stressors should be strengthened. Engineering the gene regulatory system has the potential to modulate a variety of biological processes related to biocontrol. With the rapidly developing technologies for fungal genetic engineering, T. harzianum strains with increased biocontrol activities are expected to be constructed to promote the sustainable development of agriculture

Association between immunoglobulin G N-glycosylation and lupus nephritis in female patients with systemic lupus erythematosus: A case-control study

Background: Lupus nephritis (LN) is a crucial complication of systemic lupus erythematosus (SLE) and has important clinical implications in guiding treatment. N-glycosylation of immunoglobulin G (IgG) plays a key role in the development of SLE by affecting the balance of anti-inflammatory and proinflammatory responses. This study aimed to evaluate the performance of IgG N-glycosylation for diagnosing LN in a sample of female SLE patients. Methods: This case-control study recruited 188 women with SLE, including 94 patients with LN and 94 age-matched patients without LN. The profiles of plasma IgG N-glycans were detected by hydrophilic interaction chromatography with ultra-performance liquid chromatography (HILIC-UPLC). A multivariate logistic regression model was used to explore the associations between IgG N-glycans and LN. A diagnostic model was developed using the significant glycans as well as demographic factors. The performance of IgG N-glycans in the diagnosis of LN was evaluated by receiver operating characteristic (ROC) curve analysis, and the area under the curve (AUC) and its 95% confidence interval (CI) were calculated. Results: There were significant differences in 9 initial glycans (GP2, GP4, GP6, GP8, GP10, GP14, GP16, GP18 and GP23) between women with SLE with and without LN (P \u3c 0.05). The levels of sialylated, galactosylated and fucosylated glycans were significantly lower in the LN patients than in the control group, while bisected N-acetylglucosamine (GlcNAc) glycans were increased in LN patients (P \u3c 0.05). GP8, GP10, GP18, and anemia were included in our diagnostic model, which performed well in differentiating female SLE patients with LN from those without LN (AUC = 0.792, 95% CI: 0.727 to 0.858). Conclusion: Our findings indicate that decreased sialylation, galactosylation, and core fucosylation and increased bisecting GlcNAc might play a role in the development of LN by upregulating the proinflammatory response of IgG. IgG N-glycans can serve as potential biomarkers to differentiate individuals with LN among SLE patients

Increasing Area and Decreasing Depth: Climate Change Influence on Snow Variations in the Qilian Mountains

The Qilian Mountains serve as a critical water source for the Yellow River and various inland rivers, playing a pivotal role in regulating the regional climate. Given their significance as one of the foremost water resources in the area, the spatial and temporal dynamics of the snow are crucial for understanding potential impacts on regional hydrology and ecology. This study examines the characteristics of spatial and temporal variations in snow-covered extent (SCE), snow depth (SD), snow-covered days (SCD), snow onset date (SOD), and snow end date (SED) within the Qilian Mountains region. We investigate the hydrological and ecological implications utilizing snow area and phenology data, alongside SD data. The findings indicate that: (1) the distribution of snow across the Qilian Mountains mainly splits between the central and western areas, with the central region showing deeper snow than both the eastern and western parts; (2) the area covered by snow in the Qilian Mountains is growing, but the depth of the snow is on a decline, especially in the central area; (3) in terms of snow phenology, most of the region is witnessing an earlier start of SOD, a longer SCD, and an earlier SED. An overall increase in precipitation is identified as the key factor behind the expanded SCE in the Qilian Mountains, while rising temperatures are pinpointed as the primary cause for the reduction in SD. As global climate change intensifies, the observed alterations in the snow of the Qilian Mountains present emerging challenges for regional water security and ecological equilibrium

Efficacy and Safety of Wei Bi Mei, a Chinese Herb Compound, as an Alternative to Bismuth for Eradication of Helicobacter pylori

Bismuth-containing quadruple therapy has been recommended as the first line of treatment in areas of high clarithromycin or metronidazole resistance. However, safety concerns of bismuth agents have long been raised. We first assessed the efficacy and safety of Wei Bi Mei granules, which are bismuth compounds consisting of three synthetic drugs and five medicinal herbs, compared to bismuth aluminate and colloidal bismuth subcitrate (CBS) in H. pylori-infected mouse model. We then used atomic fluorescence spectroscopy and autometallography to measure the accumulation of three bismuth agents in the brain, heart, liver, and kidneys in adult Sprague-Dawley rats. We also evaluated the safety of bismuth agents by conducting clinical biochemistry tests in blood samples of experimental animals. Wei Bi Mei granules exhibited the highest efficacy of anti-H. pylori activity and yielded the lowest bismuth accumulation when compared to CBS and bismuth aluminate. Our findings show that Wei Bi Mei granules are a safe Chinese medicinal herb with potent anti-H. pylori activity and can be considered as an alternative to current bismuth compounds. Thus, Wei Bi Mei granules merit further evaluation, particularly with regard to efficacy and safety when they are combined with other H. pylori eradication medications in the clinical setting

Layer-by-Layer Epitaxy of Multilayer MoS2 Wafers

Two-dimensional (2D) semiconductor of MoS2 has great potential for advanced electronics technologies beyond silicon1-9. So far, high-quality monolayer MoS2 wafers10-12 are already available and various demonstrations from individual transistors to integrated circuits have also been shown13-15. In addition to the monolayer, multilayers have narrower band gaps but improved carrier mobilities and current capacities over the monolayer5,16-18. However, achieving high-quality multilayer MoS2 wafers remains a challenge. Here we report the growth of high quality multilayer MoS2 4-inch wafers via the layer-by-layer epitaxy process. The epitaxy leads to well-defined stacking orders between adjacent epitaxial layers and offers a delicate control of layer numbers up to 6. Systematic evaluations on the atomic structures and electronic properties were carried out for achieved wafers with different layer numbers. Significant improvements on device performances were found in thicker-layer field effect transistors (FETs), as expected. For example, the average field-effect mobility ({\mu}FE) at room temperature (RT) can increase from ~80 cm2V-1s-1 for monolayer to ~110/145 cm2V-1s-1 for bilayer/trilayer devices. The highest RT {\mu}FE=234.7 cm2V-1s-1 and a record-high on-current densities of 1.704 mA{\mu}m-1 at Vds=2 V were also achieved in trilayer MoS2 FETs with a high on/off ratio exceeding 107. Our work hence moves a step closer to practical applications of 2D MoS2 in electronics.Comment: 13 pages,4 Figure

Room-temperature correlated states in twisted bilayer MoS2_2

Moir\'e superlattices have emerged as an exciting condensed-matter quantum simulator for exploring the exotic physics of strong electronic correlations. Notable progress has been witnessed, but such correlated states are achievable usually at low temperatures. Here, we report the transport evidences of room-temperature correlated electronic states and layer-hybridized SU(4) Hubbard model simulator in AB-stacked MoS$_2$ homo-bilayer moir\'e superlattices. Correlated insulating states at moir\'e band filling factors v = 1, 2, 3 are unambiguously established in twisted bilayer MoS$_2$. Remarkably, the correlated electronic states can persist up to a record-high critical temperature of over 285 K. The realization of room-temperature correlated states in twisted bilayer MoS$_2$ can be understood as the cooperation effects of the stacking-specific atomic reconstruction and the resonantly enhanced interlayer hybridization, which largely amplify the moir\'e superlattice effects on electronic correlations. Furthermore, extreme large non-linear Hall responses up to room-temperature are uncovered near correlated insulating states, demonstrating the quantum geometry of moir\'e flat conduction band.Comment: 13 pages, 3 figure

Heart Sound Biometric System Based on Marginal Spectrum Analysis

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