Synthesis and demulsification performance of a novel low-temperature demulsifier based on trimethyl citrate.

A significant amount of water-in-oil (W/O) emulsion is generated during petroleum extraction. However, the current commercial demulsifiers are expensive to produce and requires high demulsification temperatures, leading to increased energy and economic consumption. To enhance the efficiency of demulsifiers and reduce the cost of demulsifying W/O emulsions, we have successfully developed a novel demulsifier named TCED through a straightforward two-step process. This demulsifier features trimethyl citrate as the hydrophilic core grafted with three hydrophobic chains. Its structure was characterized using EA, FT-IR and 1H NMR spectroscopy, and the demulsification performance was comprehensively evaluated. At a low demulsification temperature of 40 °C, TCED demonstrated a remarkable demulsification efficiency (DE) of 99.06% and 98.74% in emulsions containing water contents of 70% (E70) and 50% (E50), respectively. Especially, a DE of 100% could be obtained in both E70 and E50 emulsions at a concentration of 600 mg/L. Moreover, TCED displayed a high DE even at high salinity levels of 50,000 mg/L and across a wide pH range of 2-10. Additionally, the phase interface was consistently clear after demulsification. To investigate the demulsification mechanism of TCED, various adsorption kinetics experiments were conducted, including measurements of interfacial tension (IFT), surface tension (SFT), interfacial competitive adsorption, and stability of interfacial film. The results obtained from the experiments indicated that TCED possessed remarkable diffusion and replacement capabilities within the emulsions. As a result, it effectively disrupted the original interfacial active substances, such as asphaltenes aggregates found in crude oil. TCED exhibits a high DE at low concentration and temperature. This characteristic highlights its significant potential for low-temperature demulsification applications in the petroleum industry.

Inhibition of PARP1 improves cardiac function after myocardial infarction via up-regulated NLRC5.

The incidence and mortality rate of myocardial infarction are increasing per year in China. The polarization of macrophages towards the classically activated macrophages (M1) phenotype is of utmost importance in the progression of inflammatory stress subsequent to myocardial infarction. Poly (ADP-ribose) polymerase 1(PARP1) is the ubiquitous and best characterized member of the PARP family, which has been reported to support macrophage polarization towards the pro-inflammatory phenotype. Yet, the role of PARP1 in myocardial ischemic injury remains to be elucidated. Here, we demonstrated that a myocardial infarction mouse model induced cardiac damage characterized by cardiac dysfunction and increased PARP1 expression in cardiac macrophages. Inhibition of PARP1 by the PJ34 inhibitors could effectively alleviate M1 macrophage polarization, reduce infarction size, decrease inflammation and rescue the cardiac function post-MI in mice. Mechanistically, the suppression of PARP1 increase NLRC5 gene expression, and thus inhibits the NF-κB pathway, thereby decreasing the production of inflammatory cytokines such as IL-1ß and TNF-α. Inhibition of NLRC5 promote infection by effectively abolishing the influence of this mechanism discussed above. Interestingly, inhibition of NLRC5 promotes cardiac macrophage polarization toward an M1 phenotype but without having major effects on M2 macrophages. Our results demonstrate that inhibition of PARP1 increased NLRC5 gene expression, thereby suppressing M1 polarization, improving cardiac function, decreasing infarct area and attenuating inflammatory injury. The aforementioned findings provide new insights into the proinflammatory mechanisms that drive macrophage polarization following myocardial infarction, thereby introducing novel potential targets for future therapeutic interventions in individuals affected by myocardial infarction.

Role of 7-methylxanthine in myopia prevention and control: a mini-review.

Myopia is becoming increasingly common. By 2050 around 10% of the world's population is expected to be highly myopic (<-5 diopters) and therefore particularly at risk of suffering from sight-threatening complications. Currently used myopia control treatments, such as multifocal soft contact lenses or spectacle lenses, orthokeratology, and atropine eyedrops, either do not completely arrest myopia progression or are associated with significant ocular and possibly systemic side effects. A new candidate for pharmaceutical control of myopia progression and excessive eye elongation, the non-selective adenosine antagonist 7-methylxanthine (7-MX), appears to be non-toxic and effective in reducing myopia progression and axial eye growth in experimental and clinical studies. The latest findings regarding 7-MX for myopia control and evaluate its potential as a supplement to existing treatment options were reviewed.

The Application of Dual-layer Spectral Detector CT in Abdominal Vascular Imaging.

As a convenient and non-invasive diagnostic method, computed tomography (CT) has been developing continuously, and dual-energy CT imaging is one of its current research hotspots. Dualenergy CT, using two different X-ray energies for imaging, can generate spectral image sets such as virtual monoenergetic images, virtual non-contrast images, iodine density images, uric acid images, calcium inhibition images, and effective atomic number images. These images could help to increase the contrast of vascular, improve the detection rate of lesions, reduce artifacts, reduce the dose of radiation, and characterize materials. Dual-layer spectral detector CT, a detector-based dual-energy scanning device, has an X-ray tube and a dual-layer X-ray detector that can simultaneously separate lowenergy and high-energy photons from a multi-energy X-ray beam, which means excellent time registration. This paper aims to introduce the applications of dual-layer spectral detector CT in abdominal angiography, including optimizing image quality, reducing the dose of contrast agent and radiation, providing richer diagnostic information, organ perfusion, and thrombus identification.

Corrosion Inhibition Studies of 8-Hydroxyquinoline Derivatives for N80 Steel in a 1.0 M HCl Solution: Experimental, Computational Chemistry, and Quantitative Structure-Activity Relationship Studies.

Twelve kinds of 8-hydroxyquinoline derivatives were synthesized and characterized. The weight loss method was used to evaluate their inhibition efficiencies (IEs) in a 1.0 M HCl solution at 333 K. The results showed that the alkyl chain length, heteroatoms (S, N, and O), and number of benzene rings significantly affect the IE. Herein, the IE of 5-[(dodecylthio)methyl]-8-quinolinol reached 98.71%. Meanwhile, the potentiodynamic polarization results indicated that all 8-hydroxyquinoline derivatives were mixed-type inhibitors. Electrochemical impedance spectroscopy results revealed that 8-hydroxyquinoline derivatives can increase polarization resistance, supporting their adsorption on the N80 steel surface. Moreover, according to density functional theory (DFT), the frontier orbital distribution and quantum chemical parameters (EHOMO, ELUMO, dipole moment µ, etc.) were calculated, and the results confirmed that the substituents of protonated 8-hydroxyquinoline derivatives significantly influenced the frontier orbital distribution. Molecular dynamics simulation illustrated that all protonated 8-hydroxyquinoline derivatives were adsorbed parallel to the Fe(110) surface, and the interaction energy (Eint) evidenced that the molecular size would affect their strength of adsorption on the Fe(110) surface. The linear and nonlinear quantitative structure-activity relationship models were established by linear regression (LR) methods and BP neural networks (NN), respectively. The LR model was established by using Eint and µ, and the coefficient of determination (R2) was 0.934. In addition, the nonlinear NN model was obtained according to IE and all parameters (DFT parameters and Eint). Then, the two calculation inhibition efficiencies (IEcal) were obtained from the LR and NN models, and the R2 values of the linear correlation between the IEcal and the experimental IE were 0.940 and 0.951, respectively. In addition, the IE of the tested inhibitor was 51.86% and the IEcal values predicted by the LR and NN models were 52.68% and 53.06%, respectively. Our results demonstrate that both the LR and NN models have good fits and predictive ability.

Loss of function of CMPK2 causes mitochondria deficiency and brain calcification.

Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions. Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from these patients showed impaired mitochondria-associated metabolism pathways. In situ hybridization and single-cell RNA sequencing revealed robust Cmpk2 expression in neurons and vascular endothelial cells (vECs), two cell types with high energy expenditure in the brain. The neurons in Cmpk2-knockout (KO) mice have fewer mitochondrial DNA copies, down-regulated mitochondrial proteins, reduced ATP production, and elevated intracellular inorganic phosphate (Pi) level, recapitulating the mitochondrial dysfunction observed in the PBMCs isolated from the FBC patients. Morphologically, the cristae architecture of the Cmpk2-KO murine neurons was also impaired. Notably, calcification developed in a progressive manner in the homozygous Cmpk2-KO mice thalamus region as well as in the Cmpk2-knock-in mice bearing the patient mutation, thus phenocopying the calcification pathology observed in the patients. Together, our study identifies biallelic variants of CMPK2 as novel genetic factors for FBC; and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, thereby highlighting the mitochondria dysregulation as a critical pathogenic mechanism underlying brain calcification.

Relationship between the molecular structure of different dithiocarbamates and their oil removal performance.

Six kinds of dithiocarbamates (DTCs) were synthesized from three linear amines with different amino numbers, two polyether amines with different molecular weights, and one branched amine with benzene rings, respectively. The conditions affecting oil removal rate and floc rising time of DTC were studied using simulated oily wastewater. Furthermore, the effects of the molecular structure of DTC on oil removal efficiency, floc morphology, floc rising time, and floc adhesion were investigated. When the conditions were optimal, the oil removal efficiency of DTC synthesized from polyethylene polyamine was 95.14%, which was higher than other DTCs. Meanwhile, the ferrous ion was the most suitable chelating metal ion for DTC than other transition metal ions. The increase of amino groups in the initiators improves the oil removal efficiency of DTC, while the linear structural DTC exhibits a low oil removal efficiency due to a lack of network structural flocs. The introduction of polyether structure helps reduce the volume of the flocs and make them compact, but it also increases the adhesion of the floc on the metal surface. The introduction of bisphenol A phenol amino resin structure induces the generation of the flocs in oil wastewater and improves the oil removal efficiency.

Dual-layer spectral detector CT for contrast agent concentration, dose and injection rate reduction: Utility in imaging of the superior mesenteric artery.

PURPOSE: To investigate the feasibility of contrast agent and injection rate reduction for dual-layer spectral detector computed tomography (SDCT) imaging of the superior mesenteric artery (SMA) using virtual monochromatic image (VMI). METHODS: A total of 102 patients who underwent abdominal arterial phase-enhanced SDCT examination due to suspected abdominal diseases were prospectively selected and divided into control group, low concentration/dose groups (groups 370-0.7, 300-1.0, and 300-0.9) and low injection rate groups (groups 2-370 and 2-350). Compared with the control group, low concentration/dose groups and low injection rate groups lowered the concentration/dose or injection rate of the contrast agent to varying degrees. The raw data obtained in each group were reconstructed using hybrid-iterative reconstruction and projection spatial-spectral reconstruction algorithm. The image quality of the SMA in conventional images (CI) and in VMIs40-140 kiloelectron volt (keV) (interval: 10 keV) during the arterial phase was analyzed. Multiplanar reformation images and volume rendering images of the SMA were reconstructed. Image quality objective evaluation indexes included the CT values, contrast-to-noise ratio, signal-to-noise ratio, and diameter of the SMA. The diameter of the SMA was determined by the CT values profile curve and its full width at half maximum. Two doctors independently evaluated the subjective image quality of multiplanar reformation coronal images and volume rendering images according to a 5-point scale. Repeated analysis of variance and Friedman test were used to compare the differences in the objective evaluation indexes and subjective scores between VMIs and CI in the same group. The Dunnett's t-test or Dunnett's T3 test and Kruskal-Wallis H-test were used to compare the differences in the objective evaluation indexes and subjective scores between the experimental and control groups. RESULTS: VMIs of the SMA in each group had the best image quality at 60 keV, and VMI60 keV in each group were better than their respective CI to varying degrees. Although the objective (CT values, contrast-to-noise ratio, and signal-to-noise ratio) and subjective (subjective scores) indexes of CI in the low concentration/dose groups and low injection rate groups were lower than those of CI in the control group to varying degrees, these indexes of VMI60 keV in the low concentration/dose groups and group 2-370 were equal to or even better than the CI in the control group. CONCLUSIONS: VMI60 keV using SDCT could effectively reduce the contrast agent load while providing equivalent or better SMA image quality compared with CI obtained using a conventional contrast agent protocol. When the injection rate was lowered to 2.0 ml/s for a high-concentration contrast agent (370 mgI/ml), the SMA image quality at VMI60 keV was comparable with that of the CI in the control group.

Mutation Analysis of MYORG in a Chinese Cohort With Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a progressive neurological disorder manifesting as bilateral brain calcifications in CT scan with symptoms as parkinsonism, dystonia, ataxia, psychiatric symptoms, etc. Recently, pathogenic variants in MYORG have been linked to autosomal recessive PFBC. This study aims to elucidate the mutational and clinical spectrum of MYORG mutations in a large cohort of Chinese PFBC patients with possible autosomal recessive or absent family history. Mutational analyses of MYORG were performed by Sanger sequencing in a cohort of 245 PFBC patients including 21 subjects from 10 families compatible with a possibly autosomal-recessive trait and 224 apparently sporadic cases. In-depth phenotyping and neuroimaging features were investigated in all patients with novel MYORG variants. Two nonsense variants (c.442C > T, p. Q148*; c.972C > A, p. Y324*) and two missense variants (c.1969G>C, p. G657R; c.2033C > G, p. P678R) of MYORG were identified in four sporadic PFBC patients, respectively. These four novel variants were absent in gnomAD, and their amino acid were highly conserved, suggesting these variants have a pathogenic impact. Patients with MYORG variants tend to display a homogeneous clinical spectrum, showing extensive brain calcification and parkinsonism, dysarthria, ataxia, or vertigo. Our findings supported the pathogenic role of MYORG variants in PFBC and identified two pathogenic variants (c.442C > T, c.972C > A), one likely pathogenic variant (c.2033C > G), and one variant of uncertain significance (c.1969G>C), further expanding the genetic and phenotypic spectrum of PFBC-MYORG.

Liver Fibrosis Staging with Gadolinium Ethoxybenzyl Diethylenetriamine Penta-Acetic Acid-enhanced: A Systematic Review and Meta-analysis.

OBJECTIVE: While liver biopsy is the golden standard for liver-fibrosis diagnosis, it is also invasive and has many limitations. Non-invasive techniques such as Magnetic Resonance Imaging (MRI) need to be further developed for liver fibrosis staging. This study aimed to evaluate the diagnostic accuracy of Gadolinium Ethoxybenzyl Diethylenetriamine Penta-acetic Acid (Gd-EOBDTPA)- enhanced MRI for liver fibrosis through systematic review and meta-analysis. METHODS: This study comprehensively searched relevant article in PubMed, Embase, and the Cochrane Library published from 2004 to 2018 to find studies analyzing the diagnostic accuracy of Gd-EOB-DTPA-enhanced MRI for liver fibrosis. Two reviewers independently screened the retrieved articles, extracted the required data from the included studies, and evaluated the methodological quality of the studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and Summary Receiver Operating Characteristics (SROC) curve were assessed. RESULTS: This study finally included 16 studies (n = 1,599) and selected a random-effects model based on the results of the I2 statistic to combine them. The areas under the SROC curve for the detection of F1 or greater, F2 or greater, F3 or greater, or F4 liver fibrosis were 0.8669, 0.8399, 0.8481, and 0.8858, respectively. CONCLUSION: Gd-EOB-DTPA-enhanced MRI showed a good diagnostic performance for staging liver fibrosis, especially for F4 liver fibrosis.

Dosimetric Comparison of Intensity-Modulated Radiotherapy, Volumetric Modulated Arc Therapy and Hybrid Three-Dimensional Conformal Radiotherapy/Intensity-Modulated Radiotherapy Techniques for Right Breast Cancer.

This study aimed to compare different types of right breast cancer radiotherapy planning techniques and to estimate the whole-body effective doses and the critical organ absorbed doses. The three planning techniques are intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT; two methods) and hybrid 3D-CRT/IMRT (three-dimensional conformal radiotherapy/intensity-modulated radiotherapy). The VMAT technique includes two methods to deliver a dose: non-continuous partial arc and continuous partial arc. A thermoluminescent dosimeter (TLD) is placed in the RANDO phantom to estimate the organ absorbed dose. Each planning technique applies 50.4 Gy prescription dose and treats critical organs, including the lung and heart. Dose-volume histogram was used to show the planning target volume (V95%), homogeneity index (HI), conformity index (CI), and other optimized indices. The estimation of whole-body effective dose was based on the International Commission on Radiation Protection (ICRP) Publication 60 and 103. The results were as follows: Continuous partial arc and non-continuous partial arc showed the best CI and HI. The heart absorbed doses in the continuous partial arc and hybrid 3D-CRT/IMRT were 0.07 ± 0.01% and 0% (V5% and V10%, respectively). The mean dose of the heart was lowest in hybrid 3D-CRT/IMRT (1.47 Gy ± 0.02). The dose in the left contralateral lung (V5%) was lowest in continuous partial arc (0%). The right ipsilateral lung average dose and V20% are lowest in continuous partial arc. Hybrid 3D-CRT/IMRT has the lowest mean dose to contralateral breast (organs at risk). The whole-body effective doses for ICRP-60 and ICRP-103 were highest in continuous partial arc (2.01 Sv ± 0.23 and 2.89 Sv ± 0.15, respectively). In conclusion, the use of VMAT with continuous arc has a lower risk of radiation pneumonia, while hybrid 3D-CRT/IMRT attain lower secondary malignancy risk and cardiovascular complications.

Median Nerve-Neurophysiological Index Correlates With the Survival of Patients With Amyotrophic Lateral Sclerosis.

Objective: This study aims to explore the association between median nerve-neurophysiological index (NI) and survival of patients with amyotrophic lateral sclerosis (ALS). Methods: A retrospective case series with a prospective follow-up study was performed in 238 patients with ALS. Their clinical profiles and NI were recorded. Kaplan-Meier curves and Cox regression were adopted to perform survival analysis. Results: The median survival time of all ALS cases was 33.0 months. Multivariate analysis showed that older age of onset, shorter diagnostic delay, higher ΔALSFRS-R, and faster progression {NI ≤ 2.15; hazard ratio [HR] = 1.543 [95% confidence interval (CI), 1.136-2.094]} were associated with short survival. NI was correlated with ALSFRS-R at baseline (r s = 0.3153; p < 0.0001) and ALSFRS-R at different time points of follow-up (r s = 0.5127; p < 0.0001). The higher NI slope of decline (> 0.25) showed shorter survival compared with the lower group (≤ 0.25; 34.0 vs. 52.0 months; p = 0.0003). A predictive model was constructed based on the age of onset, diagnostic delay, median nerve NI, and ΔALSFRS-R. The higher predictive score (> 14) showed significantly shorter survival compared with the lower group (≤ 14; HR = 3.907, 95% CI, 2.857-5.342). Conclusion: Median nerve NI and its slope of decline were predictive of survival of ALS.

[Construction of a striatum-specific Slc20a2 gene knockout mice model by CRISPR/Cas9 AAV system].

Primary familial brain calcification (PFBC) is a chronic progressive neurogenetic disorder. Its clinical symptoms mainly include dyskinesia, cognitive disorder and mental impairment; and the pathogenesis remains unclear. Studies have shown that SLC20A2 is the most common pathogenic gene of the disease. Since the Slc20a2 gene knockout mouse model could result in fetal growth restriction, in order to better understand the pathogenesis of PFBC, the present study used the CRISPR/Cas9 technology to construct a conditional knockout model of Slc20a2 gene in the striatum of mice. First, three sgRNAs (single guide RNAs) were designed to target the exon3 of Slc20a2 gene. The activity of the respective sgRNA was verified by constructing expression plasmids, transfecting cells and Surveyor assay. Second, the SgRNA with the highest activity was selected to generate the recombinant AAV-Cre virus, which was injected into the striatum of mice by stereotactic method. In vitro experiments showed that the three sgRNAs could effectively mediate Cas9 cleavage of the respective target DNA. The activity of Cre recombinase of the AAV-Cre was confirmed by immunofluorescence assay. Immunohistochemistry, TA clone, high-throughput sequencing and Western blot were used to detect and evaluate the efficiency of Slc20a2 gene knockout. The results showed that the Slc20a2 expression in the striatum of mice in the experimental group decreased significantly. In this study, three sgRNAs capable of knockout of Slc20a2 were successfully designed, and the conditional knockout of the Slc20a2 gene in the striatum of mouse was successfully established by the CRISPR/Cas9 technology, thereby providing an effective animal model for studying the pathogenesis of PFBC.

Novel CAPN1 mutations extend the phenotypic heterogeneity in combined spastic paraplegia and ataxia.

OBJECTIVE: Recessive mutations in the CAPN1 gene have recently been identified in spastic paraplegia 76 (SPG76), a complex hereditary spastic paraplegia (HSP) that is combined with cerebellar ataxia, resulting in an ataxia-spasticity disease spectrum. This study aims to assess the influence of CAPN1 variants on the occurrence of SPG76 and identify factors potentially contributing to phenotypic heterogeneity. METHODS: We screened a cohort of 240 unrelated HSP families for variants in CAPN1 using high-throughput sequencing analysis. We described in detail the clinical and genetic features of the SPG76 patients in our cohort and summarized all reported cases. RESULTS: Six unreported CAPN1-associated families containing eight patients with or without cerebellar ataxia were found in our cohort of HSP cases. These patients carried three previously reported homozygous truncating mutations (p.V64Gfs* 103, c.759+1G>A, and p.R285* ), and three additional novel compound heterozygous missense mutations (p.R481Q, p.P498L, and p.R618W). Lower limbs spasticity, hyperreflexia, and Babinski signs developed in about 94% of patients, with ataxia developing in 63% of cases. In total, 33 pathogenic mutations were distributed along the three reported functional domains of calpain-1 protein, encoded by CAPN1, with no hotspot region. A comparison of gender distribution between the two groups indicated that female SPG76 patients were significantly more likely to present with complicated HSP than male patients (P = 0.015). INTERPRETATION: Our study supports the clinically heterogeneous inter- and intra-family variability of SPG76 patients, and demonstrates that gender and calpain-1 linker structure may contribute to clinical heterogeneity in SPG76 cases.

A Label-Free Impedimetric Genosensor for the Nucleic Acid Amplification-Free Detection of Extracted RNA of Dengue Virus.

Developing rapid and sensitive diagnostic methods for dengue virus (DENV) infection is of prime priority because DENV infection is the most prevalent mosquito-borne viral disease. This work proposes an electrochemical impedance spectroscopy (EIS)-based genosensor for the label-free and nucleic acid amplification-free detection of extracted DENV RNA intended for a sensitive diagnosis of DENV infection. A concentration ratio of 0.04 mM 6-mercaptohexanoic acid (MHA) to 1 mM 6-mercapto-1-hexanol (MCH) was selected to modify thin-film gold electrodes as a link to control the coverage of self-designed probe DNA (pDNA) at a density of 4.5 ± 0.4 × 1011 pDNA/cm2. The pDNA/MHA/MCH-modified genosensors are proven to improve the hybridization efficiency of a synthetic 160-mer target DNA (160mtDNA) with a 140-mer electrode side overhang as compared to other MHA/MCH ratio-modified genosensors. The MHA(0.04 mM)/MCH(1 mM)-modified genosensors also present good hybridization efficiency with the extracted DENV serotype 1 (DENV1) RNA samples, having the same electrode side overhangs with the 160mtDNA, showing a low detection limit of 20 plaque forming units (PFU)/mL, a linear range of 102-105 PFU/mL and good selectivity for DENV1. The pDNA density-controlled method has great promise to construct sensitive genosensors based on the hybridization of extracted DENV nucleic acids.

Disruption of splicing-regulatory elements using CRISPR/Cas9 to rescue spinal muscular atrophy in human iPSCs and mice.

We here report a genome-editing strategy to correct spinal muscular atrophy (SMA). Rather than directly targeting the pathogenic exonic mutations, our strategy employed Cas9 and guide-sgRNA for the targeted disruption of intronic splicing-regulatory elements. We disrupted intronic splicing silencers (ISSs, including ISS-N1 and ISS + 100) of survival motor neuron (SMN) 2, a key modifier gene of SMA, to enhance exon 7 inclusion and full-length SMN expression in SMA iPSCs. Survival of splicing-corrected iPSC-derived motor neurons was rescued with SMN restoration. Furthermore, co-injection of Cas9 mRNA from Streptococcus pyogenes (SpCas9) or Cas9 from Staphylococcus aureus (SaCas9) alongside their corresponding sgRNAs targeting ISS-N1 into zygotes rescued 56% and 100% of severe SMA transgenic mice (Smn -/-, SMN2 tg/-). The median survival of the resulting mice was extended to >400 days. Collectively, our study provides proof-of-principle for a new strategy to therapeutically intervene in SMA and other RNA-splicing-related diseases.

Associating 197 Chinese herbal medicine with drug targets and diseases using the similarity ensemble approach.

Chinese herbal medicine (CHM) addresses complex diseases through polypharmacological interactions. However, systematic studies of herbal medicine pharmacology remain challenging due to the complexity of CHM ingredients and their interactions with various targets. In this study, we aim to address this challenge with computational approaches. We investigated the herb-target-disease associations of 197 commonly prescribed CHMs using the similarity ensemble approach and DisGeNET database. We demonstrated that this method can be applied to associate herbs with their putative targets. In the case study of three well-known herbs, Radix Glycyrrhizae, Flos Lonicerae, and Rhizoma Coptidis, approximately 70% of the predicted targets were supported by scientific literature. By linking 406 targets to 2439 annotated diseases, we further analyzed the pharmacological functions of 197 herbs. Finally, we proposed a strategy of target-oriented herbal formula design and illustrated the target profiles for four common chronic diseases, namely, Alzheimer's disease, depressive disorder, hypertensive disease, and non-insulin-dependent diabetes mellitus. This computational approach holds great potential in the target identification of herbs, understanding the molecular mechanisms of CHM, and designing novel herbal formulas.