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Phenol-formaldehyde resins combined with polymers have a wide range of industrial applications as plugging agents for profile control and enhanced oil recovery. Due to the structural resemblance between lignin and phenol, there are possibilities for environmentally friendly phenol-formaldehyde resin manufacturing. Sulfonated lignin–based phenol-formaldehyde resin was synthesized by partially replacing phenol with lignin, which improved the utilization rate of lignin and achieved the purpose of environmental preservation and resource conservation. Partially hydrolyzed polyacrylamide is the most widely used polymer in chemical methods for enhanced oil recovery. However, the stability of reservoirs with high salt and high temperatures is weak under these conditions. To solve the problem of low oil recovery in high-salt reservoir environments, polymer flooding is adopted, which utilizes high-molecular-weight polymers to raise the viscosity of injected fluids, thereby improving sweep efficiency and altering mobility ratio between oil and injected fluid. We focus on the stability study of different molecular weights partially hydrolyzed polyacrylamide combined with sulfonated lignin – based phenol-formaldehyde resins in metal ions and surfactants. The zeta potential and hydrodynamic diameter of the partially hydrolyzed polyacrylamide – sulfonated lignin – based phenol-formaldehyde resin system in Ca2+ were measured by dynamic light scattering and static light scattering, and the dispersion stability was analyzed. The interfacial energy – modified DLVO theory was introduced to evaluate the stability of its colloidal solution, which made it possible to predict the aggregation behavior of sulfonated lignin – based phenol-formaldehyde resin and the co-migration process of metal cations in real time. [ABSTRACT FROM AUTHOR]

Uncontrolled hemorrhage resulting from traumas causes severe health risks. There is an urgent need for expeditious hemostatic materials to treat bleeding incidents. Here, we developed a natural protein-based hemostatic sponge extracted from nonmulberry cocoons that exhibited rapid coagulation and effective absorption. We first built a degumming and dissolution system suitable for the Dictyoploca japonica cocoons to obtain regenerated silk fibroin (DSF). The DSF was then combined with carboxymethyl chitosan (CMCS) by glutaraldehyde (GA) crosslinking to ensure the structural stability of sponges. The resulting DSF–CMCS–GA exhibited remarkable hemostatic properties, displaying the highest absorption rate. It also demonstrated comparable efficacy to commercial hemostatic sponges. The blood-clotting index and hemolysis test showed that the prepared sponge possessed hemostatic activity and good hemocompatibility. Compared with mulberry silk fibroin hemostatic sponges (SF–CMCS–GA), DSF–CMCS–GA showed slightly better effects, making them a potential alternative to mulberry silk. In conclusion, our study introduces the use of Dictyoploca japonica silk fibroin for hemostasis, highlighting the exploitation of wild silkworm resources and providing an excellent silk fibroin-based hemostatic sealant for acute accident wounds and biomedical applications involving massive hemorrhage. [ABSTRACT FROM AUTHOR]

Enhanced oil recovery research focuses on the phenol–formaldehyde resin (PFR) solution (EOR). We studied PFR's morphology and aggregation kinetics at various pH levels. A hydrated layer formed on the surface of PFR as a result of hydrogen bonding between the hydroxyl and phenolic hydroxyl groups and water molecules. We quantitatively quantified the impact of pH on the morphology and aggregation kinetics of PFR by incorporating the hydrated force into the DLVO (Derjaguin Landau Verwey Overbeek) theory. We were able to predict the situation of aggregates plugging into the reservoir by altering the size of PFR aggregates in a capillary. [ABSTRACT FROM AUTHOR]

The scaling off is among the most pervasive and severe deterioration types. The scaling off developed on earthen sites in Northwest China has a special and complex binary structure composed of crusted and loose layers. Under the synergistic functions of external environmental elements such as rainfall, temperature, and wind, and rammed earth properties, this deterioration has gradually created the crust on the site's surface, and has then evolved into exfoliation and finally fallen off, leading to the reciprocating progressive destruction of earthen sites. Therefore, determining the development mechanism of scaling off and implementing targeted protection measures for the scientific conservation of earthen sites has become essential. In this review study, the properties of the building material causing the binary structure and the coupling effects of water, temperature, salt, and wind on the development of scaling off were determined, and the quantitative evaluation system for this deterioration development was elaborated. After interpreting the reasons for the development of the scaling off, protective measures including chemical grouting, electro-osmosis grouting, and overlay applications were stated. This study also pointed out the research hotspots and shortage in the study process on the scaling off. The hotspots generally focused on the development mechanism of binary structure, quantitative assessment of the degree of development, and related scientific consolidation measures. The shortcomings around the above directions include less attention to the development characteristics and mechanism of scaling off on earthen sites under special environment types, optimization and applicability of quantitative evaluation models, and the development and feasibility of reinforcement slurries and methods. This study can be beneficial in providing theoretical support for the scientific conservation and engineering practice of the scaling off on the earthen sites. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that affects social interaction and behavior. Mutations in the gene encoding chromodomain helicase DNA-binding protein 8 (CHD8) lead to autism symptoms and macrocephaly by a haploinsufficiency mechanism. However, studies of small animal models showed inconsistent findings about the mechanisms for CHD8 deficiency-mediated autism symptoms and macrocephaly. Using the nonhuman primate as a model system, we found that CRISPR/Cas9-mediated CHD8 mutations in the embryos of cynomolgus monkeys led to increased gliogenesis to cause macrocephaly in cynomolgus monkeys. Disrupting CHD8 in the fetal monkey brain prior to gliogenesis increased the number of glial cells in newborn monkeys. Moreover, knocking down CHD8 via CRISPR/Cas9 in organotypic monkey brain slices from newborn monkeys also enhanced the proliferation of glial cells. Our findings suggest that gliogenesis is critical for brain size in primates and that abnormal gliogenesis may contribute to ASD. [ABSTRACT FROM AUTHOR]

The stability of phenol–formaldehyde resin (nHAP) in the oil displacement process influences its flooding and profile control capabilities. There aren't many studies that compare how various surfactants affect PFR stability. The surfactants CTAB, Tween 60, and SDS were selected as representative ones. To look at the changes in stability, spectral turbidity and dynamic light scattering experiments were employed. It was found that the cationic surfactant CTAB can connect with the surface of PFR, just as metal cations, lowering electrostatic repulsion and facilitating the aggregation of PFR composite molecules. Anionic and nonionic surfactants both have some degree of system stability stabilizing properties. When Tween 60 and SDS adsorbed on the surface of the PFR molecule formed a hydrogen bond network with the hydroxymethyl or phenolic hydroxyl group, for example by hydrogen bond interaction, the PFR molecule's dispersion stability was increased. The Tween 60 and PFR composite systems have bigger particle sizes in addition to being more stable. Additionally, the energy barrier of the Tween 60/PFR composite system is determined using the modified DLVO theory for Lewis acid–base hydration, and it is discovered to be consistent with the experimental findings. The findings demonstrate that the stability of the composite system can be impacted by changes in the hydrophilicity and hydrophobicity of the composite system. The findings demonstrate that the stability of the composite system can be impacted by changes in the hydrophilicity and hydrophobicity of the composite system. Understanding the co-migration of PFR and surface activity during oil displacement depends heavily on the data. [ABSTRACT FROM AUTHOR]

Huntingtin-associated protein 1 (HAP1) is the first identified protein whose function is affected by its abnormal interaction with mutant huntingtin (mHTT), which causes Huntington disease. However, the expression patterns of Hap1 and Htt in the rodent brain are not correlated. Here we found that the primate HAP1, unlike the rodent Hap1, is correlatively expressed with HTT in the primate brains. CRISPR/Cas9 targeting revealed that HAP1 deficiency in the developing human neurons did not affect neuronal differentiation and gene expression as seen in the mouse neurons. However, deletion of HAP1 exacerbated neurotoxicity of mutant HTT in the organotypic brain slices of adult monkeys. These findings demonstrate differential HAP1 expression and function in the mouse and primate brains, and suggest that interaction of HAP1 with mutant HTT may be involved in mutant HTT-mediated neurotoxicity in adult primate neurons. [ABSTRACT FROM AUTHOR]

The anions in the phenol–formaldehyde resin colloid interact with the metal cations in the system to form aggregates with different fractal structures. In this study, Mg2+ and Na+ were studied. At low cationic concentrations, colloid aggregates with the reaction-limited colloidal aggregation (RLCA) mechanism, forming loose aggregates. At high cationic concentrations, colloid aggregates with the diffusion-limited cluster aggregation (DLCA) mechanism, forming dense aggregates. By establishing the triple-layer surface complexation model of phenol–formaldehyde resin, the similarities and differences in interfacial characteristics of phenol–formaldehyde resin under different valence metal cation solutions were explained. The establishment of the triple-layer surface complexation model of phenol–formaldehyde resin is helpful in understanding the change of the aggregation morphology of phenol–formaldehyde resin in the rock gap and groundwater environment, and the change of the colloid interface properties during the co-transport of aggregates and colloidal metal cations. [ABSTRACT FROM AUTHOR]

Finger vein biometrics have been extensively studied for the capability to detect aliveness, and the high security as intrinsic traits. However, vein pattern distortion caused by finger rotation degrades the performance of CNN in 2D finger vein recognition, especially in a contactless mode. To address the finger posture variation problem, we propose a 3D finger vein verification system extracting axial rotation invariant feature. An efficient 3D finger vein reconstruction optimization model is proposed and several accelerating strategies are adopted to achieve real-time 3D reconstruction on an embedded platform. The main contribution in this paper is that we are the first to propose a novel 3D point-cloud-based end-to-end neural network to extract deep axial rotation invariant feature, namely 3DFVSNet. In the network, the rotation problem is transformed to a permutation problem with the help of specially designed rotation groups. Finally, to validate the performance of the proposed network more rigorously and enrich the database resources for the finger vein recognition community, we built the largest publicly available 3D finger vein dataset with different degrees of finger rotation, namely the Large-scale Finger Multi-Biometric Database-3D Pose Varied Finger Vein (SCUT LFMB-3DPVFV) Dataset. Experimental results on 3D finger vein datasets show that our 3DFVSNet holds strong robustness against axial rotation compared to other approaches. [ABSTRACT FROM AUTHOR]

Phenol–formaldehyde resin can be used to improve oil recovery; its key lies in its aggregation behavior and blocking strength. However, the traditional phenol–formaldehyde resin used in the petroleum field is all prepared by phenol and formaldehyde. In order to get rid of the dependence on fossil resources and make full use of renewable biomass resources, we used the abandoned walnut shells of the unique agricultural and forestry crops in Gansu province, which contains lignin partially replaced phenol to synthesize the new sulfonated lignin-based phenol–formaldehyde resin (SLPFR). The results showed that the optimum conditions for microwave polymers were polystyrene substitution rate of 20 wt%, decomposition temperature of 160 ℃, decommissioning time of 20 min, and sodium hydroxide concentration of 0.3 mol/L. Infrared spectroscopes and scanning telescopes have shown that after disintegration, there was an increased concentration of phosphorus, which had more active spots and was more suitable for replacing phenylphenol-synthetic formaldehyde resins. LC–MS indicated the molecular mass of SLPFR and the possible structure of molecules, indicating the successful synthesis of SLPFR. In this work, the aggregation behavior and dispersion stability of SLPFR were investigated from the composition of formation water. The effects of metal cations (Na+, Mg2+, Ca2+) on the dispersion stability of SLPFR in formation water were determined by turbidimetry, and the effects of metal cations on the particle size and zeta potential of the SLPFR system were measured by dynamic light scattering method and electrophoretic light scattering method. The stability of the aggregate structure of the SLPFR system was calculated by combining the fractal dimension. In this paper, the surfactant + SLPFR system and partially hydrolyzed polyacrylamide (HPAM) + SLPFR system were designed for the specific conditions of oil reservoirs, and the effects of metal cations on the aggregation behavior and dispersion stability of these two systems were studied. Based on the above comprehensive analysis, aggregation models were constructed to describe the aggregation behavior and dispersion stability of the HPAM + surfactant + SLPFR system. This makes it possible to predict in real time the migration and plugging of SLPFR aggregates in formation water.Graphical abstract: Phenol–formaldehyde resin can be used to improve oil recovery; its key lies in its aggregation behavior and blocking strength. However, the traditional phenol–formaldehyde resin used in the petroleum field is all prepared by phenol and formaldehyde. In order to get rid of the dependence on fossil resources and make full use of renewable biomass resources, we used the abandoned walnut shells of the unique agricultural and forestry crops in Gansu province, which contains lignin partially replaced phenol to synthesize the new sulfonated lignin-based phenol–formaldehyde resin (SLPFR). The results showed that the optimum conditions for microwave polymers were polystyrene substitution rate of 20 wt%, decomposition temperature of 160 ℃, decommissioning time of 20 min, and sodium hydroxide concentration of 0.3 mol/L. Infrared spectroscopes and scanning telescopes have shown that after disintegration, there was an increased concentration of phosphorus, which had more active spots and was more suitable for replacing phenylphenol-synthetic formaldehyde resins. LC–MS indicated the molecular mass of SLPFR and the possible structure of molecules, indicating the successful synthesis of SLPFR. In this work, the aggregation behavior and dispersion stability of SLPFR were investigated from the composition of formation water. The effects of metal cations (Na+, Mg2+, Ca2+) on the dispersion stability of SLPFR in formation water were determined by turbidimetry, and the effects of metal cations on the particle size and zeta potential of the SLPFR system were measured by dynamic light scattering method and electrophoretic light scattering method. The stability of the aggregate structure of the SLPFR system was calculated by combining the fractal dimension. In this paper, the surfactant + SLPFR system and partially hydrolyzed polyacrylamide (HPAM) + SLPFR system were designed for the specific conditions of oil reservoirs, and the effects of metal cations on the aggregation behavior and dispersion stability of these two systems were studied. Based on the above comprehensive analysis, aggregation models were constructed to describe the aggregation behavior and dispersion stability of the HPAM + surfactant + SLPFR system. This makes it possible to predict in real time the migration and plugging of SLPFR aggregates in formation water. [ABSTRACT FROM AUTHOR]

Setting reasonable coal pillar is a key to ensure safe mining of island coal face heading goaf in deep mine. With the background of typical deeply buried non-equal width isolated working face 3201 heading goaf in one mine and based on the spatial structure theory of overlying strata, the transformation of strata structure and the stress evolution of coal pillars caused therefrom in worked-out areas was analyzed, followed by a research on the mechanism of rock burst induced by coal pillars. As a result, it's concluded that the fundamental cause of rock burst induced by coal pillars is that the high stress of coal pillars at critical state of a rock burst exceeds their comprehensive strength. By establishing a bearing and load model of coal pillars at a critical state of a rock burst, an method for estimating reasonable width of coal pillars of isolated working face in worked-out area was derived and applied to the non-equal width isolated working face 3201, thus determining that the reasonable width of coal pillars should be 130 m. The field practice verified the practicability of the method. The research result is of great significance to prevention and treatment of rock burst of isolated working face in worked-out area in deep mine. [ABSTRACT FROM AUTHOR]

Selective neuronal accumulation of misfolded proteins is a key step toward neurodegeneration in a wide range of neurodegenerative diseases, including Huntington's (HD) diseases. Our recent studies suggest that Hsp70-binding protein 1 (HspBP1), an Hsp70/CHIP inhibitor that reduces protein folding, is highly expressed in neuronal cells and accounts for the accumulation of the HD protein huntingtin (HTT) in neuronal cells. To further determine the role of HspBP1 in regulation of mutant protein accumulation, we investigated whether increasing expression of HspBP1 in glial cells can also induce the accumulation of endogenous mutant HTT in glial cells and yield non-cell-autonomous toxic effects. We performed stereotaxic injection of AAV to selectively express HspBP1 in astrocytes in the brains of HD140Q knock-in (KI) mice that express mutant HTT ubiquitously but do not display obvious neurodegeneration. However, HspBP1 expression in HD140Q astrocytes led to the increased accumulation of endogenous mutant HTT and robust neuronal loss in the striatum of HD140Q KI mice. In transgenic HD mice that selectively express mutant HTT in astrocytes, increased accumulation of mutant HTT in astrocytes via HspBP1 expression did not elicit neurodegeneration but could exacerbate neurological symptoms. Consistently, suppressing the expression of endogenous HspBp1 in the striatum of HD140Q KI mice via CRISPR/Cas9 led to a significant reduction of mutant HTT accumulation. Our findings suggest that although endogenous mutant HTT in astrocytes can exacerbate neurological symptoms, it mediates neurodegeneration only when mutant HTT is also accumulated in neuronal cells. [ABSTRACT FROM AUTHOR]

Purpose: To examine the association between the MSCT quantitative measurements of congenital lung malformations (CLM) and the selection of surgical approaches (lobectomy vs. lung-sparing surgery).Methods: This retrospective study evaluated CLM surgical cases at our institution from 2016 to 2018. MSCT quantitative measurements were generated by a semi-automated approach: the volume of the lesion (Vlesion), the volume of the lesion-involved lobe (Vlobe), the volume of the lesion-involved lung (Vlung) and the volume of the total lung (Vtotal lung). The proportions of Vlesion to Vlobe (Plesion/lobe), Vlesion to Vlung (Plesion/lung), and Vlesion to V total lung (Plesion/total lung) were calculated. We used Logistics regression to examine whether quantitative measurements were associated with the selection of surgical approaches.Results: 151 patients were included (median age at surgery 6 months). 82 patients underwent lung-sparing surgery, and 69 patients underwent lobectomy. Vlesion (OR 1.51, 95% CI 1.09-2.07), Plesion/lobe (OR 1.78, 95% CI 1.16-2.72), Plesion/lung (OR 1.63, 95% CI 1.13-2.35), and Plesion/total lung (OR 1.58, 95% CI 1.12-2.22) were positively associated with the selection of lobectomy.Conclusion: The application of quantified MSCT analysis may provide insight into the quantitative characteristics of CLM, which could be potentially useful for surgical approach selection. [ABSTRACT FROM AUTHOR]

The Yijianfang Formation of Shunbei area in Tarim Basin (southeastern China) contains a promising hydrocarbon reservoir formation. Based on borehole logging and carbonate sedimentary analysis, the diagenetic facies of this formation have been studied. Eight diagenetic subfacies are identified, which are associated with distinctive sedimentary processes: the atmospheric-freshwater-dissolution, burial-dissolution, fracture-dissolution, penecontemporaneous-dolomitic, burial-dolomitic, seabed-cement, freshwater-cement, and burial-cement subfacies. Thus, five composite sedimentary facies are proposed: the cement- hydrothermal, fracture-dissolution, fracture-cement, fracture-hydrothermal, and dolomitic-cement facies. By combining these diagenetic facies with the sequence stratigraphic framework, it is concluded that the seabed-cement subfacies are developed in the transgressive system tract; the structural-hydrothermal, fracture-hydrothermal, and cement facies in the highstand system tract; the atmospheric-freshwater-dissolution, atmospheric-freshwater-cement, and structural-hydrothermal facies in the intraplatform shoal; the burial-dolomitic, dissolution, and cement facies in the intershoal sea; and the atmospheric-freshwater-dissolution and cement subfacies in the patch reef. Finally, under the control of tectonics, sedimentary facies, and sequence, the diagenetic facies evolution is comprehensively identified from three aspects: single well, continuous well, and root mean square (RMS) amplitude property; finally, the distribution law of diagenetic facies is confirmed. [ABSTRACT FROM AUTHOR]

Rock burst of soft coal is a new strongly concealed dynamic hazard, which threatens the mining safety of deep mine due to its unknown occurrence mechanism and the difficulty in prevention and control. Taking a coal mine in a rich coal zone with hidden hazards as an example, this paper firstly studied the cause of burst hazard in the region of deformed soft coal through theoretical analysis and field measurement, analyzed the evolution of soft coal burst, revealed its mechanism and finally proposed specific prevention and control measures. The main conclusions are: (1) the primary cause of impact hazard in soft coal mines was the formation of extensive disturbance zone under high stress, which caused the dirt ban to form a structure for carrying stored energy after the stages of dispersion, suspension, sliding motion and embedded squeeze contact; (2) the evolution of the rock bust of soft coal was concealed. In the process of the formation of bearing and storage structure, external input load gradually dissipated due to the severe deformation of roadway, forming an illusion without hazard; (3) the burst of soft coal was essentially the unstable impact of dirt band, so the criteria of obtaining stress and power for structural unstable impact was reduced; (4) the measures against the burst of soft coal from identifying potential impact areas, synchronously monitoring the stress of coal and the deformation of roadway to implementing prevention measures, were proposed, which exhibited a positive effect. [ABSTRACT FROM AUTHOR]

The first-line treatment for recurrent or metastatic gastrointestinal stromal tumors (GISTs) is imatinib, but the benefit of surgical intervention has not been determined. Surgery combined with long-term imatinib treatment (> 10 years) has rarely been reported. Patients with recurrent or metastatic GISTs who received surgery combined with long-term imatinib treatment (> 10 years) were included in this study. The demographic, surgical, and clinicopathologic data were retrospectively collected and analyzed. Five patients (three men and two women) with a median age of 47 (range 37–72) years were included. The primary tumor was located in the stomach and small intestine in three and two patients, respectively. Four patients who received complete resection (R0) had a single recurrent tumor. The remaining patient had more than two recurrent lesions, and the operation was done with gross residual disease (R2 resection, > 90% of the tumor bulk removed). All patients received more than 10 (median 13.50, range 12.30–13.67) years of imatinib treatment after resection of recurrent tumors. Two patients received a reduced dose of imatinib, and the remaining received 400 mg/day. The median follow-up was 17.0 (range 14.58–20.17) years since the primary tumor was resected. Two patients developed a tumor recurrence after 11.58 and 12.0 years of imatinib treatment, respectively. Surgical intervention may be beneficial when combined with long-term imatinib treatment for selected patients with recurrent or metastatic GISTs but should be further investigated. [ABSTRACT FROM AUTHOR]

Polyglutamine expansion in proteins can cause selective neurodegeneration, although the mechanisms are not fully understood. In Huntington's disease (HD), proteolytic processing generates toxic N-terminal huntingtin (HTT) fragments that preferentially kill striatal neurons. Here, using CRISPR/Cas9 to truncate full-length mutant HTT in HD140Q knock-in (KI) mice, we show that exon 1 HTT is stably present in the brain, regardless of truncation sites in full-length HTT. This N-terminal HTT leads to similar HD-like phenotypes and age-dependent HTT accumulation in the striatum in different KI mice. We find that exon 1 HTT is constantly generated but its selective accumulation in the striatum is associated with the age-dependent expression of striatum-enriched HspBP1, a chaperone inhibitory protein. Our findings suggest that tissue-specific chaperone function contributes to the selective neuropathology in HD, and highlight the therapeutic potential in blocking generation of exon 1 HTT. The mechanisms by which mutant Huntington protein Htt leads to selective neurodegeneration are not fully understood. Here, using gene editing in HD140Q knock-in mice, the authors show that exon1 Htt is a critical pathological form of the protein. [ABSTRACT FROM AUTHOR]

The cytoplasmic accumulation of the nuclear TAR DNA-binding protein 43 (TDP-43) is a pathologic hallmark in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and other neurological disorders. However, most transgenic TDP-43 rodent models show predominant nuclear distribution of TDP-43 in the brain. By expressing mutant TDP-43 (M337V) in the brains of rhesus monkeys and mice, we verified that mutant TDP-43 is distributed in the cytoplasm of the monkey brain and that the majority of mutant TDP-43 remains in the nuclei of the mouse brain. The primate-specific caspase-4, but not mouse homologue caspase-11, could remove the NLS-containing N-terminal domain and generate fragmented TDP-43 that accumulates in the cytoplasm. Moreover, increased expression of caspase-4 in the monkey brain promotes the cytoplasmic accumulation of endogenous TDP-43, and suppressing caspase-4 reduces the cytoplasmic distribution of endogenous TDP-43 in cultured human neural cells. Our findings suggest that primate-specific caspase-4-mediated cleavage of TDP-43 accounts for its cytoplasmic mislocalization in the primate brains and may serve as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Purpose: Valproic acid (VPA) is an important drug in seizure control with great inter-individual differences in metabolism and treatment effect. This study aims to identify the effects of genetic variants on VPA clearance in a population pharmacokinetic (popPK) model in children with epilepsy.Methods: A total of 325 VPA plasma concentrations from 290 children with epilepsy were used to develop the popPK model by using the nonlinear mixed-effects modeling method. The one-compartment model was established to describe the pharmacokinetics of VPA. Twelve single nucleotide polymorphisms involved in the pharmacokinetics of VPA were identified by MassARRAY system and their effects on VPA clearance were evaluated.Results: In the two final popPK models, inclusion of a combined genotype of four variants (rs1042597, rs28365062, rs4986893, and rs4244285), total daily dose (TDD), and body surface area (BSA) significantly reduced inter-individual variability for clearance over the base model. The inter-individual clearance equals to 0.73 × (TDD/628.92)0.59 × eUGT-CYP for TDD included model and 0.70 × (BSA/0.99)0.57 × eUGT-CYP for BSA included model. The precision of all parameters were acceptable (relative standard error < 32.81%). Bootstrap and visual predictive check results indicated that both two final popPK models were stable with acceptable predictive ability.Conclusion: TDD, BSA, and genotype might affect VPA clearance in children. The popPK models may be useful for dosing adjustment in children on VPA therapy. [ABSTRACT FROM AUTHOR]

With the breakthrough of exploration in Well TP16-1, the lower Kepingtage Formation becomes a key target for petroleum exploration of deep clastic reservoir in Tahe area. In this paper we focused on the research of the reservoir characteristics and its controlling factors in two sub-member formations (S1 k and S1 k ). Based on X-ray diffraction, conventional physical properties data (porosity and permeability) and reservoir storage space data (casting thin section and scanning electron microscope), we determined that the S1k1 Formation belongs to extra-low porosity and permeability reservoir, although the upper S1 k Formation shows relative better physical characteristic than the lower S1 k Formation. The development of storage space in the study area is controlled by sedimentary microfacies, diagenesis process. Reservoirs in S1k1 Formation are mainly located in channel (S1 k sandstones) and sand flat (S1 k sandstones). The sand flat sediments with a more coarse grain size compared with the channel. In diagenesis, compaction is the major controlling factor for reducing the porosity, followed by cementation. Dissolution of diagenesis is the major controlling factor in enhancing the reservoir porosities. Compared with channel (S1 k ) sandstones, sand flat sandstones (S1 k ) have better reservoir quality for its weaker compaction, cementation and stronger dissolution. On the basis of sedimentary characteristics (grain size and subfacies), physical property (porosity and permeability) and reservoir storage space, we divide the S1k1 reservoir into three categories (I, II and III). Type I reservoir is high quality reservoir. It is mainly distributed in the south area of S1 k and S1 k reservoir. Type II is moderate reservoir. It is located in the middle of S1 k reservoir and in the north of S1 k reservoir. Type III is the poor reservoir. It is only located in the north of S1 k reservoir. [ABSTRACT FROM AUTHOR]

Previously, we reported on the crystal structures of the Fab fragments of two food and drug administration approved therapeutic antibodies, Infliximab and Adalimumab, in complex with TNFα. The structurally identified epitopes on TNFα reveal the mechanism of TNFα inhibition by partially overlapping with the TNFα-receptor interface. In this study, we launched a screen of a phage display library to isolate novel anti-TNFα antibodies based on the adalimumab epitope. Structural analysis, the phage display antibody isolation technology, step-by-step antibody optimization, complementarity-determining region residues random mutagenesis, phage ELISA, binding affinity characterization, and cell signaling assays were used for the development and optimization of the novel anti-TNFα antibodies. Moreover, one of the novel antibodies, hAta09, has a superior inhibitory effect on TNFα function and signaling. Taken together, our report established that the novel anti-TNFα antibody hAta09 may achieve clinical efficacy in a TNFα-associated disease. [ABSTRACT FROM AUTHOR]

Key message: We have constructed and annotated a web-based database of over 280 Arabidopsis genes that have characterized mutants associated with Arabidopsis acyl lipid metabolism. Abstract: Mutants have played a fundamental role in gene discovery and in understanding the function of genes involved in plant acyl lipid metabolism. The first mutant in Arabidopsis lipid metabolism ( fad4) was described in 1985. Since that time, characterization of mutants in more than 280 genes associated with acyl lipid metabolism has been reported. This review provides a brief background and history on identification of mutants in acyl lipid metabolism, an analysis of the distribution of mutants in different areas of acyl lipid metabolism and presents an annotated database (ARALIPmutantDB) of these mutants. The database provides information on the phenotypes of mutants, pathways and enzymes/proteins associated with the mutants, and allows rapid access via hyperlinks to summaries of information about each mutant and to literature that provides information on the lipid composition of the mutants. In addition, the database of mutants is integrated within the ARALIP plant acyl lipid metabolism website () so that information on mutants is displayed on and can be accessed from metabolic pathway maps. Mutants for at least 30 % of the genes in the database have multiple names, which have been compiled here to reduce ambiguities in searches for information. The database should also provide a tool for exploring the relationships between mutants in acyl lipid-related genes and their lipid phenotypes and point to opportunities for further research. [ABSTRACT FROM AUTHOR]

Complete resection is the most effective therapy for gastrointestinal stromal tumors (GISTs). Complete resection of locally advanced primary GIST by less invasive procedure is usually difficult at initial diagnosis. Imatinib has been successful in treating locally advanced and metastatic GIST and this report shares the experiences in preoperative use of imatinib for patients with locally advanced primary GISTs. The procedure of treatment and completeness of resection were retrospectively accessed for locally advanced primary GIST. Disease-free survival (DFS) and overall survival (OS) after resection were analyzed. Thirteen patients were treated with imatinib preoperatively. All patients received surgical resection after a median imatinib treatment of 7 months when most tumors shrunk. All patients achieved R0 resection without tumor rupture. Two patients received an en-bloc multivisceral resection for the invasion of surrounding organs and 3 patients underwent Mile's operation for a low rectal tumor. Eleven patients were disease-free. Median DFS or OS had not been reached, while 1- and 3-year DFS were estimated to be 92.3 and 76.9 %, respectively. 1- and 3-year OS were both estimated to be 100 %. Preoperative use of imatinib is useful in locally advanced primary GIST by downsizing the tumor in most patients and facilitating complete resection through less invasive procedures without tumor rupture. [ABSTRACT FROM AUTHOR]

When telomeres are shortened to a critical length, they will initiate chromosomal instability (CIN) and may finally cause tumorigenesis. The purpose of the present study was to evaluate the shortened telomere as a potential biomarker for tumorigenesis in gastric carcinoma. The telomeres in matched cancer and adjacent noncancer mucosa samples from 86 gastric carcinoma patients were measured by real-time polymerase chain reaction (PCR). According to the International Union Against Cancer (UICC), tumor stages were classified into four groups: stage I ( n = 23), stage II ( n = 20), stage III ( n = 23), and stage IV ( n = 20). Telomere length decreased with aging in both adjacent noncancer mucosa and cancer tissue ( r = −0.261 ( P = 0.008) and r = −0.27 ( P = 0.012), respectively). The telomere length of UICC stage I tumors was significantly shorter than the average telomere length in adjacent noncancer mucosa ( P = 0.023). Telomere length increased gradually with increasing UICC stage ( P = 0.032). The telomere length of UICC stage IV tumors was significantly longer, when compared to that in noncancer mucosa ( P = 0.019) and stage I tumors ( P = 0.002). In summary, telomere length undergoes shortening in early stage gastric carcinoma and lengthening in advanced gastric carcinoma. Additionally, telomere shortening may initiate the tumorigenesis of gastric carcinoma. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-19873-9 [ABSTRACT FROM AUTHOR]

CRISPR-Cas9 is a powerful new tool for genome editing, but this technique creates mosaic mutations that affect the efficiency and precision of its ability to edit the genome. Reducing mosaic mutations is particularly important for gene therapy and precision genome editing. Although the mechanisms underlying the CRSIPR/Cas9-mediated mosaic mutations remain elusive, the prolonged expression and activity of Cas9 in embryos could contribute to mosaicism in DNA mutations. Here we report that tagging Cas9 with ubiquitin-proteasomal degradation signals can facilitate the degradation of Cas9 in non-human primate embryos. Using embryo-splitting approach, we found that shortening the half-life of Cas9 in fertilized zygotes reduces mosaic mutations and increases its ability to modify genomes in non-human primate embryos. Also, injection of modified Cas9 in one-cell embryos leads to live monkeys with the targeted gene modifications. Our findings suggest that modifying Cas9 activity can be an effective strategy to enhance precision genome editing. [ABSTRACT FROM AUTHOR]

Several studies have suggested an important role of miR-291b-3p in the development of embryonic stem cells. In previous study, we found that the expression of miR-291b-3p was significantly upregulated in the liver of db/db mice. However, the role of miR-291b-3p in glucose metabolism and its underlying mechanisms remain unknown. In the present study, we demonstrated that miR-291b-3p was abundantly expressed in the liver. Of note, hepatic miR-291b-3p expression was upregulated in HFD-fed mice and induced by fasting in C57BL/6 J normal mice. Importantly, hepatic inhibition miR-291b-3p expression ameliorated hyperglycemia and insulin resistance in HFD-fed mice, whereas hepatic overexpression of miR-291b-3p led to hyperglycemia and insulin resistance in C57BL/6 J normal mice. Further study revealed that miR-291b-3p suppressed insulin-stimulated AKT/GSK signaling and increased the expression of gluconeogenic genes in hepatocytes. Moreover, we identified that p65, a subunit of nuclear factor-κB (NF-κB), is a target of miR-291b-3p by bioinformatics analysis and luciferase reporter assay. Silencing of p65 significantly augmented the expression of PTEN and impaired AKT activation. In conclusion, we found novel evidence suggesting that hepatic miR-291b-3p mediated glycogen synthesis and gluconeogenesis through targeting p65 to regulate PTEN expression. Our findings indicate the therapeutic potential of miR-291b-3p inhibitor in hyperglycemia and insulin resistance. [ABSTRACT FROM AUTHOR]