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This negative reception has also served to justify the transition in the Islamic world to the tafsīr of Bayḍāwī, a work which largely excised the Mu'tazilism of the Kashshāf. This article reconsiders the evidence for an overall negative Mamluk era reception of the Kashshāf, with specific reference to the activities of those scholars whose depiction contributes to an inaccurate portrayal of a crucial moment in tafsīr history, both for the activities of Mamluk era scholars themselves, as well as the subsequent shift to the use of Bayḍāwī.Here, we describe an intracellular pH-regulating nanoparticle (IPRN), coencapsulated with chemosensitizers and anticancer agents for effective and safe cancer treatment. IPRN contains a tubulysin derivative (TUB), a hydrophobic anticancer drug, and pantoprazole (PTZ), a hydrophilic proton-pump inhibitor. [https://www.selleckchem.com/products/-epicatechin.html Epicatechin chemical] IPRN with a size of 62 nm has an anionic surface charge and is stable for at least two weeks under storage conditions, though PTZ and TUB encapsulated in IPRN showed different drug release patterns. PTZ was released before TUB, controlling the cancer's intracellular pH, maintaining a pH at which TUB can work well. The encapsulated PTZ increased the pH of endolysosomes and inhibited ion trapping, with TUB ionization, thereby exhibiting increased cytotoxicity compared with free TUB observed in various cancer cell lines, such as human liver adenocarcinoma, human glioblastoma, and human pancreatic carcinoma. IPRN exhibited a 1.9-fold improved tumor growth inhibitory effect in a human liver adenocarcinoma-bearing mouse model, while minimizing the hepatotoxicity of free TUB. Thus, nanomedicines that contain both a chemosensitizer and an anticancer agent, such as IPRN, are expected to be next-generation anticancer agents that reduce the side effects of anticancer drugs and increase the therapeutic effect.Sepsis-induced acute lung injury (ALI) is mostly attributed to an outbreak of reactive oxygen species (ROS), which makes leukocytes infiltrate into the lung and results in lung hypoxia. Nitroreductase (NTR) is significantly upregulated under hypoxia, which is commonly regarded as a potential biomarker for assessing sepsis-induced acute lung hypoxia. Increasing evidence shows that NTR in the Golgi apparatus could be induced in sepsis-induced ALI. Meanwhile, the prolyl hydroxylase (PHD) inhibitor (dimethyloxalylglycine, DMOG) attenuated sepsis-induced ALI through further increasing the level of Golgi NTR by improving hypoxia inducible factor-1α (HIF-1α) activity, but as yet, no Golgi-targetable probe has been developed for monitoring and assessing treatment response of sepsis-induced ALI. Herein, we report a Golgi-targetable probe, Gol-NTR, for monitoring and assessing treatment response of sepsis-induced ALI through mapping the generation of NTR. The probe displayed high sensitivity with a low detection limit of 54.8 ng/mL and good selectivity to NTR. In addition, due to the excellent characteristics of Golgi-targetable, Gol-NTR was successfully applied in mapping the change of Golgi NTR in cells and zebrafish caused by various stimuli. Most importantly, the production of Golgi NTR in the sepsis-induced ALI and the PHD inhibitor (DMOG) against sepsis-induced ALI were visualized and precisely assessed for the first time with the assistance of Gol-NTR. The results demonstrated the practicability of Gol-NTR for the precise monitoring and assessing of the personalized treatment response of sepsis-induced ALI.β-Methoxyacrylate fungicides as complex III Qo site inhibitors play a crucial role in the control of crop diseases. In this study, the triphenylphosphonium (TPP)-driven mitochondrion-targeting strategy was used to modify the kresoxim-methyl scaffold at the toxicophore or side chain to develop novel mitochondrion-targeted QoI fungicides. These kresoxim-methyl analogues exhibited different fungicidal activities, depending on the position of TPP conjugation and the linker length. Among them, 2A-5 and 2C-4 showed excellent characteristics superior to kresoxim-methyl as candidate fungicides, in which the activity enhancement against Phytophthora capsici was the most remarkable, with an EC50 value of about 5 μM. Notably, both hyphal and zoospore structures of the pathogens were severely damaged after treatment with them. The action mechanism approach revealed that they might cause a significant decrease in ATP synthesis and ROS outbreak in different ways. The results also provided a new insight into the contribution of targeting group TPP to the fungicidal activity in TPP-driven fungicides.Obstetric volume sweep imaging (OB VSI) is a simple set of transducer movements guided by external body landmarks that can be taught to ultrasound-naive non-experts. This approach can increase access to ultrasound in rural/low-resources settings lacking trained sonographers. This study presents and evaluates a training program for OB VSI. Six trainees without previous formal ultrasound experience received a training program on the OB VSI protocol containing focused didactics and supervised live hands-on ultrasound scanning practice. Trainees then independently performed 194 OB VSI examinations on pregnancies &gt;14 weeks with known prenatal ultrasound abnormalities. Images were reviewed by maternal-fetal medicine specialists for the primary outcome (protocol deviation rates) and secondary outcomes (examination quality and image quality). Protocol deviation was present in 25.8% of cases, but only 7.7% of these errors affected the diagnostic potential of the ultrasound. Error rate differences between trainees ranged from 8.6% to 53.8% (P less then 0.0001). Image quality was excellent or acceptable in 88.2%, and 96.4% had image quality capable of yielding a diagnostic interpretation. The frequency of protocol deviations decreased over time in the majority of trainees, demonstrating retention of training program over time. This brief OB VSI training program for ultrasound-naive non-experts yielded operators capable of producing high-quality images capable of diagnostic interpretation after 3 hours of training. This training program could be adapted for use by local community members in low-resource/rural settings to increase access to obstetric ultrasound.Flavobacterium psychrophilum is the causative agent of bacterial cold-water disease (CWBD) and rainbow trout fry syndrome (RTFS), which affect salmonids. To better understand this pathogen and its interaction with the host during infection, including to support the development of resistant breeds and new vaccines and treatments, there is a pressing need for reliable and reproducible immersion challenge models that more closely mimic natural routes of infection. The aim of this present study was to evaluate a challenge model developed previously for rainbow trout for use in Atlantic salmon. First, preliminary challenges were conducted in Atlantic salmon (n = 120) and rainbow trout (n = 80) fry using two F. psychrophilum isolates collected from each fish species, respectively; fish had been pretreated with 200 mg/L hydrogen peroxide for 1 h. Thereafter, the main challenge was performed for just one F. psychrophilum isolate for each species (at 2 × 107  CFU/mL) but using larger cohorts (Atlantic salmon n = 1187; rainbow trout n = 2701). Survival in the main challenge was 81.2% in Atlantic salmon (21 days post-challenge) and 45.3% in rainbow trout (31 days post-challenge). Mortalities progressed similarly during the preliminary and main challenges for both species, demonstrating the reproducibility of this model. This is the first immersion challenge model of F. psychrophilum to be developed successfully for Atlantic salmon.Biophysical studies have established that the thyrotropin (TSH) receptor (TSHR) undergoes posttranslational modifications including dimerization. Following our earlier simulation of a TSHR-transmembrane domain (TMD) monomer (called TSHR-TMD-TRIO) we have now proceeded with a molecular dynamics simulation (MD) of TSHR-TMD dimerization using this improved membrane-embedded model. The starting structure was the TMD protein with all extracellular and intracellular loops and internal waters, which was placed in the relative orientation of the model originally generated with Brownian dynamics. Furthermore, this model was embedded in a DPPC lipid bilayer further solvated with water and added salt. Data from the MD simulation studies showed that the dimeric subunits stayed in the same relative orientation and distance during the 1000 ns of study. Comparison of representative conformations of the individual monomers when dimerized with the conformations from the monomer simulation showed subtle differences as represented by the backbone root mean square deviations. Differences in the conformations of the ligand-binding sites, suggesting variable affinities for these "hot spots," were also revealed by comparing the docking scores of 46 small-molecule ligands that included known TSHR agonists and antagonists as well as their derivatives. These data add further insight into the tendency of the TSHR-TMD to form dimeric and oligomeric structures and show that the differing conformations influence small-molecule binding sites within the TMD.Geographically distinct populations can adapt to the temperature conditions of their local environment, leading to temperature-dependent fitness differences between populations. Consistent with local adaptation, phylogeographically distinct Caenorhabditis briggsae nematodes show distinct fitness responses to temperature. The genetic mechanisms underlying local adaptation, however, remain unresolved. To investigate the potential role of small noncoding RNAs in genotype-specific responses to temperature, we quantified small RNA expression using high-throughput sequencing of C. briggsae nematodes from tropical and temperate strain genotypes reared under three temperature conditions (14 °C, 20 °C, and 30 C). Strains representing both tropical and temperate regions showed significantly lower expression of PIWI-interacting RNAs (piRNAs) at high temperatures, primarily mapping to a large ∼7 Mb long piRNA cluster on chromosome IV. We also documented decreased expression of 22G-RNAs antisense to protein-coding genes and other genomic features at high rearing temperatures for the thermally-intolerant temperate strain genotype, but not for the tropical strain genotype. Reduced 22G-RNA expression was widespread along chromosomes and among feature types, indicative of a genome-wide response. Targets of the EGO-1/CSR-1 22G-RNA pathway were most strongly impacted compared with other 22G-RNA pathways, implicating the CSR-1 Argonaute and its RNA-dependent RNA polymerase EGO-1 in the genotype-dependent modulation of C. briggsae 22G-RNAs under chronic thermal stress. Our work suggests that gene regulation via small RNAs may be an important contributor to the evolution of local adaptations.<br /><br /> Painful vertebral osteoporotic compression fractures (OCFs) are often treated with cement augmentation, although controversies exist as to whether or not this increases the secondary fracture risk. Prevention of secondary fracture includes treatment of underlying osteoporosis. The purposes of this study were to determine (1) whether cement augmentation increases the rate of secondary fracture compared with nonoperative management, (2) whether anti-osteoporotic medications reduce the rate of secondary fracture, and (3) the rate of osteoporosis treatment with medications following vertebral OCF.<br /><br /> The PearlDiver database was queried for all patients with a diagnosis of OCF from 2015 to 2019. Patients were excluded if they were &lt;50 years old, had a diagnosis of spinal neoplasm or infection, or underwent lumbar fusion in the perioperative period. Secondary fracture risk was assessed using univariate and multivariate logistic regression analysis, with kyphoplasty, vertebroplasty, anti-osteoporotic medications, age, gender, and Elixhauser Comorbidity Index as variables.