Phase-Controlled Synthesis of Cu₂ZnSnS₄ Nanocrystals: The Role of Reactivity between Zn and S

Cu₂ZnSnS₄ (CZTS) nanocrystals with different morphologies and phases have been synthesized in hot organic solvents such as dodecanethiol and oleylamine. The crystallographic phases could be controlled by the sulfur precursor and the ligand species of the metal salts used for the synthesis. When a highly reactive sulfur precursor and metal acetates were used, wurtzite CZTS nanocrystals were obtained. On the other hand, using a low-reactivity sulfur precursor or metal chlorides produced CZTS nanocrystals in a kesterite phase. The experimental results from systematic investigations indicated that the reaction rate between Zn and S precursors played a determining role for the growth of CZTS nanocrystals with different crystalline phases. A relatively faster reaction between Zn and S precursors in comparison to the Sn–S reaction favored the formation of a metastable wurtzite phase, which could be accelerated by increasing the reactivity of the S precursor. This work provided a safe and economical way to synthesize high-quality phase-controlled Cu₂ZnSnS₄ nanocrystals, especially wurtzite nanorods, for potential photovoltaic applications. Moreover, preliminary results show that the proposed mechanism also applies to the phase-controlled synthesis of other quaternary Cu₂MSnS₄ (M = Cd²⁺, Mn²⁺) nanocrystals

Data_Sheet_1_Roles of CcDFR and CcOMT9 in the cyanidin biosynthesis and development of Cordyceps cicadae.docx

IntroductionCordyceps cicadae is a traditional Chinese medicinal fungus known for its rich production of bioactive substances, particularly cyanidin, an anthocyanin commonly found in plants with notable anti-inflammatory, anti-tumor, antiviral, and antibacterial properties. This study revealed two key genes, CcDFR and CcOMT9, affecting cyanidin biosynthesis in C. cicadae.MethodsThe roles of these genes in cyanidin production, growth, and development were elucidated through the gene knockout method, phenotypic analysis, transcriptomics, and metabolomics.ResultsCcDFR deletion led to reduced cyanidin-3-O-glucoside (C3G), suppressed expression of cyanidin biosynthesis genes, impaired synnemata formation, decreased polysaccharide and adenosine content, and diminished chitinase activity. Meanwhile, the ΔCcOMT9 mutant exhibited an increase in C3G production, promoted expression of cyanidin biosynthesis genes and rising bioactive compounds, suppressed RNA methylation, and led to phenylalanine accumulation with no effect on fruiting body formation.DiscussionWe revealed a distinct anthocyanin biosynthesis pathway in C. cicadae and identified two genes with opposite functions, laying the foundation for future genetic modification of cyanidin-producing strains using modern biological techniques. This will shorten the production period of this valuable compound, facilitating the industrial-scale production of cyanidin.</p

Data_Sheet_1_The prognostic value of ASPECTS in specific regions following mechanical thrombectomy in patients with acute ischemic stroke from large-vessel occlusion.XLSX

ObjectiveThe aim of this study is to investigate the relationship between the volume of specific regional infarction and the prognosis of patients who undergo mechanical thrombectomy (MT) for acute large vessel occlusion.MethodsIn this study, we collected the clinical and imaging features of patients with unilateral acute anterior circulation ischemic stroke from January 2021 to June 2023 in the Second Affiliated Hospital of Nanchang University. All patients underwent CT perfusion and non-contrast CT scan before MT. The ASPECTS was assessed based on imaging data, and artificial intelligence was used to obtain the percentage of infarction in each of the 10 regions of ASPECTS. According to the modified Rankin Scale, the patients were divided into the good prognosis group and poor prognosis group at the 90-day follow-up. Various indicators in the two groups were compared. Multivariable logistic regression was used to assess the risk factors for poor prognosis. The relationship between core infarction volume and the probability of poor prognosis was plotted to analyze the trend of poor prognosis with changes in the proportion of infarction volume. Finally, a receiver operating characteristic curve was constructed to analyze the predictive ability on poor prognosis.ResultsA total of 91 patients were included, with 58 patients having a good prognosis (mRS ≤ 2) and 33 patients having a poor prognosis (mRS ≥ 3). Multivariate analysis showed that NIHSS score and core infarction involving the internal capsule and M6 region were independent risk factors for poor prognosis. According to the linear correlation, a higher ratio of core infarction volume in the internal capsule or M6 region was linked to an increased risk of a poor prognosis. However, the non-linear analysis revealed that the prognostic impact of core infarction volume was significant when the ratio was greater than 69.7%. The ROC curve indicated that the combination of NIHSS score, infarct location, and the ratio of infarct volume has an AUC of 0.87, with a sensitivity of 84.8% and a specificity of 84.5%.ConclusionIt is important to examine the location and volume of the infarct in the internal capsule and M6 when deciding whether to do a MT.</p

Nanocrystalline High-Entropy Alloys: A New Paradigm in High-Temperature Strength and Stability

Metals with nanometer-scale grains or nanocrystalline metals exhibit high strengths at ambient conditions, yet their strengths substantially decrease with increasing temperature, rendering them unsuitable for usage at high temperatures. Here, we show that a nanocrystalline high-entropy alloy (HEA) retains an extraordinarily high yield strength over 5 GPa up to 600 °C, 1 order of magnitude higher than that of its coarse-grained form and 5 times higher than that of its single-crystalline equivalent. As a result, such nanostructured HEAs reveal strengthening figures of merit–normalized strength by the shear modulus above 1/50 and strength-to-density ratios above 0.4 MJ/kg, which are substantially higher than any previously reported values for nanocrystalline metals in the same homologous temperature range, as well as low strain-rate sensitivity of ∼0.005. Nanocrystalline HEAs with these properties represent a new class of nanomaterials for high-stress and high-temperature applications in aerospace, civilian infrastructure, and energy sectors

Data_Sheet_2_Roles of CcDFR and CcOMT9 in the cyanidin biosynthesis and development of Cordyceps cicadae.xlsx

IntroductionCordyceps cicadae is a traditional Chinese medicinal fungus known for its rich production of bioactive substances, particularly cyanidin, an anthocyanin commonly found in plants with notable anti-inflammatory, anti-tumor, antiviral, and antibacterial properties. This study revealed two key genes, CcDFR and CcOMT9, affecting cyanidin biosynthesis in C. cicadae.MethodsThe roles of these genes in cyanidin production, growth, and development were elucidated through the gene knockout method, phenotypic analysis, transcriptomics, and metabolomics.ResultsCcDFR deletion led to reduced cyanidin-3-O-glucoside (C3G), suppressed expression of cyanidin biosynthesis genes, impaired synnemata formation, decreased polysaccharide and adenosine content, and diminished chitinase activity. Meanwhile, the ΔCcOMT9 mutant exhibited an increase in C3G production, promoted expression of cyanidin biosynthesis genes and rising bioactive compounds, suppressed RNA methylation, and led to phenylalanine accumulation with no effect on fruiting body formation.DiscussionWe revealed a distinct anthocyanin biosynthesis pathway in C. cicadae and identified two genes with opposite functions, laying the foundation for future genetic modification of cyanidin-producing strains using modern biological techniques. This will shorten the production period of this valuable compound, facilitating the industrial-scale production of cyanidin.</p

Orcein-Related Small Molecule O4 Destabilizes hIAPP Protofibrils by Interacting Mostly with the Amyloidogenic Core Region

The accumulation of the human islet amyloid polypeptide (hIAPP) deposits in the pancreas is regarded as an important factor that leads to the depletion of islet β-cells and islet transplantation failure. In recent experiments, it was reported that a small organic molecule O4 inhibits the formation of hIAPP1-37 oligomers and fibrils. However, the interaction between O4 molecules and hIAPP oligomers is largely unknown on the atomic level. In this work, we studied the influence of O4 molecules on fibril-like hIAPP pentamer and decamer by performing atomistic molecular dynamics simulations. Our results show that O4 molecules mostly bind to the amyloid core region spanning residues 22NFGAI26 for both hIAPP pentamer and decamer, which leads to the local disruption of interpeptide β-sheets. The calculation of contact probability and binding energy indicates that the binding of O4 molecules is mostly driven by aromatic stacking and hydrophobic interactions. Our work reveals the detailed disruption mechanism of full-length hIAPP protofibrils by O4 molecules and may be helpful to the design of more efficient inhibitors against hIAPP aggregation

Human Neuronal Calcium Sensor‑1 Protein Avoids Histidine Residues To Decrease pH Sensitivity

pH is highly regulated in mammalian central nervous systems. Neuronal calcium sensor-1 (NCS-1) can interact with numerous target proteins. Compared to that in the NCS-1 protein of Caenorhabditis elegans, evolution has avoided the placement of histidine residues at positions 102 and 83 in the NCS-1 protein of humans and Xenopus laevis, possibly to decrease the conformational sensitivity to pH gradients in synaptic processes. We used all-atom molecular dynamics simulations to investigate the effects of amino acid substitutions between species on human NCS-1 by substituting Arg102 and Ser83 for histidine at neutral (R102H and S83H) and acidic pHs (R102H^p and S83H^p). Our cumulative 5 μs simulations revealed that the R102H mutation slightly increases the structural flexibility of loop L2 and the R102H^p mutation decreases protein stability. Community network analysis illustrates that the R102H and S83H mutations weaken the interdomain and strengthen the intradomain communications. Secondary structure contents in the S83H and S83H^p mutants are similar to those in the wild type, whereas the global structural stabilities and salt-bridge probabilities decrease. This study highlights the conformational dynamics effects of the R102H and S83H mutations on the local structural flexibility and global stability of NCS-1, whereas protonated histidine decreases the stability of NCS-1. Thus, histidines at positions 102 and 83 may not be compatible with the function of NCS-1 whether in the neutral or protonated state

R102Q Mutation Shifts the Salt-Bridge Network and Reduces the Structural Flexibility of Human Neuronal Calcium Sensor‑1 Protein

Neuronal calcium sensor-1 (NCS-1) protein has a variety of different neuronal functions and interacts with multiple binding partners mostly through a large solvent-exposed hydrophobic crevice (HC). A single R102Q mutation in human NCS-1 protein was demonstrated to be associated with autism disease. Solution NMR study reported that this R102Q mutant had long-range chemical shift effects on the HC and the C-terminal tail (L3). To understand the influence of the R102Q mutation on the HC and L3 of NCS-1, we have investigated the conformational dynamics and the structural flexibility of wild type (WT) NCS-1 and its R102Q mutant by conducting extensive all-atom molecular dynamics (MD) simulations. On the basis of six independent 450 ns MD simulations, we have found that the R102Q mutation in NCS-1 protein (1) dramatically reduces the flexibility of loops L2 and L3, (2) facilitates L3 in a more extended state to occupy the hydrophobic crevice to a larger extent, (3) significantly affects the intersegment salt bridges, and (4) changes the subspace of the free energy landscape of NCS-1 protein. Analysis of the salt bridge network in both WT and the R102Q variant demonstrates that the R102Q-mutation-induced salt bridge alternations play a critical role on the reduced flexibility of L2 and L3. These results reveal the important role of salt bridges on the structural properties of NCS-1 protein and that R102Q mutation disables the dynamic relocation of C-terminus, which may block the binding of NCS-1 protein to its receptors. This study may provide structural insights into the autistic spectrum disorder associated with R102Q mutation

Table_3_Gut microbiota in children with split-dose bowel preparations revealed by metagenomics.xls

ObjectiveSplit-dose polyethylene glycol (PEG) is routinely used for bowel preparation before colonoscopy. This study aimed to investigate the composition of gut microbiota and its functions in pediatric patients undergoing split-dose PEG bowel preparation for colonoscopy to understand the stability and resilience of gut microbiota.Material and methodsFrom September to December 2021, 19 pediatric patients were enrolled at Shenzhen Children’s Hospital and 76 samples (4 time points) were analyzed using metagenomics. Time points included Time_1 (one day before bowel preparation), Time_2 (one day after colonoscopy), Time_3 (two weeks after bowel preparation), and Time_4 (four weeks after bowel preparation).ResultAlpha diversity comparison at both the species and gene levels showed a decrease in community richness after colonoscopy, with little statistical significance. However, the Shannon diversity index significantly decreased (PConclusionsGut microbiota at the genus level, species level, and functional pathways are impacted in pediatric patients undergoing split-dose PEG bowel preparation and colonoscopy, with recovery two weeks following bowel preparation. However, the phylum level was not impacted. Modifications in gut microbiota composition and function may be investigated in future studies of bowel preparation. This study highlights the stability and resilience of gut microbiota among pediatric patients during bowel preparation.</p

Critical Nucleus Structure and Aggregation Mechanism of the C‑terminal Fragment of Copper–Zinc Superoxide Dismutase Protein

The aggregation of the copper–zinc superoxide dismutase (SOD1) protein is linked to familial amyotrophic lateral sclerosis, a progressive neurodegenerative disease. A recent experimental study has shown that the ¹⁴⁷GVIGIAQ¹⁵³ SOD1 C-terminal segment not only forms amyloid fibrils in isolation but also accelerates the aggregation of full-length SOD1, while substitution of isoleucine at site 149 by proline blocks its fibril formation. Amyloid formation is a nucleation–polymerization process. In this study, we investigated the oligomerization and the nucleus structure of this heptapeptide. By performing extensive replica-exchange molecular dynamics (REMD) simulations and conventional MD simulations, we found that the GVIGIAQ hexamers can adopt highly ordered bilayer β-sheets and β-barrels. In contrast, substitution of I149 by proline significantly reduces the β-sheet probability and results in the disappearance of bilayer β-sheet structures and the increase of disordered hexamers. We identified mixed parallel–antiparallel bilayer β-sheets in both REMD and conventional MD simulations and provided the conformational transition from the experimentally observed parallel bilayer sheets to the mixed parallel–antiparallel bilayer β-sheets. Our simulations suggest that the critical nucleus consists of six peptide chains and two additional peptide chains strongly stabilize this critical nucleus. The stabilized octamer is able to recruit additional random peptides into the β-sheet. Therefore, our simulations provide insights into the critical nucleus formation and the smallest stable nucleus of the ¹⁴⁷GVIGIAQ¹⁵³ peptide