A subfamily classification to choreograph the diverse activities within glycoside hydrolase family 31.

The Carbohydrate-Active Enzyme classification groups enzymes that breakdown, assemble, or decorate glycans into protein families based on sequence similarity. The glycoside hydrolases (GH) are arranged into over 170 enzyme families, with some being very large and exhibiting distinct activities/specificities towards diverse substrates. Family GH31 is a large family that contains more than 20,000 sequences with a wide taxonomic diversity. Less than 1% of GH31 members are biochemically characterized and exhibit many different activities that include glycosidases, lyases, and transglycosidases. This diversity of activities limits our ability to predict the activities and roles of GH31 family members in their host organism and our ability to exploit these enzymes for practical purposes. Here, we established a subfamily classification using sequence similarity networks that was further validated by a structural analysis. While sequence similarity networks provide a sequence-based separation, we obtained good segregation between activities among the subfamilies. Our subclassification consists of 20 subfamilies with sixteen subfamilies containing at least one characterized member and eleven subfamilies that are monofunctional based on the available data. We also report the biochemical characterization of a member of the large subfamily 2 (GH31_2) that lacked any characterized members: RaGH31 from Rhodoferax aquaticus is an α-glucosidase with activity on a range of disaccharides including sucrose, trehalose, maltose, and nigerose. Our subclassification provides improved predictive power for the vast majority of uncharacterized proteins in family GH31 and highlights the remaining sequence space that remains to be functionally explored.

Assembly and evaluation of a confocal microscopy image analysis pipeline useful in revealing the secrets of plant-fungal interactions.

The ability of laser scanning confocal microscopy to generate high-contrast 2D and 3D images has become essential in studying plant-fungal interactions. Techniques such as visualization of native fluorescence, fluorescent protein tagging of microbes, GFP/RFP-fusion proteins, and fluorescent labelling of plant and fungal proteins have been widely used to aid in these investigations. Use of fluorescent proteins has several pitfalls including variability of expression in planta and the requirement of gene transformation. Here we used the unlabeled pathogens Parastagonospora nodorum, Pyrenophora teres f. teres, and Cercospora beticola infecting wheat, barley, and sugar beet respectively, to show the utility of a staining and imaging pipeline that uses propidium iodide (PI), which stains RNA and DNA, and wheat germ agglutinin labeled with fluorescein isothiocyanate (WGA-FITC), which stains chitin, to visualize fungal colonization of plants. This pipeline relies on the use of KOH to remove the cutin layer of the leaf, increasing its permeability, allowing the different stains to penetrate and effectively bind to their targets, resulting in a consistent visualization of cellular structures. To expand the utility of this pipeline, we used the staining techniques in conjunction with machine learning to analyze fungal biomass through volume analysis, as well as quantifying nuclear breakdown, an early indicator of programmed cell death (PCD). This pipeline is simple to use, robust, consistent across host and fungal species and can be applied to most plant-fungal interactions. Therefore, this pipeline can be used to characterize model systems as well as non-model interactions where transformation is not routine.

Variability in Chromosome 1 of Select Moroccan Pyrenophora teres f. teres Isolates Overcomes a Highly Effective Barley Chromosome 6H Source of Resistance.

Barley net form net blotch (NFNB) is a destructive foliar disease caused by Pyrenophora teres f. teres. Barley line CIho5791, which harbors the broadly effective chromosome 6H resistance gene Rpt5, displays dominant resistance to P. teres f. teres. To genetically characterize P. teres f. teres avirulence/virulence on the barley line CIho5791, we generated a P. teres f. teres mapping population using a cross between the Moroccan CIho5791-virulent isolate MorSM40-3 and the avirulent reference isolate 0-1. Full genome sequences were generated for 103 progenies. Saturated chromosome-level genetic maps were generated, and quantitative trait locus (QTL) mapping identified two major QTL associated with P. teres f. teres avirulence/virulence on CIho5791. The most significant QTL mapped to chromosome (Ch) 1, where the virulent allele was contributed by MorSM40-3. A second QTL mapped to Ch8; however, this virulent allele was contributed by the avirulent parent 0-1. The Ch1 and Ch8 loci accounted for 27 and 15% of the disease variation, respectively, and the avirulent allele at the Ch1 locus was epistatic over the virulent allele at the Ch8 locus. As a validation, we used a natural P. teres f. teres population in a genome-wide association study that identified the same Ch1 and Ch8 loci. We then generated a new reference quality genome assembly of parental isolate MorSM40-3 with annotation supported by deep transcriptome sequencing of infection time points. The annotation identified candidate genes predicted to encode small, secreted proteins, one or more of which are likely responsible for overcoming the CIho5791 resistance. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 "No Rights Reserved" license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.

Tailoring Interfacial Electric Field by Gold Nanoparticles Enable Electrocatalytic Lithium Polysulfides Conversion for Lithium-Sulfur Batteries.

Although lithium-sulfur batteries (LSBs) are considered as the promising next rechargeable storage system ascribing to their decent specific capacity of inorganic sulfur, the development is partially impeded by inferior electronic conductivity, severe shuttle effect, and large volume variation. To tackle the issues above, a great deal of effort is made on sulfur-containing polymer (SCP) that shows better electrochemical performance. Nevertheless, sluggish conversion of lithium polysulfides (LiPSs) obstructs battery performance yet. Herein, electrocatalytic LiPSs with full conversion by tailoring the interfacial electric field are discovered based on gold nanoparticles (AuNPs) anchored on sulfurized polyaniline (SPANI). A downhill path of Gibbs free energy from organosulfur polymer to intermediate product means more spontaneously and favorable for full conversion, as the significant enhancement of electron density of state in the vicinity of the HOMO level for the AuNPs increase the electron transition probability rate. This composite delivers satisfactory electrochemical performance, especially increased rate capacity of >300 mAh g-1. Furthermore, catalyst mechanism on molecule level is proposed that AuNPsdominate chemical enhancement and higher electron delocalizablility betweenAuNPs and LiPSs molecules. These results can erect a promising strategy for enhancing lithium polysulfides full conversion.

Photoredox-catalysed radical difluoromethylation/cyclization of N-acryloyl-2-arylbenzimidazole to access CF2H-substituted benzimidazo[2,1-a]isoquinolin-6(5H)-ones.

An efficient visible-light-promoted cascade difluoromethylation/cyclization reaction to access various CF2H-substituted benzimidazo[2,1-a]isoquinolin-6(5H)-ones was developed using difluoromethyltriphenylphosphonium bromide salt as the precursor of the -CF2H group under mild conditions. This protocol utilized an easily accessible and inexpensive organophotocatalyst, offering the benefits of a broad substrate scope, good functional group tolerance, and good to excellent yields, in addition to a simple operational procedure. Furthermore, the reaction mechanism was subjected to investigation, and it was demonstrated that a radical pathway constitutes a single electron transfer (SET) procedure.

Reponses of morphological and biochemical traits of bamboo trees under elevated atmospheric O3 enrichment.

Dwarf bamboo (Indocalamus decorus) is an O3-tolerant plant species. To identify the possible mechanism and response of leaf morphological, antioxidant, and anatomical characteristics to elevated atmospheric O3 (EO3) concentrations, we exposed three-year-old I. decorus seedlings to three O3 levels (low O3-LO: ambient air; medium O3-MO: Ambient air+70 ppb high O3-HO: Ambient air+140 ppb O3) over a growing season using open-top chambers. Leaf shape and stomatal characteristics, and leaf microscopic structure of I. decorus were examined. The results indicated that 1) the stomata O3 flux (Fst) of HO decreased more rapidly under EO3 as the exposure time increased. The foliar O3 injury of HO and MO occurred when AOT40 was 26.62 ppm h and 33.20 ppm h, respectively, 2) under EO3, leaf number, leaf mass per area, leaf area, and stomata length/width all decreased, while leaf thickness, stomatal density, width, and area increased compared to the control, 3) MDA and total soluble protein contents all showed significantly increase under HO (36.57% and 32.77%) and MO(31.91% and 19.52%) while proline contents only increased under HO(33.27%). 4) MO and HO increased bulliform cells numbers in the leaves by 6.28% and 23.01%, respectively. HO reduced the transverse area of bulliform cells by 13.73%, while MO treatments had no effect, and 5) the number of fusoid cells interspace, the transverse area of fusoid cells interspace, and mesophyll thickness of HO significantly increased by 11.16%, 28.58%, and 13.42%, respectively. In conclusion, I. decorus exhibits strong O3 tolerance characteristics, which stem from adaptions in the leaf's morphological, structural, antioxidant, and anatomical features. One critical attribute was the enlargement of the bulliform cell transverse area and the transverse area of fusoid cells interspace that drove this resistance to O3. Local bamboo species with high resistance to O3 pollution thus need to be promoted for sustained productivity and ecosystem services in areas with high O3 pollution.

A Moroccan Pyrenophora teres f. teres Population Defeats Rpt5, the Broadly Effective Resistance on Barley Chromosome 6H.

Net form net blotch (NFNB), caused by Pyrenophora teres f. teres, is an important barley disease. The centromeric region of barley chromosome 6H has often been associated with resistance or susceptibility to NFNB, including the broadly effective dominant resistance gene Rpt5 derived from barley line CIho 5791. We characterized a population of Moroccan P. teres f. teres isolates that had overcome Rpt5 resistance and identified quantitative trait loci (QTL) that were effective against these isolates. Eight Moroccan P. teres f. teres isolates were phenotyped on barley lines CIho 5791 and Tifang. Six isolates were virulent on CIho 5791, and two were avirulent. A CIho 5791 × Tifang recombinant inbred line (RIL) population was phenotyped with all eight isolates and confirmed the defeat of the 6H resistance locus formerly mapped as Rpt5 in barley line CI9819. A major QTL on chromosome 3H with the resistance allele derived from Tifang, as well as minor QTL, was identified and provided resistance against these isolates. F2 segregation ratios supported dominant inheritance for both the 3H and 6H resistance. Furthermore, inoculation of progeny isolates derived from a cross of P. teres f. teres isolates 0-1 (virulent on Tifang/avirulent on CIho 5791) and MorSM 40-3 (avirulent on Tifang/virulent on CIho 5791) onto the RIL and F2 populations determined that recombination between isolates can generate novel genotypes that overcome both resistance genes. Markers linked to the QTL identified in this study can be used to incorporate both resistance loci into elite barley cultivars for durable resistance.

Exogenous 5-aminolevulinic acid enhanced saline-alkali tolerance in pepper seedlings by regulating photosynthesis, oxidative damage, and glutathione metabolism.

KEY MESSAGE: A plant growth regulator, 5-aminolevulinic acid, enhanced the saline-alkali tolerance via photosynthetic, oxidative-reduction, and glutathione metabolism pathways in pepper seedlings. Saline-alkali stress is a prominent environmental problem, hindering growth and development of pepper. 5-Aminolevulinic acid (ALA) application effectively improves plant growth status under various abiotic stresses. Here, we evaluated morphological, physiological, and transcriptomic differences in saline-alkali-stressed pepper seedlings after ALA application to explore the impact of ALA on saline-alkali stress. The results indicated that saline-alkali stress inhibited plant growth, decreased biomass and photosynthesis, altered the osmolyte content and antioxidant system, and increased reactive oxygen species (ROS) accumulation and proline content in pepper seedlings. Conversely, the application of exogenous ALA alleviated this damage by increasing the photosynthetic rate, osmolyte content, antioxidant enzyme activity, and antioxidants, including superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase, and reducing glutathione to reduce ROS accumulation and malonaldehyde content. Moreover, the transcriptomic analysis revealed the differentially expressed genes were mainly associated with photosynthesis, oxidation-reduction process, and glutathione metabolism in saline-alkali stress + ALA treatment compared to saline-alkali treatment. Among them, the change in expression level in CaGST, CaGR, and CaGPX was close to the variation of corresponding enzyme activity. Collectively, our findings revealed the alleviating effect of ALA on saline-alkali stress in pepper seedlings, broadening the application of ALA and providing a feasible strategy for utilize saline-alkali soil.

Sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary disease.

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

Construction and Application of Autonomy Theory of Rehabilitation Program for Bronchiectasis Patients.

Objective: The autonomy theory holds that the autonomy of individuals in the rehabilitation process is crucial to the success of rehabilitation. To explore the use of autonomous rehabilitation programs in patients with bronchiectasis, This study was conducted through the construction of a stable family rehabilitation program for bronchiectasis patients and the application of patients self-determination theory. To further explore the value of autonomy theory in rehabilitation therapy. Method: The experimental group used self-determination theory as the guide for intervention on the basis of the control groups. The two groups of observation indexes included St. George's Respiratory Questionnaire, FEV1 and FEV1 values, lung capacity, V25, V50, maximal ventilation, compliance questionnaire, anxiety self-assessment scale, and depression self-assessment scale. Results: (1) The lung capacity of the experimental group patients (3.01 ± 0.82) L was higher than that of the control group (2.86 ± 0.36) L, and the V25 value (2.63 ± 0.31) L/s, V50 value (4.31 ± 1.01) L/s, and maximum ventilation volume (71.63 ± 18.35) L/min were all higher than those of the control group, with P < .05; (2) After intervention, the SGRO score of patients in the experimental group (38.66 ± 8.67)score was lower than that of the control group (56.48 ± 9.86)score. The FEV1 score of patients in the experimental group (9.35 ± 2.36)L was higher than that of the control group (1.04 ± 0.29)L. After intervention, the FEV1 score of patients in the experimental group was% (56.83 ± 9.21)% higher than that of the control group (46.37 ± 7.67)%, with P < .05; (3) Comparison of compliance scores between two groups of patients before and after intervention: the experimental group had scores for timed medication (4.89 ± 0.64)score, moderate exercise (4.61 ± 1.04)score, and dietary regulation (4.72 ± 0.87)score after intervention, all of which were higher than those of the control group (P < .05); (4) The comparison of anxiety and depression between two groups of patients showed that the anxiety score (10.16 ± 3.03)score of the experimental group after intervention was lower than that of the control group (13.03 ± 3.67)score, and the depression score (9.35 ± 2.36)score of the experimental group after intervention was lower than that of the control group (12.34 ± 3.01)score, with P < .05. Conclusion: Using the theory of autonomy to construct and apply the rehabilitation program in the home stabilization stage of bronchiectasis patients can improve respiratory and lung function. At the same time, it has a certain degree of promoting effect on improving patients' treatment compliance, and can improve patients' emotional state and reduce the occurrence of anxiety and depression. The results of this study will provide a certain theoretical basis for the construction of the treatment and rehabilitation program of clinically related diseases. In the future clinical treatment, personalized treatment intervention can be carried out according to the autonomy of patients to improve the clinical prognosis.

Antibiofilm Efficacy and Mechanism of the Marine Chlorinated Indole Sesquiterpene Against Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) can easily form biofilms on food surfaces, thus leading to cross-contamination, which is difficult to remove. Therefore, there is an urgent need to find alternatives with good antibacterial and antibiofilm effects. In this study, two indole sesquiterpene compounds, xiamycin (1) and chlorinated metabolite chloroxiamycin (2), were isolated from the fermentation liquid of marine Streptomyces sp. NBU3429 for the first time. The chemical structures of the two compounds were characterized by spectroscopic data interpretation, including 1D NMR and HRESIMS analysis. Antimicrobial test showed that chloroxiamycin (2) (minimum inhibitory concentration, MIC = 16 µg/mL) exhibited superior antibacterial activity than xiamycin (1) (MIC = 32 µg/mL) against MRSA ATCC43300. Moreover, compound (2) decreased the biofilm formation rate of MRSA ATCC43300 by 12.7%-84.6% in the concentration range of 32-512 µg/mL, which is relatively stronger than xiamycin (1) (4.1%-49.9%) as well. Antibacterial/antibiofilm mechanism investigation indicated that chloroxiamycin (2) could disrupt the cell wall and membrane of MRSA, inhibiting the production of biofilm extracellular polysaccharides. All these results illustrated that chloroxiamycin (2) is an effective antibacterial/antibiofilm agent, which makes it an attractive candidate for food preservatives.

Effects of airflow superfine pulverization on the structure, functional properties, and flavor quality of wheat bran.

BACKGROUND: Wheat bran (WB) is a byproduct of refined wheat flour production with poor edible taste and low economic value. Herein, the WB was micronized via airflow superfine pulverization (ASP), and the effects of the ASP conditions on its particle size, nutritive compositions, whiteness, hydration characteristics, moisture distribution, microstructure, cation exchange capacity, volatile flavor components, and other characteristics were investigated. RESULTS: Reducing the rotational speed of the ASP screw and increasing the number of pulverizations significantly decreased the median particle size Dx(50) of WB to a minimum of 12.97 ± 0.19 µm (P < 0.05), increased the soluble dietary fiber content from 55.05 ± 2.94 to 106.86 ± 1.60 mg g-1, and improved the whiteness and water solubility index. In addition, the water holding capacity and oil holding capacity were significantly reduced (P < 0.05), while the cation exchange and swelling capacities first increased and then decreased. Up to about 70% of water in WB exists as bound water. As the Dx(50) of WB decreased, the content of bound and immobile water increased, while the free water decreased from 14.37 ± 1.21% to 7.59 ± 1.03%. Furthermore, WB was micronized and the particles became smaller and more evenly distributed. Using gas chromatography-ion mobility spectrometry, a total of 37 volatile compounds in micronized WB (including 10 aldehydes, 9 esters, 7 alcohols, and several acids, furans, ethers, aldehydes, esters, and alcohols) were identified as the main volatile compounds of WB. CONCLUSION: Collectively, ASP improved the physicochemical properties of WB. This study provides theoretical references for the use of ASP to improve the utilization and edibility of WB. © 2024 Society of Chemical Industry.

Association of Nogo-A Gene Polymorphisms with Cerebral Palsy in Southern China: A Case-Control Study.

Cerebral palsy (CP) is a motor and postural disorder syndrome caused by the nonprogressive dysfunction of the developing brain. Previous studies strongly indicated that the Nogo-A gene might be related to the pathogenesis of CP. The objective of this research was to explore the relationship between Nogo-A polymorphisms (rs1012603, rs12464595, and rs2864052) and CP in Southern China. The Hardy-Weinberg equilibrium (HWE) testing, allele and genotype frequencies analysis, and haplotype association analysis were applied to the genotyping of 592 CP children and 600 controls. The results showed that the allele and genotype frequencies of rs1012603 of CP group were significantly different from the control group. The haplotype "TTGGG" was significantly associated with an increased risk of CP. The allele frequencies of rs1012603 were significant differences between CP with spastic diplegia, female CP cases, and controls. Furthermore, significant differences in allele and genotype frequencies were also noticed between GMFCS I of CP and controls for rs1012603, and significant differences in allele and genotype frequencies were observed between the ADL (>9) of CP and controls for rs1012603 and rs12464595. This study showed that the SNPs rs1012603 of Nogo-A were significantly correlated with CP, and the correlations were also found in spastic diplegia, GMFCS I of CP, ADL (>9) of CP, and female subgroups, indicating that Nogo-A might mainly affect mild types of CP and there might be sex-related differences.

Species of associated bryophytes and their effects on the yield and quality of Dendrobium nobile.

BACKGROUND: Dendrobium nobile has unique growth environment requirements, and unstable yields and high management costs are the key factors restricting the development of its imitation wild cultivation industry. The present study explored the effects of different associated bryophyte species on the yield and quality of D. nobile to clarify the dominant bryophyte species associated with D. nobile and to provide a scientific basis for the rational cultivation and quality evaluation of D. nobile. RESULTS: The growth of D. nobile was closely related to the microenvironment of the Danxia stone, and the different associated bryophytes had different effects on D. nobile growth. There was a rich variety of bryophytes associated with D. nobile, with a total of 15 families, 24 genera and 31 species of bryophytes identified in the study area, including 13 families, 22 genera and 29 species of mosses and 2 families, 2 genera and 2 species of liverworts, and mosses predominated in the association with D. nobile. Usually, 3-9 species of bryophytes were growing in association with D. nobile, among which associations of 5-6 bryophytes species were more common, and the bryophytes associated with D. nobile were only related to the species to which they belonged. The dry matter accumulation, quality and mineral content of D. nobile differed significantly among different bryophyte species. The coefficients of variation of dry matter accumulation, dendrobine content and content of 11 mineral elements of D. nobile in the 35 sample quadrats were 25.00%, 21.08%, and 11.33-57.96%, respectively. The biomass, dendrobine content and mineral content of D. nobile were analysed by principal component analysis (PCA) and membership function. The results showed that each evaluation method initially screened Trachycystis microphylla and Leucobryum juniperoideum as the dominant associated bryophytes in the preliminary identification analysis, and the frequency of occurrence and coverage of the two bryophytes were significantly higher than those of the remaining bryophytes. It was determined that T. microphylla and L. juniperoideum were the dominant associated bryophytes. CONCLUSIONS: There is a rich variety of bryophytes associated with D. nobile. The yield and quality of D. nobile differed significantly among different bryophyte species. T. microphylla and L. juniperoideum were the dominant associated bryophytes, and were the two bryophytes associated with D. nobile through mixed growth.

SHFL inhibits enterovirus A71 infection by triggering degradation of viral 3Dpol protein via the ubiquitin-proteasome pathway.

Enterovirus A71 (EV-A71) is a highly contagious virus that poses a major threat to global health, representing the primary etiological agent for hand-foot and mouth disease (HFMD) and neurological complications. It has been established that interferon signaling is critical to establishing a robust antiviral state in host cells, mainly mediated through the antiviral effects of numerous interferon-stimulated genes (ISGs). The host restriction factor SHFL is a novel ISG with broad antiviral activity against various viruses through diverse underlying molecular mechanisms. Although SHFL is widely acknowledged for its broad-spectrum antiviral activity, it remains elusive whether SHFL inhibits EV-A71. In this work, we validated that EV-A71 triggers the upregulation of SHFL both in cell lines and in a mouse model. Knockdown and overexpression of SHFL in EVA71-infected cells suggested that this factor could markedly suppress EV-A71 replication. Our findings further revealed an intriguing mechanism of SHFL that it could interact with the nonstructural proteins 3Dpol of EV-A71 and promoted the degradation of 3Dpol through the ubiquitin-proteasome pathway. Furthermore, the zinc-finger domain and the 36 amino acids (164-199) of SHFL were crucial to the interaction between SHFL and EV-A71 3Dpol . Overall, these findings broadened our understanding of the pivotal roles of SHFL in the interaction between the host and EV-A71.

Structure optimization and discovery of novel compound for the treatment of insertion mutations within exon 20 of EGFR and HER2.

In previous decades, patients with the most active EGFR mutations in non-small cell lung cancer (NSCLC) have significantly benefited from EGFR tyrosine kinase inhibitors (TKIs). However, a minority with EGFR and HER2 exon 20 mutations are inherently resistant to treatment. Several molecular TKIs (such as TAK788 and Poziotinib) were recently discovered and demonstrated as effective inhibitors against the most prevalent HER2 or EGFR exon 20 mutations. However, low clinical efficiency and uncertain adverse reaction indicated that the development of effective therapies is still demanded. In the present work, we designed several hybrid compounds learning from 3D modeling of kinase structure. One lead compound (compound 56) was found to be the most potent compound with IC50 value of 0.027 nM against EGFR D770-N771 ins NPG and reduced binding affinity with hERG protein. In vitro and in vivo biological results suggested that compound 56 demonstrated good oral bioavailability, and it was significantly capable of inhibiting the growth of tumor cells with a variety of HER2 exon 20 mutations and EGFR mutants with negligible toxic effects. It was identified that compound 56 might be considered a potential drug candidate for NSCLC target therapy.

Adverse events after different forms of botulinum neurotoxin A injections in children with cerebral palsy: An 8-year retrospective study.

AIM: To compare the risks of adverse events 3 months after Onabotulinumtoxin-A and Lanbotulinumtoxin-A injections in children with cerebral palsy (CP) and to identify risk factors and associations. METHOD: A total of 1037 children (682 males, 355 females; mean age 5 years 2 months [SD 3 years]; age range 2 years-17 years 10 months) with CP underwent 1013 Onabotulinumtoxin-A injections and 418 Lanbotulinumtoxin-A injections from 2012 to 2021. Information was recorded in a purpose-built database. RESULTS: The adverse event rates of Onabotulinumtoxin-A and Lanbotulinumtoxin-A were reported as 13.92% and 11.96% respectively. Most adverse events were mild and self-limiting. Children in Gross Motor Function Classification System (GMFCS) levels IV to V had a higher risk of adverse events than those in GMFCS levels I to III (odds ratio [OR] [95% confidence interval {CI}] = 3.65 [1.56, 5.40], p < 0.01). The history of recent illness and higher dose increased the likelihood of adverse events (OR [95% CI] = 2.00 [1.55, 3.00] and 2.20 [1.53, 3.07] respectively, p < 0.01). Sex, age, and the number of injections had no significant effect on adverse event rates (p > 0.05). The incidence of upper respiratory tract infection and lower respiratory tract infection after injections was weakly correlated with the incidence before injections (r = 0.36 and r = 0.27 respectively, p < 0.01). INTERPRETATION: Occurrence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with CP. Dose, GMFCS level, and health background were risk factors. WHAT THIS PAPER ADDS: The prevalence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with cerebral palsy (CP). The prevalence of adverse events increased with the severity of CP and the injected dose. Sex, age, and number of injections had no significant effect on the prevalence of adverse events.

Association of serum oleic acid level with depression in American adults: a cross-sectional study.

BACKGROUND: As the most abundant fatty acid in plasma, oleic acid has been found to be associated with multiple neurological diseases; however, results from studies of the relationship between oleic acid and depression are inconsistent. METHODS: This cross-sectional study analyzed 4,459 adults from the National Health and Nutrition Examination Survey 2011-2014. The following covariates were adjusted in multivariable logistic regression models: age, sex, race/ethnicity, education level, marital status, body mass index, physical activity, smoking status, alcohol status, metabolic syndrome, omega-3 polyunsaturated fatty acids, and total cholesterol. RESULTS: Serum oleic acid levels were positively associated with depression. After adjusting for all covariates, for every 1 mmol/L increase in oleic acid levels, the prevalence of depression increased by 40% (unadjusted OR: 1.35, 95%CI: 1.16-1.57; adjusted OR: 1.40, 95% CI: 1.03-1.90). CONCLUSIONS: Our study suggests that oleic acid may play a role in depression. Further research is needed to investigate the potential benefits of changing oleic acid levels for the treatment and prevention of depression.

Whole-Transcriptome Sequencing Reveals a ceRNA Regulatory Network Associated with the Process of Periodic Albinism under Low Temperature in Baiye No. 1 (Camellia sinensis).

The young shoots of the tea plant Baiye No. 1 display an albino phenotype in the early spring under low environmental temperatures, and the leaves re-green like those of common tea cultivars during the warm season. Periodic albinism is precisely regulated by a complex gene network that leads to metabolic differences and enhances the nutritional value of tea leaves. Here, we identified messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) to construct competing endogenous RNA (ceRNA) regulatory networks. We performed whole-transcriptome sequencing of 12 samples from four periods (Bud, leaves not expanded; Alb, albino leaves; Med, re-greening leaves; and Gre, green leaves) and identified a total of 6325 differentially expressed mRNAs (DEmRNAs), 667 differentially expressed miRNAs (DEmiRNAs), 1702 differentially expressed lncRNAs (DElncRNAs), and 122 differentially expressed circRNAs (DEcircRNAs). Furthermore, we constructed ceRNA networks on the basis of co-differential expression analyses which comprised 112, 35, 38, and 15 DEmRNAs, DEmiRNAs, DElncRNAs, and DEcircRNAs, respectively. Based on the regulatory networks, we identified important genes and their interactions with lncRNAs, circRNAs, and miRNAs during periodic albinism, including the ceRNA regulatory network centered on miR5021x, the GAMYB-miR159-lncRNA regulatory network, and the NAC035-miR319x-circRNA regulatory network. These regulatory networks might be involved in the response to cold stress, photosynthesis, chlorophyll synthesis, amino acid synthesis, and flavonoid accumulation. Our findings provide novel insights into ceRNA regulatory mechanisms involved in Baiye No. 1 during periodic albinism and will aid future studies of the molecular mechanisms underlying albinism mutants.

Study on Extraction Valuable Metal Elements by Co-Roasting Coal Gangue with Coal Gasification Coarse Slag.

Coal gangue (CG) and coal gasification coarse slag (CGCS) possess both hazardous and resourceful attributes. The present study employed co-roasting followed by H2SO4 leaching to extract Al and Fe from CG and CGCS. The activation behavior and phase transformation mechanism during the co-roasting process were investigated through TG, XRD, FTIR, and XPS characterization analysis as well as Gibbs free energy calculation. The results demonstrate that the leaching rate of total iron (TFe) reached 79.93%, and Al3+ achieved 43.78% under the optimized experimental conditions (co-roasting process: CG/CGCS mass ratio of 8/2, 600 °C, 1 h; H2SO4 leaching process: 30 wt% H2SO4, 90 °C, 5 h, liquid to solid ratio of 5:1 mL/g). Co-roasting induced the conversion of inert kaolinite to active metakaolinite, subsequently leading to the formation of sillimanite (Al2SiO5) and hercynite (FeAl2O4). The iron phases underwent a selective transformation in the following sequence: hematite (Fe2O3) → magnetite (Fe3O4) → wustite (FeO) → ferrosilite (FeSiO3), hercynite (FeAl2O4), and fayalite (Fe2SiO4). Furthermore, we found that acid solution and leached residue both have broad application prospects. This study highlights the significant potential of co-roasting CG and CGCS for high-value utilization.