Neutrophilic dermatoses as a manifestation of a systemic lupus erythematosus flare.

Neutrophilic dermatoses (NDs) refer to a group of cutaneous conditions histologically characterized by the dense accumulation of neutrophils in the skin in the absence of infection. NDs have been associated with underlying autoimmune connective tissue disorders (CTDs) such as systemic lupus erythematosus (SLE), Sjogren's syndrome, and dermatomyositis. We describe a case of neutrophilic dermatoses as a manifestation of a SLE flare.

Periodontal ligament cells-derived exosomes promote osteoclast differentiation via modulating macrophage polarization.

Several studies have demonstrated that exosomes (Exos) are involved in the regulation of macrophage polarization and osteoclast differentiation. However, the characteristics as well as roles of exosomes from human periodontal ligament cells (hPDLCs-Exos) in M1/M2 macrophage polarization and osteoclast differentiation remain unclear. Here, periodontal ligament cells were successfully extracted by method of improved Type-I collagen enzyme digestion. hPDLCs-Exos were extracted by ultracentrifugation. hPDLCs-Exos were identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting (WB). Osteoclast differentiation was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR), WB and tartrate-resistant acid phosphatase (TRAP) staining. M1/M2 macrophage polarization were evaluated by RT-qPCR and WB. The results showed hPDLCs-Exos promoted osteoclast differentiation and M2 macrophage polarization, but inhibited M1 macrophage polarization. Moreover, M1 macrophages inhibited osteoclast differentiation, whereas M2 macrophages promoted osteoclast differentiation. It has shown that hPDLCs-Exos promoted osteoclast differentiation by inhibiting M1 and promoting M2 macrophage polarization.

The V-ATPase-ATG16L1 axis recruits LRRK2 to facilitate the lysosomal stress response.

Leucine-rich repeat kinase 2 (LRRK2), a Rab kinase associated with Parkinson's disease and several inflammatory diseases, has been shown to localize to stressed lysosomes and get activated to regulate lysosomal homeostasis. However, the mechanisms of LRRK2 recruitment and activation have not been well understood. Here, we found that the ATG8 conjugation system regulates the recruitment of LRRK2 as well as LC3 onto single membranes of stressed lysosomes/phagosomes. This recruitment did not require FIP200-containing autophagy initiation complex, nor did it occur on double-membrane autophagosomes, suggesting independence from canonical autophagy. Consistently, LRRK2 recruitment was regulated by the V-ATPase-ATG16L1 axis, which requires the WD40 domain of ATG16L1 and specifically mediates ATG8 lipidation on single membranes. This mechanism was also responsible for the lysosomal stress-induced activation of LRRK2 and the resultant regulation of lysosomal secretion and enlargement. These results indicate that the V-ATPase-ATG16L1 axis serves a novel non-autophagic role in the maintenance of lysosomal homeostasis by recruiting LRRK2.

Rapid High-Temperature Liquid Shock Synthesis of High-Entropy Alloys for Hydrogen Evolution Reaction.

High-entropy-alloy nanoparticles (HEA-NPs) show great potential as electrocatalysts for water splitting, fuel cells, CO2 conversion, etc. However, fine-tuning the surface, morphology, structure, and crystal phase of HEA remains a great challenge. Here, the high-temperature liquid shock (HTLS) technique is applied to produce HEA-NPs, e.g., PtCoNiRuIr HEA-NPs, with tunable elemental components, ultrafine particle size, controlled crystal phases, and lattice strains. HTLS directly applied Joule heating on the liquid mixture of metal precursors, capping agents, and reducing agents, which is feasible for controlling the morphology and structure such as the atomic arrangement of the resulting products, thereby facilitating the rationally designed nanocatalysts. Impressively, the as-obtained PtCoNiRuIr HEA-NPs delivered superior activity and long-term stability for the hydrogen evolution reaction (HER), with low overpotentials at 10 mA cm-2 and 1 A cm-2 of only 18 and 408 mV, respectively, and 10000 CV stable cycles in 0.5 M H2SO4. Furthermore, in the near future, by combining the HTLS method with artificial intelligence (AI) and theoretical calculations, it is promising to provide an advanced platform for the high-throughput synthesis of HEA nanocatalysts with optimized performance for various energy applications, which is of great significance for achieving a carbon-neutral society with an effective and environmentally friendly energy system.

Fine mapping of powdery mildew resistance gene PmXNM in a Chinese wheat landrace Xiaonanmai.

KEY MESSAGE: Powdery mildew resistance gene PmXNM, originated from the Chinese wheat landrace Xiaonanmai, was delimited to a 300.7-kb interval enriched with resistance genes. Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease threatening the yield and quality of wheat worldwide. The use of broad-spectrum disease resistance genes from wheat landraces is an effective strategy to prevent this pathogen. Chinese wheat landrace Xiaonanmai (XNM) was immune to 23 tested Bgt isolates at the seedling stage. The F1, F2, and F2:4 progenies derived from the cross between XNM and Chinese Spring (CS) were used in this study. Genetic analysis revealed that powdery mildew resistance in XNM was controlled by a single dominant gene, temporarily designated PmXNM. Bulked segregant analysis and molecular mapping delimited PmXNM to the distal terminal region of chromosome 4AL flanked by markers caps213923 and kasp511718. The region carrying the PmXNM locus was approximately 300.7 kb and contained nine high-confidence genes according to the reference genome sequence of CS. Five of these genes, annotated as disease resistance RPP13-like proteins 1, were clustered in the target region. Haplotype analysis using the candidate gene-specific markers indicated that the majority of 267 common wheat accessions (75.3%) exhibited extensive gene losses at the PmXNM locus, as confirmed by aligning the targeted genome sequences of CS with those of other sequenced wheat cultivars. Seven candidate gene-specific markers have proven effective for marker-assisted introgression of PmXNM into modern elite cultivars.

Novel amino-modified bamboo-derived biochar-supported nano-zero-valent iron (AMBBC-nZVI) composite for efficient Cr(VI) removal from aqueous solution.

Biochar-supported nano-zero-valent iron (BC-nZVI) composites have been extensively investigated for the treatment of Cr(VI)-containing wastewater. However, the inherent oxygen-containing groups with negative charges on BC exhibit electrostatic repulsion of the electronegative Cr(VI) species, limiting Cr(VI) removal. To overcome this limitation, this study prepared and used amino-modified bamboo-derived BC (AMBBC) as a supporting matrix to synthesize a novel AMBBC-nZVI composite. The amino groups (-NH2) on AMBBC were easily protonated and transformed into positively charged ions (-NH3+), which favored the attraction of Cr(VI) to AMBBC-nZVI, enhancing Cr(VI) removal. The experimental results demonstrated that the Cr(VI) removal efficiency of AMBBC-nZVI was 95.3%, and that of BBC-nZVI was 83.8% under the same conditions. The removal of Cr(VI) by AMBBC-nZVI followed the pseudo-second-order kinetic model and Langmuir isotherm model and was found to be a monolayer chemisorption process. Thermodynamic analysis revealed that the Cr(VI) removal process was spontaneous and endothermic. The mechanism analysis of Cr(VI) removal indicated that under an acidic condition, the -NH3+ groups on AMBBC adsorbed the electronegative Cr(VI) species via electrostatic interaction, promoting the attachment of Cr(VI) on AMBBC-nZVI; the adsorbed Cr(VI) was then reduced to Cr(III) by Fe0 and Fe(II), accompanied by the formation of Fe(III); moreover, AMBBC allowed the electron shuttle of nZVI to reduce Cr(VI); finally, the Cr(III) and Fe(III) species deposited on the surface of AMBBC-nZVI as Cr(III)-Fe(III) hydroxide coprecipitates.

Machine Learning-Assisted Low-Dimensional Electrocatalysts Design for Hydrogen Evolution Reaction.

Efficient electrocatalysts are crucial for hydrogen generation from electrolyzing water. Nevertheless, the conventional "trial and error" method for producing advanced electrocatalysts is not only cost-ineffective but also time-consuming and labor-intensive. Fortunately, the advancement of machine learning brings new opportunities for electrocatalysts discovery and design. By analyzing experimental and theoretical data, machine learning can effectively predict their hydrogen evolution reaction (HER) performance. This review summarizes recent developments in machine learning for low-dimensional electrocatalysts, including zero-dimension nanoparticles and nanoclusters, one-dimensional nanotubes and nanowires, two-dimensional nanosheets, as well as other electrocatalysts. In particular, the effects of descriptors and algorithms on screening low-dimensional electrocatalysts and investigating their HER performance are highlighted. Finally, the future directions and perspectives for machine learning in electrocatalysis are discussed, emphasizing the potential for machine learning to accelerate electrocatalyst discovery, optimize their performance, and provide new insights into electrocatalytic mechanisms. Overall, this work offers an in-depth understanding of the current state of machine learning in electrocatalysis and its potential for future research.

[Clinical and genetic characteristics of children with primary dilated cardiomyopathy]. / å„¿ç«¥åŽŸå‘æ€§æ‰©å¼ åž‹å¿ƒè‚Œç— çš„ä¸´åºŠç‰¹å¾åŠé—ä¼ å­¦åˆ†æž.

OBJECTIVES: To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM). METHODS: A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data. RESULTS: Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05). CONCLUSIONS: There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.

Cell Profiling of Acute Kidney Injury to Chronic Kidney Disease Reveals Novel Oxidative Stress Characteristics in the Failed Repair of Proximal Tubule Cells.

Chronic kidney disease (CKD) is a major public health issue around the world. A significant number of CKD patients originates from acute kidney injury (AKI) patients, namely "AKI-CKD". CKD is significantly related to the consequences of AKI. Damaged renal proximal tubular (PT) cell repair has been widely confirmed to indicate the renal prognosis of AKI. Oxidative stress is a key damage-associated factor and plays a significant role throughout the development of AKI and CKD. However, the relationships between AKI-CKD progression and oxidative stress are not totally clear and the underlying mechanisms in "AKI-CKD" remain indistinct. In this research, we constructed unilateral ischemia-reperfusion injury (UIRI)-model mice and performed single-nucleus RNA sequencing (snRNA-seq) of the kidney samples from UIRI and sham mice. We obtained our snRNA-seq data and validated the findings based on the joint analysis of public databases, as well as a series of fundamental experiments. Proximal tubular cells associated with failed repair express more complete senescence and oxidative stress characteristics compared to other subgroups. Furthermore, oxidative stress-related transcription factors, including Stat3 and Dnmt3a, are significantly more active under the circumstance of failed repair. What is more, we identified abnormally active intercellular communication between PT cells associated with failed repair and macrophages through the APP-CD74 pathway. More notably, we observed that the significantly increased expression of CD74 in hypoxia-treated TECs (tubular epithelial cells) was dependent on adjacently infiltrated macrophages, which was essential for the further deterioration of failed repair in PT cells. This research provides a novel understanding of the process of AKI to CKD progression, and the oxidative stress-related characteristics that we identified might represent a potentially novel therapeutic strategy against AKI.

A CA1 circuit motif that signals the start of information integration.

Integrating information from the recent past is critical for guiding predictions and shaping behavior. The process of integrating information, such as tracking distance traveled or time elapsed, begins with establishing a starting point. Yet, the mechanisms by which neural circuits utilize relevant cues to initiate integration remain unknown. Our study sheds light on this question by identifying a subpopulation of CA1 pyramidal neurons called PyrDown. These neurons shut down their activity at the beginning of distance or time integration and then gradually ramp up their firing as the animal approaches the reward. PyrDown neurons provide a mechanism for representing integrated information through ramping activity, complementing the well-known place/time cells that respond to specific distances or time points. Our findings also reveal that parvalbumin inhibitory interneurons mediate the shutdown of PyrDown neurons, uncovering a circuit motif that enables the initiation of subsequent information integration to improve future predictions.

Identification and Molecular Mechanism of Novel Immunomodulatory Peptides from Gelatin Hydrolysates: Molecular Docking, Dynamic Simulation, and Cell Experiments.

The purpose of this study was to identify donkey-hide gelatin-derived immunomodulatory peptides targeting Toll-like receptor 4-myeloid differentiation 2 (TLR4-MD2) and elucidate their binding modes using physicochemical property prediction, molecular docking, molecular dynamics simulations, and in vitro cell experiments. After hydrolyzing gelatin, 519 peptides were identified by liquid chromatography-tandem mass spectrometry. Peptides VQLSGEEK and GFSGLDGAKG bound to TLR4-MD2 with high binding affinity. In TLR4-MD2, Arg90, Ser118, Phe126, Tyr131, and Arg264 were key residues involved in the binding of these peptides. The RMSD and Rg values demonstrated that VQLSGEEK-TLR4-MD2 and GFSGLDGAKG-TLR4-MD2 complexes had stable and compact conformations. VQLSGEEK and GFSGLDGAKG were found to increase the cell viability and phagocytic activity of RAW264.7 macrophages; significantly promote the production of cytokines TNF-α, IL-1ß, and IL-6 in cells; and inhibit the overproduction of nitric oxide (NO) and cytokines in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results provided preliminary evidence that VQLSGEEK and GFSGLDGAKG could function as two-way immunomodulatory peptides with immunostimulatory and anti-inflammatory activities.

Characteristics and Species Diversity of Semi-Natural Plant Communities on Langqi Island.

(1) Background: Islands are relatively independent and fragile ecosystems with unique habitats. Studying the relatively stable semi-natural plant communities on islands can enrich island vegetation data and provide an understanding of the factors affecting species diversity and distribution. (2) Methods: The semi-natural plant communities on Langqi Island (LI) in Fujian Province were sampled, and the redundancy method was used to analyze the correlation between species diversity, community distribution, and environmental factors. (3) Results: (i) There were 432 species of vascular plants, with 306 genera and 110 families; (ii) the semi-natural plant communities consisted of three vegetation types, 10 formations, and 10 clusters; (iii) the species diversity indices of the semi-natural plant communities presented a trend of gradually decreasing along the shrub, tree, and herb layers. Different formations varied in terms of the species diversity index; and (iv) the soil total potassium and nitrogen contents significantly affected the species diversity of the LI semi-natural plant communities, whereas the pH, soil TN content, organic matter content, AK content, and altitude significantly affected the community distribution. (4) Conclusions: Selecting appropriate tree species for mixed forests based on plant characteristics and regional conditions, together with regulating the soil nutrient content, can improve the species diversity of semi-natural plant communities.

Control of infection by LC3-associated phagocytosis, CASM, and detection of raised vacuolar pH by the V-ATPase-ATG16L1 axis.

The delivery of pathogens to lysosomes for degradation provides an important defense against infection. Degradation is enhanced when LC3 is conjugated to endosomes and phagosomes containing pathogens to facilitate fusion with lysosomes. In phagocytic cells, TLR signaling and Rubicon activate LC3-associated phagocytosis (LAP) where stabilization of the NADPH oxidase leads to sustained ROS production and raised vacuolar pH. Raised pH triggers the assembly of the vacuolar ATPase on the vacuole membrane where it binds ATG16L1 to recruit the core LC3 conjugation complex (ATG16L1:ATG5-12). This V-ATPase-ATG16L1 axis is also activated in nonphagocytic cells to conjugate LC3 to endosomes containing extracellular microbes. Pathogens provide additional signals for recruitment of LC3 when they raise vacuolar pH with pore-forming toxins and proteins, phospholipases, or specialized secretion systems. Many microbes secrete virulence factors to inhibit ROS production and/or the V-ATPase-ATG16L1 axis to slow LC3 recruitment and avoid degradation in lysosomes.

Complete Genome Sequence of a Novel Lactobacillus paracasei TK1501 and Its Application in the Biosynthesis of Isoflavone Aglycones.

Lactobacillus strains are considered safe and healthy probiotics for manufacturing "natural food" products; this is due to their ability to produce bioactive compounds that reduce the incidence of various human diseases. Lactobacillus paracasei TK1501 is a novel probiotic strain isolated from naturally fermented congee; and can produce a high yield of genistein, one of the most widely studied isoflavone aglycones with plenty of physiological functions. To better understand the molecular basis of isoflavone aglycones biosynthesis, the complete 2,942,538 bp genome of L. paracasei TK1501 was sequenced and assembled; a group of genes that are involved in isoflavone aglycones production were identified. Of note, a ß-glucosidase was analyzed in the L. paracasei TK1501. Moreover, we also found that L. paracasei TK1501 could be used in soymilk fermentation; which would remarkably increase the contents of genistein, daidzein, and glycitein. This work was meaningful to the application of L. paracasei TK1501 and the molecular mechanism analysis of isoflavone aglycones biosynthesis in Lactobacillus strains.

Survival model database of human digestive system cells exposed to electroporation pulses: An in vitro and in silico study.

Background and objectives: This study aimed to establish a mathematical survival model database containing cell-specific coefficients from human digestive system cells exposed to electroporation pulses (EPs). Materials and methods: A total of 20 types of human digestive system cell lines were selected to investigate the effect of EPs on cell viability. Cell viability was measured after exposure to various pulse settings, and a cell survival model was established using the Peleg-Fermi model. Next, the cell-specific coefficients of each cell line were determined. Results: Cell viability tended to decrease when exposed to stronger electric field strength (EFS), longer pulse duration, and more pulse number, but the decreasing tendency varied among different cell lines. When exposed to a lower EFS (<1,000 V/cm), only a slight decrease in cell viability occurred. All cell lines showed a similar tendency: the extent of electrical injury (EI) increased with the increase in pulse number and duration. However, there existed differences in heat sensitivity among organs. Conclusions: This database can be used for the application of electroporation-based treatment (EBT) in the digestive system to predict cell survival and tissue injury distribution during the treatment.

Periodontal ligament fibroblasts-derived exosomes induced by PGE2 inhibit human periodontal ligament stem cells osteogenic differentiation via activating miR-34c-5p/SATB2/ERK.

Several studies have confirmed that exosomes containing microRNAs (miRNAs) from the aseptic inflammatory microenvironment play an important role in bone remodeling. But the mechanism that induces changes in the osteogenic ability of periodontal ligament stem cells (PDLSCs) is still unclear. In the present study, the osteogenic function of periodontal ligament fibroblasts-derived exosomes induced by PGE2 on PDLSCs was detected by real-time PCR, alizarin red assay and alkaline phosphatase staining. High-throughput miRNAs sequencing was used to reveal that miR-34c-5p in exosomes-PGE2 was upregulated compared it in exosomes-normal. Real-time PCR and western blotting assay verified that overexpression of miR-34c-5p inhibited osteogenic differentiation, and reduced phosphorylation of ERK1/2. In addition, dual-luciferase reporter assay revealed that miR-34c-5p targeted special AT-rich sequence-binding protein 2 (SATB2). It was shown that exosomal miR-34c-5p inhibited osteogenic differentiation of PDLSCs via SATB2/ERK pathway.

Distinct adverse outcomes and lipid profiles of erythrocytes upon single and combined exposure to cadmium and microplastics.

The growing accumulation of environmental microplastics (MPs) has become a global concern. MPs are capable to interact with other environmental contaminants leading to altered toxicity. Red blood cells (RBCs), are the target with highest priority for most of toxic xenobiotics after entering blood stream. Whether co-existence of MPs changes the toxicity of cadmium, a typical hemolysis inducer, in RBCs is unknown. We investigated the adverse effects of CdCl2 and Polystyrene-MPs (PS-MPs) on RBCs in mice. We found that CdCl2 induced mild microcytic hypochromic anemia while PS-MPs induced polycythemia vera, indicating distinct outcomes between them. Moreover, co-treatment of PS-MPs with CdCl2 did not change the phenotype of microcytic hypochromic anemia, indicating an antagonistic relationship between CdCl2 and PS-MPs. However, the lipid profiles were also distinct between single exposure and combined exposure to CdCl2 and PS-MPs. The significant changed lipids were mainly involved in altering the physiochemical or biological properties of RBCs, including decreased membrane components, disrupted bilayer thickness and intrinsic lipid curvature. These results indicated impaired membrane functions of RBCs. The altered lipid profiles observed in the current study may represent new and previously unrecognized harmful characteristics of cadmium and MPs on erythrocytes at low dose without apparent induction of anemia.

Clinical effectiveness of different types of bone-anchored maxillary protraction devices for skeletal Class III malocclusion: Systematic review and network meta-analysis.

Objective: This study aimed to estimate the clinical effects of different types of bone-anchored maxillary protraction devices by using a network meta-analysis. Methods: We searched seven databases for randomized and controlled clinical trials that compared bone-anchored maxillary protraction with tooth-anchored maxillary protraction interventions or untreated groups up to May 2021. After literature selection, data extraction, and quality assessment, we calculated the mean differences, 95% confidence intervals, and surface under the cumulative ranking scores of eleven indicators. Statistical analysis was performed using R statistical software with the GeMTC package based on the Bayesian framework. Results: Six interventions and 667 patients were involved in 18 studies. In comparison with the tooth-anchored groups, the bone-anchored groups showed significantly more increases in Sella-Nasion-Subspinale (°), Subspinale-Nasion-Supramentale(°) and significantly fewer increases in mandibular plane angle and the labial proclination angle of upper incisors. In comparison with the control group, Sella-Nasion-Supramentale(°) decreased without any statistical significance in all treated groups. IMPA (angle of lower incisors and mandibular plane) decreased in groups with facemasks and increased in other groups. Conclusions: Bone-anchored maxillary protraction can promote greater maxillary forward movement and correct the Class III intermaxillary relationship better, in addition to showing less clockwise rotation of mandible and labial proclination of upper incisors. However, strengthening anchorage could not inhibit mandibular growth better and the lingual inclination of lower incisors caused by the treatment is related to the use of a facemask.