Cdon is essential for organ left-right patterning by regulating dorsal forerunner cells clustering and Kupffer's vesicle morphogenesis.

Cdon and boc are members of the cell adhesion molecule subfamily III Ig/fibronectin. Although they have been reported to be involved in muscle and neural development at late developmental stage, their early roles in embryonic development remain unknown. Here, we discovered that in zebrafish, cdon, but not boc, is expressed in dorsal forerunner cells (DFCs) and the epithelium of Kupffer's vesicle (KV), suggesting a potential role for cdon in organ left-right (LR) patterning. Further data showed that liver and heart LR patterning were disrupted in cdon morphants and cdon mutants. Mechanistically, we found that loss of cdon function led to defect in DFCs clustering, reduced KV lumen, and defective cilia, resulting in randomized Nodal/spaw signaling and subsequent organ LR patterning defects. Additionally, predominant distribution of a cdon morpholino (MO) in DFCs caused defects in DFC clustering, KV morphogenesis, cilia number/length, Nodal/spaw signaling, and organ LR asymmetry, similar to those observed in cdon morphants and cdon -/- embryos, indicating a cell-autonomous role for cdon in regulating KV formation during LR patterning. In conclusion, our data demonstrate that during gastrulation and early somitogenesis, cdon is essential for proper DFC clustering, KV formation, and normal cilia, thereby playing a critical role in establishing organ LR asymmetry.

Cxcr4a regulates heart progenitor development and cardiac rhythm in zebrafish.

Cxcr4a is involved in multiple organ development including coronary vasculature formation and heart left-right (LR) patterning, whether it is involved in heart progenitor determination and cardiac rhythm regulation is not addressed. Here we showed that in cxcr4a mutants, from 2 days post fertilization (dpf) to 4dpf the embryos transiently displayed pericardial edema and increased cardiac rhythm. While from 5dpf, the heart phenotype disappeared. Detailed analysis demonstrated that, at 36hpf and 48hpf, even though there was no distinct difference in the heart size between cxcr4a mutants and controls, the expression of myl7 was decreased. Further data showed that, the heart progenitors were decreased at 18SS(Somite Stage). Mechanically, RNA-seq, RT-qPCR and in situ experiments showed that the retinoic acid (RA) signaling was upregulated, and the up-regulation of RA signaling may mediate the role of cxcr4a in regulating heart progenitor development. In addition, we also identified that low dose of RA treatment accelerated the cardiac rhythm, being similar to that in cxcr4a mutants. Decreasing RA signaling partially restored the rapid cardiac rhythm in cxcr4a mutants, implying the possibility that RA signaling partially mediates the role of cxcr4a in regulating cardiac rhythm. In conclusion, our study identified cxcr4a simultaneously regulates heart progenitor determination and cardiac rhythm.

On the fluid drag reduction in scallop surface.

In the field of biomimetics, the tiny riblet structures inspired by shark skin have been extensively studied for their drag reduction properties in turbulent flows. Here, we show that the ridged surface texture of another swimming creature in the ocean, i.e., the scallops, also has some friction drag reduction effect. In this study, we investigated the potential drag reduction effects of scallop shell textures using computational fluid dynamics simulations. Specifically, we constructed a conceptual model featuring an undulating surface pattern on a conical shell geometry that mimics scallop. Simulations modeled turbulent fluid flows over the model inserted at different orientations relative to the flow direction. The results demonstrate appreciable friction drag reduction generated by the ribbed hierarchical structures encasing the scallop, while partial pressure drag reduction exhibits dependence on alignment of scallop to the predominant flow direction. Theoretical mechanisms based on classic drag reduction theory in turbulence was established to explain the drag reduction phenomena. Given the analogous working environments of scallops and seafaring vessels, these findings may shed light on the biomimetic design of surface textures to enhance maritime engineering applications. Besides, this work elucidates an additional evolutionary example of fluid drag reduction, expanding the biological repertoire of swimming species.

A Multifunctional Dye Molecule as the Interfacial Layer for Perovskite Solar Cells.

In perovskite solar cells (PSCs), defects in the interface and mismatched energy levels can damage the device performance. Improving the interface quality is an effective way to achieve efficient and stable PSCs. In this work, a multifunctional dye molecule, named ThPCyAc, was designed and synthesized to be introduced in the perovskite/HTM interface. On one hand, various functional groups on the acceptor unit can act as Lewis base to reduce defect density and suppress nonradiative combinations. On the other hand, the stepwise energy-level alignment caused by ThPCyAc decreases the accumulation of interface carriers for facilitating charge extraction and transmission. Therefore, based on the ThPCyAc molecule, the devices exhibit elevated open-circuit voltage and fill factor, resulting in the best power conversion efficiency (PCE) of 23.16%, outperforming the control sample lacking the interface layer (PCE = 21.49%). Excitingly, when attempting to apply it as a self-assembled layer in inverted devices, ThPCyAc still exhibits attractive behavior. It is worth noting that these results indicate that dye molecules have great potential in developing multifunctional interface materials to obtain higher-performance PSCs.

Dopant-Free Pyrene-Based Hole Transporting Material Enables Efficient and Stable Perovskite Solar Cells.

Dopant-free hole transporting materials (HTMs) is significant to the stability of perovskite solar cells (PSCs). Here, we developed a novel star-shape arylamine HTM, termed Py-DB, with a pyrene core and carbon-carbon double bonds as the bridge units. Compared to the reference HTM (termed Py-C), the extension of the planar conjugation backbone endows Py-DB with typical intermolecular π-π stacking interactions and excellent solubility, resulting in improved hole mobility and film morphology. In addition, the lower HOMO energy level of the Py-DB HTM provides efficient hole extraction with reduced energy loss at the perovskite/HTM interface. Consequently, an impressive power conversion efficiency (PCE) of 24.33 % was achieved for dopant-free Py-DB-based PSCs, which is the highest PCE for dopant-free small molecular HTMs in n-i-p configured PSCs. The dopant-free Py-DB-based device also exhibits improved long-term stability, retaining over 90 % of its initial efficiency after 1000 h exposure to 25 % humidity at 60 °C. These findings provide valuable insights and approaches for the further development of dopant-free HTMs for efficient and reliable PSCs.

High-Speed and Ultrasensitive Solar-Blind Ultraviolet Photodetectors Based on In Situ Grown ß-Ga2O3 Single-Crystal Films.

Deep-level defects in ß-Ga2O3 that worsen the response speed and dark current (Id) of photodetectors (PDs) have been a long-standing issue for its application. Herein, an in situ grown single-crystal Ga2O3 nanoparticle seed layer (NPSL) was used to shorten the response time and reduce the Id of metal-semiconductor-metal (MSM) PDs. With the NPSL, the Id was reduced by 4 magnitudes from 0.389 µA to 81.03 pA, and the decay time (τd1/τd2) decreased from 258/1690 to 62/142 µs at -5 V. In addition, the PDs with the NPSL also exhibit a high responsivity (43.5 A W-1), high specific detectivity (2.81 × 1014 Jones), and large linear dynamic range (61 dB) under 254 nm illumination. The mechanism behind the performance improvement can be attributed to the suppression of the deep-level defects (i.e., self-trapped holes) and increase of the Schottky barrier. The barrier height extracted is increased by 0.18 eV compared with the case without the NPSL. Our work contributes to understanding the relationship between defects and the performance of PDs based on heteroepitaxial ß-Ga2O3 thin films and provides an important reference for the development of high-speed and ultrasensitive deep ultraviolet PDs.

Protective effect of San Huang Pill and its bioactive compounds against ulcerative colitis in Drosophila via modulation of JAK/STAT, apoptosis, Toll, and Nrf2/Keap1 pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: San Huang Pill (SHP) is a prescription in Dunhuang Ancient Medical Prescription, which has the efficacy of heat-clearing and dampness-drying, and is a traditional formula for the treatment of gastrointestinal diseases. However, its efficacy and mechanism in treating ulcerative colitis (UC) are still unclear. AIM OF THE STUDY: To investigate the protective effects of SHP and its bioactive compounds against Dextran Sulfate Sodium (DSS)-induced intestinal damage using the Drosophila melanogaster model, and to detect the molecular mechanism of SHP in the treatment of UC. METHODS: Survival rate, locomotion, feeding, and excretion were used to explore the anti-inflammatory effects of SHP. The pharmacotoxicity of SHP was measured using developmental analysis. Intestinal integrity, intestinal length, intestinal acid-base homeostasis, and Tepan blue assay were used to analyze the protective effect of SHP against DSS-induced intestinal damage. The molecular mechanism of SHP was detected using DHE staining, immunofluorescence, real-time PCR, 16 S rRNA gene sequencing, and network pharmacology analysis. Survival rate, intestinal length, and integrity analysis were used to detect the protective effect of bioactive compounds of SHP against intestinal damage. RESULTS: SHP supplementation significantly increased the survival rate, restored locomotion, increased metabolic rate, maintained intestinal morphological integrity and intestinal homeostasis, protected intestinal epithelial cells, and alleviated intestinal oxidative damage in adult flies under DSS stimulation. Besides, administration of SHP had no toxic effect on flies. Moreover, SHP supplementation remarkably decreased the expression levels of genes related to JAK/STAT, apoptosis, and Toll signaling pathways, increased the gene expressions of the Nrf2/Keap1 pathway, and also reduced the relative abundance of harmful bacteria in DSS-treated flies. Additionally, the ingredients in SHP (palmatine, berberine, baicalein, wogonin, rhein, and aloeemodin) had protection against DSS-induced intestinal injury, such as prolonging survival rate, increasing intestinal length, and maintaining intestinal barrier integrity. CONCLUSION: SHP had a strong anti-inflammatory function, and remarkably alleviated DSS-induced intestinal morphological damage and intestinal homeostatic imbalance in adult flies by regulating JAK/STAT, apoptosis, Toll and Nrf2/Keap1 signaling pathways, and also gut microbial homeostasis. This suggests that SHP may be a potential complementary and alternative medicine herb therapy for UC, which provides a basis for modern pharmacodynamic evaluation of other prescriptions in Dunhuang ancient medical prescription.

Natural products targeting Nrf2/ARE signaling pathway in the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a special chronic intestinal inflammatory disease, which is mainly divided into Crohn's disease (CD) and ulcerative colitis (UC). Its occurrence is a complex process that regulated by multiple signaling pathways, including nuclear factor erythroid 2-related factor (Nrf2)/ antioxidant response element (ARE) signaling pathway. Nrf2/ARE pathway as the central defense mechanism against oxidative stress controls the expression of many antioxidant and anti-inflammatory genes in the nucleus, and plays a crucial role in the treatment of IBD. Various studies have proved that many natural compounds target Nrf2/ARE signaling pathway to treat IBD. Here, we introduced the regulatory mechanism of the Nrf2/ARE pathway, and its role in IBD and IBD complications (intestinal fibrosis and colorectal cancer (CRC)); summarized the research progress of Nrf2 targeted natural compounds and extracts in the treatment of IBD; and finally described the intestinal microbiota that alleviate or treat IBD via activating Nrf2/ARE signaling pathway. This review highlights the potential for targeting Nrf2/ARE pathway to treat IBD.

Using Drosophila melanogaster as a suitable platform for drug discovery from natural products in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic and life-treating inflammatory disease that can occur in multiple parts of the human intestine and has become a worldwide problem with a continually increasing incidence. Because of its mild early symptoms, most of them will not attract people's attention and may cause more serious consequences. There is an urgent need for new therapeutics to prevent disease progression. Natural products have a variety of active ingredients, diverse biological activities, and low toxicity or side effects, which are the new options for preventing and treating the intestinal inflammatory diseases. Because of multiple genetic models, less ethical concerns, conserved signaling pathways with mammals, and low maintenance costs, the fruit fly Drosophila melanogaster has become a suitable model for studying mechanism and treatment strategy of IBD. Here, we review the advantages of fly model as screening platform in drug discovery, describe the conserved molecular pathways as therapetic targets for IBD between mammals and flies, dissect the feasibility of Drosophila model in IBD research, and summarize the natural products for IBD treatment using flies. This review comprehensively elaborates that the benefit of flies as a perfact model to evaluate the therapeutic potential of phytochemicals against IBD.

Corrigendum: Drosophila as a model to study the mechanism of nociception.

[This corrects the article DOI: 10.3389/fphys.2022.854124.].

Drosophila as a Model to Study the Mechanism of Nociception.

Nociception refers to the process of encoding and processing noxious stimuli, which allow animals to detect and avoid potentially harmful stimuli. Several types of stimuli can trigger nociceptive sensory transduction, including thermal, noxious chemicals, and harsh mechanical stimulation that depend on the corresponding nociceptors. In view of the high evolutionary conservation of the mechanisms that govern nociception from Drosophila melanogaster to mammals, investigation in the fruit fly Drosophila help us understand how the sensory nervous system works and what happen in nociception. Here, we present an overview of currently identified conserved genetics of nociception, the nociceptive sensory neurons responsible for detecting noxious stimuli, and various assays for evaluating different nociception. Finally, we cover development of anti-pain drug using fly model. These comparisons illustrate the value of using Drosophila as model for uncovering nociception mechanisms, which are essential for identifying new treatment goals and developing novel analgesics that are applicable to human health.

Lactobacillus rhamnosus GR-1 Alleviates Escherichia coli-Induced Inflammation via NF-κB and MAPKs Signaling in Bovine Endometrial Epithelial Cells.

Escherichia coli counts as a major endometritis-causing pathogen among dairy cows, which lowered the economic benefits of dairy farming seriously. Probiotic consumption has been reported to impart beneficial effects on immunomodulation. However, the inflammatory regulation mechanism of probiotics on endometritis in dairy cows remains unexplored. The current work aimed to clarify the mechanism whereby Lactobacillus rhamnosus GR-1 (L. rhamnosus GR-1) resists bovine endometrial epithelial cells (BEECs) inflammatory injury induced by E. coli. The model of cellular inflammatory injury was established in the BEECs, which comes from the uterus of healthy dairy cows using E. coli. The outcome of L. rhamnosus GR-1 addition on inflammation was evaluated in BEECs with E. coli-induced endometritis. The underlying mechanisms of anti-inflammation by L. rhamnosus GR-1 were further explored in E. coli-stimulated BEECs. In accordance with the obtained results, the use L. rhamnosus GR-1 alone could not cause the change of inflammatory factors, while L. rhamnosus GR-1 could significantly alleviate the expression of E. coli-induced inflammatory factors. Based on further study, L. rhamnosus GR-1 significantly hindered the TLR4 and MyD88 expression stimulated by E. coli. Moreover, we observed that in BEECs, L. rhamnosus GR-1 could inhibit the E. coli-elicited expressions of pathway proteins that are associated with NF-κB and MAPKs. Briefly, L. rhamnosus GR-1 can effectively protect against E. coli-induced inflammatory response that may be closely related to the inhibition of TLR4 and MyD88 stimulating NF-κB and MAPKs.

Hierarchical Flexible Peptide Docking by Conformer Generation and Ensemble Docking of Peptides.

Given the importance of peptide-mediated protein interactions in cellular processes, protein-peptide docking has received increasing attention. Here, we have developed a Hierarchical flexible Peptide Docking approach through fast generation and ensemble docking of peptide conformations, which is referred to as HPepDock. Tested on the LEADS-PEP benchmark data set of 53 diverse complexes with peptides of 3-12 residues, HPepDock performed significantly better than the 11 docking protocols of five small-molecule docking programs (DOCK, AutoDock, AutoDock Vina, Surflex, and GOLD) in predicting near-native binding conformations. HPepDock was also evaluated on the 19 bound/unbound and 10 unbound/unbound protein-peptide complexes of the Glide SP-PEP benchmark and showed an overall better performance than Glide SP-PEP+MM-GBSA and FlexPepDock in both bound and unbound docking. HPepDock is computationally efficient, and the average running time for docking a peptide is ∼15 min with the range from about 1 min for short peptides to around 40 min for long peptides.

HDOCK: a web server for protein-protein and protein-DNA/RNA docking based on a hybrid strategy.

Protein-protein and protein-DNA/RNA interactions play a fundamental role in a variety of biological processes. Determining the complex structures of these interactions is valuable, in which molecular docking has played an important role. To automatically make use of the binding information from the PDB in docking, here we have presented HDOCK, a novel web server of our hybrid docking algorithm of template-based modeling and free docking, in which cases with misleading templates can be rescued by the free docking protocol. The server supports protein-protein and protein-DNA/RNA docking and accepts both sequence and structure inputs for proteins. The docking process is fast and consumes about 10-20 min for a docking run. Tested on the cases with weakly homologous complexes of <30% sequence identity from five docking benchmarks, the HDOCK pipeline tied with template-based modeling on the protein-protein and protein-DNA benchmarks and performed better than template-based modeling on the three protein-RNA benchmarks when the top 10 predictions were considered. The performance of HDOCK became better when more predictions were considered. Combining the results of HDOCK and template-based modeling by ranking first of the template-based model further improved the predictive power of the server. The HDOCK web server is available at http://hdock.phys.hust.edu.cn/.

[Repair of deep wound on the head due to high-voltage electrical burn].

OBJECTIVE: To explore the methods for repairing deep wound on the head due to high-voltage electrical burn (HEB). METHODS: Twenty-six patients with deep wounds on the head due to HEB were hospitalized from June 2002 to May 2012. They were all injured by high-voltage (voltage ranged from 380 V to 300 kV) electric current, involving head and several other parts over the body. The total burn area ranged from 1% to 75% TBSA, and the depth ranged from deep partial-thickness to full-thickness (including muscle or even bone). Scalp defect area ranged from 3 cm×2 cm to 20 cm×18 cm, and the maximum size of skull exposure was 12 cm×9 cm and the maximum size of skull defect was 7 cm×6 cm. The wounds of 26 patients were repaired with 7 local advance flaps, 4 bilateral rotation flaps, 18 local rotation flaps combined with thin split-thickness skin grafts in donor site, and 3 free anterolateral thigh flaps with vascular anastomosis. In four of the 26 patients, expander was used in the early stage after burn and 5 after wound healing (with thin split-thickness grafts). RESULTS: All flaps and skin grafts survived, except for one flap which was complicated by wound infection, and it was healed after dressing and secondary suturing. The implanted expander expanded smoothly. Patients were followed up for 15 days to three years after surgery. Satisfactory results were obtained, and wounds of 15 patients were repaired completely. CONCLUSIONS: Deep wound on the head due to HEB should be repaired with suitable flap combined with skin graft in donor site, and implantation of expander according to the injury area and condition of patient.

[Experience in the treatment of severe pressure sore].

OBJECTIVE: To summarize the experience in the treatment of severe pressure sore. METHODS: From Aug. 2007 to Jun. 2011, 21 cases of severe pressure sore with 43 III-IV degree lesions were treated with combination treatment, including vacuum sealing drainage technique, local fascia flaps, upper or lower gluteus maximus island myocutaneous flaps, lower gluteus maximus myocutaneous flap, neurocutaneous femoris posterior flaps, tensor fascia lata island myocutaneous flaps, free latissimus dorsi myocutaneous flaps, and skin graft, combined with stryker frame and nursing tracking guidance. 13 of 21 cases had multiple pressure sore. Among them, 5 III degree pressure sores were covered by skin grafting and 3 non-caudal III degree pressure sores (< 2 cm in width) were directly closed after debridement. 8 of 21 cases had single IV degree pressure sore. RESULTS: All the 43 wounds healed completely. 5 wounds in 3 cases had effusion under flap which healed after re-drainage. The wounds were not healed in 3 cases with flap transposition which were also healed after re-debridement. All the flaps survived completely. 16 cases were followed up for 2-26 months. Recurrence happened in 4 cases after discharge because of not following the required nursing care. CONCLUSIONS: Comprehensive application of vacuum sealing drainage technique, multiple myocutaneous flaps and skin grafting, combined with stryker frame and nursing tracking guidance after discharge can be used for the treatment of severe pressure sore with satisfactory results.

[Reverse small saphenous vein-sural neurovascular island flap for t he reconstruction ofsoft tissue defect on foot and ankle in children].

OBJECTIVE: To investigate the clinical application of reversed small saphenous vein-sural neurovascular island flap for reconstruction of soft tissue defect on foot and ankle in children. METHODS: From July 2006 to June 2008, 8 children with soft tissue defects on foot, heel or ankle were treated with reversed small saphenous vein-sural neurovascular island flaps. The size of flaps ranged from 6 cm x 5 cm to 9 cm x 7 cm. The upper margin of the flaps reached the upper third of cruris, with 1 case reaching the transverse line of popliteal fossa. RESULTS: All the flaps survived. The patients were followed up for 1 - 17 months with good aesthetic and functional results. The growth of the two legs had no difference. The sensation of the flaps improved with no heel ulcer and no dysfunction at the donor site. The upper boundary of flaps can reach the upper third of the cruris even the reansverse line of popliteal fossa. The rotation point of the flaps located at 4 - 6 cm above the lateral ankle in children. CONCLUSIONS: The reversed small saphenous vein-sural neurovascular island flap in children has a reliable survival area. The operation is easily performed without any obvious influence on the growth of the operated cruris. It is a good reconstructive method for soft tissue defect in foot and ankle.