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1.
J Invertebr Pathol ; 206: 108162, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38944151

ABSTRACT

Decapod iridescent virus 1 (DIV1) stands as a significant pathogen affecting crustaceans, posing a grave threat to the shrimp industries in aquaculture dependent nations. Within the Iridoviridae family, the conserved envelope protein DIV1-168L plays a pivotal role in virion entry. Nonetheless, the host factors that interact with 168L remain unidentified. To address this gap, we established a cDNA library derived from Litopenaeus vannamei gill tissue and conducted yeast two-hybrid screening to identify host factors that interact with 168L. Additionally, we performed co-immunoprecipitation assays to verify the interaction between cuticle protein 8 (CP8) and 168L. Expression pattern analysis revealed the presence of CP8 transcripts in the gill and epidermis. Furthermore, immunohistochemistry results demonstrated the expression of CP8 in gill cells and its localization in the gill filament epithelium. Fluorescence analysis indicated that full-length CP8 colocalized with 168L in the cytoplasm of Sf9 cells. Removal of the signal peptide from the N-terminal of CP8 eliminated its concentration in the cytoplasm. Additionally, CP8 expression was significantly inhibited during DIV1 infection. Therefore, our research contributes to a better understanding of the entry mechanism of iridovirids. The GenBank accession number for the DIV1 sequence is MF197913.1.

2.
J Fungi (Basel) ; 10(6)2024 May 31.
Article in English | MEDLINE | ID: mdl-38921379

ABSTRACT

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are central components of the machinery mediating cell membrane fusion and intracellular vesicular trafficking in eukaryotic cells, and have been well-documented to play critical roles in growth, development, and pathogenesis in the filamentous fungal plant pathogens. However, little is known about the contributions of SNAREs to the physiology and biocontrol potential in entomopathogenic filamentous fungi. Here, a genome-wide analysis of SNARE genes was performed taking advantage of the available whole genome sequence of Beauveria bassiana, a classical entomopathogenic fungus. Based on the compared genomic method, 22 genes encoding putative SNAREs were identified from the whole genome of B. bassiana, and were classified into four groups (7 Qa-, 4 Qb-, 6 Qc-, and 5 R-SNAREs) according to the conserved structural features of their encoding proteins. An R-SNARE encoding gene BbSEC22 was further functionally characterized by gene disruption and complementation. The BbSEC22 null mutant showed a fluffy appearance in mycelial growth and an obvious lag in conidial germination. The null mutant also exhibited significantly increased sensitivity to oxidative stress and cell wall perturbing agents and reduced the yield of conidia production by 43.1% compared with the wild-type strain. Moreover, disruption of BbSEC22 caused a significant decrease in conidial virulence to Spodoptera litura larvae. Overall, our results provide an overview of vesicle trafficking in B. bassiana and revealed that BbSec22 was a multifunctional protein associated with mycelial growth, sporulation, conidial germination, stress tolerance, and insecticidal virulence.

3.
Int J Mol Sci ; 25(11)2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38892450

ABSTRACT

Asexual development is the main propagation and transmission mode of Beauveria bassiana and the basis of its pathogenicity. The regulation mechanism of conidiation and the key gene resources for utilization are key links to improving the conidia yield and quality of Beauveria bassiana. Their clarification may promote the industrialization of fungal pesticides. Here, we compared the regulation of morphology, resistance to external stress, virulence, and nutrient utilization capacity between the upstream developmental regulatory gene fluG and the key genes brlA, abaA, and wetA in the central growth and development pathway. The results showed that the ΔbrlA and ΔabaA mutants completely lost the capacity to conidiate and that the ΔwetA mutant had seriously reduced conidiation capacity. Although the deletion of fluG did not reduce the conidiation ability as much as deletions of brlA, abaA, and wetA, it significantly reduced the fungal response to external stress, virulence, and nutrient utilization, while the deletion of the three other genes had little effect. Via transcriptome analysis and screening the yeast nuclear system library, we found that the differentially expressed genes in the ΔfluG mutants were concentrated in the signaling pathways of ABC transporters, propionate metabolism, tryptophan metabolism, DNA replication, mismatch repair, and fatty acid metabolism. FluG directly acted on 40 proteins that were involved in various signaling pathways such as metabolism, oxidative stress, and cell homeostasis. The analysis indicated that the regulatory function of fluG was mainly involved in DNA replication, cell homeostasis, fungal growth and metabolism, and the response to external stress. Our results revealed the biological function of fluG in asexual development and the responses to several environmental stresses as well as its influence on the asexual development regulatory network in B. bassiana.


Subject(s)
Beauveria , Fungal Proteins , Gene Expression Regulation, Fungal , Reproduction, Asexual , Spores, Fungal , Beauveria/genetics , Beauveria/growth & development , Beauveria/pathogenicity , Beauveria/physiology , Fungal Proteins/genetics , Fungal Proteins/metabolism , Reproduction, Asexual/genetics , Spores, Fungal/growth & development , Spores, Fungal/genetics , Virulence/genetics , Gene Expression Profiling , Stress, Physiological , Transcriptome
4.
Fish Shellfish Immunol ; 151: 109669, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38849106

ABSTRACT

The suppressor of cytokine signaling (SOCS) gene family is a group of genes involved in the negative regulation of cytokine signal transduction. The members of this family play a crucial role in regulating immune and inflammatory processes. However, comprehensive investigations of these genes have not yet been conducted in the economically significant fish large yellow croaker (Larimichthys crocea). In this study, a total of 13 SOCS genes (LcSOCS1a, LcSOCS1b, LcSOCS2, LcSOCS3a, LcSOCS3b, LcSOCS4, LcSOCS5a, LcSOCS5b, LcSOCS6, LcSOCS7a, LcSOCS7b, LcCISHa and LcCISHb) were identified and analyzed in L. crocea. The phylogenetic tree revealed a high conservation of SOCS genes in evolution, and the gene structure and motif analysis indicated a high similarity in the structure of LcSOCSs in the same subfamily. In addition, the expression patterns of LcSOCSs showed that LcSOCS1b was significantly down-regulated in all time under acute hypoxia stress, but it was markedly up-regulated throughout the entire process after P. plecoglossicida infection, revealing its different immune effects to two stresses. Besides, LcSOCS2a, LcSOCS6 and LcSOCS7a only participated in acute hypoxic stress, while LcSOCS5a was more sensitive to P. plecoglossicida infection. In summary, these results indicated that SOCS genes were involved in stress responses to both biological and non-biological stimuli, setting the foundation for deeper study on the functions of SOCS genes.

5.
Trials ; 25(1): 305, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711052

ABSTRACT

BACKGROUND: To analyze the perioperative bleeding and hidden blood loss (HBL) of sacroiliac screw minimally invasive treatment of pelvic posterior ring injury and explore the influential factors of HBL after operation for providing reference for clinical treatment. METHOD: A retrospective analysis was conducted on data from 369 patients with posterior pelvic ring injuries treated with sacroiliac screws internal fixation at our hospital from January 2015 to January 2022. The research was registered in the Chinese Clinical Trial Registry in July 2022 (ChiCTR2200061866). The total blood loss (TBL) and HBL of patients were counted, and the factors such as gender, age, and surgical duration were statistically analyzed. The influential factors of HBL were analyzed by multiple linear regression. RESULTS: The TBL was 417.96 ± 98.05 ml, of which the visible blood loss (VBL) was 37.00 ± 9.0 ml and the HBL was 380.96 ± 68.8 ml. The HBL accounted for 91.14 ± 7.36% of the TBL. Gender, surgical duration, fixed position, and fixed depth had significant effects on the HBL (P < 0.05). CONCLUSIONS: The HBL was the main cause of anemia after minimally invasive treatment of posterior pelvic ring injury with a sacroiliac screw. Gender, surgical duration, fixed position, and fixed depth were closely related to the occurrence of HBL. In clinical treatment, we should consider these influential factors and take effective measures to reduce the impact of HBL on patients.


Subject(s)
Blood Loss, Surgical , Bone Screws , Fracture Fixation, Internal , Pelvic Bones , Humans , Male , Female , Retrospective Studies , Pelvic Bones/injuries , Pelvic Bones/surgery , Adult , Middle Aged , Fracture Fixation, Internal/adverse effects , Fracture Fixation, Internal/instrumentation , Fracture Fixation, Internal/methods , Treatment Outcome , Risk Factors , Young Adult , Fractures, Bone/surgery , Fractures, Bone/diagnostic imaging , Time Factors , China , Aged , Minimally Invasive Surgical Procedures/methods , Anemia/etiology
6.
RSC Adv ; 14(17): 11728-11733, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38605890

ABSTRACT

As a rising star among metal oxide nanomaterials, titanium dioxide (TiO2) has been widely investigated and employed in optical applications because of its excellent optical properties. In this work, we demonstrate the efficient and broadband nonlinear photonic properties of methylene blue (MB)-loaded reduced TiO2 (TiO2-x-MB) and explore the performance of a TiO2-x-MB-microfiber photonic device in broadband ultrafast photonics. Within an erbium-doped fiber laser (EDFL) system, utilizing the TiO2-x-MB-microfiber photonic device as a saturable absorber (SA), steady mode-locked pulses together with chaotic pulses were successfully achieved at the wavelength of 1.55 µm. Furthermore, by incorporating the TiO2-x-MB SA into a thulium-doped fiber laser (TDFL) system, an ultrashort single pulse and multiple pulses were obtained at 2.0 µm. These results indicate that TiO2-x-MB is an excellent nanomaterial for use in mode-locked lasers, being an alternative candidate for ultrafast fiber lasers via exploiting the chemical and physical properties of oxide nanomaterials.

7.
Heliyon ; 10(8): e29156, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38644822

ABSTRACT

Background: The occurrence and development of sepsis are related to the excessive production of oxygen free radicals and the weakened natural clearance mechanism. Further dependable evidence is required to clarify the effectiveness of antioxidant therapy, especially its impact on short-term mortality. Objectives: The purpose of this systematic review and meta-analysis was to evaluate the effect of common antioxidant therapy on short-term mortality in patients with sepsis. Methods: According to PRISMA guidelines, a systematic literature search on antioxidants in adults sepsis patients was performed on PubMed/Medline, Embase, and the Cochrane Library from the establishment of the database to November 2023. Antioxidant supplements can be a single-drug or multi-drug combination: HAT (hydrocortisone, ascorbic acid, and thiamine), ascorbic acid, thiamine, N-acetylcysteine and selenium. The primary outcome was the effect of antioxidant treatment on short-term mortality, which included 28-day mortality, in-hospital mortality, intensive care unit mortality, and 30-day mortality. Subgroup analyses of short-term mortality were used to reduce statistical heterogeneity and publication bias. Results: Sixty studies of 130,986 sepsis patients fulfilled the predefined criteria and were quantified and meta-analyzed. Antioxidant therapy reduces the risk of short-term death in sepsis patients by multivariate meta-analysis of current data, including a reduction of in-hospital mortality (OR = 0.81, 95% CI 0.67 to 0.99; P = 0.040) and 28-day mortality (OR = 0.81, 95% CI 0.69 to 0.95]; P = 0.008). Particularly in subgroup analyses, ascorbic acid treatment can reduce in-hospital mortality (OR = 0.66, 95% CI 0.90 to 0.98; P = 0.006) and 28-day mortality (OR = 0.43, 95% CI 0.24 to 0.75; P = 0.003). However, the meta-analysis of RCTs found that antioxidant therapy drugs, especially ascorbic acid, did substantially reduce short-term mortality(OR = 0.78, 95% CI 0.62 to 0.98; P = 0.030; OR = 0.57, 95% CI 0.36 to 0.91; P = 0.020). Conclusions: According to current data of RCTs, antioxidant therapy, especially ascorbic acid, has a trend of improving short-term mortality in patients with sepsis, but the evidence remains to be further demonstrated.

8.
J Hazard Mater ; 471: 134313, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38669927

ABSTRACT

Secondary lignification of the root exodermis of Kandelia obovata is crucial for its response to adversity such as high salinity and anaerobic environment, and this lignification is also effective in blocking cadmium transport to the roots. However, how the differences in lignification of root exodermis at different developmental stages respond to Cd stress and its regulatory mechanisms have not been revealed. In this study, after analyzing the root structure and cell wall thickness using a Phenom scanning electron microscope as well as measuring cadmium content in the root cell wall, we found that the exodermis of young and mature roots of K. obovata responded to Cd stress through the polymerization of different lignin monomers, forming two different mechanisms: chelation and blocking. Through small RNA sequencing, RLM-5'-RACE and dual luciferase transient expression system, we found that miR397 targets and regulates KoLAC4/17/7 expression. The expression of KoLAC4/17 promoted the accumulation of guaiacyl lignin during lignification and enhanced the binding of cadmium to the cell wall. Meanwhile, KoLAC7 expression promotes the accumulation of syringyl lignin during lignification, which enhances the obstruction of cadmium and improves the tolerance to cadmium. These findings enhance our understanding of the molecular mechanisms underlying the differential lignification of the root exodermis of K. obovata in response to cadmium stress, and provide scientific guidance for the conservation of mangrove forests under heavy metal pollution.


Subject(s)
Cadmium , Lignin , MicroRNAs , Plant Roots , Lignin/chemistry , Cadmium/toxicity , Plant Roots/drug effects , Plant Roots/metabolism , Plant Roots/growth & development , MicroRNAs/metabolism , MicroRNAs/genetics , Stress, Physiological/drug effects , Gene Expression Regulation, Plant/drug effects , Polymerization/drug effects , Cell Wall/drug effects , Cell Wall/metabolism , Araceae/drug effects , Araceae/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics
9.
Biochem Biophys Res Commun ; 710: 149832, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38588614

ABSTRACT

BACKGROUND: Sepsis-induced acute lung injury (ALI) is associated with considerable morbidity and mortality in critically ill patients. S100A9, a key endothelial injury factor, is markedly upregulated in sepsis-induced ALI; however, its specific mechanism of action has not been fully elucidated. METHODS: The Gene Expression Omnibus database transcriptome data for sepsis-induced ALI were used to screen for key differentially expressed genes (DEGs). Using bioinformatics analysis methods such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses, the pathogenesis of sepsis-induced ALI was revealed. Intratracheal infusion of lipopolysaccharide (LPS, 10 mg/kg) induced ALI in wild-type (WT) and S100A9 knockout mice. Multiomics analyses (transcriptomics and proteomics) were performed to investigate the potential mechanisms by which S100A9 exacerbates acute lung damage. Hematoxylin-eosin, Giemsa, and TUNEL staining were used to evaluate lung injury and cell apoptosis. LPS (10 µg/mL)-induced murine lung epithelial MLE-12 cells were utilized to mimic ALI and were modulated by S100A9 lentiviral transfection. The impact of S100A9 on cell apoptosis and inflammatory responses were identified using flow cytometry and PCR. The expression of interleukin (IL)-17-nuclear factor kappa B (NFκB)-caspase-3 signaling components was identified using western blotting. RESULTS: Six common DEGs (S100A9, S100A8, IFITM6, SAA3, CD177, and MMP9) were identified in the six datasets related to ALI in sepsis. Compared to WT sepsis mice, S100A9 knockout significantly alleviated LPS-induced ALI in mice, with reduced lung structural damage and inflammatory exudation, decreased exfoliated cell and protein content in the lung lavage fluid, and reduced apoptosis and necrosis of pulmonary epithelial cells. Transcriptomic analysis revealed that knocking out S100A9 significantly affected 123 DEGs, which were enriched in immune responses, defense responses against bacteria or lipopolysaccharides, cytokine-cytokine receptor interactions, and the IL-17 signaling pathway. Proteomic analysis revealed that S100A9 knockout alleviated muscle contraction dysfunction and structural remodeling in sepsis-induced ALI. Multiomics analysis revealed that S100A9 may be closely related to interferon-induced proteins with tetratricopeptide repeats and oligoadenylate synthase-like proteins. LPS decreased MLE12 cell activity, accompanied by high expression of S100A9. The expression of IL-17RA, pNFκB, and cleaved-caspase-3 were increased by S100A9 overexpression and reduced by S100A9 knockdown in LPS-stimulated MLE12 cells. S100A9 knockdown decreases transcription of apoptosis-related markers Bax, Bcl and caspase-3, alleviating LPS-induced apoptosis. CONCLUSIONS: S100A9 as a key biomarker of sepsis-induced acute lung injury, and exacerbates lung damage and epithelial cell apoptosis induced by LPS via the IL-17-NFκB-caspase-3 signaling pathway.


Subject(s)
Acute Lung Injury , Sepsis , Humans , Mice , Animals , NF-kappa B/metabolism , Interleukin-17/metabolism , Caspase 3/metabolism , Lipopolysaccharides/pharmacology , Proteomics , Acute Lung Injury/chemically induced , Lung/pathology , Signal Transduction , Mice, Knockout , Sepsis/pathology , Calgranulin B/genetics , Calgranulin B/metabolism
10.
Zhongguo Gu Shang ; 37(2): 124-8, 2024 Feb 25.
Article in Chinese | MEDLINE | ID: mdl-38425061

ABSTRACT

OBJECTIVE: To investigate the effectiveness of real-time tracking and virtual reality technology(RTVI) used to assist the intraoperative alignment of the trauma orthopaedic surgery robot for the treatment of femoral neck fractures and its impact on the treatment outcome. METHODS: A retrospective analysis was conducted on 60 patients with femoral neck fractures treated with trauma orthopedic robotic surgery from September 2020 to September 2022. Patients were divided into two groups according to whether RTVI technology was used during surgery to assist robotic surgery. There were 28 patients in the RTVI group (12 males and 16 females), with an average age of (46.2±9.3) years old ranging from 28 to 60 years old. There were 32 patients in the simple Tianji surgical robot group, including 15 males and 17 females, aged (48.2±7.8) years old ranging from 32 to 58. The number of registered fluoroscopy, operation time, total number of intraoperative fluoroscopy, intraoperative blood loss, and hospitalization time of the two groups of patients were observed and recorded. All patients received regular follow-up after surgery, and hip X-rays were routinely reviewed to record Garden alignment index, fracture healing time, postoperative complications, and Harris score. RESULTS: All 60 patients were followed up. The RTVI group was followed up for 9 to 16 months with an average of (13.0±1.2) months, and the Tianji surgical robot group alone was followed up for 10 to 14 months with an average of (12.0±1.3) months. During the follow-up period, the femoral neck fractures of both groups of patients healed well, and no complications such as internal fixation loosening and incision infection occurred. The number of registered fluoroscopy, operation time, and number of intraoperative fluoroscopy of patients in the RTVI group were significantly better than those in the simple Tianji surgical robot group(P<0.01). There was no statistically significant difference in intraoperative blood loss, hospital stay, Garden alignment index, fracture healing time, and hip Harris score between two groups(P>0.05). CONCLUSION: Although RTVI technology assisted by the surgical robot for femoral neck fracture surgery has little impact on its postoperative outcome, it can effectively reduce the operating time, the number of intraoperative X-ray projections, and the risk of intraoperative radiation exposure to patients. It also shortened the learning curve of the operator and better reflected the precision and efficiency of the trauma orthopaedic surgery robot.


Subject(s)
Femoral Neck Fractures , Robotics , Male , Female , Humans , Adult , Middle Aged , Retrospective Studies , Blood Loss, Surgical , Femoral Neck Fractures/surgery , Fracture Fixation, Internal , Treatment Outcome
11.
Orthop Surg ; 16(4): 976-983, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38438142

ABSTRACT

OBJECTIVE: Traditional internal fixation of calcaneus fractures, involving lateral L-shaped incisions and plate fixation, has disadvantages such as increased operative exposure, eccentric plate fixation, and complications. The aim of this study was to design a Spatial Weaving Intra-calcaneal Fixator System (SWIFS) for the treatment of complex calcaneal fractures and to compare its biomechanical properties with those of traditional calcaneal plates. METHODS: The computed tomography (CT) data of the normal adult calcaneus was used for modeling, and the largest trapezoidal column structure was cut and separated from the model and related parameters were measured. The SWIFS was designed within the target trapezoid, according to the characteristics of the fracture of the calcaneus. The Sanders model classification type IV calcaneal fracture was established in finite element software, and fixation with calcaneal plate and the SWIFS examined. Overall structural strength distribution and displacement in the two groups were compared. RESULTS: The maximum 3D trapezoidal column in the calcaneus was constructed, and the dimensions were measured. The SWIFS and the corresponding guide device were successfully designed. In the one-legged erect position state, the SWIFS group exhibited a peak von Mises equivalent stress of 96.00 MPa, a maximum displacement of 0.31 mm, and a structural stiffness of 2258.06 N/mm. The conventional calcaneal plate showed a peak von Mises equivalent stress of 228.66 Mpa, a maximum displacement of 1.26 mm, and a structural stiffness of 555.56 N/mm. The SWIFS group exhibited a 75.40% decrease in displacement and a 306.45% increase in stiffness. CONCLUSION: Compared with fixation by conventional calcaneal plate, the SWIFS provides better structural stability and effective stress distribution.


Subject(s)
Ankle Injuries , Calcaneus , Fractures, Bone , Adult , Humans , Finite Element Analysis , Fractures, Bone/surgery , Fracture Fixation, Internal/methods , Calcaneus/surgery , Bone Plates , Biomechanical Phenomena
12.
Colloids Surf B Biointerfaces ; 237: 113838, 2024 May.
Article in English | MEDLINE | ID: mdl-38484445

ABSTRACT

The emergence of nanotechnology has opened up a new way for tumor therapy. Among them, self-assembled nanotechnology has received extensive attention in medicine due to its simple preparation process, high drug-loading capacity, low toxicity, and low cost. This review mainly summarizes the preparation methods of self-assembled nano-delivery systems, as well as the self-assembled mechanism of carrier-free nanomedicine, polymer-carried nanomedicine, polypeptide, and metal drugs, and their applications in tumor therapy. In addition, we discuss the advantages and disadvantages, future challenges, and opportunities of these self-assembled nanomedicines, which provide important references for the development and application of self-assembled nanotechnology in the field of medical therapy.


Subject(s)
Drug Delivery Systems , Neoplasms , Humans , Nanotechnology , Nanomedicine , Peptides/therapeutic use , Neoplasms/drug therapy
13.
Biomacromolecules ; 25(4): 2587-2596, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38527924

ABSTRACT

In response to increasing antibiotic resistance and the pressing demand for safer infected wound care, probiotics have emerged as promising bioactive agents. To address the challenges associated with the safe and efficient application of probiotics, this study successfully loaded metabolites from Lacticaseibacillus rhamnosus GG (LGG) into a gelatin cross-linked macromolecular network by an in situ blending and photopolymerization method. The obtained LM-GelMA possesses injectability and autonomous healing capabilities. Importantly, the incorporation of LGG metabolites endows LM-GelMA with excellent antibacterial properties against Staphylococcus aureus and Escherichia coli, while maintaining good biocompatibility. In vivo assessments revealed that LM-GelMA can accelerate wound healing by mitigating infections induced by pathogenic bacteria. This is accompanied by a reduction in the expression of key proinflammatory cytokines such as TNF-α, IL-6, VEGFR2, and TGF-ß, leading to increased re-epithelialization and collagen formation. Moreover, microbiological analysis confirmed that LM-GelMA can modulate the abundance of beneficial wound microbiota at family and genus levels. This study provides a facile strategy and insights into the functional design of hydrogels from the perspective of wound microenvironment regulation.


Subject(s)
Lacticaseibacillus rhamnosus , Wound Healing , Anti-Bacterial Agents/pharmacology , Cytokines , Escherichia coli , Hydrogels/pharmacology
14.
Mol Pharm ; 21(3): 1038-1055, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38344996

ABSTRACT

Antibody drug conjugates (ADCs) have emerged as a new promising class of anti- cancer agents. However, limitations such as higher costs and unavoidable immunogenicity due to their relatively large structures cannot be ignored. Therefore, the development of lightweight drugs such as small molecule-drug conjugates (SMDCs) based on the ADC design idea has become a new option for targeted therapy. SMDCs are derived from the coupling of small-molecule targeting ligands with cytotoxic drugs. They are composed of three parts: small-molecule targeting ligands, cytotoxic molecules, and linkers. Compared with ADCs, SMDCs can be more rapidly and evenly dispersed into tumor tissues, with low cost and no immunogenicity. In this article, we will give a comprehensive review of different types of SMDCs currently under clinical trials to provide ideas and inspirations for the development of clinically applicable SMDCs.


Subject(s)
Antineoplastic Agents , Immunoconjugates , Neoplasms , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Immunoconjugates/pharmacology , Immunoconjugates/therapeutic use , Immunoconjugates/chemistry , Antigens , Neoplasms/drug therapy
15.
Article in English | MEDLINE | ID: mdl-38364653

ABSTRACT

In recent years, members of the Dmrt family, TGF-ß superfamily and Sox family have been recognized as crucial genes for sex determination/differentiation across diverse animal species. Nevertheless, knowledge regarding the abundance and potential functions of these genes in abalone remains limited. In this study, a total of 5, 10, and 7 members of the Dmrt family, the TGF-ß superfamily and the Sox family, respectively, were identified in the Pacific abalone Haliotis discus hannai. Sequence characteristics, phylogenetic relationships and spatiotemporal expression profiles of these genes were investigated. Notably, HdDmrt-04 (Dmrt1/1L-like) emerged as a potential mollusc-specific gene with a preponderance for expression in the testis. Interestingly, none of the TGF-ß superfamily members exhibited specific or elevated expression in the gonads, highlighting the need for further investigation into their role in abalone sex differentiation. The Sox proteins in H. discus hannai were categorized into 7 subfamilies: B1, B2, C, D, E, F, and H. Among them, HdSox-07 (SoxH-like) was observed to play a crucial role in testis development, while HdSox-03 (SoxB1-like) and HdSox-04 (SoxC-like) probably cooperate in abalone ovary development. Taken together, the results of the present study suggested that HdDmrt-04 and HdSox-07 can be used as male-specific markers for gonad differentiation in H. discus hannai and imply conservation of their functions across invertebrates and vertebrates. Our findings provide new insights into the evolution and genetic structure of the Dmrt family, the TGF-ß superfamily and the Sox family in abalone and pave the way for a deeper understanding of sex differentiation in gastropods.


Subject(s)
Gastropoda , Phylogeny , Animals , Gastropoda/genetics , Male , Female , Sex Differentiation/genetics , Gene Expression Profiling , Transcriptome , Genome , Multigene Family
16.
BMC Genomics ; 25(1): 24, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38166626

ABSTRACT

BACKGROUND: Transforming growth factor ß (TGF-ß) superfamily genes can regulate various processes, especially in embryogenesis, adult development, and homeostasis. To understand the evolution and divergence patterns of the TGF-ß superfamily in scallops, genome-wide data from the Bay scallop (Argopecten irradians), the Zhikong scallop (Chlamys farreri) and the Yesso scallop (Mizuhopecten yessoensis) were systematically analysed using bioinformatics methods. RESULTS: Twelve members of the TGF-ß superfamily were identified for each scallop. The phylogenetic tree showed that these genes were grouped into 11 clusters, including BMPs, ADMP, NODAL, GDF, activin/inhibin and AMH. The number of exons and the conserved motif showed some differences between different clusters, while genes in the same cluster exhibited high similarity. Selective pressure analysis revealed that the TGF-ß superfamily in scallops was evolutionarily conserved. The spatiotemporal expression profiles suggested that different TGF-ß members have distinct functions. Several BMP-like and NODAL-like genes were highly expressed in early developmental stages, patterning the embryonic body plan. GDF8/11-like genes showed high expression in striated muscle and smooth muscle, suggesting that these genes may play a critical role in regulating muscle growth. Further analysis revealed a possible duplication of AMH, which played a key role in gonadal growth/maturation in scallops. In addition, this study found that several genes were involved in heat and hypoxia stress in scallops, providing new insights into the function of the TGF-ß superfamily. CONCLUSION: Characteristics of the TGF-ß superfamily in scallops were identified, including sequence structure, phylogenetic relationships, and selection pressure. The expression profiles of these genes in different tissues, at different developmental stages and under different stresses were investigated. Generally, the current study lays a foundation for further study of their pleiotropic biological functions in scallops.


Subject(s)
Pectinidae , Animals , Phylogeny , Pectinidae/genetics , Pectinidae/metabolism , Genome , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism
17.
BMC Oral Health ; 24(1): 125, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38267962

ABSTRACT

BACKGROUND: This study aimed to validate the availability of superimposing full-color mandibular digital models (DMs) by the morphological characteristics of vessels in extraction adult patients. METHODS: Twenty-eight adult patients were included, and their DMs were superimposed with pre- and posttreatment cone beam computed tomography (CBCT) and the morphological characteristics of lingual vessels. The measurements of each tooth were compared under the same coordinate system. RESULTS: The ICC results displayed exceptional agreement in intra- and interrater assessments, with scores exceeding 0.891 in the crown for intrarater agreement and scores surpassing 0.888 in the crown for interrater agreement. Furthermore, no statistically significant differences were found in the 2 superimposition methods (P > 0.05). CONCLUSION: The morphological characteristics of vessels under the mucogingival junction in the lingual side of mandible of are stable enough for the superimposition of mandibular DMs in the adult patients undergo orthodontic treatment with premolars extraction.


Subject(s)
Cone-Beam Computed Tomography , Dental Care , Adult , Humans , Reproducibility of Results , Mandible/diagnostic imaging , Patients
18.
Sci Data ; 11(1): 90, 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38238346

ABSTRACT

Echiura is a distinctive family of unsegmented sausage-shaped marine worms whose phylogenetic relationship still needs strong evidence from the phylogenomic analysis. In this family, Urechis unicinctus is known for its high nutritional and medicinal value and adaptation to harsh intertidal conditions. Herein, we combined PacBio long-read, short-read Illumina and Hi-C sequencing, generating a high-quality chromosome-level genome assembly of U. unicinctus. The assembled genome spans ~1,138.6 Mb with a scaffold N50 of 68.3 Mb, of which 1,113.8 Mb (97.82%) were anchored into 17 pseudo-chromosomes. The BUSCO analysis demonstrated the completeness of the genome assembly and gene model prediction are 93.5% and 91.5%, respectively. A total of 482.1 Mb repetitive sequences, 21,524 protein-coding genes, 1,535 miRNAs, 3,431 tRNAs, 124 rRNAs, and 348 snRNAs were annotated. This study significantly improves the quality of U. unicinctus genome assembly, sets the footsteps for molecular breeding and further study in genome evolution, genetic and molecular biology of U. unicinctus.


Subject(s)
Chromosomes , Genome , Polychaeta , Chromosomes/genetics , Phylogeny , Repetitive Sequences, Nucleic Acid , Polychaeta/genetics
19.
Fish Shellfish Immunol ; 146: 109376, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38218421

ABSTRACT

The limited tolerance of crustacean tissue physiology to a high-fat diet has captured the attention of researchers. Yet, investigations into the physiological response mechanisms of the crustacean intestinal barrier system to a high-fat diet are progressing slowly. Elucidating potential physiological mechanisms and determining the precise regulatory targets would be of great physiological and nutritional significance. This study established a high-fat diet-induced intestinal barrier damage model in Macrobrachium rosenbergii, and systematically investigated the functions of gut microbiota and its functional metabolites. The study achieved this by monitoring phenotypic indicators, conducting 16S rDNA sequencing, targeted metabolomics, and in vitro anaerobic fermentation of intestinal contents. Feeding prawns with control and high-fat diets for 8 weeks, the lipid level of 7 % in the CON diet and 12 % in the HF diet. Results showed that high-fat intake impaired the intestinal epithelial cells, intestinal barrier structure, and permeability of M. rosenbergii, activated the tight junction signaling pathway inhibiting factor NF-κB transcription factor Relish/myosin light chain kinase (MLCK), and suppressed the expression of downstream tight junction proteins zona occludens protein 1 (ZO-1) and Claudin. High-fat intake resulted in a significant increase in abundance of Aeromonas, Enterobacter, and Clostridium sensu stricto 3 genera, while Lactobacillus, Lactococcus, Bacteroides, and Ruminococcaceae UCG-010 genera were significantly decreased. Targeted metabolomics results of bile acids and short-chain fatty acids in intestinal contents and in vitro anaerobic fermentation products showed a marked rise in the abundance of DCA, 12-KetoLCA, 7,12-diketoLCA, and Isovaleric acid, and a significant reduction in the abundance of HDCA, CDCA, and Acetate in the HF group. Pearson correlation analysis revealed a substantial correlation between various genera (Clostridium sensu stricto 3, Lactobacillus, Bacteroides) and secondary metabolites (DCA, HDCA, 12-KetoLCA, Acetate), and the latter was significantly correlated with intestinal barrier function related genes (Relish, ZO-1, MLCK, vitamin D receptor, and ecdysone receptor). These findings indicate that gut microorganisms and their specific bile acids and short-chain fatty acid secondary metabolites play a crucial role in the process of high-fat-induced intestinal barrier damage of M. rosenbergii. Moreover, identifying and targeting these factors could facilitate precise regulation of high-fat nutrition for crustaceans.


Subject(s)
Gastrointestinal Microbiome , Palaemonidae , Animals , Diet, High-Fat/adverse effects , Bile Acids and Salts , Fatty Acids, Volatile , Acetates
20.
Nat Commun ; 15(1): 527, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38225234

ABSTRACT

The development of artificial spider silk with properties similar to native silk has been a challenging task in materials science. In this study, we use a microfluidic device to create continuous fibers based on recombinant MaSp2 spidroin. The strategy incorporates ion-induced liquid-liquid phase separation, pH-driven fibrillation, and shear-dependent induction of ß-sheet formation. We find that a threshold shear stress of approximately 72 Pa is required for fiber formation, and that ß-sheet formation is dependent on the presence of polyalanine blocks in the repetitive sequence. The MaSp2 fiber formed has a ß-sheet content (29.2%) comparable to that of native dragline with a shear stress requirement of 111 Pa. Interestingly, the polyalanine blocks have limited influence on the occurrence of liquid-liquid phase separation and hierarchical structure. These results offer insights into the shear-induced crystallization and sequence-structure relationship of spider silk and have significant implications for the rational design of artificially spun fibers.


Subject(s)
Fibroins , Spiders , Animals , Silk/chemistry , Microfluidics , Fibroins/chemistry , Repetitive Sequences, Nucleic Acid
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