Perilipin1 inhibits Nosema bombycis proliferation by promoting Domeless- and Hop-mediated JAK-STAT pathway activation in Bombyx mori.

Lipid droplets (LDs) are dynamic organelles that participate in the regulation of lipid metabolism and cellular homeostasis inside of cells. LD-associated proteins, also known as perilipins (PLINs), are a family of proteins found on the surface of LDs that regulate lipid metabolism, immunity, and other functions. In silkworms, pébrine disease caused by infection by the microsporidian Nosema bombycis (Nb) is a severe threat to the sericultural industry. Although we found that Nb relies on lipids from silkworms to facilitate its proliferation, the relationship between PLINs and Nb proliferation remains unknown. Here, we found Nb infection caused the accumulation of LDs in the fat bodies of silkworm larvae. The characterized perilipin1 gene (plin1) promotes the accumulation of intracellular LDs and is involved in Nb proliferation. plin1 is similar to perilipin1 in humans and is conserved in all insects. The expression of plin1 was mostly enriched in the fat body rather than in other tissues. Knockdown of plin1 enhanced Nb proliferation, whereas overexpression of plin1 inhibited its proliferation. Furthermore, we confirmed that plin1 increased the expression of the Domeless and Hop in the JAK-STAT immune pathway and inhibited Nb proliferation. Taken together, our current findings demonstrate that plin1 inhibits Nb proliferation by promoting the JAK-STAT pathway through increased expression of Domeless and Hop. This study provides new insights into the complicated connections among microsporidia pathogens, LD surface proteins, and insect immunity.IMPORTANCELipid droplets (LDs) are lipid storage sites in cells and are present in almost all animals. Many studies have found that LDs may play a role in host resistance to pathogens and are closely related to innate immunity. The present study found that a surface protein of insect lipid droplets could not only regulate the morphological changes of lipid droplets but also inhibit the proliferation of a microsporidian pathogen Nosema bombycis (Nb) by activating the JAK-STAT signaling pathway. This is the first discovery of the relationship between microsporidian pathogen and insect lipid surface protein perilipin and insect immunity.

Identification of long non-coding RNAs in response to microsporidia infection in Silkworm, Bombyx mori.

Microsporidia Nosema bombycis (Nb) is a cellular parasite responsible for pébrine disease in silkworms, significantly impacting the sericulture industry. Long non-coding RNAs (lncRNAs), which are RNA fragments longer than 200 nucleotides, are pivotal in a range of cellular and physiological functions. However, the potential role of silkworm lncRNAs in response to Nb infection remains unknown. This study conducted transcriptome sequencing on both larvae and Nb-infected midguts of silkworms, identifying 1,440 lncRNAs across all examined midgut samples. Within the Nb-infected group, 42 differentially expressed lncRNAs (DElncRNAs) and 305 differentially expressed mRNAs (DEmRNAs) were detected. Functional annotation and pathway analysis showed that these DEmRNAs are mostly involved in metabolism, apoptosis, autophagy, and other key pathways. The co-expression network of DEmRNAs and DElncRNAs illustrates that 1 gene could be regulated by multiple lncRNAs and 1 lncRNA may target multiple genes, indicating that the regulation of lncRNA is intricate and networked. In addition, the DElncRNA-miRNA-mRNA network showed that some DElncRNAs may be involved in the immune response and metabolism through miRNA. Notably, the study observed an increase in lncRNA MSTRG857.1 following Nb infection, which may promote Nb proliferation. These findings offer insights into the complex interplay between insects and microsporidia.

Novel symmetry-preserving neural network model for phylogenetic inference.

Motivation: Scientists world-wide are putting together massive efforts to understand how the biodiversity that we see on Earth evolved from single-cell organisms at the origin of life and this diversification process is represented through the Tree of Life. Low sampling rates and high heterogeneity in the rate of evolution across sites and lineages produce a phenomenon denoted "long branch attraction" (LBA) in which long nonsister lineages are estimated to be sisters regardless of their true evolutionary relationship. LBA has been a pervasive problem in phylogenetic inference affecting different types of methodologies from distance-based to likelihood-based. Results: Here, we present a novel neural network model that outperforms standard phylogenetic methods and other neural network implementations under LBA settings. Furthermore, unlike existing neural network models in phylogenetics, our model naturally accounts for the tree isomorphisms via permutation invariant functions which ultimately result in lower memory and allows the seamless extension to larger trees. Availability and implementation: We implement our novel theory on an open-source publicly available GitHub repository: https://github.com/crsl4/nn-phylogenetics.

Revolutionizing Gastric Cancer Prevention: Novel Insights on Gastric Mucosal Inflammation-Cancer Transformation and Chinese Medicine.

The progression from gastric mucosal inflammation to cancer signifies a pivotal event in the trajectory of gastric cancer (GC) development. Chinese medicine (CM) exhibits unique advantages and holds significant promise in inhibiting carcinogenesis of the gastric mucosa. This review intricately examines the critical pathological events during the transition from gastric mucosal inflammation-cancer transformation (GMICT), with a particular focus on pathological evolution mechanisms of spasmolytic polypeptide-expressing metaplasia (SPEM). Moreover, it investigates the pioneering applications and advancements of CM in intervening within the medical research domain of precancerous transformations leading to GC. Furthermore, the analysis extends to major shortcomings and challenges confronted by current research in gastric precancerous lesions, and innovative studies related to CM are presented. We offer a highly succinct yet optimistic outlook on future developmental trends. This paper endeavors to foster a profound understanding of forefront dynamics in GMICT research and scientific implications of modernizing CM. It also introduces a novel perspective for establishing a collaborative secondary prevention system for GC that integrates both Western and Chinese medicines.

Comparative analysis of the intestinal flora of BmNPV-resistant and BmNPV-sensitive silkworm varieties.

Bombyx mori nucleopolyhedrovirus (BmNPV) is a very common and infectious virus that affects silkworms and hinders silk production. To investigate the intestinal flora of BmNPV-resistant and BmNPV-sensitive silkworm varieties, 16 S rDNA high-throughput sequencing was performed. The results of the cluster analysis showed that the intestinal flora of the resistant silkworm variety was more abundant than that of the sensitive silkworm variety. This was found even when infection with BmNPV caused a sharp decline in the number of intestinal floral species in both resistant and sensitive silkworm varieties. The abundances of the intestinal flora, including Aureimonas, Ileibacterium, Peptostreptococcus, Pseudomonas, Enterococcus, and Halomonas, in the resistant variety were considerably greater after infection with BmNPV than those in the sensitive variety. After infection with BmNPV, four kinds of important intestinal bacteria, namely, f_Saccharimonadaceae, Peptostreptococcus, Aureirmonas, and f_Rhizobiaceae, were found in the resistant silkworm variety. In the sensitive silkworm variety, only Faecalibaculum was an important intestinal bacterium. The differential or important bacteria mentioned above might be involved in immunoreaction or antiviral activities, especially in the intestines of BmNPV-resistant silkworms. By conducting a functional enrichment analysis, we found that BmNPV infection did not change the abundance of important functional components of the intestinal flora in resistant or sensitive silkworm varieties. However, some functional factors, such as the biosynthesis, transport, and catabolism of secondary metabolites (e.g., terpenoids and polyketides) and lipid transport and metabolism, were more important in the resistant silkworm variety than in the sensitive variety; thus, these factors may increase the resistance of the host to BmNPV. To summarize, we found significant differences in the composition, abundance, and function of the intestinal flora between resistant and sensitive silkworm varieties, especially after infection with BmNPV, which might be closely related to the resistance of resistant silkworm varieties to BmNPV.

MiRNA-296-5p promotes the sensitivity of nasopharyngeal carcinoma cells to cisplatin via targeted inhibition of STAT3/KLF4 signaling axis.

Improving drug sensitivity is an important strategy in chemotherapy of cancer and accumulating evidence indicates that miRNAs are involved in the regulation of drug sensitivity, but the specific mechanism is still unclear. Our previous study has found that miR-296-5p was significantly downregulated in nasopharyngeal carcinoma (NPC). Here, we aim to explore whether miR-296-5p is involved in regulating cisplatin sensitivity in NPC by regulating STAT3/KLF4 signaling axis. The cell proliferation and clonogenic capacity of NPC cells were evaluated by CCK8 Assay and plate colony assay, respectively. The Annexin V-FITC staining kit was used to determine and quantify the apoptotic cells using flow cytometry. The drug efflux ability of NPC cells were determined by Rhodamine 123 efflux experiment. The expression of miR-296-5p, apoptosis-related genes and protein in NPC cell lines were detected by qPCR and Western blot, respectively. Animal study was used to evaluate the sensitivity of NPC cells to DDP treatment in vivo. Our results showed that elevated miR-296-5p expression obviously promoted the sensitivity of NPC cells to DDP by inhibiting cell proliferation and clonogenic capacity, and inducing apoptosis. In addition, we found that miR-296-5p inhibited the expression of STAT3 and KLF4 in NPC cells, while overexpression of exogenous STAT3 reversed miR-296-5p-mediated enhancement in cell death of DDP-treated NPC cells. In vivo studies further confirmed that miR-296-5p promotes the sensitivity of NPC cells to DDP treatment. miRNA-296-5p enhances the drug sensitivity of nasopharyngeal carcinoma cells to cisplatin via STAT3/KLF4 signaling pathway.

The Function of Different Subunits of the Molecular Chaperone CCT in the Microsporidium Nosema bombycis: NbCCTζ Interacts with NbCCTα.

Chaperonin containing tailless complex polypeptide 1 (CCT) is a molecular chaperone protein that consists of eight completely different subunits and assists in the folding of newly synthesized peptides. The zeta subunit of CCT is a regulatory factor for the folding and assembly of cytoskeletal proteins as individuals or complexes. In this study, the zeta subunit of Nosema bombycis (NbCCTζ) is identified for the first time. The complete ORF of the NbCCTζ gene is 1533 bp in length and encodes a 510 amino acid polypeptide. IFA results indicate that NbCCTζ is colocalized with actin and ß-tubulin in the cytoplasm during the proliferative phase and that NbCCTζ is completely colocalized with NbCCTα in the cytoplasm of N. bombycis throughout the entire life cycle. Furthermore, the yeast two-hybrid assay revealed that the NbCCTζ interacts with NbCCTα. The transcriptional level of NbCCTζ is significantly downregulated by knocking down the NbCCTα gene, while the transcriptional level of NbCCTα is downregulated after knocking down the NbCCTζ gene. These results suggest that NbCCTζ may play a vital role in the proliferation of N. bombycis by coordinating with NbCCTα.

Insights and future prospects of traditional Chinese medicine in the treatment of functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a prevalent and challenging gastrointestinal disorder. Conventional medicine often faces limitations in providing effective treatment for FD, thus indicating the need to explore alternative approaches. Traditional Chinese medicine (TCM), which is rooted in ancient Chinese traditions and has evolved over thousands of years, offers a holistic approach to well-being. TCM incorporates herbal remedies, acupuncture, and other therapies while shaping the future of complementary and alternative medicine. PURPOSE: To review the existing literature on the current status and future prospects of using TCM to treat FD. METHODS: We extensively searched the PubMed, Google Scholar, Embase, an China National Knowledge Internet databases from inception to May 31, 2023 to identify relevant literature. We also searched the reference lists of the included articles. RESULTS: Clinical evidence-based research has explored the efficacy of TCM in treating FD. Recent research has illuminated the multifaceted mechanisms through which TCM interventions affect FD. TCM is a promising alternative, as it emphasizes a holistic approach and holds potential advantages in addressing the complex nature of FD. CONCLUSIONS: The integration of TCM and Western medicine offers a comprehensive approach to understanding and managing FD by bridging traditional wisdom with modern scientific understanding. This paper highlights the practical implications of this integration, the challenges to be addressed, and the potential for international collaboration to further elucidate the efficacy of TCM. However, continued research and dialog are needed to advance the modern development of TCM and to improve the quality of life of FD patients.

Comprehensive bibliometric and visualized analysis of research on gut-liver axis published from 1998 to 2022.

Background: The concept of the gut-liver axis was proposed by Marshall in 1998, and since then, this hypothesis has been gradually accepted by the academic community. Many publications have been published on the gut-liver axis, making it important to assess the scientific implications of these studies and the trends in this field. Methods: Publications were retrieved from the Web of Science Core Collection. Microsoft Excel, CiteSpace, VOSviewer, and Scimago Graphica software were used for bibliometric analysis. Results: A total of 776 publications from the Web of Science core database were included in this study. In the past 25 years, the number of publications on the gut-liver axis has shown an upward trend, particularly in the past 3 years (2020-2022). China had the highest number of publications (267 articles, 34.4%). However, the United States was at the top regarding influence and international cooperation in this field. The University of California San Diego had contributed the most publications. Suk, Ki Tae and Schnabl, Bernd were tied for the first rank in most publications. Thematic hotspots and frontiers were focused on gut microbiota, microbial metabolite, intestinal permeability, bacterial translocation, bile acid, non-alcoholic steatohepatitis, and alcoholic liver disease. Conclusion: Our study is the first bibliometric analysis of literature using visualization software to present the current research status of the gut-liver axis over the past 25 years. The damage and repair of intestinal barrier function, as well as the disruption of gut microbiota and host metabolism, should be a focus of attention. This study can provide a reference for later researchers to understand the global research trends, hotspots, and frontiers in this field.

Association between obesity and anemia in an nationally representative sample of United States adults: a cross-sectional study.

Introduction: Few studies are about the relationship between anemia and obesity, and previous studies have only paid attention to BMI. Methods and Results: We first included body fat percentage (BF%) as an assessment indicator and divided it into quartiles, grouped participants into obesity and non-obesity used data from NHANES database. After adjustment for age, gender, ethnicity, education and family income, the level of soluble transferrin receptor (sTfR), and incidence of elevated CRP or HsCRP were progressively higher with increased BF%, whereas mean cell volume (MCV), natural logarithm (Ln) serum ferritin (SF), and Ln SF/sTfR were progressively reduced. Although a higher prevalence of anemia and lower hemoglobin was observed with increased BF%, but there was no statistical difference. Women in the highest BF% group demonstrated a significantly higher risk of iron deficiency compared to those in the lowest BF% group. Discussion: BF% should be given more attention, and women with high BF% should pay attention to iron deficiency.

Targeted delivery of Fc-fused PD-L1 for effective management of acute and chronic colitis.

The PD-1/PD-L1 pathway in mucosal immunity is currently actively explored and considered as a target for inflammatory bowel disease (IBD) treatment. However, systemic PD-L1 administration may cause unpredictable adverse effects due to immunosuppression. Here we show that reactive oxygen species (ROS)-responsive nanoparticles enhance the efficacy and safety of PD-L1 in a mouse colitis model. The nanoparticles control the accumulation and release of PD-L1 fused to Fc (PD-L1-Fc) at inflammatory sites in the colon. The nanotherapeutics shows superiority in alleviating inflammatory symptoms over systemic PD-L1-Fc administration and mitigates the adverse effects of PD-L1-Fc administration. The nanoparticles-formulated PD-L1-Fc affects production of proinflammatory and anti-inflammatory cytokines, attenuates the infiltration of macrophages, neutrophils, and dendritic cells, increases the frequencies of Treg, Th1 and Tfh cells, reshapes the gut microbiota composition; and increases short-chain fatty acid production. In summary, PD-L1-Fc-decorated nanoparticles may provide an effective and safe strategy for the targeted treatment of IBD.

Functional characterization of Nosema bombycis (microsporidia) trehalase 3.

Nosema bombycis, an obligate intracellular parasite, is a single-celled eukaryote known to infect various tissues of silkworms, leading to the manifestation of pebrine. Trehalase, a glycosidase responsible for catalyzing the hydrolysis of trehalose into two glucose molecules, assumes a crucial role in thermal stress tolerance, dehydration, desiccation stress, and asexual development. Despite its recognized importance in these processes, the specific role of trehalase in N. bombycis remains uncertain. This investigation focused on exploring the functions of trehalase 3 in N. bombycis (NbTre3). Immunofluorescence analysis of mature (dormant) spores indicated that NbTre3 primarily localizes to the spore membrane or spore wall, suggesting a potential involvement in spore germination. Reverse transcription-quantitative polymerase chain reaction results indicated that the transcriptional level of NbTre3 peaked at 6 h post N. bombycis infection, potentially contributing to energy storage for proliferation. Throughout the life cycle of N. bombycis within the host cell, NbTre3 was detected in sporoplasm during the proliferative stage rather than the sporulation stage. RNA interference experiments revealed a substantial decrease in the relative transcriptional level of NbTre3, accompanied by a certain reduction in the relative transcriptional level of Nb16S rRNA. These outcomes suggest that NbTre3 may play a role in the proliferation of N. bombycis. The application of the His pull-down technique identified 28 proteins interacting with NbTre3, predominantly originating from the host silkworm. This finding implies that NbTre3 may participate in the metabolism of the host cell, potentially utilizing the host cell's energy resources.

Recombinase-aided amplification coupled with lateral flow dipstick for efficient and accurate detection of Bombyx mori nucleopolyhedrovirus.

The infection of Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the main causes of economic losses in sericulture. Thus, it is essential to establish rapid and effective method for BmNPV detection. In the present study, we have developed a recombinase-aided amplification (RAA) to amplify the BmNPV genomic DNA at 37 °C within 30 min, and achieved a rapid detection method by coupling with a lateral flow dipstick (LFD). The RAA-LFD method had a satisfactory detection limit of 6 copies/µL of recombinant plasmid pMD19-T-IE1, and BmNPV infection of silkworm can be detected 12 h post-infection. This method was highly specific for BmNPV, and without cross-reactivity to other silkworm pathogens. In contrast to conventional polymerase chain reaction (PCR), the RAA-LFD assay showed higher sensitivity, cost-saving, and especially is apt to on-site detection of BmNPV infection in the sericulture production.

Ssn6 Interacts with Polar Tube Protein 2 and Transcriptional Repressor for RNA Polymerase II: Insight into Its Involvement in the Biological Process of Microsporidium Nosema bombycis.

Nosema bombycis is a representative species of Microsporidia, and is the pathogen that causes pebrine disease in silkworms. In the process of infection, the polar tube of N. bombycis is injected into the host cells. During proliferation, N. bombycis recruits the mitochondria of host cells. The general transcriptional corepressor Ssn6 contains six tetratricopeptide repeats (TPR) and undertakes various important functions. In this study, we isolated and characterized Nbssn6 of the microsporidium N. bombycis. The Nbssn6 gene contains a complete ORF of 1182 bp in length that encodes a 393 amino acid polypeptide. Indirect immunofluorescence assay showed that the Ssn6 protein was mainly distributed in the cytoplasm and nucleus at the proliferative phase of N. bombycis. We revealed the interaction of Nbssn6 with polar tube protein 2 (Nbptp2) and the transcriptional repressor for RNA polymerase II (Nbtrrp2) by Co-IP and yeast two-hybrid assays. Results from RNA interference further confirmed that the transcriptional level of Nbptp2 and Nbtrrp2 was regulated by Nbssn6. These results suggest that Nbssn6 impacts the infection and proliferation of N. bombycis via interacting with the polar tube protein and transcriptional repressor for RNA polymerase II.

Relationship among Chinese herb polysaccharide (CHP), gut microbiota, and chronic diarrhea and impact of CHP on chronic diarrhea.

Chronic diarrhea, including diarrhea-predominant irritable bowel syndrome (IBS-D), osmotic diarrhea, bile acid diarrhea, and antibiotic-associated diarrhea, is a common problem which is highly associated with disorders of the gut microbiota composition such as small intestinal bacterial overgrowth (SIBO) and so on. A growing number of studies have supported the view that Chinese herbal formula alleviates the symptoms of diarrhea by modulating the fecal microbiota. Chinese herbal polysaccharides (CHPs) are natural polymers composed of monosaccharides that are widely found in Chinese herbs and function as important active ingredients. Commensal gut microbiota has an extensive capacity to utilize CHPs and play a vital role in degrading polysaccharides into short-chain fatty acids (SCFAs). Many CHPs, as prebiotics, have an antidiarrheal role to promote the growth of beneficial bacteria and inhibit the colonization of pathogenic bacteria. This review systematically summarizes the relationship among gut microbiota, chronic diarrhea, and CHPs as well as recent progress on the impacts of CHPs on the gut microbiota and recent advances on the possible role of CHPs in chronic diarrhea.

Safety and efficacy of waterjet debridement vs. conventional debridement in the treatment of extremely severe burns: A retrospective analysis.

INTRODUCTION: Patients with extremely severe burns often require rapid wound closure with a tangential excision or escharectomy combined with a skin graft to reduce life-threatening complications such as infection. Traditional tangential excision surgery using the Watson or Humby knife does not allow accurate excision of necrotic tissue and often removes too much active tissue, which is detrimental to the rapid healing of the wound. Importantly, the Versajet hydrosurgical system, with its smaller handle, allows for more precise excision of necrotic burn tissue and preserves more active dermal tissue, positively affecting wound healing and scarring. This study compared the safety and efficacy of hydrosurgical combined with autologous skin grafting to conventional excision combined with autologous skin grafting in patients with extremely severe burn. METHODS: Information of sixty burn patients with total body surface area (TBSA) > 50 % treated at the first affiliated hospital of Anhui Medical University from January 2019 to August 2022 were analyzed. The patients were divided into a conventional debridement group (n = 37) and a hydrosurgical debridement group (n = 23) according to the approach used. The hydrosurgical debridement group and the conventional debridement group were compared from the difference between the duration of the first debridement surgery, wound healing time, the changes of red blood cells and hemoglobin concentration postoperative, total blood transfusion, hospitalization cost, skin grafting frequency, procalcitonin, wound bacterial culture, albumin and prealbumin. RESULTS: Information on age, gender, weight, inhalation injury, hypovolemic shock, preoperative procalcitonin, preoperative albumin, preoperative prealbumin, the operation frequency (n ≥ 3), preoperative trauma culture and postoperative trauma culture were compared between both groups (P > 0.05). Operative time and wound healing time were significantly shorter in patients with hydrosurgical debridement combined with autologous skin grafting than those in the control group (P < 0.05), while hospitalization costs were not significantly different between the two groups (P > 0.05). The changes of red blood cells and hemoglobin concentration during the postoperative period in the hydrosurgical debridement group were less significantly than those in the conventional debridement group (P < 0.05). The total amount of red blood cells transfused during hospitalization was significantly lower in the hydrosurgical debridement group than that in the conventional debridement group (P < 0.05), but the total amount of fresh frozen plasma transfused during hospitalization was not statistically significant between the two groups (P > 0.05). Albumin on the third day after surgery and prealbumin on the first, third and fifth day after surgery improved more significantly than those in the control group(P < 0.05), however, there were no significant differences between the two groups in albumin on the first and fifth postoperative days (P > 0.05). The PCT level in the conventional debridement group was significantly higher than that in the hydrosurgical debridement group on the first, third and fifth days after surgery(P < 0.05). CONCLUSION: The hydrosurgical debridement group presented with shorter operative time, less blood loss during surgery, faster postoperative nutritional recovery, less postoperative inflammatory response and faster wounds healing, and did not increase the hospitalization cost, postoperative bacterial culture of the wounds and the number of skin grafting surgeries. In patients with extremely severe burn, hydrosurgical debridement combined with autologous skin grafting group is safer and more effective than those in the conventional debridement combined with autologous skin grafting group.

Treatment of refractory or relapsed myelodysplastic neoplasms with luspatercept: a multicenter Chinese study.

Few effective therapies are available to treat patients with relapsed/refractory myelodysplastic neoplasms (MDS). Luspatercept was shown to display good efficacy in a phase 3 clinical trial for lower-risk MDS (LR-MDS) patients, yet real-world data are limited, especially in China. Therefore, data from patients diagnosed as having MDS with low blasts and SF3B1 mutation (MDS-SF3B1) and MDS with SF3B1 mutation and thrombocytosis were retrospectively analyzed. Of the 23 enrolled patients, 17 (73.9%) were males (median age 67 years: range 29 to 80 years). Previously, a total of 22 (95.7%) patients had received recombinant human erythropoietin (rhEPO), 9 (39.1%) roxadustat, 7 (30.4%) lenalidomide and 3 (13.0%) hypomethylating agents (HMA). The median treatment time was 22.9 weeks (9.0-32.4). At week 12, 60.9% (14/23) of the patients achieved a hematologic improvement-erythroid (HI-E) response. Red blood cell transfusion independence (RBC-TI) for ≥ 8 weeks was found in 57.1% (8/14) of transfusion-dependent patients. The median hemoglobin concentration was 84 g/L, and patients had significantly higher hemoglobin concentrations after 12 weeks of treatment (P < 0.001). It is noteworthy that responders had a greater reduction in serum ferritin (P = 0.021). Those with serum EPO < 500 IU/L at baseline tended to have a higher HI-E rate (P = 0.081), but only patients in non-transfusion and low transfusion burden (LTB) subgroups had statistical differences (P = 0.024). The most commonly occurring adverse events were blood bilirubin increase (17.4%), fatigue (13.0%) and dizziness (13.0%). Luspatercept was effective and tolerated well in refractory LR-MDS-SF3B1 patients. In particular, baseline non-transfusion and LTB patients exhibited a greater response rate to treatment.

Afidopyropen suppresses silkworm growth and vitality by affecting carbohydrate metabolism and immune function.

Afidopyropen has strong insecticidal toxicity to sucking pests by silencing the vanilloid-type transient receptor potential (TRPV) channels. However, the toxicity of afidopyropen to the Lepidoptera model insect silkworm remain unknown. In this study, the LC50 of afidopyropen to the silkworm at 72 h exposure was 256.82 mg/L. This indicates that afidopyropen is moderately toxic to the silkworm. Long-term exposure to concentrations of 100 mg/L, or less, of afidopyropen, significantly reduced silkworm growth, vitality, silk protein synthesis, and fecundity. A total of 220 differentially expressed genes (DEGs) were detected by transcriptome sequencing, among which 166 were downregulated and 54 were upregulated. Gene Ontology (GO) enrichment analysis showed that the DEGs were enriched in the immune system, immune response and carbohydrate metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that DEGs were primarily concentrated in carbohydrate metabolism and biosynthesis of neomycin, kanamycin and gentamicin. Genes related to carbohydrate metabolism and immune system pathways in silkworm were detected by quantitative real-time PCR. The results showed that the genes related to carbohydrate metabolism, silk protein synthesis, and immune response were significantly downregulated. These genes included BCL-6 corepressor-like protein 1 (BCORL1), hexokinase type 2 (HEXO2), phosphoserine aminotransferase 1 (PSAT1), relish (Rel), peptidoglycan recognition protein 2 (PGRP2) and 27 kda glycoprotein precursor (P27K). The data demonstrated the toxic effects of afidopyropen against the silkworm and its regulation of genes responsible for immune function and abscissa carbohydrate metabolism.

MicroRNA-199a-3p suppresses the invasion and metastasis of nasopharyngeal carcinoma through SCD1/PTEN/AKT signaling pathway.

MicroRNAs (miRs) are 18-25 nucleotides non-coding RNAs, which contribute to tumorigenesis. Previous studies have demonstrated that miR-199a-3p is dysregulated in human nasopharyngeal carcinoma (NPC), but its role in NPC progression still largely unknown. The current study aimed to determine the potential role of miR-199a-3p in NPC progression and the underlying mechanisms. In this study, miR-199a-3p was found to be prominently down-regulated in NPC tissues and cells. The cellular assay showed that transfection of miR-199a-3p markedly repressed the migration, invasion and induced epithelial-mesenchymal transition (EMT) in both 5-8F and CNE-2 cell lines. By dual-luciferase reporter, western blotting and gas chromatography assays, we found that SCD1 is not only highly expressed in NPC tissues and negatively associated with the prognosis of NPC patients but also can be apparently downregulated by miR-199a-3p in NPC cells, suggesting that SCD1 is a direct target gene of miR-199a-3p. Moreover, inhibition of miR-199a-3p expression activated PI3K/Akt signaling and up-regulated the expression of MMP-2. With tumor xenograft models in nude mice, we also showed that miR-199a-3p repressed tumor growth in vivo. Our study demonstrated that miR-199a-3p inhibited migration and invasion of NPC cells through downregulating SCD1 expression, thus providing a potential target for the treatment of NPC.

Calculation of excited states of monolayer TPPA-COF based on first principles.

Two-dimensional covalent organic frameworks (COFs) have always been a hot topic in condensed matter physics. Herein, the first 100 excited states of the TPPA-COF are calculated to investigate the optical absorption properties of the materials in the interval. The stable molecular structure of monolayer TPPA-COF is obtained by first-principles calculation, which can be regarded as a hexagon with an aperture size of 18.25 Å. By means of the band structure and density of state analysis, it is found that the monolayer band gap width of the TPPA-COF is 1.52 eV. All excited states of the TPPA-COF exhibit obvious pi → pi* (delocalized π to anti π) local excitation characteristics through analysing the spatial distribution of the electron-hole pairs of the 10 excited states with the highest oscillator strength among the first 100 excited states. In addition, the simulated UV-vis spectra show that the maximum absorption intensity of the TPPA-COF is about 357 684 mol-1 cm-1, indicating that the TPPA-COF is a potential light-absorbing material.