circSORBS1 inhibits lung cancer progression by sponging miR-6779-5p and directly binding RUFY3 mRNA.

Lung cancer is the primary cause of cancer-related death worldwide, and its global incidence and mortality rates remain high. The differential expression of circular RNAs (circRNAs) can affect the development of cancer, but the mechanisms by which circRNAs regulate lung cancer progression remain unclear. In this study, we identified circSORBS1, a circRNA that has not been previously described in lung cancer and is significantly underexpressed in lung cancer tissues, blood and cell lines, and the low expression of circSORBS1 correlated with tumour grade and prognosis. In vitro and in vivo functional experiments revealed that circSORBS1 overexpression inhibited cell proliferation and migration while enhancing apoptosis. Mechanistically, circSORBS1 acts as a sponge for miR-6779-5p, indirectly inhibiting RUFY3 mRNA degradation. Simultaneously, it binds to RUFY3 mRNA to enhance its stability. This dual regulatory mechanism leads to an increase in RUFY3 protein levels, which ultimately activates the YWHAE/BAD/BCL2 apoptotic signalling pathway and suppresses lung cancer progression. Our findings not only increase the knowledge about the regulatory pattern of circRNA expression but also provide new insights into the mechanisms by which circRNAs regulate lung cancer development.

Impact of Vitamin C on Inflammatory Response and Myocardial Injury in Sepsis Patients.

Background: Amidst the complexities of sepsis-induced inflammatory responses and myocardial injury, this study investigates the therapeutic potential of vitamin C in mitigating sepsis complications. The findings offer crucial insights into the prospective use of vitamin C, shaping future strategies for enhanced patient care. Objective: To investigate the impact of vitamin C on the inflammatory response and myocardial damage in individuals with sepsis. Methods: A total of 83 sepsis patients treated in our hospital from January 2021 to January 2023 were randomly divided into a control group (n=41, receiving basic treatment) and a study group (n=42, receiving vitamin C in addition to basic treatment). To evaluate the impact of treatment, we compared organ dysfunction, inflammatory response index, myocardial injury index, and morbidity/mortality rates before and after the intervention in both groups. It allowed for a comprehensive analysis of the treatment's effects on these key parameters. Results: After therapy, the study group exhibited lower SOFA ratings compared to the control group (P < .05). Levels of Hypersensitive C-reactive Protein (hs-CRP), Tumor Necrosis Factor (TNF), High Mobility Group Protein B1 (HMGB1), Creatine Kinase Isoenzyme (CK-MB), Troponin I (cTnI), and B-type brain natriuretic peptide (BNP) were significantly lower in the study group than in the control group after treatment (P < .05). The study group also demonstrated a lower morbidity and mortality rate (9.52%) compared to the control group (29.27%) (P < .05). Conclusions: Vitamin C supplementation holds significant therapeutic value, contributing to reduced inflammatory response, myocardial injury, morbidity, and mortality rates in sepsis patients. This intervention enhances clinical efficacy, fostering disease regression.

miR-140 and miR-200 regulate the migratory heterogeneity of location-specific Schwann cell population.

Schwann cells are functional cells in nerve regeneration and are commonly used as seed cells in tissue engineering. Enhanced Schwann cell migration capacity improves recovery effects, and thus, the identification of Schwann cells with greater migration ability is of great importance. In the present study, we examined the biological activities of Schwann cells collected from rat sciatic nerves (SN) and dorsal root ganglia (DRG). Observations from transwell migration assay and wound healing assay demonstrate that DRG Schwann cells migrate at a faster speed as compared with SN Schwann cells. Sequencing and bioinformatics suggest that differentially expressed genes between SN and DRG Schwann cells are associated with cell motility and migration. miR-140 and miR-200, two microRNAs (miRNAs) that are highly expressed in SN Schwann cells negatively influence Schwann cell migration and thus may be key regulators of Schwann cell phenotype. Igsf10, Plxna2, and Lcp1 are screened as candidate downstream targets of miR-140 and miR-200 based on bioinformatic analysis and their expression correlation with miRNAs. Our comparative analysis displays the unique characteristics of Schwann cells in different anatomical localizations and demonstrates that DRG Schwann cells are suitable seed cells for tissue engineering and regenerative medicine.

Nucleus-localized circSLC39A5 suppresses hepatocellular carcinoma development by binding to STAT1 to regulate TDG transcription.

Accumulating evidence indicates that circular RNAs (circRNAs) are inextricably linked to cancer development. However, the function and mechanism of nucleus-localized circRNAs in hepatocellular carcinoma (HCC) still require investigation. Here, qRT-PCR and receiver-operating characteristic curve were used to detect the expression and diagnostic potential of circSLC39A5 for HCC. The biological function of circSLC39A5 in HCC was investigated in vitro and in vivo. Nucleoplasmic separation assay, fluorescence in situ hybridization, RNA pulldown, RNA immunoprecipitation, the HDOCK Server, the NucleicNet Webserver, crosslinking-immunoprecipitation, MG132 treatment, and chromatin immunoprecipitation were utilized to explore the potential molecular mechanism of circSLC39A5 in HCC. The results showed that circSLC39A5 was downregulated in both HCC tissues and plasma and was associated with satellite nodules and lymph node metastasis/vascular invasion. CircSLC39A5 was stably expressed in plasma samples under different storage conditions, showing good diagnostic potential for HCC (AUC = 0.915). CircSLC39A5 inhibited proliferation, migration, and invasion, facilitated the apoptosis of HCC cells, and was associated with low expression of Ki67 and CD34. Remarkably, circSLC39A5 is mainly localized in the nucleus and binds to the transcription factor signal transducer and activator of transcription 1 (STAT1), affecting its stabilization and expression. STAT1 binds to the promoter of thymine DNA glycosylase (TDG). Overexpression of circSLC39A5 elevates TDG expression and reverses the increase of proliferating cell nuclear antigen (PCNA) expression and the overactive cell proliferation caused by TDG silencing. Our findings uncovered a novel plasma circRNA, circSLC39A5, which may be a potential circulating diagnostic marker for HCC, and the mechanism by which nucleus-localized circSLC39A5 exerts a transcriptional regulatory role in HCC by affecting STAT1/TDG/PCNA provides new insights into the mechanism of circRNAs.

Metasurfaces for generating higher-order Poincaré beams by polarization-selective focusing and overall elimination of co-polarization components.

Focused higher-order Poincaré (HOP) beams are of particular interest because they facilitate understanding the exotic properties of structured light and their applications in classical physics and quantum information. However, generating focused HOP beams using metasurfaces is challenging. In this study, we proposed a metasurface design comprising two sets of metal nanoslits for generating coaxially focused HOP beams. The nanoslits were interleaved on equispaced alternating rings. The initial rings started at the two adjacent Fresnel zones to provide opposite propagation phases for overall elimination of the co-polarization components. With the designed hyperbolic and helical profiles of the geometric phases, the two vortices of the opposite cross-circular-polarizations were formed and selectively focused, realizing HOP beams of improved quality. Simulations and experimental results demonstrated the feasibility of the proposed metasurface design. This study is of significance in the integration of miniaturized optical devices and enriches the application areas of metasurfaces.

Effect of neoadjuvant therapy on serum transforming growth factor-ß, squamous cell carcinoma associated antigen, and prognosis in patients with locally advanced esophageal cancer.

It was to explore the effect of neoadjuvant therapy (NAT) on serum-related indicators and prognosis of patients with locally advanced esophageal cancer (EC). 400 EC patients were grouped as controls (295 cases, radical EC resection alone) and research group (105 cases, NAT plus radical EC resection). The levels of serum carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), programmed death-1 (PD-1), PD-2, transforming growth factor-ß1 (TGF-ß1), and squamous cell carcinoma (SCC) antigen were detected before and after treatment. The follow-up lasted for 3 years. The quality of life (QoL) was evaluated by QLQ-OES24. The recurrence rate, recurrence time, overall survival rate (SR), disease-free SR, and complication rate were compared. Compared with controls, the levels of serum CA19-9, CEA, CYFRA21-1, PD-1, PD-2, TGF-ß1, and SCC were decreased, the QoL score was increased 3 years post-treatment, and the recurrence time was prolonged in the research group (P<0.05). The R0 resection rate, recurrence rate, 3-year overall SR, and disease-free SR of the two groups were 67.12% vs 85.71%, 21.36% vs 6.67%, 56.27% vs 77.14%, 29.83% vs 45.71%, respectively (P<0.05). The complication rates of the two groups were 32.54% and 29.52%, respectively (P>0.05). NAT plus radical resection of EC can effectively reduce the level of serum oncology markers in patients with locally advanced EC, reduce the postoperative recurrence rate, improve QoL and SR, and has high safety.

Effect of dietary antioxidants on excretion of perfluorooctanoic acid (PFOA) via regulating uptake transporters expression and intestinal permeability in mice.

Dietary antioxidants, including 2,6-di-tert-butyl-hydroxytoluene (BHT), α-tocopherol (αT) and tea polyphenol (TP), have been widely used in food. However, no data about the effect of food antioxidants on PFOA excretion were available. In this study, excretion of PFOA toward mice (four mice in each group) under the influence of co-ingested food antioxidants (i.e., BHT, αT, and TP) were investigated, and mechanism involved in excretion of PFOA, including RNA expression of uptake and efflux transporters in kidneys and liver involved in PFOA transport and intestinal permeability were also investigated. Chronic exposure to BHT (1.56 mg/kg) increased urinary PFOA excretion from 1795 ± 340 ng/mL (control) to 3340 ± 29.9 ng/mL (BHT treatment). TP treatment (12.5 mg/kg) decreased urinary excretion of PFOA, i.e., with a decrease percentage of 70% compared to the control. Organic anion transporting polypeptides (Oatps) act as uptake transporter mediate renal elimination or reabsorption of PFOA in the kidney. The decrease in urinary excretion of PFOA under TP treatment was associated with significantly (p < 0.05) enhanced expression of Oatp1a1 in the kidney (1.78 ± 0.58 vs 1.00 ± 0.18 in control), which facilitated renal reabsorption of PFOA and in turn decreased urinary excretion of PFOA. αT treatment (12.5 mg/kg) increased fecal PFOA excretion with a value of 228 ± 95.8 ng/g vs control (96.8 ± 22.7 ng/g). Mechanistic investigation revealed that αT treatment reduced intestinal permeability, resulting in increased fecal PFOA excretion.

Nuclear Factor-Kappa B-induced miRNA-518a-5p represses trophoblast cell migration and invasion by the Nuclear Factor-Kappa B pathway.

Preeclampsia is associated with the insufficient invasion of trophoblasts. NF-κB is a transcription factor in almost all mammalian cells and has been validated to be upregulated in the maternal circulation and placenta of women with preeclampsia. MiR-518a-5p is also overexpressed in pre-eclamptic placenta. The present study was designed to explore whether NF-κB can transcriptionally activate miR-518a-5p and investigate the influences of miR-518a-5p on the viability, apoptosis, migration, and invasion of HTR8/SVneo trophoblast. In situ hybridization and real time polymerase chain reaction were used to reveal miR-518a-5p expression in placenta tissues and HTR8/SVneo cells, respectively. Cell migration and invasion were detected using Transwell inserts. Our findings indicated that NF-κB p52, p50, and p65 can bind to miR-518a-5p gene promoter. MiR-518a-5p further influences the levels of p50 and p65 but not p52. HTR8/SVneo cell viability and apoptosis were not influenced by miR-518a-5p. However, miR-518a-5p represses the migratory/invasive capacities of HTR8/SVneo cell and decreased gelatinolytic activity of MMP2 and MMP9, which was reversed by an NF-κB inhibitor. To sum up, miR-518a-5p is induced by NF-κB and represses trophoblast cell migration and invasion by the NF-κB pathway.

A novel ratiometric fluorescence probe for the detection of copper (II) and silver(I) based on assembling dye-doped silica core-shell nanoparticles with gold nanoclusters.

A creatively designed and constructed a multifunctional ratiometric fluorescence probe is reported by assembling glutathione (GSH)-protected gold nanoclusters (AuNCs) with fluorescein-doped mesoporous silica nanoparticle (FS) for the detection of Cu2+ and Ag+ ions, which could eliminate most interferences by self-calibration. Under the excitation at 450 nm, the fluorescence connected with AuNCs can rapidly respond by quenching or enhancement, respectively, for Cu2+ and Ag+ ions, while the fluorescein isothiocyante (FITC) fluorescence served as reference with negligible change. The fluorescence intensity ratio showed good linear relationships with Cu2+ and Ag+ concentrations in the range 0.5-10 µM and 0.1-8 µM, respectively. The detection limits were as low as 140 nM and 60 nM for Cu2+ and Ag+ ions, respectively. The color change induced by fluorescent intensity ratio variation could also be employed for visual discrimination. The AuNC-embedded FS (FS-Au) nanoprobe was successfully used for Cu2+ and Ag+ ion determination in drinking water and intracellular Cu2+ imaging, which exhibits promising prospects in cost-effective and rapid determination of both Cu2+ and Ag+ with good sensitivity and selectivity.

Synthetic Matching of Complex Monoterpene Indole Alkaloid Chemical Space.

Monoterpene indole alkaloids (MIAs) are endowed with high structural and spatial complexity and characterized by diverse biological activities. Given this complexity-activity combination in MIAs, rapid and efficient access to chemical matter related to and with complexity similar to these alkaloids would be highly desirable, since such compound classes might display novel bioactivity. We describe the design and synthesis of a pseudo-natural product (pseudo-NP) collection obtained by the unprecedented combination of MIA fragments through complexity-generating transformations, resulting in arrangements not currently accessible by biosynthetic pathways. Cheminformatic analyses revealed that both the pseudo-NPs and the MIAs reside in a unique and common area of chemical space with high spatial complexity-density that is only sparsely populated by other natural products and drugs. Investigation of bioactivity guided by morphological profiling identified pseudo-NPs that inhibit DNA synthesis and modulate tubulin. These results demonstrate that the pseudo-NP collection occupies similar biologically relevant chemical space that Nature has endowed MIAs with.

Single-cell analyses reveal the differentiation shifts of Schwann cells in neonatal rat sciatic nerves.

Schwann cells provide essential physical and chemical support for neurons and play critical roles in the peripheral nervous system. To acquire an enhanced understanding of the genetic characteristics of Schwann cells, we analyzed single-cell transcriptional profiling of Schwann cells in neonatal rat sciatic nerves, ordered the pseudotemporal states of Schwann cells, and determined the magnitude of RNA velocity vectors as well as cell cycle stages of Schwann cell subtypes. We discovered the cellular heterogeneity of Schwann cells in neonatal rat sciatic nerves, revealed the dynamic changes of Schwann cell subtypes, and pointed out the differentiation trajectory from Timp3- and Col5a3-expressing Schwann cell subtype 3 to other Schwann cell subtypes. The functional interpretation further indicated that subtype 3 Schwann cells display genetic signatures of DNA replication and the acquisition of mesenchymal traits. Our study presents a transcriptional summarization of the differentiation states of Schwann cell subtypes in neonatal rat sciatic nerves at single-cell resolution and may serve as a foundation for a deeper comprehension of the involvement of Schwann cells in the development and regeneration of peripheral nerves.

CircUSP36 attenuates ischemic stroke injury through the miR-139-3p/SMAD3/Bcl2 signal axis.

Circular RNAs (circRNAs) play important roles in a variety of physiological and pathological processes. Researches demonstrated that circRNAs provided novel strategies for the prevention and treatment of IS. However, the biological function of hsa_circ_0045932 (circUSP36) has not been revealed yet. Here, we explored the effect of circUSP36 on IS and its mechanism. In the present study, we found that circUSP36 expression was significantly decreased in the peripheral blood of IS patients and was negatively correlated with the severity, infarct volume and poor prognosis of IS. Functionally, circUSP36 silencing inhibited cellular activity and proliferation and promoted apoptosis after oxygen-glucose deprivation/reperfusion (OGD/R) treatment, while circUSP36 overexpression reversed these cellular phenotypes in vitro. Adeno-associated virus (AAV)-mediated overexpression of circUSP36 attenuates brain injury and neurological deficit and promotes motor function recovery of transient middle cerebral artery occlusion (tMCAO) mice. Subsequently, the RNA antisense purification (RAP) and luciferase reporter assay confirmed that circUSP36 acts as a sponge to adsorb miR-139-3p, and miR-139-3p could bind and inhibit SMAD3 expression. Further rescue experiments showed that both miR-139-3p overexpression and SMAD3 silencing could abolish the antiapoptotic effect of circUSP36. In summary, we reveal for the first time that circUSP36 attenuates ischemic stroke injury through the miR-139-3p/SMAD3/Bcl2 signal axis, which make circUSP36 a potential therapeutic target for IS.

Apigenin inhibits growth of melanoma by suppressing miR-512-3p and promoting the G1 phase of cell cycle involving the p27 Kip1 protein.

In the present study, we screened multiple melanoma cell lines for treatment of Apigenin and miRNA expression, also studied the role of miR-512-3p in melanoma. RT-PCR analysis was done for screening miRNA in melanoma cell lines (WM1361B, WM983A, WM1341D, SK-MEL-3, SH-4, SK-MEL-24 and RPMI-7951) compared to normal human epidermal melanocytes. Colony formation assay for cell viability studies, cell cycle by flowcytometry and protein expression by immunoblot analysis. For in vivo analysis tumour xenograft mouse model was created. Immunohistochemistry was done for PCNA positive cells. For expression of miR-512-3p in tumour tissues fluorescence in situ hybridization was done. In silico studies were done by molecular docking studies. The WM1361B and WM983A cell lines showed overexpression of miR-512-3p and increased cell proliferation compared to normal human epidermal melanocytes. Treatment of anti-miR-512-3p to WM1361B and WM983A cells halted cell proliferation and also caused G1-phase arrest. We studied the effect of Apigenin on the expression levels of miR-512-3p and associated molecular targets. Apigenin treatment in WM1361B and WM983A cells showed inhibition in expression of miR-512-3p, arrest of G1 phase of cell cycle, cytotoxicity and revival of p27 Kip1. Apigenin treatment significantly suppressed the growth of WM1361B in tumour induced mice, the activity was associated with decreased levels of miR-512-3p, tumour cell proliferation and increased levels of p27 Kip1 protein. Docking studies confirm potential affinity of Apigenin for p27 Kip1. Apigenin acts as an inhibitor of miR-512-3p by suppressing growth of melanoma both in vitro and in vivo targeting the p27 Kip1 axis.

COVID-19 and the promise of small molecule therapeutics: Are there lessons to be learnt?

The coronavirus disease 2019 (COVID-19) pandemic had grounded the world to a standstill. As the disease continues to rage two years on, it is apparent that effective therapeutics are critical for a successful endemic living with COVID-19. A dearth in suitable antivirals has prompted researchers and healthcare professionals to investigate existing and developmental drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although some of these drugs initially appeared to be promising for the treatment of COVID-19, they were ultimately found to be ineffective. In this review, we provide a retrospective analysis on the merits and limitations of some of these drugs that were tested against SARS-CoV-2 as well as those used for adjuvant therapy. While many of these drugs are no longer part of our arsenal for the treatment of COVID-19, important lessons can be learnt. The recent inclusion of molnupiravir and Paxlovid™ as treatment options for COVID-19 represent our best hope to date for endemic living with COVID-19. Our viewpoints on these two drugs and their prospects as current and future antiviral agents will also be provided.

Characterization and functional analysis of peroxiredoxin 4 gene in the Neocaridina denticulata sinensis.

Peroxiredoxin (Prx) is an antioxidant protein family, which widely exists in organisms and plays an important role in innate immunity. In this study, the full-length cDNA of a Prx gene (NdPrx) was obtained from Neocaridina denticulata sinensis, which contains a 735 bp open reading frame (ORF) and encodes a polypeptide of 244 amino acids. It is inferred that the molecular weight of the encoded amino acid is 27261.20 Da and the theoretical isoelectric point is 6.16. Phylogenetic analysis shows that NdPrx and Prx4 have high homology, so it was named NdPrx4. Multiple alignment analysis showed that the amino acid sequence of NdPrx4 had high homology with Prx4 of other species, and the similarity with Homarus americanus was the highest, 92.86%. Quantitative real-time PCR analysis showed that NdPrx4 was expressed in various tissues of N. denticulata sinensis, and the expression in ovary was the highest. It was speculated that NdPrx4 may be related to maternal immune function. Under the stimulation of Cu2+, the expression of NdPrx4 reached the peak at 36 h, and showed a downward trend until 72 h, indicating that NdPrx4 may play an important role in the stress response of N. denticulata sinensis. Then, NdPrx4 was recombinantly expressed in E. coli, and its enzymatic characteristics of rNdPrx4 were detected. The result showed that the activity of rNdPrx4 was the highest at pH 5.0 and 55 °C. It was found that Mn2+ and Ca2+ can inhibit the activity of rNdPrx4, and Zn2+ increases the activity of rNdPrx4.

Characterization of peroxiredoxin from Neocaridina denticulata sinensis and its antioxidant and DNA protection activity analysis.

Peroxiredoxin (Prx) is an antioxidant protein that widely exists in various organisms. To further investigate the role of Prx in the antioxidant and immune responses of Neocaridina denticulata sinensis, the full-length cDNA sequence of a Prx gene (Nd-Prx) from N. denticulata sinensis was obtained. The open reading frame (ORF) of Nd-Prx is 597 bp and encodes 198 amino acids. Amino acid similarity alignment showed that Nd-Prx contained a conserved sequence region "FYPLDFTFVCPTEI". qRT-PCR assay showed that Nd-Prx was expressed in all tested tissues and its expression was highest in the ovary. Nd-Prx was most highly expressed at 36 h after copper stimulation. Nd-Prx expression levels in hepatopancreas were significantly upregulated after Vibrio parahaemolyticus challenge (P < 0.05). In addition, the recombinant Nd-Prx was prepared and its enzyme activity was most stable at 70 °C with pH of 6.0. The antioxidant activity and DNA protection of recombinant Nd-Prx was also demonstrated. In summary, this study investigated the role of Prx in antioxidant and immune responses of N. denticulata sinensis, which might provide a foundation for further exploring Prx in immune system of crustaceans and for the application in disease control.

Transcriptomic analysis of Neocaridina denticulate sinensis hepatopancreas indicates immune changes after copper exposure.

Neocaridina denticulate sinensis is a promising crustacean model species due to its merits in raising and breeding. However, its molecular responses to copper remains largely unknown. In the present research, RNA-seq was used to mine the alteration in transcriptome of N. denticulate sinensis hepatopancreas under copper exposure. A total of 16,423 DEGs was identified between control and Cu2+ treatment groups. GO enrichment analysis of all DEGs suggested down-regulated genes exceeded up-regulated genes in all the significantly enriched terms, except for RNA polymerase III complex (GO:0005666). KEGG analysis showed Cu exposure only induced two significantly enriched pathways, including Phagosome (ko04145) and Pathogenic Escherichia coli infection (ko05130). Besides, pattern recognition receptors as Toll, lectin B, CTL1 and SRB, AMPs as crustin type I, lysozyme, and NOS were down-regulated after Cu2+ exposure, while hemocyanin, MT, HSP70 and HSP90 were significantly up-regulated, implying these molecules may play vital role in Cu2+ detoxification of N. denticulate sinensis. Our results here provide research direction of heavy metal detoxification of N. denticulate sinensis, simultaneously enriched its genomic information.

Circular RNA circGLIS3 promotes bladder cancer proliferation via the miR-1273f/SKP1/Cyclin D1 axis.

Extensive research confirmed that circRNA can play a regulatory role in various stages of tumors by interacting with various molecules. Identifying the differentially expressed circRNA in bladder cancer and exploring its regulatory mechanism on bladder cancer progression are urgent. In this study, we screened out a circRNA-circGLIS3 with a significant upregulation trend in both bladder cancer tissues and cells. Bioinformatics prediction results showed that circGLIS3 may be involved in multiple tumor-related pathways. Function gain and loss experiments verified circGLIS3 can affect the proliferation, migration, and invasion of bladder cancer cells in vitro. Moreover, silencing circGLIS3 inhibited bladder cancer cell growth in vivo. Subsequent research results indicated circGLIS3 regulated the expression of cyclin D1, a cell cycle-related protein, and cell cycle progression. Mechanically, circGLIS3 upregulates the expression of SKP1 by adsorbing miR-1273f and then promotes cyclin D1 expression, ultimately promoting the proliferation of bladder cancer cells. In summary, our study indicates that circGLIS3 plays an oncogene role in the development of bladder cancer and has potential to be a candidate for bladder cancer.

Influence of Dietary Lipid Type on the Bioavailability of DDT and Its Metabolites in Soil: Mechanisms and Health Implications.

The impact of dietary lipid type on DDTr (DDT and its metabolites) relative bioavailability (RBA) in soil was investigated using an in vivo mouse model and in vitro assays. Three different lipids were long chain triglycerides (LCT), medium chain triglycerides (MCT), and short chain triglycerides (SCT). DDTr-RBA markedly (p < 0.05) increased from 51.3 ± 10.8% (control) to 94.6 ± 15.9% (10% w/w LCT) and 112 ± 20.8% (20% LCT) in LCT amended treatments. A significant increase in DDTr-RBA (92.2 ± 9.84%, p < 0.05) was also observed when mice were administered diets containing 20% MCT; however, no influence on DDTr-RBA was observed for SCT amended diets. Mechanism exploration showed that LCT and MCT enhanced DDTr solubilization by a factor of 7.31-9.59 compared to controls as a consequence of micelle formation which promoted DDTr mobilization from soil. LCT significantly enhanced DDTr intestinal absorption via increasing synthesis and secretion of apolipoprotein B 48 (32.2 ± 2.08 mg/L), compared to MCT (22.1 ± 1.32 mg/L) and SCT (15.5 ± 2.03 mg/L) treated Caco-2 cells. Mouse gut microflora analysis highlighted that LCT and MCT may increase intestinal permeability by regulating abundance of Lactobacillus, which may influence the absorption of DDTr.

Cell populations in neonatal rat peripheral nerves identified by single-cell transcriptomics.

Peripheral nerves connect central nerves with target tissues and organs and execute vital signal transduction functions. Although sub-types of neurons have been defined, the heterogeneity of cell populations in peripheral nerves, especially Schwann cells, has not been well demonstrated. Here, we collected sciatic nerves (SN) and dorsal root ganglia (DRG) from neonatal (1-day old) rats and classified cell populations by high-coverage single-cell sequencing. A total of 10 types of cells, including endothelial cells, erythrocytes, fibroblasts, monocytic cells, neurons, neutrophils, pericytes, satellite cells, Schwann cells, and vascular smooth muscle cells, were identified by transcriptome-based cell typing. The comparisons of cells in neonatal rat SN and DRG revealed distinct atlas in different tissue localizations. Investigations of ligand-receptor interactions showed that there existed direct cell-cell communications between endothelial cells and fibroblasts in SN and among endothelial cells, fibroblasts, and vascular smooth muscle cells in DRG. Schwann cells in neonatal rats were further sub-grouped to four sub-types, including LOC100134871 and Hbb expressing Schwann cell sub-type 1, Cldn19 and Emid1 expressing Schwann cell sub-type 2, Timp3 and Col5a3 expressing Schwann cell sub-type 3, and Cenpf and Mki67 expressing Schwann cell sub-type 4. These Schwann cell sub-types exhibited distinct genetic features and functional enrichments. Collectively, our results illustrated the diversity and cellular complexity of peripheral nerves at the neonatal stage and revealed the heterogeneity of Schwann cells in the peripheral nervous system.