Psychological stress to ovalbumin peptide-specific T-cell receptor transgenic mice impairs the suppressive ability of type 1 regulatory T cell.

Numerous diseases of the immune system can be traced back to the malfunctioning of the regulatory T cells. The aetiology is unclear. Psychological stress can cause disruption to the immune regulation. The synergistic effects of psychological stress and immune response on immune regulation have yet to be fully understood. The intention of this study is to analyse the interaction between psychological stress and immune responses and how it affects the functional status of type 1 regulatory T (Tr1) cells. In this study, ovalbumin peptide T-cell receptor transgenic mice were utilised. Mice were subjected to restraint stress to induce psychological stress. An airway allergy murine model was established, in which a mouse strain with RING finger protein 20 (Rnf20)-deficient CD4+ T cells were used. The results showed that concomitant exposure to restraint stress and immune response could exacerbate endoplasmic reticulum stress in Tr1 cells. Corticosterone was responsible for the elevated expression of X-box protein-1 (XBP1) in mouse Tr1 cells after exposure to both restraint stress and immune response. XBP1 mediated the effects of corticosterone on inducing Rnf20 in Tr1 cells. The reduction of the interleukin-10 expression in Tr1 cells was facilitated by Rnf20. Inhibition of Rnf20 alleviated experimental airway allergy by restoring the immune regulatory ability of Tr1 cells. In conclusion, the functions of Tr1 cells are negatively impacted by simultaneous exposure to psychological stress and immune response. Tr1 cells' immune suppressive functions can be restored by inhibiting Rnf20, which has the translational potential for the treatment of diseases of the immune system.

Allergen specific immunotherapy regulates macrophage property in the airways.

BACKGROUND: Allergen specific immunotherapy (AIT) has been widely used in allergy clinics. The therapeutic effects of it are to be improved. Macrophages occupy the largest proportion of airway immune cells. The aim of this study is to measure the effects of nasal instillation AIT (nAIT) on airway allergy by regulating macrophage functions. METHODS: An airway allergy mouse model was established with the ovalbumin-alum protocol. nAIT was conducted for mice with airway allergy through nasal instillation. The effects of nAIT were compared with subcutaneous injection AIT (SCIT) and sublingual AIT (SLIT). RESULTS: Mice with airway allergy showed the airway allergic response, including lung inflammation, airway hyper responsiveness, serum specific IgE, increase in the amounts of eosinophil peroxidase, mouse mast cell protease-1, and Th2 cytokines in bronchoalveolar lavage fluid. nAIT had a much better therapeutic effect on the airway allergic response than SCIT and SLIT. Mechanistically, we observed better absorption of allergen in macrophages, better production of IL-10 by macrophages, and better immune suppressive functions in macrophages in mice received nAIT than SCIT and SLIT. CONCLUSIONS: The nAIT has a much better therapeutic effect on suppressing the airway allergic response, in which macrophages play a critical role.

Inorganic salt starvation improves the polysaccharide production and CO2 fixation by Porphyridium purpureum.

The microalgae industry shows a promising future in the production of high-value products such as pigments, phycoerythrin, polyunsaturated fatty acids, and polysaccharides. It was found that polysaccharides have high biomedical value (such as antiviral, antibacterial, antitumor, antioxidative) and industrial application prospects (such as antioxidants). This study aimed to improve the polysaccharides accumulation of Porphyridium purpureum CoE1, which was effectuated by inorganic salt starvation strategy whilst supplying rich carbon dioxide. At a culturing temperature of 25 °C, the highest polysaccharide content (2.89 g/L) was achieved in 50% artificial seawater on the 12th day. This accounted for approximately 37.29% of the dry biomass, signifying a 25.3% increase in polysaccharide production compared to the culture in 100% artificial seawater. Subsequently, separation, purification and characterization of polysaccharides produced were conducted. Furthermore, the assessment of CO2 fixation capacity during the cultivation of P. purpureum CoE1 was conducted in a 10 L photobioreactor. This indicated that the strain exhibited an excellent CO2 fixation capacity of 1.66 g CO2/g biomass/d. This study proposed an efficient and feasible approach that not only increasing the yield of polysaccharides by P. purpureum CoE1, but also fixing CO2 with a high rate, which showed great potential in the microalgae industry and Bio-Energy with Carbon Capture and Storage.

Catalase (CAT) Gene Family in Oil Palm (Elaeis guineensis Jacq.): Genome-Wide Identification, Analysis, and Expression Profile in Response to Abiotic Stress.

Catalases (CATs) play crucial roles in scavenging H2O2 from reactive oxygen species, controlling the growth and development of plants. So far, genome-wide identification and characterization of CAT genes in oil palm have not been reported. In the present study, five EgCAT genes were obtained through a genome-wide identification approach. Phylogenetic analysis divided them into two subfamilies, with closer genes sharing similar structures. Gene structure and conserved motif analysis demonstrated the conserved nature of intron/exon organization and motifs among the EgCAT genes. Several cis-acting elements related to hormone, stress, and defense responses were identified in the promoter regions of EgCATs. Tissue-specific expression of EgCAT genes in five different tissues of oil palm was also revealed by heatmap analysis using the available transcriptome data. Stress-responsive expression analysis showed that five EgCAT genes were significantly expressed under cold, drought, and salinity stress conditions. Collectively, this study provided valuable information on the oil palm CAT gene family and the validated EgCAT genes can be used as potential candidates for improving abiotic stress tolerance in oil palm and other related crops.

Oil Palm AP2 Subfamily Gene EgAP2.25 Improves Salt Stress Tolerance in Transgenic Tobacco Plants.

AP2/ERF transcription factor genes play an important role in regulating the responses of plants to various abiotic stresses, such as cold, drought, high salinity, and high temperature. However, less is known about the function of oil palm AP2/ERF genes. We previously obtained 172 AP2/ERF genes of oil palm and found that the expression of EgAP2.25 was significantly up-regulated under salinity, cold, or drought stress conditions. In the present study, the sequence characterization and expression analysis for EgAP2.25 were conducted, showing that it was transiently over-expressed in Nicotiana tabacum L. The results indicated that transgenic tobacco plants over-expressing EgAP2.25 could have a stronger tolerance to salinity stress than wild-type tobacco plants. Compared with wild-type plants, the over-expression lines showed a significantly higher germination rate, better plant growth, and less chlorophyll damage. In addition, the improved salinity tolerance of EgAP2.25 transgenic plants was mainly attributed to higher antioxidant enzyme activities, increased proline and soluble sugar content, reduced H2O2 production, and lower MDA accumulation. Furthermore, several stress-related marker genes, including NtSOD, NtPOD, NtCAT, NtERD10B, NtDREB2B, NtERD10C, and NtP5CS, were significantly up-regulated in EgAP2.25 transgenic tobacco plants subjected to salinity stress. Overall, over-expression of the EgAP2.25 gene significantly enhanced salinity stress tolerance in transgenic tobacco plants. This study lays a foundation for further exploration of the regulatory mechanism of the EgAP2.25 gene in conferring salinity tolerance in oil palm.

Potential role of Bcl2 in lipid metabolism and synaptic dysfunction of age-related hearing loss.

Age-related hearing loss (ARHL) is a prevalent condition affecting millions of individuals globally. This study investigated the role of the cell survival regulator Bcl2 in ARHL through in vitro and in vivo experiments and metabolomics analysis. The results showed that the lack of Bcl2 in the auditory cortex affects lipid metabolism, resulting in reduced synaptic function and neurodegeneration. Immunohistochemical analysis demonstrated enrichment of Bcl2 in specific areas of the auditory cortex, including the secondary auditory cortex, dorsal and ventral areas, and primary somatosensory cortex. In ARHL rats, a significant decrease in Bcl2 expression was observed in these areas. RNAseq analysis showed that the downregulation of Bcl2 altered lipid metabolism pathways within the auditory pathway, which was further confirmed by metabolomics analysis. These results suggest that Bcl2 plays a crucial role in regulating lipid metabolism, synaptic function, and neurodegeneration in ARHL; thereby, it could be a potential therapeutic target. We also revealed that Bcl2 probably has a close connection with lipid peroxidation and reactive oxygen species (ROS) production occurring in cochlear hair cells and cortical neurons in ARHL. The study also identified changes in hair cells, spiral ganglion cells, and nerve fiber density as consequences of Bcl2 deficiency, which could potentially contribute to the inner ear nerve blockage and subsequent hearing loss. Therefore, targeting Bcl2 may be a promising potential therapeutic intervention for ARHL. These findings provide valuable insights into the molecular mechanisms underlying ARHL and may pave the way for novel treatment approaches for this prevalent age-related disorder.

Lymphocytes regulate expression of the SARS-CoV-2 cell entry factor ACE2 in the pancreas of T2DM patients.

AIMS: COVID-19 patients with type 2 diabetes mellitus (T2DM) show both poorer clinical outcomes and have an increased risk of death. SARS-CoV-2 virus infection requires simultaneous expression of the SARS-CoV-2 cell entry factors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type 2 (TMPRSS2) in the same cell. The aim of the study was to explore the underlying mechanisms of a COVID-19 infection in patients with T2DM. METHODS: The distribution and expression of AEC2 and TMPRSS2 in different pancreatic cell types in clinical samples of T2DM patients and diabetic mouse models were analysed by single-cell sequencing, bioinformatics analysis and basic experiments. RESULTS: The results showed that ACE2 and TMPRSS2 are expressed in the ducts of the human pancreas. These findings suggest that SARS-CoV-2 can infect ductal cells in vivo through ACE2 and TMPRSS2. T2DM can promote the co-expression of ACE2 and TMPRSS2 in exocrine ducts, including in the human pancreas. We hypothesize that ACE2 expression levels are associated with increased numbers of lymphocytes in vivo. CONCLUSIONS: Increased blood glucose levels are associated with increased ACE2 expression and an increased number of lymphocytes. At the same time, lymphocytes can promote ACE2 expression.

Clinical and economic benefits of image-guided system in functional endoscopicsinus surgery: a retrospective chart review study in China.

BACKGROUND: Image-guided system (IGS) has been gradually applied in the field of rhinology, making functional endoscopic sinus surgery (FESS) a truly minimally invasive and precise surgery. This study was based on real-world data from China hospitals and aimed to evaluate the clinical and economic benefits of the IGS navigation system in FESS. METHODS: This was a two-center retrospective chart review of patients with chronic rhinosinusitis who underwent FESS, including open frontal sinus between July 1, 2018 and December 31, 2019 in China. The intervention group consisted of 100 patients who underwent FESS with the IGS navigation system (IGS group), and the control group consisted of 100 patients who underwent conventional FESS (Non-IGS group). Data were collected from surgical notes and hospital medical records. The primary endpoints for clinical effectiveness and safety were avoid rehospitalization due to bleeding, avoid reoperation due to bleeding, and avoid reoperation due to recurrence. RESULTS: There were no cases of rehospitalization due to bleeding, reoperation due to bleeding, and reoperation due to recurrence in the IGS group, with an avoidance rate of 100%. In the non-IGS group, there were four cases of rehospitalization and reoperation due to bleeding, with an avoidance rate 96.00% (P = 0.121). No cases of reoperation due to recurrence were in the non-IGS group. The total hospitalization cost was 17,391.51 CNY in the IGS group and 17,742.41 CNY in the non-IGS group per patient, with no statistical difference between the two groups (P = 0.715). Compared with the non-IGS group, the IGS group had an overall cost saving of 350.90 CNY per patient. Although the procedure-related medical costs of IGS group were increased by 1,286.12 CNY compared with the non-IGS group, this was more than offset by other costs. CONCLUSION: The results of the study indicated that the IGS may avoid occurrence of rehospitalization and reoperation due to postoperative bleeding. Although the use of navigation technology increased the cost of surgery, its clinical effectiveness brought other medical cost savings, resulting in no significant difference in the overall cost of navigation surgery compared to conventional surgery. The IGS should be considered cost-effectiveness in the treatment of FESS.

Surgical treatment of preauricular fistulas: a 12-year single-center clinical observation.

OBJECTIVE: This study aimed to assess the effects of surgical timing and approach on operative duration, postoperative suture removal time, and postoperative recurrence rate in the management of preauricular fistula. A 12-year single-center clinical observation was conducted to analyze the potential effects of different surgical strategies on these critical outcomes. METHODS: The clinical data from 576 (782 ears) patients who underwent surgical resection for preauricular fistulas were examined in this retrospective study. The patients were classified into various groups based on differences in operative duration, surgical techniques and the use of intraoperative magnifying equipment. Furthermore, the specific data on operative duration, postoperative suture removal time, and postoperative recurrence rate were also recorded. RESULTS: The average operative duration for 782 ears and the average time required for postoperative suture removal were determined to be (34.57 ± 4.25) min and (3.62 ± 0.76) days, respectively. Among the cases examined, recurrence occurred in 13 ears, but all of them were cured after a second surgery, resulting in a recurrence rate of 1.67% (13/782). Interestingly, the operative and postoperative suture removal time was prolonged during the infection period (P < 0.05). The postoperative recurrence rate was significantly higher in the absence of magnifying equipment, as compared to those with the use of a microscope with 2.5× magnification (P < 0.05). No statistically significant differences were noted in the recurrence rate when comparing different anesthesia methods and types of surgical incisions, as well as the intraoperative use of methylene blue, and partial removal of cartilage of the pedicle (P > 0.05). CONCLUSION: The use of methylene blue, partial removal of the cartilage of the pedicle, and surgical incision during preauricular fistula resection did not affect the operative duration, postoperative suture removal time, and postoperative recurrence rate. Therefore, surgeons can select their preferred approaches based on their individual practices and patient-specific situations. However, the use of magnifying equipment during surgery is associated with a reduced risk of recurrence.

Odontohypophosphatasia caused by a novel combination of two heterozygous variants: a case report.

Hypophosphatasia (HPP) is a rare genetic disorder mainly characterized by skeletal dysplasia that results from a deficiency in tissue-nonspecific alkaline phosphatase (TNSALP), which is encoded by the alkaline phosphatase (ALPL) gene. Odontohypophosphatasia (odonto-HPP) is a mild form of HPP characterized by oral symptoms, such as premature loss of primary teeth. This study was to describe a 4-year-old boy with premature loss of primary teeth who was diagnosed with odonto-HPP. X-ray radiography and laboratory examinations were performed for the diagnosis. Genetic etiology was revealed by whole-exome sequencing. A novel combination of two variants in the ALPL gene was identified in this case; this combination resulted in the odonto-HPP phenotype. c.346G>A (p.Ala116Thr) was inherited from the proband's father, whereas c.1563C>G (p.Ser521Arg) was inherited from the proband's mother. The proband's 8-year-old sister was a heterozygous carrier of c.346G>A (p.Ala116Thr) in the ALPL gene. Thus far, the proband's sister has been asymptomatic. Our findings indicate that c.346G>A is a pathogenic genetic alteration; c.1563C>G might cause a predisposition to the dental phenotype in combination with c.346G>A. It is important for pediatric dentists to consider a diagnosis of odonto-HPP in children with premature loss of primary teeth.

Stemness maintenance of stem cells derived from human exfoliated deciduous teeth (SHED) in 3D spheroid formation through the TGF-ß/Smad signaling pathway.

Mesenchymal stem cells (MSCs) have shown great potential as important therapeutic tools for dental pulp tissue engineering, with the maintenance and enhancement of their stemness being crucial for successful therapeutic application in vivo and three-dimensional (3D) spheroid formation considered a reliable technique for enhancing their pluripotency. Human exfoliated deciduous tooth stem cells (SHED) were cultured in a low attachment plate to form aggregates for five days. Then, the resulting spheroids were analyzed for pluripotent marker expression, paracrine secretory function, proliferation, signaling pathways involved, and distribution of key proteins within the spheroids. The results indicated that 3D spheroid formation significantly increased the activation of the transforming growth factor beta (TGF-ß)/Smad signaling pathway and upregulated the secretion and mRNA expression levels of TGF-ß, which in turn enhanced the expression of pluripotency markers in SHED spheroids. The activation of the TGF-ß/Smad signaling pathway through 3D spheroid formation was found to preserve the stemness properties of SHED. Thus, understanding the mechanisms behind pluripotency maintenance of SHED culture through 3D spheroid formation could have implications for the therapeutic application of MSCs in regenerative medicine and tissue engineering.

Quercetin inhibits the activity and function of dendritic cells through the TLR4/IRAK4/NF-κB signalling pathway.

Introduction: To investigate the inhibitory effect of quercetin (QUE) on dendritic cells (DCs) through the toll-like receptor 4/interleukin-1 receptor-associated kinase 4/nuclear factor kappa-B (TLR4/IRAK4/NF-κB) signalling pathway. Material and methods: CCK-8 and apoptosis assays were performed to determine the optimal concentration and action time of QUE to inhibit DCs. Protein extracts from treated DCs were used for Western blotting experiments to determine the relative expression levels of TLR4, IRAK4, and NF-κB p65 proteins. Changes in the ratio of CD86 and CD11c positive cells on the DCs surface were detected using flow cytometry. The molecular docking technique was used to analyse the binding site and free energy of QUE and IRAK4. Results: CCK-8 and apoptosis assays suggested that QUE inhibited the activity and function of DCs in a time-dose-dependent manner. The results of Western blotting suggested that the relative expression levels of TLR4, IRAK4, and NF-κB p65 proteins were increased in the lipopolysaccharide (LPS) group compared with the normal control group, and the relative expression of the above proteins was decreased after treatment with QUE and IRAK4-IN-4. The results of flow cytometry suggested that LPS increased the expression of CD86 and CD11c on the surface of DCs, and QUE and IRAK4-IN-4 decreased the expression of CD86 and CD11c induced by LPS. Molecular docking results showed that the binding sites of QUE and IRAK4 were stable, with the minimum binding energies comparable to that of IRAK4-IN-4. Conclusions: Quercetin may inhibit the activity and function of DCs through the TLR4/IRAK4/NF-κB signalling pathway, and IRAK4 may be its target.

Characterization of the immune regulatory property of CD22+ CD9+ B cells.

Immunodisruptive homeostasis is recognized in allergic disorders. The mechanism of restoration of immunologic homeostasis in the body is not fully understood. Galectin-9 (Gal9) and CD22 have immune regulatory functions. The goal of this study is to test the role of CD22+ CD9+ B regulatory cells in immune homeostasis the body. A much smaller amount of IL-10 in B10 cells was detected in patients with allergic rhinitis (AR) in contrast to healthy subjects. The IL-10 expression levels in B10 cells were positively correlated with the CD22 expression. CD22 mediated the effects of Gal9 on the enhanced expression of IL-10 in AR B10 cells. Gal9 overcame the refractory induction of IL-10 in B-cells of AR subjects. The immune regulatory ability of AR B10 cells could be restored by Gal9. Combination of Gal9 and SIT induced and activated antigen-specific B10 cells. The B10 cells of Gal9/specific immunotherapy-treated AR mice showed immunosuppressive functions on T-cell activities and induction of type 1 regulatory T cells in an antigen-specific manner. Administration of Gal9 potentiated the effects of specific immunotherapy in mice with AR. In summary, a fraction of regulatory B cells, the CD19+ CD22+ CD9+ B cells, was characterized in the present study. CD22 mediates the effects of Gal9 to promote immunotherapy for allergic diseases by inducing B10 cells. In an antigen-specific manner, the B10 cells suppressed CD4+ T cell activities, and alleviated experimental AR.

5-HT is associated with the dysfunction of regulating T cells in patients with allergic rhinitis.

The dysfunction of regulating T lymphocytes (Treg) is associated with the pathogenesis of many diseases. 5-hydroxytryptamine (5-HT) is capable of interacting with immune cells. The objective of the present study is to shed light on the role of 5-HT in regulating Treg activities. Blood samples were collected from patients with perennial allergic rhinitis (AR). Tregs were isolated from blood samples by magnetic cell sorting. The levels of 5-HT and other cytokines were determined by enzyme-linked immunosorbent assay. The results showed that serum 5-HT levels in patients with AR were higher than in healthy control (HC) subjects. A positive correlation was identified in the data between 5-HT concentrations and AR-related cytokine concentrations in the serum. A negative correlation was found between serum levels of 5-HT and the peripheral frequency of Treg. Exposure to 5-HT enhanced the expression of IL-6 and IL-21 in dendritic cells (DC). Co-culture of 5-HT-primed DCs with Tregs led to the conversion of Th17 cells. STAT3 blockade efficiently abolished the 5-HT-associated conversion of Th17 cells from Tregs. In summary, patients with AR exhibited higher serum concentrations of 5-HT. 5-HT-primed DCs could convert Tregs to Th17 cells.

The emerging role of transcription factor FOXP3 in thyroid cancer.

Transcription factor FOXP3 is a crucial regulator in the development and function of regulatory T cells (Treg) that are essential for immunological tolerance and homeostasis. Numerous studies have indicated the correlation of tumor infiltrating FOXP3+ Treg upregulation with poor prognostic parameters in thyroid cancer, including lymph node metastases, extrathyroidal extension, and multifocality. Most immune-checkpoint molecules are expressed in Treg. The blockage of such signals with checkpoint inhibitors has been approved for several solid tumors, but not yet for thyroid cancer. Thyroid abnormalities may be induced by checkpoint inhibitors. For example, hypothyroidism, thyrotoxicosis, painless thyroiditis, or even thyroid storm are more frequently associated with anti-PD-1 antibodies (pembrolizumab and nivolumab). Therefore, Targeting FOXP3+ Treg may have impacts on checkpoint molecules and the growth of thyroid cancer. Several factors may impact the role and stability of FOXP3, such as alternative RNA splicing, mutations, and post-translational modification. In addition, the role of FOXP3+ Treg in the tumor microenvironment is also affected by the complex regulatory network formed by FOXP3 and its transcriptional partners. Here we discussed how the expression and function of FOXP3 were regulated and how FOXP3 interacted with its targets in Treg, aiming to help the development of FOXP3 as a potential therapeutic target for thyroid cancer.

Earth-abundant 3d-transition-metal catalysts for lignocellulosic biomass conversion.

Transformation of biomass to chemicals and fuels is a long-term goal in both science and industry. However, high cost is one of the major obstacles to the industrialization of this sustainable technology. Thus, developing catalysts with high activity and low-cost is of great importance for biomass conversion. The last two decades have witnessed the increasing achievement of the use of earth-abundant 3d-transition-metals in catalysis due to their low-cost, high efficiency and excellent stability. Here, we aim to review the fast development and recent advances of 3d-metal-based catalysts including Cu, Fe, Co, Ni and Mn in lignocellulosic biomass conversion. Moreover, present research trends and invigorating perspectives on future development are given.

LncRNA HOXC-AS1 promotes nasopharyngeal carcinoma (NPC) progression by sponging miR-4651 and subsequently upregulating FOXO6.

The incidence rate of nasopharyngeal carcinoma (NPC) is the highest among the malignant tumors of otorhinolaryngology, posing a huge burden to public health. Long noncoding RNAs (lncRNAs) exert an important role in tumorigenesis and the progression of various cancers. The present study found that HOXC-AS1 was highly expressed in NPC and in NPC cell lines, suggesting a critical role of HOXC-AS1 in NPC progression. In addition, the abundance of HOXC-AS1 was negatively correlated with the prognosis of NPC. To molecularly dissect the mechanism of HOXC-AS1 in NPC progression, we knocked down the expression of HOXC-AS1 in HNE1 and C666-1 cells. Then, we employed CCK8, colony-formation experiment and Transwell to investigate how the cell performed when HOXC-AS1 was knocked down. It could be observed that HOXC-AS1 knockdown decreases cell proliferation, migration and invasion, but induces cell apoptosis in NPC. We found that HOXC-AS1 could sponge miR-4651 subsequently binding FOXO6 and inhibiting its expression. Therefore, HOXC-AS1/miR-4651/FOXO6 may form a competing endogenous RNA (ceRNA) network that promotes NPC progression. In conclusion, our study demonstrates that HOXC-AS1 promotes NPC progression by sponging miR-4651 and regulating FOXO6 expression, thus providing potential pharmaceutical targets for developing new NPC treatments.

Synthesis of bio-based 2-thiothiophenes.

While the synthesis of bio-based compounds containing carbon, oxygen and (to a lesser extent) nitrogen is well studied, the production of organosulfur compounds from biomass has received virtually no attention, despite their widespread application throughout the chemical industry. Herein, we demonstrate that a range of bio-based 2-thiothiophenes are available from the biopolymer cellulose, proving that functionally diverse small-molecule organosulfurs can be prepared independent of fossil carbon. This article is part of the theme issue 'Bio-derived and bioinspired sustainable advanced materials for emerging technologies (part 2)'.

Molecular mechanism of arachidonic acid biosynthesis in Porphyridium purpureum promoted by nitrogen limitation.

The red alga Porphyridium purpureum has been known to produce polyunsaturated fatty acids, especially arachidonic acid (ARA), under stressful conditions. However, there is no consistent conclusion about the response of ARA in this alga to nitrogen (N) stress. Also, no research has been done to clearly elucidate the underlying molecular mechanisms of N stress. In this work, P. purpureum CoE1 was cultivated under nitrogen limitation conditions and the putative Δ5-desaturase related gene FADSD5 was isolated. The results showed that the fatty acids in P. purpureum CoE1 were significantly higher in the N limited cultures (54.3 mg g-1) than in the N-replete cultures (45.3 mg g-1) at the 18th day (t-test, p < 0.001), which was attributed to the upregulated abundance of the putative Δ5-desaturase related protein, Δ5-Des. The study also indicated that the expression of the putative Δ5-desaturase related gene, FADSD5, increased with cell growth, demonstrating considerable potentials for ARA biosynthesis in P. purpureum CoE1. These results might guide the direction in illuminating the biosynthetic pathway of fatty acids with molecular evidence and enable genetic modifications of P. purpureum CoE1 for enhancing the ARA accumulation.

SPZ1 promotes deregulation of Bim to boost apoptosis resistance in colorectal cancer.

Colorectal cancer (CRC) is the third most common malignancies in adults. Similar to other solid tumors, CRC cells show increased proliferation and suppressed apoptosis during the development and progression of the disease. Previous studies have shown that a novel tumor oncogene, spermatogenic basic helix-loop-helix transcription factor zip 1 (SPZ1), can promote proliferation. However, it is unclear whether SPZ1 plays a role in suppressing apoptosis, and the molecular mechanism behind SPZ1's suppression of apoptosis in CRC remains unclear. Here, we found that silencing endogenous SPZ1 inhibits cell growth and induces apoptosis, and overexpression of SPZ1 promotes cell growth. These findings were corroborated by in vitro and in vivo studies. Interestingly, SPZ1 overexpressing cells were resistant to 5-fluorouracil, a drug commonly used to treat cancer. Moreover, knocking down SPZ1 led to the activation of caspase through the deregulation of Bim by ERK1/2, we found that CRC tissues had significantly higher SPZ1 and lower Bim expression, and SPZ1HBimL were associated with advanced clinical stage of CRC. Collectively, our findings demonstrate that SPZ1 contributes to tumor progression by limiting apoptosis. SPZ1 reduces apoptosis by altering the stability of Bim, suggesting SPZ1 may serve as a biomarker and therapeutic target for CRC.