Neutrophils impaired by anti-galectin-3 antibodies elicit inflammation of endothelial cells to aggregate the development of lupus cutaneous vasculitis.

OBJECTIVES: To investigate whether the interplay of anti-galectin-3 antibodies (anti-Gal3 Abs) with neutrophils contributes to the development of lupus cutaneous vasculitis. METHODS: Enzyme-linked immunosorbent assay was used to determine the serum level of anti-Gal3 Abs in lupus patients. Flow cytometry, quantitative PCR and western blot were performed to investigate the expression of cell surface receptors, proinflammatory cytokines and signalling molecules in neutrophils stimulated by serum from lupus patients or healthy controls (HCs) or anti-Gal3 Ab, respectively. Immunofluorescence was performed to visualise the formation of neutrophil extracellular traps (NETs). Human umbilical vein endothelial cells were co-cultured with the supernatants from neutrophils stimulated by anti-Gal3 Ab, and cytokine production was measured at mRNA and protein levels. Immunohistochemistry was adopted to reveal the distribution of Gal3, cytokines and myeloperoxidase within lupus skin lesions. REULTS: Serum levels of anti-Gal3 Abs were negatively correlated with peripheral counts of neutrophils. Anti-Gal3 Abs positive sera from SLE patients accelerated neutrophil death, altered cell phenotype and promoted formation of NETs with the involvement of p38 MAPK pathway. Supernatants collected from neutrophils co-cultured with anti-Gal3 Ab provoked endothelial cells to produce cytokines such as IL-1, ICAM-1, SELE and particularly IL-6. Consistently, IL-6 was higher in SLE patients with anti-Gal3 Ab positive sera and enriched in the area of vascular inflammation together with enhanced expression of Gal3 protein and infiltration of neutrophils. CONCLUSIONS: Overall, these findings suggested that neutrophils were crucial mediators in anti-Gal3 Ab induced lupus cutaneous vasculitis.

[Abnormalities in signal transduction of Purkinje cells in spinocerebellar ataxias: a review].

Spinocerebellar ataxias (SCAs) are a group of autosomal dominant neurodegenerative diseases that have been currently identified with numerous subtypes exhibiting genetic heterogeneity and clinical variability. Purkinje neuronal degeneration and cerebellar atrophy are common pathological features among most SCA subtypes. The physiological functions of Purkinje cells are regulated by multiple factors, and their dysfunction in signal transduction may lead to abnormal cerebellar motor control. This review summarizes the abnormalities in voltage-gated ionic channels, intracellular calcium signaling, and glutamate signaling transduction of Purkinje cells in SCAs, aiming to provide a theoretical basis for further understanding the common pathogenesis of SCAs and developing specific treatments.

Distributed Dynamic Event-Triggered Control to Leader-Following Consensus of Nonlinear Multi-Agent Systems with Directed Graphs.

This paper investigates achieving leader-following consensus in a class of multi-agent systems with nonlinear dynamics. Initially, it introduces a dynamic event-triggered strategy designed to effectively alleviate the strain on the system's communication resources. Subsequently, a distributed control strategy is proposed and implemented in the nonlinear leader-follower system using the dynamic event-triggered mechanism, aiming to ensure synchronization across all nodes at an exponential convergence speed. Thirdly, the research shows that under the dynamic event-triggered strategy the minimum event interval of any two consecutive triggers guarantees the elimination of Zeno behavior. Lastly, the validity of the calculation results is verified by a simulation example.

Comparative evaluation of early diabetic outcomes in southeast asian patients with type 2 diabetes mellitus undergoing Roux-en-Y gastric bypass (RYGB) versus sleeve gastrectomy (LSG).

Obesity and type 2 diabetes mellitus (T2DM) is an alarming problem globally and a growing epidemic. Metabolic surgery has been shown to be successful in treating both obesity and T2DM, usually after other treatments have failed. This study aims to compare Roux-Y gastric bypass and sleeve gastrectomy in determining early diabetic outcomes in obese Malaysian patients with T2DM following surgery. A total of 172 obese patients with T2DM who were assigned to either laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) were analysed up to a year post-procedure. The patients' T2DM severity were stratified using the Individualized Metabolic Surgery (IMS) score into mild, moderate and severe. Remission rates of diabetes were compared between surgical techniques and within diabetic severity categories. T2DM remission for patients who underwent either surgical technique for mild, moderate or severe disease was 92.9%, 56.2% and 14.7% respectively. Both surgical techniques improved T2DM control for patients in the study. Comparing baseline with results 1 year postoperatively, median HbA1c reduced from 7.40% (IQR 2.60) to 5.80% (IQR 0.80) (p < 0.001), mean total antidiabetic medications use reduced from 1.48 (SD 0.99) to 0.60 (SD 0.86) [p < 0.001], insulin usage reduced from 27.9 to 10.5% (p < 0.001), and T2DM control improved from 27.9 to 82% (p < 0.001). The patients had a median excess BMI loss of 69.4% (IQR 34%) and 53.2% (IQR 36.0%) for RYGB and SG respectively (p = 0.016). At one year following surgery, there is no difference between LRYGB and LSG in terms of diabetic remission. LSG is not inferior to LRYGB in terms of early diabetic outcomes. Milder T2DM shows a better response. LSG is a simpler procedure with a lower risk profile and should be considered as an early treatment option for obese patients with T2DM.

The high-quality genome of Cryptotaenia japonica and comparative genomics analysis reveals anthocyanin biosynthesis in Apiaceae.

Cryptotaenia japonica, a traditional medicinal and edible vegetable crops, is well-known for its attractive flavors and health care functions. As a member of the Apiaceae family, the evolutionary trajectory and biological properties of C. japonica are not clearly understood. Here, we first reported a high-quality genome of C. japonica with a total length of 427 Mb and N50 length 50.76 Mb, was anchored into 10 chromosomes, which confirmed by chromosome (cytogenetic) analysis. Comparative genomic analysis revealed C. japonica exhibited low genetic redundancy, contained a higher percentage of single-cope gene families. The homoeologous blocks, Ks, and collinearity were analyzed among Apiaceae species contributed to the evidence that C. japonica lacked recent species-specific WGD. Through comparative genomic and transcriptomic analyses of Apiaceae species, we revealed the genetic basis of the production of anthocyanins. Several structural genes encoding enzymes and transcription factor genes of the anthocyanin biosynthesis pathway in different species were also identified. The CjANSa, CjDFRb, and CjF3H gene might be the target of Cjaponica_2.2062 (bHLH) and Cjaponica_1.3743 (MYB). Our findings provided a high-quality reference genome of C. japonica and offered new insights into Apiaceae evolution and biology.

Investigation of causal relationships between cortical structure and osteoporosis using two-sample Mendelian randomization.

The mutual interaction between bone characteristics and brain had been reported previously, yet whether the cortical structure has any relevance to osteoporosis is questionable. Therefore, we applied a two-sample bidirectional Mendelian randomization analysis to investigate this relationship. We utilized the bone mineral density measurements of femoral neck (n = 32,735) and lumbar spine (n = 28,498) and data on osteoporosis (7300 cases and 358,014 controls). The global surficial area and thickness and 34 specific functional regions of 51,665 patients were screened by magnetic resonance imaging. For the primary estimate, we utilized the inverse-variance weighted method. The Mendelian randomization-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis were conducted to assess heterogeneity and pleiotropy. We observed suggestive associations between decreased thickness in the precentral region (OR = 0.034, P = 0.003) and increased chance of having osteoporosis. The results also revealed suggestive causality of decreased bone mineral density in femoral neck to declined total cortical surface area (ß = 1400.230 mm2, P = 0.003), as well as the vulnerability to osteoporosis and reduced thickness in the Parstriangularis region (ß = -0.006 mm, P = 0.002). Our study supports that the brain and skeleton exhibit bidirectional crosstalk, indicating the presence of a mutual brain-bone interaction.

Protective Effects of Phellodendron Species on Bone Health: A Novel Perspective on Their Potentials in Treating Osteoporosis and Osteoarthritis.

Phellodendron (PN) species, traditionally used in Chinese medicine for centuries, hold promise as a potential treatment for osteoporosis (OP) and osteoarthritis (OA) due to their bioactive compounds. The bioactive compounds, including berberine and palmatine, exhibit anti-inflammatory, antioxidant, and bone-protective properties, contributing to their potential therapeutic benefits in promoting bone health and preventing bone loss. However, challenges such as the need for standardized preparation and dosing, limited clinical studies, and potential interactions with other medications hinder their clinical use. Nonetheless, the rich history of PN species in Chinese medicine provides a promising foundation for future investigation into their potential as alternative treatments for OP and OA. Further research is needed to fully understand the underlying mechanisms of action and explore the clinical implications of PN for bone health.

Psychosocial Determinants of Knee Osteoarthritis Progression: Results from the Promoting Independence in Our Seniors with Arthritis Study.

BACKGROUND: Knee osteoarthritis (OA) is a common cause of physical disability among older adults. While established risk factors for knee OA include age and increased body weight, few studies have examined psychosocial risk factors or progression of knee OA. METHODS: The Promoting Independence in our Seniors with Arthritis study recruited participants aged 65 years and over from orthopedic outpatients and community engagement events. Participants were invited to annual visits during which knee OA symptoms were assessed with the Knee Injury and Osteoarthritis Outcome Score (KOOS), social network using the 6-item Lubben Social Network Scale and anxiety and depression using the Hospital Anxiety and Depression scale. Knee OA worsening was defined by a 5% reduction in mean KOOS scores at the last visit compared to the first visit. RESULTS: Data were available from 148 participants, mean age 66.2±6.5 years and 74.1% female, of whom 28 (18.9%) experienced OA worsening over a median follow-up period of 29 months. Univariate analyses revealed that age, sex, height, grip strength, and social network were associated with OA worsening. Social network remained statistically significantly associated with OA worsening after adjustment for age and sex difference (odds ratio=0.924; 95% confidence interval, 0.857-0.997). The relationship between social network and OA worsening were attenuated by both depression and handgrip strength at baseline. CONCLUSION: Psychological status and muscle strength may be modifiable risk factors for social network which may in turn prevent knee OA worsening and should be targeted in future intervention studies.

Telomere-to-telomere carrot (Daucus carota) genome assembly reveals carotenoid characteristics.

Carrot (Daucus carota) is an Apiaceae plant with multi-colored fleshy roots that provides a model system for carotenoid research. In this study, we assembled a 430.40 Mb high-quality gapless genome to the telomere-to-telomere (T2T) level of "Kurodagosun" carrot. In total, 36 268 genes were identified and 34 961 of them were functionally annotated. The proportion of repeat sequences in the genome was 55.3%, mainly long terminal repeats. Depending on the coverage of the repeats, 14 telomeres and 9 centromeric regions on the chromosomes were predicted. A phylogenetic analysis showed that carrots evolved early in the family Apiaceae. Based on the T2T genome, we reconstructed the carotenoid metabolic pathway and identified the structural genes that regulate carotenoid biosynthesis. Among the 65 genes that were screened, 9 were newly identified. Additionally, some gene sequences overlapped with transposons, suggesting replication and functional differentiation of carotenoid-related genes during carrot evolution. Given that some gene copies were barely expressed during development, they might be functionally redundant. Comparison of 24 cytochrome P450 genes associated with carotenoid biosynthesis revealed the tandem or proximal duplication resulting in expansion of CYP gene family. These results provided molecular information for carrot carotenoid accumulation and contributed to a new genetic resource.

Interaction between SlMAPK3 and SlASR4 regulates drought resistance in tomato (Solanum lycopersicum L.).

Tomato is a leading vegetable in modern agriculture, and with global warming, drought has become an important factor threatening tomato production. Mitogen-activated protein kinase 3 (MAPK3) plays an important role in plant disease and stress resistance. To clarify the downstream target proteins of SlMAPK3 and the mechanism of stress resistance in tomato, this study was conducted with the SlMAPK3-overexpressing lines OE-1 and OE-2 and the CRISPR/Cas9-mediated mutant lines slmapk3-1 and slmapk3-2 under PEG 6000-simulated drought. The results of yeast two-hybrid (Y2H), pull-down, and coimmunoprecipitation (Co-IP) assays confirmed that SlASR4 (NP_001269248.1) interacted with SlMAPK3. Analyses of the SlASR4 protein structure and SlASR4 expression under PEG 6000 and BTH stress revealed that SlASR4 has a highly conserved protein structural domain involved in the drought stress response under PEG 6000 treatment. The function of the SlASR4 and SlMAPK3 downstream target protein, in drought resistance in tomato plants, was identified by virus-induced gene silencing (VIGS). This study clarified that SlMAPK3 interacts with SlASR4 to positively regulate drought resistance in tomato plants.

[Rapid determination of aesculin and aesculetin in Fraxini Cortex by high performance liquid chromatography-ultraviolet at equal absorption wavelength].

Fraxini Cortex is a traditional Chinese herbal medicine that has been used for thousands of years to treat dampness-heat diarrhea, dysentery, red or white vaginal discharge, painful swelling or redness of the eyes, and nebula. It contains various chemical components, including coumarins, iridoids, phenolic acids, and flavonoids. Coumarins are important active ingredients in Fraxini Cortex and have antibacterial, anti-inflammatory, antioxidant, antitumor, and antiviral activities. Aesculin and aesculetin are two major coumarin components of Fraxini Cortex that are widely used in its quality evaluation. Previous HPLC methods for determination of aesculin and aesculetin present several limitations, such as long analysis times and high solvent and reference compound consumption. In this study, a rapid, eco-friendly and cost saving HPLC method for the determination of aesculin and aesculetin in Fraxini Cortex was established by using the core-shell column and equal absorption wavelength (EAW). Different factors influencing the extraction process, such as the extraction solvent, temperature, and time, were assessed to obtain the optimal extraction conditions. The results showed that Fraxini Cortex samples could be well extracted by ultrasonic extraction for 5 min with a 25% ethanol aqueous solution. A core-shell column was used, and different mobile phases and flow rates were investigated to obtain the best rapid-HPLC separation conditions. The optimized HPLC conditions were as follows: a Poroshell 120 EC-C18 column (50 mm×4.6 mm, 2.7 µm), acetonitrile-0.1% formic acid aqueous solution (6∶94, v/v) as the eluent, a flow rate of 1.5 mL/min, and a column temperature of 25 ℃. The EAW of aesculin and aesculetin was a key factor in their determination using a single reference compound. EAW selection was performed in two steps. First, the UV spectra of two equimolar concentrations of the reference compounds (aesculin and aesculetin) were compared to determine the EAW of the two analytes. The EAW results were then verified by the HPLC analysis of the reference compound solutions. The final EAW of aesculin and aesculetin was 341 nm. The determination of aesculin and aesculetin using only one reference compound (i. e., aesculin) was achieved by HPLC-UV at this EAW. The newly developed HPLC method revealed a good linear relationship between the two target analytes (r=1.0000). The limits of detection (LODs) and limits of quantification (LOQs) were 1.5 µmol/L and 3.0 µmol/L, respectively, and the average recoveries of aesculin and aesculetin were 99.0% and 97.5%. The stabilities of the sample solutions were examined, and the two analytes demonstrated good stability for 24 h. The contents of the target analytes in 10 batches of Fraxini Cortex were determined using the proposed EAW method and the classic external standard method (ESM), and comparable concentrations were obtained. The contents of aesculin and aesculetin in the 10 batches of Fraxini Cortex were 0.26%-2.80% and 0.11%-1.47%, respectively. A t-test was conducted to compare the results of the proposed EAW technique with those obtained via the method reported in the Chinese Pharmacopoeia, and no significant difference between the two assay methods was noted (P>0.05). Comparison of the newly established EAW method with those reported in the literature revealed that our method required only 10 min to complete and used as little as 0.5 mL of the solvent and only one standard. Therefore, the developed EAW method is a rapid, simple, eco-friendly, and cost-effective analytical method that is suitable for the determination of aesculin and aesculetin in Fraxini Cortex and its related products. The proposed technique is an improved method for determining aesculin and aesculetin and contributes to the enhancement of the quality evaluation of Fraxini Cortex.

Physical and psychosocial characteristics differ between individuals with knee pain and different knee osteoarthritis diagnostic criteria.

PURPOSE: Knee pain and osteoarthritis (OA) are common and often lead to disability among older adults. Existing published evidence, however, utilizes differing criteria to define studies' knee OA populations. We, therefore, aimed to determine whether differences exist in the characteristics of individuals with the presence of knee pain and different diagnostic criteria for knee OA. METHODS: The Promoting Independence in Seniors with Arthritis (PISA) study is a longitudinal observational study of individuals with and without knee pain and knee OA recruited from the orthopaedics clinic of the Universiti Malaya Medical Centre and the local hospital catchment. Patients were diagnosed with OA based on the American College of Rheumatology (ACR) criteria, the presence of knee pain, and a history of physician-diagnosed knee OA. Psychosocial parameters were measured using validated measures for social participation, independence, and ability to perform activities of daily living, and life satisfaction. RESULTS: Of the 230 included participants, mean age was 66.9 years (standard deviation: 7.2) and 166 (72.2%) were women. Kappa agreement between ACR criteria and knee pain was 0.525 and for ACR and physician-diagnosed OA it was 0.325. Binomial logistic regression analysis showed that weight, anxiety, and handgrip strength (HGS) were predictive of ACR OA. Knee pain was only predicted by HGS but not weight and anxiety. Physician-diagnosed OA was predicted by weight and HGS but not anxiety. HGS was predictive of ACR OA, knee pain, and physician-diagnosed OA. CONCLUSION: Our study showed that the characteristics of patients with OA are different, physically and psychosocially, depending on the criteria used. Poor agreement was observed between radiological diagnosis and the other diagnostic criteria. Our findings have important implications for the interpretation and comparison of published studies using different OA criteria.

TNF-α promotes CXCL-1/8 production in keratinocytes by downregulating galectin-3 through NF-κB and hsa-miR-27a-3p pathway to contribute psoriasis development.

OBJECTIVE: Treatment with TNF-α inhibitors improve psoriasis with minimize/minor neutrophils infiltration and CXCL-1/8 expression in psoriatic lesions. However, the fine mechanism of TNF-α initiating psoriatic inflammation by tuning keratinocytes is unclear. Our previous research identified the deficiency of intracellular galectin-3 was sufficient to promote psoriasis inflammation characterized by neutrophil accumulation. This study aims to investigate whether TNF-α participated in psoriasis development through dysregulating galectin-3 expression. METHODS: mRNA levels were assessed through quantitative real-time PCR. Flow cytometry was used to detect cell cycle/apoptosis. Western blot was used to evaluate the activation of the NF-κB signaling pathway. HE staining and immunochemistry were used to detect epidermal thickness and MPO expression, respectively. Specific small interfering RNA (siRNA) was used to knock down hsa-miR-27a-3p while plasmids transfection was used to overexpress galectin-3. Further, the multiMiR R package was utilized to predict microRNA-target interaction. RESULTS AND DISCUSSION: We found that TNF-α stimulation altered cell proliferation and differentiation and promoted the production of psoriasis-related inflammatory mediators along with the inhibition of galectin-3 expression in keratinocytes. Supplement of galectin-3 could counteract the rise of CXCL-1/8 but not the other phenotypes of keratinocytes induced by TNF-α. Mechanistically, inhibition of the NF-κB signaling pathway could counteract the decrease of galectin-3 and the increase of hsa-miR-27a-3p expression whereas silence of hsa-miR-27a-3p could counteract the decrease of galectin-3 expression induced by TNF-α treatment in keratinocytes. Intradermal injection of murine anti-CXCL-2 antibody greatly alleviated imiquimod-induced psoriasis-like dermatitis. CONCLUSION: TNF-α initiates psoriatic inflammation by increasing CXCL-1/8 in keratinocytes mediated by the axis of NF-κB-hsa-miR-27a-3p-galectin-3 pathway.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Comparative study of ultrasound-guided microwave ablation and traditional surgery in the treatment of plasma cell mastitis: a multicenter study.

Background: Plasma cell mastitis (PCM) is a benign breast disease that is refractory and difficult to cure. We integrated microwave ablation into the treatment of PCM to compare the clinical value of ultrasound-guided microwave ablation and traditional surgery in the treatment of PCM. Methods: A total of 68 patients with PCM who were admitted to 3 centers (Zhejiang Cancer Hospital, Hebei Province Hospital of Traditional Chinese Medicine, and Yantai Affiliated Hospital of Binzhou Medical university) from January 2017 to June 2019 were selected. All patients were diagnosed with PCM after pathological and clinical manifestations. Among these, 38 cases were treated with ultrasound-guided microwave ablation, and 30 cases were treated with traditional surgery. The operation time, hospitalization time, incision healing, intraoperative blood loss, postoperative pain degree, evaluation of breast shape effect, time taken for postoperative lesion disappearance, effective rate, and recurrence were recorded in the follow-up, and the clinical efficacy was compared and observed. Results: The effective rate of the ablation group was 86.8% (33/38), that of the operation group was 46.7% (14/30), and the difference was statistically significant (95% CI: 2.311-24.618; P<0.05). The average time of the lesion completely disappearing was 75.55±43.59 days in the ablation group and 103.87±45.98 days in the operation group, and the difference was statistically significant (P<0.05). The hospital stays, operation time, and intraoperative blood loss of patients in the ablation group were less than those of the operation group, and the difference was statistically significant (95% CI: -10.69 to -6.27, 95% CI: -77.06 to -51.26, and 95% CI: -21.54 to -13.64; P<0.05). The postoperative pain scoring, operative incision healing at 14 days after the operation, and breast appearance evaluation after treatment in the ablation group were better than those of the operation group, and the difference was statistically significant (P<0.05). Conclusions: Compared with traditional surgery, ultrasound-guided microwave ablation is a more effective treatment option for PCM.

Antiferroelectrics and Magnetoresistance in La0.5Sr0.5Fe12O19 Multiferroic System.

The appearance of antiferroelectrics (AFE) in the ferrimagnetism (FM) system would give birth to a new type of multiferroic candidate, which is significant to the development of novel devices for energy storage. Here we demonstrate the realization of full antiferroelectrics in a magnetic La0.5Sr0.5Fe12O19 system (AFE+FM), which also presents a strong magnetodielectric response (MD) and magnetoresistance (MR) effect. The antiferroelectric phase was achieved at room temperature by replacing 0.5 Sr2+ ions with 0.5 La2+ ions in the SrFe12O19 compound, whose phase transition temperature of ferroelectrics (FE) to antiferroelectrics was brought down from 174 °C to -141 °C, while the temperature of antiferroelectrics converting to paraelectrics (PE) shifts from 490 °C to 234 °C after the substitution. The fully separated double P-E hysteresis loops reveal the antiferroelectrics in La0.5Sr0.5Fe12O19 ceramics. The magnitude of exerting magnetic field enables us to control the generation of spin current, which induces MD and MR effects. A 1.1T magnetic field induces a large spin current of 15.6 n A in La0.5Sr0.5Fe12O19 ceramics, lifts up dielectric constants by 540%, and lowers the resistance by -89%. The magnetic performance remains as usual. The multiple functions in one single phase allow us to develop novel intelligent devices.

Advances in engineering the production of the natural red pigment lycopene: A systematic review from a biotechnology perspective.

BACKGROUND: Lycopene is a natural red compound with potent antioxidant activity that can be utilized both as pigment and as a raw material in functional food, and so possesses good commercial prospects. The biosynthetic pathway has already been documented, which provides the foundation for lycopene production using biotechnology. AIM OF REVIEW: Although lycopene production has begun to take shape, there is still an urgent need to alleviate the yield of lycopene. Progress in this area can provide useful reference for metabolic engineering of lycopene production utilizing multiple approaches. KEY SCIENTIFIC CONCEPTS OF REVIEW: Using conventional microbial fermentation approaches, biotechnologists have enhanced the yield of lycopene by selecting suitable host strains, utilizing various additives, and optimizing culture conditions. With the development of modern biotechnology, genetic engineering, protein engineering, and metabolic engineering have been applied for lycopene production. Extraction from natural plants is the main way for lycopene production at present. Based on the molecular mechanism of lycopene accumulation, the production of lycopene by plant bioreactor through genetic engineering has a good prospect. Here we summarized common strategies for optimizing lycopene production engineering from a biotechnology perspective, which are mainly carried out by microbial cultivation. We reviewed the challenges and limitations of this approach, summarized the critical aspects, and provided suggestions with the aim of potential future breakthroughs for lycopene production in plants.

Effects of SENP1-induced deSUMOylation of STAT1 on proliferation and invasion in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is the most common nasopharyngeal squamous cell carcinoma, and recurrence and metastasis are still difficult problems in its current treatment. This study aimed to investigate the effect of SUMO modification of STAT1 protein on the proliferation and invasion of NPC, and to reveal the underlying mechanism. Two gene expression profiles (GSE12452 and GSE53819) of 49 nasopharyngeal carcinomas and 28 normal controls were analyzed to identify differentially expressed genes. In total, 448 up-regulated genes and 622 down-regulated genes were identified. In addition, 16 SUMO-related molecules in the NPC dataset GSE102349 with survival data were analyzed, and it was found that the high expression of SENP1 and SENP2 was closely related to the poor prognosis of NPC. GO and GSEA analysis suggested that immune-related biological processes, IFN-γ-STAT signaling pathway and protein modification-related molecules were significantly enriched in NPC, resulting in poor survival prognosis. In order to verify the results of bioinformatics analysis and explore its underlying molecular mechanisms, western blot, Immunofluorescence, Immunoprecipitation and Immunohistochemistry are conducted in NPC cells, animals and clinical samples. SENP1 and STAT protein levels were increased in NPC tissues. SENP1 inhibited SUMOylation of STAT1, thereby promoting the protein level of STAT1 and the nuclear translocation. SENP1 promoted the proliferation and invasion of NPC by inducing STAT1. Overall, SENP1-induced deSUMOylation of STAT1, resulting in an increased proliferation and invasion of nasopharyngeal carcinoma.

Multigene manipulation of photosynthetic carbon metabolism enhances the photosynthetic capacity and biomass yield of cucumber under low-CO2 environment.

Solar greenhouses are important in the vegetable production and widely used for the counter-season production in the world. However, the CO2 consumed by crops for photosynthesis after sunrise is not supplemented and becomes chronically deficient due to the airtight structure of solar greenhouses. Vegetable crops cannot effectively utilize light resources under low-CO2 environment, and this incapability results in reduced photosynthetic efficiency and crop yield. We used cucumber as a model plant and generated several sets of transgenic cucumber plants overexpressing individual genes, including ß-carbonic anhydrase 1 (CsßCA1), ß-carbonic anhydrase 4 (CsßCA4), and sedoheptulose-1,7-bisphosphatase (CsSBP); fructose-1,6-bisphosphate aldolase (CsFBA), and CsßCA1 co-expressing plants; CsßCA4, CsSBP, and CsFBA co-expressing plants (14SF). The results showed that the overexpression of CsßCA1, CsßCA4, and 14SF exhibited higher photosynthetic and biomass yield in transgenic cucumber plants under low-CO2 environment. Further enhancements in photosynthesis and biomass yield were observed in 14SF transgenic plants under low-CO2 environment. The net photosynthesis biomass yield and photosynthetic rate increased by 49% and 79% compared with those of the WT. However, the transgenic cucumbers of overexpressing CsFBA and CsSBP showed insignificant differences in photosynthesis and biomass yield compared with the WT under low-CO2.environment. Photosynthesis, fluorescence parameters, and enzymatic measurements indicated that CsßCA1, CsßCA4, CsSBP, and CsFBA had cumulative effects in photosynthetic carbon assimilation under low-CO2 environment. Co-expression of this four genes (CsßCA1, CsßCA4, CsSBP, and CsFBA) can increase the carboxylation activity of RuBisCO and promote the regeneration of RuBP. As a result, the 14SF transgenic plants showed a higher net photosynthetic rate and biomass yield even under low-CO2environment.These findings demonstrate the possibility of cultivating crops with high photosynthetic efficiency by manipulating genes involved in the photosynthetic carbon assimilation metabolic pathway.