Synthesis and in†vitro Anti-Inflammatory Activity of Novel Dendrobine Amide/Sulfonamide Derivatives.

A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities in vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96 µM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.

Enhancing boreal forest resilience: A four-year impact of biochar on soil quality and fungal communities.

Boreal forests commonly suffer from nutrient deficiency due to restricted biological activity and decomposition. Biochar has been used as a promising strategy to improve soil quality, yet its impacts on forest soil microbes, particularly in cold environment, remains poorly understood. In this study, we investigated the effects of biochar, produced at different pyrolysis temperatures (500 °C and 650 °C) and applied at different amounts (0.5 kg·m-2 and 1.0 kg·m-2), on soil property, soil enzyme activity, and fungal community dynamics in a boreal forest over a span of two to four years. Our results showed that, four-year post-application of biochar produced at 650 °C and applied at 1.0 kg·m-2, significantly increased the relative abundance of Mortierellomycota and enhanced fungal species richness, α-diversity and evenness compared to the control (CK) (P < 0.05). Notably, the abundance of Phialocephala fortinii increased with the application of biochar produced at 500 °C and applied at 0.5 kg·m-2, exhibiting a positively correlation with the carbon cycling-related enzyme ß-cellobiosidase. Functionally, distinct fungal gene structures were formed between different biochar pyrolysis temperatures, and between application amounts in four-year post-biochar application (P < 0.05). Additionally, correlation analyses revealed the significance of the duration post-biochar application on the soil properties, soil extracellular enzymes, soil fungal dominant phyla, fungal community and gene structures (P < 0.01). The interaction between biochar pyrolysis temperature and application amount significantly influenced fungal α-diversity (P < 0.01). Overall, these findings provide theoretical insights and practical application for biochar as soil amendment in boreal forest ecosystems.

[Modeling and comfort analysis of arrayed air cushion mattress for pressure ulcer prevention and assisted repositioning].

Assisting immobile individuals with regular repositioning to adjust pressure distribution on key prominences such as the back and buttocks is the most effective measure for preventing pressure ulcers. However, compared to active self-repositioning, passive assisted repositioning results in distinct variations in force distribution on different body parts. This incongruity can affect the comfort of repositioning and potentially lead to a risk of secondary injury, for certain trauma or critically ill patients. Therefore, it is of considerable practical importance to study the passive turning comfort and the optimal turning strategy. Initially, in this study, the load-bearing characteristics of various joints during passive repositioning were examined, and a wedge-shaped airbag configuration was proposed. The airbags coupled layout on the mattress was equivalently represented as a spring-damping system, with essential model parameters determined using experimental techniques. Subsequently, different assisted repositioning strategies were devised by adjusting force application positions and sequences. A human-mattress force-coupled simulation model was developed based on rigid human body structure and equivalent flexible springs. This model provided the force distribution across the primary pressure points on the human body. Finally, assisted repositioning experiments were conducted with 15 participants. The passive repositioning effectiveness and pressure redistribution was validated based on the simulation results, experimental data, and questionnaire responses. Furthermore, the mechanical factors influencing comfort during passive assisted repositioning were elucidated, providing a theoretical foundation for subsequent mattress design and optimization of repositioning strategies.

Genetic architecture of ecological divergence between Oryza rufipogon and Oryza nivara.

Ecological divergence due to habitat difference plays a prominent role in the formation of new species, but the genetic architecture during ecological speciation and the mechanism underlying phenotypic divergence remain less understood. Two wild ancestors of rice (Oryza rufipogon and Oryza nivara) are a progenitor-derivative species pair with ecological divergence and provide a unique system for studying ecological adaptation/speciation. Here, we constructed a high-resolution linkage map and conducted a quantitative trait locus (QTL) analysis of 19 phenotypic traits using an F2 population generated from a cross between the two Oryza species. We identified 113 QTLs associated with interspecific divergence of 16 quantitative traits, with effect sizes ranging from 1.61% to 34.1% in terms of the percentage of variation explained (PVE). The distribution of effect sizes of QTLs followed a negative exponential, suggesting that a few genes of large effect and many genes of small effect were responsible for the phenotypic divergence. We observed 18 clusters of QTLs (QTL hotspots) on 11 chromosomes, significantly more than that expected by chance, demonstrating the importance of coinheritance of loci/genes in ecological adaptation/speciation. Analysis of effect direction and v-test statistics revealed that interspecific differentiation of most traits was driven by divergent natural selection, supporting the argument that ecological adaptation/speciation would proceed rapidly under coordinated selection on multiple traits. Our findings provide new insights into the understanding of genetic architecture of ecological adaptation and speciation in plants and help effective manipulation of specific genes or gene cluster in rice breeding.

Relationship between body composition and pulmonary function in the general population-a cross-sectional study in Ningxia.

Studies considering the relationship between non-obesity-related body composition and lung function are few; therefore, this study aimed to explore these correlations and effects. This cross-sectional study conducted in rural Qingtongxia City and Pingluo County, Ningxia, China, included 776 participants aged 30-75 years. Body composition and lung function were measured using direct segmental multifrequency bioelectrical impedance analysis and a digital spirometer, respectively. Their correlation was assessed using partial correlation analysis, controlling for age and smoking status, and the body composition effect on lung function was analyzed using binomial logistic regression analysis. The body components total body water content, protein content, mineral content, muscle mass, fat-free mass (FFM), skeletal muscle mass, basal metabolic volume, and chest circumference (CC) positively correlated with pulmonary function (forced vital capacity and forced expiratory volume in one second) in both sexes. Neck circumference and hip circumference positively correlated with pulmonary function in women. Additionally, lung function declines more slowly in women (odds ratio [OR] = 0.66, 95% confidence interval [CI] = 0.44-0.98, p = 0.04); CC (OR = 0.92, 95% CI = 0.86-0.98, p = 0.01) increased as a protective factor for decreased lung function. Increased waist circumference (OR = 1.04, 95% CI = 1.00-1.09, p = 0.04) was a risk factor for reduced lung function. FFM contains body composition indicators positively correlating with lung function, excluding fat-related body composition. Abdominal obesity increases the risk of decreased lung function.

Numerical simulation modeling and kinematic analysis onto double wedge-shaped airbag of nursing appliance.

In previous studies, the numerical modeling and analyzing methods onto industrial or vehicle airbags dynamics were revealed to have high accuracy regarding their actual dynamic properties, but there are scarcely airbag stiffness modeling and comfortableness investigations of nursing cushion or mattress airbags. This study constructs a numerical model illustrating the association between the stiffness property and the internal gas mass of the wedge-shaped airbag of nursing appliance, and then the airbag stiffness variation discipline is described based on various inflation volumes. To start with, based on an averaged pressure prerequisite, a dynamic simulation model of the wedge-shaped airbag is established by the fluid cavity approach. For this modeling, the elastic mechanical behaviors of airbag material are determined according to a material constitutive model built by the quasi-static uniaxial tensile test. Besides, verification experiments clarify that the presented modeling method is accurate for airbag stiffness behavior prediction, and then can be effectively applied into design and optimization phases of wedge-shaped airbags. Ultimately, based on the simulation and experimental results, it is found that the wedge-shaped airbag stiffness exhibits a three stages characteristic evolution with the gas mass increase. Then the mathematical relationship between the airbag stiffness and gas mass is obtained by numerical fitting, which provides a vital basis for structural optimization and differentiated control of nursing equipment airbags.

Multiple domestications of Asian rice.

The origin of domesticated Asian rice (Oryza sativa L.) has been controversial for more than half a century. The debates have focused on two leading hypotheses: a single domestication event in China or multiple domestication events in geographically separate areas. These two hypotheses differ in their predicted history of genes/alleles selected during domestication. Here we amassed a dataset of 1,578 resequenced genomes, including an expanded sample of wild rice from throughout its geographic range. We identified 993 selected genes that generated phylogenetic trees on which japonica and indica formed a monophyletic group, suggesting that the domestication alleles of these genes originated only once in either japonica or indica. Importantly, the domestication alleles of most selected genes (~80%) stemmed from wild rice in China, but the domestication alleles of a substantial minority of selected genes (~20%) originated from wild rice in South and Southeast Asia, demonstrating separate domestication events of Asian rice.

Impact of the COVID-19 and psychological risk factors on non-suicidal self-injury behavior among high school students: a one-year follow-up study.

OBJECTIVES: Non-suicidal self-injury (NSSI) behavior is a severe public health issue in adolescents. This study investigated the possible impact of the coronavirus disease 2019 (COVID-19) and analyzed psychological risk factors on adolescent NSSI. METHODS: A one-year follow-up study was conducted in September 2019 (Time 1) and September 2020 (Time 2) among 3588 high school students. The completed follow-up participants (N = 2527) were classified into no NSSI (negative at both time points), emerging NSSI (negative at Time 1 but positive at Time 2), and sustained NSSI (positive at both time points) subgroups according to their NSSI behaviors before and during the COVID-19 pandemic. Perceived family functioning, perceived school climate, negative life events, personality traits (neuroticism, impulsivity, and self-control) were assessed using self-report scales. RESULTS: The data indicated an increase (10.3%) in the incidence of NSSI. Compared to no NSSI subjects, the emerging NSSI and sustained NSSI subgroups had lower perceived family functioning, higher neuroticism, higher impulse-system but lower self-control scores, and more negative life events. Logistic regressions revealed that after controlling for demographics, neuroticism and impulse-system levels at Time 1 positively predicted emerging NSSI behavior, and similarly, higher neuroticism and impulsivity and lower self-control at Time 1 predicted sustained NSSI behavior. CONCLUSIONS: These findings highlighted the aggravated impact of the COVID-19 on NSSI, and suggested that individual neuroticism, impulsivity, and self-control traits might be crucial for the development of NSSI behavior among adolescent students.

Simple and Robust Deep Learning Approach for Fast Fluorescence Lifetime Imaging.

Fluorescence lifetime imaging (FLIM) is a powerful tool that provides unique quantitative information for biomedical research. In this study, we propose a multi-layer-perceptron-based mixer (MLP-Mixer) deep learning (DL) algorithm named FLIM-MLP-Mixer for fast and robust FLIM analysis. The FLIM-MLP-Mixer has a simple network architecture yet a powerful learning ability from data. Compared with the traditional fitting and previously reported DL methods, the FLIM-MLP-Mixer shows superior performance in terms of accuracy and calculation speed, which has been validated using both synthetic and experimental data. All results indicate that our proposed method is well suited for accurately estimating lifetime parameters from measured fluorescence histograms, and it has great potential in various real-time FLIM applications.

RPVC: A Revocable Publicly Verifiable Computation Solution for Edge Computing.

With publicly verifiable computation (PVC) development, users with limited resources prefer to outsource computing tasks to cloud servers. However, existing PVC schemes are mainly proposed for cloud computing scenarios, which brings bandwidth consumption or network delay of IoT devices in edge computing. In addition, dishonest edge servers may reduce resource utilization by returning unreliable results. Therefore, we propose a revocable publicly verifiable computation(RPVC) scheme for edge computing. On the one hand, RPVC ensures that users can verify the correct results at a small cost. On the other hand, it can revoke the computing abilities of dishonest edge servers. First, polynomial commitments are employed to reduce proofs' length and generation speed. Then, we improve revocable group signature by knowledge signatures and subset covering theory. This makes it possible to revoke dishonest edge servers. Finally, theoretical analysis proves that RPVC has correctness and security, and experiments evaluate the efficiency of RPVC.

Long non-coding RNA expression in silicosis and MRAK050699 function in epithelial-mesenchymal transition.

Silicosis is a lung fibrotic disease caused by chronic silica exposure. Aberrations in long non-coding RNA (lncRNA) expression are associated with fibrotic diseases, but the role of lncRNAs in silicosis pathogenesis remains unclear. Here, we investigated the expression of lncRNAs during silicosis and the role of MRAK050699 in epithelial-mesenchymal transition (EMT). Differentially expressed lncRNAs in the lung tissues of normal and silicosis rats were compared, and their biological effects were determined using the Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. There were 1077 differentially expressed lncRNAs (378 upregulated and 699 downregulated). MRAK052509, MRAK139674, AY539881, MRAK050699, XR_6113, and BC167061 were selected to verify expression in silicosis rats using quantitative reverse transcription polymerase chain reaction. MRAK050699 was knocked down in rat alveolar type II epithelial cells, and the molecular mechanism of transforming growth factor-ß (TGF-ß)-induced EMT in these cells was studied. All selected lncRNAs were upregulated in the silicosis rats, consistent with the sequencing results. MRAK050699 knockdown inhibited EMT of RLE-6TN cells by regulating the TGF-ß/Smad3 signaling pathway. Thus, the differential expression of lncRNAs is related to silicosis development, and MRAK050699 plays an important role in EMT, suggesting a potential therapeutic target for silicosis.

Clinical value of SMI Combined with Low-Dose CT Scanning in differential diagnosis of Thyroid Lesions and Tumor Staging.

OBJECTIVES: To investigate the clinical value of Superb Microvascular Imaging (SMI) combined with low dose CT scanning in differential diagnosis of thyroid lesions and tumor staging. METHODS: A total of 120 patients with thyroid nodules admitted to the Chinese PLA General Hospital from January 2017 to July 2020 were selected. Paired design was adopted in this study. SMI and SMI combined with low-dose CT scanning were respectively carried out to these patients. The results were judged by two senior imaging physicians and two senior sonographers respectively. And t-test, χ2 test, Pearson correlation coefficient check and other methods were adopted to comparatively analyze the above two methods and the pathological results after operation or puncture. RESULTS: Compared with pathologic findings, the coincidence rate of SMI was 40%, and the coincidence rate of SMI combined with low dose CT scanning was 84%. The difference was significant (p=0.00); among the 120 thyroid nodule patients, 50 were diagnosed as malignant by pathological diagnosis, and 70 as benign; 27 malignant cases and 93 benign cases were detected by SMI; 48 malignant cases and 72 benign cases were detected by SMI combined with low dose CT scanning. The sensitivity and accuracy of the latter were significantly higher than those of the former, and the difference was statistically significant (p=0.00); the enhancement, edge sharpness and homogeneity of SMI increased with the increase of tumor malignancy, showing positive correlation property. CONCLUSION: SMI combined with low dose CT scanning has a higher diagnostic coincidence rate. Its sensitivity and accuracy are significantly superior. With the increase of tumor malignancy, the enhancement and unhomogeneity of SMI increase, and the edge is more blurred. That suggests: with the increase of tumor malignancy, neovascularization in the tumor is more obvious and more unevenly distributed; the increase of edge blur indicates more obvious tumor infiltration. The method has considerable clinical value for predicting the malignancy of tumors.

Irradiation stent insertion for inoperable malignant biliary obstruction: a meta-analysis of randomized controlled trials.

The purpose of the study was to compare the relative clinical efficacies of irradiation stent (IRS) and conventional stent (CVS) insertions for the treatment of patients with malignant biliary obstruction (MBO). Pubmed, Embase, and Cochrane Library databases were searched for relevant randomized controlled trials (RCTs) from the date of inception through to August 2020. Data analysis was performed using RevMan v5.3. This meta-analysis included eight RCTs which included a total of 319 patients who had undergone IRS insertion, and 328 who had undergone CVS insertion. No significant differences in pooled Δ total bilirubin values (MD 0.34; P = 0.92), incident rates of cholangitis (P = 0.47), hemobilia (P = 0.60), or pancreatitis (P = 0.89) were detected between two groups. The rate of stent dysfunction was significantly lower in the IRS group compared to the CVS group (22.2% vs. 37.7%, P = 0.02). The pooled stent patency (P < 0.00001) and survival (P < 0.00001) were significantly longer in the IRS group compared to the CVS group. Significant heterogeneity was detected in the endpoints of rate of stent dysfunction (I2 = 52%; P = 0.08) and survival (I2 = 77%; P = 0.0005). Subgroup analysis was performed based on the different IRS types and showed significantly longer survival in the IRS group based on both types of IRS. Funnel plot analyses did not detect any evidence of publication bias. This meta-analysis included eight RCTs which included a total of 319 patients who had undergone IRS insertion, and 328 who had undergone CVS insertion. No significant differences in pooled Δ total bilirubin values (MD 0.34; P = 0.92), incident rates of cholangitis (P = 0.47), hemobilia (P = 0.60), or pancreatitis (P = 0.89) were detected between 2 groups. The rate of stent dysfunction was significantly lower in the IRS group compared to the CVS group (22.2% vs. 37.7%, P = 0.02). The pooled stent patency (P < 0.00001) and survival (P < 0.00001) were significantly longer in the IRS group compared to the CVS group. Significant heterogeneity was detected in the endpoints of rate of stent dysfunction (I2 = 52%; P = 0.08) and survival (I2 = 77%; P = 0.0005). Subgroup analysis was performed based on the different IRS types and showed significantly longer survival in the IRS group based on both types of IRS. Funnel plot analyses did not detect any evidence of publication bias. Our meta-analysis demonstrates that IRS insertion can prolong stent patency and the survival of patients with MBO compared to CVS insertion.

[Effect of acupuncture and moxibustion on expression of signal transducers and activators of transcription 3 and hypoxia-inducible factor 1α in colon mucosa in ulcerative colitis mice].

OBJECTIVE: To investigate the effect of acupuncture or moxibustion of "Zusanli" (ST36) and "Guanyuan" (CV4) on expression of signal transducers and activators of transcription 3 (STAT3) and hypoxia-inducible factor 1α (HIF-1α) in colonic tissue in ulcerative colitis (UC) mice. METHODS: Thirty-two male Kunming mice were randomly divided into control, model, acupuncture and moxibustion groups (n=8 in each group). The UC model was induced by free drinking of 3% Dextran Sodium Sulfate for 7 days. Acupuncture or moxibustion was applied to ST36 or CV4 for 15 min, once daily for 5 days. The severity of UC was monitored using the disease activity index (DAI) which includes evaluation of weight loss, stool consistency, and presence of fecal blood. Histopathological changes of the colon mucosa were observed by H.E. staining. Immunohistochemistry and Western blot were employed to detect the expression of STAT3 and HIF-1α proteins in the colon mucosa tissue. RESULTS: After modeling, the DAI, immunoactivity and expression of STAT3 and HIF-1α in the colonic tissue were significantly increased in the model group relevant to the control group (P<0.01,P<0.05). Compared with the model group, the levels of DAI, STAT3 and HIF-1α considerably decreased in both acupuncture and moxibustion groups (P<0.05), and without significant differences between the two intervention groups in the levels of DAI, STAT3 and HIF-1α after the intervention (P>0.05). H.E. staining of the colonic tissue showed damage and infiltration of inflammatory cells in the model group, and reduction of the submucosal edema and infiltrated inflammatory cells in the acupuncture and moxibustion groups. CONCLUSION: Both acupuncture and moxibustion can improve UC in UC mice, which may be associated with its effects in down-regulating the expression of colonic STAT3 and HIF-1α proteins.

Role of Spinal Cord Akt-mTOR Signaling Pathways in Postoperative Hyperalgesia Induced by Plantar Incision in Mice.

Poor postoperative pain (POP) control increases perioperative morbidity, prolongs hospitalization days, and causes chronic pain. However, the specific mechanism(s) underlying POP is unclear and the identification of optimal perioperative treatment remains elusive. Akt and mammalian target of rapamycin (mTOR) are expressed in the spinal cord, dorsal root ganglion, and sensory axons. In this study, we explored the role of Akt and mTOR in pain-related behaviors induced by plantar incision in mice. Plantar incision activated spinal Akt and mTOR in a dose-dependent manner. Pre-treatment with Akt inhibitors intrathecally prevented the activation of mTOR dose-dependently. In addition, blocking the Akt-mTOR signaling cascade attenuated pain-related behaviors and spinal Fos protein expression induced by plantar incision. Our observations demonstrate that Akt-mTOR might be a potential therapeutic target for the treatment of POP.

Musculoskeletal ultrasound in the Differential Diagnosis of Gouty Arthritis and Rheumatoid Arthritis.

OBJECTIVE: To explore the role of musculoskeletal ultrasound (MSUS) in the differential diagnosis of gouty arthritis (GA) and rheumatoid arthritis (RA) and to analyze the ultrasound imaging features of the two diseases. METHODS: A retrospective study was carried out. A total of 66 patients who had been admitted to The First Medical Center of Chinese PLA General Hospital from May 2018 to March 2019 were enrolled. Among them, 34 patients were diagnosed with RA and were included in the RA group; 32 patients were diagnosed with gouty arthritis and were included in the GA group. The imaging features of musculoskeletal ultrasound were compared between the two groups of patients. RESULTS: A total of 34 patients were included in the RA group, including 17 males and 17 females. A total of 32 patients were included in the GA group, including 14 males and 18 females. There were no significant differences in gender composition, age, and duration of disease between the two groups (P>0.05). In the RA group, there were joint bone erosions with a clear boundary in seven cases and with a blurred boundary in 27 cases; synovial hyperplasia was observed in 27 cases, and point-like hyperechoic masses were observed in four cases. In the GA group, there were joint bone erosions with a clear boundary in 27 cases and with a blurred boundary in five cases; synovial hyperplasia was observed in four cases, tophus was observed in 23 cases, point-like hyperechoic masses were observed in 27 cases, and the tram-track sign was observed in 23 cases. The differences in bone erosion boundaries (c2=26.854, P<0.01), synovial hyperplasia (c2=29.631, P<0.01), tophus (P<0.01), point-like hyperechoic mass (c2=33.095, P<0.01), and tram-track sign (P<0.01) were statistically significant between the two groups of patients. In the RA group, blood flow signaling was Grade 0 in one case, Grade-I in five cases, Grade-II in 14 cases, and Grade-III in 14 cases. In the GA group, blood flow signaling was Grade 0 in 26 cases, Grade-I in three cases, Grade-II in three cases, and Grade-III in zero cases. The difference in the synovial blood flow signaling between the two groups of patients was statistically significant (c2=34.323, P<0.01). CONCLUSIONS: MSUS has certain diagnostic value in the differentiation of GA and RA. Moreover, the two conditions have their own ultrasound imaging features.

The Novel Compound Heterozygous Mutations of ECEL1 Identified in a Family with Distal Arthrogryposis Type 5D.

INTRODUCTION: Distal arthrogryposis type 5D (DA5D) is an autosomal recessive disease. The clinical symptoms include contractures of the joints of limbs, especially camptodactyly of the hands and/or feet, unilateral ptosis, a round-shaped face, arched eyebrows, and micrognathia, without ophthalmoplegia. ECEL1 is a DA5D causative gene that encodes a membrane-bound metalloprotease. ECEL1 plays important roles in the final axonal arborization of motor nerves in limb skeletal muscles and neuromuscular junction formation during prenatal development. METHODS: A DA5D family with webbing of the elbows and fingers was recruited. We performed whole-exome sequencing (WES) and filtered mutations by disease-causing genes of arthrogryposis multiplex congenita (AMC). Mutational analysis and cosegregation confirmation were then performed. RESULTS: We identified novel compound heterozygous mutations of ECEL1 (NM_004826: c.69C>A, p.C23∗ and c.1810G>A, p.G604R) in the proband. CONCLUSIONS: We detected causative mutations in a DA5D family, expanding the spectrum of known ECEL1 mutations and contributing to the clinical diagnosis of DA5D.

Identification of an unknown frameshift variant of NOG in a Han Chinese family with proximal symphalangism.

Proximal symphalangism (SYM1) is an autosomal dominant disorder manifested by ankylosis of the proximal interphalangeal joints of fingers, carpal and tarsal bone fusion, and conductive hearing loss in some cases. Herein, we clinically diagnosed a Chinese patient with fusions of the bilateral proximal interphalangeal joints in the 2-5 digits without conductive hearing loss. Family history investigation revealed that his mother and grandfather also suffered from SYM1. Whole exome sequencing was performed to detect the genetic lesion of the family. The candidate gene variants were validated by Sanger sequencing. By data filtering, co-segregation analysis and bioinformatics analysis, we highly suspected that an unknown heterozygous frameshift variant (c.635_636insG, p.Q213Pfs*57) in NOG was responsible for the SYM1 in the family. This variant was predicted to be deleterious and resulted in a prolonged protein. This finding broadened the spectrum of NOG mutations associated with SYM1 and contributed to genetic diagnosis and counseling of families with SYM1.

Overexpression of global regulator LaeA increases secondary metabolite production in Monascus purpureus.

Monascus is a filamentous fungus that produces several secondary metabolites. Here, we investigated the effects of the global regulator LaeA on the synthesis of pigments and monacolin K in Monascus purpureus with spectrophotometer and HPLC methods. The LaeA gene was isolated from M. purpureus M1 to create an overexpression construct. An LaeA-overexpressing strain L3 was with 48.6% higher monacolin K production than the M1 strain. The L3 strain also produced higher Monascus pigments than the M1 strain. SEM showed that LaeA overexpression resulted in altered mycelial morphology. Compared with the M1 strain, the L3 strain expressed higher levels of monacolin K synthesis-related genes mokA, mokB, mokE, and mokH. Overall, these results suggest that LaeA plays a role in regulating the production of secondary metabolites and mycelial growth in Monascus. This study provides important insights into the mechanisms underlying the effects of the LaeA gene on the secondary metabolites of M. purpureus.