Population genomics highlights structural variations in local adaptation to saline coastal environments in woolly grape.

Structural variations (SVs) are a feature of plant genomes that has been largely unexplored despite their significant impact on plant phenotypic traits and local adaptation to abiotic and biotic stress. In this study, we employed woolly grape (Vitis retordii), a species native to the tropical and subtropical regions of East Asia with both coastal and inland habitats, as a valuable model for examining the impact of SVs on local adaptation. We assembled a haplotype-resolved chromosomal reference genome for woolly grape, and conducted population genetic analyses based on whole-genome sequencing (WGS) data from coastal and inland populations. The demographic analyses revealed recent bottlenecks in all populations and asymmetric gene flow from the inland to the coastal population. In total, 1,035 genes associated with plant adaptive regulation for salt stress, radiation, and environmental adaptation were detected underlying local selection by SVs and SNPs in the coastal population, of which 37.29% and 65.26% were detected by SVs and SNPs, respectively. Candidate genes such as FSD2, RGA1, and AAP8 associated with salt tolerance were found to be highly differentiated and selected during the process of local adaptation to coastal habitats in SV regions. Our study highlights the importance of SVs in local adaptation; candidate genes related to salt stress and climatic adaptation to tropical and subtropical environments are important genomic resources for future breeding programs of grapevine and its rootstocks.

Serum globulin in children with myasthenia gravis: predicting relapse and prognosis.

OBJECTIVE: Serum globulin is associated with inflammatory or immune disorders. However, it has not been established whether it is associated with myasthenia gravis (MG). We investigated the association between globulin with relapse and prognosis in children with MG. METHODS: A cohort of 148 MG cases and 150 healthy children were retrospectively enrolled from January 2015 to December 2021. Multivariate logistic and Cox regression models were used to analyze the treatment outcomes and recurrence of case group, exploring the influence of globulin. RESULTS: Compared with the control group, globulin levels in the MG group were slightly increased (t = 7.244, p < 0.001). After a mean follow-up of 2.25 ± 1.05 years, 35 cases relapsed, with a relapse rate of 23.65%. Logistic regression analysis showed that globulin levels at admission [adjusted odds ratio (OR) = 1.233, 95% confidence interval (CI) 1.028-1.472, p = 0.018] were independent risk factors for relapse. Cox regression analysis confirmed that globulin levels at admission affects relapse-free time [adjusted hazard ratio (HR) = 0.552, 95% CI 0.357-0.852, p = 0.007]. Receiver operating characteristic curve determined 25.10 as the optimal cutoff value for globulin. Cox regression showed that high globulin levels (>25.10) at admission (adjusted HR = 0.607, 95% CI 0.383-0.961, p = 0.033) were independent risk factors for poor therapeutic outcomes at follow-up. Ordinal logistic regression showed that globulin affects the treatment plan (OR = 1.445, 95% CI 1.223-1.847, p = 0.014). CONCLUSIONS: Elevated globulin levels in children with MG on admission predicts a high relapse rate and poor long-term therapeutic efficacies.

Serum globulin in children with myasthenia gravis: predicting relapse and prognosisFirst, the globulin in the MG children was higher than in the healthy controls, and there was some correlation between the globulin and the level of systemic inflammation.Second, globulin has been associated with relapse of MG in children. The higher the globulin, the higher the relapse rate and the shorter the time to prevent a relapse.Third, both initial and final globulin were related to the effect of MG in children, and the higher the long-term effect, the worse the long-term effect. It also influenced the change in treatment plan.

Geniposide Attenuates Oxygen-glucose Deprivation/Recovery-induced Retinal Ganglion Cell Injury via Akt/Nrf-2 Signaling Pathway.

BACKGROUND: Glaucoma is an eye disease. Its pathological process involves retinal ischemia-reperfusion (I/R), which causes irreversible blindness in patients. Geniposide (Gen), a bioactive iridoid glycoside extracted from the fruit of gardenia, exhibits many biological effects, such as anti-oxidative stress, anti-inflammation, anti-apoptosis, anti-endoplasmic reticulum stress, and anti-thrombotic effects. However, its therapeutic potential for the retinal I/R injury remains unclear. This study investigated the protective effect of Gen against I/R injury by inhibiting abnormal reactive oxygen species (ROS) and retinal neuron apoptosis. METHODS: We used oxygen-glucose deprivation/reoxygenation (OGD/R) to induce R28 cells to mimic the pathological process of I/R in glaucoma. We conducted CCK-8 analysis and TUNEL staining to examine cell proliferation and apoptosis in glaucoma. Western blotting was used to assay the expressions of apoptosis and Akt/Nrf-2 pathway-related proteins. RESULTS: The production of ROS was detected by using the corresponding kit. Cell viability decreased, whereas TUNEL staining-positive cells and ROS production increased after the OGD/R injury. The contents of cleaved caspase-3 and Bax/Bcl-2 increased after the OGD/R injury. Treatment with 200 µM of Gen effectively improved the cell viability and suppressed cell apoptosis and ROS production. In addition, Gen could significantly promote the activation of the Akt/Nrf-2 signaling pathway in R28 cells, which was blocked by the inhibition of Akt/Nrf-2. We in vivo verified the neuroprotective effect of Gen by establishing an acute high intraocular pressure (aHIOP) model and obtained similar results to those of the in vitro experimental results. CONCLUSION: Hence, it can be suggested that Gen provides neuroprotection against the OGD/R-induced injury of R28 cells by activating the Akt/Nrf-2 signaling pathway, which is beneficial for the clinical treatment of glaucoma.

Associations between life's essential 8 and metabolic health among us adults: insights of NHANES from 2005 to 2018.

BACKGROUND: Metabolic unhealth (MUH) is closely associated with cardiovascular disease (CVD). Life's Essential 8 (LE8), a recently updated cardiovascular health (CVH) assessment, has some overlapping indicators with MUH but is more comprehensive and complicated than MUH. Given the close relationship between them, it is important to compare these two measurements. METHODS: This population-based cross-sectional survey included 20- to 80-year-old individuals from 7 National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2018. Based on the parameters provided by the American Heart Association, the LE8 score (which ranges from 0 to 100) was used to classify CVH into three categories: low (0-49), moderate (50-79), and high (80-100). The MUH status was evaluated by blood glucose, blood pressure, and blood lipids. The associations were assessed by multivariable regression analysis, subgroup analysis, restricted cubic spline models, and sensitivity analysis. RESULTS: A total of 22,582 participants were enrolled (median of age was 45 years old), among them, 11,127 were female (weighted percentage, 49%) and 16,595 were classified as MUH (weighted percentage, 73.5%). The weighted median LE8 scores of metabolic health (MH) and MUH individuals are 73.75 and 59.38, respectively. Higher LE8 scores were linked to lower risks of MUH (odds ratio [OR] for every 10 scores increase, 0.53; 95% CI 0.51-0.55), and a nonlinear dose-response relationship was seen after the adjustment of potential confounders. This negative correlation between LE8 scores, and MUH was strengthened among elderly population. CONCLUSIONS: Higher LE8 and its subscales scores were inversely and nonlinearly linked with the lower presence of MUH. MUH is consistent with LE8 scores, which can be considered as an alternative indicator when it is difficult to collect the information of health behaviors.

NFATc4 Knockout Promotes Neuroprotection and Retinal Ganglion Cell Regeneration After Optic Nerve Injury.

Retinal ganglion cells (RGCs), neurons transmitting visual information via the optic nerve, fail to regenerate their axons after injury. The progressive loss of RGC function underlies the pathophysiology of glaucoma and other optic neuropathies, often leading to irreversible blindness. Therefore, there is an urgent need to identify the regulators of RGC survival and the regenerative program. In this study, we investigated the role of the family of transcription factors known as nuclear factor of activated T cells (NFAT), which are expressed in the retina; however, their role in RGC survival after injury is unknown. Using the optic nerve crush (ONC) model, widely employed to study optic neuropathies and central nervous system axon injury, we found that NFATc4 is specifically but transiently up-regulated in response to mechanical injury. In the injured retina, NFATc4 immunolocalized primarily to the ganglionic cell layer. Utilizing NFATc4-/- and NFATc3-/- mice, we demonstrated that NFATc4, but not NFATc3, knockout increased RGC survival, improved retina function, and delayed axonal degeneration. Microarray screening data, along with decreased immunostaining of cleaved caspase-3, revealed that NFATc4 knockout was protective against ONC-induced degeneration by suppressing pro-apoptotic signaling. Finally, we used lentiviral-mediated NFATc4 delivery to the retina of NFATc4-/- mice and reversed the pro-survival effect of NFATc4 knockout, conclusively linking the enhanced survival of injured RGCs to NFATc4-dependent mechanisms. In summary, this study is the first to demonstrate that NFATc4 knockout may confer transient RGC neuroprotection and decelerate axonal degeneration after injury, providing a potent therapeutic strategy for optic neuropathies.

Construction of a Visible-Light-Response Photocatalysis-Self-Fenton Degradation System of Coupling Industrial Waste Red Mud to Resorcinol-Formaldehyde Resin.

Heterogeneous photocatalysis-self-Fenton technology is a sustainable strategy for treating organic pollutants in actual water bodies with high-fluent degradation and high mineralization capacity, overcoming the limitations of the safety risks caused by adding external iron sources and hazardous chemicals in the homogeneous Fenton reaction and injecting high-intensity energy fields in photo-Fenton reaction. Herein, a photo-self-Fenton system based on resorcinol-formaldehyde (RF) resin and red mud (RM) was established to generate hydrogen peroxide (H2O2) in situ and transform into hydroxy radical (•OH) for efficient degradation of tetracycline (TC) under visible light irradiation. The capturing experiments and electron spin resonance (ESR) confirmed that the hinge for the enhanced performance of this system is the superior H2O2 yield (499 µM) through the oxygen reduction process (ORR) of the two-step single-electron over the resin and the high concentration of •OH due to activation effect of RM. In addition, the Fe2+/Fe3+ cycles are accelerated by photoelectrons to effectively initiate the photo-self-Fenton reaction. Finally, the possible degradation pathways were proposed via liquid chromatography-mass spectrometry (LC-MS). This study provides a new idea for environmental recovery in a waste-based heterogeneous photocatalytic self-Fenton system.

Advances in biotin biosynthesis and biotechnological production in microorganisms.

Biotin, also known as vitamin H or B7, acts as a crucial cofactor in the central metabolism processes of fatty acids, amino acids, and carbohydrates. Biotin has important applications in food additives, biomedicine, and other fields. While the ability to synthesize biotin de novo is confined to microorganisms and plants, humans and animals require substantial daily intake, primarily through dietary sources and intestinal microflora. Currently, chemical synthesis stands as the primary method for commercial biotin production, although microbial biotin production offers an environmentally sustainable alternative with promising prospects. This review presents a comprehensive overview of the pathways involved in de novo biotin synthesis in various species of microbes and insights into its regulatory and transport systems. Furthermore, diverse strategies are discussed to improve the biotin production here, including mutation breeding, rational metabolic engineering design, artificial genetic modification, and process optimization. The review also presents the potential strategies for addressing current challenges for industrial-scale bioproduction of biotin in the future. This review is very helpful for exploring efficient and sustainable strategies for large-scale biotin production.

Extracellular vesicles-based point-of-care testing for the diagnosis and monitoring of Alzheimer's disease.

Alzheimer's disease (AD) is a debilitating condition that affects millions of people worldwide. One promising strategy for detecting and monitoring AD early on is using extracellular vesicles (EVs)-based point-of-care testing; however, diagnosing AD using EVs poses a challenge due to the low abundance of EV-biomarkers. Here, we present a fully integrated organic electrochemical transistor (OECT) that enables high accuracy, speed, and convenience in the detection of EVs from AD patients. We incorporated self-aligned acoustoelectric enhancement of EVs on a chip that rapidly propels, enriches, and specifically binds EVs to the OECT detection area. With our enhancement of pre-concentration, we increased the sensitivity to a limit of detection of 500 EV particles/µL and reduced the required detection time to just two minutes. We also tested the sensor on an AD mouse model to monitor AD progression, examined mouse Aß EVs at different time courses, and compared them with intraneuronal Aß cumulation using MRI. This innovative technology has the potential to diagnose Alzheimer's and other neurodegenerative diseases accurately and quickly, enabling monitoring of disease progression and treatment response.

HHIP protein interactions in lung cells provide insight into COPD pathogenesis.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. The primary causes of COPD are environmental, including cigarette smoking; however, genetic susceptibility also contributes to COPD risk. Genome-Wide Association Studies (GWASes) have revealed more than 80 genetic loci associated with COPD, leading to the identification of multiple COPD GWAS genes. However, the biological relationships between the identified COPD susceptibility genes are largely unknown. Genes associated with a complex disease are often in close network proximity, i.e. their protein products often interact directly with each other and/or similar proteins. In this study, we use affinity purification mass spectrometry (AP-MS) to identify protein interactions with HHIP , a well-established COPD GWAS gene which is part of the sonic hedgehog pathway, in two disease-relevant lung cell lines (IMR90 and 16HBE). To better understand the network neighborhood of HHIP , its proximity to the protein products of other COPD GWAS genes, and its functional role in COPD pathogenesis, we create HUBRIS, a protein-protein interaction network compiled from 8 publicly available databases. We identified both common and cell type-specific protein-protein interactors of HHIP. We find that our newly identified interactions shorten the network distance between HHIP and the protein products of several COPD GWAS genes, including DSP, MFAP2, TET2 , and FBLN5 . These new shorter paths include proteins that are encoded by genes involved in extracellular matrix and tissue organization. We found and validated interactions to proteins that provide new insights into COPD pathobiology, including CAVIN1 (IMR90) and TP53 (16HBE). The newly discovered HHIP interactions with CAVIN1 and TP53 implicate HHIP in response to oxidative stress.

Imaging Findings and Toxicological Mechanisms of Nervous System Injury Caused by Diquat.

Diquat (DQ) is a nonselective bipyridine herbicide with a structure resembling paraquat (PQ). In recent years, the utilization of DQ as a substitute for PQ has grown, leading to an increase in DQ poisoning cases. While the toxicity mechanism of DQ remains unclear, it is primarily attributed to the intracellular generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) through the process of reduction oxidation. This results in oxidative stress, leading to a cascade of clinical symptoms. Notably, recent reports on DQ poisoning have highlighted a concerning trend: an upsurge in cases involving neurological damage caused by DQ poisoning. These patients often present with severe illness and a high mortality rate, with no effective treatment available thus far. Imaging findings from these cases have shown that neurological damage tends to concentrate on the brainstem. However, the specific mechanisms behind this poisoning remain unclear, and no specific antidote exists. This review summarizes the research progress on DQ poisoning and explores potential mechanisms. By shedding light on the nerve damage associated with DQ poisoning, we hope to raise awareness, propose new avenues for investigating the mechanisms of DQ poisoning, and lay the groundwork for the development of treatment strategies for DQ poisoning. Trial registration number: 2024PS174K.

Ubiquitin ligase TRIM15 promotes the progression of pancreatic cancer via the upregulation of the IGF2BP2-TLR4 axis.

BACKGROUND: The tripartite motif family, predominantly characterized by its E3 ubiquitin ligase activities, is involved in various cellular processes including signal transduction, apoptosis and autophagy, protein quality control, immune regulation, and carcinogenesis. Tripartite Motif Containing 15 (TRIM15) plays an important role in melanoma progression through extracellular signal-regulated kinase activation; however, data on its role in pancreatic tumors remain lacking. We previously demonstrated that TRIM15 targeted lipid synthesis and metabolism in pancreatic cancer; however, other specific regulatory mechanisms remain elusive. METHODS: We used transcriptomics and proteomics, conducted a series of phenotypic experiments, and used a mouse orthotopic transplantation model to study the specific mechanism of TRIM15 in pancreatic cancer in vitro and in vivo. RESULTS: TRIM15 overexpression promoted the progression of pancreatic cancer by upregulating the toll-like receptor 4. The TRIM15 binding protein, IGF2BP2, could combine with TLR4 to inhibit its mRNA degradation. Furthermore, the ubiquitin level of IGF2BP2 was positively correlated with TRIM15. CONCLUSIONS: TRIM15 could ubiquitinate IGF2BP2 to enhance the function of phase separation and the maintenance of mRNA stability of TLR4. TRIM15 is a potential therapeutic target against pancreatic cancer.

GFRA4 improves the neurogenic potential of enteric neural crest stem cells via hedgehog pathway.

BACKGROUND: Hirschsprung disease (HSCR) is a congenital intestinal disease characterised by functional obstruction of the colon. Herein, we investigated the role and mechanism of the gene GFRA4 in HSCR. METHODS: GFRA4 expression in the ganglionic and aganglionic segment tissues in patients with HSCR and healthy colon tissues were detected using qRT-PCR, western blot, and immunohistochemistry. Cell proliferation, cycle distribution, apoptosis, changes in mitochondrial membrane potential, and differentiation were assessed in mouse enteric neural crest stem cells (ENCSCs) using the CCK-8 assay, EdU staining, flow cytometry, JC-1 probe, and immunofluorescence, respectively. GSEA analysis was performed to screen the signaling pathways regulated by GFRA4. RESULTS: GFRA4 was downregulated in aganglionic segment tissues compared to control and ganglionic segment tissues. GFRA4 overexpression promoted proliferation and differentiation, and inhibited apoptosis in ENCSCs, while GFRA4 down-regulation had the opposite result. GFRA4 activated the hedgehog pathway. GFRA4 overexpression enhanced the expression of key factors of the hedgehog pathway, including SMO, SHH, and GLI1. However, GFRA4 down-regulation reduced their expression. An antagonist of hedgehog pathway, cyclopamine, attenuated the effect of GFRA4 overexpression on proliferation, differentiation, and apoptosis of ENCSCs. CONCLUSION: GFRA4 promotes proliferation and differentiation but inhibits apoptosis of ENCSCs via the hedgehog pathway in HSCR. IMPACT: This study confirms that GFRA4 improves the proliferation and differentiation of ENCSCs via modulation of the hedgehog pathway. This study for the first time revealed the role and the mechanism of the action of GFRA4 in HSCR, which indicates that GFRA4 may play a role in the pathological development of HSCR. Our findings may lay the foundation for further investigation of the mechanisms underlying HSCR development and into targets of HSCR treatment.

An efficient inoculation method to evaluate virulence differentiation of field strains of sugarcane smut fungus.

Sugarcane smut, caused by the fungal pathogen Sporisorium scitamineum, is a prominent threat to the sugarcane industry. The development of smut resistant varieties is the ultimate solution for controlling this disease, due to the lack of other efficient control methods. Artificial inoculation method is used to evaluate the virulence differentiation of pathogens. The mostly used artificial inoculation methods are soaking of the seed canes in the teliospore solution and injection of teliospores or haploid sporidia into the sugarcane sprouts. However, due to the infection nature of the pathogen that invades the sugarcane plant through meristem tissue of the sprout or shoot, the rate of successful infection is often low and fluctuated, resulting in low confidence of the assays. We recently reported a rapid and high-throughput inoculation method called plantlet soaking by using tissue culture-derived sugarcane plantlets as the test plants. Here, we compare different inoculation methods and report the characterization of parameters that may affect the sensitivity and efficiency of the plantlet soaking technique. The results showed that sugarcane plantlets were highly vulnerable to infection, even with the inoculum density at 6.0 × 105 basidial spores/ml, and this method could be applied to all varieties tested. Notably, varieties showing high smut resistance in the field exhibited high susceptibility when inoculated with the plantlet soaking method, suggesting that the plantlet soaking method is a good complement to the traditional methods for screening germplasms with internal resistance. In addition, this method could also be used to monitor the variation of cellular virulence of the smut pathogen strains in the field.

Effects of executive load on crashes and near-crashes for young versus older drivers.

With the increasing use of infotainment systems in vehicles, secondary tasks requiring executive demand may increase crash risk, especially for young drivers. Naturalistic driving data were examined to determine if secondary tasks with increasing executive demand would result in increasing crash risk. Data were extracted from the Second Strategic Highway Research Program Naturalistic Driving Study, where vehicles were instrumented to record driving behavior and crash/near-crash data. executive and visual-manual tasks paired with a second executive task (also referred to as dual executive tasks) were compared to the executive and visual-manual tasks performed alone. Crash/near-crash odds ratios were computed by comparing each task condition to driving without the presence of any secondary task. Dual executive tasks resulted in greater odds ratios than those for single executive tasks. The dual visual-manual task odds ratios did not increase from single task odds ratios. These effects were only found in young drivers. The study shows that dual executive secondary task load increases crash/near-crash risk in dual task situations for young drivers. Future research should be conducted to minimize task load associated with vehicle infotainment systems that use such technologies as voice commands.

The application of machine learning based on computed tomography images in the identification of renal tumors in children.

Background: The clinical manifestations of Wilms tumor and non-Wilms tumor in children are similar, and the only way to confirm the diagnosis is by postoperative pathology. Computed tomography (CT) is one of the main methods for preoperative diagnosis of the two, but it is also difficult to distinguish because it is easily affected by the subjective influence and the experience of the radiologists. Methods: The CT images of 82 children with renal tumors admitted to the Department of Pediatric Urology, Shandong Provincial Hospital from January 2011 to March 2022 were retrospectively analyzed. First, we drew the two-dimensional (2D) region of interest (ROI) of the largest cross-section on the corticomedullary phase (CMP) and nephrogenic phase (NP) images, and extracted seven types of 107 features in the ROI. Then, the texture features with similarity greater than 95% and repetition less than 90% were screened out, and the remaining texture features were further screened by analysis of variance (ANOVA) and recursive feature elimination (RFE). Finally, 15 texture feature were used to build the machine learning (ML) models. We used the synthetic minority oversampling technique (SMOTE) and 10-fold cross-validation to build ML models and verified them in the training, testing, and internal validation sets. The area under the receiver-operating characteristic curve (AUC) and calibration curve were used to evaluate the diagnostic performance. Results: We collected 77 CMP and 81 NP images, which were randomly divided into the training set and the testing set according to the ratio of 7:3. In the internal validation of CMP, the Mean-PCC-ANOVA-5-AE pipeline model achieved the highest AUC 0.792 [95% confidence interval (CI): 0.653-0.930], and its accuracy (ACC), sensitivity (SEN), and specificity (SPE) were 0.833, 0.539 and 0.927, respectively. Correspondingly, in NP, the Mean-PCC-ANOVA-2-LR pipeline model achieved the highest AUC 0.655 (95% CI: 0.485-0.82) in the internal validation. The ACC, SEN, and SPE were 0.696, 0.539, and 0.744, respectively. Conclusions: The ML models based on CT images have good diagnostic efficiency in differentiating Wilms tumors from non-Wilms tumors in children.

Reconstruction of the genome-scale metabolic network model of Sinorhizobium fredii CCBAU45436 for free-living and symbiotic states.

Sinorhizobium fredii CCBAU45436 is an excellent rhizobium that plays an important role in agricultural production. However, there still needs more comprehensive understanding of the metabolic system of S. fredii CCBAU45436, which hinders its application in agriculture. Therefore, based on the first-generation metabolic model iCC541 we developed a new genome-scale metabolic model iAQY970, which contains 970 genes, 1,052 reactions, 942 metabolites and is scored 89% in the MEMOTE test. Cell growth phenotype predicted by iAQY970 is 81.7% consistent with the experimental data. The results of mapping the proteome data under free-living and symbiosis conditions to the model showed that the biomass production rate in the logarithmic phase was faster than that in the stable phase, and the nitrogen fixation efficiency of rhizobia parasitized in cultivated soybean was higher than that in wild-type soybean, which was consistent with the actual situation. In the symbiotic condition, there are 184 genes that would affect growth, of which 94 are essential; In the free-living condition, there are 143 genes that influence growth, of which 78 are essential. Among them, 86 of the 94 essential genes in the symbiotic condition were consistent with the prediction of iCC541, and 44 essential genes were confirmed by literature information; meanwhile, 30 genes were identified by DEG and 33 genes were identified by Geptop. In addition, we extracted four key nitrogen fixation modules from the model and predicted that sulfite reductase (EC 1.8.7.1) and nitrogenase (EC 1.18.6.1) as the target enzymes to enhance nitrogen fixation by MOMA, which provided a potential focus for strain optimization. Through the comprehensive metabolic model, we can better understand the metabolic capabilities of S. fredii CCBAU45436 and make full use of it in the future.

Engineering industrial yeast for improved tolerance and robustness.

As an important cell factory, industrial yeast has been widely used for the production of compounds ranging from bulk chemicals to complex natural products. However, various adverse conditions including toxic products, extreme pH, and hyperosmosis etc., severely restrict microbial growth and metabolic performance, limiting the fermentation efficiency and diminishing its competitiveness. Therefore, enhancing the tolerance and robustness of yeasts is critical to ensure reliable and sustainable production of metabolites in complex industrial production processes. In this review, we provide a comprehensive review of various strategies for improving the tolerance of yeast cells, including random mutagenesis, system metabolic engineering, and material-mediated immobilization cell technology. It is expected that this review will provide a new perspective to realize the response and intelligent regulation of yeast cells to environmental stresses.

(Z, Z, Z)-3,6,9-Nonadecadiene, a potential inhibitor of sex pheromone of Grey Tea Geometrid (Lepidoptera: Geometridae): electroantennogram test, wind tunnel, and in silico study.

Sex pheromone analogs have high structural similarity to sex pheromone components. They also play a role in studying many agricultural pests. In our study, (Z, Z, Z)-3,6,9-nonadecadiene (Z3Z6Z9-19:Hy) was successfully synthesized, which is an analogue to 1 of 2 sex pheromone components of Ectropis grisescens Warren (Z, Z, Z)-3,6,9-octadecatriene (Z3Z6Z9-18:Hy), and it showed potential inhibition in experiments. In the electroantennogram test, Z3Z6Z9-19:Hy showed a dose-dependent response, and only measured half the response of Z3Z9-6,7-epo-18:Hy. However, the compound significantly reduced positive response of E. grisescens males by up to 70% in the Y-tube olfactometer. Furthermore, in the wind tunnel, it significantly inhibited all types of behavioral responses. The percentage of moths contacting the pheromone odor source was reduced even at the lowest dose tested. In silico study afterward, molecular docking results showed affinity between Z3Z6Z9-19:Hy and sensory neuron membrane protein 1. Our study revealed the potential of Z3Z6Z9-19:Hy as a sex pheromone inhibitor, which would provide new tools for monitoring and mating disruption of E. grisescens.

Diversity-oriented synthesis of indole-fused scaffolds and bis(indolyl)methane from tosyl-protected tryptamine.

An efficient, diversity-oriented synthesis of indole-1,2-fused 1,4-benzodiazepines, tetrahydro-ß-carbolines, and 2,2'-bis(indolyl)methanes was established starting from tosyl-protected tryptamine. These diverse privileged skeletons were controllably constructed by adjusting different hydride donors and Brønsted acids. A variety of indole-1,2-fused 1,4-benzodiazepines were facilely accessed using benzaldehydes bearing cyclic amines as hydride donors via a cascade N-alkylation/dehydration/[1,5]-hydride transfer/Friedel-Crafts alkylation sequence. The reaction site could be switched when benzaldehydes bearing an alkoxy moiety as hydride donors were used for the generation of tetrahydro-ß-carbolines. On the other hand, the switchable synthesis of 2,2'-bis(indolyl)methanes could be achieved as well by applying p-TsOH·H2O as a catalyst. The reactions feature mild conditions, simple and practical operation, excellent efficiency and the use of EtOH as a green solvent. Using the concept of diversity-oriented, reagent-based synthesis, the inexpensive feedstock tryptamine was efficiently converted to three different types of privileged scaffolds, which facilitates rapid compound library synthesis for accelerating drug discovery.

The effects of mental fatigue on fine motor performance in humans and its neural network connectivity mechanism: a dart throwing study.

While it is well known that mental fatigue impairs fine motor performance, the investigation into its neural basis remains scant. Here, we investigate the impact of mental fatigue on fine motor performance and explore its underlying neural network connectivity mechanisms. A total of 24 healthy male university students were recruited and randomly divided into two groups: a mental fatigue group (MF) and a control group (Control). Both groups completed 50 dart throws, while electroencephalography (EEG) data were collected. Following the Stroop intervention, participants in the MF group exhibited a decrease in Stroop task accuracy and throwing performance, and an increase in reaction time along with VAS and NASA scores. The EEG data during dart-throwing revealed that the network connectivity strength of theta oscillations in the frontal and left central regions was significantly higher in the MF group compared with the Control group, while the network connectivity strength of alpha oscillations in the left parietal region was significantly enhanced. The interregional connectivity within the theta and alpha rhythm bands, particularly in the frontal-central-parietal network connections, also showed a significant increase in the MF group. Mental fatigue impairs dart throwing performance and is accompanied by increased connectivity in alpha and theta.