Cell-Type-Specific Interleukin 1 Receptor 1 Signaling in the Brain Regulates Distinct Neuroimmune Activities.

Interleukin-1 (IL-1) signaling is important for multiple potentially pathogenic processes in the central nervous system (CNS), but the cell-type-specific roles of IL-1 signaling are unclear. We used a genetic knockin reporter system in mice to track and reciprocally delete or express IL-1 receptor 1 (IL-1R1) in specific cell types, including endothelial cells, ventricular cells, peripheral myeloid cells, microglia, astrocytes, and neurons. We found that endothelial IL-1R1 was necessary and sufficient for mediating sickness behavior and drove leukocyte recruitment to the CNS and impaired neurogenesis, whereas ventricular IL-1R1 was critical for monocyte recruitment to the CNS. Although microglia did not express IL-1R1, IL-1 stimulation of endothelial cells led to the induction of IL-1 in microglia. Together, these findings describe the structure and functions of the brain's IL-1R1-expressing system and lay a foundation for the dissection and identification of IL-1R1 signaling pathways in the pathogenesis of CNS diseases.

Regulation of the AGEs-induced inflammatory response in human periodontal ligament cells via the AMPK/NF-κB/ NLRP3 signaling pathway.

The heightened prevalence and accelerated progression of periodontitis in individuals with diabetes is primarily attributed to inflammatory responses in human periodontal ligament cells (HPDLCs). This study is aimed at delineating the regulatory mechanism of nucleotide-binding oligomerization domain-like receptors (NLRs) in mediating inflammation incited by muramyl dipeptide (MDP) in HPDLCs, under the influence of advanced glycation end products (AGEs), metabolic by-products associated with diabetes. We performed RNA-seq in HPDLCs induced by AGEs treatment and delineated activation markers for the receptor of AGEs (RAGE). It showed that advanced glycation end products modulate inflammatory responses in HPDLCs by activating NLRP1 and NLRP3 inflammasomes, which are further regulated through the NF-κB signaling pathway. Furthermore, AGEs synergize with NOD2, NLRP1, and NLRP3 inflammasomes to augment MDP-induced inflammation significantly.

The intergenerational sources of the U-turn in gender segregation.

In the early 1970s, the balkanization of the US labor market into "men's occupations" and "women's occupations" began to unravel, as women entered the professions and other male-typed sectors in record numbers. This decline in gender segregation continued on for several decades but then suddenly stalled at the turn of the century and shows no signs of resuming. Although the stall is itself undisputed, its sources remain unclear. Using nearly a half-century of data from the General Social Survey, we show that a resurgence in segregation-inducing forms of intergenerational transmission stands behind the recent stall. Far from serving as impartial conduits, fathers are now disproportionately conveying male-typed occupations to their sons, whereas mothers are effectively gender-neutral in their transmission outcomes. This segregative turn among fathers accounts for 47% of the stall in the gender segregation trend (between 2000 and 2018), while the earlier integrative turn among fathers accounts for 34% of the initial downturn in segregation (between 1972 and 1999). It follows that a U-turn in intergenerational processes lies behind the U-turn in gender segregation.

Integrative analysis of transcriptome and proteome in primary Sjögren syndrome.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is a intricate autoimmune disease mainly characterized of immune-mediated destruction of exocrine tissues, such as salivary and lacrimal glands, occurring dry mouth and eyes. Although some breakthroughs in understanding pSS have been uncovered, many questions remain about its pathogenesis, especially the internal relations between exocrine glands and secretions. METHOD: Transcriptomic and proteomic analyses were conducted on salivary tissues and saliva in experimental Sjögren syndrome (ESS). The ESS model was established by immunization with salivary gland protein. The expression of mRNAs and proteins in salivary tissues and saliva were determined by high-throughput sequencing transcriptomic analysis and LC-MS/MS-based proteome, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to recognize dysregulated genes and proteins. The association between RNA and protein abundance was investigated to provides a comprehensive understanding of RNA-protein correlations in the pathogenesis of pSS. RESULTS: As a result, we successfully established the ESS model. We recognized 3221 differentially expressed genes (DEGs) and 253 differentially expressed proteins (DEPs). The sample analysis showed that 61 proteins overlapped through the integrative analysis of transcriptomics and proteomics data. The enrichment pathway analysis of DEGs and DEPs in samples showed alterations in renin-angiotensin-system (RAS), lysosome, and apoptosis. Notably, we found that some genes, such as AGT, FN1, Klk1b26, Klk1, Klk1b5, Klk1b3 had a consistent trend in the regulation at the RNA and protein levels and might be potential diagnostic biomarkers of pSS. CONCLUSION: Herein, we found critical processes and potential biomakers that may contribute to pSS pathogenesis by analyzing dysregulated genes and pathways. Additionally, the integrative multi-omics datasets provided additional insight into understanding complicated disease mechanisms.

MLKL Protects Pulmonary Endothelial Cells in Acute Lung Injury.

The role of autophagy in pulmonary microvascular endothelial cells (PMVECs) is controversial in LPS-induced acute lung injury (ALI). Mixed lineage kinase domain-like pseudokinase (MLKL) has recently been reported to maintain cell survival by facilitating autophagic flux in response to starvation rather than its well-recognized role in necroptosis. Using a mouse PMVEC and LPS-induced ALI model, we showed that in PMVECs, MLKL was phosphorylated (p-MLKL) and autophagic flux was accelerated at the early stage of LPS stimulation (1-3 h), manifested by increases in concentrations of lipidated MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 ß; LC3-II), decreases in concentrations of SQSTM1/p62 (sequestosome 1), and fusion of the autophagosome and lysosome by pHluorin-mKate2-human LC3 assay, which were all reversed by either MLKL inhibitor or siRNA MLKL. In mice, the inhibition of MLKL increased vascular permeability and aggravated mouse ALI upon 3-hour LPS stimulation. The p-MLKL induced by short-term LPS formed multimers to facilitate the closure of the phagophore by HaloTag-LC3 autophagosome completion assay. The charged multivesicular body protein 2A (CHMP2A) is essential in the process of phagophore closure into the nascent autophagosome. In agreement with the p-MLKL change, CHMP2A concentrations markedly increased during 1-3-hour LPS stimulation. CHMP2A knockdown blocked autophagic flux upon LPS stimulation, whereas CHMP2A overexpression boosted autophagic flux and attenuated mouse ALI even in the presence of MLKL inhibitor. We propose that the activated MLKL induced by short-term LPS facilitates autophagic flux by accelerating the closure of the phagophore via CHMP2A, thus protecting PMVECs and alleviating LPS-induced ALI.

Genome-wide identification and expression analysis of the Eriobotrya japonica TIFY gene family reveals its functional diversity under abiotic stress conditions.

BACKGROUND: Plant-specific TIFY proteins are widely found in terrestrial plants and play important roles in plant adversity responses. Although the genome of loquat at the chromosome level has been published, studies on the TIFY family in loquat are lacking. Therefore, the EjTIFY gene family was bioinformatically analyzed by constructing a phylogenetic tree, chromosomal localization, gene structure, and adversity expression profiling in this study. RESULTS: Twenty-six EjTIFY genes were identified and categorized into four subfamilies (ZML, JAZ, PPD, and TIFY) based on their structural domains. Twenty-four EjTIFY genes were irregularly distributed on 11 of the 17 chromosomes, and the remaining two genes were distributed in fragments. We identified 15 covariate TIFY gene pairs in the loquat genome, 13 of which were involved in large-scale interchromosomal segmental duplication events, and two of which were involved in tandem duplication events. Many abiotic stress cis-elements were widely present in the promoter region. Analysis of the Ka/Ks ratio showed that the paralogous homologs of the EjTIFY family were mainly subjected to purifying selection. Analysis of the RNA-seq data revealed that a total of five differentially expressed genes (DEGs) were expressed in the shoots under gibberellin treatment, whereas only one gene was significantly differentially expressed in the leaves; under both low-temperature and high-temperature stresses, there were significantly differentially expressed genes, and the EjJAZ15 gene was significantly upregulated under both low- and high-temperature stress. RNA-seq and qRT-PCR expression analysis under salt stress conditions revealed that EjJAZ2, EjJAZ4, and EjJAZ9 responded to salt stress in loquat plants, which promoted resistance to salt stress through the JA pathway. The response model of the TIFY genes in the jasmonic acid pathway under salt stress in loquat was systematically summarized. CONCLUSIONS: These results provide a theoretical basis for exploring the characteristics and functions of additional EjTIFY genes in the future. This study also provides a theoretical basis for further research on breeding for salt stress resistance in loquat. RT-qPCR analysis revealed that the expression of one of the three EjTIFY genes increased and the expression of two decreased under salt stress conditions, suggesting that EjTIFY exhibited different expression patterns under salt stress conditions.

Genome-wide identification and expression pattern analysis of the kiwifruit GRAS transcription factor family in response to salt stress.

BACKGROUND: GRAS is a family of plant-specific transcription factors (TFs) that play a vital role in plant growth and development and response to adversity stress. However, systematic studies of the GRAS TF family in kiwifruit have not been reported. RESULTS: In this study, we used a bioinformatics approach to identify eighty-six AcGRAS TFs located on twenty-six chromosomes and phylogenetic analysis classified them into ten subfamilies. It was found that the gene structure is relatively conserved for these genes and that fragmental duplication is the prime force for the evolution of AcGRAS genes. However, the promoter region of the AcGRAS genes mainly contains cis-acting elements related to hormones and environmental stresses, similar to the results of GO and KEGG enrichment analysis, suggesting that hormone signaling pathways of the AcGRAS family play a vital role in regulating plant growth and development and adversity stress. Protein interaction network analysis showed that the AcGRAS51 protein is a relational protein linking DELLA, SCR, and SHR subfamily proteins. The results demonstrated that 81 genes were expressed in kiwifruit AcGRAS under salt stress, including 17 differentially expressed genes, 13 upregulated, and four downregulated. This indicates that the upregulated AcGRAS55, AcGRAS69, AcGRAS86 and other GRAS genes can reduce the salt damage caused by kiwifruit plants by positively regulating salt stress, thus improving the salt tolerance of the plants. CONCLUSIONS: These results provide a theoretical basis for future exploration of the characteristics and functions of more AcGRAS genes. This study provides a basis for further research on kiwifruit breeding for resistance to salt stress. RT-qPCR analysis showed that the expression of 3 AcGRAS genes was elevated under salt stress, indicating that AcGRAS exhibited a specific expression pattern under salt stress conditions.

The insular cortex is not insular in thyroid eye disease: neuroimaging revelations of central-peripheral system interaction.

BACKGROUND: Thyroid eye disease (TED) is highly correlated with dysregulated immunoendocrine status. The insular cortex was found to regulate peripheral inflammation and immunomodulation in mice. This study aimed to explore whether the insular cortex in patients with TED played a modulatory role including the aberrant brain functional alteration and its association with immunoendocrine status. METHODS: This study included 34 active patients (AP), 30 inactive patients (IP) with TED, and 45 healthy controls (HC) matched for age, sex, and educational level. Comprehensive clinical details (especially immunoendocrine markers) and resting-state functional magnetic resonance imaging data were collected from each participant. The amplitude of low-frequency fluctuation (ALFF) was used to probe the aberrant alterations of local neural activity. The seed-based functional connectivity (FC) analysis was used to explore the relationship between the insular cortex and each voxel throughout the whole brain. The correlation analysis was conducted to assess the association between insular neurobiomarkers and immunoendocrine parameters. RESULTS: When compared with the IP and HC groups, the AP group displayed significantly higher ALFF values in the right insular cortex (INS.R) and lower FC values between the INS.R and the bilateral cerebellum. None of the neurobiomarkers differed between the IP and HC groups. Besides, correlations between insular neurobiomarkers and immunoendocrine markers (free thyroxine, the proportion of T cells, and natural killer cells) were identified in both AP and IP groups. CONCLUSIONS: This study was novel in reporting that the dysregulation of the insular cortex activity in TED was associated with abnormal peripheral immunoendocrine status. The insular cortex might play a key role in central-peripheral system interaction in TED. Further research is crucial to enhance our understanding of the central-peripheral system interaction mechanisms involved in autoimmune diseases.

3D Fast Sodium Transport Network of MoS2 Endowed by Coupling of Sulfur Vacancies and Sn Doping for Outstanding Sodium Storage.

A sulfur vacancy-rich, Sn-doped as well as carbon-coated MoS2 composite (Vs-SMS@C) is rationally synthesized via a simple hydrothermal method combined with ball-milling reduction, which enhances the sodium storage performance. Benefiting from the 3D fast Na+ transport network composed of the defective carbon coating, Mo─S─C bonds, enlarged interlayer spacing, S-vacancies, and lattice distortion in the composite, the Na+ storage kinetics is significantly accelerated. As expected, Vs-SMS@C releases an ultrahigh reversible capacity of 1089 mAh g-1 at 0.1 A g-1, higher than the theoretical capacity. It delivers a satisfactory capacity of 463 mAh g-1 at a high current density of 10 A g-1, which is the state-of-the-art rate capability compared to other MoS2 based sodium ion battery anodes to the knowledge. Moreover, a super long-term cycle stability is achieved by Vs-SMS@C, which keeps 91.6% of the initial capacity after 3000 cycles under the current density of 5 A g-1 in the voltage of 0.3-3.0 V. The sodium storage mechanism of Vs-SMS@C is investigated by employing electrochemical methods and ex situ techniques. The synergistic effect between S-vacancies and doped-Sn is evidenced by DFT calculations. This work opens new ideas for seeking excellent metal sulfide anodes.

Association of dietary flavonoid intakes with prevalence of chronic respiratory diseases in adults.

BACKGROUND AND AIMS: Flavonoids are a class of secondary plant metabolites that have been shown to have multiple health benefits, including antioxidant and anti-inflammatory. This study was to explore the association between dietary flavonoid consumption and the prevalence of chronic respiratory diseases (CRDs) in adults. METHODS AND RESULTS: The six main types of flavonoids, including isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols, were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 and 2017-2018 by the two 24-h recall interviews. The prevalence of CRDs, including asthma, emphysema, and chronic bronchitis, was determined through a self-administered questionnaire. The analysis included 15,753 participants aged 18 years or older who had completed a diet history interview. After adjustment for potential confounders, the inverse link was found with total flavonoids, anthocyanidins, flavanones, and flavones, with an OR (95%CI) of 0.86 (0.75-0.98), 0.84 (0.72-0.97), 0.80(0.69-0.92), and 0.85(0.73-0.98) for the highest group compared to the lowest group. WQS regression revealed that the mixture of flavonoids was negatively linked with the prevalence of CRDs (OR = 0.88 [0.82-0.95], P < 0.01), and the largest effect was mainly from flavanones (weight = 0.41). In addition, we found that flavonoid intake was negatively linked with inflammatory markers, and systemic inflammation significantly mediated the associations of flavonoids with CRDs, with a mediation rate of 12.64% for CRP (P < 0.01). CONCLUSION: Higher flavonoid intake was related with a lower prevalence of CRDs in adults, and this relationship may be mediated through systemic inflammation.

Whole-orbit radiomics: machine learning-based multi- and fused- region radiomics signatures for intravenous glucocorticoid response prediction in thyroid eye disease.

BACKGROUND: Radiomics analysis of orbital magnetic resonance imaging (MRI) shows preliminary potential for intravenous glucocorticoid (IVGC) response prediction of thyroid eye disease (TED). The current region of interest segmentation contains only a single organ as extraocular muscles (EOMs). It would be of great value to consider all orbital soft tissues and construct a better prediction model. METHODS: In this retrospective study, we enrolled 127 patients with TED that received 4·5 g IVGC therapy and had complete follow-up examinations. Pre-treatment orbital T2-weighted imaging (T2WI) was acquired for all subjects. Using multi-organ segmentation (MOS) strategy, we contoured the EOMs, lacrimal gland (LG), orbital fat (OF), and optic nerve (ON), respectively. By fused-organ segmentation (FOS), we contoured the aforementioned structures as a cohesive unit. Whole-orbit radiomics (WOR) models consisting of a multi-regional radiomics (MRR) model and a fused-regional radiomics (FRR) model were further constructed using six machine learning (ML) algorithms. RESULTS: The support vector machine (SVM) classifier had the best performance on the MRR model (AUC = 0·961). The MRR model outperformed the single-regional radiomics (SRR) models (highest AUC = 0·766, XGBoost on EOMs, or LR on OF) and conventional semiquantitative imaging model (highest AUC = 0·760, NaiveBayes). The application of different ML algorithms for the comparison between the MRR model and the FRR model (highest AUC = 0·916, LR) led to different conclusions. CONCLUSIONS: The WOR models achieved a satisfactory result in IVGC response prediction of TED. It would be beneficial to include more orbital structures and implement ML algorithms while constructing radiomics models. The selection of separate or overall segmentation of orbital soft tissues has not yet attained its final optimal result.

Autophagy Is Essential for Neural Stem Cell Proliferation Promoted by Hypoxia.

Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.

Using machine learning to develop preoperative model for lymph node metastasis in patients with bladder urothelial carcinoma.

BACKGROUND: Lymph node metastasis (LNM) is associated with worse prognosis in bladder urothelial carcinoma (BUC) patients. This study aimed to develop and validate machine learning (ML) models to preoperatively predict LNM in BUC patients treated with radical cystectomy (RC). METHODS: We retrospectively collected demographic, pathological, imaging, and laboratory information of BUC patients who underwent RC and bilateral lymphadenectomy in our institution. Patients were randomly categorized into training set and testing set. Five ML algorithms were utilized to establish prediction models. The performance of each model was assessed by the area under the receiver operating characteristic curve (AUC) and accuracy. Finally, we calculated the corresponding variable coefficients based on the optimal model to reveal the contribution of each variable to LNM. RESULTS: A total of 524 and 131 BUC patients were finally enrolled into training set and testing set, respectively. We identified that the support vector machine (SVM) model had the best prediction ability with an AUC of 0.934 (95% confidence interval [CI]: 0.903-0.964) and accuracy of 0.916 in the training set, and an AUC of 0.855 (95%CI: 0.777-0.933) and accuracy of 0.809 in the testing set. The SVM model contained 14 predictors, and positive lymph node in imaging contributed the most to the prediction of LNM in BUC patients. CONCLUSIONS: We developed and validated the ML models to preoperatively predict LNM in BUC patients treated with RC, and identified that the SVM model with 14 variables had the best performance and high levels of clinical applicability.

White Matter Alterations of Visual Pathway in Thyroid Eye Disease: A Fixel-Based Analysis.

BACKGROUND: Thyroid eye disease (TED), particularly its sight-threatening complication, dysthyroid optic neuropathy (DON), profoundly impacts patients' visual health. The pathological changes in the white matter (WM) fibers within the intracranial visual pathway in TED have been infrequently studied. Understanding these changes holds crucial importance for exploring the pathogenesis and prognosis of TED. PURPOSE: To utilize fixel-based analysis (FBA) to clarify the type of microstructural damage occurring in the visual pathway in TED. STUDY TYPE: Prospective. SUBJECTS: 28 TED with DON patients (11 males and 17 females), 28 TED without DON (non-DON) patients (12 males and 16 females), and 28 healthy controls (HCs) (12 males and 16 females). FIELD STRENGTH/SEQUENCE: 3 T; multishell diffusion MRI using echo planar imaging. ASSESSMENT: Fiber density (FD) and fiber-bundle cross-section (FC) were calculated to characterize WM microstructural alteration in TED visual pathway. The correlations between FBA metrics and visual field index and mean deviation were examined. STATISTICAL TESTS: One-way analysis of variance, Kruskal-Wallis, t-tests, Mann-Whitney U, Chi-square, and Pearson correlation, were conducted with false discovery rate and family wise error corrections. Significance was set at P < 0.05. RESULTS: Both DON and non-DON groups showed significant FD loss in the right optic tract compared with HCs, with DON patients experiencing more severe FD loss. Only DON patients had FD loss in the right optic radiation (OR) compared with the non-DON patients and HCs, with no FC difference across groups. FD in DON patients' ORs significantly correlated with visual field index (r = 0.857) and mean deviation (r = 0.751). DATA CONCLUSION: Both DON and non-DON affect the WM microstructure of the visual pathway to varying extents. Visual field metrics can reflect the severity of FD damage to the OR in the visual pathway of DON patients. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

Near-infrared fluorophore IR-61 delays postovulatory aging of mouse oocytes through suppressing oxidative stress mediated by mitochondrial protection.

Postovulatory aging can trigger deterioration of oocyte quality and subsequent embryonic development, and thus reduce the success rates of assisted reproductive technology (ART). The molecular mechanisms underlying postovulatory aging, and preventative strategies, remain to be explored. The near-infrared fluorophore IR-61, a novel heptamethine cyanine dye, has the potential for mitochondrial targeting and cell protection. In this study, we found that IR-61 accumulated in oocyte mitochondria and reduced the postovulatory aging-induced decline in mitochondrial function, including mitochondrial distribution, membrane potential, mtDNA number, ATP levels, and mitochondrial ultrastructure. In addition, IR-61 rescued postovulatory aging-caused oocyte fragmentation, defects in spindle structure, and embryonic developmental potential. RNA sequencing analysis indicated that the postovulatory aging-induced oxidative stress pathway might be inhibited by IR-61. We then confirmed that IR-61 decreased the levels of reactive oxygen species and MitoSOX, and increased GSH content in aged oocytes. Collectively, the results indicate that IR-61 may prevent postovulatory aging by rescuing oocyte quality, promoting successful rate in ART procedure.

Revisiting the critical roles of reactive astrocytes in neurodegeneration.

Astrocytes, an integral component of the central nervous system (CNS), contribute to the maintenance of physiological homeostasis through their roles in synaptic function, K+ buffering, blood-brain barrier (BBB) maintenance, and neuronal metabolism. Reactive astrocytes refer to astrocytes undergoing morphological, molecular and functional remodelling in response to pathological stimuli. The activation and differentiation of astrocytes are implicated in the pathogenesis of multiple neurodegenerative diseases. However, there are still controversies regarding their subset identification, function and nomenclature in neurodegeneration. In this review, we revisit the multidimensional roles of reactive astrocytes in Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Furthermore, we propose a precise linkage between astrocyte subsets and their functions based on single-cell sequencing analyses.

Friend or foe: role of pathological tau in neuronal death.

Neuronal death is one of the most common pathological hallmarks of diverse neurological diseases, which manifest varying degrees of cognitive or motor dysfunction. Neuronal death can be classified into multiple forms with complicated and unique regulatory signaling pathways. Tau is a key microtubule-associated protein that is predominantly expressed in neurons to stabilize microtubules under physiological conditions. In contrast, pathological tau always detaches from microtubules and is implicated in a series of neurological disorders that are characterized by irreversible neuronal death, such as necrosis, apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy-dependent neuronal death and phagocytosis by microglia. However, recent studies have also revealed that pathological tau can facilitate neuron escape from acute apoptosis, delay necroptosis through its action on granulovacuolar degeneration bodies (GVBs), and facilitate iron export from neurons to block ferroptosis. In this review, we briefly describe the current understanding of how pathological tau exerts dual effects on neuronal death by acting as a double-edged sword in different neurological diseases. We propose that elucidating the mechanism by which pathological tau affects neuronal death is critical for exploring novel and precise therapeutic strategies for neurological disorders.

Inhibition of hyphal formation together with biochar addition promotes erythritol production by Yarrowia lipolytica.

This study aimed to investigate the effect of hyphal formation in Yarrowia lipolytica and biochar addition on erythritol production by submerged fermentation. Hyphal formation significantly inhibited erythritol production by Y. lipolytica. Transcriptome analysis suggested that the impaired erythritol synthesis of hyphal cells was associated with the differential expression of genes involved in amino acid metabolism, lipid metabolism, and cell wall stability. Deletion of RAS2 responsible for yeast-to-hypha transition and EYD1 included in erythritol degradation blocked hyphal formation and improved erythritol production. Biochar prepared from corncob, sugarcane bagasse (SB), corn straw, peanut shell, coconut shell, and walnut shell (WS) had a positive effect on erythritol production, of which WS pyrolyzed at 500°C (WSc) performed the best in flask fermentation. In a 3.7 L bioreactor, 220.20 ± 10 g/L erythritol with a productivity of 2.30 ± 0.10 g/L/h was obtained in the presence of 1.4% (w/v) WSc and 0.7% SBc (SB pyrolyzed at 500°C) within 96 h. These results suggest that inhibition of hyphal formation together with biochar addition is an efficient way to promote erythritol production.

Molecular cloning, expression, purification, and characterization of Bacillus subtilis hydrolyzed ginsenoside Rc of α-L-arabinofuranosidase in Escherichia coli.

The α-L-arabinofuranosidase enzyme plays a crucial role in the degradation of ginsenosides. In this study, we successfully cloned and expressed a novel α-L-arabinofuranosidase bsafs gene (1503 bp, 501 amino acids, 55 kDa, and pI = 5.4) belonging to glycosyl hydrolase (GH) family 51 from Bacillus subtilis genome in Escherichia coli BL21 cells. The recombinant protein Bsafs was purified using Ni2+ sepharose fastflow affinity chromatography and exhibited a specific activity of 2.91 U/mg. Bsafs effectively hydrolyzed the α-L-arabinofuranoside at C20 site of ginsenoside Rc to produce Rd as the product. The Km values for hydrolysis of pNP-α-L-arabinofuranoside (pNPαAraf) and ginsenoside Rc were determined as 0.74 and 4.59 mmol/L, respectively; while the Vmax values for these substrates were found to be 24 and 164 µmol/min/mg, respectively; furthermore, the Kcat values for these enzymes were calculated as 22.3 and 1.58 S-1 correspondingly.

Investigation on screening, identification, and fermentation characteristics of Yunnan olive in the fermented liquid utilizing five strains of Saccharomyces cerevisiae.

Refined indigenous Saccharomyces cerevisiae can enhance refinement, sophistication, and subtlety of fruit wines by showcasing exceptional regional characteristics. In order to identify exceptional indigenous S. cerevisiae strains from Yunnan olive, this study isolated 60 yeast strains from wild Yunnan olive fermentation mash. The five S. cerevisiae strains were subjected to morphological and molecular biological identification, followed by evaluation of their fermentation performance, ethanol production capacity, ester production capacity, H2S production capacity, killing capacity, and tolerance. Strains LJM-4, LJM-10, and LJM-26 exhibited robust tolerance to 6% ethanol volume fraction, pH 2.8, sucrose concentration of 400 g/L, SO2 concentration of 0.3 g/L, glucose concentration of 400 g/L at both 40 °C and 15 °C. Additionally, strain LJM-10 demonstrated a faster fermentation rate compared to the other strains. Among the tested S. cerevisiae strains evaluated in this study for olive wine fermentation process in Yunnan region; strain LJM-10 displayed superior abilities in terms of ester and ethanol production while exhibiting the lowest H2S production levels. These findings suggest that strain LJM-10 holds great potential as an excellent candidate for optimizing fruit wine S. cerevisiae fermentation processes in Yunnan olive fruit wine.