POLM variant G312R promotes ovarian tumorigenesis through genomic instability and COL11A1-NF-κB axis.

In ovarian cancer (OC), identifying key molecular players in disease escalation and chemoresistance remains critical. Our investigation elucidates the role of the DNA Polymerase Mu (POLM) , especially G312R mutation, in propelling oncogenesis through dual pathways. POLMG312R markedly augments the ribonucleotide insertion capability of POLM, precipitating genomic instability. Additionally, our research reveals that POLMG312R perturbs Collagen alpha-1 (XI) chain (COL11A1) expression-a gene plays a key role in oncogenesis-and modulates the NF-κB signaling pathway, alters the secretion of downstream inflammatory cytokines, and promotes tumor-macrophage interactions. We illustrate a bidirectional regulatory interaction between POLM, particularly its G312R variant, and COL11A1. This interaction regulates NF-κB signaling, culminating in heightened malignancy and resistance to chemotherapy in OC cells. These insights position the POLM as a potential molecular target for OC therapy, shedding light on the intricate pathways underpinning POLM variant disease progression.

Discovery and structural mechanism of DNA endonucleases guided by RAGATH-18-derived RNAs.

CRISPR-Cas systems and IS200/IS605 transposon-associated TnpBs have been utilized for the development of genome editing technologies. Using bioinformatics analysis and biochemical experiments, here we present a new family of RNA-guided DNA endonucleases. Our bioinformatics analysis initially identifies the stable co-occurrence of conserved RAGATH-18-derived RNAs (reRNAs) and their upstream IS607 TnpBs with an average length of 390 amino acids. IS607 TnpBs form programmable DNases through interaction with reRNAs. We discover the robust dsDNA interference activity of IS607 TnpB systems in bacteria and human cells. Further characterization of the Firmicutes bacteria IS607 TnpB system (ISFba1 TnpB) reveals that its dsDNA cleavage activity is remarkably sensitive to single mismatches between the guide and target sequences in human cells. Our findings demonstrate that a length of 20 nt in the guide sequence of reRNA achieves the highest DNA cleavage activity for ISFba1 TnpB. A cryo-EM structure of the ISFba1 TnpB effector protein bound by its cognate RAGATH-18 motif-containing reRNA and a dsDNA target reveals the mechanisms underlying reRNA recognition by ISFba1 TnpB, reRNA-guided dsDNA targeting, and the sensitivity of the ISFba1 TnpB system to base mismatches between the guide and target DNA. Collectively, this study identifies the IS607 TnpB family of compact and specific RNA-guided DNases with great potential for application in gene editing.

Therapeutic potential of Lingjiao Gouteng decoction in acute alcohol intoxication and alcohol-induced brain injury involving the RhoA/ROCK2/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Alcohol misuse persists as a prevalent societal concern and precipitates diverse deleterious consequences, entailing significant associated health hazards including acute alcohol intoxication (AAI). Binge drinking, a commonplace pattern of alcohol consumption, may incite neurodegeneration and neuronal dysfunction. Clinicians tasked with managing AAI confront a dearth of pharmaceutical intervention alternatives. In contrast, natural products have garnered interest due to their compatibility with the human body and fewer side effects. Lingjiao Gouteng decoction (LGD), a classical traditional Chinese medicine decoction, represents a frequently employed prescription in cases of encephalopathy, although its efficacy in addressing acute alcoholism and alcohol-induced brain injury remains inadequately investigated. AIM OF THE STUDY: To investigate the conceivable therapeutic benefits of LGD in AAI and alcohol-induced brain injury, while delving into the underlying fundamental mechanisms involved. MATERIALS AND METHODS: We established an AAI mouse model through alcohol gavage, and LGD was administered to the mice twice at the 2 h preceding and 30 min subsequent to alcohol exposure. The study encompassed the utilization of the loss of righting reflex assay, histopathological analysis, enzyme-linked immunosorbent assays, and cerebral tissue biochemical assays to investigate the impact of LGD on AAI and alcohol-induced brain injury. These assessments included a comprehensive evaluation of various biomarkers associated with the inflammatory response and oxidative stress. Finally, RT-qPCR, Western blot, and immunofluorescence staining were carried out to explore the underlying mechanisms through which LGD exerts its therapeutic influence, potentially through the regulation of the RhoA/ROCK2/NF-κB signaling pathway. RESULTS: Our investigation underscores the therapeutic efficacy of LGD in ameliorating AAI, as evidenced by discernible alterations in the loss of righting reflex assay, pathological analysis, and assessment of inflammatory and oxidative stress biomarkers. Furthermore, the results of RT-qPCR, Western blot, and immunofluorescence staining manifest a noteworthy regulatory effect of LGD on the RhoA/ROCK2/NF-κB signaling pathway. CONCLUSIONS: The present study confirmed the therapeutic potential of LGD in AAI and alcohol-induced brain injury, and the protective effects of LGD against alcohol-induced brain injury may be intricately linked to the RhoA/ROCK2/NF-κB signaling pathway.

An electrospun three-layer nanofibrous membrane-based in situ gel separator for efficient lithium-organic batteries.

An in situ gel separator based on an electrospun three-layer nanofibrous membrane (PSE11-Gel) is developed for high-performance lithium-organic batteries (LOBs). The highly efficient shuttle effect inhibition of organic cathode molecules or lithiated intermediates has been demonstrated for PSE11-Gel to realize high-capacity stable LOBs.

15-cis-Phytoene Desaturase and 15-cis-Phytoene Synthase Can Catalyze the Synthesis of ß-Carotene and Influence the Color of Apricot Pulp.

Fruit color affects its commercial value. ß-carotene is the pigment that provides color for many fruits and vegetables. However, the molecular mechanism of ß-carotene metabolism during apricot ripening is largely unknown. Here, we investigated whether ß-carotene content affects apricot fruit color. First, the differences in ß-carotene content between orange apricot 'JTY' and white apricot 'X15' during nine developmental stages (S1-S9) were compared. ß-carotene contents highly significantly differed between 'JTY' and 'X15' from S5 (color transition stage) onwards. Whole-transcriptome analysis showed that the ß-carotene synthesis genes 15-cis-phytoene desaturase (PaPDS) and 15-cis-phytoene synthase (PaPSY) significantly differed between the two cultivars during the color transition stage. There was a 5 bp deletion in exon 11 of PaPDS in 'X15', which led to early termination of amino acid translation. Gene overexpression and virus-induced silencing analysis showed that truncated PaPDS disrupted the ß-carotene biosynthesis pathway in apricot pulp, resulting in decreased ß-carotene content and a white phenotype. Furthermore, virus-induced silencing analysis showed that PaPSY was also a key gene in ß-carotene biosynthesis. These findings provide new insights into the molecular regulation of apricot carotenoids and provide a theoretical reference for breeding new cultivars of apricot.

Discourse Task Type-Specific Linguistic Characteristics in Anomic Aphasia and Healthy Controls: Evidence From Mandarin-Chinese AphasiaBank.

PURPOSE: This study was designed to examine the hypothesis that discourse task types influence language performance in Mandarin Chinese-speaking people and to reveal the discourse task-specific linguistic properties of persons with anomic aphasia compared to neurotypical controls. METHOD: Language samples from persons with aphasia (n = 31) and age- and education-matched controls (n = 31) across four discourse tasks (sequential-picture description, single-picture description, story narrative, and procedural discourse) were collected from Mandarin AphasiaBank. Task-specific distributions of parts of speech were analyzed using mosaic plots. The main effects of tasks in each group and the between-group differences within each task for several typical linguistic variables were evaluated, including the mean length of utterance, tokens, moving-average type-token ratio, words per minute, propositional density, noun-verb ratio, noun percentage, and verb percentage. RESULTS: The results revealed an impact of discourse tasks on most language variables in both groups. In the healthy controls, story narratives yielded the highest total words and lowest verb percentage. In the aphasia group, procedural discourse elicited the fewest total words and densest expressions, whereas their single-picture descriptions had the highest noun-verb ratio. For all tasks, the aphasia group performed worse than the control group in the mean length of utterance, tokens, moving-average type-token ratio, and words per minute. For noun-verb ratio, noun percentage, and verb percentage, only one task (i.e., single-picture description) showed significant between-group differences. CONCLUSION: The selection of discourse tasks should be addressed in assessments and interventions for Mandarin Chinese-speaking individuals with aphasia to obtain more accurate and feasible outcomes.

Interactions between tDCS treatment and COMT Val158Met in poststroke cognitive impairment.

OBJECTIVE: This study aimed to explore the effect of catechol-O-methyltransferase (COMT) Val158Met and brain-derived neurotrophic factor (BDNF) Val66Met to post-stroke cognitive impairment (PSCI) and the interaction with transcranial direct current stimulation (tDCS). METHODS: Seventy-six patients with PSCI were randomly assigned to Group (1) (n = 38) to receive anodal tDCS of left dorsolateral prefrontal cortex or Group (2) (n = 38) to receive sham stimulation. The intensity of the tDCS was 2 mA, and the stimulations were applied over the left DLPFC for 10 sessions. The Montreal Cognitive Assessment (MoCA) and backward digit span test (BDST) were assessed before, immediately after, and one month after stimulation. RESULTS: After stimulation, patients in the tDCS group showed better improvement in both MoCA and BDST than those in the sham group. The results of GLMs also supported the main effects of tDCS on general cognitive function and working memory. Then we found that COMT genotype may have a main effect on the improvement of MoCA and BDST, and there may be an interaction between COMT genotype and tDCS in enhancing BDST. In contrast, BDNF genotype showed no significant main or interaction effects on any scales. CONCLUSIONS: These findings demonstrate that tDCS can improve cognition after stroke. Gene polymorphisms of COMT can affect the efficacy of tDCS on PSCI, but BDNF may not. SIGNIFICANCE: This study found that COMT Val158Met has an interaction on the efficacy of prefrontal tDCS in cognitive function, which provides reference for future tDCS research and clinical application.

Protection effects of mice liver and lung injury induced by coronavirus infection of Qingfei Paidu decoction involve inhibition of the NLRP3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Coronavirus Disease 2019 (COVID-19) is a grave and pervasive global infectious malady brought about by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), posing a significant menace to human well-being. Qingfei Paidu decoction (QFPD) represents a pioneering formulation derived from four classical Chinese medicine prescriptions. Substantiated evidence attests to its efficacy in alleviating clinical manifestations, mitigating the incidence of severe and critical conditions, and reducing mortality rates among COVID-19 patients. AIM OF THE STUDY: This study aims to investigate the protection effects of QFPD in mice afflicted with a coronavirus infection, with a particular focus on determining whether its mechanism involves the NLRP3 signaling pathway. MATERIALS AND METHODS: The coronavirus mice model was established through intranasal infection of Kunming mice with Hepatic Mouse Virus A59 (MHV-A59). In the dose-effect experiment, normal saline, ribavirin (80 mg/kg), or QFPD (5, 10, 20 g/kg) were administered to the mice 2 h following MHV-A59 infection. In the time-effect experiment, normal saline or QFPD (20 g/kg) was administered to mice 2 h post MHV-A59 infection. Following the assessment of mouse body weights, food consumption, and water intake, intragastric administration was conducted once daily at consistent intervals over a span of 5 days. The impact of QFPD on pathological alterations in the livers and lungs of MHV-A59-infected mice was evaluated through H&E staining. The viral loads of MHV-A59 in both the liver and lung were determined using qPCR. The expression levels of genes and proteins related to the NLRP3 pathway in the liver and lung were assessed through qPCR, Western Blot analysis, and immunofluorescence. RESULTS: The administration of QFPD was shown to ameliorate the reduced weight gain, decline in food consumption, and diminished water intake, all of which were repercussions of MHV-A59 infection in mice. QFPD treatment exhibited notable efficacy in safeguarding tissue integrity. The extent of hepatic and pulmonary injury, when coupled with QFPD treatment, demonstrated not only a reduction with higher treatment dosages but also a decline with prolonged treatment duration. In the dose-effect experiment, there was a notable, dose-dependent reduction in the viral loads, as well as the expression levels of IL-1ß, NLRP3, ASC, Caspase 1, Caspase-1 p20, GSDMD, GSDMD-N, and NF-κB within the liver of the QFPD-treated groups. Additionally, in the time-effects experiments, the viral loads and the expression levels of genes and proteins linked to the NLRP3 pathway were consistently lower in the QFPD-treated groups compared with the model control groups, particularly during the periods when their expressions reached their zenith in the model group. Notably, IL-18 showed only a modest elevation relative to the blank control group following QFPD treatment. CONCLUSIONS: To sum up, our current study demonstrated that QFPD treatment has the capacity to alleviate infection-related symptoms, mitigate tissue damage in infected organs, and suppress viral replication in coronavirus-infected mice. The protective attributes of QFPD in coronavirus-infected mice are plausibly associated with its modulation of the NLRP3 signaling pathway. We further infer that QFPD holds substantial promise in the context of coronavirus infection therapy.

High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke.

JOURNAL/nrgr/04.03/01300535-202408000-00031/figure1/v/2023-12-16T180322Z/r/image-tiff Proliferation of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage. Transcranial magnetic stimulation (TMS) has recently emerged as a tool for inducing endogenous neural stem cell regeneration, but its underlying mechanisms remain unclear. In this study, we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells. Additionally, repetitive TMS reduced the volume of cerebral infarction in a rat model of ischemic stroke caused by middle cerebral artery occlusion, improved rat cognitive function, and promoted the proliferation of neural stem cells in the ischemic penumbra. RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia. Furthermore, PCR analysis revealed that repetitive TMS promoted AKT phosphorylation, leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4. This effect was also associated with activation of the glycogen synthase kinase 3ß/ß-catenin signaling pathway, which ultimately promotes the proliferation of neural stem cells. Subsequently, we validated the effect of repetitive TMS on AKT phosphorylation. We found that repetitive TMS promoted Ca2+ influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway, thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3ß/ß-catenin pathway. These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+ influx-dependent phosphorylated AKT/glycogen synthase kinase 3ß/ß-catenin signaling pathway. This study has produced pioneering results on the intrinsic mechanism of repetitive TMS to promote neural function recovery after ischemic stroke. These results provide a strong scientific foundation for the clinical application of repetitive TMS. Moreover, repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications, but also provide an effective platform for the expansion of neural stem cells.

4-Electron redox enabled by a perylene diimide containing side-chain amines for efficient organic cathode development.

A perylene diimide containing side-chain amines (PDIN) was studied as an organic cathode for application in lithium batteries, showing a high capacity of 174 mA h g-1. The chemical structures, experimental results, and calculation analyses verify that PDIN performed a 4-electron redox reaction jointly involving its CO and side-chain amine groups. This study promotes the development of organic cathodes with multi-electron redox reactions.

Kiwi-derived extracellular vesicles for oral delivery of sorafenib.

Sorafenib is an oral treatment for hepatocellular carcinoma (HCC). However, poor water solubility, harsh gastrointestinal environment and off-target effects contribute to the low bioavailability of oral sorafenib. Plant-derived extracellular vesicles (PDEVs) are biological nanovesicles with various bioactive functions that offer significant advantages in the field of oral drug delivery: protection from degradation by gastrointestinal fluids; crossing the intestinal epithelial barrier; specific targeting; safety; and abundant yield. However, there are fewer studies applying PDEVs for anti-tumor drug delivery to extra-digestive tissues. In this study, kiwifruit-derived extracellular vesicles (KEVs) were isolated and purified from kiwifruit, and their natural hepatic accumulation properties were exploited for targeted delivery of sorafenib (KEVs-SFB). Evidence showed that encapsulation of KEVs reduced the leakage of sorafenib in the gastrointestinal environment and enhanced the ability to cross the intestinal epithelium; KEVs-SFB was able to achieve liver accumulation and was predominantly taken up by HepG2 cells; KEVs-SFB was effective in inhibiting 4T1 cell proliferation; in the orthotopic liver cancer model, oral administration of KEVs-SFB inhibited tumor growth and improved the side effects of SFB. This PDEVs-based oral drug delivery platform is important for improving oral bioavailability and reducing drug side effects.

Modeling and evaluating site and provenance variation in height-diameter relationships for Betula alnoides Buch.-Ham. ex D. Don in southern China.

Tree height (H) and stem diameter at breast height (DBH) (H-D) relationship is correlated with timber yield and quality as well as stability of forest and is crucial in forest management and genetic breeding. It is influenced by not only environmental factors such as site quality and climate factors but also genetic control that is mostly neglected. A dataset of H and DBH of 25 provenances of Betula alnoides Buch.-Ham. ex D. Don at four sites was used to model the H-D relationship. The dummy variable nonliner mixed-effect equations were applied to evaluate the effects of sites and provenances on variations of the H-D relationship and to select superior provenances of B. alnoides. Weibull equation was selected as the base model for the H-D relationship. The sites affected asymptotes of the H-D curves, and the provenance effect on asymptotes of the H-D curves varied across sites. Taking above-average DBH and lower asymptote of the H-D curves as indicators, five excellent provenances were screened out at each site with a rate of 20%. Their selection gains of individual volume ranged from 1.99% to 29.81%, and their asymptote parameter (kj) and H-D ratio were 7.17%-486.05% and 3.07-4.72% lower than the relevant total means at four sites, respectively. Genetic selection based on the H-D relationship could promote selection efficiency of excellent germplasms and was beneficial for the large-sized timber production of B. alnoides.

Major depressive disorder and chronic gastritis: A bidirectional two-sample Mendelian randomization study.

OBJECTIVE: Observational studies have posited a strong correlation between chronic gastritis (CG) and major depressive disorder (MDD), but the nature of this association remains uncertain, owing to the challenges of establishing the temporal sequence. The present study sought to elucidate the elusive relationship between CG and MDD by employing a bidirectional two-sample Mendelian randomization (MR) approach. METHODS: We extracted instrumental variants for MDD and CG from published genome-wide association study data, focusing on individuals of primarily European descent. A comprehensive suite of MR estimations and sensitivity analyses was performed to ensure the robustness of the findings. Each outcome database was analyzed separately in both directions. RESULTS: For MDD and CG, 221 and 5 genetic variants, respectively, were selectively extracted as instrumental variants. The results suggest that MDD is causally associated with an elevated risk of CG (IVW: 23andMe, OR = 1.33; 95% CI = 1.15-1.54; p = 1.06 × 10-4); conversely, no strong evidence was found to corroborate that CG exerts a causal effect on the incidence of MDD (IVW: OR = 1.01; 95% CI = 0.95-1.07; p = 0.68). CONCLUSIONS: These findings provide novel insights into the causal relationship between CG and MDD, which may have implications for clinical decision-making in patients with MDD and CG.

Comparative Anatomical and Transcriptomics Reveal the Larger Cell Size as a Major Contributor to Larger Fruit Size in Apricot.

Fruit size is one of the essential quality traits and influences the economic value of apricots. To explore the underlying mechanisms of the formation of differences in fruit size in apricots, we performed a comparative analysis of anatomical and transcriptomics dynamics during fruit growth and development in two apricot cultivars with contrasting fruit sizes (large-fruit Prunus armeniaca 'Sungold' and small-fruit P. sibirica 'F43'). Our analysis identified that the difference in fruit size was mainly caused by the difference in cell size between the two apricot cultivars. Compared with 'F43', the transcriptional programs exhibited significant differences in 'Sungold', mainly in the cell expansion period. After analysis, key differentially expressed genes (DEGs) most likely to influence cell size were screened out, including genes involved in auxin signal transduction and cell wall loosening mechanisms. Furthermore, weighted gene co-expression network analysis (WGCNA) revealed that PRE6/bHLH was identified as a hub gene, which interacted with 1 TIR1, 3 AUX/IAAs, 4 SAURs, 3 EXPs, and 1 CEL. Hence, a total of 13 key candidate genes were identified as positive regulators of fruit size in apricots. The results provide new insights into the molecular basis of fruit size control and lay a foundation for future breeding and cultivation of larger fruits in apricot.

Post-translational Modifications by Acyl Groups Regulate FEN1's Activities and Play Essential Roles in Cell Proliferation and DNA Repair.

BACKGROUND: Flap endonuclease 1 (FEN1), well known for its structural-specific nuclease, possessing 5'-flap endonuclease and 5'-3' exonuclease activities, is mainly involved in DNA replication and repair. Protein lysine acetylation is an important posttranslational modification that could regulate numerous proteins' activity, subcellular localization, protein-protein interaction etc., and influences many biological processes. Our previous studies on integrated succinylome profiles found that succinylation and acetylation levels of FEN1 would change under different conditions. Succinylation at FEN1 Lys200 site results in the accumulation of damaged DNA and increased susceptibility to fork-stalling agents. The interplay with other forms of modification could affects its protein interaction affinity and thus contribute to genome stability. OBJECTIVE: This article studied the biological role of FEN1 by acyl modification in HeLa cells. METHOD: In order to explore the function of FEN1 acylation in cells, we mimicked the presence or absence of acetylation or succinylation by mutating key amino acids to glutamic acid and glutamine. We carried out a series of experiments including cell cycle, MTS, enzyme kinetics measurements, immunofluorescence and so on. RESULTS: The absence of acylation of FEN1 leads to the blocked cell cycle process and the reduced efficiency of FEN1 on its DNA substrates, affecting the interaction of FEN1 with both repair and replication related proteins and thus its role in the repair of DNA damage. CONCLUSION: We have verified acyl groups could modify Lys125, Lys252 and Lys254 of FEN1. Acylation level of these three is important for enzyme activity, cell proliferation and DNA damage response, thus contributing to genome stability.

CRISPRimmunity: an interactive web server for CRISPR-associated Important Molecular events and Modulators Used in geNome edIting Tool identifYing.

The CRISPR-Cas system is a highly adaptive and RNA-guided immune system found in bacteria and archaea, which has applications as a genome editing tool and is a valuable system for studying the co-evolutionary dynamics of bacteriophage interactions. Here introduces CRISPRimmunity, a new web server designed for Acr prediction, identification of novel class 2 CRISPR-Cas loci, and dissection of key CRISPR-associated molecular events. CRISPRimmunity is built on a suite of CRISPR-oriented databases providing a comprehensive co-evolutionary perspective of the CRISPR-Cas and anti-CRISPR systems. The platform achieved a high prediction accuracy of 0.997 for Acr prediction when tested on a dataset of 99 experimentally validated Acrs and 676 non-Acrs, outperforming other existing prediction tools. Some of the newly identified class 2 CRISPR-Cas loci using CRISPRimmunity have been experimentally validated for cleavage activity in vitro. CRISPRimmunity offers the catalogues of pre-identified CRISPR systems to browse and query, the collected resources or databases to download, a well-designed graphical interface, a detailed tutorial, multi-faceted information, and exportable results in machine-readable formats, making it easy to use and facilitating future experimental design and further data mining. The platform is available at http://www.microbiome-bigdata.com/CRISPRimmunity. Moreover, the source code for batch analysis are published on Github (https://github.com/HIT-ImmunologyLab/CRISPRimmunity).

Screening diagnosis of executive dysfunction after ischemic stroke and the effects of transcranial magnetic stimulation: A prospective functional near-infrared spectroscopy study.

BACKGROUND: Post-ischemic stroke executive impairment (PISEI) is a serious obstacle for patients to returning to their society and is currently difficult to screen early and clinically ineffective. AIM: The aim of the study was to clarify whether functional near-infrared spectroscopy (fNIRS) can be used as a rapid screening tool for PISEI and to explore the efficacy of transcranial magnetic stimulation (TMS) in PISEI patients and the changes in brain function. METHODS: A single-blind, randomized controlled study design was used to detect hemodynamic differences by fNIIRS in 16 PISEI patients and 16 healthy subjects during the resting state and Stroop task, respectively. After 3 days, all subjects received a single TMS intervention and underwent simultaneous fNIRS testing for the Stroop task before and 3 days after the TMS intervention. RESULTS: PISEI patients had significantly higher HbO2 content in the left dorsolateral prefrontal cortex (DLPFC), the right pre-motor cortex (PMC) and the right primary sensorimotor cortex (SM1) during the Stroop task compared to the resting state (F = 141.966, p < 0.001), but significantly lower than healthy subjects (T = -3.413, p = 0.002). After TMS intervention, PISEI patients' time and error number scores on the Stroop test were significantly enhanced, and the functional activity of the above-mentioned brain regions was significantly more active than at baseline, while the strength of their functional connections with each other was markedly increased. CONCLUSIONS: fNIRS helped screen and diagnose PISEI. A single TMS session benefited PISEI patients with effects lasting 3 days, which may be attributed to activation of the left DLPFC, right PMC and right SM1 brain regions.

Effects of temperature fluctuations on non-volatile taste compounds in tilapia fillets (Oreochromis niloticus).

In this study, the effect of temperature fluctuations on the taste quality of tilapia fillets during frozen storage was investigated. Major temperature-responsive factors included free amino acids (FAAs) and flavor nucleotides in fish fillets, which were identified using multidimensional infrared spectroscopy (MM-IR). The main FAA in tilapia fillets is a sweet amino acid (glycine). Compared with the control group, the umami FAAs and sweetness FAAs were significantly increased, and the total FAAs content increased to 1.30 times after the ninth fluctuation, reaching the highest level (611.16 ± 73.60 mg/100 g). Considering the equivalent umami intensity values, adenosine monophosphate and inosine monophosphate were retained during the first and second temperature fluctuations. In addition, the content of Na+, K+, and Ca2+ decreased (P < 0.05). Therefore, MM-IR is an effective method to identify taste components. With regard to taste quality, temperature fluctuations in the twofold range have an umami-enhancing effect.

Identification of chondrocyte subpopulations in osteoarthritis using single-cell sequencing analysis.

Osteoarthritis (OA) is the most common joint disease. Previous studies were focused on general functions of chondrocyte population in OA without elucidating the existence of chondrocyte subpopulations. To investigate the heterogeneity of chondrocyte, here we conducted detailed analysis on the single-cell sequencing data of cartilage cells from OA patients. After quality control, unsupervised K-mean clustering identified seven different subpopulations of chondrocytes in OA. Those subpopulations of chondrocytes were nominated based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis: stress-metabolizing chondrocytes (cluster 1), rhythmic chondrocytes (cluster 2), apoptotic chondrocytes (cluster 3), matrix-synthesis-related chondrocytes (cluster 4), developmental chondrocytes (cluster 5), protein-synthesis-related chondrocytes (cluster 6 and 8), and osteogenesis chondrocytes (cluster 7). We further noticed that the stress-metabolizing chondrocytes (cluster 1) were dominant in early stages of cartilage damage with increased metabolic levels inhibiting cartilage tissue degeneration, while the matrix-synthesis-related chondrocytes (cluster 4) were mainly existed in the late stages of cartilage damage which reorganized collagen fibers with type III collagen disrupting the extracellular matrix and further cartilage damages. Besides, we identified genes NFKBIA and TUBB2B as potential markers for the stress-metabolizing chondrocytes and the matrix synthesis related chondrocytes, respectively. Our study identifies different chondrocyte subpopulations in OA, and highlights the potential different functions of chondrocyte subpopulations in the early versus late stages of cartilage damage.

Correlation of Taste Components with Consumer Preferences and Emotions in Chinese Mitten Crabs (Eriocheir sinensis): The Use of Artificial Neural Network Model.

This study took a consumer sensory perspective to investigate the relationship between taste components and consumers' preferences and emotions. Abdomen meat (M), hepatopancreas (H), and gonads (G) of Chinese mitten crabs, one from Chongming, the Jianghai 21 variety (C-JH), and two from Taixing, the Jianghai 21 (T-JH) and Yangtze II varieties (T-CJ), were used to evaluate flavor quality. The results indicated that in the abdomen meat, differences in taste components were mainly shown in the content of sweet amino acids, bitter amino acids, K+, and Ca2+; M-C-JH had the highest EUC value of 9.01 g/100 g. In the hepatopancreas, bitter amino acids were all significantly higher in H-C-JH (569.52 mg/100 g) than in the other groups (p < 0.05). In the gonads, the umami amino acid content was significantly higher in G-T-JH than in the other groups (p < 0.05) (EUC values: G-T-JH > G-C-JH > G-T-CJ). Consumer sensory responses showed that different edible parts of the crab evoked different emotions, with crab meat being closely associated with positive emotions and more complex emotional expressions for the hepatopancreas and gonads. In comparison, consumers were more emotionally positive when consuming Yangtze II crab. H-C-JH evoked negative emotions due to high bitter taste intensities. Multifactor analysis (MFA) showed arginine, alanine, glycine, proline, K+, and Ca2+ were found to have a positive correlation with consumer preference; an artificial neural network model with three neurons was built with good correlation (R2 = 0.98). This study can provide a theoretical foundation for the breeding of Chinese mitten crabs, new insights into the river crab industry, and the consumer market.