Suppression of MyD88 disturbs gut microbiota and activates the NLR pathway and hence fails to ameliorate DSS-induced colitis.

Background: Myeloid differentiation factor 88 (MyD88) is the core adaptor for Toll-like receptors defending against microbial invasion and initiating a downstream immune response during microbiota-host interaction. However, the role of MyD88 in the pathogenesis of inflammatory bowel disease is controversial. This study aims to investigate the impact of MyD88 on intestinal inflammation and the underlying mechanism. Methods: MyD88 knockout (MyD88-/-) mice and the MyD88 inhibitor (TJ-M2010-5) were used to investigate the impact of MyD88 on acute dextran sodium sulfate (DSS)-induced colitis. Disease activity index, colon length, histological score, and inflammatory cytokines were examined to evaluate the severity of colitis. RNA transcriptome analysis and 16S rDNA sequencing were used to detect the potential mechanism. Results: In an acute DSS-colitis model, the severity of colitis was not alleviated in MyD88-/- mice and TJ-M2010-5-treated mice, despite significantly lower levels of NF-κB activation being exhibited compared to control mice. Meanwhile, 16S rDNA sequencing and RNA transcriptome analysis revealed a higher abundance of intestinal Proteobacteria and an up-regulation of the nucleotide oligomerization domain-like receptors (NLRs) signaling pathway in colitis mice following MyD88 suppression. Further blockade of the NLRs signaling pathway or elimination of gut microbiota with broad-spectrum antibiotics in DSS-induced colitis mice treated with TJ-M2010-5 ameliorated the disease severity, which was not improved solely by MyD88 inhibition. After treatment with broad-spectrum antibiotics, downregulation of the NLR signaling pathway was observed. Conclusion: Our study suggests that the suppression of MyD88 might be associated with unfavorable changes in the composition of gut microbiota, leading to NLR-mediated immune activation and intestinal inflammation.

[A Survey of the Current Status and the Needs of Medical Imaging Technicians in China]. / ä¸­å›½åŒ»å­¦å½±åƒæŠ€æœ¯ä»Žä¸šäººå‘˜çŽ°çŠ¶å’Œéœ€æ±‚è°ƒæŸ¥ç ”ç©¶.

Objective: To investigate the status quo and the needs of medical imaging technicians (MITs) in the radiology department of secondary and tertiary hospitals in China, so as to provide references and support for the development of the medical imaging technology industry and the relevant policymaking by health administrative departments. Methods: The questionnaire was developed by the Chinese Society of Imaging Technology. The radiology department of each hospital involved in the survey recommended one MIT to fill out the online questionnaire. The contents included: (a) the basic information of the hospital; (b) a general overview of the MITs in the hospital; (c) daily work; (d) career development and promotion; (e) research status and needs, etc. Differences in the number of MIT staff were compared using the Mann-Whitney U test and the chi-square test was used to compare the differences in the selected numbers of MITs in need between regions or between different levels of hospitals. Results: In this investigation, valid questionnaires were finally obtained from a total of 5403 hospitals in 31 provinces in China. The total number of MITs of the hospitals covered in the sample was 67481. The number of MITs in each hospital was 9 (5, 16). The male-to-female ratio was 1.41:1. MITs who were 20 to 40 years old accounted for 78%. The proportions of MITs who had completed doctorate, master's, undergraduate, junior college, and technical secondary school or lower level education were 0.6%, 3.3%, 60.7%, 30.8%, and 4.55%, respectively. The proportions of chief MITs, deputy chief MITs, supervisor MITs, primary MITs, assistant technician and those below were 1.0%, 4.21%, 22.1%, 51.8%, and 20.9%, respectively. The overall professional satisfaction of MITs was good. "Lack of opportunities for learning and communication" was quoted as the main problem MITs encountered in regard to improving their job-related competency. 59.2% of the respondents had not published any academic papers in the past five years, and only 7.0% of the respondents had published in journals included in the Science Citation Index (SCI) in the past five years. Conclusion: MITs in China are on average relatively young and the number of MITs has greatly increased. At this stage, more attention should be given to the cultivation of talents and continuing education of MITs and the construction of the discipline should be further strengthened, so as to provide strong support for the development of the medical imaging technology industry in China.

Identification of CXCL13 as a Promising Biomarker for Immune Checkpoint Blockade Therapy and PARP Inhibitor Therapy in Ovarian Cancer.

Ovarian cancer has poor response rates to immune checkpoint blockade (ICB) therapy, despite the use of genomic sequencing to identify molecular targets. Homologous recombination deficiency (HRD) is a conventional indicator of genomic instability (GI) and has been used as a marker for targeted therapies. Indicators reflecting HRD status have shown potential in predicting the efficacy of ICB treatment. Public databases, including TCGA, ICGC, and GEO, were used to obtain data. HRD scores, neoantigen load, and TMB were obtained from the TCGA cohort. Candidate biomarkers were validated in multiple databases, such as the Imvigor210 immunotherapy cohort and the open-source single-cell sequencing database. Immunohistochemistry was performed to further validate the results in independent cohorts. CXCL10, CXCL11, and CXCL13 were found to be significantly upregulated in HRD tumors and exhibited prognostic value. A comprehensive analysis of the tumor immune microenvironment (TIME) revealed that CXCL13 expression positively correlated with neoantigen load and immune cell infiltration. In addition, single-cell sequencing data and clinical trial results supported the utility of CXCL13 as a biomarker for ICB therapy. Not only does CXCL13 serve as a biomarker reflecting HRD status, but it also introduces a potentially novel perspective on prognostic biomarkers for ICB in ovarian cancer.

WUSCHEL-RELATED HOMEOBOX genes are crucial for normal vascular organization and wood formation in poplar.

Vascular cambium in tree species is a cylindrical domain of meristematic cells that are responsible for producing secondary xylem (also called wood) inward and secondary phloem outward. The poplar (Populus trichocarpa) WUSCHEL (WUS)-RELATED HOMEOBOX (WOX) family members, PtrWUSa and PtrWOX13b, were previously shown to be expressed in vascular cambium and differentiating xylem cells in poplar stems, but their functions remain unknown. Here, we investigated roles of PtrWUSa, PtrWOX13b and their close homologs in vascular organization and wood formation. Expression analysis showed that like PtrWUSa and PtrWOX13b, their close homologs, PtrWUSb, PtrWUS4a/b and PtrWOX13a/c, were also expressed in vascular cambium and differentiating xylem cells in poplar stems. PtrWUSa also exhibited a high level of expression in developing phloem fibers. Expression of PtrWUSa fused with the dominant EAR repression domain (PtrWUSa-DR) in transgenic poplar caused retarded growth of plants with twisted stems and curled leaves and a severe disruption of vascular organization. In PtrWUSa-DR stems, a drastic proliferation of cells occurred in the phloem region between vascular cambium and phloem fibers and they formed islands of ectopic vascular tissues or phloem fiber-like sclerenchyma cells. A similar proliferation of cells was also observed in PtrWUSa-DR leaf petioles and midveins. On the other hand, overexpression of PtrWOX4a-DR caused ectopic formation of vascular bundles in the cortical region, and overexpression of PtrWOX13a-DR and PtrWOX13b-DR led to a reduction in wood formation without affecting vascular organization in transgenic poplar plants. Together, these findings indicate crucial roles of PtrWUSa and PtrWOX13a/b in regulating vascular organization and wood formation, which furthers our understanding of the functions of WOX genes in regulating vascular cambium activity in tree species.

Ancient origin of acetyltransferases catalyzing O-acetylation of plant cell wall polysaccharides.

Members of the domain of unknown function 231 (DUF231)/trichome birefringence-like (TBL) family have been shown to be O-acetyltransferases catalyzing the acetylation of plant cell wall polysaccharides, including pectins, mannan, xyloglucan and xylan. However, little is known about the origin and evolution of plant cell wall polysaccharide acetyltransferases. Here, we investigated the biochemical functions of TBL homologs from Klebsormidium nitens, a representative of an early divergent class of charophyte green algae that are considered to be the closest living relatives of land plants, and Marchantia polymorpha, a liverwort that is an extant representative of an ancient lineage of land plants. The genomes of K. nitens and M. polymorpha harbor two and six TBL homologs, respectively. Biochemical characterization of their recombinant proteins expressed in human embryonic kidney (HEK) 293 cells demonstrated that the two K. nitens TBLs exhibited acetyltransferase activities acetylating the pectin homogalacturonan (HG) and hence were named KnPOAT1 and KnPOAT2. Among the six M. polymorpha TBLs, five of them (MpPOAT1 to 5) possessed acetyltransferase activities toward pectins and the remaining one (MpMOAT1) catalyzed 2-O- and 3-O-acetylation of mannan. While MpPOAT1,2 specifically acetylated HG, MpPOAT3,4,5 could acetylate both HG and rhamnogalacturonan-I (RG-I). Consistent with the acetyltransferase activities of these TBLs, pectins isolated from K. nitens and both pectins and mannan from M. polymorpha were shown to be acetylated. These findings indicate that the TBL genes were recruited as cell wall polysaccharide O-acetyltransferases as early as in charophyte green algae with activities toward pectins and they underwent expansion and functional diversification to acetylate various cell wall polysaccharides during evolution of land plants.

Pan-cancer multi-omics analysis of PTBP1 reveals it as an inflammatory, progressive and prognostic marker in glioma.

PTBP1 is an oncogene that regulates the splicing of precursor mRNA. However, the relationship between PTBP1 expression and gene methylation, cancer prognosis, and tumor microenvironment remains unclear. The expression profiles of PTBP1 across various cancers were derived from the TCGA, as well as the GTEx and CGGA databases. The CGGA mRNA_325, CGGA mRNA_301, and CGGA mRNA_693 datasets were utilized as validation cohorts. Immune cell infiltration scores were approximated using the TIMER 2.0 tool. Functional enrichment analysis for groups with high and low PTBP1 expression was conducted using Gene Set Enrichment Analysis (GSEA). Methylation data were predominantly sourced from the SMART and Mexpress databases. Linked-omics analysis was employed to perform functional enrichment analysis of genes related to PTBP1 methylation, as well as to conduct protein functional enrichment analysis. Single-cell transcriptome analysis and spatial transcriptome analysis were carried out using Seurat version 4.10. Compared to normal tissues, PTBP1 is significantly overexpressed and hypomethylated in various cancers. It is implicated in prognosis, immune cell infiltration, immune checkpoint expression, genomic variation, tumor neoantigen load, and tumor mutational burden across a spectrum of cancers, with particularly notable effects in low-grade gliomas. In the context of gliomas, PTBP1 expression correlates with WHO grade and IDH1 mutation status. PTBP1 expression and methylation play an important role in a variety of cancers. PTBP1 can be used as a marker of inflammation, progression and prognosis in gliomas.

Levodopa modulates semantic fluency and uniqueness in non-demented patients with progressive supranuclear palsy.

INTRODUCTION: Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function. Similar to patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) scored lower than healthy adults in the well-established semantic fluency test. However, it is unclear how unique are the produced words. This study examined the relationship between semantic fluency and words' uniqueness in patients with PSP. METHODS: Twenty-seven patients with PSP Richardson's syndrome (PSP-RS), 37 patients with PD, and 41 healthy controls (HC) performed a standard semantic fluency test (animals), and their verbal responses were audio-recorded. We used the uniqueness to reflect the ability to produce both original and effective work, that is, creativity. RESULTS: The PSP-RS group produced fewer correct words and fewer unique words than the PD and HC groups. Moreover, the correlation between fluency and uniqueness was positive in the HC and PD groups but negative in the PSP-RS group. Importantly, the actual levodopa dose was positively correlated with the fluency but negatively correlated with the uniqueness in PSP-RS. The PSP-RS patients who took a greater dose of levodopa tended to produce more correct words but fewer unique words. CONCLUSIONS: These results suggested that levodopa may modulate semantic fluency and uniqueness in the early stages of PSP-RS.

Relationship Between Temporomandibular Joint Effusion, Pain, and Jaw Function Limitation: A 2D and 3D Comparative Study.

Purpose: This study aimed to investigate the relationship between temporomandibular joint (TMJ) effusion and TMJ pain, as well as jaw function limitation in patients via two-dimensional (2D) and three-dimensional (3D) magnetic resonance imaging (MRI) evaluation. Patients and Methods: 121 patients diagnosed with temporomandibular disorder (TMD) were included. TMJ effusion was assessed qualitatively using MRI and quantified with 3D Slicer software, then graded accordingly. In addition, a visual analogue scale (VAS) was employed for pain reporting and an 8-item Jaw Functional Limitations Scale (JFLS-8) was utilized to evaluate jaw function limitation. Statistical analyses were performed appropriately for group comparisons and association determination. A probability of p<0.05 was considered statistically significant. Results: 2D qualitative and 3D quantitative strategies were in high agreement for TMJ effusion grades (κ = 0.766). No significant associations were found between joint effusion and TMJ pain, nor with disc displacement and JLFS-8 scores. Moreover, the binary logistic regression analysis showed significant association between sex and the presence of TMJ effusion, exhibiting an Odds Ratio of 5.168 for females (p = 0.008). Conclusion: 2D qualitative evaluation was as effective as 3D quantitative assessment for TMJ effusion diagnosis. No significant associations were found between TMJ effusion and TMJ pain, disc displacement or jaw function limitation. However, it was suggested that female patients suffering from TMD may be at a risk for TMJ effusion. Further prospective research is needed for validation.

Development and application of a novel suspension concentrate for seed coating of rice for controlling bakanae disease and seedling rot disease.

The main rice planting areas in the middle and lower reaches of the Yangtze River are primarily affected by two types of rice seedling diseases: bakanae disease and seedling rot disease. These diseases lead to considerable losses. Seed coating technology effectively protects rice from these diseases and mitigates environmental pollution. We determined the antifungal activity of six fungicides, including phenamacril, azoxystrobin, fludioxonil, metconazole, thifluzamide and prothioconazole against Fusarium moniliforme Sheldon and Curvularia lunata in this study. In addition, the impact of fungicides and surfactants on rice seed germination were determined. Furthermore, phenamacril and fludioxonil were selected as the active components of suspension concentrate for seed coating. The antifungal activity of phenamacril against F. moniliforme Sheldon was 0.139 mg/L and fludioxonil against C. lunata was 0.110 mg/L. PEG-2000 was selected as the surfactant due to its promoting effect on rice seedling. Based on the above findings, 6% phenamacril fludioxonil FS was developed via the wet sand grinding method. The toxicity of 6% phenamacril fludioxonil FS to zebrafish was verified, and field experiments were conducted in five different regions of the Yangtze River Basin. The results indicated minimal toxicity of 6% phenamacril fludioxonil FS to zebrafish. Relative to the control agent consisting of 6.25% phenamacril metalaxyl-M FS, 6% phenamacril fludioxonil FS showed better control effect and exhibited superior efficacy in promoting growth and increasing yield in all five regions. Specifically, the control effect of 6% phenamacril fludioxonil FS on bakanae exceeded 84.83% with the highest yield increasing value recorded at 30.48%. Currently, the market offers a limited selection of suspension concentrate for seed coating of rice. The findings of this study may offer a viable alternative formulation and directions for further research concerning the application of suspension concentrate for seed coating of rice.

Interface Engineering Induced Multi-Scale Self-Assembly NiFe-LDH Heterostructures for High-Performance Water Electrolysis.

Confronted with the pressing issue of energy scarcity, the development of an economical and potent bifunctional catalyst is of paramount importance. We adopt an interface engineering strategy to modify the surface of NiFe-LDH nanoplates with O2 plasma treatment. This process enhances the local electric field of NiFe-LDH, resulting in the formation of a self-assembled polycrystalline nanowire array on the nanoplate surface. After O2 plasma treatment for 30 min, the NiFe-LDH-P30 not only formed a heterostructure with rough surface, but also regulated the exposure of crystal surfaces. Due to the strong interface coupling between the self-assembled 3D nanoflowers, 2D nanoplates and 1D nanowires, the NiFe-LDH-P30 exhibits an excellent structural stability. Moreover, it demonstrated exceptional HER and OER activities in alkaline condition, achieving a low overpotentials of 154 mV and 242 mV at 10 mA cm-2, respectively. Furthermore, NiFe-LDH-P30 as the dual-electrode material for the cathode and anode in the process of water splitting results in a low voltage of 1.63 V at a current density of 10 mA cm-2. Through the strategic application of interface engineering, this work has pioneered a novel approach to the creation of transition metal-based electrocatalysts, which is benefit to a range of practical energy applications.

Rapidly repeated visual stimulation induces long-term potentiation of VEPs and increased content of membrane AMPA and NMDA receptors in the V1 cortex of cats.

Studies report that rapidly repeated sensory stimulation can evoke LTP-like improvement of neural response in the sensory cortex. Whether this neural response potentiation is similar to the classic LTP induced by presynaptic electrical stimulation remains unclear. This study examined the effects of repeated high-frequency (9 Hz) versus low-frequency (1 Hz) visual stimulation on visually-evoked field potentials (VEPs) and the membrane protein content of AMPA / NMDA receptors in the primary visual cortex (V1) of cats. The results showed that repeated high-frequency visual stimulation (HFS) caused a long-term improvement in peak-to-peak amplitude of V1-cortical VEPs in response to visual stimuli at HFS-stimulated orientation (SO: 90°) and non-stimulated orientation (NSO: 180°), but the effect exhibited variations depending on stimulus orientation: the amplitude increase of VEPs in response to visual stimuli at SO was larger, reached a maximum earlier and lasted longer than at NSO. By contrast, repeated low-frequency visual stimulation (LFS) had not significantly affected the amplitude of V1-cortical VEPs in response to visual stimuli at both SO and NSO. Furthermore, the membrane protein content of the key subunit GluA1 of AMPA receptors and main subunit NR1 of AMPA receptors in V1 cortex was significantly increased after HFS but not LFS when compared with that of control cats. Taken together, these results indicate that HFS can induce LTP-like improvement of VEPs and an increase in membrane protein of AMPA and NMDA receptors in the V1 cortex of cats, which is similar to but less specific to stimulus orientation than the classic LTP.

Subthalamic Nucleus Stimulation Modulates Cognitive Theory of Mind in Parkinson's Disease.

BACKGROUND: Theory of mind (ToM), the ability to infer others' mental state, is essential for social interaction among human beings. It has been widely reported that both cognitive (inference of knowledge) and affective (inference of emotion) components of ToM are disrupted in Parkinson's disease (PD). Previous studies usually focused on the involvement of the prefrontal cortex. OBJECTIVE: This study investigated the causal role of the subthalamic nucleus (STN), a key hub of the fronto-basal ganglia loops, in ToM. METHODS: Thirty-four patients with idiopathic PD (15 women, aged 62.2 ± 8.3 years) completed a Yoni task with deep brain stimulation (DBS) ON and OFF. The Yoni task was designed to separate the cognitive and affective components of ToM. Volumes of tissue activated (VTA) were computed for three subregions of the STN. RESULTS: DBS showed insignificant effects on ToM inference costs at the group level, which may be due to the large interindividual variability. The associative VTA correlated with the cognitive inference cost change but not the affective inference cost change. Patients with greater associative STN stimulation infer more slowly on cognitive ToM. Stimulating associative STN can adversely affect cognitive ToM in PD patients, especially in patients with a wide range of stimulation (≥0.157) or cognitive decline (Montreal Cognitive Assessment < 26). CONCLUSIONS: The associative STN plays a causal role in cognitive ToM in patients with PD. However, stimulating the associative STN likely impairs cognitive ToM and potentially leads to social interaction deficits in PD. © 2024 International Parkinson and Movement Disorder Society.

Impaired sequence manipulation in non-demented patients with progressive supranuclear palsy.

PURPOSE: Sequential working memory is the ability to maintain and manipulate sequential information at a second time scale. Patients with progressive supranuclear palsy (PSP) or Parkinson's disease (PD) perform poorly in tests that require the flexible arrangement of thoughts or actions. This study investigated whether sequential working memory is differently impaired in patients with PSP versus PD. METHOD: Twenty-nine patients with PSP Richardson's syndrome (PSP-RS), 36 patients with PD, and 36 healthy controls (HC) completed 3 well-established neuropsychological tests, including digit span forward (DST-F), digit span backward (DST-B), and adaptive digit ordering tests (DOT-A). The DST-F required maintaining digit sequences, and the DST-B and DOT-A required maintaining and manipulating digit sequences. FINDING: The PSP-RS group scored lower than the PD and HC groups in the DST-B and DOT-A but not in the DST-F, indicating that the ability to manipulate sequences was impaired, but the maintenance ability was preserved in PSP-RS patients. Moreover, in PSP-RS, the DST-B score negatively correlated with the severity of motor symptoms. The actual levodopa dose positively correlated with the DST-B ordering cost (DST-F score vs. DST-B score). The PSP patients who took a greater dose of levodopa tended to have higher DST-B ordering cost. There was no effect of levodopa on DST-B or DOT-A in PD. CONCLUSION: These results suggested that the ability to manipulate sequence was already reduced in patients with PSP-RS and was worse than in patients with PD.

Feasibility of rib fracture detection in low-dose computed tomography images with a large, multicenter datasets-based model.

Purpose: To evaluate the feasibility of rib fracture detection in low-dose computed tomography (CT) images with a RetinaNet-based approach and to evaluate the potential of lowdose CT for rib fracture detection compared with regular-dose CT images. Materials and methods: The RetinaNet-based deep learning model was trained using 7300 scans with 50,410 rib fractures that were used as internal training datasets from four multicenter. The external test datasets consisted of both regular-dose and low-dose chest-abdomen CT images of rib fractures; the MICCAI 2020 RibFrac Challenge Dataset was used as the public dataset. Radiologists' interpretations were used as reference standards. The performance of the model in rib fracture detection was compared with the radiologists' interpretation. Results: In total, 728 traumatic rib fractures of 100 patients [60 men (60 %); mean age, 53.45 ± 11.19 (standard deviation (SD)); range, 18-77 years] were assessed in the external datasets. In these patients, the regular-dose group had a mean CT dose index volume (CTDIvol) of 7.18 mGy (SD: 2.22) and a mean dose length product (DLP) of 305.38 mGy cm (SD: 95.31); the low-dose group had a mean CTDIvol of 2.79 mGy (SD: 1.11) and a mean DLP of 131.52 mGy cm (SD: 55.58). The sensitivity of the RetinaNet-based model and that of the radiologists was 0.859 and 0.721 in the low-dose CT images and 0.886 and 0.794 in the regular-dose CT images, respectively. Conclusions: These findings indicate that the RetinaNet-based model can detect rib fractures in low-dose CT images with a robust performance, indicating its feasibility in assisting radiologists with rib fracture diagnosis.

Reducing the risk of suicidal behaviors in medical graduate students: exploration of student-supervisor relationship and subjective family socioeconomic status.

Objective: This study aimed to investigate the association between the risk of suicidal behaviors and student-supervisor relationships and subjective family socioeconomic status (SFSS) in medical graduate students, and to propose preventive strategies to reduce the suicidal risk among medical graduate students. Materials and methods: A total of 1,310 validated questionnaires were collected from medical graduate students, which included demographic information, study programs, the Suicidal Behaviors Questionnaire-Revised (SBQ-R) questionnaire, the Leader-Member Exchange 7 (LMX-7) questionnaire, and SFSS by MacArthur Scale. Multiple regression analysis was employed to examine the associations between variables and adjust for confounders. A moderation analysis, containing simple slope analysis and Johnson-Neyman interval plots were used to analyze the moderating effect of the SFSS in the association of SBQ-R and LMX-7 scores. Results: A total of 88 participants (6.7%) were at risk of suicidal behaviors. In the high-quality student-supervisor relationship group (LMX-7 score ≥ 25), SFSS was significantly higher than in the low- and moderate-quality relationship group (p=0.002). The median SBQ-R score and proportion of suicide risk was significantly lower (p<0.001) in the high-quality student-supervisor relationship group. Multiple regression analysis indicated LMX-7 scores (ß=-0.098, 95% CI [-0.118, -0.077], p<0.001) and SFSS (ß=-0.073, 95% CI [-0.127, -0.019], p=0.008) were significantly negatively associated with SBQ-R, whereas the interaction term of SFSS with LMX-7 (ß=0.018, 95% CI [0.007, 0.029], p=0.001) showed a significant positive association with SBQ-R. The Johnson-Neyman interval showed a significant association between LMX-7 and SBQ-R scores only when SFSS was less than 7.82 (p<0.05). Conclusion: The risk of suicidal behaviors was associated with student-supervisor relationships and SFSS among medical graduate students. Poor relationships with supervisor were associated with an elevated risk of suicidality, and SFSS moderated this association. Educators should pay increased attention to the suicidal risk of medical graduate students with poor supervisor relationships, especially those from families with low SFSS, and provide timely preventive strategies.

A rice GT61 glycosyltransferase possesses dual activities mediating 2-O-xylosyl and 2-O-arabinosyl substitutions of xylan.

MAIN CONCLUSION: A member of the rice GT61 clade B is capable of transferring both 2-O-xylosyl and 2-O-arabinosyl residues onto xylan and another member specifically catalyses addition of 2-O-xylosyl residue onto xylan. Grass xylan is substituted predominantly with 3-O-arabinofuranose (Araf) as well as with some minor side chains, such as 2-O-Araf and 2-O-(methyl)glucuronic acid [(Me)GlcA]. 3-O-Arabinosylation of grass xylan has been shown to be catalysed by grass-expanded clade A members of the glycosyltransferase family 61. However, glycosyltransferases mediating 2-O-arabinosylation of grass xylan remain elusive. Here, we performed biochemical studies of two rice GT61 clade B members and found that one of them was capable of transferring both xylosyl (Xyl) and Araf residues from UDP-Xyl and UDP-Araf, respectively, onto xylooligomer acceptors, whereas the other specifically catalysed Xyl transfer onto xylooligomers, indicating that the former is a xylan xylosyl/arabinosyl transferase (named OsXXAT1 herein) and the latter is a xylan xylosyltransferase (named OsXYXT2). Structural analysis of the OsXXAT1- and OsXYXT2-catalysed reaction products revealed that the Xyl and Araf residues were transferred onto O-2 positions of xylooligomers. Furthermore, we demonstrated that OsXXAT1 and OsXYXT2 were able to substitute acetylated xylooligomers, but only OsXXAT1 could xylosylate GlcA-substituted xylooligomers. OsXXAT1 and OsXYXT2 were predicted to adopt a GT-B fold structure and molecular docking revealed candidate amino acid residues at the predicted active site involved in binding of the nucleotide sugar donor and the xylohexaose acceptor substrates. Together, our results establish that OsXXAT1 is a xylan 2-O-xylosyl/2-O-arabinosyl transferase and OsXYXT2 is a xylan 2-O-xylosyltransferase, which expands our knowledge of roles of the GT61 family in grass xylan synthesis.

Inferior parietal cortex represents relational structures for explicit transitive inference.

The human brain is distinguished by its ability to perform explicit logical reasoning like transitive inference. This study investigated the functional role of the inferior parietal cortex in transitive inference with functional MRI. Participants viewed premises describing abstract relations among items. They accurately recalled the relationship between old pairs of items, effectively inferred the relationship between new pairs of items, and discriminated between true and false relationships for new pairs. First, the inferior parietal cortex, but not the hippocampus or lateral prefrontal cortex, was associated with transitive inference. The inferior parietal activity and functional connectivity were modulated by inference (new versus old pairs) and discrimination (true versus false pairs). Moreover, the new/old and true/false pairs were decodable from the inferior parietal representation. Second, the inferior parietal cortex represented an integrated relational structure (ordered and directed series). The inferior parietal activity was modulated by serial position (larger end versus center pairs). The inferior parietal representation was modulated by symbolic distance (adjacent versus distant pairs) and direction (preceding versus following pairs). It suggests that the inferior parietal cortex may flexibly integrate observed relations into a relational structure and use the relational structure to infer unobserved relations and discriminate between true and false relations.

Construction of a pathological model of skin lesions in acute herpes zoster virus infection and its molecular mechanism.

Varicella-zoster virus (VZV), a common pathogen with humans as the sole host, causes primary infection and undergoes a latent period in sensory ganglia. The recurrence of VZV is often accompanied by severe neuralgia in skin tissue, which has a serious impact on the life of patients. During the acute infection of VZV, there are few related studies on the pathophysiological mechanism of skin tissue. In this study, transcriptome sequencing data from the acute response period within 2 days of VZV antigen stimulation of the skin were used to explore a model of the trajectory of skin tissue changes during VZV infection. It was found that early VZV antigen stimulation caused activation of mainly natural immune-related signaling pathways, while in the late phase activation of mainly active immune-related signaling pathways. JAK-STAT, NFκB, and TNFα signaling pathways are gradually activated with the progression of infection, while Hypoxia is progressively inhibited. In addition, we found that dendritic cell-mediated immune responses play a dominant role in the lesion damage caused by VZV antigen stimulation of the skin. This study provides a theoretical basis for the study of the molecular mechanisms of skin lesions during acute VZV infection.