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Background and Hypothesis: Low-grade neural and peripheral inflammation are among the proposed pathophysiological mechanisms of schizophrenia. White matter impairment is one of the more consistent findings in schizophrenia but the underlying mechanism remains obscure. Many cerebral white matter components are sensitive to neuroinflammatory conditions that can result in demyelination, altered oligodendrocyte differentiation, and other changes. We tested the hypothesis that altered immune-inflammatory response system (IRS) and compensatory immune-regulatory reflex system (IRS/CIRS) dynamics are associated with reduced white matter integrity in patients with schizophrenia., Study Design: Patients with schizophrenia (SCZ, 70M/50F, age = 40.76 ± 13.10) and healthy controls (HCs, 38M/27F, age = 37.48 ± 12.31) underwent neuroimaging and plasma collection. A panel of cytokines were assessed using enzyme-linked immunosorbent assay. White matter integrity was measured by fractional anisotropy (FA) from diffusion tensor imaging using a 3-T Prisma MRI scanner. The cytokines were used to generate 3 composite scores: IRS, CIRS, and IRS/CIRS ratio., Study Results: The IRS/CIRS ratio in SCZ was significantly higher than that in HCs (P = .009). SCZ had a significantly lower whole-brain white matter average FA (P < .001), and genu of corpus callosum (GCC) was the most affected white matter tract and its FA was significantly associated with IRS/CIRS (r = 0.29, P = .002). FA of GCC was negatively associated with negative symptom scores in SCZ (r = -0.23, P = .016). There was no mediation effect taking FA of GCC as mediator, for that IRS/CIRS was not associated with negative symptom score significantly (P = .217) in SCZ., Conclusions: Elevated IRS/CIRS might partly account for the severity of negative symptoms through targeting the integrity of GCC., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Adipose-derived stem cells (ADSCs) have promising applications in tissue regeneration. Currently, there are only a few ADSC products that have been approved for clinical use. The clinical application of ADSCs still faces many challenges. Here, we review emerging strategies to improve the therapeutic efficacy of ADSCs in tissue regeneration. First, a great quantity of cells is often needed for the stem cell therapies, which requires the advanced cell expansion technologies. In addition cell-derived products are also required for the development of 'cell-free' therapies to overcome the drawbacks of cell-based therapies. Second, it is necessary to strengthen the regenerative functions of ADSCs, including viability, differentiation and paracrine ability, for the tissue repair and regeneration required for different physiological and pathophysiological conditions. Third, poor delivery efficiency also restricts the therapeutic effect of ADSCs. Effective methods to improve cell delivery include alleviating harsh microenvironments, enhancing targeting ability and prolonging cell retention. Moreover, we also point out some critical issues about the sources, effectiveness and safety of ADSCs. With these advanced strategies to improve the therapeutic efficacy of ADSCs, ADSC-based treatment holds great promise for clinical applications in tissue regeneration., (© The Author(s) 2022. Published by Oxford University Press.)

Aims: The aim was to characterize indigenous micro-organisms in oil reservoirs after polymer flooding (RAPF)., Methods: The microbial communities in the crude oil phase (Oil) and in the filter-graded aqueous phases Aqu0.22 (>0.22 μm) and Aqu0.1 (0.1-0.22 μm) were investigated by 16S rRNA gene high-throughput sequencing., Results: Indigenous micro-organisms related to hydrocarbon degradation prevailed in the three phases of each well. However, obvious differences in bacterial compositions were observed amongst the three phases of the same well and amongst the same phase of different wells. The crude oil and Aqu0.22 shared many dominant bacteria. Aqu0.1 contained a unique bacterial community in each well. Most bacteria in Aqu0.1 were affiliated to culturable genera, suggesting that they may adapt to the oil reservoir environment by reduction of cell size. Contrary to the bacterial genera, archaeal genera were similar in the three phases but varied in relative abundances. The observed microbial differences may be driven by specific environmental factors in each oil well., Conclusions: The results suggest an application potential of microbial enhanced oil recovery (MEOR) technology in RAPF. The crude oil and Aqu0.1 contain many different functional micro-organisms related to hydrocarbon degradation. Both should not be overlooked when investing and exploring the indigenous micro-organisms for MEOR., Significance and Impact of the Study: This work facilitates the understanding of microbial community structures in RAPF and provides information for microbial control in oil fields., (© 2022 Society for Applied Microbiology.)

Multiple disease resistance (MDR) in maize has attracted increasing attention. However, the interplay between cell death and metabolite changes and their contributions to MDR remains elusive in maize. In this study, we identified a mutant named as lesion mimic 30 (les30) that showed 'suicidal' lesion formation in the absence of disease and had enhanced resistance to the fungal pathogen Curvularia lunata. Using map-based cloning, we identified the causal gene encoding pheophorbide a oxidase (PAO), which is known to be involved in chlorophyll degradation and MDR, and is encoded by LETHAL LEAF SPOT1 (LLS1). LLS1 was found to be induced by both biotic and abiotic stresses. Transcriptomics analysis showed that genes involved in defense responses and secondary metabolite biosynthesis were mildly activated in leaves of the les30 mutant without lesions, whilst they were strongly activated in leaves with lesions. In addition, in les30 leaves with lesions, there was overaccumulation of defense-associated phytohormones including jasmonic acid and salicylic acid, and of phytoalexins including phenylpropanoids, lignin, and flavonoids, suggesting that their biosynthesis was activated in a lesion-dependent manner. Taken together, our study implies the existence of an interactive amplification loop of interrupted chlorophyll degradation, cell death, expression of defense-related genes, and metabolite changes that results in suicidal lesion formation and MDR, and this has the potential to be exploited by genetic manipulation to improve maize disease resistance., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Nerve transfer is an important clinical surgical procedure for nerve repair by the coaptation of a healthy donor nerve to an injured nerve. Usually, nerve transfer is performed in an end-to-end manner, which will lead to functional loss of the donor nerve. In this study, we aimed to evaluate the efficacy of 3D-printed branch nerve conduits in nerve transfer., Methods: Customized branch conduits were constructed using gelatine-methacryloyl by 3D printing. The nerve conduits were characterized both in vitro and in vivo . The efficacy of 3D-printed branch nerve conduits in nerve transfer was evaluated in rats through electrophysiology testing and histological evaluation., Results: The results obtained showed that a single nerve stump could form a complex nerve network in the 3D-printed multibranch conduit. A two-branch conduit was 3D printed for transferring the tibial nerve to the peroneal nerve in rats. In this process, the two branches were connected to the distal tibial nerve and peroneal nerve. It was found that the two nerves were successfully repaired with functional recovery., Conclusions: It is implied that the two-branch conduit could not only repair the peroneal nerve but also preserve partial function of the donor tibial nerve. This work demonstrated that 3D-printed branch nerve conduits provide a potential method for nerve transfer., (© The Author(s) 2022. Published by Oxford University Press.)

Motivation: Robust and reproducible data is essential to ensure high-quality analytical results and is particularly important for large-scale metabolomics studies where detector sensitivity drifts, retention time and mass accuracy shifts frequently occur. Therefore, raw data need to be inspected before data processing to detect measurement bias and verify system consistency., Results: Here, we present RawHummus, an R Shiny app for an automated raw data quality control (QC) in metabolomics studies. It produces a comprehensive QC report, which contains interactive plots and tables, summary statistics and detailed explanations. The versatility and limitations of RawHummus are tested with 13 metabolomics/lipidomics datasets and 1 proteomics dataset obtained from 5 different liquid chromatography mass spectrometry platforms., Availability and Implementation: RawHummus is released on CRAN repository (https://cran.r-project.org/web/packages/RawHummus), with source code being available on GitHub (https://github.com/YonghuiDong/RawHummus). The web application can be executed locally from the R console using the command 'runGui()'. Alternatively, it can be freely accessed at https://bcdd.shinyapps.io/RawHummus/., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Reduced cortical gray matter integrity and cognitive abilities are among core deficits in schizophrenia. We hypothesized that higher allostatic load (AL) that accounts for exposure to chronic stress is a contributor to structural and cognitive deficits in schizophrenia. One hundred and sixty-seven schizophrenia patients who were on average with normal weight, normal systolic, and diastolic blood pressure and 72 healthy controls were enrolled in the study. Group differences in subclinical cardiovascular, metabolic, immune, and neuroendocrine biological markers as indexed by AL and contribution of AL components to the structural and cognitive deficits in schizophrenia were explored. Compared with controls, schizophrenia patients who were normotensive, normoweight, and had low total cholesterol levels still had significantly higher AL mainly due to lower high-density lipoprotein cholesterol and higher heart rate, waist-hip ratio, hemoglobinA1c, hypersensitive C-reactive protein, and overnight-urine cortisol levels. Patients also had decreased whole-brain mean cortical thickness, and lower cognition assessed by the MATRICS consensus cognitive battery. AL was inversely correlated with mean cortical thickness and cognition in schizophrenia, while none of these relationships existed in controls. Mediation analyses showed the effect of AL on cognitive deficits in schizophrenia was significantly mediated by cortical thinning, and the most significant mediating cortical area was the left superior frontal gyrus. Cortical thickness may act as a mediator between AL and cognitive deficits in schizophrenia. Early intervention strategies to reduce cortical thinning and cognitive dysfunction in schizophrenia should target specific aspects of their high AL in addition to weight gain, hypertension and high cholesterol levels., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Nerve guide conduits (NGCs), as alternatives to nerve autografts and allografts, have been widely explored as an advanced tool for the treatment of peripheral nerve injury. However, the repairing efficiency of NGCs still needs significant improvements. Functional NGCs that provide a more favorable microenvironment for promoting axonal elongation and myelination are of great importance. In recent years, 3D printing technologies have been widely applied in the fabrication of customized and complex constructs, exhibiting great potential for tissue engineering applications, especially for the construction of functional NGCs. In this review, we introduce the 3D printing technologies for manufacturing functional NGCs, including inkjet printing, extrusion printing, stereolithography-based printing and indirect printing. Further, we summarize the current methods and strategies for constructing functional NGCs, such as designing special conduit architectures, using appropriate materials and co-printing with different biological cues. Finally, the challenges and prospects for construction of functional NGCs are also presented., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Engineered Saccharomyces cerevisiae can reduce xylose to xylitol. However, in S.cerevisiae, there are several endogenous enzymes including xylitol dehydrogenase encoded by XYL2, sorbitol dehydrogenases encoded by SOR1/SOR2 and xylulokinase encoded by XKS1 may lead to the assimilation of xylitol. In this study, to increase xylitol accumulation, these genes were separately deleted through CRISPR/Cas9 system. Their effects on xylitol yield of an industrial S. cerevisiae CK17 overexpressing Candida tropicalis XYL1 (encoding xylose reductase) were investigated. Deletion of SOR1/SOR2 or XKS1 increased the xylitol yield in both batch and fed-batch fermentation with different concentrations of glucose and xylose. The analysis of the transcription level of key genes in the mutants during fed-batch fermentation suggests that SOR1/SOR2 are more crucially responsible for xylitol oxidation than XYL2 under the genetic background of S.cerevisiae CK17. The deletion of XKS1 gene could also weaken SOR1/SOR2 expression, thereby increasing the xylitol accumulation. The XKS1-deleted strain CK17ΔXKS1 produced 46.17 g/L of xylitol and reached a xylitol yield of 0.92 g/g during simultaneous saccharification and fermentation (SSF) of pretreated corn stover slurry. Therefore, the deletion of XKS1 gene provides a promising strategy to meet the industrial demands for xylitol production from lignocellulosic biomass., (© The Author(s) 2020. Published by Oxford University Press on behalf of FEMS.)

Angiosperms have evolved the metabolic capacity to synthesize p -hydroxyphenyl, guaiacyl (G), and syringyl (S) lignin subunits in their cell walls to better adapt to the harsh terrestrial environment. The structural characteristics of lignin subunits are essentially determined by three cytochrome P450-catalzyed reactions. NADPH-dependent cytochrome P450 oxidoreductase (CPR) is commonly regarded as the electron carrier for P450-catalyzed reactions during monolignol biosynthesis. Here, we show that cytochrome b 5 isoform D (CB5D) is an indispensable electron shuttle protein specific for S-lignin biosynthesis. Arabidopsis ( Arabidopsis thaliana ) CB5D localizes to the endoplasmic reticulum membrane and physically associates with monolignol P450 enzymes. Disrupting CB5D in Arabidopsis resulted in a >60% reduction in S-lignin subunit levels but no impairment in G-lignin formation compared with the wild type, which sharply contrasts with the impaired G- and S-lignin synthesis observed after disrupting ATR2 , encoding Arabidopsis CPR. The defective S-lignin synthesis in cb5d mutants was rescued by the expression of the gene encoding CB5D but not with mutant CB5D devoid of its electron shuttle properties. Disrupting ATR2 suppressed the catalytic activity of both cinnamic acid 4-hydroxylase and ferulate 5-hydroxylase (F5H), but eliminating CB5D specifically depleted the latter's activity. Therefore, CB5D functions as an obligate electron shuttle intermediate that specifically augments F5H-catalyzed reactions, thereby controlling S-lignin biosynthesis., (© 2019 American Society of Plant Biologists. All rights reserved.)

Extensive burns and full-thickness skin wounds are difficult to repair. Autologous split-thickness skin graft (ASSG) is still used as the gold standard in the clinic. However, the shortage of donor skin tissues is a serious problem. A potential solution to this problem is to fabricate skin constructs using biomaterial scaffolds with or without cells. Bioprinting is being applied to address the need for skin tissues suitable for transplantation, and can lead to the development of skin equivalents for wound healing therapy. Here, we summarize strategies of bioprinting and review current advances of bioprinting of skin constructs. There will be challenges on the way of 3D bioprinting for skin regeneration, but we still believe bioprinting will be potential skills for wounds healing in the foreseeable future., Competing Interests: Not applicableNot applicableThe authors declare that they have no competing interests.

Phenylalanine ammonia-lyase (PAL) catalyzes the first rate-limiting step in the phenylpropanoid pathway, which controls carbon flux to a variety of bioactive small-molecule aromatic compounds, and to lignin, the structural component of the cell wall. PAL is regulated at both the transcriptional and translational levels. Our knowledge about the transcriptional regulation of PAL is relatively comprehensive, but our knowledge of the molecular basis of the posttranslational regulation of PAL remains limited. Here, we demonstrate that the Arabidopsis thaliana Kelch repeat F-box (KFB) proteins KFB01, KFB20, and KFB50 physically interact with four PAL isozymes and mediate their proteolytic turnover via the ubiquitination-26S proteasome pathway. The KFB genes are differentially expressed in Arabidopsis tissues and respond to developmental and environmental cues. Up- or downregulation of their expression reciprocally affects the stability of the PAL enzymes, consequently altering the levels of phenylpropanoids. These data suggest that the KFB-mediated protein ubiquitination and degradation regulates the proteolysis of PALs, thus posttranslationally regulating phenylpropanoid metabolism. Characterizing the KFB-mediated proteolysis of PAL enzymes may inform future strategies for manipulating the synthesis of bioactive phenolics.

Fast and sensitive liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) method for the specific determination of viaminate in 14 kinds of rat tissues pre-treated with simple procedure was developed and validated. Biological samples were prepared by direct precipitation to skin, stomach, intestine, and liver and extracted by liquid-liquid extraction to lung, kidney, muscle, spleen, brain, fat, testes (male and female), eye, and heart. After addition of menaquinon as internal standard to tissue homogenate, the supernatant was injected into the isocratic chromatographic system using a Waters Symmetry C8 column and methanol-water-formic acid (93:7:0.1) as the eluent. The eluate was completely led into an APCI interface with selected ion monitoring mode and the analytes were quantified using triple quadrupole MS. The assays were successfully validated in the ranges 0.02-20 ng/mL for lung, 0.02-10 ng/mL for kidney, spleen, muscle, brain, fat, eye, and heart, 0.05-10 ng/mL for testicle, 0.4-100 ng/mL for liver, skin and intestine, and 1.0-200 ng/mL for stomach. The accurate and precise studies showed good reproducibility with coefficients of variation below 8.5% and the recoveries range from 90 to 109%. The analytes were chemically stable under all relevant conditions and the assays were applied in tissue distribution study. The results showed that the viaminate concentration was high in skin, low in kidney, and almost undetectable in eye and brain.