Heterointerface engineering of layered double hydroxide/MAPbBr3 heterostructures enabling tunable synapse behaviors in a two-terminal optoelectronic device.

Solution-processable semiconductor heterostructures enable scalable fabrication of high performance electronic and optoelectronic devices with tunable functions via heterointerface control. In particular, artificial optical synapses require interface manipulation for nonlinear signal processing. However, the limited combinations of materials for heterostructure construction have restricted the tunability of synaptic behaviors with simple device configurations. Herein, MAPbBr3 nanocrystals were hybridized with MgAl layered double hydroxide (LDH) nanoplates through a room temperature self-assembly process. The formation of such heterostructures, which exhibited an epitaxial relationship, enabled effective hole transfer from MAPbBr3 to LDH, and greatly reduced the defect states in MAPbBr3. Importantly, the ion-conductive nature of LDH and its ability to form a charged surface layer even under low humidity conditions allowed it to attract and trap holes from MAPbBr3. This imparted tunable synaptic behaviors and short-term plasticity (STP) to long-term plasticity (LTP) transition to a two-terminal device based on the LDH-MAPbBr3 heterostructures. The further neuromorphic computing simulation under varying humidity conditions showcased their potential in learning and recognition tasks under ambient conditions. Our work presents a new type of epitaxial heterostructure comprising metal halide perovskites and layered ion-conductive materials, and provides a new way of realizing charge-trapping induced synaptic behaviors.

Sexual stage-specific A-to-I mRNA editing is mediated by tRNA-editing enzymes in fungi.

A-to-I RNA editing catalyzed by adenosine-deaminase-acting-on-RNA (ADARs) was assumed to be unique to metazoans because fungi and plants lack ADAR homologs. However, genome-wide messenger RNA (mRNA) editing was found to occur specifically during sexual reproduction in filamentous ascomycetes. Because systematic characterization of adenosine/cytosine deaminase genes has implicated the involvement of TAD2 and TAD3 orthologs in A-to-I editing, in this study, we used genetic and biochemical approaches to characterize the role of FgTAD2, an essential adenosine-deaminase-acting-on-tRNA (ADAT) gene, in mRNA editing in Fusarium graminearum. FgTAD2 had a sexual-stage-specific isoform and formed heterodimers with enzymatically inactive FgTAD3. Using a repeat-induced point (RIP) mutation approach, we identified 17 mutations in FgTAD2 that affected mRNA editing during sexual reproduction but had no effect on transfer RNA (tRNA) editing and vegetative growth. The functional importance of the H352Y and Q375*(nonsense) mutations in sexual reproduction and mRNA editing were confirmed by introducing specific point mutations into the endogenous FgTAD2 allele in the wild type. An in vitro assay was developed to show that FgTad2-His proteins purified from perithecia, but not from vegetative hyphae, had mRNA editing activities. Moreover, the H352Y mutation affected the enzymatic activity of FgTad2 to edit mRNA but had no effect on its ADAT activity. We also identified proteins co-purified with FgTad2-His by mass spectrometry analysis and found that two of them have the RNA recognition motif. Taken together, genetic and biochemical data from this study demonstrated that FgTad2, an ADAT, catalyzes A-to-I mRNA editing with the stage-specific isoform and cofactors during sexual reproduction in fungi.

Uncovering Microbial Composition of the Tissue Microenvironment in Bladder Cancer using RNA Sequencing Data.

Purpose: Bladder cancer (BC) is one of the top 10 common tumors in the world. It has been reported that microbiota can colonize tissues and play important roles in tumorigenesis and progression. However, the current understanding of microorganisms in the BC tissue microenvironment remains unclear. Methods: In this study, we integrated the RNA-seq data of 479 BC tissue samples from seven datasets combined with a range of bioinformatics tools to explore the landscape of microbiome in the BC tissue microenvironment. Results: The pan-microbiome was estimated to surpass 1,400 genera. A total of seven core microbiota (Bacillus, Corynebacterium, Cutibacterium, Escherichia, Halomonas, Pasteurella, and Streptomyces) were identified. Among them, Bacillus was widely distributed in all datasets with a high relative abundance (10.11% of all samples on average). Moreover, some biological factors, including tissue source and tumor grade, were found significant effects on the microbial composition of the bladder tissue. Pseudomonas, Porphyrobacter, and Acinetobacter were enriched in tumor tissues, while Mycolicibacterium and Streptomyces were enriched in patients who showed durable response to BCG therapy. In addition, we established microbial co-occurrence networks and found that the BCG therapy may attenuate the microbiological interactions. Conclusions: This study clearly provided a microbial landscape of the BC tissue microenvironment, which was important for exploring the interactions between microorganisms and BC tissues. The identified specific taxa might be potential biomarkers for BC.

CD4+CD25+ regulatory T cells ex vivo generated from autologous naïve CD4+ T cells suppress EAE progression.

CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4+CD25highCD127low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 104 cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS.

Regulation of TRI5 expression and deoxynivalenol biosynthesis by a long non-coding RNA in Fusarium graminearum.

Deoxynivalenol (DON) is the most frequently detected mycotoxin in cereal grains and processed food or feed. Two transcription factors, Tri6 and Tri10, are essential for DON biosynthesis in Fusarium graminearum. In this study we conduct stranded RNA-seq analysis with tri6 and tri10 mutants and show that Tri10 acts as a master regulator controlling the expression of sense and antisense transcripts of TRI6 and over 450 genes with diverse functions. TRI6 is more specific for regulating TRI genes although it negatively regulates TRI10. Two other TRI genes, including TRI5 that encodes a key enzyme for DON biosynthesis, also have antisense transcripts. Both Tri6 and Tri10 are essential for TRI5 expression and for suppression of antisense-TRI5. Furthermore, we identify a long non-coding RNA (named RNA5P) that is transcribed from the TRI5 promoter region and is also regulated by Tri6 and Tri10. Deletion of RNA5P by replacing the promoter region of TRI5 with that of TRI12 increases TRI5 expression and DON biosynthesis, indicating that RNA5P suppresses TRI5 expression. However, ectopic constitutive overexpression of RNA5P has no effect on DON biosynthesis and TRI5 expression. Nevertheless, elevated expression of RNA5P in situ reduces TRI5 expression and DON production. Our results indicate that TRI10 and TRI6 regulate each other's expression, and both are important for suppressing the expression of RNA5P, a long non-coding RNA with cis-acting inhibitory effects on TRI5 expression and DON biosynthesis in F. graminearum.

High voltage electrolytes for lithium-ion batteries with micro-sized silicon anodes.

Micro-sized silicon anodes can significantly increase the energy density of lithium-ion batteries with low cost. However, the large silicon volume changes during cycling cause cracks for both organic-inorganic interphases and silicon particles. The liquid electrolytes further penetrate the cracked silicon particles and reform the interphases, resulting in huge electrode swelling and quick capacity decay. Here we resolve these challenges by designing a high-voltage electrolyte that forms silicon-phobic interphases with weak bonding to lithium-silicon alloys. The designed electrolyte enables micro-sized silicon anodes (5 µm, 4.1 mAh cm-2) to achieve a Coulombic efficiency of 99.8% and capacity of 2175 mAh g-1 for >250 cycles and enable 100 mAh LiNi0.8Co0.15Al0.05O2 pouch full cells to deliver a high capacity of 172 mAh g-1 for 120 cycles with Coulombic efficiency of >99.9%. The high-voltage electrolytes that are capable of forming silicon-phobic interphases pave new ways for the commercialization of lithium-ion batteries using micro-sized silicon anodes.

Modulation of learning safety signals by acute stress: paraventricular thalamus and prefrontal inhibition.

Distinguishing between cues predicting safety and danger is crucial for survival. Impaired learning of safety cues is a central characteristic of anxiety-related disorders. Despite recent advances in dissecting the neural circuitry underlying the formation and extinction of conditioned fear, the neuronal basis mediating safety learning remains elusive. Here, we showed that safety learning reduces the responses of paraventricular thalamus (PVT) neurons to safety cues, while activation of these neurons controls both the formation and expression of safety memory. Additionally, the PVT preferentially activates prefrontal cortex somatostatin interneurons (SOM-INs), which subsequently inhibit parvalbumin interneurons (PV-INs) to modulate safety memory. Importantly, we demonstrate that acute stress impairs the expression of safety learning, and this impairment can be mitigated when the PVT is inhibited, indicating PVT mediates the stress effect. Altogether, our findings provide insights into the mechanism by which acute stress modulates safety learning.

Photosynthetic characteristics, yield and quality of sunflower response to deficit irrigation in a cold and arid environment.

In arid regions, deficit irrigation stands as an efficacious strategy for augmenting agricultural water conservation and fostering sustainable crop production. The Hexi Oasis, an irrigation zone situated in Northwest China, serves as a pivotal area to produce grain and cash crops. Nonetheless, due to the predominant conditions of low rainfall and high evaporation, the scarcity of irrigation water has emerged as a critical constraint affecting crop growth and yield in the area. In order to evaluate the effects of deficit irrigation on photosynthetic characteristics, yield, quality, and water use efficiency of sunflower, a two-year field experiment with under-mulched drip irrigation was conducted in the cold and arid environment of the Hexi Oasis region. Water deficits were implemented at sunflower seedling and maturity and consisted of three deficit levels: mild deficit (65-75% field capacity, FC), moderate deficit (55-65% FC), and severe deficit (45-55% FC). A total of six combined water deficit treatments were applied, using full irrigation (75-85% FC) throughout the entire crop-growing season as the control (CK). The results illustrated that water deficit engendered a decrease in leaf net photosynthetic rate, transpiration rate, and stomatal conductance of sunflower compared to CK, with the decrease becoming significant with the water deficit increasing. A mild water deficit, both at the seedling and maturity phases, precipitated a significant enhancement (p< 0.05) in leaf water use efficiency. Under mild water deficit, stomatal limitation emerged as the predominant factor inducing a reduction in the photosynthetic capacity of sunflower leaves, while as the water deficit escalated, non-stomatal limitation progressively assumed dominance. Moreover, a mild/moderate water deficit at seedling and a mild water deficit at maturity (WD1 and WD3) significantly improved sunflower seed quality under consistent yield conditions and significantly increased irrigation water use efficiency, with an average increase of 15.3% and 18.5% over the two years, respectively. Evaluations utilizing principal component analysis and membership function methods revealed that WD1 attained the highest comprehensive score. Consequently, a mild water deficit at both seedling and maturity (WD1) is advocated as the optimal deficit irrigation strategy for sunflower production within the cold and arid environment of Northwest China.

A Pilot Study on Tocilizumab in Very-Late-Onset Myasthenia Gravis.

Objective: This study aimed to initially investigate the efficacy and safety of low-dose tocilizumab combined with glucocorticoid for the treatment of very-late-onset myasthenia gravis (VLOMG). Methods: We conducted a retrospective study in VLOMG patients who were administered intravenous methylprednisolone therapy and subsequently received low-dose oral corticosteroid, in combination with intravenous injection of tocilizumab given once every month for three months. Results: Five patients (mean age 75.0 ± 4.5 years) were included, and all of them were new-onset, and anti-acetylcholine receptor (AChR) antibody-positive generalized MG. The Quantitative Myasthenia Gravis Scale (QMGS) and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores before treatment were 15.4 ± 4.3 and 9.6 ± 2.3, respectively, and they exhibited a continuously decreasing trend after the first, second, and third injection of tocilizumab until 6 months after treatment. At 6 months post-treatment, the QMGS and MG-ADL scores were 5.0 ± 2.9 and 2.0 ± 1.2, respectively, and the difference between scores at baseline and 6-month follow-up was significant (P = 0.005 and P < 0.0001, respectively). No serious adverse drug reactions were reported in any patient during the study period. Discussions and Conclusion: The therapeutic efficacy of tocilizumab in VLOMG remains uncertain. The results from our study support the efficacy and safety of this combination treatment option for VLOMG, and strongly suggests the therapeutic potential of tocilizumab in VLOMG. However, considering the limitation of retrospective nature and small sample size in this study, prospective randomized controlled studies including a larger sample size of selected patients are needed to validate our results.

A non-pheromone GPCR is essential for meiosis and ascosporogenesis in the wheat scab fungus.

Meiosis is essential for generating genetic diversity and sexual spores, but the regulation of meiosis and ascosporogenesis is not clear in filamentous fungi, in which dikaryotic and diploid cells formed inside fruiting bodies are not free living and independent of pheromones or pheromone receptors. In this study, Gia1, a non-pheromone GPCR (G protein-coupled receptor) with sexual-specific expression in Fusarium graminearum, is found to be essential for ascosporogenesis. The gia1 mutant was normal in perithecium development, crozier formation, and karyogamy but failed to undergo meiosis, which could be partially rescued by a dominant active mutation in GPA1 and activation of the Gpmk1 pathway. GIA1 orthologs have conserved functions in regulating meiosis and ascosporogenesis in Sordariomycetes. GIA1 has a paralog, GIP1, in F. graminearum and other Hypocreales species which is essential for perithecium formation. GIP1 differed from GIA1 in expression profiles and downstream signaling during sexual reproduction. Whereas the C-terminal tail and IR3 were important for intracellular signaling, the N-terminal region and EL3 of Gia1 were responsible for recognizing its ligand, which is likely a protein enriched in developing perithecia, particularly in the gia1 mutant. Taken together, these results showed that GIA1 encodes a non-pheromone GPCR that regulates the entry into meiosis and ascosporogenesis via the downstream Gpmk1 MAP kinase pathway in F. graminearum and other filamentous ascomycetes.

Interface design for all-solid-state lithium batteries.

The operation of high-energy all-solid-state lithium-metal batteries at low stack pressure is challenging owing to the Li dendrite growth at the Li anodes and the high interfacial resistance at the cathodes1-4. Here we design a Mg16Bi84 interlayer at the Li/Li6PS5Cl interface to suppress the Li dendrite growth, and a F-rich interlayer on LiNi0.8Mn0.1Co0.1O2 (NMC811) cathodes to reduce the interfacial resistance. During Li plating-stripping cycles, Mg migrates from the Mg16Bi84 interlayer to the Li anode converting Mg16Bi84 into a multifunctional LiMgSx-Li3Bi-LiMg structure with the layers functioning as a solid electrolyte interphase, a porous Li3Bi sublayer and a solid binder (welding porous Li3Bi onto the Li anode), respectively. The Li3Bi sublayer with its high ionic/electronic conductivity ratio allows Li to deposit only on the Li anode surface and grow into the porous Li3Bi sublayer, which ameliorates pressure (stress) changes. The NMC811 with the F-rich interlayer converts into F-doped NMC811 cathodes owing to the electrochemical migration of the F anion into the NMC811 at a high potential of 4.3 V stabilizing the cathodes. The anode and cathode interlayer designs enable the NMC811/Li6PS5Cl/Li cell to achieve a capacity of 7.2 mAh cm-2 at 2.55 mA cm-2, and the LiNiO2/Li6PS5Cl/Li cell to achieve a capacity of 11.1 mAh cm-2 with a cell-level energy density of 310 Wh kg-1 at a low stack pressure of 2.5 MPa. The Mg16Bi84 anode interlayer and F-rich cathode interlayer provide a general solution for all-solid-state lithium-metal batteries to achieve high energy and fast charging capability at low stack pressure.

B4C/Ce co-modified Ti/PbO2 dimensionally stable anode: Facile one-step electrodeposition preparation and highly efficient electrocatalytic degradation of tetracycline.

The application of PbO2 for electrochemical oxidation technology is limited by its low electrocatalytic activity and short service life. Herein, based on the facile one-step electrodeposition, we prepared a boron carbide (B4C) and cerium (Ce) co-modified Ti/PbO2 (Ti/PbO2-B4C-Ce) electrode to overcome these shortcomings. Compared with Ti/PbO2 electrode, the denser surface is displayed by Ti/PbO2-B4C-Ce electrode. Meanwhile, electrochemical characterization indicates that the introduction of B4C and Ce significantly enhance the electrochemical performance of PbO2 electrode. In degradation experiments, under optimized conditions (current density 20 mA cm-2, pH 9, 0.15 M Na2SO4 and 30 °C), the fully degradation of tetracycline (TC) can be completed within 30 min. Furthermore, the trapping experiment demonstrates that ∙OH and SO4·- radicals have a synergistic effect in the degradation process of TC. Based on results of liquid chromatography-mass spectrometer, the generated ·OH preferentially attacks amides, phenols and conjugated double bond groups in TC. Importantly, Ti/PbO2-B4C-Ce electrode maintains a constant degradation efficiency even after 10 recycling tests, and its service life is 2.4 times of traditional Ti/PbO2 electrode. Hence, Ti/PbO2-B4C-Ce electrode is a promising electrode for degradation of organic wastewater containing amides, phenols, and conjugated double bond groups.

Mechanisms of Xiaozheng decoction for anti-bladder cancer effects via affecting the GSK3ß/ß-catenin signaling pathways: a network pharmacology-directed experimental investigation.

PURPOSE: The combination of Xiaozheng decoction with postoperative intravesical instillation has been shown to improve the prognosis of bladder cancer patients and prevent recurrence. However, the mechanisms underlying the efficacy of this herbal formula remain largely unclear. This research aims to identify the important components of Xiaozheng decoction and explore their anti-bladder cancer effect and mechanism using network pharmacology-based experiments. METHODS: The chemical ingredients of each herb in the Xiaozheng decoction were collected from the Traditional Chinese Medicine (TCM) database. Network pharmacology was employed to predict the target proteins and pathways of action. Disease databases were utilized to identify target genes associated with bladder cancer. A Protein-Protein Interaction (PPI) network was constructed to illustrate the interaction with intersected target proteins. Key targets were identified using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. A compound-target-pathway network was established after molecular docking predictions. In vitro experiments with bladder cancer cell lines were conducted using core chemical components confirmed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) to verify the conclusions of network pharmacology. RESULTS: 45 active compounds were extracted, and their relationships with Traditional Chinese Medicines (TCMs) and protein targets were presented, comprising 7 herbs, 45 active compounds, and 557 protein targets. The intersection between potential TCM target genes and bladder cancer-related genes yielded 322 genes. GO and KEGG analyses indicated that these targets may be involved in numerous cancer-related pathways. Molecular docking results showed that candidate compounds except mandenol could form stable conformations with the receptor. In vitro experiments on three bladder cancer cell lines demonstrated that quercetin and two other impressive new compounds, bisdemethoxycurcumin (BDMC) and kumatakenin, significantly promoted cancer cell apoptosis through the B-cell lymphoma 2/Bcl-2-associated X (Bcl-2/BAX) pathway and inhibited proliferation and migration through the glycogen synthase kinase 3 beta (GSK3ß)/ß-catenin pathway. CONCLUSION: By employing network pharmacology and conducting in vitro experiments, the mechanism of Xiaozheng decoction's effect against bladder cancer was tentatively elucidated, and its main active ingredients and targets were identified, providing a scientific basis for future research.

Crop coefficient determination and evapotranspiration estimation of watermelon under water deficit in a cold and arid environment.

To investigate the evapotranspiration and crop coefficient of oasis watermelon under water deficit (WD), mild (60%-70% field capacity, FC)and moderate (50%-60% FC) WD levels were set up at the various growth stages of watermelon, including seedling stage (SS), vine stage (VS), flowering and fruiting stage (FS), expansion stage (ES), and maturity stage (MS), with adequate water supply (70%-80% FC) during the growing season as a control. A two-year (2020-2021) field trial was carried out in the Hexi oasis area of China to explore the effect of WD on watermelon evapotranspiration characteristics and crop coefficient under sub-membrane drip irrigation. The results indicated that the daily reference crop evapotranspiration showed a sawtooth fluctuation which was extremely significantly and positively correlated with temperature, sunshine hours, and wind speed. The water consumption during the entire growing season of watermelon varied from 281-323 mm (2020) and 290-334 mm (2021), among which the phasic evapotranspiration valued the maximum during ES, accounting for 37.85% (2020) and 38.94% (2021) in total, followed in the order of VS, SS, MS, and FS. The evapotranspiration intensity of watermelon increased rapidly from SS to VS, reaching the maximum with 5.82 mm·d-1 at ES, after which it gradually decreased. The crop coefficient at SS, VS, FS, ES, and MS varied from 0.400 to 0.477, from 0.550 to 0.771, from 0.824 to 1.168, from 0.910 to 1.247, and from 0.541 to 0.803, respectively. Any period of WD reduced the crop coefficient and evapotranspiration intensity of watermelon at that stage. And then the relationship between LAI and crop coefficient can be characterized better by an exponential regression, thereby establishing a model for estimating the evapotranspiration of watermelon with a Nash efficiency coefficient of 0.9 or more. Hence, the water demand characteristics of oasis watermelon differ significantly during different growth stages, and reasonable irrigation and water control management measures need to be conducted in conjunction with the water requirements features of each growth stage. Also, this work aims to provide a theoretical basis for the irrigation management of watermelon under sub-membrane drip irrigation in desert oases of cold and arid environments.

Highly Sensitive Temperature Detection Based on a Frost- and Dehydration-Resistive Ion-Doped Hydrogel-MXene Composite.

Wearable temperature sensors with high sensitivity and stability hold great potential for human health monitoring. However, hydrogels, which are commonly used for wearable devices, often show poor thermal and electrical conductivity and are susceptible to dehydration and freezing. Herein, we developed a frost- and dehydration-resistive temperature sensor based on Fe2+/Ti2CTx/κ-carrageenan (CA)-polyacrylamide (PAM) hydrogel. The Fe2+ ions within the hydrogel existed in two forms: as free ions and bonded ions. The free Fe2+ ions could complex with water molecules, resulting in the improved resistance to dehydration and freezing, as well as enhanced ionic conductivity in the hydrogel. On the other hand, the remaining Fe2+ ions acted as linkers to form coordination bonds with the sulfate groups of CA chains, resulting in the greatly enhanced mechanical strength of the hydrogel. In addition, the Ti2CTx nanosheet-based fillers formed a well-defined porous laminar structure, which reduced the phonon scattering and improved the phonon adsorption within the hydrogel. The Fe2+/Ti2CTx/CA-PAM hydrogel sensor exhibited excellent temperature sensing performance including a good linearity (R2 = 0.998) within a broad working range (-10 to 60 °C), high resolution (0.1 °C), and good repeatability. Furthermore, the sensor was integrated into a wireless system for continuous monitoring of body temperature, demonstrating its potential in healthcare monitoring, electronic skins, and intelligent robots.

Specificity in Generalization Effects of Transcranial Direct Current Stimulation Over the Left Inferior Frontal Gyrus in Primary Progressive Aphasia.

OBJECTIVES: Generalization (or near-transfer) effects of an intervention to tasks not explicitly trained are the most desirable intervention outcomes. However, they are rarely reported and even more rarely explained. One hypothesis for generalization effects is that the tasks improved share the same brain function/computation with the intervention task. We tested this hypothesis in this study of transcranial direct current stimulation (tDCS) over the left inferior frontal gyrus (IFG) that is claimed to be involved in selective semantic retrieval of information from the temporal lobes. MATERIALS AND METHODS: In this study, we examined whether tDCS over the left IFG in a group of patients with primary progressive aphasia (PPA), paired with a lexical/semantic retrieval intervention (oral and written naming), may specifically improve semantic fluency, a nontrained near-transfer task that relies on selective semantic retrieval, in patients with PPA. RESULTS: Semantic fluency improved significantly more in the active tDCS than in the sham tDCS condition immediately after and two weeks after treatment. This improvement was marginally significant two months after treatment. We also found that the active tDCS effect was specific to tasks that require this IFG computation (selective semantic retrieval) but not to other tasks that may require different computations of the frontal lobes. CONCLUSIONS: We provided interventional evidence that the left IFG is critical for selective semantic retrieval, and tDCS over the left IFG may have a near-transfer effect on tasks that depend on the same computation, even if they are not specifically trained. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02606422.

A comparative study of H2 sensing performance of stoichiometric polymorphs of titanium carbide MXenes loaded with Pd nanodots.

Although titanium-based MXenes have been widely reported for gas sensing, the effect of crystal stoichiometric variations on the sensing properties has been rarely reported. Herein, stoichiometric polymorphs of titanium carbide MXenes (i.e., Ti3C2Tx and Ti2CTx) loaded with Pd nanodots (NDs) prepared by photochemical reduction were investigated for room-temperature H2 sensing. Interestingly, we found that Pd/Ti2CTx exhibited greatly enhanced sensitivity to H2, along with faster response and recovery rates compared to Pd/Ti3C2Tx. The H2 adsorption induced resistance change in Pd/Ti2CTx was higher than that of Pd/Ti3C2Tx due to the more effective charge transfer at the heterointerface of Pd/Ti2CTx, which was confirmed by shifts of binding energies and theoretical calculation results. We hope this work could be helpful to design more high-performance MXene-based gas sensors.

Characterization of antigen-specific CD8+ memory T cell subsets in peripheral blood of patients with multiple sclerosis.

Background: Increasing evidence indicates the importance of CD8+ T cells in autoimmune attack against CNS myelin and axon in multiple sclerosis (MS). Previous research has also discovered that myelin-reactive T cells have memory phenotype functions in MS patients. However, limited evidence is available regarding the role of CD8+ memory T cell subsets in MS. This study aimed to explore potential antigen-specific memory T cell-related biomarkers and their association with disease activity. Methods: The myelin oligodendrocyte glycoprotein (MOG)-specific CD8+ memory T cell subsets and their related cytokines (perforin, granzyme B, interferon (IFN)-γ) and negative co-stimulatory molecules (programmed cell death protein 1 (PD-1), T- cell Ig and mucin domain 3 (Tim-3)) were analyzed by flow cytometry and real-time PCR in peripheral blood of patients with relapsing-remitting MS. Results: We found that MS patients had elevated frequency of MOG-specific CD8+ T cells, MOG-specific central memory T cells (TCM), MOG-specific CD8+ effector memory T cells (TEM), and MOG-specific CD8+ terminally differentiated cells (TEMRA); elevated granzyme B expression on MOG-specific CD8+ TCM; and, on MOG-specific CD8+ TEM, elevated granzyme B and reduced PD-1 expression. The Expanded Disability Status Scale score (EDSS) in MS patients was correlated with the frequency of MOG-specific CD8+ TCM, granzyme B expression in CD8+ TCM, and granzyme B and perforin expression on CD8+ TEM, but with reduced PD-1 expression on CD8+ TEM. Conclusion: The dysregulation of antigen-specific CD8+ memory T cell subsets, along with the abnormal expression of their related cytokines and negative co-stimulatory molecules, may reflect an excessive or persistent inflammatory response induced during early stages of the illness. Our findings strongly suggest positive regulatory roles for memory T cell populations in MS pathogenesis, probably via molecular mimicry to trigger or promote abnormal peripheral immune responses. Furthermore, downregulated PD-1 expression may stimulate a positive feedback effect, promoting MS-related inflammatory responses via the interaction of PD-1 ligands. Therefore, these parameters are potential serological biomarkers for predicting disease development in MS.

Paraventricular Thalamus Dynamically Modulates Aversive Memory via Tuning Prefrontal Inhibitory Circuitry.

The impact of stress on the formation and expression of memory is well studied, especially on the contributions of stress hormones. But how stress affects brain circuitry dynamically to modulate memory is far less understood. Here, we used male C57BL6/J mice in an auditory fear conditioning as a model system to examine this question and focused on the impact of stress on dorsomedial prefrontal cortex (dmPFC) neurons which play an important role in probabilistic fear memory. We found that paraventricular thalamus (PVT) neurons are robustly activated by acute restraining stress. Elevated PVT activity during probabilistic fear memory expression increases spiking in the dmPFC somatostatin neurons which in turn suppresses spiking of dmPFC parvalbumin (PV) neurons, and reverts the usual low fear responses associated with probabilistic fear memory to high fear. This dynamic and reversible modulation allows the original memory to be preserved and modulated during memory expression. In contrast, elevated PVT activity during fear conditioning impairs synaptic modifications in the dmPFC PV-neurons and abolishes the formation of probabilistic fear memory. Thus, PVT functions as a stress sensor to modulate the formation and expression of aversive memory by tuning inhibitory functions in the prefrontal circuitry.SIGNIFICANCE STATEMENT The impact of stress on cognitive functions, such as memory and executive functions, are well documented especially on the impact by stress hormone. However, the contributions of brain circuitry are far less understood. Here, we show that a circuitry-based mechanism can dynamically modulate memory formation and expression, namely, higher stress-induced activity in paraventricular thalamus (PVT) impairs the formation and expression of probabilistic fear memory by elevating the activity of somatostatin-neurons to suppress spiking in dorsomedial prefrontal parvalbumin (PV) neurons. This stress impact on memory via dynamic tuning of prefrontal inhibition preserves the formed memory but enables a dynamic expression of memory. These findings have implications for better stress coping strategies as well as treatment options including better drug targets/mechanisms.