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Abstract Autoimmune uveitis is a leading cause of severe vision loss, and animal models provide unique opportunities for studying its pathogenesis and therapeutic strategies. Here we employ scRNA-seq, RNA-seq and various molecular and cellular approaches to characterize mouse models of classical experimental autoimmune uveitis (EAU), revealing that EAU causes broad retinal neuron degeneration and marker downregulation, and that Müller glia may act as antigen-presenting cells. Moreover, EAU immune response is primarily driven by Th1 cells, and results in dramatic upregulation of CC chemokines, especially CCL5, in the EAU retina. Accordingly, overexpression of CCR5, a CCL5 receptor, in mesenchymal stem cells (MSCs) enhances their homing capacity and improves their immunomodulatory outcomes in preventing EAU, by reducing infiltrating T cells and activated microglia and suppressing Nlrp3 inflammasome activation. Taken together, our data not only provide valuable insights into the molecular characteristics of EAU but also open an avenue for innovative MSC-based therapy.

Naturally synthesized secondary metabolites in plants are considered an important source of drugs, food additives, etc. Among them, research on natural plant medicinal components and their synthesis mechanisms has always been of high concern. We identified a novel medicinal floral crop, Plumbago auriculata L., that can be treated with methyl jasmonate (MeJA) for the rapid or sustainable production of natural bioactives from hairy roots. In the study, we globally analyzed the changes in the accumulation of plumbagin and others in the hairy roots of Plumbago auriculata L. hairy roots (PAHR) 15834 in P. auriculata L. based on 100 μmol/L of MeJA treatment by RNA-seq profiling, and we found that there was a significant increase in the accumulation of plumbagin and saponin before 24 h. To explain the principle of co-accumulation, it showed that MeJA induced JA signaling and the shikimic acid pathway, and the methylvaleric acid (MVA) pathway was activated downstream subsequently by the Mfuzz and weighted gene co-expression analysis. Under the shared metabolic pathway, the high expression of PAL3 and HMGR promoted the activity of the “gateway enzymes” phenylalanine ammonia lyase (PAL) and 3-hydroxy-3-methylglutaryl CoA reductase (HMGR), which respectively induced the high expression of key reaction enzyme genes, including chalcone synthase (CHS), isopentenyl diphosphate (IPP), and farnesyl pyrophosphate synthase (FPS), that led to the synthesis of plumbagin and saponin. We speculated that large amounts of ketones and/or aldehydes were formed under the action of these characteristic enzymes, ultimately achieving their co-accumulation through polyketone and high-level sugar and amino acid metabolism. The study results provided a theoretical basis for carrying out the factory refinement and biosynthesis of plumbagin and saponins and also provided new ideas for fully exploiting multifunctional agricultural crops and plants and developing new agricultural by-products.

Antibiotics play a vital role in safeguarding people's health since most bacterial infection can be efficiently controlled and cured by treating with suitable antibiotics. However, excessive use of antibiotics in husbandry and aquaculture leaded to the pollution of eco-environment. Thus, it is important to develop simple facile methods and effective functional materials for quick on-site analysis of antibiotics. Covalent organic frameworks (COFs), as a kind of porous crystalline covalent bond linked polymers, have demonstrated its power in multiple fields. Herein, we will discuss COFs-based materials utilized as antibiotics sensors with fluorescence method. For each sensor, we will mainly discuss the mechanism for antibiotics recognition, the preparation, characterization and fluorescence sensing performance of specific antibiotics. The mechanism to illustrate the interaction between sensors and antibiotics analytes would also be stressed.

Monkeypox has been spreading worldwide since May 2022, when the World Health Organization (WHO) declared the outbreak a “public health emergency of international concern.” The spread of monkeypox has posed a serious threat to the health of people around the world, but few studies have been conducted, and the molecular mechanism of monkeypox after infection remains unclear. We therefore implemented a transcriptome analysis to identify signaling pathways and biomarkers in monkeypox-infected cells to help understand monkeypox-host cell interactions. In this study, datasets GSE36854 and GSE11234 were obtained from GEO. Of these, 84 significantly different genes were identified in the dataset GSE36854, followed by KEGG, GO analysis protein-protein interaction (PPI) construction, and Hub gene extraction. We also analyzed the expression regulation of hub genes and screened for drugs targeting hub genes. The results showed that monkeypox-infected cells significantly activated the cellular immune response. The top 10 hub genes are IER3, IFIT2, IL11, ZC3H12A, EREG, IER2, NFKBIE, FST, IFIT1 and AREG. AP-26113 and itraconazole can be used to counteract the inhibitory effect of monkeypox on IFIT1 and IFIT2 and serve as candidate drugs for the treatment of monkeypox virus infection. IRF1 may also be a transcription factor of IFIT. Our results provide a new entry point for understanding how monkeypox virus interacts with its host.

Abstract HIV affects more than 38 million people worldwide. Although HIV can be effectively treated by lifelong combination antiretroviral therapy, only a handful of patients have been cured. Therapeutic vaccines that induce robust de novo immune responses targeting HIV proteins and latent reservoirs will likely be integral for functional HIV cure. Our study shows that immunization of naïve rhesus macaques with arenavirus-derived vaccine vectors encoding simian immunodeficiency virus (SIVSME543 Gag, Env, and Pol) immunogens is safe, immunogenic, and efficacious. Immunization induced robust SIV-specific CD8+ and CD4+ T-cell responses with expanded cellular breadth, polyfunctionality, and Env-binding antibodies with antibody-dependent cellular cytotoxicity. Vaccinated animals had significant reductions in median SIV viral load (1.45-log10 copies/mL) after SIVMAC251 challenge compared with placebo. Peak viral control correlated with the breadth of Gag-specific T cells and tier 1 neutralizing antibodies. These results support clinical investigation of arenavirus-based vectors as a central component of therapeutic vaccination for HIV cure.

Under salt stress, recretohalophyte Plumbago auriculata tetraploids enhance salt tolerance by increasing selective secretion of Na+ compared with that in diploids, although the mechanism is unclear. Using non-invasive micro-test technology, the effect of salt gland Ca2+ content on Na+ and K+ secretion were investigated in diploid and tetraploid P. auriculata under salt stress. Salt gland Ca2+ content and secretion rates of Na+ and K+ were higher in tetraploids than in diploids under salt stress. Addition of exogenous Ca2+ increased the Ca2+ content of the salt gland in diploids and is accompanied by an increase in the rate of Na+ and K+ secretion. With addition of a Ca2+ channel inhibitor, diploid salt glands retained large amounts of Ca2+, leading to higher Ca2+ content and Na+ secretion rate than those of tetraploids. Inhibiting H2O2 generation and H+-ATPase activity altered Na+ and K+ secretion rates in diploids and tetraploids under salt stress, indicating involvement in regulating Na+ and K+ secretion. Our results indicate that the increased Na+ secretion rate of salt gland in tetraploids under salt stress was associated with elevated Ca2+ content in salt gland.

Abstract Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.

AbstractPurpose To compare short-term anatomical outcomes observed in optical coherence tomography (OCT) between intravitreal injection (IVI) with anti-vascular endothelial growth factor (VEGF) agent aflibercept (IVA) and subthreshold micropulse laser (SML) therapy in chronic central serous chorioretinopathy (cCSC).Methods Thirty-nine eyes of 36 patients with symptomatic cCSC in this retrospective study received either IVA or SML between December 2020 and August 2022. Spectral-domain-OCT (SD-OCT) findings were compared between the two treatment groups in terms of central macular thickness (CMT), serous subretinal fluid (SRF) height, the presence of pigment epithelial detachment (PED) and subretinal hyperreflective foci (HF) at baseline and one-month follow-up visits.Results Both groups showed significant reductions in CMT and SRF at one-month follow-up visit. However, there were no statistically significant differences between the IVA and SML groups. Complete SRF resolution was observed in 10 out of 21 and 7 out of 18 eyes in the IVA and SML groups, respectively; however, retinal pigment epithelial (RPE) damage remained persistent in patients with PEDs at baseline.Conclusions Both IVA and SML were effective in treating cCSC. IVA and SML treatments had comparable effects in reducing CMT and SRF in eyes with cCSC. Further prospective studies with larger sample sizes and long-term follow-up visits are warranted to identify the long-term efficacy.

Abstract Acorales is the sister lineage to all the other extant monocot plants. Genomic resource enhancement of this genus can help to reveal early monocot genomic architecture and evolution. Here, we assemble the genome of Acorus gramineus and reveal that it has ~45% fewer genes than the majority of monocots, although they have similar genome size. Phylogenetic analyses based on both chloroplast and nuclear genes consistently support that A. gramineus is the sister to the remaining monocots. In addition, we assemble a 2.2 Mb mitochondrial genome and observe many genes exhibit higher mutation rates than that of most angiosperms, which could be the reason leading to the controversies of nuclear genes- and mitochondrial genes-based phylogenetic trees existing in the literature. Further, Acorales did not experience tau (τ) whole-genome duplication, unlike majority of monocot clades, and no large-scale gene expansion is observed. Moreover, we identify gene contractions and expansions likely linking to plant architecture, stress resistance, light harvesting, and essential oil metabolism. These findings shed light on the evolution of early monocots and genomic footprints of wetland plant adaptations.

Remdesivir (RDV) is a broad-spectrum nucleotide analog prodrug approved for the treatment of COVID-19 in hospitalized and non-hospitalized patients with clinical benefit demonstrated in multiple Phase 3 trials. Here we present SARS-CoV-2 resistance analyses from the Phase 3 SIMPLE clinical studies evaluating RDV in hospitalized participants with severe or moderate COVID-19 disease. The severe and moderate studies enrolled participants with radiologic evidence of pneumonia and a room-air oxygen saturation of ≤94% or >94%, respectively. Virology sample collection was optional in the study protocols. Sequencing and related viral load data were obtained retrospectively from participants at a subset of study sites with local sequencing capabilities (10 of 183 sites) at timepoints with detectable viral load. Among participants with both baseline and post-baseline sequencing data treated with RDV, emergent Nsp12 substitutions were observed in 4 of 19 (21%) participants in the severe study and none of the 2 participants in the moderate study. The following 5 substitutions emerged: T76I, A526V, A554V, E665K, and C697F. The substitutions T76I, A526V, A554V, and C697F had an EC50 fold change of ≤1.5 relative to the wildtype reference using a SARS-CoV-2 subgenomic replicon system, indicating no significant change in the susceptibility to RDV. The phenotyping of E665K could not be determined due to a lack of replication. These data reveal no evidence of relevant resistance emergence and further confirm the established efficacy profile of RDV with a high resistance barrier in COVID-19 patients.

Genomic sequencing of clinical samples to identify emerging variants of SARS-CoV-2 has been a key public health tool for curbing the spread of the virus. As a result, an unprecedented number of SARS-CoV-2 genomes were sequenced during the COVID-19 pandemic, which allowed for rapid identification of genetic variants, enabling the timely design and testing of therapies and deployment of new vaccine formulations to combat the new variants. However, despite the technological advances of deep sequencing, the analysis of the raw sequence data generated globally is neither standardized nor consistent, leading to vastly disparate sequences that may impact identification of variants. Here, we show that for both Illumina and Oxford Nanopore sequencing platforms, downstream bioinformatic protocols used by industry, government, and academic groups resulted in different virus sequences from same sample. These bioinformatic workflows produced consensus genomes with differences in single nucleotide polymorphisms, inclusion and exclusion of insertions, and/or deletions, despite using the same raw sequence as input datasets. Here, we compared and characterized such discrepancies and propose a specific suite of parameters and protocols that should be adopted across the field. Consistent results from bioinformatic workflows are fundamental to SARS-CoV-2 and future pathogen surveillance efforts, including pandemic preparation, to allow for a data-driven and timely public health response.

Abstract The characteristics of internal short circuits (ISC) play a critical role in determining the thermal runaway behaviors and associated hazards of lithium‐ion batteries (LIBs). However, due to safety concerns and limitations in operando characterization at high state‐of‐charges (SoCs), the fundamental understanding of stress‐driven ISCs under high SOC situations (above 30%) is still lacking. In this study, combined post‐mortem characterization and multiphysics modeling is employed to clarify the evolution of ISC modes in LIBs with high SOCs. These findings reveal that the triggered ISC mode is SOC‐dependent, with the Al current collector (Al)‐Anode coating (An) mode dominant in high SOC situations. Experimentally obtained ISC resistance for the specified ISC mode is then assigned to the corresponding ISC region in the established multiphysics model, allowing for accurate coupling of the electromechanical relationship and prediction of mechanical‐electrical‐thermal responses of the LIB. Finally, a simple yet effective approach is proposed for avoiding the Al‐An mode after battery fractures, achieved through surface notches on electrodes. Results discover novel phenomena for ISC in high SOC cells and reveal the underlying mechanisms, highlighting the importance and potential of battery structural design for developing next‐generation robust batteries.

Age-related macular degeneration (AMD) causes irreversible vision-loss among the elderly in industrial countries. Neovascular AMD (nAMD), which refers to late-stage AMD, is characterized by severe vision-threatening choroidal neovascularization (CNV). Herein, we constructed a global metabolic network of nAMD, based on untargeted metabolomic and lipidomic analysis of plasma samples collected from sixty subjects (30 nAMD patients and 30 age-matched controls). Among the nAMD and control groups, 62 and 44 significantly different metabolites were detected in the positive and negative ion modes, respectively. Grouping analysis further showed that lipid and lipid-like molecule-based superclasses contained the highest number of significantly different metabolites. Lipidomic analysis revealed that 53 lipids among the nAMD and control groups differed significantly; these belonged to four major lipid categories (glycerophospholipids, sphingolipids, glycerolipids, and fatty acids). A discriminative biomarker panel comprising 16 metabolites and lipids, which was constructed using multivariate statistical machine learning methods, could effectively identify nAMD cases. Among these 16 compounds, eight were lipids that belonged to three lipid categories (glycerophospholipids, sphingolipids, and prenol lipids). The top three biomarkers with the highest importance scores were all lipids (a glycerophospholipid and two sphingolipids), highlighting the crucial role played by glycerophospholipid and sphingolipid pathways in nAMD. These differences between the metabolic and lipid profiles of nAMD patients and elderly individuals without AMD provide a readout of the overall metabolic status of nAMD. Further insights into the identified discriminative biomarkers may pave the way for future diagnostic and therapeutic interventions for nAMD.

How to efficiently activate peroxymonosulfate (PMS) in a complex water matrix to degrade organic pollutants still needs greater efforts, and cobalt-based bimetallic nanomaterials are desirable catalysts. In this paper, sea urchin-like NiCo2O4 nanomaterials were successfully prepared and comprehensively characterized for their structural, morphological and chemical properties via techniques, such as X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), among others. The sea urchin-like NiCo2O4 nanomaterials exhibited remarkable catalytic performance in activating PMS to degrade phenol. Within the NiCo2O4/PMS system, the removal rate of phenol (50 mg L−1, 250 mL) reached 100% after 45 min, with a reaction rate constant k of 0.091 min−1, which was 1.4-times higher than that of the monometallic compound Co3O4/PMS system. The outstanding catalytic activity of sea urchin-like NiCo2O4 primarily arises from the synergistic effect between Ni and Co ions. Additionally, a comprehensive analysis of key parameters influencing the catalytic activity of the sea urchin-like NiCo2O4/PMS system, including reaction temperature, initial pH of solution, initial concentration, catalyst and PMS dosages and coexisting anions (HCO3−, Cl−, NO3− and humic acid), was conducted. Cycling experiments show that the material has good chemical stability. Electron paramagnetic resonance (EPR) and quenching experiments verified that both radical activation (SO4•−, •OH, O2•−) and nonradical activation (1O2) are present in the NiCo2O4/PMS system. Finally, the possible degradation pathways in the NiCo2O4/PMS system were proposed based on gas chromatography–mass spectrometry (GC-MS). Favorably, sea urchin-like NiCo2O4-activated PMS is a promising technology for environmental treatment and the remediation of phenol-induced water pollution problems.

Plumbago indica L. is a perennial herb with ornamental and anticancer medicinal functions widely distributed in the tropics. It is affected by temperature and cannot bloom normally in colder subtropical regions, which seriously affects its ornamental value. To create low-temperature resistance mutants and enrich new germplasm resources, this study used tissue culture and chemical reagent (0.5 mmol/L NaN3) and low-temperature stress (0°C, full darkness for 48h) induction to target and screen for cold-resistance mutants. The results showed that the ISSR band polymorphism ratio of the 24 suspected mutant materials was 87.5%. The DNA profiles of the 9 mutants initially identified were altered. The content of plumbagin in the stems and leaves of the mutants was examined, and it was found that the accumulation in the leaves of the mutant SA24 could be as high as 3.84 times that of the control, which was 0.5991%. There were significant differences in the anatomical structures of roots, stems and leaves. The mutants mostly exhibited reduced root diameter (only 0.17-0.69 times that of CK), increased stem diameter (up to 2.19 times that of CK), enlarged mesophyll cells, increased thickness (up to 1.83 times that of CK) and high specificity, which are thought to be important for the different cold resistance obtained by the mutants. In the cold resistance experiment, four cold-tolerant mutants were successfully screened according to their morphological characteristics and physiological indexes, and the mutagenesis efficiency could be as high as 2.22% and did not affect the accumulation of plumbagin in their stems and leaves, even higher than CK. The responses of the screened mutants SA15, SA19, SA23 and SA24 to low temperature showed slower leaf wilting, higher light energy conversion efficiency, less accumulation of MDA content, increased enzymatic activities of antioxidant enzymes (SOD, CAT, POD) and more accumulation of soluble sugars and proline content. These characteristics are consistent with the response of cold-resistance plants to low temperatures. The cold- resistance mutants cultivated in soil were observed of agronomic and ornamental traits for one year, mainly manifested as delayed flowering and delayed entry into the senescence stage. This study provides a more rapid and accurate technique for identifying and screening cold-tolerant mutants, and lays the foundation for future experiments on the creation of new cold-resistant varieties.

Biochar materials have attracted people’s attention because of their environmental friendliness, abundant resources, and the use of waste resources for reuse. As a potassium-ion anode material, biomass char materials synthesized by different methods have broad application prospects. However, due to the problems of low initial magnification and limited potassium-storage capacity, it is necessary to improve the electrochemical performance through modifications, such as atomic doping. Atomic doping is an effective way to improve battery conductivity and potassium storage. In this paper, the synthesis method of biochar as an anode material for potassium-ion batteries and the influence of atomic doping on its modification in recent years are reviewed.

Accurate determination of extra-cellular pH (pHe) and intra-cellular pH (pHi) is important to cancer diagnosis and treatment because tumor cells exhibit a lower pHe and a slightly higher pHi than normal cells. In this work, the characteristic absorption of water in the near-infrared (NIR) region was utilized for the determination of pHe and pHi. Dulbecco’s modified eagle medium (DMEM) and bis (2-ethylhexyl) succinate sodium sulfonate reverse micelles (RM) were employed to simulate the extra- and intra-cellular fluids, respectively. Continuous wavelet transform (CWT) was used to enhance the resolution of the spectra. Quantitative models for pHe and pHi were established using partial least squares (PLS) regression, producing relative errors of validation samples in a range of −0.74–2.07% and −1.40–0.83%, respectively. Variable selection was performed, and the correspondence between the selected wavenumbers and water structures was obtained. Therefore, water with different hydrogen bonds may serve as a good probe to sense pH within biological systems.

Abstract Cumulative evidence suggests that pyroptosis, a new sort of programmed cell death, is closely related to cerebral ischemia/reperfusion (I/R) injury. Our previous studies have testified that vagus nerve stimulation (VNS) was involved in many different neuroprotective and neuroplasticity pathways via α7 nicotinic acetylcholine receptor (α7nAchR), a vital node of the cholinergic anti-inflammatory pathway during cerebral I/R injury. We aimed to determine the neuroprotective effects of VNS through α7nAchR-mediated inhibition of pyroptosis. Focal cerebral ischemic stroke rat models were obtained by middle cerebral artery occlusion for 120 min. Expression of the NLRP3 inflammasome was evaluated using western blotting and immunofluorescence (IF) staining. The neurological deficit score, infarct volume, TUNEL staining findings, transmission electron microscopy findings, and expression of inflammatory cytokines were assessed 3 days after I/R injury. Our findings suggested that the protein expression levels of NLRP3, GSDMD-N, cleaved caspase-1, and ASC gradually increased until they peaked on day 3 after I/R injury. VNS inhibited the expression of pyroptosis-related molecules and decreased the number of pyroptotic cells and membrane pores. Administration of α7nAchR-antagonist and agonist helped in further assessment of the role of α7nAchR in pyroptosis. α7nAchR-agonist mimicked VNS’s neuroprotective effects on the improvement of neurological deficits, the reduction of infarct volumes, and the inhibition of neuronal pyroptosis after cerebral I/R injury. Conversely, the neuroprotection provided by VNS could be reversed by the administration of α7nAchR-antagonist. In conclusion, VNS-induced neuroprotection via inhibition of neuronal pyroptosis was α7nAchR-dependent, highlighting the pivotal role of α7nAChR in suppressing cellular pyroptosis and neuroinflammation. These findings may allow a better understanding of treatment principles for cerebral I/R injury.

Intermittent fasting (IF), an alternative to caloric restriction, is a form of time restricted eating. IF conditioning has been suggested to have neuroprotective effects and potential long-term brain health benefits. But the mechanism underlying remains unclear. The present study focused on the cerebral angiogenesis effect of IF on ischemic rats. Using a rat middle cerebral artery occlusion model, we assessed neurological outcomes and various vascular parameters such as microvessel density (MVD), regional cerebral blood flow (rCBF), proliferation of endothelial cells (ECs), and functional vessels in the peri-infarct area. IF conditioning ameliorated the modified neurological severity score and adhesive removal test, increased MVD, and activated growth differentiation factor 11 (GDF11)/activin-like kinase 5 (ALK5) pathways in a time-dependent manner. In addition, long-term IF conditioning stimulated proliferation of ECs, promoted rCBF, and upregulated the total vessel surface area as well as the number of microvessel branch points through GDF11/ALK5 pathways. These data suggest that long-term IF conditioning improves neurological outcomes after cerebral ischemia, and that this positive effect is mediated partly by angiogenesis in the peri-infarct area and improvement of functional perfusion microvessels in part by activating the GDF11/ALK5 signaling pathway.

The investigation on propagation of shock waves with terahertz frequency in field-effect transistors has promoted the development of terahertz radiators and detectors. In this paper, we analyze the nonlinear behavior of shock waves with THz frequency in field-effect transistors and study their propagation characteristics at different viscosity coefficients and times. Using reductive perturbation expansion, the hydrodynamic equations are reduced to a Burgers equation governing the characteristic of shock structures in field-effect transistors. We investigate the evolution of shock waves with different viscosity coefficients and times numerically. The analytical and numerical results show that there are monotone shock waves and oscillatory shock waves in this system and an increase in the viscosity coefficient will lead to the diminishment of oscillation. These properties could make the field-effect transistors advantageous for realization of practical terahertz radiation and detection.

Photoreduction of permanent gas faces challenges in reactant diffusion and activation at the three-phase interface. Here the authors showed porous metal-organic framework membranes decorated by metal single atoms can boost the photoreduction of CO2 and O2 at the high-throughput gas-solid interface.

Covalent organic frameworks (COFs) are a novel class of porous crystalline organic materials with organic small molecule units connected by strong covalent bonds and extending in two- or three-dimension in an ordered mode. The tunability, porosity, and crystallinity have endowed covalent organic frameworks the capability of multi-faceted functionality. Introduction of fluorophores into their backbones or side-chains creates emissive covalent organic frameworks. Compared with common fluorescent organic solid materials, COFs possess several intrinsic advantages being as a type of irreplaceable fluorescence materials mainly because its highly developed pore structures can accommodate various types of guest analytes by specific or non-specific chemical bonding and non-bonding interaction. Developments in fluorescent COFs have provided opportunities to enhance sensing performance. Moreover, due to its inherent rigidified structures and fixed conformations, the intramolecular rotation, vibration, and motion occurred in common organic small molecules, and organic solid systems can be greatly inhibited. This inhibition decreases the decay of excited-state energy as heat and blocks the non-radiative quenching channel. Thus, fluorescent COFs can be designed, synthesized, and precisely tuned to exhibit optimal luminescence properties in comparison with common homogeneous dissolved organic small molecule dyes and can even compete with the currently mainstream organic solid semiconductor-based luminescence materials. This mini-review discusses the major design principle and the state-of-the-art paragon examples of fluorescent COFs and their typical applications in the detection and monitoring of some key explosive chemicals by fluorescence analysis. The challenges and the future direction of fluorescent COFs are also covered in detail in the concluding section.

The tropical plant Plumbago auriculata can tolerate subzero temperatures without induction of apoptosis after cold acclimation in autumn, making it more cold tolerant than conventional tropical plants. In this study, we found that low temperatures significantly affected the photosynthetic system of P. auriculata. Using transcriptome sequencing, PaDREB1A was identified as a key transcription factor involved in the response to cold stress in P. auriculata. This transcription factor may be regulated by upstream JA signaling and regulates downstream ERD4 and ERD7 expression to resist cold stress. Overexpression of PaDREB1A significantly enhanced freezing resistance, protected the photosynthetic system, and enhanced the ROS scavenging mechanism under cold stress in Arabidopsis thaliana. Additionally, PaDREB1A significantly enhanced the expression of CORs and CAT1 in A. thaliana, which further activated the downstream pathway to enhance plant cold tolerance. This study explored the possible different regulatory modes of CBFs in tropical plants and can serve as an important reference for the introduction of tropical plants to low-temperature regions.

The development and commercialization of direct ethanol fuel cells requires active and durable electro-catalysts towards the ethanol oxidation reactions (EOR). Rational composition and morphology control of Pt-based alloy nanocrystals can not only enhance their EOR reactivity but also reduce the consumption of precious Pt. Herein, PtCu nanocubes (NCs)/CB enclosed by well-defined (100) facets were prepared by solution synthesis, exhibiting much higher mass activity (4.96 A mgPt−1) than PtCu nanoparticles (NPs)/CB with irregular shapes (3.26 A mgPt−1) and commercial Pt/C (1.67 A mgPt−1). CO stripping and in situ Fourier transform infrared spectroscopy (FTIR) experiments indicate that the alloying of Cu enhanced the adsorption of ethanol, accelerated the subsequent oxidation of intermediate species, and increased the resistance to CO poisoning of PtCu NCs/CB, as compared with commercial Pt/C. Therefore, alloying Pt with earth-abundant Cu under rational composition and surface control can optimize its surface and electronic structures and represents a promising strategy to promote the performance of electro-catalysts while reduce the use of precious metals.

Background and PurposeWe aim to investigate whether the higher admission fibrin degradation products (FDPs) levels are associated with parenchymal hematomas (PHs) and unfavorable outcome after intravenous thrombolysis (IVT).MethodsConsecutive patients with acute ischemic stroke treated with IVT were studied. The FDP level was obtained on admission. PH was evaluated 24 h after treatment. The unfavorable outcome was defined as a 90-day modified Rankin Scale >2. The multivariable linear stepwise regression was used to assess independent factors associated with the log-transformed FDP (lgFDP). The receiver operating characteristics (ROCs) curve analysis was used to determine the predictive value of the FDP level for PH and unfavorable outcome. The logistic regression was used to identify independent predictors for PH and unfavorable outcome. The mediation analyses were performed to investigate associations among the FDP level, PH, and outcome.ResultsA total of 181 patients were included in the final analyses [median age, 73 (63–79) years; 102 (56.4%) males; and the median baseline National Institutes of Health Stroke Scale (NIHSS) score, 8 (5–15)]. The lgFDP was independently associated with age (B = 0.011, 95% CI 0.006–0.015, p < 0.001) and the baseline NIHSS score (B = 0.016, 95% CI 0.008–0.025, p < 0.001). The FDP was positively associated with PH [odds ratio (OR) 1.034, 95% CI 1.000–1.069; p = 0.047]. According to the ROC analysis, the best discriminating factor for unfavorable outcome was the FDP ≥3.085 μg/ml. The FDP ≥3.085 μg/ml was an independent predictor of unfavorable outcome (OR 7.086, 95% CI 2.818–17.822; p < 0.001). Mediation analysis revealed that the association of the FDP ≥3.085 μg/ml with unfavorable outcome was not mediated by PH (p = 0.161).ConclusionThe admission FDP levels can predict PH and unfavorable outcome in patients with acute ischemic stroke after IVT. PH does not mediate the effect of the FDP level on the outcome.

The effects of straw input, including three strategies: chopped straw, straw-derived compost and biochar, on bacterial communities and chemical composition in maize rhizosphere were investigated according to a three-year field experiment. Illumina MiSeq sequencing showed that biochar input increased bacterial richness but decreased bacterial diversity in rhizosphere when compared with the results from no straw control. The functional prediction of Kyoto Encyclopedia of Genes and Genome pathways confirmed that soil subjected to straw input changed the abundance of microbiomes involved in carbohydrate metabolism significantly. Metabolomics analysis showed that straw input changed the metabolite profile of the rhizosphere soil of maize, which was most evident in the treatment of chopped-straw input. The match between the global metabolic profiles and bacterial distribution patterns was weak by performing Procrustes analysis (m2 = 0.851, R = 0.386, P < 0.05). However, the associations between the special members of genera, predicted function involved in carbohydrate metabolism, and rhizosphere metabolites, including sugars and organic acid, were significant (P < 0.05).

This study focuses on the formation of bullied individuals’ friendships and romantic relationships. Individuals bullied in their past may be more likely to form connections with those who share similar oppressive experiences. Thus, we investigated the possibility that implicit homophily underlies the formation of interpersonal relationships among previously bullied individuals. Moreover, we investigated whether these individuals were aware of their friends’ and romantic partners’ similarly oppressive experiences prior to initiating the relationship. Our findings suggest that the young adults in our sample bullied in grade school are significantly more likely to have a close friend and or significant other who also experienced bullying. The findings of this study contribute to the relatively small, yet growing, body of research on implicit homophily, add to research extending homophily processes to bullies and victims, and are in line with research suggesting that deselection (a form of induced homophily) can coexist with homophily by personal preference.

Both tetrabromobisphenol A (TBBPA) and titanium dioxide nanoparticle (TiO2 NP) have widespread commercial applications, resulting in their ubiquitous co-presence in the environment and biota. Although environmental chemicals exist as mixtures, toxicity studies are nearly always conducted with single chemicals. Few studies explore potential interactions of different chemical mixtures. In this study, we employ the sensitive developing nerve system in zebrafish to assess the neurotoxicity of TBBPA/TiO2 NP mixtures. Specifically, zebrafish embryos were exposed to solvent control (0.1% DMSO), 2 μM TBBPA, 0.1 mg/L TiO2 NP, and their mixture from 8 to 120 h post fertilization (hpf), and motor/social behavioral assessments were conducted on embryos/larvae at different developmental stages. Our results showed that TBBPA/TiO2 NP single or co-exposures increased spontaneous movement, decreased touch response and swim speed, and affected social behaviors of light/dark preference, shoaling, mirror attack and social contact. In particular, many of these phenotypes were manifested with higher magnitude of changes from the mixture exposure. These behavioral deficits were also accompanied with increased cell death in olfactory region and neuromasts in the lateral line system, increased ROS in gallbladder, pancreas, liver, and intestine, as well as increased lipid peroxidation and decreased ATP levels in whole larval tissue homogenates. Further, genes coding for key cell apoptosis marker and antioxidant enzyme were significantly upregulated by these two chemicals, in particular to their mixture. Interestingly, the co-presence of TBBPA also increased the mean particle size of TiO2 NP in the exposure solutions and the TiO2 NP content in larval tissue. Together, our analysis suggests that TBBPA/TiO2 NP induced behavioral changes may be due to physical accumulation of these two chemicals in the target organs, and TiO2 NP may serve as carriers for increased accumulation of TBBPA. To conclude, we demonstrated that TBBPA/TiO2 NP together cause increased bioaccumulation of TiO2, and heightened responses in behavior, cell apoptosis and oxidative stress. Our findings also highlight the importance of toxicity assessment using chemical mixtures.

Regulatory T (Treg) cells are a subtype of CD4+ T cells that play a significant role in the protection from autoimmunity and the maintenance of immune tolerance via immune regulation. Epigenetic modifications of Treg cells (i.e., cytosine methylation at the promoter region of the transcription factor, Forkhead Box P3) have been found to be closely associated with allergic diseases, including allergic rhinitis, asthma, and food allergies. In this study, we highlighted the recent evidence on the contribution of epigenetic modifications in Treg cells to the pathogenesis of allergic diseases. Moreover, we also discussed directions for future clinical treatment approaches, with a particular emphasis on Treg cell-targeted therapies for allergic disorders.

The S-phase checkpoint plays an essential role in regulation of the ribonucleotide reductase (RNR) activity to maintain the dNTP pools. How eukaryotic cells respond appropriately to different levels of replication threats remains elusive. Here, we have identified that a conserved GSK-3 kinase Mck1 cooperates with Dun1 in regulating this process. Deleting MCK1 sensitizes dun1Δ to hydroxyurea (HU) reminiscent of mec1Δ or rad53Δ. While Mck1 is downstream of Rad53, it does not participate in the post-translational regulation of RNR as Dun1 does. Mck1 phosphorylates and releases the Crt1 repressor from the promoters of DNA damage-inducible genes as RNR2-4 and HUG1. Hug1, an Rnr2 inhibitor normally silenced, is induced as a counterweight to excessive RNR. When cells suffer a more severe threat, Mck1 inhibits HUG1 transcription. Consistently, only a combined deletion of HUG1 and CRT1, confers a dramatic boost of dNTP levels and the survival of mck1Δdun1Δ or mec1Δ cells assaulted by a lethal dose of HU. These findings reveal the division-of-labor between Mck1 and Dun1 at the S-phase checkpoint pathway to fine-tune dNTP homeostasis.

The temporal slip behavior of a fault from displaced landforms when there are no chronological data remains poorly understood. The southern segment of the Xiaojiang fault zone (XJFZ) plays an important role in accommodating the lateral extrusion of the SE Tibetan plateau. However, there are few reports on the evolution of the offset landforms and slip behavior of the fault due to the dense vegetation in the region. Here, offset landforms along the Jianshui fault (JSF) in the southern segment of the XJFZ are systematically interpreted and measured using high-resolution satellite imagery, field investigations, and airborne lidar. The risers on the right banks of three stream channels feature similar left-lateral offset characteristics near the town of Dongshanzhai. The left-lateral offsets consist of multiple inflections produced by seismic events, and the offset of each event is similar. These inflections are distributed downstream in a stair-stepped manner. The newly formed inflections are located close to the fault, and the earlier formed ones are eroded by flowing water and migrate downstream. The difference between the amount of downstream erosion of two adjacent inflections varies. Assuming the stream’s long-term erosion rate remains steady, the estimated time intervals between seismic events are different. Combined with the cumulative offset probability density calculation for 92 offsets, the JSF is considered to show a nonperiodic characteristic earthquake recurrence pattern. We also propose a multistage offset evolution model of the stream channel riser. This provides a new way to analyze the seismic recurrence pattern of the fault over a relative time scale.

Spinal cord stimulation (SCS) has been shown to improve the consciousness levels of patients with disorder of consciousness (DOC). However, the underlying mechanisms of SCS remain poorly understood. This study recorded resting-state electroencephalograms (EEG) from 16 patients with minimally conscious state (MCS), before and after SCS, and investigated the mechanisms of SCS on the neuronal dynamics in MCS patients. Detrended fluctuation analysis (DFA), combined with surrogate data method, was employed to measure the long-range temporal correlations (LRTCs) of the EEG signals. A surrogate data method was utilized to acquire the genuine DFA exponents (GDFAE) reflecting the genuine LRTCs of brain activity. We analyzed the GDFAE in four brain regions (frontal, central, posterior, and occipital) at five EEG frequency bands [delta (1–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz), and gamma (30–45 Hz)]. The GDFAE values ranged from 0.5 to 1, and showed temporal and spatial variation between the pre-SCS and the post-SCS states. We found that the channels with GDFAE spread wider after SCS. This phenomenon may indicate that more cortical areas were engaged in the information integration after SCS. In addition, the GDFAE values increased significantly in the frontal area at delta, theta, and alpha bands after SCS. At the theta band, a significant increase in GDFAE was observed in the occipital area. No significant change was found at beta or gamma bands in any brain region. These findings show that the enhanced LRTCs after SCS occurred primarily at low-frequency bands in the frontal and occipital regions. As the LRTCs reflect the long-range temporal integration of EEG signals, our results indicate that information integration became more “complex” after SCS. We concluded that the brain activities at low-frequency oscillations, particularly in the frontal and occipital regions, were improved by SCS.

Ultrasound-assisted extraction (UAE) was applied to extract rutin (RU), nicotiflorin (NI), narcissoside (NA), kaempferol (KA), isorhamnetin (IS), quercetin (QU), and total flavonoids of Flos Sophorae Immaturus (TFFSI) from Flos Sophorae Immaturus (FSI). Through single factor test and response surface methodology (RSM), the optimal extraction conditions were concluded as follows: ethanol concentration 70%, time 30 min, temperature 61 °C, and liquid/solid ratio 15.30 mL/g, respectively. The actual extraction rates of RU, NI, NA, KA, IS, QU, and TFFSI were 14.6101%, 2.9310%, 7.1987%, 0.1041%, 0.4920%, 2.7998%, and 26.4260%, respectively. The experimental results demonstrated that the extraction method with accuracy and efficiency could be used for the comprehensive evaluation quality control of extracts from FSI. The antioxidant activities of hydroalcoholic extraction from FSI on 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+), superoxide anion (•O2−) free radicals, and ferric reducing/antioxidant power (FRAP) were assessed. The results showed that the antioxidation activities of extracts on DPPH, ABTS•+, and •O2− free radicals were reached 89.29%, 97.86%, and 56.61%, and 81.4% in FRAP at 1.0 mg/mL, respectively. The antioxidant capacity of FSI extract was positively correlated with the amount of total flavonoids.

Lithium plating is considered an undesirable side reaction because it can induce capacity fading and pose safety concerns in Li-ion batteries. The timely detection of lithium plating onset is crucial for both mechanistic investigations and ensuring the safe and durable operation of batteries. In this study, discharging tests were conducted by varying the set capacity in graphite/Li cells to induce lithium plating on the graphite electrode. Based on a comprehensive analysis of the voltage curves and the morphological characterization of disassembled cells, the inflection point on the differential voltage curve during the discharging process was identified as the precise onset time of lithium plating. Electrochemical models were developed to further elucidate the mechanisms governing the onset of lithium plating. Compared with the model based on the potential criterion, the model employing the concentration criterion demonstrated enhanced precision in predicting lithium plating, particularly under high C rates. Based on the model with the concentration criterion, the discharging protocol was optimized parametrically to achieve high discharging efficiency and restrain lithium plating. This nuanced understanding contributes to determining the onset of lithium plating more accurately, thereby facilitating a more robust battery design and durable yet fast charging protocols. [ABSTRACT FROM AUTHOR]

Under salt stress, recretohalophyte Plumbago auriculata tetraploids enhance salt tolerance by increasing selective secretion of Na+ compared with that in diploids, although the mechanism is unclear. Using non-invasive micro-test technology, the effect of salt gland Ca2+ content on Na+ and K+ secretion were investigated in diploid and tetraploid P. auriculata under salt stress. Salt gland Ca2+ content and secretion rates of Na+ and K+ were higher in tetraploids than in diploids under salt stress. Addition of exogenous Ca2+ increased the Ca2+ content of the salt gland in diploids and is accompanied by an increase in the rate of Na+ and K+ secretion. With addition of a Ca2+ channel inhibitor, diploid salt glands retained large amounts of Ca2+, leading to higher Ca2+ content and Na+ secretion rate than those of tetraploids. Inhibiting H2O2 generation and H+-ATPase activity altered Na+ and K+ secretion rates in diploids and tetraploids under salt stress, indicating involvement in regulating Na+ and K+ secretion. Our results indicate that the increased Na+ secretion rate of salt gland in tetraploids under salt stress was associated with elevated Ca2+ content in salt gland. [ABSTRACT FROM AUTHOR]