Anxiety is common in patients suffering from chronic pain. Here, we report anxiety-like behaviors in mouse models of chronic pain and reveal that nNOS-expressing neurons in ventromedial prefrontal ...cortex (vmPFC) are essential for pain-induced anxiety but not algesia, using optogenetic and chemogenetic strategies. Additionally, we determined that excitatory projections from the posterior subregion of paraventricular thalamic nucleus (pPVT) provide a neuronal input that drives the activation of vmPFC nNOS-expressing neurons in our chronic pain models. Our results suggest that the pain signal becomes an anxiety signal after activation of vmPFC nNOS-expressing neurons, which causes subsequent release of nitric oxide (NO). Finally, we show that the downstream molecular mechanisms of NO likely involve enhanced glutamate transmission in vmPFC CaMKIIα-expressing neurons through S-nitrosylation-induced AMPAR trafficking. Overall, our data suggest that pPVT excitatory neurons drive chronic pain-induced anxiety through activation of vmPFC nNOS-expressing neurons, resulting in NO-mediated AMPAR trafficking in vmPFC pyramidal neurons.
Mice are widely used as experimental models for gut microbiome (GM) studies, yet the majority of mouse GM members remain uncharacterized. Here, we report the construction of a mouse gut microbial ...biobank (mGMB) that contains 126 species, represented by 244 strains that have been deposited in the China General Microorganism Culture Collection. We sequence and phenotypically characterize 77 potential new species and propose their nomenclatures. The mGMB includes 22 and 17 species that are significantly enriched in ob/ob and wild-type C57BL/6J mouse cecal samples, respectively. The genomes of the 126 species in the mGMB cover 52% of the metagenomic nonredundant gene catalog (sequence identity ≥ 60%) and represent 93-95% of the KEGG-Orthology-annotated functions of the sampled mouse GMs. The microbial and genome data assembled in the mGMB enlarges the taxonomic characterization of mouse GMs and represents a useful resource for studies of host-microbe interactions and of GM functions associated with host health and diseases.
The blood-spinal cord barrier (BSCB), a physical barrier between the blood and spinal cord parenchyma, prevents the toxins, blood cells, and pathogens from entering the spinal cord and maintains a ...tightly controlled chemical balance in the spinal environment, which is necessary for proper neural function. A BSCB disruption, however, plays an important role in primary and secondary injury processes related to spinal cord injury (SCI). After SCI, the structure of the BSCB is broken down, which leads directly to leakage of blood components. At the same time, the permeability of the BSCB is also increased. Repairing the disruption of the BSCB could alleviate the SCI pathology. We review the morphology and pathology of the BSCB and progression of therapeutic methods targeting BSCB in SCI.
Abstract
Background
In gut microbiome studies, the cultured gut microbial resource plays essential roles, such as helping to unravel gut microbial functions and host-microbe interactions. Although ...several major studies have been performed to elucidate the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species have not been cultured to date. Large-scale gut microbial isolation and identification as well as availability to the public are imperative for gut microbial studies and further characterizing human gut microbial functions.
Results
In this study, we constructed a human Gut Microbial Biobank (hGMB; homepage:
hgmb.nmdc.cn
) through the cultivation of 10,558 isolates from 31 sample mixtures of 239 fresh fecal samples from healthy Chinese volunteers, and deposited 1170 strains representing 400 different species in culture collections of the International Depository Authority for long-term preservation and public access worldwide. Following the rules of the International Code of Nomenclature of Prokaryotes, 102 new species were characterized and denominated, while 28 new genera and 3 new families were proposed. hGMB represented over 80% of the common and dominant human gut microbial genera and species characterized from global human gut 16S rRNA gene amplicon data (
n
= 11,647) and cultured 24 “most-wanted” and “medium priority” taxa proposed by the Human Microbiome Project. We in total sequenced 115 genomes representing 102 novel taxa and 13 previously known species. Further in silico analysis revealed that the newly sequenced hGMB genomes represented 22 previously uncultured species in the Unified Human Gastrointestinal Genome (UHGG) and contributed 24 representatives of potentially “dark taxa” that had not been discovered by UHGG. The nonredundant gene catalogs generated from the hGMB genomes covered over 50% of the functionally known genes (KEGG orthologs) in the largest global human gut gene catalogs and approximately 10% of the “most wanted” functionally unknown proteins in the FUnkFams database.
Conclusions
A publicly accessible human Gut Microbial Biobank (hGMB) was established that contained 1170 strains and represents 400 human gut microbial species. hGMB expands the gut microbial resources and genomic repository by adding 102 novel species, 28 new genera, 3 new families, and 115 new genomes of human gut microbes.
Aims
Acyl‐CoA synthetase long chain family member 4 (ACSL4) is closely related to tumor genesis and development in certain tissues. However, the function of ACSL4 in early brain injury (EBI) caused ...by subarachnoid hemorrhage (SAH) is unclear. In this study, we investigated the expression patterns and role of ACSL4 in SAH and post‐SAH EBI using a rat model of SAH.
Methods
The rat model of SAH was induced by autologous blood injection into the prechiasmatic cistern of rats. We also used two specific inhibitors of ferroptosis (Ferrostatin‐1 and Liproxstatin‐1) to investigate the role of ferroptosis in EBI.
Results
We found that ACSL4 levels in brain tissue increased significantly in post‐SAH EBI. Inhibiting the expression of ACSL4 using small interfering RNAs alleviated inflammation, blood‐brain barrier (BBB) impairment, oxidative stress, brain edema, and behavioral and cognitive deficits, and increased the number of surviving neurons, after SAH. Similar effects were obtained by suppressing ferroptosis.
Conclusions
ACSL4 exacerbated SAH‐induced EBI by mediating ferroptosis. These findings may provide a theoretical basis for potential therapy aimed at alleviating post‐SAH EBI.
ACSL4 levels in brain tissue of rats increase significantly in EBI and brain damage after SAH could be reduced by down‐regulation of ACSL4. ACSL4 could trigger ferroptosis and aggravate brain damage via catalyzing lipid metabolism. It may provide a theoretical basis for potential therapy to alleviate EBI after SAH
Metal‐organic frameworks (MOFs), as a class of new inorganic‐organic hybrid crystal materials, could have important applications in near‐infrared (NIR) photothermal conversion. Herein, a new ...charge‐transfer MOF (Co‐MOF) with mixed ligands of H4TTFTB and bpmNDI incorporating redox‐active tetrathiafulvalene/naphthalene diimide (TTF/NDI) units into one system is reported. Due to the presence of TTF/NDI oxidative and reductive couples, stable radicals can be observed in the MOF. In addition, charge transfer from the electron donor (TTF) to the acceptor (NDI) results in a broad absorption in the NIR region. The Co‐MOF exhibited an efficient photothermal effect induced by irradiation with a NIR laser. Under the 808 nm laser (0.7 W cm−2) illumination, the temperature of the Co‐MOF increased from room temperature to 201 °C in only 10 s. Furthermore, a series of polydimethylsiloxane (PDMS) films doped with trace amounts of Co‐MOF showed efficient NIR photothermal conversion. When a Co‐MOF@PDMS (0.6 wt %) film is irradiated by 808 nm laser with power of 0.5 W cm−2, it′s temperature can reach a plateau at 62 °C from 20 °C within 100 s. Our experimental results from the Co‐MOF@PDMS film demonstrate that the effectiveness and feasibility of the material is promising for photothermal applications.
The heat is on: A charge‐transfer MOF based on redox‐active TTF/NDI units has been prepared and structurally characterized. Due to the efficient charge‐transfer absorption in the NIR region, the MOF shows excellent photothermal conversion performance. Co‐MOF@PDMS composite films have been studied and could be new candidates for stable and processable materials in photothermal therapy.
Oral squamous cell carcinoma (OSCC) is a highly aggressive cancer and the fourth leading malignancy among males in Taiwan. Some pathogenic bacteria are associated with periodontitis and oral cancer. ...However, the comprehensive profile of the oral microbiome during the cancer's progression from the early stage to the late stage is still unclear. We profiled the oral microbiota and identified bacteria biomarkers associated with OSCC. The microbiota of an oral rinse from 51 healthy individuals and 197 OSCC patients at different stages were investigated using 16S rRNA V3V4 amplicon sequencing, followed by bioinformatics and statistical analyses. The oral microbiota communities from stage 4 patients showed significantly higher complexity than those from healthy controls. The populations also dynamically changed with the cancer's progression from stage 1 to stage 4. The predominant phyla in the oral samples showed variation in the relative abundance of
, and
. The abundance of
increased significantly with the progression of oral cancer from the healthy controls (2.98%) to OSCC stage 1 (4.35%) through stage 4 (7.92%). At the genus level, the abundance of
increased, while the number of
, and
decreased with cancer progression.
, and
were associated with OSCC, and they progressively increased in abundance from stage 1 to stage 4. The abundances of
, and
were inversely associated with OSCC progression. We selected a bacterial marker panel of three bacteria (upregulated
, down-regulated
, and
), which had an AUC of 0.956 (95% CI = 0.925-0.986) in discriminating OSCC stage 4 from the healthy controls. Furthermore, the functional prediction of oral bacterial communities showed that genes involved in carbohydrate-related metabolism, such as methane metabolism, and energy-metabolism-related parameters, such as oxidative phosphorylation and carbon fixation in photosynthetic organisms, were enriched in late-stage OSCC, while those responsible for amino acid metabolism, such as folate biosynthesis and valine, leucine, and isoleucine biosynthesis, were significantly associated with the healthy controls. In conclusion, our results provided evidence of oral bacteria community changes during oral cancer progression and suggested the possibility of using bacteria as OSCC diagnostic markers.
is a Chinese endemic genus comprising two species,
and
. In this study, we sequenced the complete chloroplast (cp) genomes of these two species and of their relative
. Illumina sequencing technology ...was used to compare sequences, elucidate the intra- and interspecies variations, and infer the phylogeny relationship with other Ranunculaceae family species. A typical quadripartite structure was detected, with a genome size from 158,473 to 158,512 bp, consisting of a pair of inverted repeats separated by a small single-copy region and a large single-copy region. We analyzed the nucleotide diversity and repeated sequences components and conducted a positive selection analysis by the codon-based substitution on single-copy coding sequence (CDS). Seven regions were found to possess relatively high nucleotide diversity, and numerous variable repeats and simple sequence repeats (SSR) markers were detected. Six single-copy genes (
,
,
,
,
, and
) resulted to have high posterior probabilities of codon sites in the positive selection analysis, which means that the six genes may be under a great selection pressure. The visualization results of the six genes showed that the amino acid properties across each column of all species are variable in different genera. All these regions with high nucleotide diversity, abundant repeats, and under positive selection will provide potential plastid markers for further taxonomic, phylogenetic, and population genetics studies in
and its relatives. Phylogenetic analyses based on the 79 single-copy genes, the whole complete genome sequences, and all CDS sequences showed same topologies with high support, and
was closely clustered with
within the
genus, with
as their closest relative. Therefore, the complete cp genomes in
species provide interesting insights and valuable information that can be used to identify related species and reconstruct their phylogeny.
Cytoskeletal proteins are involved in neuronal survival.Brain-derived neurotrophic factor can increase expression of cytoskeletal proteins during regeneration after axonal injury.However,the effect ...of neural stem cells genetically modified by brain-derived neurotrophic factor transplantation on neuronal survival in the injury site still remains unclear.To examine this,we established a rat model of traumatic brain injury by controlled cortical impact.At 72 hours after injury,2 × 10~7 cells/m L neural stem cells overexpressing brain-derived neurotrophic factor or naive neural stem cells（3 m L） were injected into the injured cortex.At 1–3 weeks after transplantation,expression of neurofilament 200,microtubule-associated protein 2,actin,calmodulin,and beta-catenin were remarkably increased in the injury sites.These findings confirm that brain-derived neurotrophic factor-transfected neural stem cells contribute to neuronal survival,growth,and differentiation in the injury sites.The underlying mechanisms may be associated with increased expression of cytoskeletal proteins and the Wnt/β-catenin signaling pathway.
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