Molecular Architecture of the SARS-CoV-2 Virus.

SARS-CoV-2 is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins, the detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryoelectron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in pre- and postfusion conformations were determined to average resolutions of 8.7-11 Å. Compositions of the N-linked glycans from the native spikes were analyzed by mass spectrometry, which revealed overall processing states of the native glycans highly similar to that of the recombinant glycoprotein glycans. The native conformation of the ribonucleoproteins (RNPs) and their higher-order assemblies were revealed. Overall, these characterizations revealed the architecture of the SARS-CoV-2 virus in exceptional detail and shed light on how the virus packs its ∼30-kb-long single-segmented RNA in the ∼80-nm-diameter lumen.

Force-induced tail-autotomy mitochondrial fission and biogenesis of matrix-excluded mitochondrial-derived vesicles for quality control.

Mitochondria constantly fuse and divide for mitochondrial inheritance and functions. Here, we identified a distinct type of naturally occurring fission, tail-autotomy fission, wherein a tail-like thin tubule protrudes from the mitochondrial body and disconnects, resembling autotomy. Next, utilizing an optogenetic mitochondria-specific mechanostimulator, we revealed that mechanical tensile force drives tail-autotomy fission. This force-induced fission involves DRP1/MFF and endoplasmic reticulum tubule wrapping. It redistributes mitochondrial DNA, producing mitochondrial fragments with or without mitochondrial DNA for different fates. Moreover, tensile force can decouple outer and inner mitochondrial membranes, pulling out matrix-excluded tubule segments. Subsequent tail-autotomy fission separates the matrix-excluded tubule segments into matrix-excluded mitochondrial-derived vesicles (MDVs) which recruit Parkin and LC3B, indicating the unique role of tail-autotomy fission in segregating only outer membrane components for mitophagy. Sustained force promotes fission and MDV biogenesis more effectively than transient one. Our results uncover a mechanistically and functionally distinct type of fission and unveil the role of tensile forces in modulating fission and MDV biogenesis for quality control, underscoring the heterogeneity of fission and mechanoregulation of mitochondrial dynamics.

In situ architecture and membrane fusion of SARS-CoV-2 Delta variant.

Among the current five Variants of Concern, infections caused by SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, the architecture of intact Delta virions remains veiled. Moreover, pieces of molecular evidence for the detailed mechanism of S-mediated membrane fusion are missing. Here, we showed the pleomorphic nature of Delta virions from electron beam inactivated samples and reported the in situ structure and distribution of S on the authentic Delta variant. We also captured the virus-virus fusion events, which provided pieces of structural evidence for Delta's attenuated dependency on cellular factors for fusion activation, and proposed a model of S-mediated membrane fusion. Besides, site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S than that of the WT S. Together, these results disclose distinctive factors of Delta being the most virulent SARS-CoV-2 variant.

EEF1D stabilized by SRSF9 promotes colorectal cancer via enhancing the proliferation and metastasis.

Colorectal cancer (CRC) is the third most common cancer and causes high mortality worldwide. Although CRC has been studied widely, the molecular mechanism is not completely known. Eukaryotic translation elongation factor 1 delta (EEF1D) participates in the progression of various tumors, however, the effect of EEF1D on CRC remains unclear. Here, we aimed to identify the potential mechanism of EEF1D in CRC. The expression levels of EEF1D were assessed in CRC samples. Functional analysis of EEF1D in CRC was detected in vitro and in vivo. The regulatory mechanism of EEF1D was identified with RNA immunoprecipitation, RNA pull-down assay, and proteomics analysis. Our findings confirmed that EEF1D was upregulated in human CRC tissues. Functionally, EEF1D overexpression accelerated cell proliferation and metastasis, whereas EEF1D knockdown inhibited cell proliferation and metastasis both in vitro and in vivo CRC models. Furthermore, we showed that EEF1D was upregulated by SRSF9 via binding to 3'UTR of EEF1D mRNA. EEF1D knockdown reversed the malignant phenotype induced by SRSF9 overexpression. These findings demonstrated that EEF1D promotes CRC progression, and EEF1D may be a molecular target against CRC.

Scalable live-attenuated SARS-CoV-2 vaccine candidate demonstrates preclinical safety and efficacy.

Successfully combating the COVID-19 pandemic depends on mass vaccination with suitable vaccines to achieve herd immunity. Here, we describe COVI-VAC, the only live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine currently in clinical development. COVI-VAC was developed by recoding a segment of the viral spike protein with synonymous suboptimal codon pairs (codon-pair deoptimization), thereby introducing 283 silent (point) mutations. In addition, the furin cleavage site within the spike protein was deleted from the viral genome for added safety of the vaccine strain. Except for the furin cleavage site deletion, the COVI-VAC and parental SARS-CoV-2 amino acid sequences are identical, ensuring that all viral proteins can engage with the host immune system of vaccine recipients. COVI-VAC was temperature sensitive in vitro yet grew robustly (>107 plaque forming units/mL) at the permissive temperature. Tissue viral loads were consistently lower, lung pathology milder, and weight loss reduced in Syrian golden hamsters (Mesocricetus auratus) vaccinated intranasally with COVI-VAC compared to those inoculated with wild-type (WT) virus. COVI-VAC inoculation generated spike IgG antibody levels and plaque reduction neutralization titers similar to those in hamsters inoculated with WT virus. Upon challenge with WT virus, COVI-VAC vaccination reduced lung challenge viral titers, resulted in undetectable virus in the brain, and protected hamsters from almost all SARS-CoV-2-associated weight loss. Highly attenuated COVI-VAC is protective at a single intranasal dose in a relevant in vivo model. This, coupled with its large-scale manufacturing potential, supports its potential use in mass vaccination programs.

Corrective mechanisms of motion extrapolation.

Transmission and processing of sensory information in the visual system takes time. For motion perception, our brain can overcome this intrinsic neural delay through extrapolation mechanisms and accurately predict the current position of a continuously moving object. But how does the system behave when the motion abruptly changes and the prediction becomes wrong? Here we address this question by studying the perceived position of a moving object with various abrupt motion changes by human observers. We developed a task in which a bar is monotonously moving horizontally, and then motion suddenly stops, reverses, or disappears-then-reverses around two vertical stationary reference lines. Our results showed that participants overestimated the position of the stopping bar but did not perceive an overshoot in the motion reversal condition. When a temporal gap was added at the reverse point, the perceptual overshoot of the end point scaled with the gap durations. Our model suggests that the overestimation of the object position when it disappears is not linear as a function of its speeds but gradually fades out. These results can thus be reconciled in a single process where there is an interplay of the cortical motion prediction mechanisms and the late sensory transient visual inputs.

"They're scared that somebody's gonna judge them": Female African American youth in foster care's perspectives on sexual and reproductive health communication with caregivers.

BACKGROUND: Obtaining accurate information is critical for youth's sexual and reproductive health (SRH). Youth not in foster care often learn about SRH from their biological parents. Separated from their biological parents, youth in care depend on healthcare providers and caregivers for SRH information. However, they often receive insufficient information and feel unsupported in meeting their needs for SRH information. PURPOSE: This study explored female African American adolescents in foster care's perspectives on effective SRH communication with caregivers to help them avoid sexual risks. METHODS: A qualitative study was conducted using semi-structured interviews. We used purposive sampling to recruit 16 adolescents aged 18 to 20 years old with a history of foster care placement. The transcribed interviews underwent inductive thematic analysis. The Positive Youth Development theory underpinned this research. RESULTS: Two prominent themes emerged: establishing a relationship and preferred communication approach. Youth reported that for caregivers to engage in effective SRH communication, they must first establish a relationship by being aware of the youth's childhood trauma, building trust, having patience, and being vulnerable. Youth also appreciated caregivers who ensured comfortability and were honest and straightforward. DISCUSSION: Caregivers should be trained on adverse childhood experiences, trauma-informed approaches, SRH knowledge, and communication. IMPLICATIONS TO PRACTICE: Healthcare providers should make use of the time spent with youth and discuss SRH topics during clinical encounters. This time spent with youth may be their only chance to obtain accurate SRH information. Youth's perspectives regarding communication about SRH should be implemented in future SRH communication interventions.

Role of corticosteroids in the treatment of critically ill sepsis patients: a meta-analysis review.

OBJECTIVE: It was to systematically evaluate the effect of corticosteroids on 28d all-cause mortality (ACM), in-hospital death rate, and ICU death rate in critically ill sepsis patients. METHODS: PubMed, Embase, and Medline databases were used to screen the published literatures on the therapeutic effect of corticosteroids in the treatment of critically ill sepsis patients. After evaluating the quality of the included literatures, RevMan 5.3 software was used for meta-analysis. 4524 literatures regarding the application of corticosteroids to treat critically ill sepsis patients were preliminarily searched. After screening was carried out, 9 literatures were finally included. 2,850 patients were treated with corticosteroids and 2867 patients were treated with placebo. RESULTS: The meta-analysis of the effect of corticosteroids versus placebo on 28dACM showed [OR = 0.87, 95% CI 0.78-0.98, Z = 2.22, P = 0.03], P < 0.05; the meta-analysis of the outcome of corticosteroids versus placebo on ICU death rate showed [OR = 0.77, 95% CI 0.63-0.94, Z = 2.60, P = 0.009], P < 0.05; and the meta-analysis of the effect of corticosteroids versus placebo on in-hospital death rate showed [OR = 0.80, 95% CI 0.66-0.96, Z = 2.34, P = 0.002], P < 0.05. CONCLUSION: In summary, corticosteroids can reduce the death rate of critically ill sepsis patients to a certain extent and have good clinical application value.

Patterns and drivers of anaerobic nitrogen transformations in sediments of thermokarst lakes.

Significant attention has been given to the way in which the soil nitrogen (N) cycle responds to permafrost thaw in recent years, yet little is known about anaerobic N transformations in thermokarst lakes, which account for more than one-third of thermokarst landforms across permafrost regions. Based on the N isotope dilution and tracing technique, combined with qPCR and high-throughput sequencing, we presented large-scale measurements of anaerobic N transformations of sediments across 30 thermokarst lakes over the Tibetan alpine permafrost region. Our results showed that gross N mineralization, ammonium immobilization, and dissimilatory nitrate reduction rates in thermokarst lakes were higher in the eastern part of our study area than in the west. Denitrification dominated in the dissimilatory nitrate reduction processes, being two and one orders of magnitude higher than anaerobic ammonium oxidation (anammox) and dissimilatory nitrate reduction to ammonium (DNRA), respectively. The abundances of the dissimilatory nitrate reduction genes (nirK, nirS, hzsB, and nrfA) exhibited patterns consistent with sediment N transformation rates, while α diversity did not. The inter-lake variability in gross N mineralization and ammonium immobilization was dominantly driven by microbial biomass, while the variability in anammox and DNRA was driven by substrate supply and organic carbon content, respectively. Denitrification was jointly affected by nirS abundance and organic carbon content. Overall, the patterns and drivers of anaerobic N transformation rates detected in this study provide a new perspective on potential N release, retention, and removal upon the formation and development of thermokarst lakes.

Design and Simulation of Au/SiO2 Nanospheres Based on SPR Refractive Index Sensor.

In this paper, three different structures of surface plasmon resonance (SPR) sensors based on the Kretschmann configuration: Au/SiO2 thin film structure, Au/SiO2 nanospheres and Au/SiO2 nanorods are designed by adding three different forms of SiO2 materials behind the gold film of conventional Au-based SPR sensors. The effects of SiO2 shapes on the SPR sensor are investigated through modeling and simulation with the refractive index of the media to be measured ranging from 1.330 to 1.365. The results show that the sensitivity of Au/SiO2 nanospheres could be as high as 2875.4 nm/RIU, which is 25.96% higher than that of the sensor with a gold array. More interestingly, the increase in sensor sensitivity is attributed to the change in SiO2 material morphology. Therefore, this paper mainly explores the influence of the shape of the sensor-sensitizing material on the performance of the sensor.

Stochastic processes regulate belowground community assembly in alpine grasslands on the Tibetan Plateau.

Understanding biogeographical patterns and underlying processes of belowground community assembly is crucial for predicting soil functions and their responses to global environmental change. However, little is known about potential differences of belowground community assembly among bacteria, fungi, protists and soil animals, particularly for alpine ecosystems. Based on the combination of large-scale field sampling, high-throughput marker-gene sequencing and multiple statistical analyses, we explored patterns and drivers of belowground community assembly in alpine grasslands on the Tibetan Plateau. Our results revealed that the distance-decay rates varied among trophic levels, with organisms of higher trophic level having weaker distance-decay pattern. The spatial and environmental variables explained limited variations of belowground communities. By contrast, the stochastic processes, mainly consisting of dispersal limitation and drift, played a primary role in regulating belowground community assembly. Moreover, the relative importance of stochastic processes varied among trophic levels, with the role of dispersal limitation weakening whereas that of drift enhancing in the order of bacteria, fungi, protists and soil animals. These findings advance our understanding of patterns and mechanisms driving belowground community assembly in alpine ecosystems and provide a reference basis for predicting the dynamics of ecosystem functions under changing environment.

Prognostic value of preoperative platelet-related parameters and plasma fibrinogen in patients with non-muscle invasive bladder cancer after transurethral resection of bladder tumor.

Aim: To investigate the prognostic value of preoperative mean platelet volume (MPV), MPV/lymphocyte ratio (MPVLR), MPV/platelet count ratio and plasma fibrinogen in patients with non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). Methods: A total of 371 patients who underwent TURBT were enrolled. The main end points were disease-free survival (DFS) and overall survival (OS). Results: MPVLR, tumor size, tumor number and pathological grade were independent risk factors for postoperative DFS. Age and pathological grade were independent risk factors for postoperative OS. Conclusion: MPVLR is an independent risk factor for DFS in NMIBC patients and could be used as a parameter to predict postoperative tumor recurrence in patients after TURBT.

The current study investigated the prognostic value of preoperative mean platelet volume (MPV), MPV/lymphocyte ratio (MPVLR), MPV/platelet count ratio (MPVPCR) and plasma fibrinogen (PF) in peripheral blood of patients with non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). Included were 371 patients who underwent TURBT and were followed up. A high level of PF indicated worse survival and age and pathological grade were independent risk factors for postoperative survival. High levels of MPV, MPVLR and MPVPCR were associated with recurrence. MPVLR, tumor size, tumor number and pathological grade were independent risk factors for postoperative recurrence. MPVLR could be used as a parameter to predict postoperative tumor recurrence in patients after TURBT.

Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation.

A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity. The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation. Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells. We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure. Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans. These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.

Molecular basis for histone H3 "K4me3-K9me3/2" methylation pattern readout by Spindlin1.

Histone recognition by "reader" modules serves as a fundamental mechanism in epigenetic regulation. Previous studies have shown that Spindlin1 is a reader of histone H3K4me3 as well as "K4me3-R8me2a" and promotes transcription of rDNA or Wnt/TCF4 target genes. Here we show that Spindlin1 also acts as a potent reader of histone H3 "K4me3-K9me3/2" bivalent methylation pattern. Calorimetric titration revealed a binding affinity of 16 nm between Spindlin1 and H3 "K4me3-K9me3" peptide, which is one to three orders of magnitude stronger than most other histone readout events at peptide level. Structural studies revealed concurrent recognition of H3K4me3 and H3K9me3/2 by aromatic pockets 2 and 1 of Spindlin1, respectively. Epigenomic profiling studies showed that Spindlin1 colocalizes with both H3K4me3 and H3K9me3 peaks in a subset of genes enriched in biological processes of transcription and its regulation. Moreover, the distribution of Spindlin1 peaks is primarily associated with H3K4me3 but not H3K9me3, which suggests that Spindlin1 is a downstream effector of H3K4me3 generated in heterochromatic regions. Collectively, our work calls attention to an intriguing function of Spindlin1 as a potent H3 "K4me3-K9me3/2" bivalent mark reader, thereby balancing gene expression and silencing in H3K9me3/2-enriched regions.

Methanogenic Community, CH4 Production Potential and Its Determinants in the Active Layer and Permafrost Deposits on the Tibetan Plateau.

Permafrost thaw could increase methane (CH4) emissions, which largely depends on CH4 production driven by methanogenic archaea. However, large-scale evidence regarding key methanogenic taxa and their relative importance to abiotic factors in mediating methanogenesis remains limited. Here, we explored the methanogenic community, potential CH4 production and its determinants in the active layer and permafrost deposits based on soil samples acquired from 12 swamp meadow sites along a ∼1000 km permafrost transect on the Tibetan Plateau. Our results revealed lower CH4 production potential, mcrA gene abundance, and richness in the permafrost layer than those in the active layer. CH4 production potential in both soil layers was regulated by microbial and abiotic factors. Of the microbial properties, marker OTUs, rather than the abundance and diversity of methanogens, stimulated CH4 production potential. Marker OTUs differed between the two soil layers with hydrogenotrophic Methanocellales and facultative acetoclastic Methanosarcina predominant in regulating CH4 production potential in the permafrost and active layer, respectively. Besides microbial drivers, CH4 production potential increased with the carbon/nitrogen (C/N) ratio in both soil layers and was also stimulated by soil moisture in the permafrost layer. These results provide empirical evidence for model improvements to better predict permafrost carbon feedback to climate warming.

Accommodation and binocular vision changes after wearing orthokeratology lens in 8- to 14-year-old myopic children.

PURPOSE: The study aimed to observe and analyze the dynamic accommodation and binocular vision changes in myopic children after they switched from spectacles to orthokeratology (ortho-k) lenses. METHODS: Thirty-six myopic children aged 8-14 years were enrolled in this prospective, self-controlled study from West China Hospital. General information was gathered, and examinations were performed at baseline and at 1, 3, 6, and 12 months after switching to ortho-k lenses. The examination included assessments of distance/near visual acuity, distance/near horizontal and vertical ocular alignment, distance/near horizontal vergence range, accommodative amplitude, monocular/binocular accommodative facility, accommodative response, positive and negative relative accommodation (PRA/NRA), accommodation convergence/accommodation (AC/A), stereopsis, and reading ability. RESULTS: After the children switched to ortho-k lenses, distance and near ocular alignment showed an exophoric shift (distance: p = 0.001, near: p = 0.002), and the horizontal vergence range decreased by different degrees (convergence: distance blur point (p = 0.002), distance break point (p = 0.005), near blur point (p = 0.011), near break point (p = 0.043); divergence: distance break point (p < 0.001), distance recover point (p < 0.001), near recover point (p = 0.005)). The stereopsis ability (p < 0.001), monocular/binocular accommodative facility (p < 0.001), and PRA (p = 0.010) increased. The accommodative lag (p < 0.001), accommodative amplitude (p < 0.001), and calculated and gradient AC/A (calculated: p = 0.001, gradient: p = 0.025) decreased. The adjusted horizontal and vertical reading times and their ratio decreased (all p < 0.001). CONCLUSION: The subjects showed distance and near exophoric shifts after switching to ortho-k lenses; improvements in accommodative function, stereopsis, and ocular motility; and a decrease in the binocular horizontal vergence range. The relationships between these changes and the ortho-k myopic control effects require further investigation.

Effects of Hyaluronic Acid on Stability of Bleomycin Foam.

BACKGROUND: Bleomycin (BLM) foam sclerotherapy is effective in the treatment of venous malformations (VMs). Foam stability is influenced by factors such as sclerosant concentration, viscosity, and liquid-gas ratio. OBJECTIVE: To investigate whether hyaluronic acid (HA) could increase the stability of BLM foam and to evaluate the safety and efficacy of HA-BLM foam. MATERIALS AND METHODS: Experiment: BLM 6.0 IU + human serum albumin (HSA, 2, 1.95, 1.90, and 1.85 mL, respectively) + 1% HA (0, 0.05, 0.10, and 0.15 mL, respectively) + air 6 mL to create foam using the Tessari method. The foam half-life (FHL) was used to evaluate foam stability. Clinical study: Twenty-eight patients with head and neck VMs were enrolled between June 2018 and August 2019 treated by HA-BLM foam to evaluate the safety and efficacy. RESULTS: The FHL of the BLM foam was 8.46, 8.95, 10.45, and 14.51 minutes, respectively. All patients achieved significant efficacy, and no obvious side effects were observed. CONCLUSION: Addition of HA could improve the stability of BLM foam.

Limits of variation, specific infectivity, and genome packaging of massively recoded poliovirus genomes.

Computer design and chemical synthesis generated viable variants of poliovirus type 1 (PV1), whose ORF (6,189 nucleotides) carried up to 1,297 "Max" mutations (excess of overrepresented synonymous codon pairs) or up to 2,104 "SD" mutations (randomly scrambled synonymous codons). "Min" variants (excess of underrepresented synonymous codon pairs) are nonviable except for P2Min, a variant temperature-sensitive at 33 and 39.5 °C. Compared with WT PV1, P2Min displayed a vastly reduced specific infectivity (si) (WT, 1 PFU/118 particles vs. P2Min, 1 PFU/35,000 particles), a phenotype that will be discussed broadly. Si of haploid PV presents cellular infectivity of a single genotype. We performed a comprehensive analysis of sequence and structures of the PV genome to determine if evolutionary conserved cis-acting packaging signal(s) were preserved after recoding. We showed that conserved synonymous sites and/or local secondary structures that might play a role in determining packaging specificity do not survive codon pair recoding. This makes it unlikely that numerous "cryptic, sequence-degenerate, dispersed RNA packaging signals mapping along the entire viral genome" [Patel N, et al. (2017) Nat Microbiol 2:17098] play the critical role in poliovirus packaging specificity. Considering all available evidence, we propose a two-step assembly strategy for +ssRNA viruses: step I, acquisition of packaging specificity, either (a) by specific recognition between capsid protein(s) and replication proteins (poliovirus), or (b) by the high affinity interaction of a single RNA packaging signal (PS) with capsid protein(s) (most +ssRNA viruses so far studied); step II, cocondensation of genome/capsid precursors in which an array of hairpin structures plays a role in virion formation.

Zweigelt and Niagara skin extracts suppress cyclobutane pyrimidine dimer formation due to UV irradiation in NHEK cells: first attempt.

The grape skins after pressing the juice are a major problem for winery. However, because it contains a large amount of polyphenols, development of effective usages are expected to construct sustainable waste use. In this study, we examined whether grape skin extract is effective for recovery of DNA damage caused by UV irradiation. Extract from Zweigelt and Niagara skin was prepared by methanol, and UV irradiation was performed at 10 mJ/cm2 (250 nm) and 15 mJ/cm2 (290 nm) using human normal skin cells. As results, the decreased cell viability due to UV irradiation was improved by adding Niagara or Zweigelt skin extract. On the other hand, cyclobutane pyrimidine dimer production due to UV irradiation decreased significantly by Niagara or Zweigelt extract. In addition, the effects of grape skin extracts on the expression of sirtuin gene were also examined.

HDAC2 hyperexpression alters hippocampal neuronal transcription and microglial activity in neuroinflammation-induced cognitive dysfunction.

BACKGROUND: Inflammation can induce cognitive dysfunction in patients who undergo surgery. Previous studies have demonstrated that both acute peripheral inflammation and anaesthetic insults, especially isoflurane (ISO), are risk factors for memory impairment. Few studies are currently investigating the role of ISO under acute peri-inflammatory conditions, and it is difficult to predict whether ISO can aggravate inflammation-induced cognitive deficits. HDACs, which are essential for learning, participate in the deacetylation of lysine residues and the regulation of gene transcription. However, the cell-specific mechanism of HDACs in inflammation-induced cognitive impairment remains unknown. METHODS: Three-month-old C57BL/6 mice were treated with single versus combined exposure to LPS injected intraperitoneally (i.p.) to simulate acute abdominal inflammation and isoflurane to investigate the role of anaesthesia and acute peripheral inflammation in cognitive impairment. Behavioural tests, Western blotting, ELISA, immunofluorescence, qRT-PCR, and ChIP assays were performed to detect memory, the expressions of inflammatory cytokines, HDAC2, BDNF, c-Fos, acetyl-H3, microglial activity, Bdnf mRNA, c-fos mRNA, and Bdnf and c-fos transcription in the hippocampus. RESULTS: LPS, but not isoflurane, induced neuroinflammation-induced memory impairment and reduced histone acetylation by upregulating histone deacetylase 2 (HDAC2) in dorsal hippocampal CaMKII+ neurons. The hyperexpression of HDAC2 in neurons was mediated by the activation of microglia. The decreased level of histone acetylation suppressed the transcription of Bdnf and c-fos and the expressions of BDNF and c-Fos, which subsequently impaired memory. The adeno-associated virus ShHdac2, which suppresses Hdac2 after injection into the dorsal hippocampus, reversed microglial activation, hippocampal glutamatergic BDNF and c-Fos expressions, and memory deficits. CONCLUSIONS: Reversing HDAC2 in hippocampal CaMKII+ neurons exert a neuroprotective effect against neuroinflammation-induced memory deficits.