Carbon monoxide-releasing molecule-3 ameliorates traumatic brain injury-induced cardiac dysfunctions via inhibition of pyroptosis and apoptosis.

Traumatic brain injury (TBI) frequently results in cardiac dysfunction and impacts the quality of survivors' life. It has been reported that carbon monoxide-releasing molecule-3 (CORM-3) administration immediately after hemorrhagic shock and resuscitation (HSR) ameliorated the HSR­induced cardiac dysfunctions. The purpose of this study was to determine whether the application of CORM-3 on TBI exerted therapeutic effects against TBI-induced cardiac dysfunctions. Rats were randomly divided into four groups (n = 12) including Sham, TBI, TBI/CORM-3 and TBI/inactive CORM-3 (iCORM-3) groups. TBI was established by a weight-drop model. The rats in the TBI/CORM-3 group and TBI/iCORM-3 group were intravenously injected with CORM-3 and iCORM-3 (4 mg/kg) following TBI, respectively. The time of death in the rats that did not survive within 24 h was recorded. 24 h post-trauma, the cardiac function, pathological change, serum troponin T and creatine kinase-MB (CK-MB) levels, pyroptosis, apoptosis and expressions of TUNEL staining, Gasdermin D (GSDMD), IL-1ß, IL-18, ratio Bax/Bcl-2 were assessed by echocardiography, hematoxylin-eosin staining, chemiluminescence, immunofluorescence, and western blot assays, respectively. TBI-treated rats exhibited dramatically decreased ejection fraction and aggravated myocardial injury, increased mortality rate, elevated levels of serum troponin T and CK-MB, promoted cardiac pyroptosis and apoptosis, and upregulated expressions of cleaved caspase-3, GSDMD N-terminal fragments, IL-1ß, IL-18, and ratio of Bax/Bcl-2, whereas CORM-3 partially reversed these changes. CORM-3 ameliorated TBI-induced cardiac injury and dysfunction. This mechanism may be responsible for the inhibition of pyroptosis and apoptosis in cardiomyocyte.

A Breakthrough in Kitavirids: Genetic Variability, Reverse Genetics, Koch's Postulates, and Transmission of Hibiscus Green Spot Virus 2.

Hibiscus green spot virus 2 (HGSV-2), a member of the genus Higrevirus (family Kitaviridae), is a positive-stranded RNA virus associated with leprosis-like symptoms in citrus and green spots on leaves in hibiscus. HGSV-2 has only been reported in Hawaii, and while it is speculated that mites in the genus Brevipalpus might be responsible for its transmission, proper transmission assays have yet to be conducted. This study characterizes additional citrus and hibiscus isolates of HGSV-2 collected from two Hawaiian Islands. We constructed an infectious cDNA clone from a hibiscus isolate of HGSV-2 collected on Oahu and demonstrated its ability to infect several experimental hosts, including Phaseolus vulgaris, Nicotiana tabacum, and N. benthamiana, as well as natural hosts, Citrus reticulata and Hibiscus arnottianus. Bacilliform virions with varied sizes of 33 to 120 nm (length) and 14 to 70 nm (diameter) were observed in partially purified preparations obtained from agroinoculated leaves. Virus progeny from the infectious cDNA clone was found to be infectious after mechanical transmission to N. benthamiana and to cause local lesions. Finally, an isoline colony of the mite Brevipalpus azores had vector competence to transmit a citrus isolate of HGSV-2 collected from Maui to citrus and hibiscus plants, demonstrating the mite-borne nature of HGSV-2. The infectious cDNA clone developed in this study is the first reverse-genetics system for a kitavirid and will be fundamental to better characterize basic biology of HGSV-2 and its interactions with host plants and mite vectors.

Characterization of Two Novel Viruses Within a Complex Virome from Flowering Ginger in Hawaii.

Flowering ginger (Alpinia purpurata) is economically and culturally important in Hawaii. In the past decade, a slow decline syndrome has impacted the production of this crop in the state. RNA sequencing analyses and virus indexing surveys were done on samples collected from four of the Hawaiian Islands. Viral sequences corresponding to six viruses were recovered from transcriptomic data from samples with virus-like symptoms. Canna yellow mottle virus (CaYMV, genus Badnavirus) and two novel viruses, Alpinia vein clearing virus (ApVCV, genus Ampelovirus) and Alpinia vein streaking virus (ApVSV, genus Betanucleorhabdovirus), were found at a moderate incidence in diseased plants. Conversely, three other viruses, including the two potyviruses, banana bract mosaic virus and bean common mosaic virus, and a badnavirus, banana streak GF virus, were also found but at a low incidence. Virus detection in potential insect vectors and transmission assays identified the mealybug Planococcus citri as a vector of CaYMV and ApVCV, whereas the aphid Pentalonia caladii was identified as a vector of the novel ApVSV. Both P. citri and P. caladii are common pests of flowering ginger in Hawaii. Transmission of ApVSV was achieved using P. caladii colonies either established in the laboratory or naturally feeding on infected plants, although no transmission was obtained using viruliferous aphids originally reared on taro (Colocasia esculenta). Our study provides insights into the potential association between viral infections and the observed decline symptoms of flowering ginger in Hawaii. However, more definitive studies are needed to link single or mixed viral infections with decline symptoms.

Diffusion Models-Based Purification for Common Corruptions on Robust 3D Object Detection.

LiDAR sensors have been shown to generate data with various common corruptions, which seriously affect their applications in 3D vision tasks, particularly object detection. At the same time, it has been demonstrated that traditional defense strategies, including adversarial training, are prone to suffering from gradient confusion during training. Moreover, they can only improve their robustness against specific types of data corruption. In this work, we propose LiDARPure, which leverages the powerful generation ability of diffusion models to purify corruption in the LiDAR scene data. By dividing the entire scene into voxels to facilitate the processes of diffusion and reverse diffusion, LiDARPure overcomes challenges induced from adversarial training, such as sparse point clouds in large-scale LiDAR data and gradient confusion. In addition, we utilize the latent geometric features of a scene as a condition to assist the generation of diffusion models. Detailed experiments show that LiDARPure can effectively purify 19 common types of LiDAR data corruption. Further evaluation results demonstrate that it can improve the average precision of 3D object detectors to an extent of 20% in the face of data corruption, much higher than existing defence strategies.

NLRP3-GABA signaling pathway contributes to the pathogenesis of impulsive-like behaviors and cognitive deficits in aged mice.

BACKGROUND: Perioperative neurocognitive disorders (PND), such as delirium and cognitive impairment, are commonly encountered complications in aged patients. The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is aberrantly synthesized from reactive astrocytes following inflammatory stimulation and is implicated in the pathophysiology of neurodegenerative diseases. Additionally, the activation of NOD-like receptor protein 3 (NLRP3) inflammasome is involved in PND. Herein, we aimed to investigate whether the NLRP3-GABA signaling pathway contributes to the pathogenesis of aging mice's PND. METHODS: 24-month-old C57BL/6 and astrocyte-specific NLRP3 knockout male mice were used to establish a PND model via tibial fracture surgery. The monoamine oxidase-B (MAOB) inhibitor selegiline (1 mg/kg) was intraperitoneally administered once a day for 7 days after the surgery. PND, including impulsive-like behaviors and cognitive impairment, was evaluated by open field test, elevated plus maze, and fear conditioning. Thereafter, pathological changes of neurodegeneration were explored by western blot and immunofluorescence assays. RESULTS: Selegiline administration significantly ameliorated TF-induced impulsive-like behaviors and reduced excessive GABA production in reactive hippocampal astrocytes. Moreover, astrocyte-specific NLRP3 knockout mice reversed TF-induced impulsive-like and cognitive impairment behaviors, decreased GABA levels in reactive astrocytes, ameliorated NLRP3-associated inflammatory responses during the early stage, and restored neuronal degeneration in the hippocampus. CONCLUSIONS: Our findings suggest that anesthesia and surgical procedures trigger neuroinflammation and cognitive deficits, which may be due to NLRP3-GABA activation in the hippocampus of aged mice.

taVNS Alleviates Sevoflurane-Induced Cognitive Dysfunction in Aged Rats Via Activating Basal Forebrain Cholinergic Neurons.

Postoperative cognitive dysfunction (POCD) is a common complication of central nervous system after anesthesia or surgery. Sevoflurane, an inhalation anesthetic, may inhibit cholinergic pathway that induce neuronal death and neuroinflammation, ultimately leading to POCD. Transauricular vagus nerve stimulation (taVNS) has neuroprotective effects in POCD rats, but the mechanisms related to cholinergic system have not been revealed. Sprague-Dawley rats were anesthetized with sevoflurane to construct the POCD model. The immunotoxin 192-IgG-saporin (192-sap) selectively lesioned cholinergic neurons in the basal forebrain, which is the major source of cholinergic projections to hippocampus. After lesion, rats received 5 days of taVNS treatment (30 min per day) starting 24 h before anesthesia. Open field test and Morris water maze were used to test the cognitive function. In this study, rats exposed to sevoflurane exhibited cognitive impairment that was attenuated by taVNS. In addition, taVNS treatment activated cholinergic system in the basal forebrain and hippocampus, and downregulated the expression of apoptosis- and necroptosis-related proteins, such as cleaved Caspase-3 and p-MLKL, in the hippocampus. Meanwhile, the activation of Iba1+ microglial by sevoflurane was reduced by taVNS. 192-sap blocked the cholinergic system activation in the basal forebrain and hippocampus and inhibited taVNS-mediated neuroprotection and anti-inflammation effects in the hippocampus. Generally, our study indicated that taVNS might alleviate sevoflurane-induced hippocampal neuronal apoptosis, necroptosis and microglial activation though activating cholinergic system in the basal forebrain.

First detection and complete genome sequence of a new tobamovirus naturally infecting Hibiscus rosa-sinensis in Hawaii.

High-throughput sequencing was used to analyze Hibiscus rosa-sinensis (family Malvaceae) plants with virus-like symptoms in Hawaii. Bioinformatic and phylogenetic analysis revealed the presence of two tobamoviruses, hibiscus latent Fort Pierce virus (HLFPV) and a new tobamovirus with the proposed name "hibiscus latent Hawaii virus" (HLHV). This is the first report of the complete sequence, genome organization, and phylogenetic characterization of a tobamovirus infecting hibiscus in Hawaii. RT-PCR with virus-specific primers and Sanger sequencing further confirmed the presence of these viruses. Inoculation experiments showed that HLFPV could be mechanically transmitted to Nicotiana benthamiana and N. tabacum, while HLHV could only be mechanically transmitted to N. benthamiana.

Effect of pre-infusion of hypertonic saline on postoperative delirium in geriatric patients undergoing shoulder arthroscopy: a randomized controlled trial.

BACKGROUND: Neuroinflammation may be a potential mechanism of postoperative delirium (POD) in geriatric patients, and hypertonic saline (HS) has immunomodulatory properties. The purpose of this study was to investigate whether HS could reduce the incidence of POD in elderly patients and its effect on neutrophil activation and inflammatory cytokine expression. METHODS: We studied the effect of pre-infusion of 4 mL/kg 3% hypertonic saline vs. 4 mL/kg 0.9% normal saline on POD in patients undergoing shoulder arthroscopy in a prospective, randomized, double-blind, controlled trial. Neutrophil surface molecules (CD11b, CD66b and CD64) were analyzed by flow cytometry. Circulating concentrations of inflammatory factors IL-1ß, IL-6, TNF-α and neurological damage factor S100ß were assessed by enzyme immunoassay. The Confusion Assessment Method-Chinese Revision (CAM-CR) was applied for the assessment of POD 1-3 days after surgery. RESULTS: The incidence of POD in group H was significantly lower than that in group N (7.14% vs 26.83%, P = 0.036). The expression levels of inflammatory cytokines ( IL-6 and TNF-α) and neutrophil surface markers (CD11b and CD66b) were significantly lower in group H than in group N at 24 h after surgery (P = 0.018, P < 0.001, P < 0.001, P = 0.024). There were no significant differences in postoperative pain, nausea and vomiting, infection, phlebitis, and patients satisfaction between the two groups. CONCLUSION: Pre-infusion of HS can reduce the incidence of POD and the immune-inflammatory response. TRIAL REGISTRATION: Chinese Clinical Trial Registry (14/4/2022, registration number: ChiCTR2200058681.

Survey of Viruses Infecting Basella alba in Hawaii.

Malabar spinach plants (Basella alba, Basellaceae) with leaves exhibiting symptoms of mosaic, rugosity, and malformation were found in a community garden on Oahu, HI in 2018. Preliminary studies using enzyme-linked immunosorbent assay and reverse-transcription (RT)-PCR identified Basella rugose mosaic virus (BaRMV) in symptomatic plants. However, nucleotide sequence analysis of RT-PCR amplicons indicated that additional potyviruses were also present in the symptomatic Malabar spinach. High-throughput sequencing (HTS) analysis was conducted on ribosomal RNA-depleted composite RNA samples of potyvirus-positive plants from three locations. Assembled contigs shared sequences similar to BaRMV, chilli veinal mottle virus (ChiVMV), Alternanthera mosaic virus (AltMV), Basella alba endornavirus (BaEV), broad bean wilt virus 2 (BBWV2), and Iresine viroid 1. Virus- and viroid-specific primers were designed based on HTS sequencing results and used in RT-PCR and Sanger sequencing to confirm the presence of these viruses and the viroid. We tested 63 additional samples from six community gardens for a survey of viruses in Malabar spinach and found that 21 of them were positive for BaRMV, 57 for ChiVMV, 21 for AltMV, 19 for BaEV, and 14 for BBWV2. This is the first characterization of the virome from B. alba.

Genome sequence of pineapple secovirus B, a second sadwavirus reported infecting Ananas comosus.

The complete genome sequence of pineapple secovirus B (PSV-B), a new virus infecting pineapple (Ananas comosus) on the island of Oahu, Hawaii, was determined by high-throughput sequencing (HTS). The genome comprises two RNAs that are 5,956 and 3,808 nt long, excluding the 3'-end poly-A tails, both coding for a single large polyprotein. The RNA1 polyprotein contains five conserved domains associated with replication, while the RNA2 polyprotein is cleaved into the movement protein and coat protein. PSV-B is representative of a new species in the subgenus Cholivirus (genus Sadwavirus; family Secoviridae), as the level of amino acid sequence identity to recognized members of this subgenus in the Pro-Pol and coat protein regions is below currently valid species demarcation thresholds.

Complete genome organization and characterization of Hippeastrum latent virus.

The complete genome sequences of two carlaviruses were determined by high-throughput sequencing of RNA extracted from ringspot and mosaic, disease symptoms on leaves of spider lily plants (Crinum asiaticum, family Amaryllidaceae) growing as landscape plants in Hawaii. One, named Nerine latent virus (NeLV)-Hawaii with a genome of 8281 nucleotide exhibited the highest nucleotide identity and amino acid similarity of 95.5% and 96.0%, respectively, to the genome sequence of an isolate of NeLV from Narcissus sp. in Australia (JQ395044). The second, named Hippeastrum latent virus (HiLV)-Hawaii with a genome of 8497 nucleotides exhibited the highest nucleotide identity and amino acid similarity, 84.3% and 88.7%, respectively, to the sequence of a previously uncharacterized HiLV isolate from a potted flowering plant, Amaryllis (Hippeastrum hybridum Hort) in Taiwan (DQ098905). The amino acid sequence similarities of replicase (Rep) and coat protein (CP) between HiLV-Hawaii and NeLV-Hawaii were 44.8% and 38.4%, respectively. Results of viral protein Rep and CP amino acid sequence comparisons from various carlaviruses provide evidence that HiLV and NeLV, previously classified as synonymous viruses are in fact unique viruses. This is the first report for the complete sequence, organization, and phylogenetic characterization of HiLV and the first detection of HiLV both in C. asiaticum and in the USA.

Effect of transcutaneous auricular vagus nerve stimulation on delayed neurocognitive recovery in elderly patients.

BACKGROUND: The aim of this study was to investigate whether transauricular vagus nerve stimulation (taVNS) could decrease the incidence of delayed neurocognitive recovery (dNCR) in elderly adults after total joint arthroplasty (TJA). METHODS: A prospective, randomized, double-blind, sham-controlled trial was designed. In total, 124 elderly patients undergoing TJA were enrolled and randomly assigned to taVNS group (n = 62), who received taVNS at 1 h before anesthetic induction until the end of surgery, or sham stimulation (SS) group (n = 62), who received SS in the same manner. Neuropsychological batteries were performed before and at 1 week after surgery to assess the incidence of dNCR. Blood samples were collected before surgery and at 1 day after surgery to detect the activity of cholinesterase (AChE and BChE), as well as the levels of inflammatory factors (TNF-α, IL-1ß, IL-6, and HMGB1) and brain damage factor S100ß. RESULTS: Of 124 patients, 119 completed 1 week neuropsychological tests. The incidence of dNCR was significantly decreased in taVNS group [10% (6/60)] compared with the SS group [27.1% (16/59)] (P < 0.05). Patients who received taVNS had lower blood levels of AChE, BChE, IL-6, HMGB1, and S100ß after surgery (P < 0.05), as compared with those in the SS group. There was no difference in TNF-α between the two groups. CONCLUSION: The taVNS can decrease the incidence of dNCR after TJA in elderly patients, which may be related to the inhibition of inflammatory cytokine production and the reduction of cholinesterase activity.

First report of the hibiscus strain of citrus leprosis virus C2 infecting passionfruit (Passiflora edulis).

In Hawaii, passionfruit (Passiflora edulis; Passifloraceae) is grown primarily in residential properties and community gardens (CG). In 2019, passionfruit plants displaying chlorotic spots on young leaves, and green spots in senescing leaves were observed at two CG in Honolulu. Symptoms resembled those of passionfruit green spot virus (PfGSV) infection in Passiflora spp. (Ramos-González et al. 2020) and of the hibiscus strain of citrus leprosis virus C2 (CiLV-C2H) infection in hibiscus in Hawaii (Melzer et al. 2013). Both viruses belong to the genus Cilevirus, family Kitaviridae. Total RNA was extracted from two sample pools comprised of 40 symptomatic leaves collected from both the CG following a CTAB-based procedure (Li et al. 2008). To identify the virus associated with the P. edulis infection, reverse transcription (RT)-polymerase chain reaction (PCR) was performed using CiLV-C2 (Olmedo-Velarde et al. 2021) and PfGSV specific primers (Ramos-González et al. 2020). RT-PCR assay amplified the CiLV-C2 amplicon but failed to produce the PfGSV amplicon from infected leaves. Amplicon sequencing followed by a BLASTn search showed the nucleotide sequence had >99% identity with the CiLV-C2H-RNA1 (KC626783). A ribo-depleted RNA library created using the TruSeq Stranded Total RNA Library Prep kit (Illumina) underwent high throughput sequencing (HTS) on a NextSeq550 Illumina platform (2x75 cycles). The 6.5 million raw reads obtained were trimmed, filtered, and de novo assembled using Metaviral SPAdes v. 3.15.02 (Antipov et al. 2020). The resulting contigs were searched against an in-house database generated from GenBank virus and viroid sequences using BLASTn. This identified 12 and 3 contigs corresponding to CiLV-C2H and watermelon mosaic virus, respectively, with the latter being previously reported in passionfruit (Watanabe et al. 2016). RNA1 contigs covered 80.17% of the CiLV-C2H genome, whereas RNA2 contigs covered 94.5% with an average coverage depth of 31.660 and 57.121, respectively. To obtain the near complete genome of CiLV-C2H, gaps from the assembled HTS data were filled by overlapping RT-PCR followed by Sanger sequencing. RNA1 (8,536 nt, Acc. No. MW413437) and RNA2 (4,878 nt, MW413438) genome sequences shared 99.2% and 97.0% identity with CiLV-C2H-RNA1 (KC626783) and -RNA2 (KC626784). To further confirm the presence of CiLV-C2H in symptomatic P. edulis plants, 40 symptomatic leaf samples were individually tested by RT-PCR, and 30 samples were positive. Brevipalpus mites collected from CiLV-C2H-positive P. edulis leaves were transferred to common bean (Phaseolus vulgaris) seedlings (Garita et al. 2013). At 15-30 days post-transfer, RNA extracted from lesions observed in recipient plants tested positive for CiLV-C2H by RT-PCR. Total RNA from individual Brevipalpus mites was isolated, and cDNA was prepared to tentatively identify the mite species involved in CiLV-C2H transmission in passionfruit (Druciarek et al 2019, Olmedo-Velarde et al. 2021). CiLV-C2H was detected in individual mites, and the 28S ribosomal mite RNA sequence (MZ478051) shared 99-100% nucleotide identity with B. yothersi (MK293678 and MT812697), a vector of CiLV-C2 (Roy et al. 2013). CiLV-C2 currently has a host range limited to the families Malvaceae, Araceae, and Rutaceae (Roy et al. 2015). CiLV-C2H infects hibiscus alone and citrus in mixed infection with CiLV-C2 (Roy et al; 2018) which is responsible for causing citrus leprosis disease. Detection of CiLV-C2H in passionfruit expands the number of host families of CiLV-C2H.

High-grade pivot-shift phenomenon after anterior cruciate ligament injury is associated with asymmetry of lateral and medial compartment anterior tibial translation and lateral meniscus posterior horn tears.

PURPOSE: To investigate whether the high-grade pivot-shift phenomenon is associated with asymmetry of the lateral and medial compartment anterior tibial translation (L-ATT and M-ATT) and lateral meniscus posterior horn (LMPH) tears in anterior cruciate ligament (ACL) injuries. METHODS: A retrospective analysis was performed on 192 consecutive patients who had complete ACL injuries between January 2019 and December 2020. Among these, 156 met the inclusion criteria. L-ATT and M-ATT were measured using preoperative weight-bearing magnetic resonance imaging (MRI), and the differences between L-ATT and M-ATT were calculated. Thirty-five patients who demonstrated excessive differences in L-ATT and M-ATT (> 6.0 mm) were regarded as asymmetric (study group), and 36 patients with minimal or no differences in L-ATT and M-ATT (< 3.0 mm) were allocated to the control group. Demographic data, grade of the pivot-shift test, integrality of LMPH, and medial meniscus posterior horn (MMPH) were compared between the groups. Moreover, predictors of high-grade pivot-shift phenomenon, including asymmetry of L-ATT and M-ATT, integrity of LMPH and MMPH, time from injury to surgery, sex, age, and body mass index (BMI) were assessed using multivariable logistic regression analysis. RESULTS: The difference between L-ATT and M-ATT in the study group was significantly higher than that in the control group (mean ± SD: 8.4 ± 2.1 mm vs. 1.5 ± 1.0 mm, P < 0.001). A higher proportion of patients with high-grade pivot-shift phenomenon (2 + and 3 +) and LMPH tears were identified in the study group (high-grade pivot-shift phenomenon: 25/35 vs. 13/36, P = 0.003; LMPH tears: 18/35 vs. 5/36, P = 0.001). Additionally, asymmetry of L-ATT, M-ATT (odds ratio 5.8; 95% CI 1.7-19.8; P = 0.005), and LMPH tears (odds ratio 3.8; 95% CI 1.3-11.6; P = 0.018) were found to be good predictors of the high-grade pivot-shift phenomenon after ACL injury, whereas MMPH tears, time from injury to surgery, sex, age, and BMI were not. CONCLUSION: In patients with ACL injury, the high-grade pivot-shift phenomenon is associated with asymmetry between L-ATT and M-ATT, and LMPH tears. LEVEL OF EVIDENCE: III.

A novel ampelovirus associated with mealybug wilt of pineapple (Ananas comosus).

Mealybug wilt of pineapple (MWP) is the most important and complex viral disease affecting pineapple worldwide. High-throughput sequencing was conducted to characterize a new virus identified only in symptomatic pineapple plants and tentatively named pineapple mealybug wilt-associated virus 6 (PMWaV-6). Data analyses revealed a genome of 17,854 nucleotides with an organization resembling members of the genus Ampelovirus, family Closteroviridae. Encoded proteins shared sequence identity with the corresponding proteins of grapevine leafroll-associated virus 3, blackberry vein banding-associated virus, and PMWaV-2. The present study reports the discovery of PMWaV-6, a putative and distinct new member of the genus Ampelovirus, subgroup I, its potential involvement in MWP, and the development of PMWaV-6-specific RT-PCR assays to detect and monitor this virus in field samples.

Genome characterization of fig umbra-like virus.

The complete genome of a new umbra-like virus from edible fig (Ficus carica) was identified by high-throughput sequencing. Based on its similarity to umbra-like virus genome sequences available in GenBank, the proposed name of this new virus is "fig umbra-like virus" (FULV). The genome of full-length FULV-1 consists of 3049 nucleotides organized into three open reading frames (ORFs). Pairwise comparisons showed that the complete nucleotide sequence of the virus had the highest identity (71.3%) to citrus yellow vein-associated virus (CYVaV). In addition, phylogenetic trees based on whole-genome nucleotide sequences and amino acid sequences of the RNA-dependent RNA polymerase showed that FULV forms a monophyletic lineage with CYVaV and other umbra-like viruses. Based on the demarcation criteria of the genus Umbravirus, and lack of two umbravirus ORFs, we propose that FULV is a putative new member of the umbra-like virus clade within the family Tombusviridae.

Identification and complete genomic sequence of a novel sadwavirus discovered in pineapple (Ananas comosus).

The complete genomic sequence of a putative novel member of the family Secoviridae was determined by high-throughput sequencing of a pineapple accession obtained from the National Plant Germplasm Repository in Hilo, Hawaii. The predicted genome of the putative virus was composed of two RNA molecules of 6,128 and 4,161 nucleotides in length, excluding the poly-A tails. Each genome segment contained one large open reading frame (ORF) that shares homology and phylogenetic identity with members of the family Secoviridae. The presence of this new virus in pineapple was confirmed using RT-PCR and Sanger sequencing from six samples collected in Oahu, Hawaii. The name "pineapple secovirus A" (PSVA) is proposed for this putative new sadwavirus.

Propofol suppresses proliferation, invasion, and migration of human melanoma cells via regulating microRNA-137 and fibroblast growth factor 9.

Propofol is an intravenous anesthetic widely used in clinical surgeries, such as tumor resection. Propofol affects the growth of many cancers, though its effect on melanoma is unknown. Our study aimed to explore how propofol affects melanoma cells. Melanoma cells A2058 and WM793B were cultured with propofol for 24 hr. Propofol significantly suppressed proliferation, migration, and invasion of A2058 and WM793B cells. Lower miR-137 level was observed in A2058 and WM793B cells, compared with normal human epidermal melanocyte HEMa-LP cells. Propofol-induced miR-137 upregulation and decreased proliferation, invasive ability, and migrated ability of A2058 and WM793B cells. Transfection with the miR-137 inhibitor reversed these effects. Additionally, miR-137 was verified to target and negatively regulate fibroblast growth factor 9 (FGF9) expression. Propofol efficiently downregulated FGF9 protein expression by upregulating miR-137. Furthermore, FGF9 overexpression abrogated propofol's repressive effects on the malignant potential of A2058 and WM793B cells. These findings indicate that propofol suppressed melanoma cell proliferation, invasion, and migration by regulating miR-137 and FGF9.

The Downregulation of ITGAX Exacerbates Amyloid-ß Plaque Deposition in Alzheimer's Disease by Increasing Polarization of M1 Microglia.

Background: Alzheimer's disease (AD) is the most common sort of neurodegenerative dementia, characterized by its challenging, diverse, and progressive nature. Despite significant progress in neuroscience, the current treatment strategies remain suboptimal. Objective: Identifying a more accurate molecular target for the involvement of microglia in the pathogenic process of AD and exploring potential mechanisms via which it could influence disease. Methods: We utilized single-cell RNA sequencing (scRNA-seq) analysis in conjunction with APP/PS1 mouse models to find out the molecular mechanism of AD. With the goal of investigating the cellular heterogeneity of AD, we downloaded the scRNA-seq data from the Gene Expression Omnibus (GEO) database and identified differentially expressed genes (DEGs). Additionally, we evaluated learning and memory capacity using the behavioral experiment. We also examined the expression of proteins associated with memory using western blotting. Immunofluorescence was employed to investigate alterations in amyloid plaques and microglia. Results: Our findings revealed an upregulation of ITGAX expression in APP/PS1 transgenic mice, which coincided with a downregulation of synaptic plasticity-related proteins, an increase in amyloid-ß (Aß) plaques, and an elevation in the number of M1 microglia. Interestingly, deletion of ITGAX resulted in increased Aß plaque deposition, a rise in the M1 microglial phenotype, and decreased production of synaptic plasticity-related proteins, all of which contributed to a decline in learning and memory. Conclusions: This research suggested that ITGAX may have a beneficial impact on the APP/PS1 mice model, as its decreased expression could exacerbate the impairment of synaptic plasticity and worsen cognitive dysfunction.

IL-17A deficiency alleviates cerebral ischemia-reperfusion injury via activating ERK/MAPK pathway in hippocampal CA1 region.

Cognitive impairment is a major complication of cerebral ischemia-reperfusion (CIR) injury and has an important impact on the quality of life of patients. However, the precise mechanisms underlying cognitive impairment after CIR injury remain elusive. In the current study, we investigated the role of interleukin 17 A (IL-17A) on CIR injury-induced cognitive impairment in wild-type and IL-17A knockout mice using RNA sequencing analysis, neurological assessments, Golgi-Cox staining, dendritic spine analysis, immunofluorescence assay, and western blot analysis. RNA sequencing identified 195 CIR-induced differentially expressed genes (83 upregulated and 112 downregulated), highlighting several enriched biological processes (negative regulation of phosphorylation, transcription regulator complex, and receptor ligand activity) and signaling pathways (mitogen-activated protein kinase [MAPK], tumor necrosis factor, and IL-17 signaling pathways). We also injected adeno-associated virus into the bilateral hippocampal CA1 regions of CIR mice to upregulate or downregulate cyclic AMP response element-binding protein. IL-17A knockout activated the extracellular signal-regulated kinase (ERK)/MAPK signaling pathway and further improved synaptic plasticity, structure, and function in CIR mice. Together, our findings suggest that IL-17A deficiency alleviates CIR injury by activating the ERK/MAPK signaling pathway and enhancing hippocampal synaptic plasticity.