Characteristics of beta parapapillary atrophy in primary angle-closure suspect.

OBJECTIVE: To investigate the characteristics of beta parapapillary atrophy (ß-PPA) in patients with primary angle-closure suspect (PACS). METHODS AND ANALYSIS: In total, 215 and 259 eyes with PACS and non-PACS (NPACS), respectively, were enrolled in this observational, cross-sectional study. Stereoscopic fundus and optical coherence tomography images were used to characterise ß-PPA; the former was also used to measure the major ß-PPA parameters. Univariate and multiple logistic regression analyses were used to identify the factors correlated with the presence of ß-PPA and with ß-PPA parameters. RESULTS: The ß-PPA occurrence rates were 48.80% and 44.40% in the PACS and NPACS groups, respectively, with no significant difference between groups. Compared with that in the NPACS group, the ß-PPA area was significantly larger (p=0.005) in the PACS group, but the angular extent and maximum radial length did not differ between groups (p=0.110 and 0.657, respectively) after adjusting for age and axial length. The presence of ß-PPA was associated with older age (OR 1.057, 95% CI 1.028 to 1.088, p<0.001) and larger disc area (OR 1.716, 95% CI 1.170 to 2.517, p=0.006). A larger ß-PPA area was associated with older age (p=0.014), greater vertical cup-to-disc ratio (p=0.028), larger disc area (p<0.001) and PACS diagnosis (p=0.035). CONCLUSION: 48.80% of participants with PACS had ß-PPA, which is slightly larger than NPACS. The area of ß-PPA was larger in PACS, while the angular extent and maximum radial length did not differ between groups.

H2S Increases Blood Pressure via Activation of L-Type Calcium Channels with Mediation by HS• Generated from Reactions with Oxyhemoglobin.

Although the gasotransmitter hydrogen sulfide (H2S) is well known for its vasodilatory effects, H2S also exhibits vasoconstricting properties. Herein, it is demonstrated that administration of H2S as intravenous sodium sulfide (Na2S) increased blood pressure in sheep and rats, and this effect persisted after H2S has disappeared from the blood. Inhibition of the L-type calcium channel (LTCC) diminished the hypertensive effects. Incubation of Na2S with whole blood, red blood cells, methemoglobin, or oxyhemoglobin produced a hypertensive product of H2S, which is not hydrogen thioperoxide, metHb-SH- complexes, per-/poly- sulfides, or thiolsulfate, but rather a labile intermediate. One-electron oxidation of H2S by oxyhemoglobin generated its redox cousin, sulfhydryl radical (HS•). Consistent with the role of HS• as the hypertensive intermediate, scavenging HS• inhibited Na2S-induced vasoconstriction and activation of LTCCs. In conclusion, H2S causes vasoconstriction that is dependent on the activation of LTCCs and generation of HS• by oxyhemoglobin.

Role of long non-coding RNA DLY6E in regulating TMUV infection.

Long non-coding RNA (lncRNA) is a type of RNA with a length greater than 200 nt and lacking coding ability. In recent years, a considerable number of lncRNAs have been found to have important functions. The lncRNA plays an important role in growth and development, body metabolism, immune function, and regulation of viral replication. A lncRNA, MSTRG8505.2, was screened and named lncRNA DLY6E, which was a new duck-derived lncRNA. The lncRNADLY6E in this study has a complex secondary structure, specifically distributed in the heart, liver and other organs. The expression of lncRNA DLY6E was significantly up-regulated after TMUV infection, which was time-dependent and non-dose-dependent. Overexpression of three structural proteins and seven non-structural proteins of TMUV in DEF cells showed no significant difference in the expression of lncRNADLY6E. Meanwhile, using lipopolysaccharides (LPS) and poly (I:C) to stimulate DEF cells, the results showed that the induced expression of lncRNA DLY6E was associated with the dsRNA-related TLR3/RIG-I/MDA5 pathway rather than the LPS activated signaling pathway. To further explore the function of lncRNA DLY6E, an eukaryotic expression vector was constructed. Overexpression of lncRNA DLY6E in DEF cells can increase the replication of TMUV. After overexpression of lncRNADLY6E, the transcriptional level of its target gene LY6E was detected, and the results showed that lncRNADLY6E did not act through its target gene. Overexpression of lncRNA DLY6E significantly inhibited the mRNA levels of OAS, Mx and PKR, suggesting that lncRNA DLY6E may promote the virus by inhibiting the transcription of antiviral proteins in innate immunity. This phenomenon provides new ideas for the prevention and control of TMUV, which is worth further thinking and exploration.

A Prediction Model for Clinical Outcomes of COVID-19 Hospitalized Patients: Construction and Accuracy Assessment.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic spread rapidly with considerable morbidity nationwide since China's liberalization in December 2022. Our work has focused on identifying different predictive factors from the laboratory examination of critically ill patients, and forecasting the unfavorable outcome of critically ill patients with COVID-19 through a combined diagnosis of biological markers. METHODS: We conducted a retrospective study at the Department of First Affiliated Hospital of Wenzhou Medical University, China, from December 24, 2022, to January 10, 2023, where 434 critically ill patients who met the inclusion criteria were involved. Machine analysis was employed to search for the parameters with the highest predictive value to calculate COVID-19 mortality by exploiting 66 typical laboratory results. RESULTS: Combined diagnosis of serum albumin (ALB), lactate dehydrogenase (LDH), direct bilirubin (Dbil), ferritin, pulse oxygen saturation (SpO2), and neutrophil count (NEUT#) was evaluated, and the result with the highest predictive value (NEUT#) was selected as the predictor for COVID-19 mortality with a sensitivity of 89.2% and a specificity of 77.4%. CONCLUSIONS: The increased levels of LDH, Dbil, ferritin, and NEUT#, along with lowered ALB and SpO2 levels are the most decisive variables for forecasting the mortality for COVID-19 according to our machine-learning-based model. The combined diagnosis could be used to improve further diagnostic performance.

A novel starch-active lytic polysaccharide monooxygenase discovered with bioinformatics screening and its application in textile desizing.

BACKGROUND: Lytic polysaccharide monooxygenases (LPMOs) catalyzing the oxidative cleavage of different types of polysaccharides have potential to be used in various industries. However, AA13 family LPMOs which specifically catalyze starch substrates have relatively less members than AA9 and AA10 families to limit their application range. Amylase has been used in enzymatic desizing treatment of cotton fabric for semicentury which urgently need for new assistant enzymes to improve reaction efficiency and reduce cost so as to promote their application in the textile industry. RESULTS: A total of 380 unannotated new genes which probably encode AA13 family LPMOs were discovered by the Hidden Markov model scanning in this study. Ten of them have been successfully heterologous overexpressed. AlLPMO13 with the highest activity has been purified and determined its optimum pH and temperature as pH 5.0 and 50 °C. It also showed various oxidative activities on different substrates (modified corn starch > amylose > amylopectin > corn starch). The results of enzymatic textile desizing application showed that the best combination of amylase (5 g/L), AlLPMO13 (5 mg/L), and H2O2 (3 g/L) made the desizing level and the capillary effects increased by 3 grades and more than 20%, respectively, compared with the results treated by only amylase. CONCLUSION: The Hidden Markov model constructed basing on 34 AA13 family LPMOs was proved to be a valid bioinformatics tool for discovering novel starch-active LPMOs. The novel enzyme AlLPMO13 has strong development potential in the enzymatic textile industry both concerning on economy and on application effect.

The association between urine ketone and new-onset atrial fibrillation in critically ill patients.

BACKGROUND AND AIMS: New-onset atrial fibrillation (NOAF) is a common manifestation in critically ill patients. There is a paucity of evidence indicating a relationship between urinary ketones and NOAF. METHODS: Critically ill patients with urinary ketone measurements from the Medical Information Mart for Intensive Care (MIMIC-IV) database were included. The primary outcome was NOAF Propensity score matching was performed following by multivariable logistic regression. RESULTS: A total of 24,688 patients with available data of urine ketone were included in this study. The urine ketone of 4014 patients was tested positive. The average age of the included participants was 63.8 years old, and 54.5% of them were male. Result of the fully-adjusted binary logistic regression model showed that patients with positive urinary ketone was associated with a significantly lower risk of NOAF (Odds ratio, 0.79, 95% CI 0.7-0.9), compared with those with negative urinary ketone. In the subgroup analysis according to diabetic status, compared with nondiabetics, patients with diabetes had lower risk of NOAF (p-values for interaction < 0.05). Results of other subgroup analyses according to gender, age, infection, myocardial infarction, and congestive heart failure were consistent with the primary analysis. CONCLUSIONS: Positive urinary ketone body may be associated with reduced risk of NOAF in critically ill patients during intensive care unit hospitalization. Further studies are needed to clarify the underlying mechanisms.

Growth arrest specific protein 6 alleviated white matter injury after experimental ischemic stroke.

Ischemic white matter injury leads to long-term neurological deficits and lacks effective medication. Growth arrest specific protein 6 (Gas6) clears myelin debris, which is hypothesized to promote white matter integrity in experimental stroke models. By the middle cerebral artery occlusion (MCAO) stroke model, we observed that Gas6 reduced infarcted volume and behavior deficits 4 weeks after MCAO. Compared with control mice, Gas6-treatment mice represented higher FA values in the ipsilateral external capsules by MRI DTI scan. The SMI32/MBP ratio of the ipsilateral cortex and striatum was profoundly alleviated by Gas6 administration. Gas6-treatment group manifested thicker myelin sheaths than the control group by electron microscopy. We observed that Gas6 mainly promoted OPC maturation, which was closely related to microglia. Mechanically, Gas6 accelerated microglia-mediated myelin debris clearance and cholesterol transport protein expression (abca1, abcg1, apoc1, apoe) in vivo and in vitro, accordingly less myelin debris and lipid deposited in Gas6 treated stroke mice. HX531 (RXR inhibitor) administration mitigated the functions of Gas6 in speeding up debris clearance and cholesterol transport protein expression. Generally, we concluded that Gas6 cleared myelin debris and promoted cholesterol transportation protein expression through activating RXR, which could be one critical mechanism contributing to white matter repair after stroke.

Pathogenicity of duck circovirus 1 in experimentally infected specific pathogen-free ducks.

Ducks infected with duck circovirus (DuCV) show symptoms such as feather loss, growth retardation and low body weight in the flock. The virus induces immunosuppression and increases the prevalence of infection with other pathogens. However, most studies on duck circovirus were focused on coinfection, and fewer studies had been conducted on the pathogenicity of duck circovirus alone. The aim of the present study was to investigate the pathogenesis of DuCV-1 in experimentally infected specific pathogen-free ducks. In this study, we sequenced the whole genome of a strain of duck circovirus and identified the virus genotype as DuCV-1b. This strain of duck circovirus was named SDLH(OR567883). Animal pathogenicity experiments were then conducted, wherein specific pathogen-free ducks were infected by mucosal injection and abdominal injection. Infected ducks were sampled for 4 consecutive weeks after infection and showed symptoms of dwarfism. We further examined the replication of DuCV-1 in the ducks. The highest virus titers in the 2 infection groups were found in the liver and spleen, with different results for the different routes of infection. Pathological sections of duck organs were made and it was found that organs such as the liver and spleen were damaged by DuCV-1. In conclusion, our experimental results indicate that DuCV-1 can infect ducks individually and cause widespread organ damage in infected ducks.

Immune checkpoint inhibitor induced colitis and arthritis: A case report.

RATIONALE: As a programmed cell death 1 (PD-1) inhibitor, camrelizumab is used in the treatment of a variety of malignancies. However, a variety of immune-mediated adverse reactions have been reported in a wide range of clinical applications, including immune-related colitis, arthritis, hepatitis, etc. PATIENT CONCERNS: This 56-year-old male patient experienced diarrhea, bloody stool, and knee pain after receiving camrelizumab for metastatic esophageal squamous cell carcinoma. Colonoscopy showed granular changes in the whole colonic mucosa and blurred or even disappeared vascular texture. Pathology showed chronic inflammation of the colonic mucosa. Magnetic resonance imaging of knee joint showed exudative inflammatory changes in bilateral knee joints. DIAGNOSIS: Immune checkpoint inhibitor-induced colitis and arthritis. INTERVENTIONS: Mesalazine oral (extended-release granules, 1000 mg/quarter in die daily). Dexamethasone sodium phosphate (once daily, 5mg in the evening) and compound cypress liquid (once daily, 100ml in the evening) were given by enema. Anti-inflammatory and analgesic treatment of bone pain plaster. OUTCOMES: The patient had diarrhea reduced to 3 times/day, no more bloody stools, and the knee pain was relieved. LESSONS: This article describes the cases of immune-related colitis and arthritis caused by camrelizumab, and recommends considering the risk of colitis and arthritis with camrelizumab monotherapy or combination therapy.

Safety and immunogenicity of the COVID-19 mRNA vaccine CS-2034: A randomized, double-blind, dose-exploration, placebo-controlled multicenter Phase I clinical trial in healthy Chinese adults.

BACKGROUND: The novel coronavirus pneumonia (COVID-19) is an infectious disease caused by the infection of a novel coronavirus known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has resulted in millions of deaths. We aimed to evaluate the safety and immunogenicity of the COVID-19 mRNA vaccine (CS-2034, CanSino, Shanghai, China) in adults without COVID-19 infection from China. METHOD: This is a multicenter Phase I clinical trial with a randomized, double-blinded, dose-exploration, placebo-controlled design. The trial recruited 40 seronegative participants aged 18-59 years who had neither received any COVID-19 vaccine nor been infected before. They were divided into a low-dose group (administered with either the CS-2034 vaccine containing 30 µg of mRNA or a placebo of 0.3 ml type 5 adenovirus vector) and a high-dose group (administered with either the CS-2034 vaccine containing 50 µg of mRNA or a placebo of 0.5 ml type 5 adenovirus vector). Participants were randomly assigned in a 3:1 ratio to receive either the mRNA vaccine or a placebo on days 0 and 21 according to a two-dose immunization schedule. The first six participants in each dosage group were assigned as sentinel subjects. Participants were sequentially enrolled in a dose-escalation manner from low to high dose and from sentinel to non-sentinel subjects. Blood samples were collected from all participants on the day before the first dose (Day 0), the day before the second dose (day 21), 14 days after the second dose (day 35), and 28 days after the second dose (day 49) to evaluate the immunogenicity of the CS-2034 vaccine. Participants were monitored for safety throughout the 28-day follow-up period, including solicited adverse events, unsolicited adverse events, adverse events of special interest (AESI), and medically attended adverse events (MAE). This report focuses solely on the safety and immunogenicity analysis of adult participants aged 18-59 years, while the long-term phase of the study is still ongoing. This study is registered at ClinicalTrials.gov, NCT05373485. FINDINGS: During the period from May 17, 2022, to August 8, 2022, a total of 155 participants aged 18-59 years were screened for this study. Among them, 115 participants failed the screening process, and 40 participants were randomly enrolled (15 in the low-dose group, 15 in the high-dose group, and 10 in the placebo group). Throughout the 28-day follow-up period, the overall incidence of adverse reactions (related to vaccine administration) in the low-dose group, high-dose group, and placebo group was 93.33% (14/15), 100.00% (15/15), and 80.00% (8/10), respectively. There was a statistically significant difference in the incidence of local adverse reactions (soreness, pruritus, swelling at the injection site) among the low-dose group, high-dose group, and placebo group (P = 0.002). All adverse reactions were mainly of severity grade 1 (mild) or 2 (moderate), and no adverse events of severity grade 4 or higher occurred. Based on the analysis of Spike protein Receptor Binding Domain (S-RBD) IgG antibodies against the BA.1 strain, the seroconversion rates of antibodies at day 21 after the first dose were 86.67%, 93.33%, and 0.00% in the low-dose group, high-dose group, and placebo group, respectively. The geometric mean titer (GMT) of antibodies was 61.2(95%CI 35.3-106.2), 55.4(95%CI 36.3-84.4), and 15.0(95%CI 15.0-15.0), and the geometric mean fold increase (GMI) was 4.08(95%CI 2.35-7.08), 3.69(95%CI 2.42-5.63), and 1.00(95%CI 1.00-1.00) for each group. At day 28 after the full vaccination, the seroconversion rates of antibodies were 100.00%, 93.33%, and 0.00%, and the GMT of antibodies was 810.0(95%CI 511.4-1283.0), 832.2(95%CI 368.1-1881.6), and 15.0(95%CI 15.0-15.0), and the GMI was 54.00(95%CI 34.09-85.53), 55.48(95%CI 24.54-125.44), and 1.00(95%CI 1.00-1.00) for each group, respectively. Based on the analysis of CD3+/CD4+ cell cytokine response, the percentages of IL-2+, IL-4+, IFN-γ+, and TNF-α+ cells increased after 14 days and 28 days of full vaccination in both the low-dose group and high-dose group. The increase was most pronounced in the high-dose group. INTERPRETATION: At day 28 after the full vaccination, both the low-dose and the high-dose CS-2034 vaccine were able to induce the production of high titers of S-RBD IgG antibodies against the BA.1 strain. Adverse reactions in the low-dose and high-dose groups were mainly of severity grade 1 or 2, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine.

Artifacts Introduced by Sample Handling in Chemiluminescence Assays of Nitric Oxide Metabolites.

We recently developed a combination of four chemiluminescence-based assays for selective detection of different nitric oxide (NO) metabolites, including nitrite, S-nitrosothiols (SNOs), heme-nitrosyl (heme-NO), and dinitrosyl iron complexes (DNICs). However, these NO species (NOx) may be under dynamic equilibria during sample handling, which affects the final determination made from the readout of assays. Using fetal and maternal sheep from low and high altitudes (300 and 3801 m, respectively) as models of different NOx levels and compositions, we tested the hypothesis that sample handling introduces artifacts in chemiluminescence assays of NOx. Here, we demonstrate the following: (1) room temperature placement is associated with an increase and decrease in NOx in plasma and whole blood samples, respectively; (2) snap freezing and thawing lead to the interconversion of different NOx in plasma; (3) snap freezing and homogenization in liquid nitrogen eliminate a significant fraction of NOx in the aorta of stressed animals; (4) A "stop solution" commonly used to preserve nitrite and SNOs leads to the interconversion of different NOx in blood, while deproteinization results in a significant increase in detectable NOx; (5) some reagents widely used in sample pretreatments, such as mercury chloride, acid sulfanilamide, N-ethylmaleimide, ferricyanide, and anticoagulant ethylenediaminetetraacetic acid, have unintended effects that destabilize SNO, DNICs, and/or heme-NO; (6) blood, including the residual blood clot left in the washed purge vessel, quenches the signal of nitrite when using ascorbic acid and acetic acid as the purge vessel reagent; and (7) new limitations to the four chemiluminescence-based assays. This study points out the need for re-evaluation of previous chemiluminescence measurements of NOx, and calls for special attention to be paid to sample handling, as it can introduce significant artifacts into NOx assays.

Nonlinear Relationship Between Interleukin-6 and NT-proBNP at Admission in Hospitalized COVID-19 Patients.

Purpose: Elevated levels of the inflammatory marker interleukin-6 (IL-6) and cardiac injury marker N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been observed in patients with coronavirus disease 2019 (COVID-19). However, the relationship between IL-6 and NT-proBNP levels remains unclear. Therefore, we investigated the relationship between IL-6 and NT-proBNP levels in patients with COVID-19. Patients and Methods: This was a cross-sectional study. Consecutive patients with COVID-19 were included herein. The independent and dependent target variables were the IL-6 and NT-proBNP levels, respectively, measured at baseline. Univariate and multivariate linear regression analyses and curve fitting were also performed. Results: The average age of the 121 selected participants was 49.8 ± 15.8 years old, and 48.8% (59/121) were male. The estimated ß value between Ln-transformed IL-6 and NT-proBNP was 0.28 (95% confidence interval [CI] 0.12-0.44, P = 0.001) in univariate logistic regression analysis and 0.09 (95% CI -0.04-0.21, P = 0.176) in the fully adjusted model. This relationship was nonlinear, with a point of 2.7, and the ß values (and CIs) for the left (<2.7) and right (≥2.7) sides of the inflection point were -0.06 (95% CI -0.23-0.12, P = 0.534) and 0.77 (95% CI 0.18-1.37, P = 0.016) in the fully adjusted model, respectively. Conclusion: Our results suggest a nonlinear association between IL-6 and NT-proBNP levels. Higher IL-6 levels are associated with NT-proBNP in patients with COVID-19.

ARHGAP4 promotes leukemogenesis in acute myeloid leukemia by inhibiting DRAM1 signaling.

Rho GTPase-activating protein 4 (ARHGAP4) is an important Rho family GTPase-activating protein that is strongly associated with the onset and progression of some tumors. We found that ARHGAP4 mRNA and protein are overexpressed in human acute myeloid leukemia (AML) patients and are associated with a poor prognosis. ARHGAP4 knockdown significantly impairs viability and colony formation capacity and induces apoptosis in AML cells. Further results demonstrate that ARHGAP4 deletion impairs AML progression in vivo. Interestingly, DRAM1 signaling is significantly activated in AML cells with ARHGAP4 knockdown. Our results also indicated that ARHGAP4 might function in AML cells by binding with p53 to inhibit DRAM1. Moreover, knockdown of DRAM1 rescues the defects of ARHGAP4 in AML cells. This newly described role of the ARHGAP4/DRAM1 axis in regulating AML progression may have important therapeutic implications.

Noncanonical contribution of microglial transcription factor NR4A1 to post-stroke recovery through TNF mRNA destabilization.

Microglia-mediated neuroinflammation is involved in various neurological diseases, including ischemic stroke, but the endogenous mechanisms preventing unstrained inflammation is still unclear. The anti-inflammatory role of transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) in macrophages and microglia has previously been identified. However, the endogenous mechanisms that how NR4A1 restricts unstrained inflammation remain elusive. Here, we observed that NR4A1 is up-regulated in the cytoplasm of activated microglia and localizes to processing bodies (P-bodies). In addition, we found that cytoplasmic NR4A1 functions as an RNA-binding protein (RBP) that directly binds and destabilizes Tnf mRNA in an N6-methyladenosine (m6A)-dependent manner. Remarkably, conditional microglial deletion of Nr4a1 elevates Tnf expression and worsens outcomes in a mouse model of ischemic stroke, in which case NR4A1 expression is significantly induced in the cytoplasm of microglia. Thus, our study illustrates a novel mechanism that NR4A1 posttranscriptionally regulates Tnf expression in microglia and determines stroke outcomes.

The Roles of Trust and Its Antecedent Variables in Healthcare Consumers' Acceptance of Online Medical Consultation during the COVID-19 Pandemic in China.

Online medical consultation (OMC) is generating considerable interest among researchers and practitioners due to the mandatory quarantine measures implemented during the COVID-19 pandemic in China. However, the acceptance rate of OMC has declined over time. This paper aims to empirically investigate OMC acceptance using a proposed research model by integrating the technology acceptance model (TAM) with trust and its antecedent variables. A quantitative self-administered cross-sectional survey was conducted to collect data from 260 healthcare consumers. A partial least squares structural equation modeling method was used to examine the data. Results revealed that healthcare consumers' behavioral intention was influenced by attitudes, while perceived usefulness and trust significantly influenced behavioral intention through attitude as a mediator. In addition, perceived risk, perceived privacy protection, network externalities, cognitive reputation, and interactivity directly influenced trust. Overall, the research model explained 50% of the variance in attitude and 71% of the variance in behavioral intention. The study's findings should provide useful insights into making effective design, development, and implementation decisions for OMC services.

Absent in melanoma 2 mediates aging-related cognitive dysfunction by acting on complement-dependent microglial phagocytosis.

Pattern separation (PS) dysfunction is a type of cognitive impairment that presents early during the aging process, and this deficit has been attributed to structural and functional alterations in the dentate gyrus (DG) of the hippocampus. Absent in melanoma 2 (AIM2) is an essential component of the inflammasome. However, whether AIM2 plays a role in aging-associated cognitive dysfunction remains unclear. Here, we found that PS function was impaired in aging mice and was accompanied by marked synaptic loss and increased expression of AIM2 in the DG. Subsequently, we used an AIM2 overexpression virus and mice with AIM2 deletion to investigate the role of AIM2 in regulating PS function and synaptic plasticity and the mechanisms involved. Our study revealed that AIM2 regulates microglial activation during synaptic pruning in the DG region via the complement pathway, leading to impaired synaptic plasticity and PS function in aging mice. These results suggest a critical role for AIM2 in regulating synaptic plasticity and PS function and provide a new direction for ameliorating aging-associated cognitive dysfunction.

Long noncoding RNA SENCR facilitates the progression of acute myeloid leukemia through the miR-4731-5p/IRF2 pathway.

BACKGROUND: Acute myeloid leukemia (AML) is a type of hematological tumor caused by malignant clone hematopoietic stem cells. The relationship between lncRNAs and tumor occurrence and progression has been gaining attention. Research has shown that Smooth muscle and endothelial cell-enriched migration/differentiation-associated lncRNA (SENCR) is abnormally expressed in various diseases, whereas its role in AML is still poorly understood. METHODS: The expression of SENCR, microRNA-4731-5p (miR-4731-5p) and Interferon regulatory factor 2 (IRF2) were measured using qRT-PCR. The proliferation, cycle and apoptosis of AML cells with or without knockdown of SENCR were detected by CCK-8 assay, EdU assay, flow cytometry, western blotting and TUNEL assay, respectively. Consistently, SENCR knockdown was impaired the AML progression in immunodeficient mice. In addition, the binding of miR-4731-5p to SENCR or IRF2 was confirmed by luciferase reporter genes assay. Finally, rescue experiments were conducted to confirm the role of SENCR/miR-4731-5p/IRF2 axis in AML. RESULTS: SENCR is highly expressed in AML patients and cell lines. The patients with high SENCR expression had poorer prognosis compared with those with low SENCR expression. Interestingly, knockdown of SENCR inhibits the growth of AML cells. Further results demonstrated that the reduction of SENCR slows the progression of AML in vivo. SENCR could function as a competing endogenous RNA (ceRNA) to negatively regulate miR-4731-5p in AML cells. Furthermore, IRF2 was validated as a direct target gene of miR-4731-5p in AML cells. CONCLUSIONS: Our findings underscore the important role of SENCR in regulating the malignant phenotype of AML cells by targeting the miR-4731-5p/IRF2 axis.

Variation in Retinal Nerve Fiber Layer and Ganglion Cell Complex Associated With Optic Nerve Head Size in Healthy Eyes.

Purpose: To investigate whether the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) change with optic nerve head (ONH) size in healthy eyes. Methods: This cross-sectional observational study recruited participants aged ≥50 years. Participants underwent optical coherence tomography-assisted measurements of the peripapillary RNFL and macular GCC and were divided into small, medium, and large ONH groups according to optic disc area (≤1.9 mm2, >1.9 mm2 and ≤2.4 mm2, and >2.4 mm2, respectively). The groups were compared for RNFL and GCC. Linear regression models were used to evaluate the correlation of RNFL and GCC with ocular and systemic factors. Results: There were 366 participants. The whole, temporal, and superior RNFLs were significantly different among the groups (P = 0.035, 0.034, and 0.013, respectively) with no significant difference in the nasal and inferior RNFL (P = 0.214, 0.267, respectively). The average, superior, and inferior GCCs were not significantly different among the groups (P = 0.583, 0.467, and 0.820, respectively). Thinner RNFL was independently associated with older age (P = 0.003), male sex (P = 0.018), smaller disc area (P < 0.001), higher vertical cup disc ratio (VCDR) (P < 0.001), and larger maximum cup depth (P = 0.007); thinner GCC was independently associated with older age (P = 0.018), larger best-corrected visual acuity (P = 0.023), and higher VCDR (P = 0.002). Conclusions: RNFL but not GCC significantly increased with ONH size in healthy eyes. GCC may be more suitable than RNFL for evaluating early glaucoma in patients with large or small ONH. Translational Relevance: GCC may be a better index than RNFL for early glaucoma evaluation in patients with large or small ONH.

Proteomic and Transcriptomic Responses of the Desiccation-Tolerant Moss Racomitrium canescens in the Rapid Rehydration Processes.

The moss Racomitrium canescens (R. canescens) has strong desiccation tolerance. It can remain desiccated for years and yet recover within minutes of rehydration. Understanding the responses and mechanisms underlying this rapid rehydration capacity in bryophytes could identify candidate genes that improve crop drought tolerance. We explored these responses using physiology, proteomics, and transcriptomics. Label-free quantitative proteomics comparing desiccated plants and samples rehydrated for 1 min or 6 h suggesting that damage to chromatin and the cytoskeleton had occurred during desiccation, and pointing to the large-scale degradation of proteins, the production of mannose and xylose, and the degradation of trehalose immediately after rehydration. The assembly and quantification of transcriptomes from R. canescens across different stages of rehydration established that desiccation was physiologically stressful for the plants; however, the plants recovered rapidly once rehydrated. According to the transcriptomics data, vacuoles appear to play a crucial role in the early stages of R. canescens recovery. Mitochondria and cell reproduction might recover before photosynthesis; most biological functions potentially restarted after ~6 h. Furthermore, we identified novel genes and proteins related to desiccation tolerance in bryophytes. Overall, this study provides new strategies for analyzing desiccation-tolerant bryophytes and identifying candidate genes for improving plant drought tolerance.

CD11c+ microglia promote white matter repair after ischemic stroke.

Ischemic stroke leads to white matter damage and neurological deficits. However, the characteristics of white matter injury and repair after stroke are unclear. Additionally, the precise molecular communications between microglia and white matter repair during the stroke rehabilitation phase remain elusive. In this current study, MRI DTI scan and immunofluorescence staining were performed to trace white matter and microglia in the mouse transient middle cerebral artery occlusion (tMCAO) stroke model. We found that the most serious white matter damage was on Day 7 after the ischemic stroke, then it recovered gradually from Day 7 to Day 30. Parallel to white matter recovery, we observed that microglia centered around the damaged myelin sheath and swallowed myelin debris in the ischemic areas. Then, microglia of the ischemic hemisphere were sorted by flow cytometry for RNA sequencing and subpopulation analysis. We found that CD11c+ microglia increased from Day 7 to Day 30, demonstrating high phagocytotic capabilities, myelin-supportive genes, and lipid metabolism associated genes. CD11c+ microglia population was partly depleted by the stereotactic injecting of rAAV2/6M-taCasp3 (rAAV2/6M-CMV-DIO-taCasp3-TEVp) into CD11c-cre mice. Selective depletion of CD11c+ microglia disrupted white matter repair, oligodendrocyte maturation, and functional recovery after stroke by Rotarod test, Adhesive Removal test, and Morris Water Maze test. These findings suggest that spontaneous white matter repair occurs after ischemic stroke, while CD11c+ microglia play critical roles in this white matter restorative progress.