Notch1 hyperactivity drives ubiquitination of NOX2 and dysfunction of CD8+ regulatory T cells in patients with systemic lupus erythematosus.

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) display heightened immune activation and elevated IgG autoantibody levels, indicating compromised regulatory T cell (Tregs) function. Our recent findings pinpoint CD8+ Tregs as crucial regulators within secondary lymphoid organs, operating in a NOX2-dependent mechanism. However, the specific involvement of CD8+ Tregs in SLE pathogenesis and the mechanisms underlying their role remain uncertain. METHODS: SLE and healthy individuals were enlisted to assess the quantity and efficacy of Tregs. CD8+CD45RA+CCR7+ Tregs were generated ex vivo, and their suppressive capability was gauged by measuring pZAP70 levels in targeted T cells. Notch1 activity was evaluated by examining activated Notch1 and HES1, with manipulation of Notch1 accomplished with Notch inhibitor DAPT, Notch1 shRNA, and Notch1-ICD. To create humanized SLE chimeras, immune-deficient NSG mice were engrafted with PBMCs from SLE patients. RESULTS: We observed a reduced frequency and impaired functionality of CD8+ Tregs in SLE patients. There was a downregulation of NOX2 in CD8+ Tregs from SLE patients, leading to a dysfunction. Mechanistically, the reduction of NOX2 in SLE CD8+ Tregs occurred at a post-translational level rather than at the transcriptional level. SLE CD8+ Tregs exhibited heightened Notch1 activity, resulting in increased expression of STUB1, an E3 ubiquitin ligase that binds to NOX2 and facilitates its ubiquitination. Consequently, restoring NOX2 levels and inhibiting Notch1 activity could alleviate the severity of the disease in humanized SLE chimeras. CONCLUSION: Notch1 is the cell-intrinsic mechanism underlying NOX2 deficiency and CD8+ Treg dysfunction, serving as a therapeutic target for clinical management of SLE.

Comparison between computer recognition and manual measurement methods for the estimation of leaf area.

BACKGROUND AND AIMS: Leaf area (A) is a crucial indicator of the photosynthetic capacity of plants. The Montgomery equation (ME), which hypothesizes that A is proportional to the product of leaf length (L) and width (W), is a valid tool for nondestructively measuring A for many broad-leaved plants. At present, the methods used to compute L and W for ME can be broadly divided into two kinds: using computer recognition, and measuring manually. However, the potential difference in the prediction accuracy using either method has not been thoroughly examined in prior studies. METHODS: In the present study, we measured 540 Alangium chinense leaves, 489 Liquidambar formosana leaves, and 215 Liriodendron × sinoamericanum leaves, utilizing computer recognition and manual measurement methods to determine L and W. ME was used to fit the data determined by the two methods, and the goodness of fits were compared. The prediction errors of A were analyzed by examining the correlations with two leaf symmetry indices (areal ratio of the left side to the right side, and standardized index for bilateral asymmetry), as well as the leaf shape complexity index (the leaf dissection index). KEY RESULTS: The results indicate that there is a neglectable difference in the estimation of A between both methods. This further validates that ME is an effective method for estimating A in broad-leaved tree species, including those with lobes. Additionally, leaf shape complexity significantly influenced the estimation of A. CONCLUSIONS: These results show that the use of computer recognition and manual measurement in the field are both effective and feasible, although the influence of leaf shape complexity should be considered when applying ME to estimate A in the future.

Electrosynthesis of Ammonia from Nitrate Using a Self-Activated Carbon Fiber Paper.

While electrochemically upcycling nitrate wastes to valuable ammonia is considered a very promising pathway for tackling the environmental and energy challenges underlying the nitrogen cycle, the effective catalysts involved are mainly limited to metal-based materials. Here, we report that commercial carbon fiber paper, which is a classical current collector and is typically assumed to be electrochemically inert, can be significantly activated during the reaction. As a result, it shows a high NH3 Faradaic efficiency of 87.39% at an industrial-level current density of 300 mA cm-2 for over 90 h of continuous operation, with a NH3 production rate of as high as 1.22 mmol cm-2 h-1. Through experimental and theoretical analysis, the in situ-formed oxygen functional groups are demonstrated to be responsible for the NO3RR performance. Among them, the C-O-C group is finally identified as the active center, which lowers the thermodynamic energy barrier and simultaneously improves the hydrogenation kinetics. Moreover, high-purity NH4Cl and NH3·H2O were obtained by coupling the NO3RR with an air-stripping approach, providing an effective way for converting nitrate waste into high-value-added NH3 products.

Monomeric CXCL12-Engineered Adipose-Derived Stem Cells Transplantation for the Treatment of Ischemic Stroke.

Adipose-derived stem cells (ASCs) possess therapeutic potential for ischemic brain injury, and the chemokine CXCL12 has been shown to enhance their functional properties. However, the cumulative effects of ASCs when combined with various structures of CXCL12 on ischemic stroke and its underlying molecular mechanisms remain unclear. In this study, we genetically engineered mouse adipose-derived ASCs with CXCL12 variants and transplanted them to the infarct region in a mice transient middle cerebral artery occlusion (tMCAO) model of stroke. We subsequently compared the post-ischemic stroke efficacy of ASC-mCXCL12 with ASC-dCXCL12, ASC-wtCXCL12, and unmodified ASCs. Neurobehavior recovery was assessed using modified neurological severity scores, the hanging wire test, and the elevated body swing test. Changes at the tissue level were evaluated through cresyl violet and immunofluorescent staining, while molecular level alterations were examined via Western blot and real-time PCR. The results of the modified neurological severity score and cresyl violet staining indicated that both ASC-mCXCL12 and ASC-dCXCL12 treatment enhanced neurobehavioral recovery and mitigated brain atrophy at the third and fifth weeks post-tMCAO. Additionally, we observed that ASC-mCXCL12 and ASC-dCXCL12 promoted angiogenesis and neurogenesis, accompanied by an increased expression of bFGF and VEGF in the peri-infarct area of the brain. Notably, in the third week after tMCAO, the ASC-mCXCL12 exhibited superior outcomes compared to ASC-dCXCL12. However, when treated with the CXCR4 antagonist AMD3100, the beneficial effects of ASC-mCXCL12 were reversed. The AMD3100-treated group demonstrated worsened neurological function, aggravated edema volume, and brain atrophy. This outcome is likely attributed to the interaction of monomeric CXCL12 with CXCR4, which regulates the recruitment of bFGF and VEGF. This study introduces an innovative approach to enhance the therapeutic potential of ASCs in treating ischemic stroke by genetically engineering them with the monomeric structure of CXCL12.

Characterization of an Aptamer Targeting Neu5Gc, as an Endogenous Pathogenic Factor Derived from Red Meat.

N-glycolylneuraminic acid (Neu5Gc), a sialic acid predominantly found in the non-neurohumoral fluids of hind-mouthed animals, is incapable of synthesizing Neu5Gc due to a deletion in the CMAH exon of the gene encoding human CMP-Neu5Gc hydroxylase. But consumption of animal-derived foods that contain Neu5Gc, such as red meat, can instigate an immune response in humans, as Neu5Gc is recognized as a foreign substance by the human immune system. This recognition leads to the production of anti-Neu5Gc antibodies, subsequently resulting in chronic inflammation. When Neu5Gc is consumed excessively or frequently, it may contribute to the development of heart disease and cancer. This makes Neu5Gc, an endogenous pathogenic factor derived from red meat, a new hot topic in red meat safety research. In this study, aptamers obtained by the magnetic bead SELEX technique were subjected to homology and secondary structure prediction analysis as well as affinity determination. The result indicated that the aptamer 2B.N2A9 exhibited a robust binding affinity, with an affinity constant (Ka) of 1.87 × 108 L/mol. This aptamer demonstrated optimal binding specificity within a pH range of 5.4 to 7.4. Molecular docking analysis further revealed that aptamer 2B.N2A9 formed stable binding interactions with the target Neu5Gc at specific sites, namely G-14, C-15, G-13, G-58, G-60, and C-59. An Enzyme-Linked Oligonucleotide Sorbent Assay (ELOSA) methodology was established to detect the endogenous pathogenic factor Neu5Gc present in red meat. This method demonstrated a limit of detection (LOD) of 0.71 ng/mL, along with an average recovery rate of 92.23%. The aptamer obtained in this study exhibited favorable binding properties to Neu5Gc. The assay was relatively convenient and demonstrated good sensitivity. Further investigation into the distribution of Neu5Gc in various red meats is of public health significance and scientific potential. A practical detection method should be provided to guide red meat diets and ensure the nutrition and safety of meat products.

ANP32B-mediated repression of p53 contributes to maintenance of normal and CML stem cells.

Proper regulation of p53 signaling is critical for the maintenance of hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs). The hematopoietic cell-specific mechanisms regulating p53 activity remain largely unknown. Here, we demonstrate that conditional deletion of acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) in hematopoietic cells impairs repopulation capacity and postinjury regeneration of HSCs. Mechanistically, ANP32B forms a repressive complex with p53 and thus inhibits the transcriptional activity of p53 in hematopoietic cells, and p53 deletion rescues the functional defect in Anp32b-deficient HSCs. Of great interest, ANP32B is highly expressed in leukemic cells from patients with chronic myelogenous leukemia (CML). Anp32b deletion enhances p53 transcriptional activity to impair LSC function in a murine CML model and exhibits synergistic therapeutic effects with tyrosine kinase inhibitors in inhibiting CML propagation. In summary, our findings provide a novel strategy to enhance p53 activity in LSCs by inhibiting ANP32B and identify ANP32B as a potential therapeutic target in treating CML.

Shift work is associated with an increased risk of type 2 diabetes and elevated RBP4 level: cross sectional analysis from the OHSPIW cohort study.

BACKGROUND: Shift work, with its growing prevalence globally, disrupts the body's inherent circadian rhythm. This disruption may escalate the risk of chronic diseasesxacerbate chronic disease risk by dysregulating physiological, behavioral, and psychosocial pathways. This study aimed to evaluate the effect of shift work on type 2 diabetes (T2DM) and Retinol binding protein 4 (RBP4) level. METHODS: The current study employed a multi-stage stratified cluster sampling technique, examining 1499 oilfield workers from the OHSPIW cohort who participated in occupational health assessments between March 2017 and June 2018.The evaluation involved shift work, sleep quality, T2DM status with questionnaires and plasma RBP4 levels in blood samples. Statistical analysis includes, Chi-square tests, t-tests, multivariate logistic regression analyses, and multivariate linear mixed models. RESULTS: The prevalence rate of T2DM in shift workers (6.56%) was significantly higher than in day workers (4.21%) (OR = 1.60, 95% CI: 1.01-2.53), with no significant difference found in the family history of diabetes, hypertension, or other chronic heart diseases (P = 0.378). The shift worker (6.89 ± 3.35) also exhibited distinctly higher PSQI scores than day workers (5.99 ± 2.87) (P < 0.001). Adjusting the age, gender, BMI, family income, tobacco smoking, alcohol drinking and PSQI, hailed shift work as a risk factor for T2DM (OR = 1.91, 95% CI: 1.17-3.14). The pairwise comparison revealed significant differences in RBP4 levels across different groups: shift and non-shift workers both with and without T2DM (P < 0.001). The RBP4 level of the shift group without T2DM was higher than the non-shift group without T2DM (P < 0.05). The levels of RBP4 level in shift and non-shift groups with T2DM was higher than those without T2DM (P < 0.05). The multivariate linear mixed model showed that when age, gender, BMI, diabetes, PSQI, family income, smoking and drinking remained unchanged, the RBP4 level of the shift workers increased by an average of 9.51 µg/mL compared with the day workers. CONCLUSIONS: Shift work is associated with an increased risk of T2DM and high levels of RBP4. Follow-up of RBP4 could facilitateearly detection of T2DM among shift workers.

Wheat straw return can lead to biogenic toluene emissions.

As a common practice in agricultural system, straw return has been reported to release a large number of trace gases and attracted much attention. However, the role of straw return in toluene emission remains poorly understood. In this study we measured the emissions of toluene as well as other 50 volatile organic compounds (VOCs) from wheat straw return for 66 days under flooded and non-flooded conditions, respectively. The results showed that substantial toluene was released from the returned wheat straw particularly under flooded condition, and primarily derived from the secondary product. Toluene emissions from the returned wheat straw were 36.8 and 8.45 mg C/kg, sharing 28.0% and 8.6% of total VOCs released, and over 90% of toluene emissions occurred between days 24-56 and 0-17 under flooded and non-flooded conditions, respectively. The emission rates of toluene were relatively high but decreased sharply at the beginning 2 days, and then was steady until 24 days under the two moisture conditions. After the initial decrease these rose again to form one "peak emission window" between days 24-56 under flooded condition, while these were still very low and steady until the end under non-flooded condition. The toluene emission rates significantly positively correlated with microbial biomass C under flooded condition, but negatively associated with bacteria and fungus number, microbial biomass C, and CO2 flux under non-flooded condition, suggesting that microorganism might play an important role in toluene emissions from wheat straw return. A rough estimate indicated that straw return might be important for biogenic toluene.

Scaling relationships of leaf vein and areole traits versus leaf size for nine Magnoliaceae species differing in venation density.

PREMISE: Across species, main leaf vein density scales inversely with leaf area (A). Yet, minor vein density manifests no clear relationship with respect to A, despite having the potential to provide important insights into the trade-off among the investments in leaf mechanical support, hydraulics, and light interception. METHODS: To examine this phenomenon, the leaves of nine Magnoliaceae leaves were sampled, and the scaling relationships among A and midrib length (ML), total vein length (TVL), total vein area (TVA), total areole area (TAA), and mean areole area (MAA) were determined. The scaling relationships between MAA and areole density (the number of areoles per unit leaf area) and between MAA and A were also analyzed. RESULTS: For five of the nine species, A was proportional to ML2 . For eight of the nine species, TVL and TVA were both proportional to A. The numerical values of the scaling exponents for TAA vs. A were between 1.0 and 1.07 for eight species; i.e., as expected, TAA was isometrically proportional to A. There was no correlation between MAA and A, but MAA scaled inversely with respect to areole density for each species. CONCLUSIONS: The correlation between midrib "density" (i.e., ML/A) and A, and the lack of correlation between total leaf vein density and A result from the A ∝$\propto $ ML2 scaling relationship and the proportional relationship between TVL and A, respectively. Leaves with the same size can have widely varying MAA. Thus, leaf size itself does not directly constrain leaf hydraulic efficiency and redundancy.

Assessing the impact of green nudges on ozone concentration: Evidence from China's night refueling policy.

Ozone (O3) pollution poses health risks and premature mortality, and gas stations are one of the largest sources of urban volatile organic compounds (VOCs, the main precursor to O3). This paper investigates whether the government's call for night refueling, which can be regarded as a green nudge, can guide changes in consumer behavior and consequently improve environmental quality. Using a difference-in-differences (DID) estimation and weekly monitoring site air quality panel data, we analyze the effect of the Night Refueling Preferential Policy on O3 concentrations. We find that the policy can reduce O3 concentrations by 10% by encouraging consumers to refuel at night. The reduction in O3 has brought great benefits to human health, leading to a 4-5‰ reduction in non-accidental mortality and a 6-8‰ reduction in cardiovascular mortality in Jiangsu province. The economic benefits of this policy would be approximately 62-189 billion Chinese Yuan (CNY) if it were implemented nationwide. The findings of this study suggest that the government can influence consumer behavior to promote environmental quality.

Policy Implementation Inconsistency and Emission Leakage: Evidence from The Closure of Polluting Firms.

Public policies often fail to address the unintended behavior of regulated firms and are therefore inconsistent in their implementation, resulting in ineffectiveness. In the process of environmental policy, policy implementation inconsistencies also exist, which is known as emission leakage. Existing studies on the topic focus more on spatial dimension and less attention to time dimension. The reasons for emission leakage over time are two: regulatory laxness and inefficiencies. In this study, we examine whether emission leakage occurs during enterprises' end-of-life cycles. Based on unique high-frequency facility-level monitoring data, we construct a difference-in-differences (DID) model to investigate differences in environmental performance between hazardous chemical production firms in the process of closing and those in the same industry within 20 kilometers. This study finds no emission leakage problem in the processes of relocation and closure, and the concentration of chemical oxygen demand (COD) discharged declines by 28.53 percent. This result is mainly due to top-down regulatory requirements. Nevertheless, policymakers should remain aware of emission leakage when formulating environmental policies and create more substantial supervision to prevent potential leakage.

"Diminishing returns" for leaves of five age-groups of Phyllostachys edulis culms.

PREMISE: Leaf mass (M) and lamina surface area (A) are important functional traits reported to obey a scaling relationship called "diminishing returns" (i.e., M ∝ Aα>1 ). Previous studies have focused primarily on eudicots and ignored whether the age of leaves affects the numerical value of the scaling exponent (i.e., α). METHODS: The effect of age was examined using 1623 Phyllostachys edulis leaves from culms differing in age collected in Nanjing, China. The scaling relationships among leaf A, fresh mass (FM), and dry mass (DM) were evaluated using reduced major axis protocols. The bootstrap percentile method was used to test the significance of differences in α-values. RESULTS: Overall, the numerical values of α exceeded 1.0. The scaling relationship between FM and A was statistically more robust than that between DM and A. The scaling exponents of FM vs. A exhibited a "high-low-high-low-high" numerical trend from the oldest to the youngest age-group. FM increased linearly as culm age decreased; the leaf DM per unit area (LMA) exhibited a parabolic trend across the age-groups. CONCLUSIONS: "Diminishing returns" is confirmed for all but one age-group of an important monocot species. The relationship between FM and A was statistically more robust than that between DM and A for each age-group. The FM per unit A decreased with increasing age-groups, whereas the middle age-groups had a greater LMA than the oldest and youngest age-groups. These data are the first to show that the age of shoots affects the scaling relationship between leaf mass and area.

Cyanobacteria blooms potentially enhance volatile organic compound (VOC) emissions from a eutrophic lake: Field and experimental evidence.

Eutrophication promotes massive cyanobacteria blooms (CBBs), leading to the release of volatile organic compounds (VOCs). To investigate the effects of cyanobacteria on VOC emissions, field campaigns were carried out in eutrophic Chaohu Lake at six sites with different microalgae densities during CBBs in summer 2019, and incubation experiments were performed in the laboratory. The results showed that the lake water was the primary source of VOCs at six sampling sites in Chaohu Lake during CBBs, with an average total VOC flux of 81.2 ± 20.6 µg m-2 h-1. Alkanes were the most abundantly emitted VOCs, with a share of 23.1-63.7% of total emitted VOCs, followed by aromatics (16.6-46.3%). The fluxes of total VOCs were significantly greater at sites B and/or C than at site A in July, and at site B' and/or C' than at site A' in August in Chaohu Lake. The fluxes of total VOCs from living and decayed cyanobacteria in the experimental treatments were two orders of magnitude higher than the corresponding values in the control treatments in the laboratory incubation. Taken together, these results suggested that CBBs potentially enhanced VOC emissions from the eutrophic lake, and that cyanobacteria acted as an important source of VOCs. Additionally, non-methane hydrocarbons (i.e., alkanes, alkenes, and aromatics) predominated among the released VOCs during the stabilization and senescence stages, while oxygenated volatile organic compounds (i.e. alcohols, aldehydes, ketones, esters, and furans) prevailed during the apoptosis stage and aromatics and volatile organic sulfur compounds predominated during the decomposition stage, suggesting that VOC emissions varied markedly at different life stages.

Can public-private partnerships (PPPs) improve the environmental performance of urban sewage treatment?

Insufficient sewage treatment facility is one important reason for wastewater entering and affecting aquatic ecosystems. The PPP mode, serving as one of the fastest-growing mechanisms for public service provision in recent decades, is considered to be an effective way to alleviate the pressure of funding shortages and to improve the efficiency of sewage treatment. However, the performance of PPPs has been questioned, especially the service quality given the inherent nature of the private sectors' pursuit of maximizing economic profit and the shortcoming of incomplete contracts. This paper evaluates the service quality, namely the environmental performance, of the PPP mode in China's urban sewage treatment sector. Based on detailed firm-level data in Jiangsu Province, China, we find that the PPP mode has improved the pollutant treatment performance, and increased operation cost and promoted sewage treatment efficiency serve as the main mechanism for the improvement of environmental performance. The research findings could help both developed and developing countries to apply and design a public-private partnerships mechanism.

Cladribine Induces ATF4 Mediated Apoptosis and Synergizes with SAHA in Diffuse Large B-Cell Lymphoma Cells.

Cladribine is a purine nucleoside analog used to treat B-cell chronic lymphocytic leukemia and hairy cell leukemia, also functions as an inhibitor of DNA synthesis to block the repair of the damaged DNA. The therapeutic role of cladribine against diffuse large B-cell lymphoma cells (DLBCL) is still undefined. In the present study, we demonstrated that cladribine inhibited cell proliferation and induced G1 phase arrest in human DLBCL cells. Furthermore, we showed that cladribine induced apoptosis by decreasing the expression of c-FLIPL and increasing the expression of DR4 and the cleaved form of caspase8. Cladribine also upregulated the expression of Bax, and downregulated the expression of Mcl-1 and Bcl-2 in a dose-dependent manner. It also activated endoplasmic reticulum (ER) stress, and ATF4 expression was required for cladribine induced apoptosis. Also, we showed that suberoylanilide hydroxamic acid (SAHA) enhanced the pro-apoptotic role of cladribine. Collectively, cladribine activated extrinsic and intrinsic apoptotic signaling pathways via stimulating ER stress signaling pathway and eliciting synergistic effect with SAHA in DLBCL cells.

An investigation of the time trends, risk factors, role of ultrasonic preoperative diagnosis of 79 ovarian pregnancy.

BACKGROUND: Ovarian pregnancy (OP) is a rare form of ectopic pregnancy and is still a medical challenge. Therefore, more studies about the time trends, risk factors and diagnostic measurements are needed for the efficient treatment of OP. METHODS: The datum of OP patients who were treated at the Second Hospital of Hebei Medical University from 2003 to 2018 was collected and a retrospective cohort study was preformed between OP and tubal pregnancy. RESULTS: 79 of all 6943 ectopic pregnancy (1.14%) were OP. The prevalence of OP following assisted reproductive technology showed an increasing trend over time, from 8.33% to 15.22%. Previous abdominal surgery was one of the risk factors of OP (OR 0.41, 95% CI 0.18-0.95, p = 0.04). Merely 2 (2.53%) patients were sonographically diagnosed as OP accorded with their discharge diagnosis. However, 56 (80.0%) accumulation of blood in the pelvis formed echo free areas could be clearly found by ultrasonography. A significant difference was found in serum ß-hCG level among OP patients and tubal pregnancy patients (2762.73 ± 1915.24 mmol/L vs 1034.20 ± 915.32 mmol/L, p < 0.001). CONCLUSIONS: The prevalence of OP following assisted reproductive technology is on the rise. History of abdominal surgery may be a high risk factor for OP patients who have the tendency of high ß-hCG levels. The ultrasonic preoperative diagnosis is conductive to the early diagnosis of OP though the diagnosis accuracy is low.

The Synthetic Flavonoid Derivative GL-V9 Induces Apoptosis and Autophagy in Cutaneous Squamous Cell Carcinoma via Suppressing AKT-Regulated HK2 and mTOR Signals.

Cutaneous squamous-cell carcinoma (cSCC) is one of most common type of non-black skin cancer. The malignancy degree and the death risk of cSCC patients are significantly higher than basal cell carcinoma patients. GL-V9 is a synthesized flavonoid derived from natural active ingredient wogonin and shows potent growth inhibitory effects in liver and breast cancer cells. In this study, we investigated the anti-cSCC effect and the underlying mechanism of GL-V9. The results showed that GL-V9 induced both apoptosis and autophagy in human cSCC cell line A431 cells, and prevented the growth progression of chemical induced primary skin cancer in mice. Metabolomics assay showed that GL-V9 potentially affected mitochondrial function, inhibiting glucose metabolism and Warburg effect. Further mechanism studies demonstrated that AKT played important roles in the anti-cSCC effect of GL-V9. On one hand, GL-V9 suppressed AKT-modulated mitochondrial localization of HK2 and promoted the protein degradation of HK2, resulting in cell apoptosis and glycolytic inhibition. On the other hand, GL-V9 induced autophagy via inhibiting Akt/mTOR pathway. Interestingly, though the autophagy induced by GL-V9 potentially antagonized its effect of apoptosis induction, the anti-cSCC effect of GL-V9 was not diluted. All above, our studies suggest that GL-V9 is a potent candidate for cSCC treatment.

[Risk factors for poor prognosis of neonatal bacterial meningitis].

OBJECTIVE: To investigate the risk factors for poor prognosis of neonatal bacterial meningitis. METHODS: A retrospective analysis was performed for the clinical data of 152 children with neonatal bacterial meningitis. According to their prognosis, they were divided into a good prognosis group with 122 children and a poor prognosis group with 30 children. The two groups were compared in terms of general status, initial symptoms, and laboratory findings, and the risk factors for poor prognosis were analyzed. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of children with a very low birth weight, a peripheral blood white blood cell count (WBC) of <5×109/L or >20×109/L, a C-reactive protein level of >50 mg/L, a cerebrospinal fluid (CSF) WBC of >500×106/L, a CSF glucose level of <1 mmol/L, or a CSF protein level of >2 g/L, as well as significantly higher positive rates of blood culture and/or CSF culture, Gram-positive bacteria, and Streptococcus agalactiae (P<0.05). The multivariate logistic regression analysis showed that a CSF glucose level of <1 mmol/L and a CSF protein level of >2 g/L were independent risk factors for poor prognosis of neonatal bacterial meningitis. CONCLUSIONS: A CSF glucose level of <1 mmol/L and a CSF protein level of >2 g/L are risk factors for poor prognosis of neonatal bacterial meningitis.

The inverted pattern of circulating miR-221-3p and miR-222-3p associated with isolated low HDL-C phenotype.

BACKGROUND: We investigated the baseline characterization of cardiovascular disease (CVD)-derived circulating miR-221-3p/222-3p in isolated low HDL-C phenotype (ILHP) to enhance our understanding on their molecular pathological pattern prior to disease onset. METHODS: We screened 174 asymptomatic subjects with isolated low HDL-C phenotype (n = 88) and normal lipid phenotype (n = 86), and detected circulating levels of CVD-derived circulating miR-221-3p/222-3p using TaqMan miRNA Real-time PCR detection system. RESULTS: We found the inverted pattern of decreased circulating miR-221-3p (0.415 [0.249, 1.004] vs 0.658 [0.347, 1.534], p = 0.002) versus increased miR-222-3p levels (0.379 [0.101, 0.701] vs 0.156 [0.043, 0.407], p < 0.001) in ILHP. The baseline levels of circulating miR-221-3p and miR-222-3p are correlated with serum HDL-C levels (miR-221-3p: r = 0.306, p < 0.001; miR-222-3p: r = - 0.201, p = 0.008). Gender-based analysis showed female-specific elevation of circulating miR-221-3p in asymptomatic individual. Multiple logistic regression analysis showed that circulating miR-222-3p is robustly independent factor (adjusted OR = 8.42, 95%CI: 2.53-27.98, p < 0.001) and significantly improved the performance of the predictive clinical model distinguished ILHP from normal lipid phenotype (AUC: 0.816, 95%CI (0.754, 0.879) vs AUC: 0.771, 95%CI (0.702, 0.840); Z = 2.169, p = 0.030). Moreover, the increased original Ct ratio of miR-221-3p to miR-222-3p in male ILHP (1.003 [0.927, 1.063] vs 0.927 [0.858, 0.967], p < 0.001) significantly enhanced the ability to classify male ILHP compared with the male predictive clinical model (AUC: 0.851, 95%CI (0.770, 0.933) vs AUC: 0.759, 95%CI (0.659, 0.859); Z = 2.474, p < 0.05). CONCLUSIONS: The inverted pattern of circulating miR-221-3p and miR-222-3p are potentially clinically actionable signature for molecular pathology in isolated low HDL-C phenotype.