The effect and mechanism of patchouli alcohol on cognitive dysfunction in AD mice induced by Aß1-42 oligomers through AMPK/mTOR pathway.

Alzheimer's disease (AD) is a neurodegenerative brain disorder that progressively impairs long-term and working memory. The function and mechanism of PA(Patchouli alcohol) in improving AD in the external treatment of encephalopathy remain unclear. This study aimed to investigate the therapeutic effect of PA on AD using an Aß1-42 induced AD mouse model with LPS(Lipopolysaccharide) stimulation of BV2 microglial cells. Additionally, we aimed to explore the potential mechanism of PA in enhancing autophagy and reducing neuroinflammation through the AMPK (AMP-activated protein kinase)/mTOR (Mammaliam target of rapamycin) signaling pathway. The Morris water maze was used to assess cognitive function, and cortical and hippocampal tissues were collected for further analysis of the corresponding signaling pathways and inflammatory changes through biological experiments. Our research findings demonstrate that PA has a significant positive impact on cognitive and memory impairments in mice that have been induced with Aß1-42-induced AD. Additionally, PA was also found to revert the activation of microglia induced by LPS. These effects may be attributed to the reduction of neuroinflammation and enhancement of the AMPK/mTOR autophagy pathway. Therefore, PA may serve as an effective therapeutic option to prevent or delay the progression of AD-associated memory dysfunction.

Periodontal disease increases the severity of chronic obstructive pulmonary disease: a Mendelian randomization study.

BACKGROUND: Recent research suggests that periodontitis can increase the risk of chronic obstructive pulmonary disease (COPD). In this study, we performed two-sample Mendelian randomization (MR) and investigated the causal effect of periodontitis (PD) on the genetic prediction of COPD. The study aimed to estimate how exposures affected outcomes. METHODS: Published data from the Gene-Lifestyle Interaction in the Dental Endpoints (GLIDE) Consortium's genome-wide association studies (GWAS) for periodontitis (17,353 cases and 28,210 controls) and COPD (16,488 cases and 169,688 controls) from European ancestry were utilized. This study employed a two-sample MR analysis approach and applied several complementary methods, including weighted median, inverse variance weighted (IVW), and MR-Egger regression. Multivariable Mendelian randomization (MVMR) analysis was further conducted to mitigate the influence of smoking on COPD. RESULTS: We chose five single-nucleotide polymorphisms (SNPs) as instrumental variables for periodontitis. A strong genetically predicted causal link between periodontitis and COPD, that is, periodontitis as an independent risk factor for COPD was detected. PD (OR = 1.102951, 95% CI: 1.005-1.211, p = 0.039) MR-Egger regression and weighted median analysis results were coincident with those of the IVW method. According to the sensitivity analysis, horizontal pleiotropy's effect on causal estimations seemed unlikely. However, reverse MR analysis revealed no significant genetic causal association between COPD and periodontitis. IVW (OR = 1.048 > 1, 95%CI: 0.973-1.128, p = 0.2082) MR Egger (OR = 0.826, 95%CI:0.658-1.037, p = 0.1104) and weighted median (OR = 1.043, 95%CI: 0.941-1.156, p = 0.4239). The results of multivariable Mendelian randomization (MVMR) analysis, after adjusting for the confounding effect of smoking, suggest a potential causal relationship between periodontitis and COPD (P = 0.035). CONCLUSION: In this study, periodontitis was found to be independent of COPD and a significant risk factor, providing new insights into periodontitis-mediated mechanisms underlying COPD development.

Detection and diagnosis of automated breast ultrasound in patients with BI-RADS category 4 microcalcifications: a retrospective study.

BACKGROUND: Automated Breast Ultrasound (AB US) has shown good application value and prospects in breast disease screening and diagnosis. The aim of the study was to explore the ability of AB US to detect and diagnose mammographically Breast Imaging Reporting and Data System (BI-RADS) category 4 microcalcifications. METHODS: 575 pathologically confirmed mammographically BI-RADS category 4 microcalcifications from January 2017 to June 2021 were included. All patients also completed AB US examinations. Based on the final pathological results, analyzed and summarized the AB US image features, and compared the evaluation results with mammography, to explore the detection and diagnostic ability of AB US for these suspicious microcalcifications. RESULTS: 250 were finally confirmed as malignant and 325 were benign. Mammographic findings including microcalcifications morphology (61/80 with amorphous, coarse heterogeneous and fine pleomorphic, 13/14 with fine-linear or branching), calcification distribution (189/346 with grouped, 40/67 with linear and segmental), associated features (70/96 with asymmetric shadow), higher BI-RADS category with 4B (88/120) and 4 C (73/38) showed higher incidence in malignant lesions, and were the independent factors associated with malignant microcalcifications. 477 (477/575, 83.0%) microcalcifications were detected by AB US, including 223 malignant and 254 benign, with a significantly higher detection rate for malignant lesions (x2 = 12.20, P < 0.001). Logistic regression analysis showed microcalcifications with architectural distortion (odds ratio [OR] = 0.30, P = 0.014), with amorphous, coarse heterogeneous and fine pleomorphic morphology (OR = 3.15, P = 0.037), grouped (OR = 1.90, P = 0.017), liner and segmental distribution (OR = 8.93, P = 0.004) were the independent factors which could affect the detectability of AB US for microcalcifications. In AB US, malignant calcification was more frequent in a mass (104/154) or intraductal (20/32), and with ductal changes (30/41) or architectural distortion (58/68), especially with the both (12/12). BI-RADS category results also showed that AB US had higher sensitivity to malignant calcification than mammography (64.8% vs. 46.8%). CONCLUSIONS: AB US has good detectability for mammographically BI-RADS category 4 microcalcifications, especially for malignant lesions. Malignant calcification is more common in a mass and intraductal in AB US, and tend to associated with architectural distortion or duct changes. Also, AB US has higher sensitivity than mammography to malignant microcalcification, which is expected to become an effective supplementary examination method for breast microcalcifications, especially in dense breasts.

Mitochondrial antioxidant elamipretide improves learning and memory impairment induced by chronic sleep deprivation in mice.

BACKGROUND: The inflammation and synaptic dysfunction induced by mitochondrial dysfunction play essential roles in the learning and memory impairment associated with sleep dysfunction. Elamipretide (SS-31), a novel mitochondrion-targeted antioxidant, was proven to improve mitochondrial dysfunction, the inflammatory response, synaptic dysfunction, and cognitive impairment in models of cerebral ischemia, sepsis, and type 2 diabetes. However, the potential for SS-31 to improve the cognitive impairment induced by chronic sleep deprivation (CSD) and its underlying mechanisms is unknown. METHODS: Adult c57BL/6J mice were subjected to CSD for 21 days using an activity wheel accompanied by daily intraperitoneal injection of SS-31 (5 mg/kg). The novel object recognition and Morris water maze test were used to evaluate hippocampus-dependent cognitive function. Western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to determine the effects of CSD and SS-31 on markers of mitochondria, inflammation response, and synaptic function. Enzyme-linked immunosorbent assays were used to examine the levels of proinflammatory cytokines. RESULTS: SS-31 could improve the cognitive impairment induced by CSD. In particular, SS-31 treatment restored the CSD-induced decrease in sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator alpha levels and the increase in levels nuclear factor kappa-B and inflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha. Furthermore, SS-31 significantly increased the levels of brain-derived neurotrophic factor, postsynaptic density protein-95, and synaptophysin in CSD mice. CONCLUSION: Taken together, these results suggest that SS-31 could improve CSD-induced mitochondrial biogenesis dysfunction, inflammatory response, synaptic dysfunction, and cognitive impairment by increasing SIRT1 expression levels.

Long non-coding RNAFOXD1-AS1 modulated CTCs epithelial-mesenchymal transition and immune escape in hepatocellular carcinoma in vitro by sponging miR-615-3p.

BACKGROUND: Hepatocellular carcinoma (HCC) is widely recognized as a globally prevalent malignancy. Immunotherapy is a promising therapy for HCC patients. Increasing evidence suggests that lncRNAs are involved in HCC progression and immunotherapy. AIM: The study reveals the mechanistic role of long non-coding RNA (lncRNA) FOXD1-AS1 in regulating migration, invasion, circulating tumor cells (CTCs), epithelial-mesenchymal transition (EMT), and immune escape in HCC in vitro. METHODS: This study employed real-time PCR (RT-qPCR) to measure FOXD1-AS1, miR-615-3p, and programmed death-ligand 1 (PD-L1). The interactions of FOXD1-AS1, miR-615-3p, and PD-L1 were validated via dual-luciferase reporter gene and ribonucleoprotein immunoprecipitation (RIP) assay. In vivo experimentation involves BALB/c mice and BALB/c nude mice to investigate the impact of HCC metastasis. RESULTS: The upregulation of lncRNA FOXD1-AS1 in malignant tissues significantly correlates with poor prognosis. The investigation was implemented on the impact of lncRNA FOXD1-AS1 on the migratory, invasive, and EMT of HCC cells. It has been observed that the lncRNA FOXD1-AS1 significantly influences the generation and metastasis of MCTC in vivo analysis. In mechanistic analysis, lncRNA FOXD1-AS1 enhanced immune escape in HCC via upregulation of PD-L1, which acted as a ceRNA by sequestering miR-615-3p. Additionally, lncRNA FOXD1-AS1 was found to modulate the EMT of CTCs through the activation of the PI3K/AKT pathway. CONCLUSION: This study presents compelling evidence supporting the role of lncRNA FOXD1-AS1 as a miRNA sponge that sequesters miR-655-3p and protects PD-L1 from suppression.

Progress in the Application of Lung Ultrasound for the Evaluation of Neonates with Respiratory Distress Syndrome.

Neonatal respiratory distress syndrome (NRDS) is a common critical disease in neonates. Early diagnosis and timely treatment are crucial. Historically, X-ray imaging was the primary method for diagnosing NRDS. However, this method carries radiation exposure risks, making it unsuitable for dynamic lung condition monitoring. In addition, neonates who are critically ill require bedside imaging, but diagnostic delays are often unavoidable due to equipment transportation and positioning limitations. These challenges have been resolved with the introduction of lung ultrasound (LUS) in neonatal intensive care. The diagnostic efficacy and specificity of LUS for NRDS is superior to that of X-ray. The non-invasive, dynamic, and real-time benefits of LUS also allow for real-time monitoring of lung changes throughout treatment for NRDS, yielding important insights for guiding therapy. In this paper, we examine the ultrasonographic characteristics of NRDS and the recent progress in the application of ultrasound in the diagnosis and treatment of NRDS while aiming to promote wider adoption of this method.

Inadequate gastric preparation and its associated factors for magnetically controlled capsule endoscopy.

Goals: To explore factors associated with inadequate gastric preparation for MCE. Background: Factors associated with inadequate gastric preparation for magnetically controlled capsule endoscopy (MCE) remains unclear. Study: Data of patients who underwent MCE from June 2021 to July 2022 were prospectively collected. The gastric cleanliness score (GCS) of the six stomach regions (gastric cardia, fundus, body, angulus, antrum, and pylorus) was recorded. Patients with GCS score ≥18 were defined as the adequate preparation. Factors related to inadequate gastric preparation were analyzed using a logistic regression model with estimated odds ratios (OR). Results: The mean GCS score of 211 patients was 17.01 ± 2.82. In the multivariable analysis, proton pump inhibitor (PPI) use (OR 3.57; 95% CI 1.69-7.95; p < 0.01) and premedication time after administering simethicone <30 min (OR 2.86; 95% CI 1.10-7.39; p = 0.03) were independent risk factors for inadequate gastric preparation. Comparing the gastric cleanliness of different locations, the median GCS of the lower stomach [10.00, IQR (9.50, 11.00)] was significantly higher than that of the upper stomach [7.00, IQR (6.00, 8.00)] (p <0.001). Conclusion: PPI use and inadequate premedication time (<30 min) may reduce the quality of gastric preparation for MCE. The type, dose, duration of medication, and discontinuation time of PPIs was well worth further exploration. Appropriate control of the type and time of premedication may be the key to improving overall gastric cleanliness.

Subsequent maternal sleep deprivation aggravates neurobehavioral abnormalities, inflammation, and synaptic function in adult male mice exposed to prenatal inflammation.

Objective: Studies have suggested that prenatal exposure to inflammation increases the risk of neuropsychiatric disorders, including anxiety, depression, and cognitive dysfunction. Because of anatomical and hormonal alterations, pregnant women frequently experience sleep dysfunction, which can enhance the inflammatory response. The aim of this study was to explore the effects of maternal sleep deprivation on prenatal inflammation exposure-induced behavioral phenotypes in offspring and identify the associated mechanisms. Methods: Pregnant mice received an intraperitoneal injection of lipopolysaccharide (LPS) on gestational day 15 and were subsequently subjected to sleep deprivation during gestational days 15-21. Anxiety-like behavior was evaluated by the open field test and the elevated plus maze test. Depression-like behavior was assessed by the tail suspension test and the forced swimming test. Cognitive function was determined using the Morris water maze test. The levels of markers of inflammation and synaptic function were examined employing general molecular biological techniques. Results: The results showed that prenatal exposure to LPS resulted in anxiety- and depression-like symptoms and learning and memory deficits, and these effects were exacerbated by maternal sleep deprivation. Furthermore, maternal sleep deprivation aggravated the prenatal LPS exposure-induced increase in the expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α and decrease in the levels of postsynaptic density-95 and synaptophysin in the hippocampus. Discussion: Collectively, these results suggested that maternal sleep deprivation exacerbates anxiety, depression, and cognitive impairment induced by prenatal LPS exposure, effects that were associated with an inflammatory response and synaptic dysfunction.

The multiple phonological activation in Chinese spoken word production: An ERP study supporting cascaded model.

A central issue in spoken word production concerns how activation is transmitted from semantic to phonological levels. The current study investigated the issue of seriality and cascadedness in Chinese spoken word production, via the combined semantic blocked paradigm (with homogeneous and heterogeneous blocks) and picture-word interference paradigm (with phonologically related, mediated and unrelated distractors). Naming latencies data showed a mediated effect via comparing mediated and unrelated distractors in homogeneous blocks, a phonological facilitation effect via comparing phonologically related and unrelated distractors in homogeneous and heterogeneous blocks, and a semantic interference effect via comparing homogeneous and heterogeneous blocks. Critically, cluster-based permutation test of ERP data demonstrated a mediated effect around 266-326ms and an overlapped pattern of semantic interference effect around 264-418ms and phonological facilitation effect around 210-310ms in homogeneous or around 236-316ms in heterogeneous blocks. These findings indicated that speakers activate phonological nodes of non-targets, and present a cascadedness pattern of the transmission from semantics to phonology in Chinese spoken production. The present study sheds new insight on the neural correlates of semantic and phonological effects, and provides behavioral and electrophysiological evidences for the cascaded model within a theoretical framework of lexical competition in speech production.

Mutational signatures of synchronous and metachronous brain metastases from lung adenocarcinoma.

Brain metastasis (BM) is an important cause of mortality for cancer patients. Many patients were diagnosed with brain metastases at their first visit who have not received any treatment while a subset of patients did not have distant metastases at the first visit and brain metastases were detected during the course of systemic therapies. The difference in their genomic characterization is unclear. 96 lung adenocarcinoma patients were enrolled in our study. 53 patients (55%) had synchronous metastatic brain tumors. 43 (45%) patients had metachronous brain metastases. We performed 168 panel-targeted gene sequencing cerebrospinal fluid (CSF) and plasma samples from patients to identify genomic features of synchronous brain metastases (SBM) and metachronous brain metastases (MBM). In conclusion, CSF liquid biopsies have a priority in detecting gene alteration. A comprehensive comparison of molecular profiling between SBM and MBM revealed the most frequently altered genes in both groups were EGFR and TP53, but with different exon point mutations. RTK-RAS and TP53 pathways were the most affected pathways.

Resveratrol ameliorates maternal separation-induced anxiety- and depression-like behaviors and reduces Sirt1-NF-kB signaling-mediated neuroinflammation.

Maternal separation in early life has a detrimental effect on the physiological and biochemical functions of the brains of offspring and can lead to anxiety- and depression-like behaviors later in life. Resveratrol possesses a variety of pharmacological properties, including anti-inflammatory, anxiolytic, and anti-depressive effects. In rodents, resveratrol can attenuate anxiety- and depression-like behaviors induced by chronic unpredictable mild stress, estrogen deficiency, and lipopolysaccharide. However, whether resveratrol administration during adolescence can counteract these behaviors when they result from maternal separation is unknown. In this study, male C57BL/6J mice were separated from their mothers for 4 h per day from postnatal day 2 (PND 2) to PND 21; starting on PND 61, resveratrol was administered intraperitoneally at 40 mg/(kg/day-1) for 4 weeks. At 3 months of age, anxiety and depression-like behaviors were assessed in the male offspring using a series of tasks consisting of an open field test, an elevated plus maze test, a forced swimming test, and a tail suspension test. The hippocampal levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α) were measured by ELISA, while those of sirtuin 1 (Sirt1) and nuclear factor kappa B (NF-κB) p65 were determined by western blotting and PCR. The results showed that maternal separation led to increased anxiety- and depression-like behaviors, enhanced the levels of pro-inflammatory cytokines, and downregulated the Sirt1/NF-κB signaling pathway in the male offspring; however, these effects could be reversed by treatment with resveratrol. Our findings suggested that resveratrol can ameliorate inflammation and anxiety- and depression-like behaviors induced by maternal separation via the activation of the Sirt1/NF-κB pathway.

Genetic Predisposition to Periodontitis and Risk of Migraine: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: Previous observational studies have associated periodontitis (PD) with migraine; however, the results are inconclusive and the causality of the association between PD and migraine remains unclear. This two-sample Mendelian randomization (MR) study was performed to explore the bi-directional causal relationship between PD and migraine. METHODS: To investigate the relationship between PD (17,353 cases; 28,210 controls) and migraine (1072 cases; 360,122 controls), we used genetic tools from the largest available genome-wide association study of European descent. Inverse variance-weighted (IVW) and a series of sensitivity analyses were used to explore the association between migraine and PD. We performed an MR study using seven SNPs (single nucleotide polymorphisms) as instrumental variables for PD to investigate the causal relationship between migraine and PD. RESULTS: We found no significant causal relationship between PD and migraine (odds ratio, OR = 1.000; 95% confidence interval, CI = 0.99-1.00; p = 0.65). Similarly, no evidence supported a causal relationship between migraine and PD (OR = 0.07; CI = 2.04 × 10-9-2.65 × 106; p = 0.77). A sensitivity analysis revealed that no potential polymorphic effect (p = 0.356) and heterogeneity (p = 0.652) exists for the variants used in constructing the genetic instrument. CONCLUSIONS: Based on the results of our MR study, there is no causal relationship between PD and migraines or migraines and PD.

Transporter Associated with Antigen Processing 1 Gene Polymorphisms Increase the Susceptibility to Tuberculosis.

Purpose: Tuberculosis (TB) is known to result from a complex interaction between the host immune response and Mycobacterium infection. The transporter associated with antigen processing (TAP) plays an important role in the processing and presentation pathways for the Mycobacterium tuberculosis (M. tb) antigen. To investigate the possible association of the TAP1 and TAP2 genes with TB. Patients and Methods: A total of 449 TB patients and 435 control subjects were included in this study, and single nucleotide polymorphisms (SNPs) in the TAP gene, as well as TAP1 and TAP2 alleles, were genotyped. Results: TAP gene association analysis of TB diseases showed that rs41551515-T in the TAP1 gene was significantly associated with susceptibility to TB (P=7.96E-04, OR=4.124, 95% CI: 1.683-10.102), especially pulmonary TB (PTB, P=6.84E-04, OR=4.350, 95% CI: 1.727-10.945), and the combination of rs1057141-T-rs1135216-C in the TAP1 gene significantly increased the risk of TB susceptibility (P=5.51E-05, OR=10.899, 95% CI: 2.555-46.493). Five novel TAP1 alleles were detected in Yunnan Han people, and the allele frequency of TAP1*unknown_3 (rs41555220-rs41549617-rs1057141-rs1135216-rs1057149-rs41551515: C-A-T-C-C-T) was notably increased in all TB patients, including in the PTB and EPTB subgroups, and was significantly associated with the risk of susceptibility to TB. However, no association between the TAP2 gene and TB was found in this study. Conclusion: Host genetic variants of rs41551515-T and the combination rs1057141-T-rs1135216-C, as well as TAP1*unknown_3 may play a critical role in susceptibility to TB disease.

Relationship between Materialism and Social Networking Site Addiction among Adolescents: A Moderated Mediation Model.

Materialism has been consistently linked to Internet-related addictions, including compulsive online shopping, problematic online gaming, and excessive smartphone use; however, the relationship between materialism and social networking site (SNS) addiction has remained unclear. Thus, this study aims to examine the association between materialism and SNS addiction and investigate the mediating effect of fatalism and moderating effect of self-concept clarity in this relationship among 703 Chinese adolescents. Materialism was significantly positively associated with SNS addiction in adolescents, and fatalism partially mediated this association. Moreover, self-concept clarity moderated the direct and indirect relationships between materialism and SNS addiction. Specifically, for adolescents with low (versus high) self-concept clarity, those who also had high levels of materialism were more likely to develop fatalistic beliefs and showed further symptoms of SNS addiction. This study's findings imply that decreasing materialism and fatalism and developing self-concept clarity might be effective interventions for reducing SNS addiction among adolescents.

Effects of gestational inflammation on age-related cognitive decline and hippocampal Gdnf-GFRα1 levels in F1 and F2 generations of CD-1 Mice.

BACKGROUND: It has been reported that age-associated cognitive decline (AACD) accelerated by maternal lipopolysaccharide (LPS) insult during late pregnancy can be transmitted to the second generation in a sex-specificity manner. In turn, recent studies indicated that glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor (GFRα1) are critical for normal cognitive function. Based on this evidence, we aimed to explore whether Gdnf-GFRα1 expression contributes to cognitive decline in the F1 and F2 generations of mouse dams exposed to lipopolysaccharide (LPS) during late gestation, and to evaluate also the potential interference effect of pro-inflammatory cytokines. METHODS: During gestational days 15-17, pregnant CD-1 mice (8-10 weeks old) received a daily intraperitoneal injection of LPS (50 µg/kg) or saline (control). In utero LPS-exposed F1 generation mice were selectively mated to produce F2 generation mice. In F1 and F2 mice aged 3 and 15 months, the Morris water maze (MWM) was used to evaluated the spatial learning and memory ability, the western blotting and RT-PCR were used for analyses of hippocampal Gdnf and GFRα1 expression, and ELISA was used to analyse IL-1ß, IL-6 and TNF-α levels in serum. RESULTS: Middle-aged F1 offspring from LPS-treated mothers exhibited longer swimming latency and distance during the learning phase, lower percentage swimming time and distance in targe quadrant during memory phase, and lower hippocampal levels of Gdnf and GFRα1 gene products compared to age-matched controls. Similarly, the middle-aged F2 offspring from the Parents-LPS group had longer swimming latency and distance in the learning phase, and lower percentage swimming time and distance in memory phase than the F2-CON group. Moreover, the 3-month-old Parents-LPS and 15-month-old Parents- and Father-LPS groups had lower GDNF and GFRα1 protein and mRNAs levels compared to the age-matched F2-CON group. Furthermore, hippocampal levels of Gdnf and GFRα1 were correlated with impaired cognitive performance in the Morris water maze after controlling for circulating pro-inflammatory cytokine levels. CONCLUSIONS: Our findings indicate that accelerated AACD by maternal LPS exposure can be transmitted across at least two generations through declined Gdnf and GFRα1 expression, mainly via paternal linage.

Lung ultrasound to diagnose infectious pneumonia of newborns: A prospective multicenter study.

INTRODUCTION: Whether lung ultrasound (LUS) can be used for pathogenic diagnosis remains controversial. This study was conducted to clarify whether ultrasound has diagnostic value for etiology. METHODS: A total of 135 neonatal pneumonia patients with an identified pathogen were enrolled from the newborn intensive care units of 10 tertiary hospitals in China. The study ran from November 2020 to December 2021. The infants were divided into various groups according to pathogens, time of infection, gestational age, and disease severity. The distribution of pleural line abnormalities, B-line signs, and pulmonary consolidation, as well as the incidence of air bronchogram and pleural effusion based on LUS, were compared between these groups. RESULTS: There were significant differences in pulmonary consolidation. The sensitivity and specificity of the diagnosis of severe pneumonia based on the extent of pulmonary consolidation were 83.3% and 85.2%, respectively. The area under the receiver operating characteristic curve for the identification of mild or severe pneumonia based on the distribution of pulmonary consolidation was 0.776. CONCLUSION: LUS has good performance in diagnosing and differentiating the severity of neonatal pneumonia but cannot be used for pathogenic identification in the early stages of pneumonia.

Competition between H4PteGlu and H2PtePAS Confers para-Aminosalicylic Acid Resistance in Mycobacterium tuberculosis.

Tuberculosis remains a serious challenge to human health worldwide. para-Aminosalicylic acid (PAS) is an important anti-tuberculosis drug, which requires sequential activation by Mycobacterium tuberculosis (M. tuberculosis) dihydropteroate synthase and dihydrofolate synthase (DHFS, FolC). Previous studies showed that loss of function mutations of a thymidylate synthase coding gene thyA caused PAS resistance in M. tuberculosis, but the mechanism is unclear. Here we showed that deleting thyA in M. tuberculosis resulted in increased content of tetrahydrofolate (H4PteGlu) in bacterial cells as they rely on the other thymidylate synthase ThyX to synthesize thymidylate, which produces H4PteGlu during the process. Subsequently, data of in vitro enzymatic activity experiments showed that H4PteGlu hinders PAS activation by competing with hydroxy dihydropteroate (H2PtePAS) for FolC catalysis. Meanwhile, over-expressing folC in ΔthyA strain and a PAS resistant clinical isolate with known thyA mutation partially restored PAS sensitivity, which relieved the competition between H4PteGlu and H2PtePAS. Thus, loss of function mutations in thyA led to increased H4PteGlu content in bacterial cells, which competed with H2PtePAS for catalysis by FolC and hence hindered the activation of PAS, leading to decreased production of hydroxyl dihydrofolate (H2PtePAS-Glu) and finally caused PAS resistance. On the other hand, functional deficiency of thyA in M. tuberculosis pushes the bacterium switch to an unidentified dihydrofolate reductase for H4PteGlu biosynthesis, which might also contribute to the PAS resistance phenotype. Our study revealed how thyA mutations confer PAS resistance in M. tuberculosis and provided new insights into studies on the folate metabolism of the bacterium.

Environmental enrichment improves declined cognition induced by prenatal inflammatory exposure in aged CD-1 mice: Role of NGPF2 and PSD-95.

Introduction: Research suggests that prenatal inflammatory exposure could accelerate age-related cognitive decline that may be resulted from neuroinflammation and synaptic dysfunction during aging. Environmental enrichment (EE) may mitigate the cognitive and synaptic deficits. Neurite growth-promoting factor 2 (NGPF2) and postsynaptic density protein 95 (PSD-95) play critical roles in neuroinflammation and synaptic function, respectively. Methods: We examined whether this adversity and EE exposure can cause alterations in Ngpf2 and Psd-95 expression. In this study, CD-1 mice received intraperitoneal injection of lipopolysaccharide (50 µg/kg) or normal saline from gestational days 15-17. After weaning, half of the male offspring under each treatment were exposed to EE. The Morris water maze was used to assess spatial learning and memory at 3 and 15 months of age, whereas quantitative real-time polymerase chain reaction and Western blotting were used to measure hippocampal mRNA and protein levels of NGPF2 and PSD-95, respectively. Meanwhile, serum levels of IL-6, IL-1ß, and TNF-α were determined by enzyme-linked immunosorbent assay. Results: The results showed that aged mice exhibited poor spatial learning and memory ability, elevated NGPF2 mRNA and protein levels, and decreased PSD-95 mRNA and protein levels relative to their young counterparts during natural aging. Embryonic inflammatory exposure accelerated age-related changes in spatial cognition, and in Ngpf2 and Psd-95 expression. Additionally, the levels of Ngpf2 and Psd-95 products were significantly positively and negatively correlated with cognitive dysfunction, respectively, particularly in prenatal inflammation-exposed aged mice. Changes in serum levels of IL-6, IL-1ß, and TNF-α reflective of systemic inflammation and their correlation with cognitive decline during accelerated aging were similar to those of hippocampal NGPF2. EE exposure could partially restore the accelerated decline in age-related cognitive function and in Psd-95 expression, especially in aged mice. Discussion: Overall, the aggravated cognitive disabilities in aged mice may be related to the alterations in Ngpf2 and Psd-95 expression and in systemic state of inflammation due to prenatal inflammatory exposure, and long-term EE exposure may ameliorate this cognitive impairment by upregulating Psd-95 expression.