The calcium-dependent protein kinase CPK16 regulates hypoxia-induced ROS production by phosphorylating the NADPH oxidase RBOHD in Arabidopsis.

Reactive oxygen species (ROS) production is a key event in modulating plant responses to hypoxia and post-hypoxia reoxygenation. However, the molecular mechanism by which hypoxia-associated ROS homeostasis is controlled remains largely unknown. Here, we showed that the calcium-dependent protein kinase CPK16 regulates plant hypoxia tolerance by phosphorylating the plasma membrane-anchored NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD) to regulate ROS production in Arabidopsis (Arabidopsis thaliana). In response to hypoxia or reoxygenation, CPK16 was activated through phosphorylation of its Ser274 residue. The cpk16 knockout mutant displayed enhanced hypoxia tolerance, whereas CPK16-overexpressing (CPK16-OE) lines showed increased sensitivity to hypoxic stress. In agreement with these observations, hypoxia and reoxygenation both induced ROS accumulation in the rosettes of CPK16-OEs more strongly than in rosettes of the cpk16-1 mutant or the wild type. Moreover, CPK16 interacted with and phosphorylated the N terminus of RBOHD at four serine residues (Ser133, Ser148, Ser163, and Ser347) that were necessary for hypoxia- and reoxygenation-induced ROS accumulation. Furthermore, the hypoxia-tolerant phenotype of cpk16-1 was fully abolished in the cpk16 rbohd double mutant. Thus, we have uncovered a regulatory mechanism by which the CPK16-RBOHD module shapes ROS production during hypoxia and reoxygenation in Arabidopsis.

Karyotype and LTR-RTs analysis provide insights into oak genomic evolution.

BACKGROUND: Whole-genome duplication and long terminal repeat retrotransposons (LTR-RTs) amplification in organisms are essential factors that affect speciation, local adaptation, and diversification of organisms. Understanding the karyotype projection and LTR-RTs amplification could contribute to untangling evolutionary history. This study compared the karyotype and LTR-RTs evolution in the genomes of eight oaks, a dominant lineage in Northern Hemisphere forests. RESULTS: Karyotype projections showed that chromosomal evolution was relatively conservative in oaks, especially on chromosomes 1 and 7. Modern oak chromosomes formed through multiple fusions, fissions, and rearrangements after an ancestral triplication event. Species-specific chromosomal rearrangements revealed fragments preserved through natural selection and adaptive evolution. A total of 441,449 full-length LTR-RTs were identified from eight oak genomes, and the number of LTR-RTs for oaks from section Cyclobalanopsis was larger than in other sections. Recent amplification of the species-specific LTR-RTs lineages resulted in significant variation in the abundance and composition of LTR-RTs among oaks. The LTR-RTs insertion suppresses gene expression, and the suppressed intensity in gene regions was larger than in promoter regions. Some centromere and rearrangement regions indicated high-density peaks of LTR/Copia and LTR/Gypsy. Different centromeric regional repeat units (32, 78, 79 bp) were detected on different Q. glauca chromosomes. CONCLUSION: Chromosome fusions and arm exchanges contribute to the formation of oak karyotypes. The composition and abundance of LTR-RTs are affected by its recent amplification. LTR-RTs random retrotransposition suppresses gene expression and is enriched in centromere and chromosomal rearrangement regions. This study provides novel insights into the evolutionary history of oak karyotypes and the organization, amplification, and function of LTR-RTs.

Effect of Negative Online Reviews and Physician Responses on Health Consumers' Choice: Experimental Study.

BACKGROUND: The COVID-19 pandemic has highlighted the importance of online medical services. Although some researchers have investigated how numerical ratings affect consumer choice, limited studies have focused on the effect of negative reviews that most concern physicians. OBJECTIVE: This study aimed to investigate how negative review features, including proportion (low/high), claim type (evaluative/factual), and physician response (absence/presence), influence consumers' physician evaluation process under conditions in which a physician's overall rating is high. METHODS: Using a 2×2×2 between-subject decision-controlled experiment, this study examined participants' judgment on physicians with different textual reviews. Collected data were analyzed using the t test and partial least squares-structural equation modeling. RESULTS: Negative reviews decreased consumers' physician selection intention. The negative review proportion (ß=-0.371, P<.001) and claim type (ß=-0.343, P<.001) had a greater effect on consumers' physician selection intention compared to the physician response (ß=0.194, P<.001). A high negative review proportion, factual negative reviews, and the absence of a physician response significantly reduced consumers' physician selection intention compared to their counterparts. Consumers' locus attributions on the negative reviews affected their evaluation process. Physician attribution mediated the effects of review proportion (ß=-0.150, P<.001), review claim type (ß=-0.068, P=.01), and physician response (ß=0.167, P<.001) on consumer choice. Reviewer attribution also mediated the effects of review proportion (ß=-0.071, P<.001), review claim type (ß=-0.025, P=.01), and physician response (ß=0.096, P<.001) on consumer choice. The moderating effects of the physician response on the relationship between review proportion and physician attribution (ß=-0.185, P<.001), review proportion and reviewer attribution (ß=-0.110, P<.001), claim type and physician attribution (ß=-0.123, P=.003), and claim type and reviewer attribution (ß=-0.074, P=.04) were all significant. CONCLUSIONS: Negative review features and the physician response significantly influence consumer choice through the causal attribution to physicians and reviewers. Physician attribution has a greater effect on consumers' physician selection intention than reviewer attribution does. The presence of a physician response decreases the influence of negative reviews through direct and moderating effects. We propose some practical implications for physicians, health care providers, and online medical service platforms.

Photoredox Cleavage of a Csp3-Csp3 Bond in Aromatic Hydrocarbons.

Functionalizing molecules through the selective cleavage of carbon-carbon bonds is an attractive approach in synthetic chemistry. Despite recent advances in both transition-metal catalysis and radical chemistry, the selective cleavage of inert Csp3-Csp3 bonds in hydrocarbon feedstocks remains challenging. Examples reported in the literature typically involve substrates containing redox functional groups or highly strained molecules. In this article, we present a straightforward protocol for the cleavage and functionalization of Csp3-Csp3 bonds in alkylbenzenes using photoredox catalysis. Our method employs two distinct bond scission pathways. For substrates with tertiary benzylic substituents, a carbocation-coupled electron transfer mechanism is prevalent. For substrates with primary or secondary benzylic substituents, a triple single-electron oxidation cascade is applicable. Our strategy offers a practical means of cleaving inert Csp3-Csp3 bonds in molecules without any heteroatoms, resulting in primary, secondary, tertiary, and benzylic radical species.

HIV-1 Tat-mediated astrocytic amyloidosis involves the HIF-1α/lncRNA BACE1-AS axis.

Increased life expectancy of patients diagnosed with HIV in the current era of antiretroviral therapy is unfortunately accompanied with the prevalence of HIV-associated neurocognitive disorders (HANDs) and risk of comorbidities such as Alzheimer-like pathology. HIV-1 transactivator of transcription (Tat) protein has been shown to induce the production of toxic neuronal amyloid protein and also enhance neurotoxicity. The contribution of astrocytes in Tat-mediated amyloidosis remains an enigma. We report here, in simian immunodeficiency virus (SIV)+ rhesus macaques and patients diagnosed with HIV, brain region-specific up-regulation of amyloid precursor protein (APP) and Aß (40 and 42) in astrocytes. In addition, we find increased expression of ß-site cleaving enzyme (BACE1), APP, and Aß in human primary astrocytes (HPAs) exposed to Tat. Mechanisms involved up-regulation of hypoxia-inducible factor (HIF-1α), its translocation and binding to the long noncoding RNA (lncRNA) BACE1-antisense transcript (BACE1-AS), resulting, in turn, in the formation of the BACE1-AS/BACE1 RNA complex, subsequently leading to increased BACE1 protein, and activity and generation of Aß-42. Gene silencing approaches confirmed the regulatory role of HIF-1α in BACE1-AS/BACE1 in Tat-mediated amyloidosis. This is the first report implicating the role of the HIF-1α/lncRNABACE1-AS/BACE1 axis in Tat-mediated induction of astrocytic amyloidosis, which could be targeted as adjunctive therapies for HAND-associated Alzheimer-like comorbidity.

ANi5Bi5.6+δ (A = K, Rb, and Cs): Quasi-One-Dimensional Metals Featuring [Ni5Bi5.6+δ]- Double-Walled Column with Strong Diamagnetism.

A new series of compounds, ANi5Bi5.6+δ (where A = K, Rb, and Cs) are discovered with a quasi-one-dimensional (Q1D) [Ni5Bi5.6+δ]- double-walled column and a coaxial inner one-dimensional Bi atomic chain. The columns are linked to each other by intercolumn Bi-Bi bonds and separated by an A+ cation. Typical metallic behaviors with strong correlation of itinerant electrons and the Sommerfeld coefficient enhanced with the increasing cationic radius were experimentally observed and supported by first-principles calculations. Compared to AMn6Bi5 (where A = K, Rb, and Cs), the enhanced intercolumn distances and the substitution of Ni for Mn give rise to strong diamagnetic susceptibilities in ANi5Bi5.6+δ. First-principles calculations reveal possible uncharged Ni atoms with even number of electrons in ANi5Bi5.6+δ, which may explain the emergence of diamagnetism. ANi5Bi5.6+δ, as Q1D diamagnetic metals with strong electron correlation, provide a unique platform to understand exotic magnetism and explore novel quantum effects.

Block2: A comprehensive open source framework to develop and apply state-of-the-art DMRG algorithms in electronic structure and beyond.

block2 is an open source framework to implement and perform density matrix renormalization group and matrix product state algorithms. Out-of-the-box it supports the eigenstate, time-dependent, response, and finite-temperature algorithms. In addition, it carries special optimizations for ab initio electronic structure Hamiltonians and implements many quantum chemistry extensions to the density matrix renormalization group, such as dynamical correlation theories. The code is designed with an emphasis on flexibility, extensibility, and efficiency and to support integration with external numerical packages. Here, we explain the design principles and currently supported features and present numerical examples in a range of applications.

A meta-analysis result: Uneven influences of season, geo-spatial scale and latitude on relationship between meteorological factors and the COVID-19 transmission.

Meteorological factors have been confirmed to affect the COVID-19 transmission, but current studied conclusions varied greatly. The underlying causes of the variance remain unclear. Here, we proposed two scientific questions: (1) whether meteorological factors have a consistent influence on virus transmission after combining all the data from the studies; (2) whether the impact of meteorological factors on the COVID-19 transmission can be influenced by season, geospatial scale and latitude. We employed a meta-analysis to address these two questions using results from 2813 published articles. Our results showed that, the influence of meteorological factors on the newly-confirmed COVID-19 cases varied greatly among existing studies, and no consistent conclusion can be drawn. After grouping outbreak time into cold and warm seasons, we found daily maximum and daily minimum temperatures have significant positive influences on the newly-confirmed COVID-19 cases in cold season, while significant negative influences in warm season. After dividing the scope of the outbreak into national and urban scales, relative humidity significantly inhibited the COVID-19 transmission at the national scale, but no effect on the urban scale. The negative impact of relative humidity, and the positive impacts of maximum temperatures and wind speed on the newly-confirmed COVID-19 cases increased with latitude. The relationship of maximum and minimum temperatures with the newly-confirmed COVID-19 cases were more susceptible to season, while relative humidity's relationship was more affected by latitude and geospatial scale. Our results suggested that relationship between meteorological factors and the COVID-19 transmission can be affected by season, geospatial scale and latitude. A rise in temperature would promote virus transmission in cold seasons. We suggested that the formulation and implementation of epidemic prevention and control should mainly refer to studies at the urban scale. The control measures should be developed according to local meteorological properties for individual city.

Laparoscopic middle-hepatic-vein-guided anatomical hemihepatectomy in the treatment of hepatolithiasis: a 10-year case study.

BACKGROUND: This retrospective 10-year case study evaluated the perioperative results and long-term efficacy of laparoscopic middle-hepatic-vein-guided hemihepatectomy (L-MHV-H) and traditional anatomical hemihepatectomy (TAH) in the treatment of hepatolithiasis (HL). METHODS: From January 2010 to December 2019, 99 patients with regional HL underwent laparoscopic anatomical hemihepatectomy (LAH) at our centre, including 43 patients in the L-MHV-H group and 56 patients in the TAH group. RESULTS: All patients in both groups were Child-Pugh grade A before operation. No significant between-group differences in general information, stone distribution, comorbidities, history of previous abdominal surgery or co-occurrence of gallstones and common bile duct stones were observed. The L-MHV-H group exhibited a higher intraoperative stone clearance rate (95.3% vs. 75.0%, p = 0.014) and a lower postoperative complication rate (10.1% vs. 48.2%, p = 0.005) compared with the TAH group. In the median follow-up time of 60 months (range 6-125 months), the L-MHV-H group had lower stone recurrence (2.3% vs. 19.6%, p = 0.013) and cholangitis recurrence (2.3% vs. 17.9%, p = 0.034) rates. No significant between-group differences in the other results were observed. CONCLUSIONS: L-MHV-H is safe and feasible for HL with certain advantages over TAH in improving the intraoperative stone clearance rate, reducing postoperative complication incidence and reducing stone and cholangitis recurrence rates.

Prenatal docosahexaenoic acid supplementation has long-term effects on childhood behavioral and brain responses during performance on an inhibitory task.

Introduction: Offsprings from a prenatal docosahexaenoic acid (DHA) supplementation trial, in which pregnant women were assigned to placebo or 600mg DHA/day, were followed to determine the effect of prenatal DHA supplementation on the behavior and brain function at 5.5 years (n=81 placebo, n=86 supplemented).Methods: Event-related potentials (ERP) were recorded during a visual task requiring a button press (Go) to frequent target stimuli and response inhibition to the rare stimuli (No-Go). Univariate ANOVAs were used to test differences between group and sex for behavioral measures. ERP differences were tested using a three-way mixed-design multivariate analysis of variance (MANOVA).Results: There was a significant sex × group interaction for hit rate and errors of omission; there was no difference between males and females in the placebo group, but DHA males outperformed DHA females. Males overall and the placebo group made more errors requiring response inhibition; DHA females were significantly better than placebo females and DHA males. ERP P2 amplitude was larger in the DHA group. A significant N2 amplitude condition effect was observed in females and DHA group males, but not in placebo group males.Discussion: Prenatal DHA supplementation improved inhibitory performance overall, especially for females in the DHA group, possibly accounting for their conservative behavior during Go trials. Development of brain regions responsible for visual processing may be sensitive to maternal DHA status, evidenced by greater P2 amplitude. Males may benefit more from maternal DHA supplementation, indicated by the N2 condition effect seen only in males in the DHA group.

Biogenesis, physiological functions and potential applications of extracellular vesicles in substance use disorders.

Substance use disorder (SUD) is a growing health problem that affects several millions of people worldwide, resulting in negative socioeconomic impacts and increased health care costs. Emerging evidence suggests that extracellular vesicles (EVs) play a crucial role in SUD pathogenesis. EVs, including exosomes and microvesicles, are membrane-encapsulated particles that are released into the extracellular space by most types of cells. EVs are important players in mediating cell-to-cell communication through transfer of cargo such as proteins, lipids and nucleic acids. The EV cargo can alter the status of recipient cells, thereby contributing to both physiological and pathological processes; some of these play critical roles in SUD. Although the functions of EVs under several pathological conditions have been extensively reviewed, EV functions and potential applications in SUD remain less studied. In this review, we provide an overview of the current knowledge of the role of EVs in SUD, including alcohol, cocaine, heroin, marijuana, nicotine and opiate abuse. The review will focus on the biogenesis and cargo composition of EVs as well as the potential use of EVs as biomarkers of SUD or therapeutic targets in SUD.

Cortical Correlates of Increased Postural Task Difficulty in Young Adults: A Combined Pupillometry and EEG Study.

The pupillary response reflects mental effort (or cognitive workload) during cognitive and/or motor tasks including standing postural control. EEG has been shown to be a non-invasive measure to assess the cortical involvement of postural control. The purpose of this study was to understand the effect of increasing postural task difficulty on the pupillary response and EEG outcomes and their relationship in young adults. Fifteen adults completed multiple trials of standing: eyes open, eyes open while performing a dual-task (auditory two-back), eyes occluded, and eyes occluded with a dual-task. Participants stood on a force plate and wore an eye tracker and 256-channel EEG cap during the conditions. The power spectrum was analyzed for absolute theta (4−7 Hz), alpha (8−13 Hz), and beta (13−30 Hz) frequency bands. Increased postural task difficulty was associated with greater pupillary response (p < 0.001) and increased posterior region alpha power (p = 0.001) and fronto-central region theta/beta power ratio (p = 0.01). Greater pupillary response correlated with lower posterior EEG alpha power during eyes-occluded standing with (r = −0.67, p = 0.01) and without (r = −0.69, p = 0.01) dual-task. A greater pupillary response was associated with lower CoP displacement in the anterior−posterior direction during dual-task eyes-occluded standing (r = −0.60, p = 0.04). The pupillary response and EEG alpha power appear to capture similar cortical processes that are increasingly utilized during progressively more challenging postural task conditions. As the pupillary response also correlated with task performance, this measurement may serve as a valuable stand-alone or adjunct tool to understand the underlying neurophysiological mechanisms of postural control.

Brassinosteroids Antagonize Jasmonate-Activated Plant Defense Responses through BRI1-EMS-SUPPRESSOR1 (BES1).

Brassinosteroids (BRs) and jasmonates (JAs) regulate plant growth, development, and defense responses, but how these phytohormones mediate the growth-defense tradeoff is unclear. Here, we identified the Arabidopsis (Arabidopsis thaliana) dwarf at early stages1 (dwe1) mutant, which exhibits enhanced expression of defensin genes PLANT DEFENSIN1.2a (PDF1.2a) and PDF1.2b The dwe1 mutant showed increased resistance to herbivory by beet armyworms (Spodoptera exigua) and infection by botrytis (Botrytis cinerea). DWE1 encodes ROTUNDIFOLIA3, a cytochrome P450 protein essential for BR biosynthesis. The JA-inducible transcription of PDF1.2a and PDF1.2b was significantly reduced in the BRASSINOSTEROID INSENSITIVE1-ETHYL METHANESULFONATE-SUPPRESSOR1 (BES1) gain-of-function mutant bes1- D, which was highly susceptible to S. exigua and B. cinerea BES1 directly targeted the terminator regions of PDF1.2a/PDF1.2b and suppressed their expression. PDF1.2a overexpression diminished the enhanced susceptibility of bes1- D to B. cinerea but did not improve resistance of bes1- D to S. exigua In response to S. exigua herbivory, BES1 inhibited biosynthesis of the JA-induced insect defense-related metabolite indolic glucosinolate by interacting with transcription factors MYB DOMAIN PROTEIN34 (MYB34), MYB51, and MYB122 and suppressing expression of genes encoding CYTOCHROME P450 FAMILY79 SUBFAMILY B POLYPEPTIDE3 (CYP79B3) and UDP-GLUCOSYL TRANSFERASE 74B1 (UGT74B1). Thus, BR contributes to the growth-defense tradeoff by suppressing expression of defensin and glucosinolate biosynthesis genes.

Laparoscopic anterior hepatic transection for resecting lesions originating in the paracaval portion of the caudate lobe (with videos).

BACKGROUND: The paracaval portion of the caudate lobe is located in the core of the liver. Lesions originating in the paracaval portion often cling to or even invade major hepatic vascular structures. The traditional open anterior hepatic transection approach has been adopted to treat paracaval-originating lesions. With the development of laparoscopic surgery, paracaval-originating lesions are no longer an absolute contraindication for laparoscopic liver resection. This study aimed to evaluate the safety and feasibility of laparoscopic anterior hepatic transection for resecting paracaval-originating lesions. METHODS: This study included 15 patients who underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection between August 2017 and April 2020. The perioperative indicators, follow-up results, operative techniques and surgical indications were retrospectively evaluated. RESULTS: All patients underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection. The median operation time was 305 min (220-740 min), the median intraoperative blood loss was 400 ml (250-3600 ml), and the median length of postoperative hospital stay was 9 days (5-20 days). No conversion to laparotomy or perioperative deaths occurred. Six patients had Clavien grade III-IV complications (III/IV, 5/1). Two patients developed tumor recurrence after 13 months and 8 months. CONCLUSION: Although technically challenging, laparoscopic anterior hepatic transection is still a safe and feasible procedure for resecting paracaval-originating lesions in select patients.

Current use of rivaroxaban in elderly patients with venous thromboembolism (VTE).

Venous thromboembolism (VTE), which is characterized by pulmonary embolism and deep vein thrombosis, has become a serious public concern. Notably, over half of the patients with VTE are over 70 years of age, but elderly patients are at high risk of anti-coagulation and bleeding, which increase with age. Moreover, risk factors and frailty also show a difference between elderly patients and ordinary patients diagnosed with VTE. Rivaroxaban is a direct inhibitor of activated factor Xa and has the advantage of predictable pharmacodynamics and pharmacokinetics, no coagulation monitoring, and few drug interactions. As a first-line therapy for VTE, this drug is more advantageous than traditional therapy and exhibits good efficacy and safety for ordinary patients. However, the effectiveness and safety of rivaroxaban in elderly patients have not been fully elucidated. This article reviewed the use of rivaroxaban in elderly patients, including drug interactions, monitoring, reversal agents of rivaroxaban, and the use of small dosages of rivaroxaban in elderly patients.

Successful cholangioscopic electrocoagulation for biliary papillomatosis: Report covering six cases (with video).

BACKGROUND: Biliary papillomatosis is a rare type of papillomatosis. Depending on the location of the disease, radical surgical resection or liver transplants are the treatment of choice. These radical surgical options may be unrealistic in patients who are not surgical candidates or who are unwilling to consider surgery. AIMS: To evaluate the effectiveness of endoscopic electrocoagulation for the biliary papillomatosis. METHODS: In this case series, we report six patients with unresectable biliary papillomatosis who underwent cholangioscopic electrocoagulation using needle knife and their clinic follow up information. RESULTS: After patients received cholangioscopy with electrocoagulation of the residual biliary papilloma, the daily T-tube drainage volume increased to 200-400ml with improvement in the drainage content and significant relief of clinical symptoms, such as jaundice and abdominal pain. CONCLUSION: This method of using electrocoagulation to directly target and destroy tumor tissue is a safe and effective alternative for those with unresectable disease, and this method has shown to enhance T-tube drainage volume and improve patients' overall clinical symptoms.

Resting frontal EEG asymmetry and schizotypal traits: a test-retest study.

Introduction: Increase in right relative to left frontal electroencephalography (EEG) activity has been observed in patients with schizophrenia, both in cognitive tasks and during rest; and this lateralisation may be related to the severity of schizotypal traits. Methods: We used the Schizotypal Personality Questionnaire (SPQ) to assess schizotypal traits, and examined the correlation between these traits and resting EEG frontal asymmetry (left-right) in 52 college students, as well as the reliability of this correlation over a three-month interval. Results: A higher total score on the SPQ was correlated with reduced asymmetry in different frequency bands: gamma and beta2 frequency bands at baseline, and delta and alpha frequency bands three months later. Additionally, the reduced left relative to right frontal gamma and beta2 asymmetry was correlated with the participants' verbal fluency ability. However, this correlation was no longer statistically significant after the total SPQ score was controlled. Conclusions: These findings suggest that resting frontal EEG asymmetry is correlated with powers in different frequency bands, and may be an endophenotype for schizophrenia spectrum disorders.

Long-chain polyunsaturated fatty acid supplementation in the first year of life affects brain function, structure, and metabolism at age nine years.

The present study sought to determine whether supplementation of long-chain polyunsaturated fatty acids (LCPUFA) during the first year of life influenced brain function, structure, and metabolism at 9 years of age. Newborns were randomly assigned to consume formula containing either no LCPUFA (control) or formula with 0.64% of total fatty acids as arachidonic acid (ARA; 20:4n6) and variable amounts of docosahexaenoic acid (DHA; 22:6n3) (0.32%, 0.64%, or 0.96% of total fatty acids) from birth to 12 months. At age 9 years (±0.6), 42 children enrolled in a follow-up multimodal magnetic resonance imaging (MRI) study including functional (fMRI, Flanker task), resting state (rsMRI), anatomic, and proton magnetic resonance spectroscopy (1 H MRS). fMRI analysis using the Flanker task found that trials requiring greater inhibition elicited greater brain activation in LCPUFA-supplemented children in anterior cingulate cortex (ACC) and parietal regions. rsMRI analysis showed that children in the 0.64% group exhibited greater connectivity between prefrontal and parietal regions compared to all other groups. In addition, voxel-based analysis (VBM) revealed that the 0.32% and 0.64% groups had greater white matter volume in ACC and parietal regions compared to controls and the 0.96% group. Finally, 1 H MRS data analysis identified that N-acetylaspartate (NAA) and myo-inositol (mI) were higher in LCPUFA groups compared to the control group. LCPUFA supplementation during infancy has lasting effects on brain structure, function, and neurochemical concentrations in regions associated with attention (parietal) and inhibition (ACC), as well as neurochemicals associated with neuronal integrity (NAA) and brain cell signaling (mI).

HIV-1 Tat Primes and Activates Microglial NLRP3 Inflammasome-Mediated Neuroinflammation.

Neuroinflammation associated with HIV-1 infection is a problem affecting ∼50% of HIV-infected individuals. NLR family pyrin domain containing 3 (NLRP3) inflammasome has been implicated in HIV-induced microglial activation, but the mechanism(s) remain unclear. Because HIV-1 Transactivator of Transcription (Tat) protein continues to be present despite antiretroviral therapy and activates NF-kB, we hypothesized that Tat could prime the NLRP3 inflammasome. We found a dose- and time-dependent induction of NLRP3 expression in microglia exposed to Tat compared with control. Tat exposure also time-dependently increased the mature caspase-1 and IL-1ß levels and enhanced the IL-1ß secretion. These in vitro findings were validated in archival brain tissues from Simian Immunodeficiency Virus (SIV)-infected and uninfected rhesus macaques. Further validation of NLRP3 priming in vivo involved administration of lipopolysaccharide (LPS) to HIV transgenic (Tg) rats followed by assessment of IL-1ß mRNA expression and inflammasome activation (ASC oligomers and mature IL-1ß). Intriguingly, LPS potentiated upregulation of IL-1ß mRNA and inflammasome activation in HIV-Tg rats compared with the wild-type controls. Interestingly, we found an inverse relationship in the expression of NLRP3 and its negative regulator, miR-223, suggesting a miR-223-mediated mechanism for Tat-induced NLRP3 priming. Furthermore, blockade of NLRP3 resulted in decreased IL-1ß secretion. Collectively, these findings suggest a novel role of Tat in priming and activating the NLRP3 inflammasome. Therefore, NLRP3 can be envisioned as a therapeutic target for ameliorating Tat-mediated neuroinflammation.SIGNIFICANCE STATEMENT Despite successful suppression of viremia with increased longevity in the era of combined antiretroviral therapy, chronic inflammation with underlying neurocognitive impairment continues to afflict almost 50% of infected individuals. Viral, bacterial, and cellular products have all been implicated in promoting the chronic inflammation found in these individuals. Understanding the molecular mechanism(s) by which viral proteins such as HIV-1 Transactivator of Transcription (Tat) protein can activate microglia is thus of paramount importance. Herein, we demonstrate a novel role of Tat in priming and activating NLR family pyrin domain containing 3 (NLRP3) inflammasomes in microglial cells and in HIV-Tg rats administered lipopolysaccharide. Targeting NLRP3 inflammasome pathway mediators could thus be developed as therapeutic interventions to alleviate or prevent neuroinflammation and subsequent cognitive impairment in HIV-positive patients.

Study on the cephalopelvic relationship with cephalic presentation in nulliparous full-term Chinese pregnant women by MRI with three-dimensional reconstruction.

PURPOSE: To analyze the relationship between fetal head size and maternal pelvis size using magnetic resonance imaging (MRI) with a 3-D reconstruction technique. METHODS: A total of 301 nulliparous full-term Chinese pregnant women with cephalic presentation were enrolled and received MRI examinations before labor onset. Data were collected and imported into Mimics software to reconstruct the maternal pelvis and fetus. RESULTS: Of 301 pregnant women, 212 underwent vaginal delivery and 32 received cesarean section. The body mass index (BMI) was significantly different between the vaginal delivery group and the suspected cephalopelvic disproportion (CPD) group; the larger the BMI, the higher was the risk of CPD. The transverse diameter of the pelvic inlet and the posterior sagittal diameter of the midpelvis were significantly larger in the vaginal delivery group, compared with the suspected CPD group. Fetal weight > 3.5 kg could be used as a diagnostic indicator for CPD. CONCLUSIONS: BMI is a risk factor for CPD, and fetal weight < 3.5 kg is an important diagnostic indicator for natural delivery in Chinese pregnant women.