Key Residue in the Precursor Region of M Protein Contributes to the Neurovirulence and Neuroinvasiveness of the African Lineage of Zika Virus.

The Zika virus (ZIKV) represents an important global health threat due to its unusual association with congenital Zika syndrome. ZIKV strains are phylogenetically grouped into the African and Asian lineages. However, the viral determinants underlying the phenotypic differences between the lineages remain unknown. Here, multiple sequence alignment revealed a highly conserved residue at position 21 of the premembrane (prM) protein, which is glutamic acid and lysine in the Asian and African lineages, respectively. Using reverse genetics, we generated a recombinant virus carrying an E21K mutation based on the genomic backbone of the Asian lineage strain FSS13025 (termed E21K). The E21K mutation significantly increased viral replication in multiple neural cell lines with a higher ratio of M to prM production. Animal studies showed E21K exhibited increased neurovirulence in suckling mice, leading to more severe defects in mouse brains by causing more neural cell death and destruction of hippocampus integrity. Moreover, the E21K substitution enhanced neuroinvasiveness in interferon alpha/beta (IFN-α/ß) receptor knockout mice, as indicated by the increased mortality, and enhanced replication in mouse brains. The global transcriptional analysis showed E21K infection profoundly altered neuron development networks and induced stronger antiviral immune response than wild type (WT) in both neural cells and mouse brains. More importantly, the reverse K21E mutation based on the genomic backbone of the African strain MR766 caused less mouse neurovirulence. Overall, our findings support the 21st residue of prM functions as a determinant for neurovirulence and neuroinvasiveness of the African lineage of ZIKV. IMPORTANCE The suspected link of Zika virus (ZIKV) to birth defects led the World Health Organization to declare ZIKV a Public Health Emergency of International Concern. ZIKV has been identified to have two dominant phylogenetic lineages, African and Asian. Significant differences exist between the two lineages in terms of neurovirulence and neuroinvasiveness in mice. However, the viral determinants underlying the phenotypic differences are still unknown. Here, combining reverse genetics, animal studies, and global transcriptional analysis, we provide evidence that a single E21K mutation of prM confers to the Asian lineage strain FSS130125 significantly enhanced replication in neural cell lines and more neurovirulent and neuroinvasiveness phenotypes in mice. Our findings support that the highly conserved residue at position 21 of prM functions as a determinant of neurovirulence and neuroinvasiveness of the African lineage of ZIKV in mice.

Association between abnormal body weight and stroke outcome: A meta-analysis and systematic review.

BACKGROUND AND PURPOSE: To test the hypothesis that "obesity paradox" exists in stroke patients, we conducted a meta-analysis and systematic review on the association between abnormal body weight (obesity, overweight, or underweight) and the outcome of different types of stroke. METHODS: This meta-analysis and systematic review was performed in conformity to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines in Appendix S2. Studies investigating the association between abnormal body weight and the outcome of different types of stroke were searched for in the PubMed and Embase databases from their inception to 20 March 2021. RESULTS: Thirty-three articles including 84,660 patients were included in this study. Obesity and overweight were associated with longer survival in mixed-stroke patients (acute ischemic stroke [AIS] combined with one or more other stroke subtypes) than was normal weight, whereas underweight was related to shorter survival; the pooled hazard ratios (HRs) of mortality were 0.77 (95% confidence interval [CI] = 0.71-0.83) for obesity, 0.76 (95% CI = 0.72-0.80) for overweight, and 1.71 (95% CI = 1.56-1.87) for underweight. However, only obesity was associated with longer survival in AIS patients compared with normal weight, and underweight was related to shorter survival; the pooled HR of mortality was 0.75 (95% CI = 0.64-0.88) for obesity and 1.53 (95% CI = 1.27-1.85) for underweight. After merging mixed-stroke and AIS patients, we obtained similar results as in mixed-stroke patients. CONCLUSIONS: Our results suggested that in patients with mixed stroke or AIS, obesity was associated with a longer survival time than normal weight, whereas underweight was associated with a shorter survival time.

Safety and efficacy of tirofiban combined with endovascular therapy compared with endovascular therapy alone in acute ischemic stroke: a meta-analysis.

Endovascular treatment (EVT) has been widely used for treating acute ischemic stroke (AIS). However, the safety and efficacy of treating AIS with tirofiban combined with EVT remain controversial. Therefore, we conducted a meta-analysis to evaluate this treatment. Randomized controlled trials and cohort studies that compared treatment with tirofiban combined with EVT and EVT alone were included in our meta-analysis. Those published from inception to March 31, 2020, were searched using the PubMed, Web of Science, Embase, and Cochrane Library databases. Safety was assessed based on symptomatic intracranial hemorrhage (sICH) incidence and 3-month mortality. Efficacy was assessed based on modified Rankin Scale (mRS) scores at 3 months post-EVT and recanalization rates. Data were analyzed using either the random-effects or fixed-effects model based on the heterogeneity of studies. In total, one RCT, six prospective studies, and four retrospective studies (2387 AIS cases) were assessed. Our meta-analysis showed that tirofiban combined with EVT did not increase sICH risk (RR, 1.06; 95%CI, 0.79 to 1.42; P = 0.72) and 3-month mortality (RR, 0.87; 95%CI, 0.74 to 1.04; P = 0.12). Recanalization rates were not significantly different between patients treated with tirofiban combined with EVT and those treated with EVT alone (RR, 1.04; 95%CI, 1.00 to 1.08; P = 0.07), but tirofiban combined with EVT was significantly associated with favorable functional outcomes (mRS score, 0-2) in AIS patients (RR, 1.13; 95%CI, 1.02 to 1.25; P = 0.02). Tirofiban combined with EVT appears to be safe and potentially effective in treating AIS.

The Impact of Remote Ischaemic Conditioning on Beat-to-Beat Heart Rate Variability Circadian Rhythm in Healthy Adults.

BACKGROUND: Remote ischaemic conditioning (RIC) is an intervention that may exert a protective effect over multiple tissues or organs by regulating neuronal signal transduction. Heart rate variability (HRV) can assess the state of the autonomic nervous system. However, whether RIC can also regulate HRV in humans remains unknown. METHOD: This was a self-controlled interventional study in which serial beat-to-beat monitoring was performed at the same seven time points (7, 9, and 11 AM; 2, 5, and 8 PM; and 8 AM on the next day) with or without RIC in 50 healthy adults. The seven time points on the RIC day were defined as baseline, 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours after RIC. The RIC protocol consisted of 4×5-minute inflation/deflation in one arm and one thigh cuff at 200 mmHg pressure from 7:20 to 8 AM. This study is registered on ClinicalTrials.gov (NCT02965547). RESULTS: We included 50 healthy adult volunteers (aged 34.54±12.01 years, 22 men [44%], all Asian). The variables analysed in frequency-domain measures performed as power of low-frequency in normalised units (0.04-0.15 Hz), high-frequency in normalised units (0.15-0.40 Hz), and ratio of low frequency to high frequency. The time-domain parameters standard deviation (SD) of all normal to normal (NN) intervals (SDNN), mean of the 5-minute SD of the NN intervals, SD of the consecutive 5-minute averages of NN intervals, and the root mean square of successive differences of NN intervals, and time-domain parameters calculated from Poincaré plots, SD of the short diagonal axis in Poincaré plot (SD1), SD of the long diagonal axis in Poincaré plot (SD2), and SD1/SD2 were also obtained. The SDNN and SD2 significantly increased 1 hour after RIC (p=0.029 and p=0.045, respectively). Additionally, the SD2 increased a second time 12 hours after RIC (p=0.041), which represented inhibited sympathetic activity. CONCLUSIONS: Heart rate variability increase and sympathetic inhibition induced by RIC appeared both on the early and delayed protective window of RIC, which may indicate some of the underlying mechanisms by which RIC may offer protection.

Mapping a double flower phenotype-associated gene DcAP2L in Dianthus chinensis.

The double flower is a highly important breeding trait that affects the ornamental value in many flowering plants. To get a better understanding of the genetic mechanism of double flower formation in Dianthus chinensis, we have constructed a high-density genetic map using 140 F2 progenies derived from a cross between a single flower genotype and a double flower genotype. The linkage map was constructed using double-digest restriction site-associated DNA sequencing (ddRAD-seq) with 2353 single nucleotide polymorphisms (SNPs). Quantitative trait locus (QTL) mapping analysis was conducted for 12 horticultural traits, and major QTLs were identified for nine of the 12 traits. Among them, two major QTLs accounted for 20.7% and 78.1% of the total petal number variation, respectively. Bulked segregant RNA-seq (BSR-seq) was performed to search accurately for candidate genes associated with the double flower trait. Integrative analysis of QTL mapping and BSR-seq analysis using the reference genome of Dianthus caryophyllus suggested that an SNP mutation in the miR172 cleavage site of the A-class flower organ identity gene APETALA2 (DcAP2L) is responsible for double flower formation in Dianthus through regulating the expression of DcAG genes.

Venous sinus stenting improves cerebral autoregulation in a patient with venous sinus stenosis: a case report.

BACKGROUND: Venous sinus stenosis (VSS) is a type of cerebral venous vascular disease. Cerebral autoregulation is an indicator of cerebral arterial function. The cerebral circulatory system is composed of the venous system and arterial system. Impaired venous function may affect arterial function. Thus, cerebral venous stenosis may influence cerebral autoregulation. CASE PRESENTATION: In this case, a 50-year-old woman with transient blindness and headache was admitted to the hospital. The patient was diagnosed with VSS. A stent was placed at the stenosis. The stent released the intravenous pressure and remitted the patient's symptoms. Measurements of dynamic cerebral autoregulation (dCA) were performed at 3 time points: before stenting, after stenting, and 3 months later. The dCA gradually improved after stenting. CONCLUSION: VSS may have an influence on cerebral autoregulation, and effective treatment improves cerebral autoregulation in patients with VSS.

Hydrogenation of CO2 to Methanol Catalyzed by Cp*Co Complexes: Mechanistic Insights and Ligand Design.

A direct hydride transfer mechanism with three cascade cycles for the conversion of carbon dioxide and dihydrogen to methanol (CO2 + 3H2 → CH3OH + H2O) catalyzed by a half-sandwich cobalt complex [Cp*Co(bpy-Me)OH2]2+ (1) is proposed based on density functional theory calculations. The formation of methanediol via hydride transfer from Co to formic acid (4 → TS8,11) is the rate-determining step with a total barrier of 26.0 kcal/mol in free energy. Furthermore, 15 analogues of 1 are constructed by replacing the hydrogen atoms at the two meta and para positions of the bipyridine ligand with different functional groups (1b-1l), the carbon atoms in the bipyridine ligand with nitrogen atoms (1m-1o), and one pyridine ligand with N-heterocyclic carbene (1p). Among all newly proposed complexes, [Cp*Co(2,2'-bipyrazine)OH2]2+ (1n) is the most active one with a total barrier of 19.6 kcal/mol in free energy. Such a low barrier indicates 1n is a promising catalyst for efficient conversion of CO2 and H2 to methanol at room temperature.

Characteristics of cardio-Cerebrovascular modulation in patients with generalized anxiety disorder: an observational study.

BACKGROUND: Generalized anxiety disorder (GAD) has been shown in previous studies to display abnormal cerebral blood flow velocity (CBFV); however, the characteristics of cardio-cerebrovascular modulation are unknown. We aimed to analyze cardio-cerebrovascular modulation using parameters from a supine-to-standing test. METHODS: There are 2 parts to this study; in Part 1, 125 participants with Hamilton Anxiety scale scores ≥14 were enrolled, and 33 age- and sex-matched medically and psychiatrically healthy volunteers were recruited as control participants. Patients were divided by score into mild, moderate, and severe anxiety groups. The cardio-cerebrovascular modulation using the parameters of dynamic changes of CBFV and heart rate in response to an orthostatic challenge were investigated. In Part 2, we followed up the severe GAD patients for 6 months and repeated the supine-to-standing test, and severe GAD patients were divided into recovery and non-recovery groups. RESULTS: In part 1, the GAD group displayed more marked CBFV and heart rate changes than the healthy group, but there was no difference in the CBFV and heart rate changes from the supine to upright position in mild, moderate, and severe anxiety groups. In part 2, The recovery group demonstrated significant improvement in changes in the CBFV and heart rate values from the supine to the upright position after treatment compared with before treatment. In the non-recovery group, the CBFV and heart rate changes were significantly higher than the healthy group regardless of treatment. CONCLUSIONS: Cardio-cerebrovascular modulation is compromised in patients with GAD, however, this impairment can be restored to normal after the disappearance of anxiety.

[Genetic analysis of two pediatric patients with Beckwith-Wiedemann syndrome].

OBJECTIVE: To explore the genetic cause for two children with omphalocele. METHODS: The patients were examined, and the medical history of their families was collected. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to detect potential mutation in the patients. RESULTS: Loss of methylation of imprinting center 2 (IC2) at the 11p15.5 region of the maternal chromosome was detected in both children. CONCLUSION: The two patients were diagnosed with Beckwith-Wiedemann syndrome by MS-MLPA. The loss of methylation of IC2 probably underlies the disease in both patients.

Directivity pattern of the sound radiated from axisymmetric stepped plates.

For the purpose of optimal design and efficient utilization of the kind of stepped plate radiator in air, in this contribution, an approach for calculation of the directivity pattern of the sound radiated from a stepped plate in flexural vibration with a free edge is developed based on Kirchhoff-Love hypothesis and Rayleigh integral principle. Experimental tests of directivity pattern for a fabricated flat plate and two fabricated plates with one and two step radiators were carried out. It shows that the configuration of the measured directivity patterns by the proposed analytic approach is similar to those of the calculated approach. Comparison of the agreement between the calculated directivity pattern of a stepped plate and its corresponding theoretical piston show that the former radiator is equivalent to the latter, and the diffraction field generated by the unbaffled upper surface may be small. It also shows that the directivity pattern of a stepped radiator is independent of the metallic material but dependent on the thickness of base plate and resonant frequency. The thicker the thickness of base plate, the more directive the radiation is. The proposed analytic approach in this work may be adopted for any other plates with multi-steps.

Effects of a Planned Web-Based Educational Intervention Based on the Health Belief Model for Patients With Ischemic Stroke in Promoting Secondary Prevention During the COVID-19 Lockdown in China: Quasi-Experimental Study.

Background: Some common modified vascular risk factors remain poorly controlled among stroke survivors, and educational programs may help improve these conditions. Objective: This study aimed to evaluate the effect of a planned web-based educational intervention based on the health belief model (HBM) in promoting secondary prevention among patients with ischemic stroke. Methods: An evaluation-blinded quasi-experimental trial with a historical control group was conducted. Patients admitted from March to June 2020 were assigned to the historical control group, and patients admitted from July to October 2020 were assigned to the intervention group. The control group received routine health management. The intervention group received 6 additional sessions based on the HBM via Tencent Meeting, an audio and video conferencing application, within 3 months after discharge. Sessions were held every 2 weeks, with each session lasting approximately 40 minutes. These sessions were conducted in small groups, with about 8 to 10 people in each group. The primary outcomes were changes in blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1c), and the proportion of patients achieving the treatment target. The secondary outcomes were medication adherence, assessed with the Morisky Medicine Adherence Scale (MMAS), and disability, assessed with the modified Rankin scale. Results: In total, 315 patients experiencing their first-ever stroke were analyzed. More patients in the intervention group had controlled BP (41.9% vs 28.4%; adjusted odds ratio [aOR] 1.93; P=.01), LDL-C (83.1% vs 67.7%; aOR 2.66; P=.001), and HbA1c (91.9% vs 83.9%; aOR: 3.37; P=.04) levels as well as a significant postintervention decrease in the systolic BP (adjusted ß -3.94; P=.02), LDL-C (adjusted ß -0.21; P=.008), and HbA1c (adjusted ß -0.27; P<.001), compared with control groups. Significant between-group differences were observed in medication adherence (79.4% vs 63.2%; aOR 2.31; P=.002) but not in favorable functional outcomes. Conclusions: A web-based education program based on the HBM may be more effective than current methods used to educate patients having strokes on optimal vascular risk factors and medication adherence.

Effect of acupuncture for patients with knee osteoarthritis: study protocol for a double-dummy randomized controlled trial.

BACKGROUND: Acupuncture has been used to relieve chronic pain in patients with knee osteoarthritis (KOA), but the evidence is contradictory. Therefore, we carefully designed a double-dummy randomized controlled trial (RCT) to explore the therapeutic effect of acupuncture for KOA. METHODS/DESIGN: A total of 138 eligible participants with KOA who consent to participate will be randomly divided into Groups A, B, and C in a ratio of 1:1:1. Participants in Group A will receive verum acupuncture and placebo gel, while those in Groups B and C will be treated with diclofenac diethylammon gel and sham acupuncture, sham acupuncture and placebo gel, respectively. The patients will receive 4 weeks of treatment, five times a week, including acupuncture treatment once a day for 30 min and gel treatment three times a day. The primary outcome will be the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at week 4. The secondary outcomes will include visual analog scale (VAS), Arthritis Quality of Life Measurement Scale Simplified Scale (AIMS2-SF), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Credibility/Expectancy Questionnaire. The evaluation will be performed at baseline, week 4, 8, and 12 after randomization. DISCUSSION: This double-dummy RCT used diclofenac diethylammon gel as a positive control, and the completion of this trial will provide detailed and accurate evidence of the efficacy and safety of acupuncture for KOA. TRIAL REGISTRATION: China Clinical Trials Registry No.ChiCTR2100043947. Registered on September 24, 2020. https://www.chictr.org.cn/showproj.html?proj=122536 .

Huangqi Decoction, a compound Chinese herbal medicine, inhibits the proliferation and activation of hepatic stellate cells by regulating the long noncoding RNA-C18orf26-1/microRNA-663a/transforming growth factor-ß axis.

OBJECTIVE: Huangqi Decoction (HQD), a classical traditional Chinese medicine formula, has been used as a valid treatment for alleviating liver fibrosis; however, the underlying molecular mechanism is still unknown. Although our previous studies showed that microRNA-663a (miR-663a) suppresses the proliferation and activation of hepatic stellate cells (HSCs) and the transforming growth factor-ß/small mothers against decapentaplegic (TGF-ß/Smad) pathway, whether long noncoding RNAs (lncRNAs) are involved in HSC activation via the miR-663a/TGF-ß/Smad signaling pathway has not yet reported. The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis. METHODS: The expression levels of lnc-C18orf26-1, miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction. HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs. The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs. Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs. RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs. Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA. The expression levels of collagen α-2(I) chain (COL1A2), α-smooth muscle actin (α-SMA) and TGF-ß/Smad signaling pathway-related proteins were determined using Western blotting. RESULTS: Lnc-C18orf26-1 was upregulated in TGF-ß1-activated HSCs and competitively bound to miR-663a. Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation, downregulated TGF-ß1-stimulated α-SMA and COL1A2 expression, and inhibited the TGF-ß1/Smad signaling pathway. HQD suppressed the proliferation and activation of HSCs. HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs. Further studies showed that HQD inhibited the expression of COL1A2, α-SMA, TGF-ß1, TGF-ß type I receptor (TGF-ßRI) and phosphorylated Smad2 (p-Smad2) in HSCs, and these effects were reversed by miR-663a inhibitor treatment. CONCLUSION: Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis. HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-ß1/TGF-ßRI/p-Smad2 axis.

Development and Optimization of Network Music Course Resources Based on Data Mining Technology under the Personalized Online Education Environment.

The ever-evolving Internet technology has brought more information resources for music teaching than ever before. For music educators, figuring out how to create and use these tools more effectively has become a pressing concern. China will usher in a new age of innovation and integration between the Internet and different traditional businesses with the idea of "Internet Plus." MOOCs present significant challenges to traditional teachers and teaching methods as a typical practice of the transformation of education informatization to innovation, and they also drive global education toward a new process of informatization development. This paper adopts Internet thinking as the guiding ideology for the development of future music education concepts and, concurrently, conducts specific transformation research based on Internet technology from four aspects: music teaching content, music teaching methods, music education concepts, and the passing down of traditional music culture. The improved association rule algorithm is used to organise the students' access data, decide which high-frequency websites are accessible to the students, and realize the intuitive positioning of high-frequency access and learning issues. Assist the school's decision-making and educational levels in identifying the issues that students have with their learning, and then, improve the network teaching platform's material to complete the task of personalized network education.

Impact of Stroke Severity on the Smoking Paradox in Patients Treated with Intravenous Thrombolysis.

OBJECTIVE: To our knowledge, no previous studies have investigated the impact of stroke severity on the smoking paradox after intravenous thrombolysis (IVT). We aimed to explore the contribution of stroke severity to the association between smoking and stroke prognosis after IVT. METHODS: We enrolled consecutive patients who received IVT within 4.5 hours from stroke onset. A logistic regression model was used to estimate the unadjusted and adjusted odds ratios (ORs) with their 95% confidence intervals (CIs) for poor functional outcome and mortality at 3 months. RESULTS: Among patients with moderate stroke, smokers experienced a lower risk of 3-month poor outcomes than non-smokers (33.0% vs. 44.4%, unadjusted OR: 0.616; 95% CI: 0.402-0.945). However, among those with severe stroke, smokers had a higher risk of 3-month poor outcomes than non-smokers (81.6% vs. 55.9%, unadjusted OR: 3.496; 95% CI: 1.207-10.127). After adjustment, the negative correlation between smoking and 3-month poor outcome following IVT lost statistical significance in patients with moderate stroke (OR: 0.677 [95% CI: 0.418-1.097]). However, smoking remained a risk factor for 3-month poor outcomes in patients with severe stroke (OR: 4.216 [95% CI: 1.236-14.385]). We also observed a significant interaction between smoking and stroke severity with regard to the risk of poor functional outcomes (p=0.023). However, no such interaction influenced mortality (p=0.901). CONCLUSION: Stroke severity affects the association between smoking and 3-month clinical functional outcomes following IVT.

Nitrogen isotope constraint on the zonation of multiple transformations between dissolved and particulate organic nitrogen in the Changjiang plume.

Information on the sources and transformations of particulate organic N (PN) and dissolved organic N (DON) at the coastal interface remains insufficient due to technological difficulties and complicated features of intensive physical mixing and rapid biological activities. Here, we investigated the spatial distribution of concentrations and isotopic compositions of PN and DON in the Changjiang plume during the summer flood period. In average, DON and PN accounted for 25.6 ± 12.1% and 8.1 ± 9.1% (n = 55), respectively, of the total N pool, with the remaining N primarily in the form of nitrate (NO3-). Mean δ15N values were the lowest for DON (-0.1 ± 2.7‰, n = 58) and slightly higher for PN (2.0 ± 1.6‰, n = 101), and the highest for NO3- (6.5 ± 2.2‰, n = 67), suggesting multiple transformations had occurred to differentiate isotopic characteristics among the three N pools. By applying a conservative mixing model, we found DON deficits (-3.5 ± 3.7 µmol L-1, n = 43) and negative shift in δ15NDON (-3.6 ± 2.2‰, n = 43) in the Changjiang plume, revealing nonconservative DON behaviors. In the offshore surface plume where Chlorophyll a was high, the most likely cause is the DON uptake by phytoplankton with a strong inverse isotope effect (around -40‰). This DON assimilation by phytoplankton contributed to ~16 ± 12% of the PN production, with the remaining supported by NO3- assimilation, producing an overall isotope effect of 4-9‰. However, in waters near the river mouth and at the bottom of the offshore plume where total suspended matter concentrations were high (>5 mg L-1), the DON deficit was most likely induced by the selective adsorption of 15N enriched moieties of DON onto particulate surfaces (with an isotope effect of -20‰ to -5‰). Unlike dissolved organic carbon to behave conservatively in most estuaries, our results show that active transformations had occurred between the DON and PN pools in the Changjiang plume.

Individualized Nutritional Support for Hospitalized Patients With Oropharyngeal Dysphagia After Stroke: A Randomized Controlled Trial.

Objectives: Post-stroke dysphagia may cause aspiration pneumonia, malnutrition, dehydration, and other complications. However, data on the effects of nutritional supplementation and its value after stroke are insufficient. We aimed to evaluate the effect of an individualized 1-week nutrition intervention program on swallowing function and nutritional status in stroke patients with oropharyngeal dysphagia. Methods: This study comprised the control group receiving oral nutritional support and continuous nasogastric tube feeding according to the results of the water swallow test (WST). The intervention group additionally underwent a volume-viscosity swallowing test (V-VST) and intermittent oroesophageal tube feeding based on WST. The outcomes were measured after 7 days of intervention, including the improvement of swallowing function assessment by WST, biochemical parameters, such as total serum protein, serum albumin, hemoglobin levels and body composition. This trial was registered with the Chinese Clinical Trial Registry, identifier ChiCTR 2100054054. Results: In total, 173 participants completed the study between September 1, 2020, and April 30, 2021. Patients receiving individualized nutritional support showed a more significant improvement in the total effective rate of swallowing function (95.3% vs. 85.1%, P < 0.05). After the intervention, the total serum protein level (0.97 ± 0.41 vs. -0.83 ± 0.47 g/L; P < 0.05), serum albumin level (0.33 ± 0.28 vs. -1.39 ± 0.36 g/L; P < 0.001) and lean tissue mass (0.13 ± 0.35 vs. -1.00 ± 0.40 g/L; P < 0.05) increased in the intervention group. The decrease of hemoglobin levels in the control group was more evident (-6.17 ± 1.63 vs. -0.64 ± 1.40 g/L; 95%CI, -9.78 to -1.28; P = 0.001). The difference of phase angle between the two groups was statistically significant (5.93 ± 0.88° vs. 5.77 ± 0.78°; P = 0.035), but not in body fat mass. Conclusions: In stroke patients with oropharyngeal dysphagia, the use of individualized nutritional support based on V-VST and intermittent oroesophageal tube feeding during the first week of hospitalization improved swallowing function and maintained nutritional status. Clinical Trial Registration: https://clinicaltrials.gov/, identifier: ChiCTR 2100054054.

Diel change in inorganic nitrogenous nutrient dynamics and associated oxygen stoichiometry along the Pearl River Estuary.

The reactive nitrogen (N) emitted from continents significantly perturbs the pristine N cycle around the land-ocean boundary resulting in eutrophication and hypoxia. As nutrients are transported downstream through an estuary, various types of biological processes co-occur to modulate nitrogen speciation to influence the biogeochemical habitats for downstream microorganisms. We surveyed the Pearl River Estuary to examine the N transfer dynamics among nitrogen species with considering process-specific oxygen production and consumption. By using 15N pulse-tracing techniques, we measured ammonia oxidation and uptakes of ammonium, nitrite, and nitrate simultaneously under dark and light conditions in parallel. Light strongly inhibited nitrification but enhanced N uptake, and such light effect was further considered in the calculation for nitrogen transformation rates over a diel cycle. We found both oxidation and uptake of ammonium decreased seaward as substrate decreased. The nitrifier and phytoplankton work in antiphase to draw down incoming ammonium rapidly. Contrary to ammonium uptake, uptake of nitrite and nitrate showed a seaward increasing pattern. Such an inverse spatial pattern implies a shift in N preference for phytoplankton. Such high ammonium preference inhibits nitrate/nitrite uptake allowing them to behave conservatively in the estuary and to travel farther to outer estuary. By integrating oxygen consumption and production induced by N transformation processes over the diel cycle, oxygen was produced although allochthonous ammonium input is high (∼250 µM). For most stations, ammonium was completely consumed within 2 days, some stations even less than 0.5 days, implying that although the water residence time is short (2-15 days), tremendous input of ammonium N from upstream was transformed into particulate organic or nitrate forms during traveling to modulate the biogeochemical niche, including substrate, organics and oxygen, of coastal microbes in water column and sediments.

Sedimentary processes dominate nitrous oxide production and emission in the hypoxic zone off the Changjiang River estuary.

Coastal oceans, known as the major nitrous oxide (N2O) source to the atmosphere, are increasingly subject to eutrophication and concurrent near-bottom hypoxia. The natural nitrogen cycle is likely to be altered markedly in hypoxic coastal oceans. However, the processes responsible for N2O production and emission remain elusive because of lacking field rate measurements simultaneously conducted in the water column and sediment. Here, we quantified N2O production rates using a 15N-labeled technique in the water-column and surface sediments off the Changjiang (Yangtze) River estuary, the largest hypoxic zone in the Pacific margins. Our results showed that the estuarine surface sediments were the major source for N2O production, accounting for approximately 90% of the total water-column accumulation and consequent efflux of N2O in the hypoxic zone, whereas the water-column nitrification and denitrification combined only contributed <10%. More importantly, the coupling of nitrification and denitrification at the presence of abundant supply and remineralization of labile organic matter was the main driver of the N2O release from the sediment-water interface in this region. This study highlights the dominant role of benthic processes occurring at the sediment-water interface controlling the coastal N2O budget, as the anthropogenic eutrophication and hypoxia are expanding in coastal oceans.

Platelet-to-lymphocyte ratio at 24h after thrombolysis is a prognostic marker in acute ischemic stroke patients.

Background: The changes in the platelet-to-lymphocyte ratio (PLR) before and after recombinant tissue plasminogen activator (rtPA) treatment and the time point at which the PLR is a potentially valuable prognostic predictor in patients wit ischemic stroke remain largely unknown. Therefore, the purpose of this study was to explore the characteristics of the PLR and evaluate their effects on clinical outcomes before and 24 h after rtPA treatment. Methods: This study included 741 consecutive patients with acute ischemic stroke who underwent intravenous thrombolysis with rtPA. We collected data on demographics, vascular risk factors, medication history, and other clinical information pertaining to all patients. Specifically, blood samples for PLR measurement were collected on admission and 24 h after stroke. The outcome was assessed by using the Modified Rankin Scale (mRS) at 3 months and whether death occurred within 3 months or not. Univariate and multivariate logistic regression analysis was used to assess the association of the PLR with the risks of poor outcome (mRS>2) and death. An individualized prediction model was established to predict poor outcome. Results: Of the 741 patients, 255 (34.4%) had poor outcome, and 43 (5.8%) died. The PLR significantly increased 24 h after rtPA in patients with poor outcome and death. Logistic analysis revealed that higher PLR 24 h after rtPA was independently associated with increased risks of poor outcome and death. However, the PLR on admission was not associated with the risks of poor outcome and death. The individualized prediction model for poor outcome based on the 24-h PLR exhibited favorable discrimination (areas under the curves of the training and validation groups: 0.743 and 0.729, respectively), calibration (P > 0.05), and clinical usefulness. Conclusions: We found the PLR to be a variable that potentially predicts the risks of poor outcome and death in patients with acute ischemic stroke 24 h after rtPA; however, it cannot make the same prediction on admission.