Efficacy of SARS-CoV-2 vaccines and the dose-response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody concentrations can predict the efficacy is also uncertain. We aimed to assess the efficacy of these vaccines in preventing SARS-CoV-2 infections of different severities and the dose-response relationship between the antibody concentrations and efficacy. METHODS: We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, WHO, bioRxiv, and medRxiv for papers published between Jan 1, 2020 and Sep 12, 2022. RCTs on the efficacy of SARS-CoV-2 vaccines were eligible. Risk of bias was assessed using the Cochrane tool. A frequentist, random-effects model was used to combine efficacy for common outcomes (ie, symptomatic and asymptomatic infections) and a Bayesian random-effects model was used for rare outcomes (ie, hospital admission, severe infection, and death). Potential sources of heterogeneity were investigated. The dose-response relationships of neutralising, spike-specific IgG and receptor binding domain-specific IgG antibody titres with efficacy in preventing SARS-CoV-2 symptomatic and severe infections were examined by meta-regression. This systematic review is registered with PROSPERO, CRD42021287238. FINDINGS: 28 RCTs (n=286 915 in vaccination groups and n=233 236 in placebo groups; median follow-up 1-6 months after last vaccination) across 32 publications were included in this review. The combined efficacy of full vaccination was 44·5% (95% CI 27·8-57·4) for preventing asymptomatic infections, 76·5% (69·8-81·7) for preventing symptomatic infections, 95·4% (95% credible interval 88·0-98·7) for preventing hospitalisation, 90·8% (85·5-95·1) for preventing severe infection, and 85·8% (68·7-94·6) for preventing death. There was heterogeneity in the efficacy of SARS-CoV-2 vaccines against asymptomatic and symptomatic infections but insufficient evidence to suggest whether the efficacy could differ according to the type of vaccine, age of the vaccinated individual, and between-dose interval (p>0·05 for all). Vaccine efficacy against symptomatic infection waned over time after full vaccination, with an average decrease of 13·6% (95% CI 5·5-22·3; p=0·0007) per month but can be enhanced by a booster. We found a significant non-linear relationship between each type of antibody and efficacy against symptomatic and severe infections (p<0·0001 for all), but there remained considerable heterogeneity in the efficacy, which cannot be explained by antibody concentrations. The risk of bias was low in most studies. INTERPRETATION: The efficacy of SARS-CoV-2 vaccines is higher for preventing severe infection and death than for preventing milder infection. Vaccine efficacy wanes over time but can be enhanced by a booster. Higher antibody titres are associated with higher estimates of efficacy but precise predictions are difficult due to large unexplained heterogeneity. These findings provide an important knowledge base for interpretation and application of future studies on these issues. FUNDING: Shenzhen Science and Technology Programs.

Surgical treatment versus observation in moderate intermittent exotropia (SOMIX): study protocol for a randomized controlled trial.

BACKGROUND: Intermittent exotropia (IXT) is the most common type of strabismus in China, but the best treatment and optimal timing of intervention for IXT remain controversial, particularly for children with moderate IXT who manifest obvious exodeviation frequently but with only partial impairment of binocular single vision. The lack of randomized controlled trial (RCT) evidence means that the true effectiveness of the surgical treatment in curing moderate IXT is still unknown. The SOMIX (surgical treatment versus observation in moderate intermittent exotropia) study has been designed to determine the long-term effectiveness of surgery for the treatment and the natural history of IXT among patients aged 5 to 18 years old. METHODS/DESIGN: A total of 280 patients between 5 and 18 years of age with moderate IXT will be enrolled at Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. After initial clinical assessment, all participants will be randomized to receive surgical treatment or observation, and then be followed up for 5 years. The primary objective is to compare the cure rate of IXT between the surgical treatment and observation group. The secondary objectives are to identify the predictive factors affecting long-term outcomes in each group and to observe the natural course of IXT. DISCUSSION: The SOMIX trial will provide important guidance regarding the moderate IXT and its managements and modify the treatment strategies of IXT. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02736526 . Registered April 13, 2016.

Dietary choline metabolite TMAO impairs cognitive function and induces hippocampal synaptic plasticity declining through the mTOR/P70S6K/4EBP1 pathway.

Mild cognitive impairment (MCI) is an intermediate state between "healthy" and "dementia", which affects memory and cognitive function. Timely intervention and treatment of MCI can effectively prevent it from developing into an incurable neurodegenerative disease. Lifestyle factors, such as dietary habits, were highlighted as risk factors for MCI. The effect of a high-choline diet on cognitive function is contentious. In this study, we focus our attention on the choline metabolite trimethylamine-oxide (TMAO), an acknowledged pathogenic molecule of cardiovascular disease (CVD). With recent studies indicating that TMAO also plays a potential role in the central nervous system (CNS), we aim to explore the effect of TMAO on synaptic plasticity in the hippocampus, the basic structure of studying and memory. Using various hippocampal-dependent spatial references or working memory-related behavioral texts, we found that TMAO treatment caused both long-term memory (LTM) and short-term memory (STM) deficits in vivo. Simultaneously, the plasm and whole brain levels of choline and TMAO were measured by employing liquid phase mass spectrometry (LC/MS). Furthermore, the effects of TMAO on the hippocampus were further explored by applying Nissl staining and transmission electron microscopy (TEM). Moreover, the expression of synaptic plasticity-related proteins, including synaptophysin (SYN), postsynaptic density protein95 (PSD95), and N-methyl-aspartate receptor (NMDAR), was examined by western blotting and immunohistochemical (IHC). The results showed that TMAO treatment contributes to neuron loss, synapse ultrastructure alteration, and synaptic plasticity impairments. In mechanism, the mammalian target of rapamycin (mTOR) regulates synaptic function, and the activation of the mTOR signaling pathway was observed in TMAO groups. In conclusion, this study confirmed that the choline metabolite TMAO can induce hippocampal-dependent learning and memory ability impairment with synaptic plasticity deficits by activating the mTOR signaling pathway. The effects of choline metabolites on cognitive function may provide a theoretical basis for establishing the daily reference intakes (DRIs) of choline.

[Discrimination of cultivation modes of Dendrobium nobile based on content of mineral elements and ratios of nitrogen stable isotopes].

This study explored the feasibility of mineral element content and ratios of nitrogen isotopes to discriminate the cultivation mode of Dendrobium nobile in order to provide theoretical support for the discrimination of the cultivation mode of D. nobile. The content of 11 mineral elements(N, K, Ca, P, Mg, Na, Fe, Cu, Zn, Mn, and B) and nitrogen isotope ratios in D. nobile and its substrate samples in three cultivation methods(greenhouse cultivation, tree-attached cultivation, and stone-attached cultivation) were determined. According to the analysis of variance, principal component analysis, and stepwise discriminant analysis, the samples of different cultivation types were classified. The results showed that the nitrogen isotope ratios and the content of elements except for Zn were significantly different among different cultivation types of D. nobile(P<0.05). The results of correlation analysis showed that the nitrogen isotope ratios, mineral element content, and effective component content in D. nobile were correlated with the nitrogen isotope ratio and mineral element content in the corresponding substrate samples to varying degrees. Principal component analysis can preliminarily classify the samples of D. nobile, but some samples overlapped. Through stepwise discriminant analysis, six indicators, including δ~(15)N, K, Cu, P, Na, and Ca, were screened out, which could be used to establish the discriminant model of D. nobile cultivation methods, and the overall correct discrimination rates after back-substitution test, cross-check, and external validation were all 100%. Therefore, nitrogen isotope ratios and mineral element fingerprints combined with multivariate statistical analysis could effectively discriminate the cultivation types of D. nobile. The results of this study provide a new method for the identification of the cultivation type and production area of D. nobile and an experimental basis for the quality evaluation and quality control of D. nobile.

[Quality evaluation of Cnidii Fructus in commodity grade based on theory of "quality evaluation through morphological identification"].

From the perspective of market classification of Cnidii Fructus, this paper revealed the scientific connotation of evaluating the quality grade of Cnidii Fructus by its appearance traits. Thirty batches of Cnidii Fructus in different grades were selected as the research objects. The canonical correlation analysis and principal component analysis(PCA) were used to explore the measurement values of 15 appearance traits and intrinsic content indexes. The results of correlation analysis showed that except the aspect ratio, the 5 appearance trait indexes(length, width, 1 000-grain weight, broken grain weight proportion, and chroma) and 9 internal content indexes(the content of moisture, total ash, acid insoluble ash, osthole, imperatorin, 5-methoxy psoralen, isopimpinellin, xanthotoxin, and xanthotol) showed significant correlation to varying degrees. In addition, there was a significant positive correlation between the first typical variable U_1 composed of appearance traits and the first typical variable V_1 composed of internal content indexes(CR_1=0.963, P<0.01). The results of PCA showed that the classification results of appearance traits for 30 batches of Cnidii Fructus were consistent with the actual information of the samples. Under the same analysis conditions, 30 batches of Cnidii Fructus were reclassified by 9 groups of internal content indexes, and the analysis results were consistent. From the classification standard of the appearance traits of the system study, the statistical results of 6 appearance traits of Cnidii Fructus showed a correlation with grades. There was a good correlation between the appearance and the internal content of Cnidii Fructus, and the appearance quality effectively predicted the level of the internal content. There is a certain scientific basis for the quality classification of Cnidii Fructus by main appearance traits. Appearance classification can replace quality grading to realize the "quality evaluation through morphological identification" of Cnidii Fructus.

Early postsurgical lethal outcome due to splenic littoral cell angioma: A case report.

BACKGROUND: Littoral cell angioma (LCA) is a rare benign vascular tumor of the spleen. Given its rarity, standard diagnostic and therapeutic recommendations have yet to be developed for reported cases. Splenectomy is the only method of obtaining a pathological diagnosis and providing treatment to obtain a favorable prognosis. CASE SUMMARY: A 33-year-old female presented with abdominal pain for one month. Computed tomography and ultrasound revealed splenomegaly with multiple lesions and two accessory spleens. The patient underwent laparoscopic total splenectomy and accessory splenectomy, and splenic LCA was confirmed by pathology. Four months after surgery, the patient presented with acute liver failure, was readmitted, rapidly progressed to multiple organ dysfunction syndrome and died. CONCLUSION: Preoperative diagnosis of LCA is challenging. We systematically reviewed online databases to identify the relevant literature and found a close relationship between malignancy and immunodysregulation. When a patient suffers from both splenic tumors and malignancy or immune-related disease, LCA is possible. Due to potential malignancy, total splenectomy (including accessory spleen) and regular follow-up after surgery are recommended. If LCA is diagnosed after surgery, a comprehensive postoperative examination is needed.

Structural characteristics and diversity of the rhizosphere bacterial communities of wild Fritillaria przewalskii Maxim. in the northeastern Tibetan Plateau.

Introduction: Fritillaria przewalskii Maxim. is a Chinese endemic species with high medicinal value distributed in the northeastern part of the Tibetan Plateau. F. przewalskii root-associated rhizosphere bacterial communities shaped by soil properties may maintain the stability of soil structure and regulate F. przewalskii growth, but the rhizosphere bacterial community structure of wild F. przewalskii from natural populations is not clear. Methods: In the current study, soil samples from 12 sites within the natural range of wild F. przewalskii were collected to investigate the compositions of bacterial communities via high-throughput sequencing of 16S rRNA genes and multivariate statistical analysis combined with soil properties and plant phenotypic characteristics. Results: Bacterial communities varied between rhizosphere and bulk soil, and also between sites. Co-occurrence networks were more complex in rhizosphere soil (1,169 edges) than in bulk soil (676 edges). There were differences in bacterial communities between regions, including diversity and composition. Proteobacteria (26.47-37.61%), Bacteroidetes (10.53-25.22%), and Acidobacteria (10.45-23.54%) were the dominant bacteria, and all are associated with nutrient cycling. In multivariate statistical analysis, both soil properties and plant phenotypic characteristics were significantly associated with the bacterial community (p < 0.05). Soil physicochemical properties accounted for most community differences, and pH was a key factor (p < 0.01). Interestingly, when the rhizosphere soil environment remained alkaline, the C and N contents were lowest, as was the biomass of the medicinal part bulb. This might relate to the specific distribution of genera, such as Pseudonocardia, Ohtaekwangia, Flavobacterium (relative abundance >0.01), which all have significantly correlated with the biomass of F. przewalskii (p < 0.05). Discussion: F. przewalskii is evidently averse to alkaline soil with high potassium contents, but this requires future verification. The results of the present study may provide theoretical guidance and new insights for the cultivation and domestication of F. przewalskii.

Skin infectome of patients with a tick bite history.

Introduction: Ticks are the most important obligate blood-feeding vectors of human pathogens. With the advance of high-throughput sequencing, more and more bacterial community and virome in tick has been reported, which seems to pose a great threat to people. Methods: A total of 14 skin specimens collected from tick-bite patients with mild to severe symptoms were analyzed through meta-transcriptomic sequencings. Results: Four bacteria genera were both detected in the skins and ticks, including Pseudomonas, Acinetobacter, Corynebacterium and Propionibacterium, and three tick-associated viruses, Jingmen tick virus (JMTV), Bole tick virus 4 (BLTV4) and Deer tick mononegavirales-like virus (DTMV) were identified in the skin samples. Except of known pathogens such as pathogenic rickettsia, Coxiella burnetii and JMTV, we suggest Roseomonas cervicalis and BLTV4 as potential new agents amplified in the skins and then disseminated into the blood. As early as 1 day after a tick-bite, these pathogens can transmit to skins and at most four ones can co-infect in skins. Discussion: Advances in sequencing technologies have revealed that the diversity of tick microbiome and virome goes far beyond our previous understanding. This report not only identifies three new potential pathogens in humans but also shows that the skin barrier is vital in preventing horizontal transmissions of tick-associated bacteria or virus communities to the host. It is the first research on patients' skin infectome after a tick bite and demonstrates that more attention should be paid to the cutaneous response to prevent tick-borne illness.

Investigation of the antibacterial mechanism of the novel bactericide dioctyldiethylenetriamine (Xinjunan).

BACKGROUND: Chemical control is an important method for controlling crop diseases. Clarifying the antibacterial mechanisms of bactericides is useful for developing new bactericides and for continuous plant disease control. In this study, the antibacterial mechanism of a novel bactericide, dioctyldiethylenetriamine (Xinjunan), which affects adenosine triphosphate (ATP) synthesis, was investigated. RESULTS: The results of an in vitro inhibition activity assay showed that dioctyldiethylenetriamine inhibited the growth of a variety of plant pathogenic bacteria, especially for Xanthomonas spp. Scanning electron microscopy that dioctyldiethylenetriamine caused cell distortion and rupture. To investigate the molecular mechanism underlying the antibacterial effect of dioctyldiethylenetriamine, transcriptome sequencing (RNA-seq) was performed for Xanthomonas oryzae pv. oryzae (Xoo, PXO99A) treated with dioctyldiethylenetriamine, which has strong antibacterial effects against xanthomonads. The results showed, differentially expressed genes were mainly enriched in the oxidative phosphorylation and tricarboxylic acid (TCA) cycle pathways after treatment. Moreover, it was found that the treatment with dioctyldiethylenetriamine exhibited reduction in enzyme activities in the TCA cycle, decreased intracellular nicotinamide adenine dinucleotide and ATP contents, and increased accumulation of reactive oxygen species. In addition, dioctyldiethylenetriamine exhibited the inhibitory effect on the growth of other bacterial pathogens by reducing ATP synthesis. CONCLUSION: This is the first report of the mechanism by which dioctyldiethylenetriamine inhibits ATP synthesis by affecting oxidative phosphorylation and TCA cycle pathways in bacteria.

Corrigendum: Efficacy and safety of riociguat replacing PDE-5is for patients with pulmonary arterial hypertension: A systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fphar.2023.1052546.].

Rapid screening of diarylpentanoids from Daphne bholua.

Fractionation motivated by biological activity screening and NMR characteristic signals analysis led to the isolation of seventeen diarylpentanoids from the whole plant of Daphne bholua Buch.-Ham. ex D. Don, among which nine compounds were undescribed. Their structures and stereochemistry were determined by comprehensive spectroscopic data, J-based configurational analysis, and quantum chemical calculations. The inhibitory potentials of all isolates against acetylcholinesterase were evaluated in vitro and in silico.

The Outcome-Present State Test Model of Clinical Reasoning to Promote Critical Thinking in Psychiatric Nursing Practice among Nursing Students: A Mixed Research Study.

This study determined whether teaching intervention using the outcome-present state test (OPT) clinical reasoning model can effectively improve critical thinking in nursing students during a psychiatry internship. In addition, it evaluates the experiences of the students using this model in clinical practice. METHODS: In this interventional study, 19 students were taught critical thinking skills using the OPT clinical reasoning model during a psychiatry clinical practice. Work-learning forms were used in daily 1 h individual and group discussions with students. The critical thinking disposition scale was completed by every student before and after the intervention. Moreover, the students were asked to the complete reflection experience forms. RESULTS: The average critical thinking disposition pre-intervention score was 95.21, whereas the average post-intervention score was 97.05, indicating an increase of 1.84. There was a significant increase in the fourth dimension of open-mindedness (z = -2.80, p < 0.01). The learning experience has been likened to a process of clearing the fog, and it involves the use of limited known conditions, thinking outside the box, and adaptation to complex care issues. CONCLUSION: Using the OPT clinical reasoning model as a teaching strategy during a psychiatric nursing internship significantly improved the open-mindedness dimension among the students. The student reflective experience of talking to teachers as peers helped students identify clues and reframe problems related to clinical care. Additionally, the students reported that this led to more harmonious interactions with their teachers.

Translocation and metabolism of tricresyl phosphate in rice and microbiome system: Isomer-specific processes and overlooked metabolites.

Tricresyl phosphate (TCP) is extensively used organophosphorus flame retardants and plasticizers that posed risks to organisms and human beings. In this study, the translocation and biotransformation behavior of isomers tri-p-cresyl phosphate (TpCP), tri-m-cresyl phosphate (TmCP), and tri-o-cresyl phosphate (ToCP) in rice and rhizosphere microbiome was explored by hydroponic exposure. TpCP and TmCP were found more liable to be translocated acropetally, compared with ToCP, although they have same molecular weight and similar Kow. Rhizosphere microbiome named microbial consortium GY could reduce the uptake of TpCP, TmCP, and ToCP in rice tissues, and promote rice growth. New metabolites were successfully identified in rice and microbiome, including hydrolysis, hydroxylated, methylated, demethylated, methoxylated, and glucuronide- products. The methylation, demethylation, methoxylation, and glycosylation pathways of TCP isomers were observed for the first time in organisms. What is more important is that the demethylation of TCPs could be an important and overlooked source of triphenyl phosphate (TPHP), which broke the traditional understanding of the only manmade source of toxic TPHP in the environment. Active members of the microbial consortium GY during degradation were revealed and metagenomic analysis indicated that most of active populations contained TCP-degrading genes. It is noteworthy that the strains and function genes in microbial consortium GY that responsible for TCP isomers' transformation were different. These results can improve our understanding of the translocation and transformation of organic pollutant isomers in plants and rhizosphere microbiome.

Light-Induced Flavonoid Biosynthesis in Sinopodophyllum hexandrum with High-Altitude Adaptation.

Sinopodophyllum hexandrum is a perennial alpine herb producing the anti-cancer metabolite podophyllotoxin (PPT). Although the adaptation of S. hexandrum to high altitudes has been demonstrated and the effects of temperature, precipitation, and UV-B light on plant growth and metabolite accumulation have been studied, knowledge on the role of flavonoid biosynthesis in adapting to high altitudes is limited. In this study, light intensity, amount and type of flavonoids, and differentially expressed proteins (DEPs) and genes (DEGs) at 2300 and 3300 m were analyzed by HPLC, proteomic, transcriptomic, and qRT-PCR analysis. We found that higher light intensity correlated with greater flavonoid, flavonol, and anthocyanin content as well as higher anthocyanin to total flavonoid and flavonol ratios observed at the higher altitude. Based on proteomic and transcriptomic analyses, nine DEPs and 41 DEGs were identified to be involved in flavonoid biosynthesis and light response at 3300 m. The relative expression of nine genes (PAL, CHS1, IFRL, ANS, MYB4, BHLH137, CYP6, PPO1, and ABCB19) involved in flavonoid biosynthesis and seven genes (HSP18.1, HSP70, UBC4, ERF5, ERF9, APX3, and EX2) involved in light stress were observed to be up-regulated at 3300 m compared with 2300 m. These findings indicate that light intensity may play a regulatory role in enhancing flavonoid accumulation that allows S. hexandrum to adapt to elevated-altitude coupled with high light intensity.

Crouzon syndrome complicated with binocular strabismus and extraocular muscle fibrosis: a case report.

BACKGROUND: Crouzon syndrome, a rare genetic disorder characterized by premature closure of coronal sutures, results in skull and facial deformities along with abnormal brain and ocular development. CASE PRESENTATION: Here, we report a case of a 27-year-old ethnic han male patient who presented with complex binocular strabismus secondary to Crouzon syndrome. At the time of surgery, extraocular muscles were found to be fibrotic and results of the pathological examination revealed degeneration of muscle fibers, which were replaced by adipose tissue. The entire exome sequencing DNA testing indicated that the patient and his father possessed the fibroblast growth factor receptor 2 (FGFR2) gene c.G812T:p.G271V heterozygous mutation. Binocular strabismus corrective surgery was performed in this patient with a satisfactory outcome. CONCLUSIONS: This case demonstrates that Crouzon syndrome patients can show an FGFR2 gene c.G812T:p.G271V mutation and display clinical symptoms such as extraocular muscle fibrosis, exotropia, exophthalmos, and a pointed head deformity.

[Coal-carbon-pollutant Coordinated Control of Coal Chemical Industry Under Carbon Peak and Carbon Neutrality Constraints].

Under carbon peak and carbon neutrality constraints, the coal chemical industry should take stricter measures to tackle carbon reduction. Based on the intensity differences of five major coal and carbon reduction measures applied by the coal chemical industry, which include raw material structure adjustment, fuel structure adjustment, energy-saving technology transformation, terminal capture technology, and industrial structure adjustment, this study adopted the downstream sector demand method and project method, combined with the air pollution reduction model, to predict three scenarios (benchmark, policy, and enhancement) of coal chemical industry peak year and peak amount of coal consumption and carbon dioxide emission, associated with air pollutant reduction row effects. The results showed that coal consumption under the benchmark and policy scenarios of the coal chemical industry is expected to reach a peak in the late period of China's "14th Five-Year Plan", with peak values of 0.96 billion and 0.93 billion tons, respectively. By contrast, under the enhanced scenario, it is expected to peak in the early period of the "14th Five-Year Plan" with a value of 0.91 billion tons. The carbon peak will arrive in the late period of the "15th Five-Year Plan" under the benchmark scenario but in the early and late period of the "14th Five-Year Plan" under the policy and enhanced scenarios, with peak values of approximately 0.64 billion, 0.57 billion, and 0.55 billion tons, respectively. Controlling the construction scale of new coal chemical projects, tapping the space for raw material substitution, and speeding up the energy-saving technological transformation are important measures for coal and carbon control in the coal chemical industry. The implementation of coal and carbon reduction measures of the coal chemical industry will coordinately reduce air pollutant emissions, such as SO2, NOx, PM, and VOCs by 37, 43, 11, and 28 thousand tons per year after 2035.

Efficacy and safety of riociguat replacing PDE-5is for patients with pulmonary arterial hypertension: A systematic review and meta-analysis.

Introduction: Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Some patients treated with phosphodiesterase type 5 inhibitors (PDE-5is) fail to reach treatment goals. As a novel soluble guanylate cyclase agonist, riociguat acts on the same pathway as PDE-5is but functions via different mechanisms. Whether riociguat is more effective and safer than PDE-5is is ambiguous. We aimed to evaluate the efficacy and safety of switching from PDE-5is to riociguat among these patients. Methods: Original published articles were retrieved from PubMed/Medline, Embase, Web of Science, Open Grey and Google Scholar. Studies that assessed the World Health Organization functional class (WHO-FC), 6-min walking distance (6MWD), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), cardiac index (CI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were collected. Adverse events after switching were evaluated. Results: Ten published studies were included. Compared to PDE-5is, riociguat significantly increased the 6MWD by 26.45 m weighted mean difference (WMD) = 26.45 m, 95% confidence intervals (CIs): 9.70-43.2 m, p = 0.002) and improved mPAP (WMD = -3.53, 95% CIs: -5.62-1.44 mmHg, p = 0.0009), PVR (WMD = -130.24 dyn·s·cm-5, 95% CI -187.43-73.05, p < 0.0001), CIs (WMD = 0.36 L/min·cm-2, 95% CIs: 0.25-0.47, p < 0.00001) and WHO-FC (OR = 0.11, 95% CIs: 0.08-0.16, p < 0.0001) but not NT-proBNP. In addition, we did not observe the most common side effects during the replacement of riociguat for PDE-5is. Conclusions: PAH patients benefit from PDE-5is compared to riociguat, including in hemodynamic parameters, 6MWD, WHO-FC and biomarkers.

Experimental Study on Performance Optimization of Grouting Backfill Material Based on Mechanically Ground Coal Gangue Utilizing Urea and Quicklime.

Previously conducted studies have established that grouting backfill in mining-induced overburden bed separation and mined-out areas with broken rocks provides an efficient strategy to control strata movement and surface subsidence caused by underground mining. Grouting backfill materials (GBMs) based on coal gangue (CG) are highly desirable in coal mining for accessibility to abundant CG and urgent demand for CG disposal. However, CG is generally employed as coarse aggregate due to rather rigid and inert properties, limiting its application in GBMs. Herein, to reduce reliance on fine aggregates, such as fly ash and clay, cemented GBM formulations using ground CG powder as a dominant component were proposed. Urea and quicklime were utilized as additives to optimize slurry transportability and compressive strength. Besides typical grinding without additives, CG powder was also prepared via grinding with urea, intending to enhance the hydrogen bonding (HB) interaction between urea and minerals contained in CG. The effect of grinding time and urea on CG particle size and phase composition was investigated. Then, the dependence of slurry transportability and compressive strength on grinding time, solid concentration, urea, and quicklime dosage were revealed. It has been experimentally proved that grinding for 30~90 min significantly decreased CG particle size and even induced crystal deformation of dolomite and kaolinite. For GBMs, urea improved slurry flowability, possibly caused by decreased water absorption on the CG surface and the release of water encapsulated in hydrated cement particles. Moreover, quicklime strengthened GBM bodies, which could be explained by an accelerated pozzolanic reaction between CG powder and additional CH supplied by quicklime hydration. G60U3-based GBM-B2 with 5% quicklime provided a stable and smooth slurry with a bleeding rate of 1.25%, a slump flow of 205 mm, and a hardened body with a seven-day UCS of 1.51 MPa.

Investigation of the antifungal activity of the dicarboximide fungicide iprodione against Bipolaris maydis.

Southern corn leaf blight (SCLB), mainly caused by Bipolaris maydis, is a destructive disease of maize worldwide. Iprodione is a widely used dicarboximide fungicide (DCF); however, its antifungal activity against B. maydis has not been well studied until now. In this study, the sensitivity of 103 B. maydis isolates to iprodione was determined, followed by biochemistry and physiology assays to ascertain the fungicide's effect on the morphology and other biological properties of B. maydis. The results indicated that iprodione exhibited strong inhibitory activity against B. maydis, and the EC50 values in inhibiting mycelial growth ranged from 0.088 to 1.712 µg/mL, with a mean value of 0.685 ± 0.687 µg/mL. After treatment with iprodione, conidial production of B. maydis was decreased significantly, and the mycelia branches increased with obvious shrinkage, distortion and fracture. Moreover, the expression levels of the osmotic pressure-related regulation genes histidine kinase (hk) and Ssk2-type mitogen-activated protein kinase (ssk2) were upregulated, the glycerin content of mycelia increased significantly, the relative conductivity of mycelia increased, and the cell wall membrane integrity was destroyed. The in vivo assay showed that iprodione at 200 µg/mL provided 79.16% protective efficacy and 90.92% curative efficacy, suggesting that the curative effect was better than the protective effect. All these results proved that iprodione exhibited strong inhibitory activity against B. maydis and provided excellent efficacy in controlling SCLB, indicating that iprodione could be an alternative candidate for the control of SCLB in China.

The role of positive affect processes in the association between posttraumatic stress disorder symptoms and sleep: A multi-study design.

OBJECTIVES: Posttraumatic stress disorder (PTSD) symptoms have been linked to sleep disturbances. Limited work has explored how positive affect processes may account for this relationship. Advancing research in this area, we utilized a multi-study design to investigate the role of positive affect processes (levels of positive affect, positive emotionality, hedonic deficits, negative affect interference) in the PTSD-sleep association. METHODS: Data from 149 trauma-exposed firefighters (Mage = 38.93 ± 9.65, 5.40 % women) were collected between September 2021 and November 2021, and data from 119 trauma-exposed community members (Mage = 29.60 ± 8.67, 68.10 % women) were collected between February 2021 and December 2021. Participants completed an online survey on PTSD symptoms, sleep disturbances, and positive affect processes. RESULTS: Positive affect levels (b = 0.03, 95 % confidence interval [CI] [0.01, 0.06]; firefighter sample), positive emotionality (b = 0.07, CI [0.03, 0.13]; community sample), and negative affect interference (b = 0.06, CI [0.01, 0.14]; community sample) significantly accounted for the associations between PTSD symptom severity and sleep disturbances controlling for the effects of gender and age. CONCLUSION: Findings highlight the role of positive affect processes in the link between PTSD and sleep, and support addressing positive affect processes as potential targets in clinical interventions for co-occurring PTSD-sleep problems.