The Zinc sulfide (ZnS) sample was synthesized using Zinc acetate dihydrate, and thiourea as ingredients by the hydrothermal reaction without using any dispersants and surfactants were used in the reaction process. The product composition and morphology were confirmed by XRD and SEM. The experimental results showed that after hydrothermal reaction at 150℃ for 8 h, the as-obtained ZnS microspheres diameter was about 3μm. Then, ZnS microspheres were used as photocatalyst, and the photocatalytic degradation rate of methylene blue solution reached 91.1% after ultraviolet light irradiation for 150 min.

Background Antenatal corticosteroids (ACS) are recommended in threatened preterm labour to improve short term neonatal outcome. Preclinical animal studies suggest detrimental effects of ACS exposure on offspring cardiac development; their effects in humans are unknown. Objectives To systematically review the human clinical literature to determine the effects of ACS on offspring cardiovascular function. Main results Twenty-six studies including 1921 patients were included, of which most were cohort studies of mixed quality. The type of ACS exposure, gestational age at exposure, dose and number of administrations varied widely. Offspring cardiovascular outcomes were assessed from one day to 36 years postnatally. The most commonly assessed parameter was arterial blood pressure (18 studies), followed by echocardiography (8 studies), heart rate (5 studies), electrocardiogram (ECG, 3 studies) and cardiac magnetic resonance imaging (MRI, 1 study). There were no clinically significant effects of ACS exposure on offspring blood pressure. However, there were insufficient studies assessing cardiac structure and function using echocardiography or cardiac MRI to be able to determine an effect. Conclusions Administration of ACS is not associated with long-term effects on blood pressure in exposed human offspring. The effects on cardiac structure and other measures of cardiac function were unclear due to the small number of studies, study heterogeneity and mixed quality. Given the emerging preclinical evidence of harm following ACS exposure, there is a need for further research to assess central cardiac function in human offspring exposed to ACS. Keywords: Antenatal corticosteroids, ACS, cardiovascular, offspring, blood pressure

Human metapneumovirus can be detected in adult community-acquired pneumonia. The chest image in this case was too massive to suspect human metapneumovirus pneumonia and clinically indistinguishable from Mycoplasma pneumoniae pneumonia. This case illustrates the difficulty of diagnostic imaging and importance of molecular diagnosis to avoid inappropriate use of antibiotics.

Previously treated pulmonary tuberculosis and Corona Virus Disease -2019 predispose to CPA and other pulmonary fungal diseases due to residual lung damage. We report a case of CPA in a 63-years-old Cameroonian woman with a history of PTB, 13 months after suffering from COVID-19 and treated with itraconazole 100mg.

Background and Purpose: Aberrant overexpression of UHRF1 has been reported in several cancer types and UHRF1 is regarded as a novel drug target for cancer therapy. However, no UHRF1-targeted specific small compound inhibitor has been registered in clinical trials. Experimental Approach: Network pharmacology together with molecular docking were used to screened a natural molecule bank for PCa treatment. The expression of related protein or mRNA were evaluated by WB and RT-PCR. The ubiquitination levels were assessed by WB. CCK8 assess was used to measuring cells viability. Additionally, PCa cells cycle were analysed by cytofluorimetry, genomic DNA methylation was assessed by Dot blot analysis. Cellular senescence was assessed by Senescence-Associated β-Galactosidase Staining Kit. DU145 cell xenograft models were used to assess the in vivo effect of DSG inhibition. Key Results: Identified DSG as a new natural compound specifically targeting UHRF1 protein degradation through the ubiquitin-proteasome pathway, DSG-induced UHRF1 protein degradation reduced the level of genomic DNA methylation, and re-activated the expression of such TSGs as p21, p16 and LXN, thereby resulted in cell cycle arrest, cell senescence and reduced DU145 xenograft tumor growth. Altogether, clarified DSG anticancer mechanism as an epigenetic regulatory drug for the treatment of PCa. Conclusions and Implications: Our results first time identified DSG which extract from natural plants specifically targeting UHRF1 protein. This vpresent study provided a promising strategy to discover new molecule-targeted drug from natural compounds. KEYWORDS: Traditional Chinese Medicine; Prostate cancer; Diosgenin; DNA methylation; Tumor suppressor genes;

A patient with lung cancer was administrated osimertinib. She developed symptomatic heart failure due to Takotsubo-cardiomyopathy (TC). As her condition improved after discontinuing osimertinib, TC was thought to be caused by osimertinib. Re-occurrence of TC was seen after re-administraing half dose of osimernitib.

Aim: N,N-dimethyltryptamine (DMT) is a psychedelic compound under development for the treatment of major depressive disorder (MDD). This study evaluated the in vitro metabolism and clinical pharmacokinetics (PK) of DMT fumarate (SPL026) in healthy subjects. Methods: Results are from the Phase I component of an ongoing Phase I/IIa randomised, double-blind, placebo-controlled, parallel-group, dose-escalation trial. Healthy adults received escalating doses of SPL026 via a 2-phase intravenous (IV) infusion. Dosing regimens were calculated based on PK modelling and predictions, with progression to each subsequent dose level according to safety and tolerability. In vitro experiments assessed hepatic clearance and metabolism of DMT by monoamine oxidase (MAO) and cytochrome P450 enzymes. Results: 24 healthy subjects received escalating doses of SPL026 which were safe and well-tolerated. Dose-proportional increases in DMT exposure were observed over the range of 9–21.5 mg. For all doses, median time to peak plasma concentration was ~10 min and mean elimination half-life was 9–12 min. There was no relationship between peak DMT plasma concentration and body mass index, weight or age. In vitro hepatic mitochondrial fraction clearance of SPL026 was inhibited by MAO-A, but not MAO-B, inhibition. CYP2D6 and CYP2C19 modified SPL026 clearance in vitro. The unbound fraction of SPL026 was approximately 70%. Conclusion: This is the first study to determine, in detail, the full PK profile of DMT in humans, confirming rapid attainment of peak plasma concentrations followed by accelerated clearance. These findings provide evidence which support the development of novel DMT infusion regimens for the treatment of MDD.

An accurate and stable data-driven model is proposed in this work for fatigue life prediction in presence of mean stresses. In the model, multiple independent extreme learning machines are trained using different training data and neural network configurations, and are then combined equally in an ensemble to model the complex correlations between fatigue life, material properties and mechanical responses. Meanwhile, theoretical prediction, as a representation of domain knowledge, is integrated to optimize the data-driven processes of model training and prediction, diversifying the information source of fatigue life modeling. Extensive experimental results covering thirteen metallic materials and a wide range of mean stress levels are collected from the open literature for model training and evaluation. The results demonstrate that the proposed model can achieve high accuracy and good stability [simultaneously](javascript:;), even with a small training dataset, showing great applicability for fatigue life prediction under mean stress loading conditions.

Climate warming is a ubiquitous stressor in freshwater ecosystems, yet its interactive effects with other stressors are poorly understood. We address this by testing the ability of three contrasting null models to predict the joint impacts of warming and a second stressor using a new database of 296 experimental combinations. Despite concerns that stressors will interact to cause synergisms, we found that net impacts were best explained by the effect of the stronger stressor (the dominance null model), especially if it was associated with human land use. Prediction accuracy depended on stressor identity and the magnitude of asymmetry between their effects. These findings suggest we can often effectively forecast impacts of multiple stressors by focusing on the stronger stressor, as habitat alteration and contamination often override the biological consequences of higher temperatures in freshwater ecosystems.

Abstract Background and Purpose: Gpr17 is an orphan receptor involved in the process of myelination due to its ability to inhibit the maturation of oligodendrocyte progenitor cells into myelinating oligodendrocytes. Despite multiple claims that the biological ligand has been identified, it remains an orphan receptor. Experimental Approach: Seventy-seven oxysterols were screened in a cell-free [35S]- GTPgS binding assay using membranes from cells expressing Gpr17. The positive hits were characterised using cAMP, IP1, and calcium mobilisation assays, with results confirmed in rat primary oligodendrocytes. Rat and pig brain extracts were separated by HPLC chromatography and endogenous activator(s) were identified in receptor activation assays. Gene expression studies of Gpr17 and Cyp46a1, the enzymes responsible for the conversion of cholesterol into specific oxysterols, were performed using quantitative real time PCR. Key Results: Eight oxysterols were able to stimulate Gpr17 activity, including the brain cholesterol, 24(S)-hydroxycholesterol. A specific brain fraction from rat and pig extracts containing 24S-HC activates Gpr17 in vitro assays. Expression of Gpr17 during mouse brain development correlates with the expression of Cyp46a1 and the levels of 24S-HC itself. Other active oxysterols have low brain concentrations below effective ranges. Conclusions and Implications: Oxysterols, including but not limited to 24S-HC, could be physiological activators for Gpr17 and thus potentially regulate OPC differentiation and myelination through activation of the receptor.

Objectives: Tinnitus is a sensation of ringing in the ears in the absence of any physical source in the environment. 15-25% of adults experience some form of tinnitus. A common cause of tinnitus is noise, head injury, ototoxic substances, as well as disorders of blood and blood vessels. Vascular causes include: head - neck tumours, turbulent blood flow, problems with blood supply and inner ear cell damage. The aspect of rheology in terms of tinnitus has not been described yet. Participants: Twelve patients with tinnitus, aged 30 to 74 years. Main outcome measures: The subjects all underwent audiological and neurological evaluation. Rheological properties of whole blood and plasma were assessed as well. The Quemada model was used to describe the variability of red blood cells shape, as well as their tendency to form aggregates. Results: Reduced whole blood viscosity in the low shear rate range is observed in the studied patient group. Conclusion: On the basis of the experimental study, statistically different results of hemorheological measurements were observed in the evaluated group in comparison to a reference group

Background and Purpose Bladder pain syndrome/interstitial cystitis (BPS/IC) has been clinically treated with glycosaminoglycan (GAG) replenishment therapy. [1, 2] This study was designed to further understand the physiological mechanism behind chondroitin sulfate (CS) treatment and to determine the effect of CS-therapy on recovery of urothelial barrier in an in-vitro chronic injury model. Experimental Approach In differentiated porcine urothelial cells the functional barrier was measured by transepithelial electrical resistance (TEER). A chronic urothelium was inflicted by multiple protamine instillations (3/day for 3 days), to approximate BPS/IC urothelium conditions. CS was instilled afterwards. Recovery of barrier function was followed in time. Additional analyses were performed for immunohistochemistry for barrier markers (tight junctions, GAG’s, umbrella cells) and scanning electron microscopy. Statistics were described by means ± standard error, α = 0.05. Key Results Barrier recovery (TEER) improved significantly with CS instillations compared to protamine only (T=7, 899.1 [Ω.cm2] versus 589.6 [Ω.cm2], p<0.001, 95% CI -394;-255). This recovery effect was seen on all three days and resulted in a significantly higher average TEER value in the CS group after 3 days (2606 Ω.cm2 vs 750.5 Ω.cm2). Immunohistochemistry and scanning electron microscopy showed decreased barrier markers after protamine treatment and enhanced recovery of urothelial GAG’s and other barrier markers after therapeutic instillations. Conclusion and Implications GAG replenishment with CS can improve recovery of barrier function of chronically damaged urothelium in-vitro. This preclinical study supports the hypothesis behind the use of clinical GAG replenishment therapy for patients with a chronically impaired urothelium.

Although COVID-19 is known to affect peripheral as well as cranial nerves, there is a paucity of reports on vocal fold paresis in COVID-19, bilateral vocal fold paresis (BVFP) in particular. We describe a case of BVFP and glottal bridge synechia following COVID-19-pneumonia discussing pathomechanisms and treatment options.

The uptake of water through leaves is commonly referred to as foliar water uptake (FWU). The phenomenon has been documented in many species and is increasingly recognized as a non-trivial factor in plant-water relations. However, it remains unknown whether FWU is a wide-spread phenomenon in Pinus species, and how it may relate to needle traits such as the form and structure of stomatal wax plugs. Here we studied these questions in current-year and one-year old needles of seven Pinus species. We analyzed the surface and stomatal structure with cryo-scanning electron microscopy. Additionally, we considered the effect of artificial wax erosion by application of the surfactant Triton TM X-100, which is able to alter wax crystals. The results show for all species 1) that FWU occurred, 2) that FWU is higher in old needles compared to young needles, and 3) that there is substantial erosion of stomatal wax plugs in old needles. Additionally, FWU in young needles was enhanced by the surfactant treatment, and was highest in P. canariensis showing a thin wax plug. The results of this study provide evidence 1) for widespread FWU in Pinus and 2) for the influence of age-related needle surface erosion on FWU.

Abscisic acid (ABA) is a vital stress resistant hormone of plant in coping with adverse environmental conditions, such as drought stress. Sensitivity of seed germination to exogenous ABA treatment could link to different drought tolerance ability of different plant species. Here, we selected alfalfa seedlings (S0-50) from seeds germinated under 50 μM ABA treatment. The S0-50 plant showed more sensitivity in stomatal closure to exogenous ABA and PEG treatments, and also stronger drought tolerance than the plant of ABA-sensitive seed during germination (S0-0). Testing of ABA content in leaf indicated that the S0-50 had a higher ABA content in normal and under drought stress growth conditions than that of the S0-0 plants. The seed of S0-50 next generation (S1-50) showed significantly higher germination ratio under 50 μM ABA treatment, and also had longer root after 15% PEG6000 treatment than the segregated ABA-sensitive seed (S1-0). We found a cytosol-nucleus dual-localized PPR protein gene MsSOAR1 was significantly highly expressed in S0-50 than in S0-0 plant. Overexpression of AtSOAR1, a negative regulator in ABA-mediated Arabidopsis seed germination inhibition, and also a homologous gene of MsSOAR1, significantly improved alfalfa drought tolerance, branch number and plant height, and reduced the expression level of ABA receptors MsPYL5 and MsPYL6. The results suggest that ABA-insensitive during seed germination could associate with repression of ABA signaling transduction. Selection of alfalfa seedling during seed germination with exogenous ABA could be a way to obtain drought tolerance germplasm, at least in ‘Zhongmu No.1’ alfalfa cultivar the plant material we used in the experiment.

The purpose of this study is to improve prediction rate with a novel model of bidirectional encoder representations for transformers (BERT) compared with random forest algorithms. A dataset of size 1100 is used to compare Novel BERT’s performance with Random Forests. With Random Forest, a framework for identifying fake news in electronic media networks is proposed. clinical calculates a sample size of 20 according to the framework. With regard to Precision rate, the Novel Bert algorithm beats the Random Forest algorithm by 8.33%. In comparison to the random forest algorithm, BERT achieves a rate of 0.002 that is significantly better than it. It is concluded that the novel BERT algorithm outperforms Random Forest in the prediction of fake news in this study.

Background: The ongoing outbreak of SARS-CoV-2 Omicron BA.2 infections in Hong Kong, the world model city of universal masking, has resulted in a major public health crisis. Although the third heterologous BNT162b2 vaccination after 2-dose CoronaVac generated higher neutralizing antibody responses than the third homologous CoronaVac booster, vaccine efficacy and corelates of immune protection against the major circulating Omicron BA.2 remains to be investigated. Methods: We investigated the vaccine efficacy against the Omicron BA.2 breakthrough infection among 481 public servants who had been received with SARS-CoV-2 vaccines including two-dose BNT162b2 (2×BNT, n=169), three-dose BNT162b2 (2×BNT, n=175), two-dose CoronaVac (2×CorV, n=37), three-dose CoronaVac (3×CorV, n=68) and third-dose BNT162b2 following 2×CorV (2×CorV+1BNT, n=32). Humoral and cellular immune responses after three-dose vaccination were characterized and correlated with clinical characteristics of BA.2 infection. Results: During the BA.2 outbreak, 29.3% vaccinees were infected. Three-dose vaccination provided protection with lower incidence rates of breakthrough infections (2×BNT 49.2% vs 3×BNT 16.6%, p<0.0001; 2×CorV 48.6% vs 3×CoV 20.6%, p=0.003). The third heterologous vaccination showed the lowest incidence (2×CorV+1×BNT 6.3%). Although BA.2 conferred the highest neutralization resistance compared with variants of concern tested, the third dose vaccination-activated spike-specific memory B and Omicron cross-reactive T cell responses contributed to reduced frequencies of breakthrough infection and disease severity. Conclusions: Our results have implications to timely boost vaccination and immune responses likely required for vaccine-mediated protection against Omicron BA.2 pandemic.

Article Type: Letter to the EditorTitle : The impact of maternal-fetal omalizumab transfer on peanut-specific responses in an ex vivo placental perfusion model

This letter suggests to the LDO regulator with the high reliability ESD protection circuit that achieves low peak voltage through analog switch structure. The proposed LDO regulator has the function of detecting the output voltage fluctuations depending on the load via an analog switch structure and effectively controlling the peak voltage. The proposed ESD protection circuit is placed on I / O and power lines to prevent the IC circuit from being destroyed from the inevitable ESD phenomenon. It was verified that the reliability of the IC can be improved through effective current discharge due to ESD surge. The proposed LDO regulator, implemented in a 0.18μm BCD process, achieves an undershoot voltage of 25 mV and an overshoot voltage of 28 mV for a load current of 300 mA.

Primary Hypothesis: We hypothesized that higher alveolar dead space fraction (AVDSf) at PARDS onset would be associated with right ventricular (RV) systolic dysfunction within the first 24 hours of PARDS. Study Design and Methods: We performed a retrospective single-center cohort study of PARDS patients with clinically obtained echocardiograms within 24 hours. Primary exposure was AVDSf at PARDS onset. Primary outcome was RV systolic dysfunction as defined by RV global longitudinal strain (GLS) (> - 18%). Secondary outcomes included pulmonary hypertension (PH) and RV systolic dysfunction as defined by other echocardiogram parameters, and measures of oxygenation. Unadjusted and adjusted logistic and linear regression were used to investigate AVDSf associations with outcomes. Results: Seventy-six patients were included: median age 6.2 years, 50% female, and 66% with moderate or severe PARDS. Median AVDSf was 0.2 (IQR 0.1-0.3), 32% had RV dysfunction, and 24% had PH. Unadjusted and adjusted logistic regression showed no association between AVDSf and RV systolic dysfunction or PH by any echocardiographic measure. Unadjusted and adjusted linear regression demonstrated the association of AVDSf with both oxygenation index and PaO 2/FiO 2. AVDSf did not discriminate RV dysfunction (AUROC for RV GLS was 0.51, 95% CI 0.36-0.66). Conclusion: AVDSf at PARDS onset was not associated with RV systolic dysfunction or PH within 24 hours but was associated with metrics of hypoxemia and may be more reflective of pulmonary causes of ventilation-perfusion mismatch. Future investigations should focus on clarifying the clinical utility of AVDSf in relation to existing metrics throughout the course of PARDS.

Dear Sir,With great interest we read the article by Godbehere et al on vincristine (VCR)-induced vocal cord paralysis (VI-VCP) in pediatric patients.1 The subject is clinically relevant and the authors provide a practical algorithm for diagnosing and treating VI-VCP. We strongly support early ENT referral following stridor in children to assess for potentially life-threatening complications of VCR administration.2 Our recently published case report and literature review (in Dutch) have found similar type and onset of symptoms.1-2In a recent review (published in Dutch literature, see Table 1 ) we summarized 22 studies including 45 patients, and we, remarkably, found some data that were slightly contrasting with findings of Godbehere et al. 1 First, we found that 11 out of 45 children between 5 and 17 years of age presented with VI-VCP, which suggests that airway obstruction might also affect older children following VCR administration. For example, one 16-year-old and one 17-year-old child needed ICU management and intubation respectively following VCR treatment. Six of the seven cases (85%) described by Godbehere et al 1 presented with bilateral vocal cord paralysis, which suggests that this is more common than unilateral paralysis. In contrast, we found that 26 out of the 35 cases (74%) that reported laterality presented with bilateral vocal cord paralysis. VI-VCP laterality was not reported in 11 cases, which could further affect this prevalence. Report of relatively more unilateral paralysis could consequently result in lower (overall) indication of invasive airway management.Remarkably, in contrast to Godbehere et al 1 we found that dose reduction resulted in reversion of paralysis in four cases. Complete cessation of therapy might therefore not be needed in all cases (contrasting findings of Godbehere et al 1. In addition, we retrieved six cases that showed partial recovery and even two cases showing no recovery.We also found (Table 1 ) that respiratory support is not always needed to facilitate VCR continuation: 10 children with bilateral vocal cord palsy received VCR dose reduction and did not need invasive airway management. One 7-year-old child with bilateral vocal cord palsy even continued VCR at full dose. Finally, we found 3 cases receiving tracheostomy as airway management, but still required discontinuation of VCR treatment, indicating that invasive airway management does not always facilitate continuation of VCR treatment.In conclusion, we agree with Godbehere et al 1that awareness of this potentially life-threatening complication is essential. Maybe our Table 1 could facilitate implementation of treatment decision (trees) in patients suffering from VI-VCP.References :Godbehere J, Payne J, Thevasagayam R. Vocal cord paralysis secondary to vincristine treatment in children: A case series of seven children and literature review. Clin. Otolaryngol. 2021;46:1114-1118.J.E. Swartz, H.P.H. Hundscheid, H. Bruijnzeel, et al . Vincristine-induced vocal cord paralysis: a rare but potentially life-threatening complication, Ned Tijdschr Oncol 2021;18:16-21.

Background: In 2016-2019, the WHO Expert Committee on Drug Dependence scientifically reviewed cannabis products. In that context, multiple references to a previous and similar assessment dating back to 1935 were made; but the content, outcome, and stakeholders involved in the 1935 review were unclear. Method: Transnational historiography of the international conversation on cannabis control in and around 1935, based on previously-unavailable primary material from international organisations, archives, and literature searches. Results: Two evaluations were undertaken in 1935 and 1938 by the “Comité des Experts Pharmacologistes” convened under the “Office International d’Hygiène Publique” (OIHP), predecessor of the WHO. Five specific medicines marketed by Parke-Davis were briefly reviewed, based on which the Experts recommended placing under international control all cannabis medicines –prior to that, only pure extracts were under control. The measure was confusing; few State Parties to the 1925 Convention implemented it; the second World War precipitated its oblivion. The international community resumed work on cannabis under the WHO in 1952; that same year, the OIHP was definitely closing its doors. No trace of the 1935 events appeared in any post-war proceeding. Conclusion: Political biasses and numerous methodological and ethical issues surround the 1935 episode: it cannot legitimately be called a “scientific assessment.” The role of stakeholders like Egypt and the OIHP in norm entrepreneurship and advocacy for multilateral controls over cannabis have been largely forgotten; that of the USA somewhat exaggerated. There might be other forgotten pieces of History: predecessor of WHO, the under-documented OIHP had mandates on other important fields, be it drug or epidemics control. Much knowledge on the History of humankind lays in unexplored archival records; errors made and lessons learnt from the past could inform our management of the conflict between public health and politics today. HighlightsSome parts of the history of global cannabis prohibition are not enough researchedThe predecessor of WHO in charge of drug control (and pandemics) is under-documentedIn the 1930s, numerous medical marijuana formulations were used worldwideEgypt pushed the League of Nations into attempting to control cannabisThe first international scientific assessment of cannabis was not in 1935 but in 2016-2019

Industrial scale production of therapeutic monoclonal antibodies (mAbs) is commonly achieved with Protein A chromatography, a process that requires exposure of the antibody to strongly acidic conditions during the eluting step. Exposure to acid inactivates virus contaminants but may, in parallel, lead to antibody aggregation that must be eliminated or kept at acceptably low levels. This report seeks to provide a practical method for overcoming a long-standing problem. We show how Brij-O20 detergent micelles, conjugated by the amphiphilic [(bathophenanthroline)3:Fe2+] complex in the presence of amino acid monomers: phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), isoleucine (Ile) or valine (Val), efficiently capture polyclonal human IgG (hIgG) at neutral pH and allow its recovery by extraction either at pH 4 (85-97% yield) or at pH 6.3 (72-84% yield). Of the five amino acid monomers surveyed, Phe or Tyr produced the highest overall process yield at both pH 4 and 6.3. The monomeric state of the purified hIgG’s was confirmed by dynamic light scattering (DLS). Potential advantages of the purification method are discussed.

The coronary sinus musculature connects to the right and the left atrium, forming electrical interatrial bridges and can be a critical part of various left atrial and biatrial flutter circuits. We herein present a rare case of a macroreentrant tachycardia around the coronary sinus using interatrial connections at its orifice and the inferolateral left atrium and the adjacent left atrial myocardium.