Isogenic pairs of induced-pluripotent stem-derived endothelial cells identify DYRK1A/PPARG/EGR1 pathway is responsible for Down syndrome-associated pulmonary hypertension.

Down syndrome (DS) is the most prevalent chromosomal disorder associated with a higher incidence of pulmonary arterial hypertension (PAH). The dysfunction of vascular endothelial cells (ECs) is known to cause pulmonary arterial remodeling in PAH, although the physiological characteristics of ECs harboring trisomy 21 (T21) are still unknown. In this study, we analyzed the human vascular ECs by utilizing the isogenic pairs of T21-induced pluripotent stem cells (iPSCs) and corrected disomy 21 (cDi21)-iPSCs. In T21-iPSC-derived ECs, apoptosis and mitochondrial reactive oxygen species (mROS) were significantly increased, and angiogenesis and oxygen consumption rate (OCR) were significantly impaired as compared with cDi21-iPSC-derived ECs. The RNA-sequencing identified that EGR1 on chromosome 5 was significantly upregulated in T21-ECs. Both EGR1 suppression by siRNA and pharmacological inhibitor could recover the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Alternately, the study also revealed that DYRK1A was responsible to increase EGR1 expression via PPARG suppression, and that chemical inhibition of DYRK1A could restore the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Finally, we demonstrated that EGR1 was significantly upregulated in the pulmonary arterial ECs from lung specimens of a patient with DS and PAH. In conclusion, DYRK1A/PPARG/EGR1 pathway could play a central role for the pulmonary EC functions and thus be associated with the pathogenesis of PAH in DS.

Seed germination ecology of endangered plant Horsfieldia hainanensis Merr. In China.

BACKGROUND: Horsfieldia hainanensis Merr., an indicator species of China's humid tropical rainforests, is endangered due to difficulties with population regeneration. In this study, the biological characteristics and germination adaptability of the seeds were studied for the first time, in order to provide a basis for analyzing the causes of endangerment and strategies for the artificial cultivation of H. hainanensis. The effects of biological characteristics (population, arils, seed coat, seed weight, seed moisture content) and environmental factors (temperature, light, drought, substrate, burial depth) on seed germination and seedling growth of H. hainanensis were studied. RESULTS AND DISCUSSION: The fruits were found to be capsules containing seeds wrapped in a pericarp and fleshy aril, which provide protection and assist in seed dispersal, but also pose risks to the seeds, as the peel and fleshy aril can become moldy under high temperature and humidity conditions. There were significant differences in fruit morphology and germination characteristics among different populations, and the seed quality of populations in Niandian village, Daxin County, Chongzuo City, Guangxi Zhuang Autonomous Region was better. The arils significantly inhibited seed germination, the germination of large seeds was better, and seedling growth from medium seeds was superior. H. hainanensis seeds were sensitive to dehydration, and intolerant to drought and low temperature, which is typical of recalcitrant seeds. The seeds are suitable for germination on a moist substrate surface with good water retention and breathability at 30-35℃.

Organocatalyzed Asymmetric Michael Addition of 3-Fluorooxindole to Vinylidene Bisphosphonates.

Both the 3-fluorooxindole and germinal bisphosphonate structural motifs are prevalent in bioactive molecules because of their associated biological activities. We describe an approach to accessing 3,3-disubstituted 3-fluorooxindoles bearing a geminal bisphosphate fragment through a highly enantioselective Michael addition reaction between 3-fluorooxindoles and vinylidene bisphosphonates. These reactions are catalyzed by a commercially available cinchona alkaloid catalyst, have a broad substrate scope concerning 3-fluorooxindoles, and provide the corresponding addition products in a yield of up to 95% with an enantiomeric excess of up to 95%. A reasonable reaction pathway to explain the observed stereochemistry is also proposed.

Self-Calibrated Ion-Selective Electrodes.

Ion-selective electrode (ISE) potentiometry is reliable only if on-site calibration using a standard solution is performed before ion measurements. The complex device and operation required for calibration hinder the implementation of ISEs in decentralized sensing. Reported herein is a new type of ISE that is calibrated by a built-in component of the sensor without requiring any fluid handling processes. The indicator and reference electrodes are connected by a thin ionic conductor such as an aqueous phase containing the measuring ions in a capillary tube. This connection establishes a baseline electromotive force (EMF) that incorporates phase boundary potentials across multiple interfaces of the electrochemical cell and serves as a one-point calibration. Unlike conventional ISEs that rely on one EMF reading for each measurement, the proposed sensor utilizes a sample-induced EMF change relative to the baseline for each ion measurement. The variability in relative EMF is found to be <2.0 mV for multiple full potentiometric sensors consisting of plasticizer-based K+ ISEs and hydrogel-based Ag/AgCl reference electrodes. This value is significantly smaller than the variability of absolute EMF readouts in similar sensors without the self-calibration design. Moreover, when the ion-conducting calibration bridge has a low concentration of primary ions, low ion mobility, and/or a small contact area with the indicator and reference phases, it does not compromise the Nernstian response slope toward the analyte ions in the sample and therefore does not need to be removed for sample testing. The accuracy of the single-use self-calibrated K+ sensor in testing undiluted human blood samples is validated using a commercial blood gas analyzer as the reference method. Although this study focuses on disposable sensors consisting of tubes, the fluidics-free self-calibration strategy may be adapted to other sensor configurations such as planar sensors.

Ultrasensitive Ionophore-Based Liquid Sensors for Colorimetric Ion Measurements in Blood.

The self-monitoring of electrolytes using a small volume of capillary blood is needed for the management of many chronic diseases. Herein, we report an ionophore-based colorimetric sensor for electrolyte measurements in a few microliters of blood. The sensor is a pipet microtip preloaded with a segment of oil (plasticizer) containing a pH-sensitive chromoionophore, a cation exchanger, and an ionophore. The analyte is extracted from the sample into the oil via a mixing protocol controlled by a stepper motor. The oil with an optimized ratio of sensing chemicals shows an unprecedentedly large color response for electrolytes in a very narrow concentration range that is clinically relevant. This ultrahigh sensitivity is based on an exhaustive response mode with a novel mechanism for defining the lower and higher limits of detection. Compared to previous optodes and molecular probes for ions, the proposed platform is especially suitable for at-home blood electrolyte measurements because (1) the oil sensor is interrogated independent of the sample and therefore works for whole blood without requiring plasma separation; (2) the sensor does not need individual calibration as the consistency between liquid sensors is high compared to solid sensors, such as ion-selective electrodes and optodes; and (3) the sensing system consisting of a disposable oil sensor, a programmed stepper motor, and a smartphone is portable, cost-effective, and user-friendly. The accuracy and precision of Ca2+ sensors are validated in 51 blood samples with varying concentrations of total plasma Ca2+. Oil sensors with an ultrasensitive response can also be obtained for other ions, such as K+.

Surface PEGylation of ionophore-based microspheres enables determination of serum sodium and potassium ion concentration under flow cytometry.

We present here an ionophore-based ion-selective optode (ISO) platform to detect potassium and sodium concentrations in serum through flow cytometry. The ion-selective microsensors were based on polyethylene glycol (PEG)-modified polystyrene (PS) microspheres (PEG-PS). Ratiometric response curves were observed using peak channel fluorescence intensities for K+ (10-6 M to 0.1 M) and Na+ (10-4 M to 0.2 M) with sufficient selectivity for clinical diagnosis. Due to the matrix effect, proteins such as albumin and immunoglobulin caused an obvious increase in response for serum sample determination. To solve this problem, 4-arm PEG chains were covalently attached onto the surface of PS microspheres through a two-step reaction, which improved the stability and combated pollution of microspheres. As a preliminary application, potassium and sodium concentrations in human serums were successfully determined by the PEG-PS microsensors through flow cytometry.

A risk signature of ubiquitin-specific protease family predict the prognosis and therapy of kidney cancer patients.

Ubiquitin-specific proteases (USPs) are closely related to protein fate and cellular processes through various molecular signalling pathways, including DNA damage repair, p53, and transforming growth factor-ß (TGF-ß) pathways. In recent years, increasing evidence has revealed the pivotal role of ubiquitination in tumorigenesis of KIRC. However, USPs' molecular mechanism and clinical relevance in kidney cancer still need further exploration. Our study first determined prognosis-related ubiquitin-specific proteases (PRUSPs) in KIRC. We found these genes co-expressed with each other and might regulate different substrates. Based on the USPs' expression, the PRUSPs risk signature was constructed to predict the survival probability of KIRC patients. The patients in high-PRUSPs-risk group showed a low survival rate. ROC and calibration curve indicated a discriminate capacity of the signature, and uni-/multi-variate Cox regression analysis revealed that the PRUSPs score is an independent prognostic factor. In different KIRC clinical subgroups and external validation cohorts (including E-MTAB-1980 and TCGA-KIRP cohorts), the PRUSPs risk signature showed strong robustness and practicability. Further analysis found that high-risk group showed activation of immune-related pathways and high PD-1/CTLA4 expression, revealing that high-risk patients might be sensitive to immunotherapy. In summary, we constructed the USPs risk signature to predict kidney cancer prognosis, which provided the theoretical foundation for further clinical or pre-clinical experiments.

Sequencing and Bioinformatics analysis of lncRNA/circRNA-miRNA-mRNA in Glioblastoma multiforme.

Evidence suggests that non-coding RNAs have a role in glioblastoma multiforme (GBM), although the regulatory mechanisms controlled by competing endogenous RNAs (ceRNAs) in GBM are still poorly understood and infrequently described. This research extensively analyzed circRNA, lncRNA, miRNA, and mRNA expression changes in GBM patients. RNA-sequencing analyses were conducted to investigate differentially expressed genes (DEGs), lncRNAs (DELs), miRNAs (DEMs), and circRNAs (DECs) in the GBM. In this study, researchers found that GBM patients and healthy controls differed in the presence of 1224 DECs, 1406 DELs, 229 DEMs, and 2740 DEGs. PPI network analysis demonstrated that CEACAM5, CXCL17, FAM83A, TMPRSS4, and GGPRC5A were hub genes and enriched in modules. Then a ceRNA network was constructed with 8 circRNA, 7 lncRNAs, 16 miRNAs, and 17 mRNAs. Overall, the ceRNA interaction axes that were found may prove to be pivotal therapeutic targets for treating GBM.

AI-Based Optimal Treatment Strategy Selection for Female Infertility for First and Subsequent IVF-ET Cycles.

Over the last 20 years, China's infertility rate has risen from 3% to 12.5%-15%. Infertility has become the third largest disease following cancer and cardiovascular disease. Then, the in vitro fertilization and embryo transfer (IVF-ET) becomes more and more important in infertility treatment field. However, the reported success rate for IVT-ET is 30%-40% and costs are gradually rising. Meanwhile, to increase success rates and decrease costs, the optimal selection of the IVF-ET treatment strategy is crucial. In a clinical work, the IVF-ET treatment strategy selection is always based on the experience of the doctor without a uniform standard. To solve this important and complex problem, we proposed an artificial intelligence (AI)-based optimal treatment strategy selection system to extract implicit knowledge from clinical data for new and returning patients, by mimicking the IVF-ET process and analysing a myriad of treatment decisions. We demonstrated that the performance of the model was different in 10 AI classification algorithms. Hence, we need to select the optimal method for predicting patient pregnancy result in different IVF-ET treatment strategies. Moreover, feature ranking is determined in the proposed model to measure the importance of each patient characteristics. Therefore, better advice can be provided for individual patient characteristics, doctors can provide more valid suggestions regarding certain patient characteristics to improve the accuracy of diagnosis and efficiency.

Effect of different hypoxic and hypobaric interventions on blood gas and erythrocyte-related indicators in rats. / ä¸åŒç¼ºæ°§å¹²é¢„å¯¹ä½ŽåŽ‹ä½Žæ°§æ¨¡åž‹é¼ è¡€æ°”åŠçº¢ç»†èƒžç›¸å ³æŒ‡æ ‡çš„å½±å“.

OBJECTIVES: To explore the effects of hypoxic and hypobaric conditions on blood gas and erythrocyte-related indicators in rats. METHODS: SD male rats were exposed to low-pressure hypoxic conditions simulating an altitude of 6500 m in a small or a large experimental cabin. Abdominal aortic blood samples were collected and blood gas indicators, red blood cells (RBCs) count, and hemoglobin (Hb) content were measured. The effects of exposure to different hypoxia times, different hypoxia modes, normal oxygen recovery after hypoxia, and re-hypoxia after hypoxia preconditioning on blood gas indicators, RBCs count and Hb content were investigated. RESULTS: The effect of blood gas indicators was correlated with the length of exposure time of hypoxia and the reoxygenation after leaving the cabin. Hypoxia caused acid-base imbalance and its severity was associated with the duration of hypoxia; hypoxia also led to an increase in RBCs count and Hb content, and the increase was also related to the time exposed to hypoxia. The effects of reoxygenation on acid-base imbalance in rats caged in a small animal cabin were more severe that those in a large experimental cabin. Acetazolamide alleviated the effects of reoxygenation after leaving the cabin. Different hypoxia modes and administration of acetazolamide had little effect on RBCs count and Hb content. Normal oxygen recovery can alleviate the reoxygenation and acid-base imbalance of hypoxic rats after leaving the cabin and improve the increase in red blood cell and hemoglobin content caused by hypoxia. The improvement of hypoxia preconditioning on post hypoxia reoxygenation is not significant, but it can alleviate the acid-base imbalance caused by hypoxia in rats and to some extent improve the increase in red blood cell and hemoglobin content caused by hypoxia. CONCLUSIONS: Due to excessive ventilation and elevated RBCs count and Hb content after hypoxia reoxygenation, oxygen partial pressure and other oxygenation indicators in hypoxic rats are prone to become abnormal, while blood gas acid-base balance indicators are relatively stable, which are more suitable for evaluating the degree of hypoxia injury and related pharmacological effects in rats.

Medication rule of traditional Chinese medicine in the treatment of plateau hypoxia based on data mining. / 基于数据挖掘中药治疗高原性缺氧的组方规律.

OBJECTIVES: The development of traditional Chinese medicine (TCM) in the plateau area is relatively backward. There is a lack of system to analyze the effects of the special environment of plateau low pressure and hypoxia on human meridians qi and blood, as well as the etiology and pathogenesis of plateau hypoxic diseases. To analyze the composition rules of anti-hypoxia TCM formulation with data mining methods. METHODS: The experimental literatures related to high altitude hypoxia were searched in China National Knowledge Infrastructure (CNKI), Wanfang Med Online, VIP, China Biology Medicine disc and other databases, a standardized prescription database was established after screening and standardization of prescription data in the literature. The composition rules of these prescription including drug frequency, drug attributes, drug efficacy, drug combination, and core prescription were analyzed and displayed with visual charts. RESULTS: A total of 135 TCM prescriptions were included, and 229 flavored drugs were included. Among these prescriptions, the TCM with high frequency of use were Astragalus, Danshen, Ginseng, and Angelica, etc. Four natures of the TCM were mostly warm and calm. Five flavours of the TCM were mostly sweet, bitter, and pungent. And channel tropism of the TCM mostly entered the heart, lung, and liver meridians. The frequency combination of TCM was Astragalus-Danshen and Astragalus-Angelica. The core medicines of these prescriptions were Astragalus, Danshen, Angelica, Rhodiola, Goji, and Ginseng. TCM could alleviate symptoms such as chest tightness, chest pain, coughing and wheezing, coughing, vomiting, fatigue, and loss of appetite caused by hypoxia at high altitude. CONCLUSIONS: Through data mining, it is concluded that the prevention or treatment of plateau hypoxic diseases mostly utilized products can nourish blood, replenish qi and dispel stasis, and help yang and dispel qi, most of them are compatible with qi tonic drugs and blood circulation and stasis dissolving drugs, and pay attention to the combination of virtual and real, yin and yang.

Rapid and Label-Free Classification of Blood Leukocytes for Immune State Monitoring.

A fully automated and label-free sample-to-answer white blood cell (WBC) cytometry platform for rapid immune state monitoring is demonstrated. The platform integrates (1) a WBC separation process using the multidimensional double spiral (MDDS) device and (2) an imaging process where images of the separated WBCs are captured and analyzed. Using the deep-learning-based image processing technique, we analyzed the captured bright-field images to classify the WBCs into their subtypes. Furthermore, in addition to cell classification, we can detect activation-induced morphological changes in WBCs for functional immune assessment, which could allow the early detection of various diseases. The integrated platform operates in a rapid (<30 min), fully automated, and label-free manner. The platform could provide a promising solution to future point-of-care WBC diagnostics applications.

Immunopathogenesis of patients with COVID-19: from the perspective of immune system 'evolution' and 'revolution'.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 is sweeping the world, threatening millions of lives and drastically altering our ways of living. According to current studies, failure to either activate or eliminate inflammatory responses timely and properly at certain stages could result in the progression of the disease. In other words, robust immune responses to coronavirus disease 2019 (COVID-19) are critical. However, they do not theoretically present in some special groups of people, including the young, the aged, patients with autoimmunity or cancer. Differences also do occur between men and women. Our immune system evolves to ensure delicate coordination at different stages of life. The innate immune cells mainly consisted of myeloid lineage cells, including neutrophils, basophils, eosinophils, dendritic cells and mast cells; they possess phagocytic capacity to different degrees at different stages of life. They are firstly recruited upon infection and may activate the adaptive immunity when needed. The adaptive immune cells, on the other way, are comprised mainly of lymphoid lineages. As one grows up, the adaptive immunity matures and expands its memory repertoire, accompanied by an adjustment in quantity and quality. In this review, we would summarise and analyse the immunological characteristics of these groups from the perspective of the immune system 'evolution' as well as 'revolution' that has been studied and speculated so far, which would aid the comprehensive understanding of COVID-19 and personalised-treatment strategy.

Bulk and single-cell transcriptome profiling reveal necroptosis-based molecular classification, tumor microenvironment infiltration characterization, and prognosis prediction in colorectal cancer.

BACKGROUND: Necroptosis is a new form of programmed cell death that is associated with cancer initiation, progression, immunity, and chemoresistance. However, the roles of necroptosis-related genes (NRGs) in colorectal cancer (CRC) have not been explored comprehensively. METHODS: In this study, we obtained NRGs and performed consensus molecular subtyping by "ConsensusClusterPlus" to determine necroptosis-related subtypes in CRC bulk transcriptomic data. The ssGSEA and CIBERSORT algorithms were used to evaluate the relative infiltration levels of different cell types in the tumor microenvironment (TME). Single-cell transcriptomic analysis was performed to confirm classification related to NRGs. NRG_score was developed to predict patients' survival outcomes with low-throughput validation in a patients' cohort from Fudan University Shanghai Cancer Center. RESULTS: We identified three distinct necroptosis-related classifications (NRCs) with discrepant clinical outcomes and biological functions. Characterization of TME revealed that there were two stable necroptosis-related phenotypes in CRC: a phenotype characterized by few TME cells infiltration but with EMT/TGF-pathways activation, and another phenotype recognized as immune-excluded. NRG_score for predicting survival outcomes was established and its predictive capability was verified. In addition, we found NRCs and NRG_score could be used for patient or drug selection when considering immunotherapy and chemotherapy. CONCLUSIONS: Based on comprehensive analysis, we revealed the potential roles of NRGs in the TME, and their correlations with clinicopathological parameters and patients' prognosis in CRC. These findings could enhance our understanding of the biological functions of necroptosis, which thus may aid in prognosis prediction, drug selection, and therapeutics development.

Acute ammonia stress-induced oxidative and heat shock responses modulated by transcription factors in Litopenaeus vannamei.

The present study aimed to examine the effects of short-term exposure to ammonia on stress and oxidative responses in shrimp (Litopenaeus vannamei) and to determine whether the antioxidant system related to the regulatory role of transcription factors and stress proteins was activated. Shrimp were exposed ammonia-N at four concentrations: 0 (control), 5, 10, and 15 mg/L, for 48 h. The hepatopancreas was sampled to measure the levels of glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO); the activities of superoxide dismutase (SOD), catalase (CAT), nitric oxide synthase (NOS); and the expression levels of GSH-px (encoding glutathione peroxidase), GST (encoding glutathione-S-transferase), HSP70 (encoding heat shock protein 70), HSP90 (encoding heat shock protein 90), p53, RELISH, and AKIRIN. We observed that exposure to a high ammonia content increased the abundance of oxidative factors (MDA, CAT, SOD, NOS, and NO), reduced the levels of GSH, and upregulated the mRNA expression levels of antioxidant genes (GSH-px and GST), stress-related genes (HSP70 and HSP90), and transcription factor genes (p53, RELISH, and AKIRIN). These results indicated that ammonia induced oxidative stress and inflammation. Both enzymatic and nonenzymatic antioxidant defense systems are involved, which might be regulated by HSPs, as well as certain transcription factors, such as p53 and nuclear factor kappa B (NF-κB), thus mounting an adaptive response to help rebalance redox homoeostasis.

Fully inkjet-printed paper-based Pb2+ optodes for water analysis without interference from the chloramine disinfectant.

We developed a paper-based colorimetric sensor for facile and cost-effective detection of Pb2+ in drinking and environmental water samples. The Pb2+ ion-selective optodes are fabricated by inkjet printing of ionophore, chromoionophore, and ion exchanger on cellulose paper. Pb2+ in water samples induces deprotonation of the pH chromoionophore and changes the optode color, which is acquired and analyzed by a smartphone. The paper-based optode without any plasticizer or polymer has a dynamic range and selectivity comparable to those of traditional optodes using PVC polymer and/or plasticizer. Furthermore, the response time of the plasticizer/polymer-free paper-based optode is much shorter than those of plasticized PVC-based optodes on paper and glass (5 min vs. 15 and 50 min). Moreover, the plasticizer/polymer-free optode preserves the water-wicking capability of porous cellulose paper, allowing for the design of pump-free microfluidic devices. Chloramine, a widely used disinfectant in drinking water, was found to be a strong and generic interference species for heavy metal ion detection via ion-selective optodes. A fully inkjet-printed lateral-flow paper-based device consisting of a sodium thiosulfate-based chloramine elimination zone and a plasticizer/polymer-free sensing zone was designed for Pb2+ detection in tap water disinfected by chloramine. The dynamic range of the Pb2+ sensor may be shifted from the current 10-6 to 10-5 M to lower concentrations by using stronger ionophores, but this work lays a foundation for the design of paper-based heavy metal ion sensors without detrimental interference from disinfectants.

Chest physiotherapy for pneumonia in adults.

BACKGROUND: Despite conflicting evidence, chest physiotherapy has been widely used as an adjunctive treatment for adults with pneumonia. This is an update of a review first published in 2010 and updated in 2013. OBJECTIVES: To assess the effectiveness and safety of chest physiotherapy for pneumonia in adults. SEARCH METHODS: We updated our searches in the following databases to May 2022: the Cochrane Central Register of Controlled Trials (CENTRAL) via OvidSP, MEDLINE via OvidSP (from 1966), Embase via embase.com (from 1974), Physiotherapy Evidence Database (PEDro) (from 1929), CINAHL via EBSCO (from 2009), and the Chinese Biomedical Literature Database (CBM) (from 1978). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs assessing the efficacy of chest physiotherapy for treating pneumonia in adults. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included two new trials in this update (540 participants), for a total of eight RCTs (974 participants). Four RCTs were conducted in the United States, two in Sweden, one in China, and one in the United Kingdom. The studies looked at five types of chest physiotherapy: conventional chest physiotherapy; osteopathic manipulative treatment (OMT, which includes paraspinal inhibition, rib raising, and myofascial release); active cycle of breathing techniques (which includes active breathing control, thoracic expansion exercises, and forced expiration techniques); positive expiratory pressure; and high-frequency chest wall oscillation. We assessed four trials as at unclear risk of bias and four trials as at high risk of bias. Conventional chest physiotherapy (versus no physiotherapy) may have little to no effect on improving mortality, but the certainty of evidence is very low (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.15 to 7.13; 2 trials, 225 participants; I² = 0%). OMT (versus placebo) may have little to no effect on improving mortality, but the certainty of evidence is very low (RR 0.43, 95% CI 0.12 to 1.50; 3 trials, 327 participants; I² = 0%). Similarly, high-frequency chest wall oscillation (versus no physiotherapy) may also have little to no effect on improving mortality, but the certainty of evidence is very low (RR 0.75, 95% CI 0.17 to 3.29; 1 trial, 286 participants). Conventional chest physiotherapy (versus no physiotherapy) may have little to no effect on improving cure rate, but the certainty of evidence is very low (RR 0.93, 95% CI 0.56 to 1.55; 2 trials, 225 participants; I² = 85%). Active cycle of breathing techniques (versus no physiotherapy) may have little to no effect on improving cure rate, but the certainty of evidence is very low (RR 0.60, 95% CI 0.29 to 1.23; 1 trial, 32 participants). OMT (versus placebo) may improve cure rate, but the certainty of evidence is very low (RR 1.59, 95% CI 1.01 to 2.51; 2 trials, 79 participants; I² = 0%). OMT (versus placebo) may have little to no effect on mean duration of hospital stay, but the certainty of evidence is very low (mean difference (MD) -1.08 days, 95% CI -2.39 to 0.23; 3 trials, 333 participants; I² = 50%). Conventional chest physiotherapy (versus no physiotherapy, MD 0.7 days, 95% CI -1.39 to 2.79; 1 trial, 54 participants) and active cycle of breathing techniques (versus no physiotherapy, MD 1.4 days, 95% CI -0.69 to 3.49; 1 trial, 32 participants) may also have little to no effect on duration of hospital stay, but the certainty of evidence is very low. Positive expiratory pressure (versus no physiotherapy) may reduce the mean duration of hospital stay by 1.4 days, but the certainty of evidence is very low (MD -1.4 days, 95% CI -2.77 to -0.03; 1 trial, 98 participants). Positive expiratory pressure (versus no physiotherapy) may reduce the duration of fever by 0.7 days, but the certainty of evidence is very low (MD -0.7 days, 95% CI -1.36 to -0.04; 1 trial, 98 participants). Conventional chest physiotherapy (versus no physiotherapy, MD 0.4 days, 95% CI -1.01 to 1.81; 1 trial, 54 participants) and OMT (versus placebo, MD 0.6 days, 95% CI -1.60 to 2.80; 1 trial, 21 participants) may have little to no effect on duration of fever, but the certainty of evidence is very low. OMT (versus placebo) may have little to no effect on the mean duration of total antibiotic therapy, but the certainty of evidence is very low (MD -1.07 days, 95% CI -2.37 to 0.23; 3 trials, 333 participants; I² = 61%). Active cycle of breathing techniques (versus no physiotherapy) may have little to no effect on duration of total antibiotic therapy, but the certainty of evidence is very low (MD 0.2 days, 95% CI -4.39 to 4.69; 1 trial, 32 participants). High-frequency chest wall oscillation plus fibrobronchoscope alveolar lavage (versus fibrobronchoscope alveolar lavage alone) may reduce the MD of intensive care unit (ICU) stay by 3.8 days (MD -3.8 days, 95% CI -5.00 to -2.60; 1 trial, 286 participants) and the MD of mechanical ventilation by three days (MD -3 days, 95% CI -3.68 to -2.32; 1 trial, 286 participants), but the certainty of evidence is very low. One trial reported transient muscle tenderness emerging after OMT in two participants. In another trial, three serious adverse events led to early withdrawal after OMT. One trial reported no adverse events after positive expiratory pressure treatment. Limitations of this review were the small sample size and unclear or high risk of bias of the included trials. AUTHORS' CONCLUSIONS: The inclusion of two new trials in this update did not change the main conclusions of the original review. The current evidence is very uncertain about the effect of chest physiotherapy on improving mortality and cure rate in adults with pneumonia. Some physiotherapies may slightly shorten hospital stays, fever duration, and ICU stays, as well as mechanical ventilation. However, all of these findings are based on very low certainty evidence and need to be further validated.

Monoazadichalcogenasumanenes: Synthesis, Structures, and Ring Reconstruction via Atom Transfer under Acidic Conditions.

Buckybowls have unique properties that can be tailored by embedding main-group elements into their π-scaffolds. Herein, a synthetic approach is developed for producing monoazadichalcogenasumanenes (4 a/4 b, 6 a/6 b, 7 a/7 b) derived from sumanene by replacing its three benzylic carbons with one nitrogen and two chalcogen atoms (S for 4 a/4 b, Se for 6 a/6 b, Te for 7 a/7 b). Monoazadichalcogenasumanenes are deeper π-bowls than trichalcogensumanenes as the C-N bond is much shorter than C-X (X=S, Se, Te). The bowl-depth of 4 b (0.95 Å) is greater than that of corannulene (0.85 Å). The nitrogen atom donates electron density to the entire π-system that makes monoazadichalcogenasumanenes electron-rich. They undergo ring reconstruction of chalcogenophene ring via transferring a chalcogen atom from one molecule to another under acidic conditions. The nitrogen and chalcogen atoms play crucial role on this reaction.

Ion-Induced Phase Transfer of Cationic Dyes for Fluorescence-Based Electrolyte Sensing in Droplet Microfluidics.

Fluorescence-based sensing in droplet microfluidics requires small sample volumes, allows for high-throughput assays, and does not suffer from photobleaching as each flowing sensor is only scanned one time. In this paper, we report a selective and sensitive fluorescence-based ion-sensing methodology in droplet microfluidics using a T-junction PDMS chip. The oil stream is doped with sensor ingredients including an ionophore, a cation exchanger, and a permanently cationic fluorophore as the optical reporter. Electrolyte cations from the aqueous sample are extracted into oil segments and displace the cationic dyes into aqueous droplets. Laser-induced fluorescence of the two immiscible phases is collected alternately, which is in clear contrast to most other ion-selective optode configurations such as nanoparticle suspensions that rely on mixed optical signals of two phases. The cation exchanger, tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, is found to dramatically enhance the dye emission in the nonpolar sensing oil by preventing ion-pairing interactions and aggregations of the dye molecules, providing new insights into the mechanism of cationic dye-based ion sensors. The high dye brightness allows us to use low concentrations of sensing chemicals (e.g., 10 µM) in the oil and attain high sensitivity for detection of ions in an equal volume of sample. Using valinomycin as the ionophore and methylene blue as the dye, K+ is detected with a response time of ∼11 s, a logarithmic linear range of 10-5 to 10-2 M, a 20-fold total fluorescence response, >1000-fold selectivity against other electrolyte cations, and negligible cross-sensitivity toward the sample pH. The K+ concentration in untreated and undiluted whole blood and sweat samples is successfully determined by this microfluidic sensing method without optical interference from the droplet sample to the sensing oil. Detection of other ionic analytes can be achieved using the corresponding ionophores.

Digital printing of selective and reversible ion optodes on fabrics: toward smart clothes for epidermal chemical sensing.

While wearable chemical sensors often rely on electrochemical techniques, optical chemical sensors coupled with a smartphone or a miniaturized camera represent an attractive approach to the monitoring of sweat composition. In this paper, we modify real sports fabrics such as polyester-spandex fabrics with rational combinations of sensing chemicals including a pH indicator, an ion exchanger, and an ionophore via one-step inkjet printing. Highly selective and fully reversible pH optodes as well as Na+- and K+-selective optodes are obtained only when the most hydrophobic sensing chemicals are used (e.g., sodium ionophore VIII vs. sodium ionophore VI). These sensors exhibit large color-based responses that can be readily identified by naked eye or analyzed via an iPhone app. Their dynamic ranges well cover the physiological sweat concentrations of the analytes. Compared to most other sensors created on garments, our fabric-based optodes are cost-effective, mass-reproducible by the digital printing technology currently used in the textile industry, and do not significantly compromise the essential properties of fabrics such as flexibility, stretchability, wickability, and breathability.