The neuroprotection of controlled decompression after traumatic epidural intracranial hypertension through suppression of autophagy via PI3K/Akt signaling pathway.

Acute intracranial hypertension (AIH) is a common and tricky symptom that inflicts upon patients after traumatic brain injury (TBI). A variety of clinical options have been applied for the management of AIH, such as physiotherapy, medication, surgery and combination therapy. Specifically, controlled decompression (CDC) alleviates the extent of brain injury and reduces the incidence of a series of post-TBI complications, thereby enhancing the prognosis of patients suffering from acute intracranial hypertension. The objective of the present project is to illuminate the potential molecular mechanism that underlies the neuroprotective effects of CDC in a rat model of traumatic epidural intracranial hypertension (TEIH). Herein, we observed the functional recovery, the degree of brain edema, the level of apoptosis, the expressions of neuronal cell autophagy-related signaling pathway proteins (including Akt, p-Akt, LC3 and Beclin-1) in rat TEIH model at 24 h post-surgery. The results showed in comparison with rapid decompression (RDC), CDC reduced the degree of brain edema, diminished the level of cellular apoptosis and enhanced neurological function, and whereas the neuroprotective effect of CDC could be reversed by rapamycin (Rap). The expressions of Beclin-1 and LC3 in CDC group were significantly lower than those of RDC group, and the expression levels of these two proteins were significantly elevated after the addition of Rap. The expression of p-Akt in CDC group was considerably enhanced than RDC group. After the addition of LY294002, a PI3K/Akt pathway inhibitor, p-Akt protein expression was reduced, and the neuroprotective effect of the rats was markedly inhibited. Taken together, our data demonstrate the superior neuroprotective effect of CDC with regard to alleviating early brain edema, improving the neurological status, suppressing apoptosis and inhibiting neuronal autophagy via triggering PI3K/Akt signaling pathway.

Naked-Eye Readable Microarray for Rapid Profiling of Antibodies against Multiple SARS-CoV-2 Variants.

Novel high-throughput protein detection technologies are critically needed for population-based large-scale SARS-CoV-2 antibody detection as well as for monitoring quality and duration of immunity against virus variants. Current protein microarray techniques rely heavily on labeled transduction methods that require sophisticated instruments and complex operations, limiting their clinical potential, particularly for point-of-care (POC) applications. Here, we developed a label-free and naked-eye readable microarray (NRM) based on a thickness-sensing plasmon ruler, enabling antibody profiling within 30 min. The NRM chips provide 100% accuracy for neutralizing antibody detection by efficiently screening antigen types and experimental conditions and allow for the profiling of antibodies against multiple SARS-CoV-2 variants in clinical samples. We further established a flexible "barcode" NRM assay with a simple tape-based operation, enabling an effective smartphone-based readout and analysis. These results demonstrate new strategies for high-throughput protein detection and highlight the potential of novel protein microarray techniques for realistic clinical applications.

Controlled Decompression Alleviates Motor Dysfunction by Regulating Microglial Polarization via the HIF-1α Signaling Pathway in Intracranial Hypertension.

Decompressive craniectomy (DC) is a major form of surgery that is used to reduce intracranial hypertension (IH), the most frequent cause of death and disability following severe traumatic brain injury (sTBI) and stroke. Our previous research showed that controlled decompression (CDC) was more effective than rapid decompression (RDC) with regard to reducing the incidence of complications and improving outcomes after sTBI; however, the specific mechanisms involved have yet to be elucidated. In the present study, we investigated the effects of CDC in regulating inflammation after IH and attempted to identify the mechanisms involved. Analysis showed that CDC was more effective than RDC in alleviating motor dysfunction and neuronal death in a rat model of traumatic intracranial hypertension (TIH) created by epidural balloon pressurization. Moreover, RDC induced M1 microglia polarization and the release of pro-inflammatory cytokines. However, CDC treatment resulted in microglia primarily polarizing into the M2 phenotype and induced the significant release of anti-inflammatory cytokines. Mechanistically, the establishment of the TIH model led to the increased expression of hypoxia-inducible factor-1α (HIF-1α); CDC ameliorated cerebral hypoxia and reduced the expression of HIF-1α. In addition, 2-methoxyestradiol (2-ME2), a specific inhibitor of HIF-1α, significantly attenuated RDC-induced inflammation and improved motor function by promoting M1 to M2 phenotype transformation in microglial and enhancing the release of anti-inflammatory cytokines. However, dimethyloxaloylglycine (DMOG), an agonist of HIF-1α, abrogated the protective effects of CDC treatment by suppressing M2 microglia polarization and the release of anti-inflammatory cytokines. Collectively, our results indicated that CDC effectively alleviated IH-induced inflammation, neuronal death, and motor dysfunction by regulating HIF-1α-mediated microglial phenotype polarization. Our findings provide a better understanding of the mechanisms that underlie the protective effects of CDC and promote clinical translational research for HIF-1α in IH.

Retraction Notice to: Exosomes Derived from miR-143-Overexpressing MSCs Inhibit Cell Migration and Invasion in Human Prostate Cancer by Downregulating TFF3.

[This retracts the article DOI: 10.1016/j.omtn.2019.08.010.].

Thermal-annealing-regulated plasmonic enhanced fluorescence platform enables accurate detection of antigen/antibody against infectious diseases.

Plasmonic enhanced fluorescence (PEF) technology is a powerful strategy to improve the sensitivity of immunofluorescence microarrays (IFMA), however, current approaches to constructing PEF platforms are either expensive/time-consuming or reliant on specialized instruments. Here, we develop a completely alternative approach relying on a two-step protocol that includes the self-assembly of gold nanoparticles (GNPs) at the water-oil interface and subsequent annealing-assisted regulation of gold nanogap. Our optimized thermal-annealing GNPs (TA-GNP) platform generates adequate hot spots, and thus produces high-density electromagnetic coupling, eventually enabling 240-fold fluorescence enhancement of probed dyes in the near-infrared region. For clinical detection of human samples, TA-GNP provides super-high sensitivity and low detection limits for both hepatitis B surface antigen and SARS-CoV-2 binding antibody, coupled with a much-improved detection dynamic range up to six orders of magnitude. With fast detection, high sensitivity, and low detection limit, TA-GNP could not only substantially improve the outcomes of IFMA-based precision medicine but also find applications in fields of proteomic research and clinical pathology. Electronic Supplementary Material: Supplementary material (UV-Vis absorption and transmission spectra of GNPs, SEM, microscopy and digital images of PEF platforms, and fluorescence images of IFMA on PEF platforms) is available in the online version of this article at 10.1007/s12274-022-5035-6.

A newborn with convulsions 12 days after birth was misdiagnosed as neonatal intracranial hemorrhage: Case report.

INTRODUCTION: Cases with early diagnosis of neonatal tuberous sclerosis syndrome (TSC) are relatively seldom seen, and misdiagnosis of intracranial hemorrhage is even more rare. We retrospectively analyzed the clinical data of a case of neonatal tuberous sclerosis with atypical early symptoms and misdiagnosed as more common intracranial hemorrhage of the newborn. PATIENT CONCERNS: The child was female and had no obvious cause of convulsion 12 days after birth. The local hospital was initially diagnosed as "neonatal intracranial hemorrhage, congenital heart disease," and still had convulsions after 5 days of treatment, so it was transferred to neonatal intensive care unit of our hospital. DIAGNOSIS: After admission, cardiac color ultrasound, magnetic resonance imaging, and electroencephalogram were performed, and TSC was diagnosed in combination with clinical symptoms. However, no known pathogenic mutations such as TSC1 and TSC2 were detected by peripheral blood whole exon sequencing. INTERVENTION: After a clear diagnosis, sirolimus, and vigabatrin were given. But there were still convulsions. Topiramate, valproic acid, and oxcarbazepine were successively added to the outpatient department for antiepileptic treatment, and vigabatrin gradually decreased. OUTCOME: Up to now, although the seizures have decreased, they have not been completely controlled. CONCLUSIONS: The TSC of neonatal tuberous sclerosis is different from that of older children. It is usually characterized by respiratory distress and arrhythmia, and may be accompanied by convulsions, but the activity between attacks is normal. However, neonatal intracranial hemorrhage can be caused by premature delivery, birth injury, hypoxia, etc. Its characteristics are acute onset, severe illness, and rapid progression. Consequently, the diagnosis of these 2 diseases should not only be based on medical imaging, but also be combined with their clinical characteristics. When the imaging features are inconsistent with the clinical diagnosis, a comprehensive evaluation should be made again. The timing and pattern of onset of neonatal convulsions can help in differential diagnosis. If there is cardiac rhabdomyoma, subependymal or cortical nodule, skin low melanoma, etc, the possibility of neonatal TSC should be considered, and the diagnosis should be made according to its diagnostic criteria to avoid or reduce misdiagnosis.

Thickness-Sensing Sandwiched Plasmonic Biosensors Enable Label-Free Naked-Eye Antibody Quantification.

Clinical serology assays for detecting the antibodies of the virus are time-consuming, are less sensitive/selective, or rely on sophisticated detection instruments. Here, we develop a sandwiched plasmonic biosensor (SPB) for supersensitive thickness-sensing via utilizing the distance-dependent electromagnetic coupling in sandwiched plasmonic nanostructures. SPBs quantitatively amplify the thickness changes on the nanoscale range (sensitivity: ∼2% nm-1) into macroscopically visible signals, thereby enabling the rapid, label-free, and naked-eye detection of targeted biomolecular species (via the thickness change caused by immunobinding events). As a proof of concept, this assay affords a broad dynamic range (7 orders of magnitude) and a low LOD (∼0.3 pM), allowing for the extremely accurate SARS-CoV-2 antibody quantification (sensitivity/specificity: 100%/∼99%, with a portable optical fiber device). This strategy is suitable for high-throughput multiplexed detection and smartphone-based sensing at the point-of-care, which can be expanded for various sensing applications beyond the fields of viral infections and vaccination.

Case report: A novel de novo variant of SCN8A in a child with benign convulsions with mild gastroenteritis.

Benign convulsions with mild gastroenteritis (CwG) is characterized by afebrile convulsions accompanied by mild gastroenteritis, and it can be considered after central nervous system infection, hypoglycemia, electrolyte disturbance, and moderate and severe dehydration are excluded. Previous studies have suggested that genetics may be involved in CWG. Herein, we reported a novel de novo variant of SCN8A in a child with CwG. This is the first report that SCN8A may be associated with CwG. Our report may provides evidence for the genetic etiology of CwG and expands the phenotypic and genetic spectrum of SCN8A-related disorders, which previously included severe developmental and epileptic encephalopathy (DEE) phenotype, benign epilepsy phenotype, spectrum of intermediate epilepsies, and patients with cognitive and/or behavioral disturbances without epilepsy. Phenotype of CwG has a good prognosis, and it does not require long-term antiepileptic therapy. Overtreatment should be avoided clinically. However, the conclusion needs to be further defined by long-term follow-up and similar clinical reports. In spite of this, our clinical observation provides possible evidence for future studies on the relationship between SCN8A and CwG.

MiR-135b Alleviates Airway Inflammation in Asthmatic Children and Experimental Mice with Asthma via Regulating CXCL12.

OBJECTIVE: To clarify the possible influence of miR-135b on CXCL12 and airway inflammation in children and experimental mice with asthma. METHODS: The expressions of miR-135b and CXCL12 were detected using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in the serum of asthmatic children. Besides, the experimental asthmatic mice were established by aerosol inhalation of ovalbumin (OVA) followed by the treatment with agomiR-135b and antagomir-135b. Pathological changes of lung tissues were observed via HE staining and PAS staining. Besides, the airway hyperresponsiveness of mice was elevated and bronchoalveolar lavage fluid (BALF) was isolated for cell categorization and counting. The inflammatory cytokines in BALF were determined by enzyme-linked immunosorbent assay (ELISA), and the infiltration of Th17 cells in lung tissues was measured using flow cytometry. RESULTS: MiR-135b was downregulated and CXCL12 was upregulated in asthmatic children and mice. Overexpression of miR-135b may down-regulate CXCL12 expression in the lung of OVA mice, resulting in significant decreases in inflammatory infiltration, hyperplasia of goblet cell, airway hyperresponsiveness, cell quantity, as well as the quantity of eosinophilic granulocytes, neutrophils and lymphocytes in BALF. Also, the levels of inflammatory cytokines (IL-4, IL-5, IL-13 and IL-17) and the ratio of Th17 cells and IL-17 levels in lung tissues were decreased. However, miR-135b downregulation reversed these changes in OVA mice. CONCLUSION: MiR-135b may inhibit immune responses of Th17 cells to alleviate airway inflammation and hyperresponsiveness in asthma possibly by targeting CXCL12, showing the potential value in asthma treatment.

IP3R-mediated activation of BK channels contributes to mGluR5-induced protection against spinal cord ischemia-reperfusion injury.

Spinal cord ischemia-reperfusion injury (SCIRI) can cause dramatic neuron loss and lead to paraplegia in patients. In this research, the role of mGluR5, a member of the metabotropic glutamate receptors (mGluRs) family, was investigated both in vitro and in vivo to explore a possible method to treat this complication. In vitro experiment, after activating mGluR5 via pretreating cells with (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG) and 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB), excitotoxicity induced by glutamate (Glu) was attenuated in primary spinal cord neurons, evidenced by higher neuron viability, decreased lactate dehydrogenase (LDH) release and less detected TUNEL-positive cells. According to Western Blot (WB) results, Glu treatment resulted in a high level of large-conductance Ca2+- and voltage-activated K+ (BK) channels, with activation relying on the mGluR5-IP3R (inositol triphosphate) pathway. In vivo part, a rat model of SCIRI was built to further investigate the role of mGluR5. After pretreating them with CHPG and CDPPB, the rats showed markedly lower spinal water content, attenuated motor neuron injury in the spinal cord of L4 segments, and better neurological function. This effect could be partially reversed by paxilline, a blocker of BK channels. In addition, activating BK channels alone using specific openers: NS1619 or NS11021 can protect spinal cord neurons from injury induced by either SCIRI or Glu. In conclusion, in this research, we proved that mGluR5 exerts a protective role in SCIRI, and this effect partially works via IP3R-mediated activation of BK channels.

Efficient Synthesis of α-FeOOH from Pickling Wastewater in Falling Film Tower and Its Kinetics.

An efficient way to synthesize α-FeOOH from pickling wastewater in a falling film tower was proposed for the first time. This method overcomes the shortcomings of the traditional air oxidation method, and its production efficiency is increased by 16 times. The purity of α-FeOOH synthesized from pickling wastewater can reach 96.3%, and the iron recovery rate is greater than 90%. At the same time, we have systematically studied its kinetics in the falling film tower. The reaction rate constant k at different temperatures was also determined with the activation energy E a = 32.2497 kJ/mol and the pre-exponential A = 47.4132 s-1. In addition, based on the double-film theory, a corresponding macrokinetic model was established. Also, the Hatta number in the reaction system was obtained, which proved the excellent gas-liquid mass transfer performance in the falling film tower. This work provides a promising method for the efficient production of α-FeOOH and the recycling of pickling wastewater.

When Does Fusing Two Rings Not Yield a Larger Ring? The Curious Case of BOPHY.

Structural and electronic features of ground and excited states of the bis(difluoroboron)-1,2-bis-(pyrrol-2-yl)methylene-hydrazine (BOPHY) fluorophore, a seemingly extended version of the popular 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophore, are presented. Geometries of S0 and S1 electronic states are highly puckered, as confirmed by a combination of density functional theory (DFT), time-dependent (TD)-DFT, CASSCF-PT2, EOM-CCSD calculations and density functional theory-based molecular dynamics (DFT-MD). Packing effects are responsible for planarization in the solid state. Without the network of a solid matrix, planar conformation of BOPHY is an easily accessible transition state of inversion between two puckered conformations and hence solvated BOPHY is suggested to sample the conformational space between the two puckered geometries. The peculiar features of puckering as well as inversion via a planar TS are unaltered with a large range of lateral substitutions. Concentration-dependent electronic absorbance measurements were carried, which showed that the transformation of the low activation energy between the puckered and planar conformations is responsible for the broadening of the absorption spectrum. BOPHY, a four-ring system, is not an electronic extension of the three-ring BODIPY system since the excitation characteristics suggest BOPHY to behave as two electronically unlinked fragments despite the fact that the two subunits are covalently bonded.

Genetic variant rs72613567 of HSD17B13 gene reduces alcohol-related liver disease risk in Chinese Han population.

BACKGROUND & AIMS: Recently, the variant rs72613567:TA in the 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) has been associated with reduced levels of ALT and AST and a reduced risk of alcohol-related liver disease (ALD) in the European population. Therefore, the aim of this study was to investigate the association between the polymorphisms of HSD17B13 and ALD, liver serum markers and patatin-like phospholipase domain-containing protein 3 (PNPLA3) p.I148M in the Chinese Han population. METHODS: A case-control study was performed from five centres and included 769 ALD patients and 767 healthy controls. Two SNPs (rs72613567 and rs6834314) in HSD17B13 were genotyped using the Sequenom MassArray system and allele association analysis was performed using PLINK 1.90 software. RESULTS: HSD17B13 rs72613567:TA allele was associated with a reduced risk of ALD by 19% (95% confidence interval [CI]: 0.05-0.31, P = .01), uniformly, the G allele in the rs6834314 reduced the risk of ALD by 19% (95% CI: 0.05-0.31, P = 8.28 × 10-3). And the genotypes of two SNPs were associated with reducing the risk of ALD in three genetic model analysis. In addition, we found that TA allele was associated with lower levels of serum ALT, AST and GGT (P = .005, .007 and .02, respectively), higher level of serum ALB (P = .02), but not associated with ALP. In this cohort, the interaction between HSD17B13 rs72613567 and the steatogenic allele PNPLA3 rs738409 was not validated. CONCLUSION: The present study revealed that HSD17B13 rs72613567 was significantly associated with a reduced risk of ALD in Chinese Han population.

Dexmedetomidine-mediated regulation of miR-17-3p in H9C2 cells after hypoxia/reoxygenation injury.

Patients with heart disease often suffer from ischemia, which can be treated by reperfusion. However, this treatment can lead to the development of ischemia/reperfusion (I/R) injury, an inflammatory condition that can cause further heart damage. Dexmedetomidine (Dex), an α2-adrenoceptor agonist, and the microRNA (miR)-17-3p, have both been suggested to alleviate I/R injury and cardiac tissue inflammation. The aim of the present study was to investigate whether Dex and miR-17-3p could act together to prevent I/R injury. H9C2 cells, a myoblast cell line used as a model of rat cardiomyocytes, were cultured in a hypoxic environment for 3 h, and then reoxygenated for 3 h. This hypoxia/reoxygenation (H/R) was used to model I/R. Cell Counting kit-8 was used to determine cell viability and an annexin V-FITC/propidium iodide apoptosis kit used to analyze cell apoptosis. A dual luciferase reporter assay was used to determine the interaction between miR-17-3p and toll-like receptor 4 (TLR4). Western blotting and reverse transcription-quantitative PCR were used to determine protein levels and mRNA expression of TLR4 and galectin-3. A concentration of 0.1-10 µmol/l Dex attenuated H/R injury, which was accompanied by increased miR-17-3p levels. Additionally, the inhibition of miR-17-3p exacerbated H/R injury and reduced the effect of Dex on H/R injury. H/R led to an increased galectin-3 level compared with that in control cells, and Dex or miR-17-3p inhibitor did not markedly affect the level of galectin-3, indicating that Dex alleviated the effects of I/R injury through other pathways. Inhibition of miR-17-3p in Dex-induced H9C2 cells during H/R increased the expression of inflammatory mediators including tumor necrosis factor-α, interleukin (IL)-6, IL-1ß and phosphorylated NFκB subunit p65, while Dex reduced the H/R-induced expression of these inflammatory mediators. Inhibition of TLR4 also attenuated H/R injury. In summary, the findings of the present study indicated that Dex reduced H/R injury in H9C2 cell via the modulation of inflammatory signaling pathways, and these inflammatory factors could be regulated by miR-17-3p.

Palladium-Catalyzed Electrophilic Functionalization of Pyridine Derivatives through Phosphonium Salts.

Herein, we report a highly efficient and practical method for pyridine-derived heterobiaryl synthesis through palladium-catalyzed electrophilic functionalization of easily available pyridine-derived quaternary phosphonium salts. The nice generality of this reaction was goes beyond arylation, enabling facile incorporation of diverse carbon-based fragments, including alkenyl, alkynyl, and also allyl fragments, onto the pyridine core. Notably, the silver salt additive is revealed to be of vital importance for the success of this transformation and its pivotal role as transmetallation mediator, which guarantees a smooth transfer of pyridyl group to palladium intermediate, is also described.

Resveratrol prevents liver damage in MCD-induced steatohepatitis mice by promoting SIGIRR gene transcription.

Persistent inflammation is one of the main reasons that nonalcoholic fatty liver disease develops into cirrhosis and liver cancer, and reducing the expression of inflammatory factors may be an effective strategy to alleviate the development of nonalcoholic steatohepatitis (NASH). SIGIRR, a member of the interleukin-1 receptor family, has been shown to inhibit the production of inflammatory cytokines, and its down-regulation or deletion has been suggested to be an important cause of inflammatory damage to organs. In this study, we identified that resveratrol efficiently induced the transcriptional activity of the SIGIRR promoter and also increased SIGIRR mRNA levels in human hepatocytes and mouse livers. Furthermore, the potential effects of resveratrol on a methionine/choline-deficient diet-induced NASH mouse model were investigated. Resveratrol maintained the expression level of SIGIRR in the mouse liver. Resveratrol intervention alleviated NASH progression; decreased the levels of alanine aminotransferase and aspartate aminotransferase; and down-regulated tumor necrosis factor-α, interleukin (IL)-6, IL-1ß and transforming growth factor-ß mRNA and protein levels. Additionally, increased SIGIRR potentially blocked the activity of the Toll-like receptor/nuclear factor-κB signaling pathway both in vivo and in vitro. In vitro, resveratrol pretreatment protected against hepatocyte injury caused by foamy macrophage-released inflammatory cytokines, which are involved in the development of NASH. However, resveratrol did not effectively induce hepatocyte SIGIRR gene transcription in the inflammatory cytokine microenvironment. In conclusion, resveratrol is practical and acts as an agonist of the SIGIRR protein to negatively regulate the expression of inflammatory factors in liver, suggesting that appropriate intake may be a potential way to prevent the occurrence and development of NASH.

Improved drug delivery and anti-tumor efficacy of combinatorial liposomal formulation of genistein and plumbagin by targeting Glut1 and Akt3 proteins in mice bearing prostate tumor.

Despite the plethora of significant research progress made to develop novel strategies for the treatment of prostate cancer, this disease remains one of the major global health challenges among men. However, using a co-treatment approach utilizing two or more anticancer drugs has shown tremendous success in the treatment of many cancer types. Nanoliposomes are well known to encapsulate multiple drugs and deliver them at the desired site. In this work, we report the synthesis of nanoliposomes (∼100 nm) encapsulating two drugs, plumbagin, and genistein, to synergistically inhibit the growth of prostate cancer cells. The combination of plumbagin and genistein drugs was found inhibiting xenograft prostate tumor growth by ∼80 % without any appreciable toxicity. Mechanistically, the combination of plumbagin and genistein containing nanoliposomes leads to the inhibition of PI3K/AKT3 signaling pathway as well as the decreased population of Glut-1 transporters to impart the retardation in tumor growth. Decrease in proliferative cells and blood vessels are early biological processes that laid the foundation of the observed anti-tumor effect. Thus, a novel, and non-toxic liposomal formulation, containing plumbagin and genistein drugs, is reported, which can deliver anticancer agents to prostate tumors and inhibit the growth.

Effect of lung recruitment on blood gas index, hemodynamics, lung compliance, and rehabilitation index in children with acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common pediatric disease, with an increasing mortality rate in recent years. This study aims to explore the effects of lung recruitment on blood gas indexes, hemodynamics, lung compliance, and rehabilitation index in children with ARDS. METHODS: Seventy children with ARDS admitted to our hospital from December 2017 to December 2018 were selected as the study subjects, and were divided into a study group (35 cases, treated with lung recruitment strategy) and a control group (35 cases, treated with routine therapy). The changes of blood gas indexes, such as partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), and partial pressure of oxygen/fraction of inspired oxygen (PO2/FiO2) levels, as well as hemodynamic indexes, including cardiac output (CO), heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), were compared before and after treatment in the two groups. RESULTS: Results showed that the difference in blood gas indexes between the two groups was statistically significant after treatment (P<0.05), and that the levels of PaO2, PaCO2, pondus Hydrogenii (pH), and PO2/FiO2 in the study group were all higher compared to the control group (P<0.05). The hemodynamic indexes showed that CO was significantly different between the two groups (P<0.05), but HR, MAP, and CVP were not (P>0.05). The lung compliance values of the two groups continued to increase at different time points after treatment (P<0.05), and the lung compliance of the study group was higher than that of the control group immediately after recruitment, as well as at 10 and 60 min of lung recruitment (P<0.05). In addition, the ventilator use, ICU stay, and hospital stay times of the study group were shorter than those in the control group (P<0.05), and the mortality rate of the study group was lower than that of the control group (P>0.05). CONCLUSIONS: The lung recruitment strategy has a significant therapeutic effect on children with ARDS. It can effectively improve blood and gas function and lung compliance, and has a positive effect on the hemodynamic stability of children with ARDS.

Exosomes Derived from miR-143-Overexpressing MSCs Inhibit Cell Migration and Invasion in Human Prostate Cancer by Downregulating TFF3.

Exosomes are membrane-enclosed nanovesicles that shuttle active cargoes, such as mRNAs and microRNAs (miRNAs), between different cells. Mesenchymal stem cells (MSCs) are able to migrate to the tumor sites and exert complex functions over tumor progress. We investigated the effect of human bone marrow-derived MSC (BMSC)-derived exosomal miR-143 on prostate cancer. During the co-culture experiments, we disrupted exosome secretion by the inhibitor GW4869 and overexpressed exosomal miR-143 using miR-143 plasmid. miR-143 was involved in the progression of prostate cancer via trefoil factor 3 (TFF3). Moreover, miR-143 was downregulated while TFF3 was upregulated in prostate cancer cells and tissues, and miR-143 was found to specifically inhibit TFF3 expression. Human MSC-derived exosomes enriched miR-143 and transferred miR-143 to prostate cancer cells. Furthermore, elevated miR-143 or exosome-miR-143 or silencing TFF3 inhibited the expression of TFF3, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP)-2, and MMP-9 and PC3 cell proliferation, migration, invasion, and tumor growth, whereas it promoted apoptosis. In conclusion, hMSC-derived exosomal miR-143 directly and negatively targets TFF3 to suppress prostate cancer.

Sulfinate-Engaged Nucleophilic Addition Induced Allylic Alkylation of Allenoates.

A strategically novel Pd-catalyzed nucleophilic addition induced allylic alkylation reaction (NAAA) of allenoates has been successfully accomplished. By judiciously integrating ZnCl2-promoted Michael addition with Pd-catalyzed allylic alkylation, allenoates readily undergo allyl-sunfonylation at the internal double bond, thus providing a straightforward avenue for the rapid assembly of a host of structurally diversified α-allyl-ß-sufonylbut-3-enoate derivatives. The success of this transformation profits from a delicate control of the reaction kinetic of each elementary step, thanks to the synergistic interaction of Pd/Zn bimetallic system, thus suppressing either direct allylic sulfonylation or premature quenching of therein in situ generated ester enolate intermediate. Furthermore, by expanding the scope of workable Michael acceptor beyond those previously required doubly activated ones, such as methylenemalononitrile, the present work substantially enriches the repertoire of NAAA reactions.