The primordial differentiation of tumor-specific memory CD8+ T cells as bona fide responders to PD-1/PD-L1 blockade in draining lymph nodes.

Blocking PD-1/PD-L1 signaling transforms cancer therapy and is assumed to unleash exhausted tumor-reactive CD8+ T cells in the tumor microenvironment (TME). However, recent studies have also indicated that the systemic tumor-reactive CD8+ T cells may respond to PD-1/PD-L1 immunotherapy. These discrepancies highlight the importance of further defining tumor-specific CD8+ T cell responders to PD-1/PD-L1 blockade. Here, using multiple preclinical tumor models, we revealed that a subset of tumor-specific CD8+ cells in the tumor draining lymph nodes (TdLNs) was not functionally exhausted but exhibited canonical memory characteristics. TdLN-derived tumor-specific memory (TTSM) cells established memory-associated epigenetic program early during tumorigenesis. More importantly, TdLN-TTSM cells exhibited superior anti-tumor therapeutic efficacy after adoptive transfer and were characterized as bona fide responders to PD-1/PD-L1 blockade. These findings highlight that TdLN-TTSM cells could be harnessed to potentiate anti-tumor immunotherapy.

The kinase complex mTORC2 promotes the longevity of virus-specific memory CD4+ T cells by preventing ferroptosis.

Antigen-specific memory CD4+ T cells can persist and confer rapid and efficient protection from microbial reinfection. However, the mechanisms underlying the long-term maintenance of the memory CD4+ T cell pool remain largely unknown. Here, using a mouse model of acute infection with lymphocytic choriomeningitis virus (LCMV), we found that the serine/threonine kinase complex mammalian target of rapamycin complex 2 (mTORC2) is critical for the long-term persistence of virus-specific memory CD4+ T cells. The perturbation of mTORC2 signaling at memory phase led to an enormous loss of virus-specific memory CD4+ T cells by a unique form of regulated cell death (RCD), ferroptosis. Mechanistically, mTORC2 inactivation resulted in the impaired phosphorylation of downstream AKT and GSK3ß kinases, which induced aberrant mitochondrial reactive oxygen species (ROS) accumulation and ensuing ferroptosis-causative lipid peroxidation in virus-specific memory CD4+ T cells; furthermore, the disruption of this signaling cascade also inhibited glutathione peroxidase 4 (GPX4), a major scavenger of lipid peroxidation. Thus, the mTORC2-AKT-GSK3ß axis functions as a key signaling hub to promote the longevity of virus-specific memory CD4+ T cells by preventing ferroptosis.

Comparative genomics on chloroplasts of Rubus (Rosaceae).

Rubus, the largest genus in Rosaceae, contains over 1400 species that distributed in multiple habitats across the world, with high species diversity in the temperate regions of Northern Hemisphere. Multiple Rubus species are cultivated for their valuable fruits. However, the intrageneric classification and phylogenetic relationships are still poorly understood. In this study, we sequenced, assembled, and characterized 17 plastomes of Rubus, and conducted comparative genomics integrating with 47 previously issued plastomes of this genus. The 64 plastomes of Rubus exhibited typical quadripartite structure with sizes ranging from 155,144 to 156,700 bp, and contained 132 genes including 87 protein-coding genes, 37 tRNA genes and eight rRNA genes. All plastomes are conservative in the gene order, the frequency of different types of long repeats and simple sequence repeats (SSRs), the codon usage, and the selection pressure of protein-coding genes. However, there are also some differences in the Rubus plastomes, including slight contraction and expansion of the IRs, a variation in the numbers of SSRs and long repeats, and some genes in certain clades undergoing intensified or relaxed purifying selection. Phylogenetic analysis based on whole plastomes showed that the monophyly of Rubus was strongly supported and resolved it into six clades corresponding to six subgenera. Moreover, we identified 12 highly variable regions that could be potential molecular markers for phylogenetic, population genetic, and barcoding studies. Overall, our study provided insight into plastomic structure and sequence diversification of Rubus, which could be beneficial for future studies on identification, evolution, and phylogeny in this genus.

Rapid in situ diversification rates in Rhamnaceae explain the parallel evolution of high diversity in temperate biomes from global to local scales.

The macroevolutionary processes that have shaped biodiversity across the temperate realm remain poorly understood and may have resulted from evolutionary dynamics related to diversification rates, dispersal rates, and colonization times, closely coupled with Cenozoic climate change. We integrated phylogenomic, environmental ordination, and macroevolutionary analyses for the cosmopolitan angiosperm family Rhamnaceae to disentangle the evolutionary processes that have contributed to high species diversity within and across temperate biomes. Our results show independent colonization of environmentally similar but geographically separated temperate regions mainly during the Oligocene, consistent with the global expansion of temperate biomes. High global, regional, and local temperate diversity was the result of high in situ diversification rates, rather than high immigration rates or accumulation time, except for Southern China, which was colonized much earlier than the other regions. The relatively common lineage dispersals out of temperate hotspots highlight strong source-sink dynamics across the cosmopolitan distribution of Rhamnaceae. The proliferation of temperate environments since the Oligocene may have provided the ecological opportunity for rapid in situ diversification of Rhamnaceae across the temperate realm. Our study illustrates the importance of high in situ diversification rates for the establishment of modern temperate biomes and biodiversity hotspots across spatial scales.

High-throughput virtual screening of organic second-order nonlinear optical chromophores within the donor-π-bridge-acceptor framework.

In view of the theoretical importance and huge application potential of second-order nonlinear optical (NLO) materials, it is of great significance to conduct high-throughput virtual screening (HTVS) on a compound library to find candidate NLO chromophores. Under the donor-π-bridge-acceptor structural framework, a virtual compound library (size = 27 090) was constructed by enumeration of structural fragments. The kernel property adopted for optimization is the static first hyperpolarizability (ß0). By combining machine learning and quantum chemical calculations, we have performed an HTVS procedure to sieve NLO chromophores out, and the response mechanism of the selected optimal NLO chromophores was examined. We have found: (a) The multi-layer perceptron/extended connectivity fingerprint combination with 20% selection ratio gives the highest prediction accuracy for the studied systems. (b) The two optimal donors are bis(4-diphenylaminophenyl)aminyl and bis(4-tert-butylphenyl)aminyl; the optimal π-bridges are composed of two thiophenyl, selenophenyl or furanyl units; and the two optimal acceptors are tri-s-triazinyl and 2,3-dicyanopyrazinyl. (c) The no. 1 candidate molecule can exhibit a calculated ß0 equal to 8.55 × 104 a.u. (d) The difference in NLO responses of the optimal 16 molecules comes from the synergistic interaction of ES1, Δµ and f, by employing the two-level model. In addition, the sizable Δµ and f allow the studied optimal molecules to obtain a large NLO response in the meantime keeping a not-too-low excitation energy (retaining good optical transparency in the restricted range of the visible spectrum region). (e) With further modification on the acceptor, the designed DPA-π-TRZ-A' (A' = CN or NO2, π = oligo-thiophenyl or selenophenyl) systems can exhibit a rather large NLO response (maximum ß0 = 3.17 × 105 a.u.), hence should have considerable potential as second-order NLO chromophores. With the above observations, we expect to provide some insight for the research community into the HTVS of organic second-order NLO chromophores.

A Transportable Atomic Gravimeter with Constraint-Structured Active Vibration Isolation.

Many efforts have been taken in recent years to push atomic gravimeters toward practical applications. We demonstrate an atomic gravimeter named NIM-AGRb2 that is transportable and suitable for high-precision gravity measurements. Constraint-structured active vibration isolation (CS-AVI) is used to reduce the ground vibration noise. The constraint structure in CS-AVI ensures that the isolation platform only has vertical translation, with all other degrees of freedom (DoFs) being constrained. Therefore, the stability of active vibration isolation is enhanced. With the implementation of CS-AVI, the sensitivity of NIM-AGRb2 reached as low as 20.5 µGal/Hz1/2. The short-term sensitivity could be further reduced to 10.8 µGal/Hz1/2 in a seismologic observation station. Moreover, we evaluated the system noise of the gravimeter, and the results were consistent with our observations.

Nasal Spray of Neutralizing Monoclonal Antibody 35B5 Confers Potential Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern: A Small-Scale Clinical Trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), especially the Delta and Omicron variants, have been reported to show significant resistance to approved neutralizing monoclonal antibodies (mAbs) and vaccines. We previously identified a mAb named 35B5 that harbors broad neutralization to SARS-CoV-2 VOCs. Herein, we explored the protection efficacy of a 35B5-based nasal spray against SARS-CoV-2 VOCs in a small-scale clinical trial. METHODS: We enrolled 30 healthy volunteers who were nasally administered the modified 35B5 formulation. At 12, 24, 48, and 72 hours after nasal spray, the neutralization efficacy of nasal mucosal samples was assayed with pseudoviruses coated with SARS-CoV-2 spike protein of the wild-type strain or the Alpha, Beta, Delta, or Omicron variants. RESULTS: The nasal mucosal samples collected within 24 hours after nasal spray effectively neutralized SARS-CoV-2 VOCs (including Delta and Omicron). Meanwhile, the protection efficacy was 60% effective and 20% effective at 48 and 72 hours after nasal spray, respectively. CONCLUSIONS: A single nasal spray of 35B5 formation conveys 24-hour effective protection against SARS-CoV-2 VOCs, including the Alpha, Beta, Delta, or Omicron variants. Thus, 35B5 nasal spray might be potential in strengthening SARS-CoV-2 prevention, especially in high-risk populations. CLINICAL TRIALS REGISTRATION: 2022-005-02-KY.

Radiative transfer model and validation for infrared management optical properties of porous polymer materials incorporating impacts of micro-voids.

In order to characterize the infrared (IR) radiation absorption and/or emission performances of functional porous polymers which claim to have healthcare functions due to IR excitation and emission by processing technologies, a radiative transfer model was constructed based on the principle of IR radiation, the Beer-Lambert law, the Fresnel's formula and Planck's law. The theoretical analysis was conducted for the IR management optical properties of the porous sheet polymer materials, including IR reflection, transmission, absorption and emission behaviours during the dynamic process of IR radiation. A modeling method for characterization and revealing of IR management optical properties and optical and thermal transfer behaviours of the reflection and transmission was then investigated from the structural parameters and the temperature rise characteristics of the porous sheet polymer materials during the dynamic IR radiation process. The model was validated by comparing the predicted values from the radiative transfer model with the measured values from the test results of the validation experiments of eight typical porous sheet polymers in an experimental setup. The model was modified by consideration of the influences of two types of micro-voids defects represented by the porosity of micro structure and the thickness compression ratio. The micro-voids defects factors were added to the structural parameters, and therefore the model was improved and the maximum prediction errors of the transmission and reflection surfaces were mostly less than 10%. The radiative transfer model provides the theoretical fundamentals for the evaluation and guidance of IR management optical performances for new products design, development, fabrication and processing in industrial application of functional porous polymers.

Human papillomavirus 16 E6/E7 contributes to immune escape and progression of cervical cancer by regulating miR-142-5p/PD-L1 axis.

Persistent infection of human papillomavirus (HPV) and immune escape are the main causes of cervical cancer. E6/E7 encoded by HPV16 may be closely related to carcinogenesis. HPV infection may upregulate PD-L1 expression, resulting in immune escape and cervical cancerigenesis. Evidence indicates that miRNAs may mediate the regulation of E6/E7 on PD-L1. Therefore, we aimed to screen the miRNA, and further verify its expression and functions. Bioinformatics approaches were used to screen the miRNAs that mediate the regulation of E6/E7 on PD-L1. The expression of the miRNA and PD-L1 in HPV+ and HPV- cervical cancer cells were compared, and the effect of E6E7 on them was evaluated. Then, the effect of the miRNA on PD-L1 was assessed by the Gain- and Loss-of-function test. Finally, in vivo experiments were conducted to verify the effects of the miRNA on tumor growth and survival of tumor-bearing mice. Six miRNAs were screened, of which miR-142-5p was identified. MiR-142-5p was downregulated and PD-L1 was upregulated in HPV- cells after transfection of E6, E7, or E6/E7. The rescue test showed that the upregulation of miR-142-5p attenuated the effect of E6/E7 on PD-L1. The reverse relationship between PD-L1 and miR-142-5p was confirmed. In vivo experiments suggest that miR-142-5p upregulation inhibits the growth of the transplanted tumors by targeting PD-L1. MiR-142-5p acts as a tumor suppressor in cervical cancer. HPV16 E6E7 may promote the immune escape of cervical cancer cells by regulating the miR-142-5p/PD-L1 axis. Using miR-142-5p in tumor immunotherapy as a new strategy is proposed.

Nupr1 mediates renal fibrosis via activating fibroblast and promoting epithelial-mesenchymal transition.

Renal interstitial fibrosis (RIF) is a pathological process that fibrotic components are excessively deposited in the renal interstitial space due to kidney injury, resulting in impaired renal function and chronic kidney disease. The molecular mechanisms controlling renal fibrosis are not fully understood. In this present study, we identified Nuclear protein 1 (Nupr1), a transcription factor also called p8, as a novel regulator promoting renal fibrosis. Unilateral ureteral obstruction (UUO) time-dependently induced Nupr1 mRNA and protein expression in mouse kidneys while causing renal damage and fibrosis. Nupr1 deficiency (Nupr1-/- ) attenuated the renal tubule dilatation, tubular epithelial cell atrophy, and interstitial collagen accumulation caused by UUO. Consistently, Nupr1-/- significantly decreased the expression of type I collagen, myofibroblast markers smooth muscle α-actin (α-SMA), fibroblast-specific protein 1 (FSP-1), and vimentin in mouse kidney that were upregulated by UUO. These results suggest that Nupr1 protein was essential for fibroblast activation and/or epithelial-mesenchymal transition (EMT) during renal fibrogenesis. Indeed, Nupr1 was indispensable for TGF-ß-induced myofibroblast activation of kidney interstitial NRK-49F fibroblasts, multipotent mesenchymal C3H10T1/2 cells, and the EMT of kidney epithelial NRK-52E cells. It appears that Nupr1 mediated TGF-ß-induced α-SMA expression and collagen synthesis by initiating Smad3 signaling pathway. Importantly, trifluoperazine (TFP), a Nupr1 inhibitor, alleviated UUO-induced renal fibrosis. Taken together, our results demonstrate that Nupr1 promotes renal fibrosis by activating myofibroblast transformation from both fibroblasts and tubular epithelial cells.

Activatable endoplasmic reticulum-targeted NIR fluorescent probe with a large Stokes shift for detecting and imaging chymotrypsin.

In this work, the first endoplasmic reticulum-targeted near-infrared fluorescent probe, ISO-Chy, with a dicyanoisophorone derivative as a fluorophore is reported by introducing the recognition group of 4-bromobutyl for chymotrypsin detection. The probe can be easily synthesized and has shown satisfactory sensitivity and selectivity to chymotrypsin. Meanwhile, ISO-Chy has a large Stokes shift (135 nm) to minimize self-absorption and interference from autofluorescence and then generate significant fluorescence enhancement upon incubation with chymotrypsin. Additionally, ISO-Chy has an excellent ability to target the endoplasmic reticulum, along with preferable Pearson's correlation coefficients (Rr) of 0.9411 and 0.9522 in P815 cells and HepG2 cells, respectively. Moreover, ISO-Chy was successfully utilized to visualize endogenous chymotrypsin in P815 cells and HepG2 cells and was first used to detect chymotrypsin activity in HepG2 tumor-bearing mice. These findings indicate that ISO-Chy could be an effective tool for detecting endogenous chymotrypsin activity, supporting its use for investigating chymotrypsin function in pathologic processes.

[Application of single-sperm sequencing technology in preimplantation genetic testing for men with autosomal dominant polycystic kidney disease].

OBJECTIVE: To investigate the value of single-sperm sequencing technology in preimplantation genetic testing. METHODS: Haplotypes were constructed by single-sperm isolation combined with single-sperm sequencing for a patient with autosomal dominant polycystic kidney disease (ADPKD) caused by de novo mutation of the PKD1 gene c.3815T>G. 50. Single-sperm samples were isolated by mechanical braking, whole-genome amplification was performed, and mutation loci and their 187 upstream and downstream single nucleotide polymorphisms (SNP) were designed. The amplified products were verified for determination of the chromosome haplotypes carrying or not carrying pathogenic mutations. The embryos carrying pathogenic mutations were identified in 7 embryonic trophectoderm cell biopsy samples by high-throughput sequencing after whole-genome amplification. Available blastocysts were selected for embryo transfer, and amniotic fluid samples were collected at 18 weeks of gestation to determine whether the fetuses carried pathogenic mutations. RESULTS: A total of 30 SNPs were identified by single-sperm sequencing, and haplotypes were successfully constructed. Preimplantation haplotype analysis indicated that 5 embryos carried pathogenic mutations and 2 did not. mid-gestation amniotic fluid genetic testing revealed no PKD1 gene c.3815T>G mutation in the fetuses. CONCLUSION: SNPs can be identified by single-sperm sequencing in males carrying de novo pathogenic mutation, and haplotypes can be constructed by linkage analysis for preimplantation genetic testing of embryos.

The Epigenetic Regulator EZH2 Instructs CD4 T Cell Response to Acute Viral Infection via Coupling of Cell Expansion and Metabolic Fitness.

The protection of a majority of viral vaccines is mediated by CD4 T cell-dependent humoral immunity. The methyltransferase enhancer of zeste homolog 2 (EZH2) dictates the differentiation of naive CD4 T cells into distinct effector T helper subsets at the onset of acute viral infection. However, whether and how EZH2 manipulates differentiated virus-specific CD4 T cell expansion remain to be elucidated. Here, we found that EZH2 is integral for virus-specific CD4 T cell expansion in a mouse model of acute viral infection. By a mechanism that involves fine-tuning the mechanistic target of rapamycin (mTOR) signaling, EZH2 participates in integrating metabolic pathways to support cell expansion. The genetic ablation of EZH2 leads to impaired cellular metabolism and, consequently, poor CD4 T cell response to acute viral infection. Thus, we identified EZH2 as a novel regulator in virus-specific CD4 T cell expansion during acute viral infection.IMPORTANCE The CD4 T cell response is critical in curtailing viral infection or eliciting efficacious viral vaccination. Highly efficient expansion of virus-specific CD4 T cells culminates in a qualified CD4 T cell response. Here, we found that the epigenetic regulator EZH2 is a prerequisite for the virus-specific CD4 T cell response, with a mechanism coupling cell expansion and metabolism. Thus, our study provides valuable insights for strategies targeting EZH2 to improve the efficacy of CD4 T cell-based viral vaccines and to help treat diseases associated with aberrant CD4 T cell responses.

Occult primary white matter impairment in Leber hereditary optic neuropathy.

BACKGROUND AND PURPOSE: Leber hereditary optic neuropathy (LHON) is a disease maternally inherited from mitochondria that predominantly impairs the retinal ganglion cells and their axons. To identify whether occult brain white matter (WM) impairment is involved, a voxel-based analysis (VBA) of diffusion metrics was carried out in LHON patients with normal-appearing brain parenchyma. METHODS: Fifty-four symptomatic LHON patients (including 22 acute LHON with vision loss for ≤12 months, and 32 chronic LHON) without any visible brain lesions and 36 healthy controls (HCs) were enrolled in this study. VBA was applied to quantify the WM microstructural changes of LHON patients. Finally, the associations of the severity of WM impairment with disease duration and ophthalmologic deficits were assessed. RESULTS: Compared with the HCs, the average retinal nerve fiber layer (RNFL) thickness was significantly reduced in patients with chronic LHON, whereas it was increased in patients with acute LHON (p < 0.05, corrected). VBA identified significantly decreased fractional anisotropy widely in WM in both the acute and chronic LHON patients, including the left anterior thalamic radiation and superior longitudinal fasciculus, and bilateral corticospinal tract, dentate nuclei, inferior longitudinal fasciculus, forceps major, and optic radiation (OR; p < 0.05, corrected). The integrity of most WM structures (except for the OR) was correlated with neither disease duration nor RNFL thickness (p > 0.05, corrected). CONCLUSIONS: Occult primary impairment of widespread brain WM is present in LHON patients. The coexisting primary and secondary WM impairment may jointly contribute to the pathological process of LHON.

Aminolactonization of Unactivated Alkenes Catalyzed by Aryl Iodine.

A one-step protocol of the aryl iodine-catalyzed aminolactonization of unactivated alkenes under oxidation conditions was first reported to efficiently construct diverse amino lactones in a short time using HNTs2 as the compatible nitrogen source. In addition, we investigated the influence of the reaction rate based on the structure of the iodoarene precatalyst, which revealed the selective adjustment effect on aminolactonization and oxylactonization. Finally, preliminary experiments verified the feasibility of asymmetric aminolactonization catalyzed by a chiral iodoarene precatalyst.

Genomic signatures and candidate genes of lint yield and fibre quality improvement in Upland cotton in Xinjiang.

Xinjiang has been the largest and highest yield cotton production region not only in China, but also in the world. Improvements in Upland cotton cultivars in Xinjiang have occurred via pedigree selection and/or crossing of elite alleles from the former Soviet Union and other cotton producing regions of China. But it is unclear how genomic constitutions from foundation parents have been selected and inherited. Here, we deep-sequenced seven historic foundation parents, comprising four cultivars introduced from the former Soviet Union (108Ф, C1470, 611Б and KK1543) and three from United States and Africa (DPL15, STV2B and UGDM), and re-sequenced sixty-nine Xinjiang modern cultivars. Phylogenetic analysis of more than 2 million high-quality single nucleotide polymorphisms allowed their classification two groups, suggesting that Xinjiang Upland cotton cultivars were not only spawned from 108Ф, C1470, 611Б and KK1543, but also had a close kinship with DPL15, STV2B and UGDM. Notably, identity-by-descent (IBD) tracking demonstrated that the former Soviet Union cultivars have made a huge contribution to modern cultivar improvement in Xinjiang. A total of 156 selective sweeps were identified. Among them, apoptosis-antagonizing transcription factor gene (GhAATF1) and mitochondrial transcription termination factor family protein gene (GhmTERF1) were highly involved in the determination of lint percentage. Additionally, the auxin response factor gene (GhARF3) located in inherited IBD segments from 108Ф and 611Б was highly correlated with fibre quality. These results provide an insight into the genomics of artificial selection for improving cotton production and facilitate next-generation precision breeding of cotton and other crops.

Genome-wide quantitative trait loci reveal the genetic basis of cotton fibre quality and yield-related traits in a Gossypium hirsutum recombinant inbred line population.

Cotton is widely cultivated globally because it provides natural fibre for the textile industry and human use. To identify quantitative trait loci (QTLs)/genes associated with fibre quality and yield, a recombinant inbred line (RIL) population was developed in upland cotton. A consensus map covering the whole genome was constructed with three types of markers (8295 markers, 5197.17 centimorgans (cM)). Six fibre yield and quality traits were evaluated in 17 environments, and 983 QTLs were identified, 198 of which were stable and mainly distributed on chromosomes 4, 6, 7, 13, 21 and 25. Thirty-seven QTL clusters were identified, in which 92.8% of paired traits with significant medium or high positive correlations had the same QTL additive effect directions, and all of the paired traits with significant medium or high negative correlations had opposite additive effect directions. In total, 1297 genes were discovered in the QTL clusters, 414 of which were expressed in two RNA-Seq data sets. Many genes were discovered, 23 of which were promising candidates. Six important QTL clusters that included both fibre quality and yield traits were identified with opposite additive effect directions, and those on chromosome 13 (qClu-chr13-2) could increase fibre quality but reduce yield; this result was validated in a natural population using three markers. These data could provide information about the genetic basis of cotton fibre quality and yield and help cotton breeders to improve fibre quality and yield simultaneously.

Cascaded Fabry-Perot interferometer-regenerated fiber Bragg grating structure for temperature-strain measurement under extreme temperature conditions.

We demonstrated an optical fiber sensor based on a cascaded fiber Fabry-Perot interferometer (FPI)-regenerated fiber Bragg grating (RFBG) for simultaneous measurement of temperature and strain under high temperature environments. The FPI is manufactured from a ∼74 µm long hollow core silica tube (HCST) sandwiched between two single mode fibers (SMFs). The RFBG is inscribed in one of the SMF arms which is embedded inside an alundum tube, making it insensitive to the applied strain on the entire fiber sensor, just in case the temperature and strain recovery process are described using the strain-free RFBG instead of a characteristic due-parameter matrix. This feature is intended for thermal compensation for the FPI structure that is sensitive to both temperature and strain. In the characterization tests, the proposed device has exhibited a temperature sensitivity ∼ 18.01 pm/°C in the range of 100 °C - 1000 °C and excellent linear response to strain in the range of 300 °C - 1000 °C. The measured strain sensitivity is as high as ∼ 2.17 pm/µÉ› for a detection range from 0 µÉ› to 450 µÉ› at 800 °C, which is ∼ 1.5 times that of a FPI-RFBG without the alundum tube.

Intranasal dexmedetomidine is an effective sedative agent for electroencephalography in children.

BACKGROUND: Intranasal dexmedetomidine (DEX), as a novel sedation method, has been used in many clinical examinations of infants and children. However, the safety and efficacy of this method for electroencephalography (EEG) in children is limited. In this study, we performed a large-scale clinical case analysis of patients who received this sedation method. The purpose of this study was to evaluate the safety and efficacy of intranasal DEX for sedation in children during EEG. METHODS: This was a retrospective study. The inclusion criteria were children who underwent EEG from October 2016 to October 2018 at the Children's Hospital affiliated with Chongqing Medical University. All the children received 2.5 µg·kg- 1 of intranasal DEX for sedation during the procedure. We used the Modified Observer Assessment of Alertness/Sedation Scale (MOAA/S) and the Modified Aldrete score (MAS) to evaluate the effects of the treatment on sedation and resuscitation. The sex, age, weight, American Society of Anesthesiologists physical status (ASAPS), vital signs, sedation onset and recovery times, sedation success rate, and adverse patient events were recorded. RESULTS: A total of 3475 cases were collected and analysed in this study. The success rate of the initial dose was 87.0% (3024/3475 cases), and the success rate of intranasal sedation rescue was 60.8% (274/451 cases). The median sedation onset time was 19 mins (IQR: 17-22 min), and the sedation recovery time was 41 mins (IQR: 36-47 min). The total incidence of adverse events was 0.95% (33/3475 cases), and no serious adverse events occurred. CONCLUSIONS: Intranasal DEX (2.5 µg·kg- 1) can be safely and effectively used for EEG sedation in children.

Fifty Percent Effective Dose of Intranasal Dexmedetomidine Sedation for Transthoracic Echocardiography in Children With Cyanotic and Acyanotic Congenital Heart Disease.

OBJECTIVES: To determine the 50% and 95% effective dose of intranasal dexmedetomidine sedation for transthoracic echocardiography in children with cyanotic and acyanotic congenital heart disease. DESIGN: A prospective, nonrandomized study. SETTING: A tertiary care teaching hospital. PARTICIPANTS: Patients younger than 18 months with known or suspected congenital heart disease scheduled for transthoracic echocardiography with sedation. INTERVENTIONS: Patients were divided into a cyanotic group (blood oxygen saturation <85%) or an acyanotic group (blood oxygen saturation ≥85%). This study used Dixon's up-and-down method sequential allocation design. In both groups, the initial dose of intranasal dexmedetomidine was 2 µg/kg and the gradient of increase or decrease was 0.25 µg/kg. MEASUREMENTS AND MAIN RESULTS: The 50% effective dose (95% confidence interval) of intranasal dexmedetomidine sedation for transthoracic echocardiography was 3.2 (2.78-3.55) µg/kg and 1.9 (1.69-2.06) µg/kg in the cyanotic and acyanotic groups, respectively. None of the patients experienced significant adverse events. CONCLUSION: The 50% (95% confidence intervals) effective doses of intranasal dexmedetomidine sedation for transthoracic echocardiography were 3.2 (2.78-3.55) µg/kg and 1.9 (1.69-2.06) µg/kg in children with cyanotic and acyanotic congenital heart disease, respectively.