Divergent sensory pathways of sneezing and coughing.

Sneezing and coughing are primary symptoms of many respiratory viral infections and allergies. It is generally assumed that sneezing and coughing involve common sensory receptors and molecular neurotransmission mechanisms. Here, we show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3-) mediates sneezing responses to a multitude of nasal irritants, allergens, and viruses. Although this population also innervates the trachea, it does not mediate coughing, as revealed by our newly established cough model. Instead, a distinct sensory population (somatostatin [SST+]) mediates coughing but not sneezing, unraveling an unforeseen sensory difference between sneezing and coughing. At the circuit level, sneeze and cough signals are transmitted and modulated by divergent neuropathways. Together, our study reveals the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing, offering neuronal drug targets for symptom management in respiratory viral infections and allergies.

Application of artificial intelligence-assisted image diagnosis software based on volume data reconstruction technique in medical imaging practice teaching.

BACKGROUND: In medical imaging courses, due to the complexity of anatomical relationships, limited number of practical course hours and instructors, how to improve the teaching quality of practical skills and self-directed learning ability has always been a challenge for higher medical education. Artificial intelligence-assisted diagnostic (AISD) software based on volume data reconstruction (VDR) technique is gradually entering radiology. It converts two-dimensional images into three-dimensional images, and AI can assist in image diagnosis. However, the application of artificial intelligence in medical education is still in its early stages. The purpose of this study is to explore the application value of AISD software based on VDR technique in medical imaging practical teaching, and to provide a basis for improving medical imaging practical teaching. METHODS: Totally 41 students majoring in clinical medicine in 2017 were enrolled as the experiment group. AISD software based on VDR was used in practical teaching of medical imaging to display 3D images and mark lesions with AISD. Then annotations were provided and diagnostic suggestions were given. Also 43 students majoring in clinical medicine from 2016 were chosen as the control group, who were taught with the conventional film and multimedia teaching methods. The exam results and evaluation scales were compared statistically between groups. RESULTS: The total skill scores of the test group were significantly higher compared with the control group (84.51 ± 3.81 vs. 80.67 ± 5.43). The scores of computed tomography (CT) diagnosis (49.93 ± 3.59 vs. 46.60 ± 4.89) and magnetic resonance (MR) diagnosis (17.41 ± 1.00 vs. 16.93 ± 1.14) of the experiment group were both significantly higher. The scores of academic self-efficacy (82.17 ± 4.67) and self-directed learning ability (235.56 ± 13.50) of the group were significantly higher compared with the control group (78.93 ± 6.29, 226.35 ± 13.90). CONCLUSIONS: Applying AISD software based on VDR to medical imaging practice teaching can enable students to timely obtain AI annotated lesion information and 3D images, which may help improve their image reading skills and enhance their academic self-efficacy and self-directed learning abilities.

[Two cases of neonatal Legionella pneumonia]. / 新生儿嗜肺军团菌肺炎2例.

Patient 1, a 12-day-old female infant, presented with fever, cough, dyspnea, and elevated infection markers, requiring respiratory support. Metagenomic next-generation sequencing (mNGS) of blood and bronchoalveolar lavage fluid revealed Legionella pneumophila (LP), leading to diagnoses of LP pneumonia and LP sepsis. The patient was treated with erythromycin for 15 days and azithromycin for 5 days, resulting in recovery and discharge. Patient 2, an 11-day-old female infant, presented with dyspnea, fever, elevated infection markers, and multiple organ dysfunction, requiring mechanical ventilation. mNGS of blood and cerebrospinal fluid indicated LP, leading to diagnoses of LP pneumonia, LP sepsis, and LP intracranial infection. The patient was treated with erythromycin for 19 days and was discharged after recovery. Neonatal LP pneumonia lacks specific clinical symptoms, and azithromycin is the preferred antimicrobial agent. The use of mNGS can provide early and definitive diagnosis for severe neonatal pneumonia of unknown origin.

All-solution-processed perovskite/gallium nitride particles hybrid visible-blind ultraviolet photodetectors.

Last decades have witnessed the rapid development of ultraviolet (UV) photodetectors in diversity of applications. The III-nitride semiconductor and metal halide perovskite have both performed promising UV-sensing optoelectronic properties. However, they are still suffering from either the high temperature epitaxial-growth or low photocurrent generated in UV range. In this work, we demonstrate an innovative MAPbCl3/GaN particle hybrid device with all-solution-processed deposition methods. Comparing to the control MAPbCl3photoconductors, the photo-sensing ability of the hybrid device with the optimal concentration of GaN particles is more than one order of magnitude enhanced, and report a responsivity of 86 mA W-1, a detectivity of 3.1 × 1011Jones and a rise/fall time of 1.1/10.7 ms at 360 nm. The photocurrent increment could be attributed to the enhanced UV absorption of GaN particles and facilitated charge separation and photoconductive gain at MAPbCl3/GaN heterojunction. This work paves a pathway towards the large-scale low-cost UV photodetectors in versatile applications.

The Novel Fluorescent Probe Toward Yttrium(III) and its Bioimaging.

In this paper, the novel fluorescence probe XP based on Schiff-base was designed, synthesized and characterized, which could detect Y3+selectively and sensitively. The recognition mechanism of XP toward Y3+ was studied by Job's plot and HRMS. It was investigated that stoichiometric ratio of the probe XP conjugated with Y3+ was 1:2. And the detection limit was calculated as 0.30 µM. In addition, Y3+ was recognized by the test paper made from XP. And the probe XP could detect  Y3+ selectively in Caenorhabditis elegans and the main organs of mice. Thus, XP was considered to have some potential for application in bioimaging.

Pharmacokinetics and tissue distribution of five bioactive components in the Corydalis yanhusuo total alkaloids transdermal patch following Shenque acupoint application in rats assessed by ultra-performance liquid chromatography-tandem mass spectrometry.

The purpose of this study was to evaluate the pharmacokinetics and tissue distribution of the Corydalis yanhusuo total alkaloids transdermal patch (CTTP) following Shenque acupoint application in rats. The concentrations of corydaline, tetrahydropalmatine, tetrahydrocolumbamine, protopine, and dehydrocorydaline in rat plasma and various tissues were simultaneously detected by ultra-performance liquid chromatography-tandem mass spectrometry after Shenque acupoint administration of CTTP. Plasma, heart, liver, spleen, lung, and kidney tissue samples were collected at specific times and separated by gradient elution on an ACQUITY UPLC HSS T3 column (1.8 µm, 100 mm × 2.1 mm) with a mobile phase of 0.01% formic acid aqueous solution and acetonitrile-0.01% formic acid. The methodological results showed that the selectivity, linear range, accuracy, precision, stability, matrix effect, and extraction recovery of the established method met the requirements of biological sample analysis. The results indicated that CTTP following Shenque acupoint administration rapidly delivered adequate drug into rat blood and maintained an effective plasma level for a significantly longer time than non-acupoint administration. Furthermore, CTTP effectively reached the liver through Shenque acupoint administration and showed tissue selectivity. The data obtained could provide a prospect for the treatment of chronic pain with CTTP following Shenque acupoint application.

Effects of multicomponent exercise training on muscle oxygenation in young and older adults.

Objective: Though multicomponent exercise training was found beneficial in improving the physical functionality, the effects of multicomponent exercise training on muscle oxygenation are still unclear. The purpose of this study was to investigate the effects of multicomponent exercise training on muscle oxygenation in young and older participants. Methods: In this study, 17 young adults (Y) and 18 healthy older adults (E) were recruited to receive a multicomponent exercise training for 12 weeks, 2-3 sessions per week. Muscle oxygenation, muscle strength, and electromyography data were collected and compared pre- and post-training. Muscle oxygen saturation (SpO2) during isometric knee extension tests involving voluntary contraction (VOL) and electrical stimulation (ES) was measured by near-infrared spectroscopy. The SpO2 kinetics in the contraction and recovery phases were calculated using a tangential model to extract ΔSpO2 and inflection time (IF). Results: Muscle strength significantly increased in the post-training (234.31 ± 83.2 N·m, p < 0.05). The post-training ΔSpO2 of the ES in the Y (8.43 ± 5.35%) significantly increased and was higher than that in the E (2.78 ± 3.03%, p < 0.05). In the recovery phase, the post-training IF of VOL (7.07 ± 3.31s) was significantly shorter than that of the pre-training period (8.73 ± 4.46s, p < 0.05). Additionally, the median frequency of electromyography significantly decreased in the post-training period (103.84 ± 21.75 Hz, p < 0.05). Conclusion: The multicomponent exercise training improved the muscle strength, neuromuscular performance, and muscle aerobic function irrespective of age. The primary adaptation of the muscles to the multicomponent exercise training between the two groups varied.

Characterization of diterpene metabolism in rats with ingestion of seed products from Euphorbia lathyris L. (Semen Euphorbiae and Semen Euphorbiae Pulveratum) using UHPLC-Q-Exactive MS.

Previous pharmacological studies have indicated that diterpenoids are the primary effective chemical cluster in the seeds of Euphorbia lathyris L. The seed products are used in traditional Chinese medicine in the forms of Semen Euphorbiae (SE) and Semen Euphorbiae Pulveratum (SEP). However, the metabolism of the plant's diterpenoids has not been well elucidated, which means that the in vivo metabolite products have not been identified. The current study screened the physiological metabolites of six diterpenes [Euphorbia factor L1 (L1), L2 (L2), L3 (L3), L7a (L7a), L7b (L7b), and L8 (L8)] in feces and urine of rats after oral administration of SE and SEP using UHPLC-Q-Exactive MS. A total of 22 metabolites were detected in feces and 8 in urine, indicating that the major elimination route of diterpenoids is via the colon. Hydrolysis, methylation, and glucuronidation served as the primary metabolic pathways of these diterpenoids. In sum, this study contributed to the elucidation of new metabolites and metabolic pathways of SE and SEP, and the new chemical identities can be used to guide further pharmacokinetic studies.

Metabonomics analysis of semen euphorbiae and semen Euphorbiae Pulveratum using UPLC-Q-TOF/MS.

Semen Euphorbiae (SE), the dry and mature seed of Euphorbia lathyris L., a common traditional Chinese medicine, has significant pharmacological activity. However, its toxicity limits its clinical application, and less toxic Semen Euphorbiae Pulveratum (SEP) is often used clinically. To explore the possible mechanism of SE frost-making and attenuation, this study used ultrahigh-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry to perform a comprehensive metabolomics analysis of serum and urine samples from rats treated with SE and SEP, and performed histopathological evaluation of liver, kidney and colon tissues. Meanwhile, the different metabolites were visualized through multivariate statistical analysis and the HMDB and KEGG databases were used to distinguish the differential metabolites of SE and SEP to reveal related metabolic pathways and their significance. In total, 32 potential biomarkers, 14 in serum and 18 in urine, were identified. The metabolic pathway analysis revealed that arachidonic acid metabolism, sphingolipid metabolism, tyrosine and tryptophan biosynthesis, the tricarboxylic acid cycle and seven other metabolic pathways were significantly altered. Importantly, compared with SE, SEP reduced the metabolic disorder related to endogenous components. The mechanism may be related to the regulation of lipid metabolism, intestinal flora metabolites, amino acid metabolism and energy metabolism. This study provided new insights into the possible mechanism of SE freezing and attenuation.

[Optimization of formulation of paclitaxel nanosuspension encapsulated by erythrocyte membrane based on Box-Behnken method].

In view of the longevity and innate immune escape of red blood cells, this study designed the red blood cell membrane-coated paclitaxel nanosuspension [RBC-(PTX)NS] and investigated its physicochemical properties and antitumor effect in vitro. Paclitaxel nanosuspension [(PTX)NS] was prepared by ultrasonic precipitation and then RBC-(PTX)NS by ultrasonic coating. The formulation of(PTX)NS was optimized with Box-Behnken method and indexes of particle diameter, zeta potential, and stability. The morphology, particle diameter, stability, in vitro dissolution, and antitumor effect of(PTX)NS and RBC-(PTX)NS were characterized. The results showed that the particle diameter and zeta potential were(129.38±0.92) nm and(-22.41±0.48) mV, respectively, for the optimized(PTX)NS, while(142.5±0.68) nm and(-29.85±0.53) mV, respectively, for RBC-(PTX)NS. Under the transmission electron microscope,(PTX)NS was spherical and RBC-(PTX)NS had obvious core-shell structure. RBC-(PTX)NS remained stable for 5 days at 4 ℃. The in vitro dissolution test demonstrated that the cumulative release rate of RBC-(PTX)NS reached 79% within 20 min, which was significantly higher than that(25%) of(PTX)NS(P<0.05). As evidenced by MTT assay, RBC-(PTX)NS highly inhibited the proliferation of HepG2 cells in a dose-dependent manner. The cell membrane-coated nano-preparation preparation method is simple and reproducible. It improves the solubility of PTX and endows RBC-(PTX)NS with higher stability and stronger cytotoxicity. Thus, it is a new method for the delivery of PTX via nanocrystallization.

Measuring refractive indices of a uniaxial crystal by structured light with non-uniform correlation.

We introduce an effective method for measuring the refractive indices of a uniaxial crystal based on the independent self-focusing property of non-uniformly correlated beams along the $x$ and $y$ directions. We demonstrate how the positions of the independent foci can be changed by adjusting coherence lengths to determine the characteristic coherence lengths of the beams in a uniaxial crystal, and how this information can be used to determine the refractive indices by relating the propagation characteristics of the beam in free space and in the crystal. Furthermore, it is demonstrated that, by choosing a high beam order, one can reduce the measuring error caused by CCD detection precision. These results present an example of how non-uniformly correlated beams can be used for applications in anisotropic materials.

Selective dispersion of neutral nanoplates and the interfacial structure of copolymers based on coarse-grained molecular dynamics simulations.

The selective dispersion of neutral nanoplates (NNP) and the control of the interfacial structure of copolymers are challenging. In this work, we employ coarse-grained molecular dynamics (CGMD) to investigate the dispersion of NNP and the interfacial structure. The introduction of NNP significantly changes the interfacial structure and formation mechanism of diblock copolymers (DBCP), which is related to the matrix phase, distribution, composition, and length of two different chain segments (A and B) in AmBn-DBCP. The phase-weak groups that have a poor interaction with NNP will stack easily, whereas the stacking degree for the phase-rich groups that have a strong interaction with NNP decreases due to the addition of NNP. The interaction between two phases will be enhanced, which is favorable for the formation of a random network structure. Due to the strong interaction of the phase-rich groups with NNP, the NNP change the accumulation types of phase-weak groups and enhances the combination of two chain segments in favor of the formation of a cylindrical micelle-like structure. The transmission electron microscopy (TEM) images show that layered double hydroxide (LDH) orientationally distributes in the acrylic acid chain segments in ethylene acrylic acid (EAA) random copolymers, which is in agreement with the theoretical simulation results. This proves that the selective dispersion of LDH in copolymers affects their interfacial structure.

Hybrid membrane-coated nanosuspensions for multi-modal anti-glioma therapy via drug and antigen delivery.

BACKGROUND: Glioma is one of the deadliest human cancers. Although many therapeutic strategies for glioma have been explored, these strategies are seldom used in the clinic. The challenges facing the treatment of glioma not only involve the development of chemotherapeutic drugs and immunotherapeutic agents, but also the lack of a powerful platform that could deliver these two moieties to the targeted sites. Herein, we developed chemoimmunotherapy delivery vehicles based on C6 cell membranes and DC membranes to create hybrid membrane-coated DTX nanosuspensions (DNS-[C6&DC]m). RESULTS: Results demonstrated successful hybrid membrane fusion and nanosuspension functionalization, and DNS-[C6&DC]m could be used for different modes of anti-glioma therapy. For drug delivery, membrane coating could be applied to target the source cancer cells via a homotypic-targeting mechanism of the C6 cell membrane. For cancer immunotherapy, biomimetic nanosuspension enabled an immune response based on the professional antigen-presenting characteristic of the dendritic cell membrane (DCm), which carry the full array of cancer cell membrane antigens and facilitate the uptake of membrane-bound tumor antigens for efficient presentation and downstream immune n. CONCLUSION: DNS-[C6&DC]m is a multifunctional biomimetic nano-drug delivery system with the potential to treat gliomas through tumor-targeted drug delivery combined with immunotherapy, thereby presenting a promising approach that may be utilized for multiple modes of cancer therapy.

Chikungunya infection: First autochthonous cases in Taiwan.

The first autochthonous case and the first outbreak of chikungunya in Taiwan occurred during July-October 2019, with a total of 21 cases confirmed. Genetic analysis revealed the strains belonged to East/Central/South African genotype and had 99.95%-100% identity with the strains from the imported cases from Myanmar in 2019. This event confirmed that the imported chikungunya cases has the potential to cause autochthonous transmission in Taiwan; intensified surveillance and vector control measures are essential to contain the outbreak.

Cancer Cell Membrane-Coated Nanosuspensions for Enhanced Chemotherapeutic Treatment of Glioma.

Effective intracerebral delivery is key for glioma treatment. However, the drug delivery system within the brain is largely limited by its own adverse physical and chemical properties, low targeting efficiency, the blood-brain barrier and the blood-brain tumor barrier. Herein, we developed a simple, safe and efficient biomimetic nanosuspension. The C6 cell membrane (CCM) was utilized to camouflaged the 10-hydroxycamptothecin nanosuspension (HCPT-NS) in order to obtain HCPT-NS/CCM. Through the use of immune escape and homotypic binding of the cancer cell membrane, HCPT-NS/CCM was able to penetrate the blood-brain barrier and target tumors. The HCPT-NS is only comprised of drugs, as well as a small amount of stabilizers that are characterized by a simple preparation method and high drug loading. Similarly, the HCPT-NS/CCM is able to achieve targeted treatment of glioma without any ligand modification, which leads it to be stable and efficient. Cellular uptake and in vivo imaging experiments demonstrated that HCPT-NS/CCM is able to effectively cross the blood-brain barrier and was concentrated at the glioma site due to the natural homing pathway. Our results reveal that the glioma cancer cell membrane is able to promote drug transport into the brain and enter the tumor via a homologous targeting mechanism.

Early Introduction of Severe Acute Respiratory Syndrome Coronavirus 2 into Europe.

Early infections with severe acute respiratory syndrome coronavirus 2 in Europe were detected in travelers from Wuhan, China, in January 2020. In 1 tour group, 5 of 30 members were ill; 3 cases were laboratory confirmed. In addition, a healthcare worker was infected. This event documents early importation and subsequent spread of the virus in Europe.

Human Case of Severe Fever with Thrombocytopenia Syndrome Virus Infection, Taiwan, 2019.

We report on a 70-year-old man with fever, leukopenia, thrombocytopenia, vomiting, malaise, dyspnea, and consciousness disturbance who was infected with severe fever with thrombocytopenia syndrome virus in northern Taiwan, 2019. This autochthonous case was confirmed by reverse transcription PCR, virus isolation, and genomic sequencing.

Containing COVID-19 Among 627,386 Persons in Contact With the Diamond Princess Cruise Ship Passengers Who Disembarked in Taiwan: Big Data Analytics.

BACKGROUND: Low infection and case-fatality rates have been thus far observed in Taiwan. One of the reasons for this major success is better use of big data analytics in efficient contact tracing and management and surveillance of those who require quarantine and isolation. OBJECTIVE: We present here a unique application of big data analytics among Taiwanese people who had contact with more than 3000 passengers that disembarked at Keelung harbor in Taiwan for a 1-day tour on January 31, 2020, 5 days before the outbreak of coronavirus disease (COVID-19) on the Diamond Princess cruise ship on February 5, 2020, after an index case was identified on January 20, 2020. METHODS: The smart contact tracing-based mobile sensor data, cross-validated by other big sensor surveillance data, were analyzed by the mobile geopositioning method and rapid analysis to identify 627,386 potential contact-persons. Information on self-monitoring and self-quarantine was provided via SMS, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests were offered for symptomatic contacts. National Health Insurance claims big data were linked, to follow-up on the outcome related to COVID-19 among those who were hospitalized due to pneumonia and advised to undergo screening for SARS-CoV-2. RESULTS: As of February 29, a total of 67 contacts who were tested by reverse transcription-polymerase chain reaction were all negative and no confirmed COVID-19 cases were found. Less cases of respiratory syndrome and pneumonia were found after the follow-up of the contact population compared with the general population until March 10, 2020. CONCLUSIONS: Big data analytics with smart contact tracing, automated alert messaging for self-restriction, and follow-up of the outcome related to COVID-19 using health insurance data could curtail the resources required for conventional epidemiological contact tracing.

A Two-Step Ferric Chloride and Dilute Alkaline Pretreatment for Enhancing Enzymatic Hydrolysis and Fermentable Sugar Recovery from Miscanthus sinensis.

A two-step process was proposed to enhance enzymatic hydrolysis of Miscanthus sinensis based on a comparative study of acid/alkaline pretreatments. Ferric chloride pretreatment (FP) effectively removed hemicellulose and recovered soluble sugars, but the enzymatic hydrolysis was not efficient. Dilute alkaline pretreatment (ALP) resulted in much better delignification and stronger morphological changes of the sample, making it more accessible to enzymes. While ALP obtained the highest sugar yield during enzymatic hydrolysis, the soluble sugar recovery from the pretreatment stage was still limited. Furthermore, a two-step ferric chloride and dilute alkaline pretreatment (F-ALP) has been successfully developed by effectively recovering soluble sugars in the first FP step and further removing lignin of the FP sample in the second ALP step to improve its enzymatic hydrolysis. As a result, the two-step process yielded the highest total sugar recovery (418.8 mg/g raw stalk) through the whole process.

Recycling of Chemical Eluent and Soil Improvement After Leaching.

Ethylenediaminetetraacetic acid disodium salt (EDTA) was selected among various eluents due to its highest removal efficiency for lead (Pb) (43.7%) and zinc (Zn) (57.1%) leaching from Pb-Zn contaminated soil by soil column experiment. Compared with newly prepared EDTA eluent, using recycled EDTA eluent can still leaching down 71.1% of Pb and 63.2% of Zn respectively, which showed the reusable benefits of recycled EDTA eluent. After soils were leached by EDTA, soil quality decline, such as reducing of urease, catalase, invertase activities and microorganism numbers. However, adding 5% nutrition soil or earthworm fertilizer can significantly improve the quality of EDTA leached soil, and promote growth of peas and ryegrass compared with EDTA treatments. Overall, the improvement of EDTA leached soil by adding nutrition soil or earthworm fertilizer is important, and recycled EDTA eluent can recycle and re-use for Pb-Zn contaminated soil remediation.