Challenges and support needs in psychological and physical health among pilots: a qualitative study.

Introduction: Physical and mental health problems among pilots affect their working state and impact flight safety. Although pilots' physical and mental health problems have become increasingly prominent, their health has not been taken seriously. This study aimed to clarify challenges and support needs related to psychological and physical health among pilots to inform development of a more scientific and comprehensive physical and mental health system for civil aviation pilots. Methods: This qualitative study recruited pilots from nine civil aviation companies. Focus group interviews via an online conference platform were conducted in August 2022. Colaizzi analysis was used to derive themes from the data and explore pilots' experiences, challenges, and support needs. Results: The main sub-themes capturing pilots' psychological and physical health challenges were: (1) imbalance between family life and work; (2) pressure from assessment and physical examination eligibility requirements; (3) pressure from worries about being infected with COVID-19; (4) nutrition deficiency during working hours; (5) changes in eating habits because of the COVID-19 pandemic; (6) sleep deprivation; (7) occupational diseases; (8) lack of support from the company in coping with stress; (9) pilots' yearly examination standards; (10) support with sports equipment; (11) respecting planned rest time; and (12) isolation periods. Discussion: The interviewed pilots experienced major psychological pressure from various sources, and their physical health condition was concerning. We offer several suggestions that could be addressed to improve pilots' physical and mental health. However, more research is needed to compare standard health measures for pilots around the world in order to improve their physical and mental health and contribute to overall aviation safety.

Mechanical Properties of Nano-SiO2 Reinforced Geopolymer Concrete under the Coupling Effect of a Wet-Thermal and Chloride Salt Environment.

In this study, the mechanical behaviors of nano-SiO2 reinforced geopolymer concrete (NS-GPC) under the coupling effect of a wet-thermal and chloride salt environment were investigated through a series of basic experiments, and a simulation on the coupling effect of a wet-thermal and chloride salt environment and SEM test were also included. During the experiments for the coupling effect of the wet-thermal and chloride salt environment, an environment simulation test chamber was utilized to simulate the wet-thermal and chloride salt environment, in which the parameters of relative humidity, temperature, mass fraction of NaCl solution and action time were set as 100%, 45 °C, 5% and 60 d, respectively. The content of nano-SiO2 (NS) particles added in geopolymer concrete (GPC) were 0, 0.5%, 1.0%, 1.5% and 2.0%. The result indicated that the mechanical properties of NS reinforced GPC decreased under the coupling effect of the wet-thermal and chloride salt environment compared to the control group in the natural environment. When the NS content was 1.5%, the cube and splitting tensile strength, elastic modulus and impact toughness of GPC under the coupling environment of wet-thermal and chloride salt were decreased by 9.7%, 9.8%, 19.2% and 44.4%, respectively, relative to that of the GPC under the natural environment. The addition of NS improved the mechanical properties of GPC under the coupling effect of the wet-thermal and chloride salt environment. Compared to the control group without NS, the maximum increment in cube compressive strength, splitting tensile strength and elastic modulus of NS-GPC under the coupling effect of the wet-thermal and chloride salt environment due to the incorporation of NS reached 25.8%, 9.6% and 17.2%, respectively. Specifically, 1.5% content of NS increased the impact toughness, impact numbers of initial crack and the ultimate failure of GPC by 122.3%, 109% and 109.5%, respectively.

Research on fully parallel matrix algorithm of ternary optical computer for the shortest path problem.

The shortest path is an extensive algorithm problem in graph theory. When faced with a huge amount of data in the shortest path problem, the problem with using traditional algorithms is the slow operation speed and high power consumption. To address these problems, this paper proposes a fully parallel matrix (FPM) algorithm. It uses the matrix multiplication principle and one-step modified signed-digit (MSD) adder, which can effectively implement parallel computing in ternary optical computers (TOCs). Finally, we compare clock cycles, and the results show that the TOC-based FPM algorithm can efficiently reduce the calculation time when solving the shortest path problem.

Bioorthogonal SERS Nanotags as a Precision Theranostic Platform for in Vivo SERS Imaging and Cancer Photothermal Therapy.

Precise detection and effective treatment are crucial to prolong cancer patients' lives. Surface-enhanced Raman scattering (SERS) imaging coupled with photothermal therapy has been considered a precise and effective strategy for cancer theranostics. Nevertheless, Raman reporters employed in the literature usually possessed multiple shift peaks in the fingerprint region, which are overlapped with background signals from endogenous biological molecules. Herein, we fabricated a new kind of bioorthogonal Raman reporter and aptamer functionalized SERS nanotags. The SERS nanotags demonstrated a strong Raman signal at 2205 cm-1 in the biologically Raman-silent region and recognized MCF-7 breast cancer cells for Raman imaging with high specificity. Laser irradiation induced serious toxicity of MCF-7 cells due to the excellent photothermal capability of the SERS nanotags. After intravenous administration of the SERS nanotags, tumor Raman spectral detection and mapping in living mice were successfully achieved. Further in vivo antitumor experiments manifested that the aptamer-modified SERS nanotags significantly restrained tumor growth after laser irradiation with 99% inhibition rate and good biocompatibility. These results clearly revealed that the SERS nanotags could serve as a novel and precise theranostic platform for in vivo cancer diagnosis and photothermal therapy.

Design, synthesis and biological evaluation of substituted 2-(thiophen-2-yl)-1,3,5-triazine derivatives as potential dual PI3Kα/mTOR inhibitors.

The phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) have been regarded as promising targets for the treatment of cancer. Herein, we synthesized a new series of substituted 2-(thiophen-2-yl)-1,3,5-triazine derivatives as novel PI3Kα/mTOR dual inhibitors for cancer therapy. All compounds were evaluated for the IC50 values against three cancer cell lines (A549, MCF-7 and Hela). Most of the target compounds exhibited moderate to excellent anti-tumor activities against these three tested cancer cell lines especially against A549 and Hela cancer cell lines. Among them, the most promising compound 13g showed excellent anti-tumor potency for A549, MCF-7 and Hela cell lines with IC50 values of 0.20 ± 0.05 µM, 1.25 ± 0.11 µM and 1.03 ± 0.24 µM, respectively. Notably, according to the result of enzymatic activity assay, compound 13g was identified as a novel PI3Kα/mTOR dual inhibitor, which had an approximately 10-fold improvement in mTOR inhibition, compared to the class I PI3K inhibitor 1 (pictilisib, GDC-0941), with IC50 values of 525 nM to 48 nM. And western blot analysis indicated compound 13g could efficiently suppress the phosphorylation of AKT at the dose of 0.1 µM, which further demonstrated compound 13g had significant inhibitory effect on the PI3K/Akt/mTOR pathway. Furthermore, compound 13g could stimulate A549 cells arrest at G0/G1 phase in a dose-dependent manner, and induced apoptosis at a low concentration.

Research progress and clinical application of predictive biomarker for immune checkpoint inhibitors.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have emerged as epochal milestones in the field of anti-cancer immunotherapy. With promising clinical effectiveness, ICIs can significantly prolong the overall survival of patients with advanced cancer of different types. Although their remarkable effectiveness has been demonstrated in clinical application, ICIs display limitations in terms of unique response patterns. Only a subset of patients exhibits objective responses, while others show rapid disease progression. Considering that there is a fair representation of both subsets of patients (responders and non-responders), clinicians ought to effectively stratify patients who will potentially benefit from ICI therapy, and optimize a strategy for patient selection. Areas covered: In this review, the authors have summarized several key factors involved in the biomarker development of ICI therapy, such as neoantigen production and presentation, the tumor microenvironment, and alternation in specific gene signaling pathways. Expert opinion: Considering the extreme complexity of the immune system, a single biomarker may fail to appropriately stratify patients for ICI therapy. Therefore, future biomarker research should focus on designing an integrated biomarker system that will successfully guide combination therapies to overcome resistance to immunotherapy.

Multicolor Raman Beads for Multiplexed Tumor Cell and Tissue Imaging and in Vivo Tumor Spectral Detection.

Developing new nanomaterials with strong and distinctive Raman vibrations in the biological Raman-silent region (1800-2800 cm-1) were highly desirable for Raman hyperspectral detection and imaging in living cells and animals. Herein, polymeric nanoparticles with monomers containing alkyne, cyanide, azide, and carbon-deuterate were prepared as Raman-active nanomaterials (Raman beads) for bioimaging applications. Intense Raman signals were obtained due to the high density of alkyne, cyanide, azide, and carbon-deuterate in single nanoparticles, in absence of metal (such as Au or Ag) as Raman enhancers. We have developed a library of Raman beads for frequency multiplexing through the end-capping substitutions of monomers and demonstrated five-color SRS imaging of mixed nanoparticles with distinct Raman frequencies. In addition, with further surface functionalization of targeting moieties (such as nucleic acid aptamers and targeting peptides), targetable Raman beads were successfully used as probes for tumor targeting and Raman spectroscopic detection, including multicolor SRS imaging in living tumor cells and tissues with high specificity. Further in vivo studies indicated that Raman beads anchored with targeting moieties were successfully employed to target tumors in living mice after tail intravenous injection, and Raman spectral detection of tumor in live mice was achieved only through spontaneous Raman signal at the biological Raman-silent region without any signal enhancement due to a high density of Raman reporters in Raman beads. With further copolymerization of these monomers, Raman beads with supermultiplex barcoding could be readily achieved.

Simultaneous adsorption and oxidative degradation of Bisphenol A by zero-valent iron/iron carbide nanoparticles encapsulated in N-doped carbon matrix.

The increased release and accumulation of Bisphenol A (BPA) in contaminated wastewater has resulted in the world wide concerns because of its potential negative effects on human health and aquatic ecosystems. Starting with metal-organic frameworks, we present a simple method to synthesize magnetic porous microcubes (N-doped Fe0/Fe3C@C) with graphitized shell and highly dispersed active kernel via the pyrolysis process under N2 atmosphere. Batch adsorption experimental results showed that N-doped Fe0/Fe3C@C had high adsorption capacity for BPA (∼138 mg g-1 at pH = 7 and 298 K). Degradation of BPA adsorbed on N-doped Fe0/Fe3C@C was further investigated as a function of BPA concentration, persulfate amount, temperature and solution pH. It was found that potassium peroxodisulfate could be activated by N-doped Fe0/Fe3C@C, and a large number of free radicals were generated which was crucial for the degradation of BPA. The concentration of BPA was barely changed in the individual persulfate system. BPA (10 mg L-1) was almost completely degraded within 60 min in the presence of N-doped Fe0/Fe3C@C (∼0.2 g L-1). When the BPA content increased to 25 mg L-1, the removal efficiency of BPA achieved to 98.4% after 150 min. From the XRD, Raman, and XPS analysis, the main adsorption mechanism of BPA was π-π interactions between the π orbital on the carbon basal planes and the electronic density in the BPA aromatic rings. While the superior degradation was attributed to the radical generation and evolution in phenol oxidation. This work not only proved the potential application of N-doped Fe0/Fe3C@C in the adsorption and degradation of BPA, but also opened the new possibilities to eliminate organic pollutants using this kind of magnetic materials in organic pollutants' cleanup.

Selective tracking of ovarian-cancer-specific γ-glutamyltranspeptidase using a ratiometric two-photon fluorescent probe.

Real-time tracking of GGT enzymatic activity in human ovarian cancer cells is a reliable method for accurate prediction of cancer diagnosis and management. Here, we report the two-photon ratiometric tracking of GGT activity in cancer cells based on a probe with switchable Förster resonance energy transfer properties. In the absence of GGT, the designed probe showed two well-resolved emission bands at 461 and 610 nm, corresponding to the 7-hydroxycoumarin donor and BODIPY acceptor, respectively. In contrast, GGT catalyzed cascade reactions including cleavage of the γ-glutamyl group and subsequent aromatic hydrocarbon transfer from the S to N atom increased the distance between the two chromophores, thus decreasing the FRET efficiency, with the recovery of the donor fluorescence at 461 nm. By exploiting this enzyme-triggered ratiometric measurement, successful differentiation of ovarian cancer cells from normal cells with this probe was realized by two-photon fluorescence confocal microscopy.

A Photochemical Avenue to Photoluminescent N-Dots and their Upconversion Cell Imaging.

A photochemical avenue to synthesize nitrogen-rich quantum dots (N-dots) using 2-azido imidazole as the starting material was established for the first time. A production yield of up to 92.7% was obtained. The N-dots were then fully characterized by elemental analysis, IR, XPS, XRD, AFM and TEM. On the basis of the N2 production and in situ IR results, the underlying mechanism for the photochemical formation of N-dots was proposed. These N-dots showed promising optical properties including wavelength-dependent upconversion photoluminescence, and were successfully used in upconversion cell imaging.

Bioorthogonal SERS Nanoprobes for Mulitplex Spectroscopic Detection, Tumor Cell Targeting, and Tissue Imaging.

A surface-enhanced Raman scattering (SERS) technique shows extraordinary features for a range of biological and biomedical applications. Herein, a series of novel bioorthogonal SERS nanoprobes were constructed with Gold nanoflower (AuNF) and Raman reporters, the signals of which were located in a Raman-silent region of biological samples. AS1411 aptamer was also co-conjugated with AuNF through a self-assembled monolayer coverage strategy. Multiplex SERS imaging using these nanoprobes with three different bioorthogonal small-molecule Raman reporters is successfully achieved with high multiplexing capacity in a biologically Raman-silent region. These Raman nanoprobes co-conjugated with AS1411 showed high affinity for tumor cells with overexpressed nucleolin and can be used for selective tumor cell screening and tissue imaging.

Heavy atom quenched coumarin probes for sensitive and selective detection of biothiols in living cells.

A series of turn-on fluorescent probes with halogen acetyl amide at the 3-position of coumarin derivatives were synthesized. Fluorescence of these probes was efficiently quenched by heavy halogen atoms (Br and I, not Cl), which could be successfully used for selective detection of biothiols with the sensitivity of Cys > GSH > Hcy and much higher than thiol containing proteins. These represent the smallest fluorescence quenchers in designing fluorescent probes for detecting both endogenous and exogenous biothiols in living cells.

[The Research Advances of the Pathomechanism of Phantom Limb Pain (PLP)].

Phantom limb pain (PLP) is a hallucination that the patient feels the existence off the limb after its loss and experiences somewhat pain of the missing limb. Such a pain normally appears in the distal end of the missing limb. Currently, the pathomechanism of PLP is still unclear, and the clinical research of PLP mainly relies on the subjective report of the patients and the psychophysical measurements. In this paper, we discuss extensively the pathomechanism of PLP, and summarize comprehensively the advanced methods for studying the pathomechanism of PLP. In short, the paper could deepen our understanding of the pathomechanism of PLP, and could serve as an effective instruction basis for researchers and doctors to diagnose and treat the PLP.

Synthesis and unique photoluminescence properties of nitrogen-rich quantum dots and their applications.

Nitrogen-rich quantum dots (N-dots) were serendipitously synthesized in methanol or aqueous solution at a reaction temperature as low as 50 °C. These N-dots have a small size (less than 10 nm) and contain a high percentage of the element nitrogen, and are thus a new member of quantum-dot family. These N-dots show unique and distinct photoluminescence properties with an increasing percentage of nitrogen compared to the neighboring carbon dots. The photoluminescence behavior was adjusted from blue to green simply through variation of the reaction temperature. Furthermore, the detailed mechanism of N-dot formation was also proposed with the trapped intermediate. These N-dots have also shown promising applications as fluorescent ink and biocompatible staining in C. elegans.

Chemoselective reduction and self-immolation based FRET probes for detecting hydrogen sulfide in solution and in cells.

Hydrogen sulfide (H2S) has been regarded as the third gaseous transmitter. Based on the mechanism of chemoselective azido reduction and self-immolation, five fluorescence resonance energy transfer (FRET) probes for the detection of H2S were designed and synthesized. The effect of functional substitution of the self-immolative moiety on azido reduction and quinone-methide rearrangement were investigated. Their fluorescence responses and chemoselectivity for H2S detection were evaluated in solutions and in cells. This strategy may provide a general route for designing H2S probes with many commercially available FRET pairs.

[Study on the complete sequence of CA24 variant isolated during the acute hemorrhagic conjunctivitis outbreaks in Zhejiang province during 2002 to 2010].

OBJECTIVE: To analyze the genetic characteristics of the complete sequence of coxsackievirus A24 variant (CA24v) isolated from acute hemorrhagic conjunctivitis (AHC) outbreaks in Zhejiang province during 2002 to 2010. METHODS: Complete sequences of CA24v epidemic strains isolated in different years were amplified under the RT-PCR assay, while the sequences of whole genome, VP1, and 3C region of Zhejiang strains were compared with epidemic strains isolated in other areas of China and abroad. RESULTS: The whole genome of Zhejiang CA24v strains isolated in 2002 and 2010 was 7456 - 7458 bp in length, encoding a polyglutamine protein which containing 2214 amino acid residues. There was a insertion with T on site 97 and 119 within 5'non-coding region between epidemic strain Zhejiang/08/10 and strains isolated in 2002. The rates of amino acid homology among Zhejiang/08/10 and other strains isolated since 2002 were between 94.7% and 100.0%. Compared with the representative strains circulated within the recent 60 years, the largest average amino acid variations had been occurred on region 2A and 3A, with the ratios as 8.4% and 7.3% respectively. The smallest variation happened in region 3D, with the ratio only as 1.9%. The rates of stable amino acid variation on the whole genome between strains isolated since 1987 and 2002 were 38 and 20. P-distance within groups appeared that region 3C was more stable than VP1 of strains isolated in 2002 - 2010, and the 3D of early strain Jamaica/10628/87 might have had a nature of recombination but not observed on those epidemic strains in recent years. CONCLUSION: Within the evolution of CA24v strains, the time course was more significant than the geographical differences. There had been sporadic epidemics of AHC caused by CA24v in Zhejiang province since 2002.

[Molecular evolution of two lineages related to influenza B virus based on HA1 gene].

OBJECTIVE: To study the evolutionary characteristics and rules of two lineages on influenza B virus. METHODS: A total of 126 HA1 sequences of strains isolated during 1940 to 2012 were downloaded from the GenBank. Time of the most recent common ancestor (TMRCA) and divergence of the two lineages were calculated based on the data from phylogenetic analysis of HA1 gene, using Bayesian Markov Chain Monte Carlo (Bayesian-MCMC) and molecular clock method. RESULTS: The average amino acid variant ratios were ranged from 5.4% to 10.2% within the strains of influenza B virus isolated during 1978 to 2010. Compared with the Victoria-like strains, all Yamagata-like strains showed an amino acid deletion at 163(th) site, while some of them showing a deletion at position 166. HA1 gene of influenza B virus seemed not have been affected by positive selection except a few sites. The evolutionary average rate on HA1 gene was 2.138×10(-3) substitutions/site/year (95% HPD: 1.833×10(-3) - 2.437×10(-3) substitutions/site/year). The estimated dates for TMRCA of the two lineages of influenza B virus could be dated back to 1971 (95% HPD: 1969 - 1972), while the divergence times of the two lineages were 1973 (95% HPD: 1971 - 1974) and 1977 (95% HPD: 1975 - 1978) respectively. CONCLUSION: Significant differences were found on HA1 gene between earlier and recent identified strains of Victoria and Yamagata lineage. Differences between the two lineages increased and showing the potential of dividing themselves into different subtypes in the future. More attention should be paid to these trends and the related epidemiological significance.

[Study on the genome sequence of measles viruses circulated in Zhejiang province during 1999 to 2011].

OBJECTIVE: To study the genetic variations between measles vaccine strain S191 and strains that circulated in Zhejiang province causing the epidemics during 1999 to 2011. METHODS: Complete sequence of the nine Zhejiang measles strains were amplified by RT-PCR assay. Products were sequenced and the obtained sequences were aligned and analyzed with vaccine strains S191 and the major epidemic strains isolated in foreign countries. RESULTS: The homology of amino acid among the nine Zhejiang strains were 98.77% - 99.89%. The strains were not affected by positive selection and the variations on each gene were still in random drift. Compared to vaccine strain S191, there were 135 to 159 amino acid changes in Zhejiang measles virus, in which 113 points were common variable positions, resulting in mutations on five glycosylation sites. At the nucleotide level, the biggest differences between the Zhejiang strains and the vaccine strain S191 were found on N gene, with the average divergent ratio as 5.5%, while the biggest one was P protein, in the amino acid level, with the average mutation rate as 7.7%. In addition, with the complete genome sequences, the genetic distance between Zhejiang epidemic strains and vaccine strains was greater than the distances between epidemic strains of genotype D(4), B(3) and vaccine strains (t = -9.76, P < 0.05; t = -12.39, P < 0.05). CONCLUSION: There were significant differences found in the each of the genes between Zhejiang epidemic strains and the vaccine strain S191. The differences between the current vaccine strains and H genotype epidemic strains were much larger than the differences between the vaccine and the foreign epidemic strains (genotype D(4), B(3)). Therefore, we should pay close attention to this trend, and to develop candidates for the development of vaccines, as early as possible.