Construction of Multi-Mode Photoelectrochemical Immunoassays for Accurate Detection of Cancer Markers: Assisted with MOF-Confined Plasmonic Nanozyme.

In clinical diagnostics, sensitive and accurate biomarker monitoring is greatly challenged by the limitations of false positive/negative errors in single-modal photoelectrochemical analysis. Herein, we propose a multimode immunoassay by integrating photoelectrochemical, colorimetric, and photothermal imaging analysis into one electrode. The immunosensors could simultaneously achieve three detection modes at one electrode, which provided a new pathway for the accurate detection of the target prostate-specific antigen (PSA) and circumvented false-positive or negative errors during the detection process. To this end, an integrated multifunctional chip (TiO2/ZIF-8/Cu(II)) was first constructed via in situ embedding of Cu(II) in the Metal-organic framework growth process. Then, an alkaline phosphatase-labeled magnetic probe was designed to achieve split-type detection for PSA. In a sodium thiophosphate solution, the in situ generated H2S could react with Cu(II) to form small-size CuS due to the nanoconfinement of ZIF-8 and thus result in the formation of p-n heterojunctions (TiO2/ZIF-8/CuS). The TiO2/ZIF-8/CuS could efficiently improve the light-harvesting ability and facilitate the charge separation efficiency, thus finally resulting in an increased photocurrent in the PEC mode. Furthermore, by constructing the portable colorimetric and photothermal sensors based on the Arduino microcontroller and photothermal imager, the TiO2/ZIF-8/CuS also provided point-of-care and visual detection modes, as the in situ-formed CuS exhibited peroxidase-mimicking activity and outstanding photothermal properties. The work had important prospects for establishing multimode immunoassays for the accurate detection of cancer markers in early disease diagnosis.

Construction of smartphone-adapted signal visualization platform for dual-mode detection of H2S based on integrated metal-organic framework nanoprobes.

Hydrogen sulfide (H2S) is a toxic contaminant and has great influence on many physiological processes. Due to various pathophysiological roles and environmental pollution problems, it is necessary to construct and develop simple and portable monitoring sensors for the precise detection of H2S. Herein, we developed a smartphone-adapted dual-mode detection platform by integrating the colorimetric and photothermal imaging analysis into a metal-organic framework-based chip (ZIF-8/Cu). Due to the nanoconfinement effect of ZIF-8, small-sized plasmonic CuS could be in-situ formed during the detection procedure of H2S and endowed the chips with excellent photothermal properties. By constructing a smartphone-adapted photothermal imager, the metal-organic framework-based chip could achieve a portable photothermal imaging analysis of H2S. Moreover, as the formed CuS was a good peroxidase-like nanozyme, the chips could also be used to trigger the enzymic catalytic reaction toward the chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB)-H2O2, thus providing another colorimetric sensing mode by using a smartphone App. In this smartphone-adapted visualization platform, the portable chemosensors could simultaneously achieve double detection modes at one electrode, which provided a new pathway for the accurate detection of H2S and circumvented the false-positive or negative errors during the detection process. Besides, by using the finite difference time domain (FDTD) simulation method, the in-depth mechanism, including the plasmonic effect and spatial electromagnetic field distribution, was explored to provide a possible reason for the excellent sensing performance of the dual-mode visualization platform. This work provides a new insight into the construction of the accurate, portable and smart sensing platform in the visual screening of H2S.

Fabrication and nano-engineering of non-/noble metal-coupled plasmonic heterostructures for ultrasensitive photoelectrochemical immunoassays.

To achieve reliable and ultrasensitive detection for disease markers in PEC bioanalysis, constructing and nano-engineering of ideal photoelectrodes and signal transduction strategies are of vital importance. Herein, a non-/noble metal coupled plasmonic nanostructure (TiO2/r-STO/Au) was tactically designed with high-efficient PEC performance. Evidenced by the DFT and FDTD calculations, the reduced SrTiO3 (r-STO) was found to support the localized surface plasmon resonance due to the sufficiently increased and delocalized local charge in r-STO. Under the synergistic coupling of plasmonic r-STO and AuNPs, the PEC performance of TiO2/r-STO/Au was found remarkably promoted with reduced onset potential. This merit supported TiO2/r-STO/Au as a self-powered immunoassay via a proposed oxygen-evolution-reaction mediated signal transduction strategy. With the increase of the target biomolecules (PSA), the catalytic active sites of TiO2/r-STO/Au would be blocked and result in the decrease of the oxygen evaluation reaction. Under optimal conditions, the immunoassays exhibited an excellent detection performance with a LOD as low as 1.1 fg/mL. This work proposed a new type of plasmonic nanomaterial for ultrasensitive PEC bioanalysis.

Ion-Exchange Reaction-Mediated Hierarchical Dual Z-Scheme Heterojunction for Split-Type Photoelectrochemical Immunoassays.

Photoelectrochemical (PEC) immunoassays with ultrasensitive detection abilities are highly desirable for in vitro PEC diagnosis and biological detection. In this paper, dual Z-scheme PEC immunoassays with hierarchical nanostructures (TiO2@NH2-MIL-125@CdS) are synthesized through epitaxial growth of MOF-on-MOF and further in situ derivatization. The dual Z-scheme configuration not only extends the light absorption range but also increases the redox ability due to the interface structure nanoengineering, which synergistically suppresses bulk carrier recombination and promotes the charge transfer efficiency at the electron level. Furthermore, a smart MOF-derived labeling probe (CuO@ZnO nanocube) is designed to develop a split-type PEC biosensor by using prostate-specific antigen (PSA) as a target biomarker. In the presence of PSA, the Ab2-labeled CuO@ZnO would specifically bond to the dual Z-scheme electrode. Then, the MOF-derived CuO@ZnO is dissolved by hydrochloric acid to release Cu2+, which could replace Cd2+ via an ion-exchange reaction, thus leading to the decrease of the photocurrent due to the destruction of the dual Z-scheme configuration. In typical applications, the split-type PEC immunoassay exhibits an excellent detection performance for PSA with a LOD as low as 0.025 pg·mL-1.

Effect of electrohydrodynamic printing scaffold with different spacing on chondrocyte dedifferentiation.

Background: Osteoarthritis (OA) is a common degenerative disease. Chondrocyte dedifferentiation can accelerate the progress of OA. Three-dimensional printing (3DP) is widely used in tissue regeneration applications. A three-dimensional (3D) culture system with 3D printed scaffolds could reduce the dedifferentiation of chondrocytes during passages, which would be a potential method for chondrocyte expansion. Methods: The viability and proliferation of chondrocytes on scaffolds and effects of scaffolds with 100, 150, 200, 250 or 300 µm spacing on chondrocyte dedifferentiation were analyzed in vitro. The morphology of scaffolds and cell/scaffold constructs was observed by scanning electron microscopy (SEM). Glycosaminoglycan (GAG) was evaluated by Alcian blue staining. The effects of different spacing on chondrocyte dedifferentiation were evaluated by the messenger RNA (mRNA) and protein levels of cartilage-related genes. Results: With more binding sites, the proliferation and viability of chondrocytes on scaffolds with 100 and 150 µm spacing were better than those with 200, 250 and 300 µm spacing on day 1, but this advantage diminished over time. The histology and quantitative real-time polymerase chain reaction (qRT-PCR) results showed that 200 µm spacing inhibits chondrocyte dedifferentiation better. Conclusions: 3D printed scaffolds with 200 µm spacing can inhibit chondrocyte dedifferentiation, providing a basis for the future study of 3D printed scaffolds as an effective method for chondrocyte expansion.

How epidemic information and policy information impact anti-infection behaviors: a cross-cultural study under social influence framing.

Three preregistered experiments examined to what extent information about an epidemic situation provided by experts and information about anti-infection policies promoted by governments/media influenced anti-infection behaviors. The above effects were examined among populations from different countries (in Experiments 2 and 3) and across self-construals (in Experiment 3). In three experiments, participants (N =706) were presented with a scenario where experts provided (or did not provide) information about an epidemic situation and governments/media promoted (or did not promote) information about anti-infection policies. After that, participants indicated their willingness to adopt anti-infection behaviors. Results across three experiments showed that both types of information independently increased participants' anti-infection behaviors. In Experiments 2 and 3, we further found that the epidemic information had a larger impact on inducing anti-infection behaviors than the policy information, which was robust and consistent across countries and self-construals. Findings were discussed under the framework of social influence and in terms of practical implications for pandemic situations like the COVID-19.

Rhabdomyolysis in a Civil Aviation Pilot.

BACKGROUND: Rhabdomyolysis is a potentially fatal disease caused by trauma, infections, and toxins. Rhabdomyolysis has not been reported in Chinese civil aircrew, but in our case report a male civil copilot contracted rhabdomyolysis after excessive exercise, showing potential for morbidity in pilots.CASE REPORT: After excessive exercise, a 29-yr-old male civil aviation copilot complained of serious myalgia and weakness in lower limb muscles and gross hematuria, whose values of alanine transaminase (ALT), aspartate transaminase (AST), myohemoglobin (Mb), creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), and -hydroxybutyrate dehydrogenase (-HBDH) were conspicuously increased. Magnetic resonance imaging showed abnormal signal intensities in the lower limbs. The patient was diagnosed with rhabdomyolysis. He was treated with hydration and urine alkalinization. When his condition was stabilized, the patient was discharged. After remaining asymptomatic for 3 mo and getting documentation of normalized lab results, he was granted a first-class medical certificate and returned to work.DISCUSSION: This was the first case of rhabdomyolysis reported in Chinese civil aircrew. Excessive exercise in an overweight pilot may induce rhabdomyolysis. This condition can be controlled and cured by early and effective treatment. Rhabdomyolysis could occur in a population suffering from overweight, obesity, or hyperlipidemia. This case fits in with several other cases of military pilots exercising excessively. The progression could lead to acute kidney injury without prompt and effective intervention. And common symptoms like muscular weakness or myalgia may induce sudden in-flight incapacitation, so early medical intervention should be adopted. Moreover, recurrence of rhabdomyolysis should be considered when resuming flying duties.Liu X, Meng X, Zhang C, Chen J, Li P, Wu X, Fan H. Rhabdomyolysis in a civil aviation pilot. Aerosp Med Hum Res. 2020; 91(11):901903.

The effect of micro-nutrients on malnutrition, immunity and therapeutic effect in patients with pulmonary tuberculosis: A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: Micro-nutrients are closely related to pulmonary tuberculosis (PTB). Most patients with PTB suffer from micro-nutrients deficiency. We aimed to evaluate the efficacy of micro-nutrients support on clinical therapy and chronic inflammation in patients with PTB. METHODS: We searched Pubmed, Springer link, Web of Science, Cochrane, Wan Fang and CNKI databases for randomised controlled trials (RCTs). The patients with anti-TB treatments were divided into two groups, the control group with nutritional advice or placebo, and the experimental group with micro-nutrients support for more than 2 weeks. Two reviewers conducted data extraction and quality assessment of the studies independently, and ReviewManager 5.2 software was used to input and analyse the data. The dichotomous variable was expressed in the risk ratios (RRS) and 95% CI, the continuous data were expressed in the mean difference (MD) and 95% CI, and the heterogeneity of subgroup was evaluated by I (Kerantzas and Jacobs, Jr., 2017) [2] test. RESULTS: A total of 13 trials (2847 participants) were included. First, micro-nutrients improved sputum smears or culture negative conversion rates (OR 0.16 0.03-0.77, 2.29; MD -2.36, -4.72~-0.01, z = 1.97). Meanwhile, micro-nutrients support increased lymphocytes and decreased leukocytes, neutrophils, CRP and ESR (MD 0.20, 0.06-0.35, z = 2.78; MD -0.42, -0.65~-0.18, z = 3.48; MD -0.66, -1.12~-0.20, z = 2.82). However it had not impact on body weight, MUAC, haemoglobin, albumin or monocytes (p > 0.05). CONCLUSION: Micro-nutrients support can reduce chronic inflammation and improve sputum smears or culture conversions to contribute to anti-TB treatment.

Hyperbaric oxygen treatment mitigates liver damage in mice with noise exposure.

Noise exposure relates to various pathological disorders including liver damage, preventive measures of which are being demanded. Hyperbaric oxygen treatment (HBOT), as a non-invasive procedure, exerts convincing therapeutic potency on multiple liver diseases. The efficacy of HBOT in mitigating noise induced liver damage (NILD) and associated mechanisms would be elucidated here. Mice were subject to broad band noise (20-20k Hz, 90-110 dB) for 5 days by 3 hours/day. HBOT with 2.5 atmosphere absolute (ata) was employed before noise exposure. Morphology of liver tissue was examined by hematoxylin-eosin (HE) staining. Oil Red O (ORO), transferase-mediated dUTP nick end labelling (TUNEL) test and western blot were utilized to detect lipid accumulation, apoptotic cells and protein expression, respectively. Ceramide (Cer) level was assayed by immunohistochemistry (IHC) analysis. With noise exposure, conspicuous structural derangement and lipid deposition occurred in liver tissue of mice, which was alleviated significantly by the application of HBOT. Meanwhile, HBOT reduced the proportion of apoptotic hepatocytes, restraining the superoxide production in noise exposed mice. In view of underlying mechanisms, noise enhanced the acid sphingomyelinase (ASM) protein expression and the Cer generation in liver tissue of mice which was reversed substantially by HBOT. Altogether, HBOT ameliorates the structural and functional derangement of liver by neutralizing the ASM/Cer pathway in noise exposed mice.

Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway.

BACKGROUND: The study examines the expression and function of hypoxia-inducible gene 2 (HIG2) in hepatocellular carcinoma (HCC) tissues and cells. METHODS: Forty patients with HCC were included in the study. Bioinformatic analysis was used to analyze the clinical relevance of HIG2 expression in HCC tissue samples. Immunohistochemistry was employed to determine the expression of target proteins in tumor tissues. Hepatic HepG2 and SMMC-7721 cells were transfected with HIG2-targeting siRNA with Lipofectamine 2000. qRT-PCR was carried out to determine gene expression levels, while Western blotting was used to determine protein expression. A CCK-8 assay was performed to detect proliferation of cells, while migration and invasion of cells were studied by Transwell assay. Flow cytometry was carried out to detect surface markers and effector molecules in Nature killercells, as well as the killing effect of NK cells. RESULTS: HIG2 expression was upregulated in HCC. Silencing of HIG2 suppressed HCC cell migration and invasion. The killing effect of NK cells on HCC cells was enhanced after HIG2 was silenced in HCC cells. Conditioned media from HIG2-silenced SMMC-7721 cells inhibited the phenotype and function of NK cells. HCC cells with silenced expression of HIG2 modulated the activity of NK cells via STAT3. HIG2 promoted the evasion of HCC cells from killing by NK cells through upregulation of IL-10 expression. CONCLUSION: The study demonstrates that HIG2 activates the STAT3 signaling pathway in NK cells by promoting IL-10 release by HCC cells, thereby inhibiting the killing activity of NK cells, and subsequently promoting the recurrence and metastasis of HCC.

Acid sphingomyelinase mediates the noise-induced liver disorder in mice.

Noise-induced structural and functional disorder of the liver has been realized, but the underlying mechanism remains to be characterized, which has limited the introduction of precautious measures. Over-activation of acid sphingomyelinase (ASM)/ceramide (Cer) pathway takes centre stage in hepatocyte injury entailed by various stimulus. We aimed to investigate whether it mediated the noise elicited liver disorder on infrastructure, lipid metabolism, apoptosis, and oxidative stress. Mice were exposed to broad band noise (20-20k Hz, 90-110 dB) for 1, 3, 5 or 7 days by 3 hr/d. Doxepin hydrochloride (DOX), an ASM inhibitor was given by 5 mg/kg/d gavage. We showed that 5 or 7 days intense, broad band noise exposure caused significant infrastructure derangement and lipid droplets storage in hepatocytes. The content of cholesterol, free fatty acids or triglyceride was increased significantly in liver tissue upon noise stimulation. Moreover, the noise promoted apoptosis and superoxide generation in hepatocytes significantly, enhancing activity of aspartate aminotransferase (AST) or alanine amino transferase (ALT) in serum. Acid sphingomyelinase activity and Cer generation in liver tissue were elevated by noise exposure, which was normalized with DOX administrated. Accordingly, DOX alleviated steatosis, apoptosis, oxidative stress and enzymatic change in hepatocytes or serum of noise exposed mice substantially. In summary, our results suggest the ASM/Cer pathway contributes to the broad band noise elicited liver damage in mice.

Correlates of HBV infection among high school students in Guangxi / 中国学校卫生

Objective@#To understand hepatitis B virus(HBV) infection in high school students in Guangxi, and to provide scientific foundation for hepatitis B prevention and control strategies.@*Methods@#A selfdesigned epidemiological questionnaire was used among 2 632 participants. Information regarding general demographic characteristics, lifestyle habits, HBV infection history, knowledge of viral hepatitis prevention and control, as well as hepatitis B vaccination. Univariate and multivariate logistics regression analysis was used to analyze associated factors for hepatitis B infection.@*Results@#A total of 192 out of 2 632 participants were found HBsAg positive and 2 440 were HBsAg negative. Multivariate analysis showed that family liver disease history and hairdressing injury positively associated with hepatitis B virus infection risk (OR=3.62, 95% CI=2.28-5.73;OR=3.06, 95%CI=1.94-4.83), and hepatitis B vaccination was negatively associated with hepatitis B virus infection risk (OR=0.08, 95%CI=0.05-0.11).@*Conclusion@#Family history of liver disease, hairdressing injury experiences, as well as low rate of hepatitis B vaccination may associate with relatively high prevalence of hepatitis B virus infection among high school students in Guangxi.

Diagnostic and prognostic values of the mRNA expression of excision repair cross-complementation enzymes in hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: The current study aims at using the whole genome expression profile chips for systematically investigating the diagnostic and prognostic values of excision repair cross-complementation (ERCC) genes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Whole genome expression profile chips were obtained from the GSE14520. The receiver-operating characteristic (ROC) curve, survival analysis, and nomogram were used to investigate the diagnostic and prognostic values of ERCC genes. Investigation of the potential function of ERCC8 was carried out by gene set enrichment analysis (GSEA) and genome-wide coexpression analysis. RESULTS: ROC analysis suggests that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated and may have potential to distinguish between HBV-related HCC tumor and paracancerous tissues (area under the curve of ROC ranged from 0.623 to 0.744). Survival analysis demonstrated that high ERCC8 expression was associated with a significantly decreased risk of recurrence (adjusted P=0.021; HR=0.643; 95% CI=0.442-0.937) and death (adjusted P=0.049; HR=0.631; 95% CI=0.399-0.998) in HBV-related HCC. Then, we also developed two nomograms for the HBV-related HCC individualized prognosis predictions. GSEA suggests that the high expression of ERCC8 may have involvement in the energy metabolism biological processes. As the genome-wide coexpression analysis and functional assessment of ERCC8 suggest, those coexpressed genes were significantly enriched in multiple biological processes of DNA damage and repair. CONCLUSION: The present study indicates that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated between HBV-related HCC tumor and paracancerous tissues and that the mRNA expression of ERCC8 may serve as a potential biomarker for the HBV-related HCC prognosis.

Doxepin Mitigates Noise-induced Neuronal Damage in Primary Auditory Cortex of Mice via Suppression of Acid Sphingomyelinase/Ceramide Pathway.

Neuronal damage in primary auditory cortex (A1) underlies complex manifestations of noise exposure, prevention of which is critical for health maintenance. Acid sphingomyelinase (ASM) catalyzes generation of ceramide (Cer) which if over-activated mediates neuronal disorders in various diseases. Tricyclic antidepressants (TCAs), by restraining ASM/Cer, benefits multiple neuronal anomalies, so we aimed to elucidate the effect of TCA on noise induced hearing loss and auditory cortex derangement, unraveling mechanism involved. The mice were exposed to noise with frequencies of 20-20 KHz and intensity of 95 dB. Doxepin hydrochloride (DOX), a kind of TCAs, was given intragastrically by 5 mg kg-1  days-1 . Morphology of neurons was examined using hematoxylin-eosin (HE) and Nissl staining. Apoptosis was assayed through transferase-mediated dUTP nick end labeling (TUNEL). The content of ASM, Cer or acid ceramidase (AC) was detected by western blot and immunohistochemistry analysis. We demonstrated intense, broad band noise caused upward shift of auditory brainstem response (ABR) threshold to sound over frequencies 4-32 KHz, with prominent morphologic changes and enhanced apoptosis in neurons of primary auditory cortex (A1) (P < 0.05). DOX partly restored noise-caused hearing loss alleviating morphologic changes or apoptosis remarkably (P < 0.05). Both ASM and Cer abundance were elevated significantly by noise which was reversed upon DOX treatment (P < 0.05), but neither noise nor DOX altered AC content. DOX had no influence on hearing, neuronal morphology or ASM/Cer in control mice. Our result suggests DOX palliates noise induced hearing loss and neuronal damage in auditory cortex by correcting over-activation of ASM/Cer without hampering intrinsic behavior of it. Anat Rec, 300:2220-2232, 2017. © 2017 Wiley Periodicals, Inc.

Acid sphingomyelinase/ceramide regulates carotid intima-media thickness in simulated weightless rats.

Structural adaptation of arteries to weightlessness might lower the working ability or even threaten the physical health of astronauts, but the underlying mechanism is unclear. Acid sphingomyelinase (ASM) catalyzes ceramide (Cer) generation controlling arterial remodeling through multiple signaling pathways. In the present study, we aimed to investigate the contribution of ASM/Cer to the changes of common carotid artery intima-media thickness (CIMT) induced by simulated weightlessness. Hindlimb-unloaded tail-suspended (HU) rats were used to simulate the effect of weightlessness. Morphology of the carotid artery (CA) was examined by hematoxylin-eosin staining. Protein content of ASM or proliferating cell nuclear antigen (PCNA) was detected by Western blot. Cer level was measured by immunohistochemistry analysis. Apoptosis events were observed by transferase-mediated dUTP nick end labeling (TUNEL) staining. During 4 weeks of tail suspension, CIMT was increased gradually in HU but not in their synchronous control rats (P < 0.05). Correspondingly, the CA of HU rats had a lower apoptosis and higher proliferation of vascular smooth muscle cells (VSMCs). As compared to the control, both ASM protein expression and Cer content were reduced significantly in CA of HU rats (P < 0.05), incubation of which with permeable Cer reversed the changes in apoptosis and proliferation substantially. Furthermore, when the ASM protein content as well as Cer level in CA of control rats was diminished by using an ASM inhibitor, an increase of CIMT along with reduced apoptosis and enhanced proliferation of VSMCs was found. Our results suggest that by controlling the balance between apoptosis and proliferation, ASM/Cer plays an important role in the regulation of CIMT during simulated weightlessness.