Simple thiol derivatives, such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), play key roles in biological processes, and the fluorescent probes to detect such thiols in vivo ...selectively with high sensitivity and fast response times are critical for understanding their numerous functions. However, the similar structures and reactivities of these thiols pose considerable challenges to the development of such probes. This review focuses on various strategies for the design of fluorescent probes for the selective detection of biothiols. We classify the fluorescent probes for discrimination among biothiols according to reaction types between the probes and thiols such as cyclization with aldehydes, conjugate addition-cyclization with acrylates, native chemical ligation, and aromatic substitution-rearrangement.
Exhaustion of cytotoxic effector natural killer (NK) and CD8
T cells have important functions in the establishment of persistent viral infections, but how exhaustion is induced during chronic ...hepatitis C virus (HCV) infection remains poorly defined. Here we show, using the humanized C/O
mice permissive for persistent HCV infection, that NK and CD8
T cells become sequentially exhausted shortly after their transient hepatic infiltration and activation in acute HCV infection. HCV infection upregulates Qa-1 expression in hepatocytes, which ligates NKG2A to induce NK cell exhaustion. Antibodies targeting NKG2A or Qa-1 prevents NK exhaustion and promotes NK-dependent HCV clearance. Moreover, reactivated NK cells provide sufficient IFN-γ that helps rejuvenate polyclonal HCV CD8
T cell response and clearance of HCV. Our data thus show that NKG2A serves as a critical checkpoint for HCV-induced NK exhaustion, and that NKG2A blockade sequentially boosts interdependent NK and CD8
T cell functions to prevent persistent HCV infection.
People with serious mental illness are at great risk of suicide, but little is known about the suicide rates among this population. We aimed to quantify the suicide rates among people with serious ...mental illness (bipolar disorder, major depression, or schizophrenia).
PubMed and Web of Science were searched to identify studies published from 1 January 1975 to 10 December 2020. We assessed English-language studies for the suicide rates among people with serious mental illness. Random-effects meta-analysis was used. Changes in follow-up time and the suicide rates were presented by a locally weighted scatter-plot smoothing (LOESS) curve. Suicide rate ratio was estimated for assessments of difference in suicide rate by sex.
Of 5014 identified studies, 41 were included in this analysis. The pooled suicide rate was 312.8 per 100 000 person-years (95% CI 230.3-406.8). Europe was reported to have the highest pooled suicide rate of 335.2 per 100 000 person-years (95% CI 261.5-417.6). Major depression had the highest suicide rate of 534.3 per 100 000 person-years (95% CI 30.4-1448.7). There is a downward trend in suicide rate estimates over follow-up time. Excess risk of suicide in males was found 1.90 (95% CI 1.60-2.25). The most common suicide method was poisoning 21.9 per 100 000 person-years (95% CI 3.7-50.4).
The suicide rates among people with serious mental illness were high, highlighting the requirements for increasing psychological assessment and monitoring. Further study should focus on region and age differences in suicide among this population.
Acoustic metamaterials with artificial microstructures are attractive to realize intriguing functions, including efficient waveguiding, which requires large impedance mismatches to realize total side ...reflection with negligible transmission and absorption. While large impedance mismatch can be readily realized in an air environment, acoustic waveguiding in an underwater environment remains elusive due to insufficient impedance mismatch of state‐of‐the‐art metamaterials. Here, a superhydrophobic acoustic metasurface of microstructured poly(vinylidene fluoride) membrane, referred to as a “meta‐skin” insulator, which is able to confine acoustic waves in an all‐angle and wide spectrum range due to tremendous impedance mismatch at stable air/water interfaces, viz., the Cassie–Baxter state is demonstrated. By utilizing the meta‐skin insulator with broadband and high throughput, orbital‐angular‐momentum multiplexing at a high spectral efficiency and binary coding along large‐angle bending channels for bit‐error‐free acoustic data transmission in an underwater environment are demonstrated. Very different from optical and/or electrical cable communications, acoustic waves can be simply and effectively coupled into remote meta‐skin acoustic fibers from free space, which is technologically significant for long‐haul and anti‐interference communication. This work can enlighten many fluidic applications based on efficient waveguiding, such as in vivo ultrasound medical treatment and imaging.
Underwater acoustic wave confinement in an all‐angle and wide spectrum range can be realized in a meta‐skin insulator due to the tremendous impedance mismatch originating from the stable Cassie–Baxter state. Acoustic‐wave‐based underwater orbital‐angular‐momentum multiplexing and binary coding are implemented, which is promising for long‐haul and anti‐interference communication. This work also benefits in vivo ultrasound medical treatment and imaging.
Objective
To quantitatively examine the relationship between social support and suicidal ideation (SI) among patients with cancer and identify the moderators that influence the magnitude of this ...association.
Methods
Publications were searched in PubMed, PsycINFO, EMBASE, Cochrane Library and Chinese National Knowledge Infrastructure from database inception to May, 2020. Correlation coefficients (r) were chosen as the effect size with a random model to evaluate the overall effect size between social support and SI in patients with cancer. To assess statistical heterogeneity, we examined potential moderator variables on the social support and SI.
Results
A total of 881 studies were identified in initial search, and twelve studies were eligible. A negative, small but significant correlation (r = −0.22, 95% CIs: −0.30,−0.14, p < 0.001) was observed between social support and SI in patients with cancer, with a significant heterogeneity (I2 = 95.24%, Q = 231.27, p < 0.001). Moderator analyses indicated that race/ethnicity (Q(1) = 8.4, p < 0.05) and measurements of social support (Q(3) = 9.78, p < 0.05) and SI (Q(3) = 9.69, p < 0.05) significantly moderate the effect size between social support and SI.
Conclusion
Taken together, we found a negative yet significant association between social support and SI in patients with cancer, which supported the importance of social support for the prevention of SI in patients with cancer.
Background
Data on the incidence, mortality, and other burden of oral cancer as well as their secular trends are necessary to provide policy‐makers with the information needed to allocate resources ...appropriately. The purpose of this study was to use the Global Burden of Disease (GBD) 2017 results to estimate the incidence, mortality, and disability‐adjusted life years (DALYs) for oral cancer from 1990 to 2017.
Methods
We collected detailed data on oral cancer from 1990 to 2017 from the GBD 2017. The global incidence, mortality, and DALYs attributable to oral cancer as well as the corresponding age‐standardized rates (ASRs) were calculated. The estimated annual percentage changes in the ASRs of incidence (ASRI) and mortality (ASRM) and age‐standardized DALYs of oral cancer were also calculated according to regions and countries to quantify the secular trends in these rates.
Results
We tracked the incidence, mortality, and DALYs of oral cancer in 195 countries/territories over 28 years. Globally, the incidence, mortality, and DALYs of oral cancer increased by about 1.0‐fold from 1990 to 2017. The ASRI of oral cancer showed a similar trend, increasing from 4.41 to 4.84 per 100,000 person‐years during the study period. The ASRM remained approximately stable at about 2.4 per 100,000 from 1990 to 2017, as did the age‐standardized DALYs, at about 64.0 per 100,000 person‐years. ASRI was highest in Pakistan (27.03/100,000, 95% CI = 22.13‐32.75/100,000), followed by Taiwan China, and lowest in Iraq (0.96/100,000, 95% CI = 0.86‐1.06/100,000). ASRM was highest in Pakistan (16.85/100,000, 95% CI = 13.92‐20.17/100,000) and lowest in Kuwait (0.51/100,000, 95% CI = 0.45‐0.58/100,000).
Conclusions
The ASRI of oral cancer has increased slightly worldwide, while the ASRM and age‐standardized DALY have remained stable. However, these characteristics vary between countries, suggesting that current prevention strategies should be reoriented, and much more targeted and specific strategies should be established in some countries to forestall the increase in oral cancer.
Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an unknown cause. Infection with ...Anaplasma phagocytophilum has been suggested as a cause, but the pathogen has not been detected in most patients on laboratory testing.
We obtained blood samples from patients with the case definition of SFTS in six provinces in China. The blood samples were used to isolate the causal pathogen by inoculation of cell culture and for detection of viral RNA on polymerase-chain-reaction assay. The pathogen was characterized on electron microscopy and nucleic acid sequencing. We used enzyme-linked immunosorbent assay, indirect immunofluorescence assay, and neutralization testing to analyze the level of virus-specific antibody in patients' serum samples.
We isolated a novel virus, designated SFTS bunyavirus, from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction. RNA sequence analysis revealed that the virus was a newly identified member of the genus phlebovirus in the Bunyaviridae family. Electron-microscopical examination revealed virions with the morphologic characteristics of a bunyavirus. The presence of the virus was confirmed in 171 patients with SFTS from six provinces by detection of viral RNA, specific antibodies to the virus in blood, or both. Serologic assays showed a virus-specific immune response in all 35 pairs of serum samples collected from patients during the acute and convalescent phases of the illness.
A novel phlebovirus was identified in patients with a life-threatening illness associated with fever and thrombocytopenia in China. (Funded by the China Mega-Project for Infectious Diseases and others.).
Based on OR logic gate, we proposed a smart near-infrared (NIR) fluorescent probe, named
, for simultaneously monitoring local microviscosity, micropolarity, and carboxylesterases (CEs) in living ...cells through blue and red channels. This proposed probe was capable of distinguishing cancer cells from normal cells and had good potential for identifying living liver cell lines. Furthermore, the fluctuations of the three analytes of interest in different cell status was successfully explored. Particularly, facilitated with high-content analysis (HCA) and
, a simple and efficient high-throughput screening (HTS) platform was first constructed for screening antitumor drugs and studying their effect on the analytes. For the first time, we found that sorafenib-induced ferroptosis led to an increase in the microviscosity and up-regulation of CEs at the same time. Additionally, the procedure that aristolochic acid (AA) induced the overexpression of CEs was verified. Besides,
was utilized for imaging the variations of the two microenvironment parameters and CEs in the inflammation model. Finally,
was able to image the tumor ex vivo and in vivo through two channels and one channel separately, as well as to visualize the kidneys and liver ex vivo with dual emissions, which indicated that the probe had great potential for imaging applications such as medical diagnosis, preclinical research, and imaging-guided surgery.
Chronic Obstructive Pulmonary Disease (COPD) is associated with T lymphocytes subset (Th1/Th2, Th17/Treg) imbalance. Notch signaling pathway plays a key role in the development of the adaptive ...immunity. The immune disorder induced by fine particulate matter (PM2.5) is related to COPD. The aim of this study was to investigate the mechanism by which PM2.5 influences the Notch signaling pathway leading to worsening immune disorder and accelerating COPD development. A COPD mouse model was established by cigarette smoke exposure. PM2.5 exposure was performed by aerosol inhalation. γ-secretase inhibitor (GSI) was given using intraperitoneal injection. Splenic T lymphocytes were purified using a density gradient centrifugation method. CD4+ T lymphocyte subsets (Th1/Th2, Th17/Treg) were detected using flow cytometry. mRNA and proteins of Notch1/2/3/4, Hes1/5, and Hey1 were detected using RT-PCR and Western blot. Serum INF-γ, IL-4, IL-17 and IL-10 concentrations were measured using ELISA. The results showed that in COPD mice Th1% and Th17%, Th1/Th2 and Th17/Treg were increased, and the levels of mRNA and protein in Notch1/2/3/4, Hes1/5, and Hey1 and serum INF-γ and IL-17 concentrations were significantly increased, and Th2%, Treg%, and serum IL-4 and IL-10 concentrations were significantly decreased. COPD Mice have Th1- and Th17-mediated immune disorder, and the Notch signaling pathway is in an overactivated state. PM2.5 promotes the overactivation of the Notch signaling pathway and aggravates the immune disorder of COPD. GSI can partially inhibit the activation of the Notch signaling pathway and alleviate the immune disorder under basal state and the immune disorder of COPD caused by PM2.5. This result suggests that PM2.5 is involved in the immune disorder of mice with COPD by affecting the Notch signaling pathway and that PM2.5 aggravates COPD.
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•The COPD mice demonstrated Th1 and Th17 dominant immune imbalance.•PM2.5 aggravates the Th1/Th2 and Th17/Treg immune imbalance in COPD mice.•The Notch pathway regulates T cell differentiation and participates in the immune imbalance in the pathogenesis of COPD.•PM2.5 can promote the activation of the Notch pathway while GSI can block this pathway's activation partially.
This study suggests that PM2.5 causes immune dysfunction via Notch signaling pathway, which is involved in the pathogenesis of COPD.
•The incidence of suicide death among patients with cancer was disturbingly high, with 39.72 per 100,000 person-years.•The reported rate of suicide varied in different geographic region and ...site-specific cancers remarkably.•Suicide rate in cancer patients decreases with years after diagnosis, with the highest rate in the first six months.
Growing evidence indicated the higher risk of suicide in cancer survivors compared with general population. Our aim is to systematically quantify the extent of suicide death and identify risk factors associated with the incidence of suicide in cancer patients.
We conducted a meta-analysis of relevant studies published in English or Chinese before May 20, 2020. Suicide rate and the number of suicide death were extracted. Our main outcome was suicide rate per 100,000 person-years with 95% CIs using random-effects model.
The pooled incidence of suicide death was 39.72 per 100,000 person-years (95%CI, 33.91–46.52, I 2= 99.6%, P <0 .001). The suicide rate for cancer patients was higher in men (57.78, 95%CI, 47.31–70.56) than in women (14.47, 95%CI, 11.27–18.57). For both sexes combined, esophagus cancer had the highest rate of suicide (87.71, 95%CI, 27.42–280.54). By sex, suicide rates ranked first in males and females were pancreas cancer (195.70, 95%CI, 129.55–295.61) and esophagus cancer (18.34, 95%CI, 5.92–56.84), respectively. The highest suicide rate was 61.02(95%CI, 53.66–69.40) in Asia, and Oceania (24.07, 95%CI, 20.78–27.88) had lowest suicide rate. Suicide rate had a downward trend by years after diagnosis, with the first six months after cancer diagnosis clearly standing out (89.33, 95%CI, 50.64–157.58).
Included studies came from high-income countries and our results might not represent the suicide rate among cancer patients in low- and middle-income countries.
The incidence of suicide among cancer patients was high despite the declined trend recent years, which emphasized psychological health aspects of interventions and perfecting suicide prevention programs.
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