Current enzyme‐responsive, fluorogenic probes fail to provide in situ information because the released fluorophores tend to diffuse away from the reaction sites. The problem of diffusive signal ...dilution can be addressed by designing a probe that upon enzyme conversion releases a fluorophore that precipitates. An excited‐state intramolecular proton transfer (ESIPT)‐based solid‐state fluorophore HTPQ was developed that is strictly insoluble in water and emits intense fluorescence in the solid state, with λex/em=410/550 nm, thus making it far better suited to use with a commercial confocal microscope. HTPQ was further utilized in the design of an enzyme‐responsive, fluorogenic probe (HTPQA), targeting alkaline phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion‐resistant in situ detection of endogenous ALP in live cells. It was also employed in the visualizing of different levels of ALP in osteosarcoma cells and tissue, thus demonstrating its interest for the diagnosis of this type of cancer.
A solid‐state fluorophore (HTPQ) that is well‐suited to confocal microscopy was developed. HTPQ was used to design an enzyme‐responsive, fluorogenic probe (HTPQA) targeting alkaline phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion‐resistant detection of endogenous ALP in live cells and visualization of ALP levels in Saos‐2 and U‐2OS osteosarcoma cells and tissue.
Nontoxic prodrugs, especially activated by tumor microenvironment, are urgently required for reducing the side effects of cancer therapy. And combination of chemo-photodynamic therapy prodrugs show ...effectively synergetic therapeutic efficiency, however, this goal has not been achieved in a single molecule. In this work, we developed a mitochondrial-targeted prodrug
for near infrared (NIR) fluorescence imaging guided and synergetic chemo-photodynamic precise cancer therapy for the first time.
contains a NIR photosensitizer (
) and an anticancer drug 5'-deoxy-5-fluorouridine (5'-DFUR). These two parts are linked and caged through a bisboronate group, displaying no fluorescence and very low cytotoxicity. In the presence of H
O
, the bisboronate group is broken, resulting in activation of
for NIR photodynamic therapy and activation of 5'-DFUR for chemotherapy. The activated
can also provide a NIR fluorescence signal for monitoring the release of activated drug. Taking advantage of the high H
O
concentration in cancer cells,
exhibits higher cytotoxicity to cancer cells than normal cells, resulting in lower side effects. In addition, based on its mitochondrial-targeted ability,
exhibits enhanced chemotherapy efficiency compare to free 5'-DFUR. It also demonstrated a remarkably improved and synergistic chemo-photodynamic therapeutic effect for cancer cells. Moreover,
exhibits excellent tumor microenvironment-activated performance when intravenously injected into tumor-bearing nude mice, as demonstrated by
fluorescence imaging. Thus,
is a promising prodrug for cancer therapy based on its tumor microenvironment-activated drug release, synergistic therapeutic effect and "turn-on" NIR imaging guide.
Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress ...to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.
From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.
Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.
LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Ascorbic acid (AA), as one of the most important vitamins, participates in various physiological reactions in the human body and is implicated with many diseases. Therefore, the development of ...effective methods for monitoring the AA level in living systems is of great significance. Up to date, various technologies have been developed for the detection of AA. However, few methods can realize the direct detection of endogenous AA in living cells. In this work, we for the first time reported that near-infrared (NIR) graphene quantum dots (GQD) possessed good two-photon fluorescence properties with a NIR emission at 660 nm upon exciting with 810 nm femtosecond pulses and a two-photon (TP) excitation action cross-section (δΦ) of 25.12 GM. They were then employed to construct a TP nanoprobe for detection and bioimaging of endogenous AA in living cells. In this nanosystem, NIR GQDs (NGs), which exhibited lower fluorescence background in living system to afford improved fluorescence imaging resolution, were acted as fluorescence reporters. Also CoOOH nanoflakes were chosen as fluorescence quenchers by forming on the surface of NGs. Once AA was introduced, CoOOH was reduced to Co
, which resulted in a "turn-on" fluorescence signal of NGs. The proposed nanoprobe demonstrated high sensitivity toward AA, with the observed LOD of 270 nM. It also showed high selectivity to AA with excellent photostability. Moreover, the nanoprobe was successfully used for TP imaging of endogenous AA in living cells as well as deep tissue imaging.
The strong interface is an essential requirement to ensure the effective load transfer of graphene/Cu composites. Here we attempted to improve the interface adhesion and mechanical properties of ...reduced graphene oxide (RGO)/CuCr composites by matrix-alloying with ∼0.2 at.% Cr. It was found that a trace amount of Cr7C3 layers/nanoparticles was in-situ formed at the RGO-CuCr interface, which contributed to the dramatically improved interfacial bonding of the composites. The 2.5 vol% RGO/CuCr composite exhibited a tensile strength of 352 MPa, 82% and 19% higher than that of unreinforced CuCr and 2.5 vol% RGO/Cu composite without Cr alloying, respectively. The enhanced strength of RGO/CuCr composite was ascribed to the dual role of Cr7C3 layers/nanoparticles that not only enhanced the load transfer efficiency, but also promoted the dislocation strengthening ability of RGO itself. Furthermore, we proposed the possible Cr7C3 formation/evolution mechanism that involved the four steps of amorphous carbon formation, Cr7C3 nucleation in amorphous carbon, Cr7C3 growth and Cr7C3 coalescence. The formation of medium sized Cr7C3 layers/nanoparticles at 1053 K resulted in the highest strength of RGO/CuCr composite with a satisfactory strength-ductility combination. This study provides new insights into the interface structure, strengthening mechanism and carbide formation/evolution mechanism of graphene/CuX composites.
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ObjectiveTo investigate the relationship between job satisfaction, work stress, work–family conflict and turnover intention, and explore factors associated with turnover intention, among physicians ...in Guangdong Province, China.MethodsFrom August to October 2013, physicians completed questionnaires and scales with regard to their job satisfaction, work stress, work–family conflict, and turnover intention. Binary logistic regression and structural equation modelling (SEM) were used in data analysis.ResultsA total of 3963 physicians were approached, with 3563 completing the questionnaire. The mean score of the overall perception of turnover intention of physicians who worked in Guangdong was 2.71 on a scale ranging from 1 to 6. Hours worked per week, working in an urban/rural area, type of institution, and age significantly impacted on turnover intention. Turnover intention was directly and negatively related to job satisfaction, and it was directly, indirectly and positively related to work stress and work–family conflict.ConclusionJob satisfaction, work stress, work–family conflict, hours worked per week, working in an urban/rural area, types of institution and age are influencing factors of turnover intention. Reducing working hours, raising salary, providing more opportunities for career development and training, supporting and encouraging physicians by senior managers could potentially contribute to the reduction in turnover intention.
Relapsed and refractory (R/R) multiple myeloma (MM) patients have very poor prognosis. Chimeric antigen receptor modified T (CAR T) cells is an emerging approach in treating hematopoietic ...malignancies. Here we conducted the clinical trial of a biepitope-targeting CAR T against B cell maturation antigen (BCMA) (LCAR-B38M) in 17 R/R MM cases. CAR T cells were i.v. infused after lymphodepleting chemotherapy. Two delivery methods, three infusions versus one infusion of the total CAR T dose, were tested in, respectively, 8 and 9 cases. No response differences were noted among the two delivery subgroups. Together, after CAR T cell infusion, 10 cases experienced a mild cytokine release syndrome (CRS), 6 had severe but manageable CRS, and 1 died of a very severe toxic reaction. The abundance of BCMA and cytogenetic marker del(17p) and the elevation of IL-6 were the key indicators for severe CRS. Among 17 cases, the overall response rate was 88.2%, with 13 achieving stringent complete response (sCR) and 2 reaching very good partial response (VGPR), while 1 was a nonresponder. With a median follow-up of 417 days, 8 patients remained in sCR or VGPR, whereas 6 relapsed after sCR and 1 had progressive disease (PD) after VGPR. CAR T cells were high in most cases with stable response but low in 6 out of 7 relapse/PD cases. Notably, positive anti-CAR antibody constituted a high-risk factor for relapse/PD, and patients who received prior autologous hematopoietic stem cell transplantation had more durable response. Thus, biepitopic CAR T against BCMA represents a promising therapy for R/R MM, while most adverse effects are clinically manageable.
The ongoing new coronavirus pneumonia (Corona Virus Disease 2019, COVID-19) outbreak is spreading in China, but it has not yet reached its peak. Five million people emigrated from Wuhan before ...lockdown, potentially representing a source of virus infection. Determining case distribution and its correlation with population emigration from Wuhan in the early stage of the epidemic is of great importance for early warning and for the prevention of future outbreaks.
The official case report on the COVID-19 epidemic was collected as of January 30, 2020. Time and location information on COVID-19 cases was extracted and analyzed using ArcGIS and WinBUGS software. Data on population migration from Wuhan city and Hubei province were extracted from Baidu Qianxi, and their correlation with the number of cases was analyzed.
The COVID-19 confirmed and death cases in Hubei province accounted for 59.91% (5806/9692) and 95.77% (204/213) of the total cases in China, respectively. Hot spot provinces included Sichuan and Yunnan, which are adjacent to Hubei. The time risk of Hubei province on the following day was 1.960 times that on the previous day. The number of cases in some cities was relatively low, but the time risk appeared to be continuously rising. The correlation coefficient between the provincial number of cases and emigration from Wuhan was up to 0.943. The lockdown of 17 cities in Hubei province and the implementation of nationwide control measures efficiently prevented an exponential growth in the number of cases.
The population that emigrated from Wuhan was the main infection source in other cities and provinces. Some cities with a low number of cases showed a rapid increase in case load. Owing to the upcoming Spring Festival return wave, understanding the risk trends in different regions is crucial to ensure preparedness at both the individual and organization levels and to prevent new outbreaks.
Antimony sulfide (Sb2S3) is emerging as a promising light harvesting material owing to its brilliant photoelectric property. However, the performance of Sb2S3‐based solar cells is partly limited by ...serious back contact interface recombination and hole transportation resistance. High‐efficiency Sb2S3 devices typically use Spiro‐OMeTAD and/or Au as back contact materials, but their stability and cost are a concern. In this sense, a surface modification scheme by lithium‐doping is first introduced for Sb2S3 via a facile molten salt method. The ions in the molten state have high mobility and activity, enabling doping reactions to complete within a short time. The lithium‐doped Sb2S3 thin film has a smooth and well‐bonded surface, preferred (hk1) orientations, and an upshifted valence band maximum (VBM), which favors the hole extraction. Finally, a device using carbon as an electrode, which is more than a dozen times cheaper than gold, raises the short‐circuit current density (JSC) from 12.35 to 14.40 mA cm−2, and the power conversion efficiency (PCE) from 4.47% to 6.16%. This is among the highest PCE reported for full‐inorganic Sb2S3 solar cells, which demonstrates a facile interface modification technique via molten alkali salt to improve the performance of Sb2S3 solar cells.
Sb2S3 is a kind of new light‐absorbing material possessing high stability in ambient environment, high absorption coefficient in the visible range, and abundant elemental storage. Here, a surface modification scheme by lithium‐doping is first introduced for Sb2S3 via a facile molten salt method. The device with the low‐cost carbon electrode delivers a power conversion efficiency (PCE) of 6.16%, which is among the highest PCE reported for the full‐inorganic Sb2S3 solar cells.
Peroxynitrite (ONOO
), an extremely reactive nitrogen species (RNS), is implicated in diverse pathophysiological conditions, including cancer, neurodegenerative diseases, and inflammation. Sensing ...and imaging of ONOO
in living systems remains challenging due to the high autofluorescence and the limited light penetration depth. In this work, we developed a bioluminescent probe BP-PN, based on luciferase-luciferin pairs and the ONOO
-responded group α-ketoamide, for highly sensitive detection and imaging of endogenous ONOO
in living cells and mice for the first time. Attributed to the BL without external excitation, the probe BP-PN exhibits a high signal-to-noise ratio with relatively low autofluorescence. Furthermore, we examine the application of the probe BP-PN using the mice model of inflammation, and BP-PN shows high sensitivity for imaging endogenous ONOO
in inflamed mice. This newly developed bioluminescent probe would be a potentially useful tool for in vivo imaging of ONOO
in wider physiological and pathological processes.
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