Despite rapid advances in modern medical technology and significant improvements in survival rates of many cancers, pancreatic cancer is still a highly lethal gastrointestinal cancer with a low ...5-year survival rate and difficulty in early detection. At present, the incidence and mortality of pancreatic cancer are increasing year by year worldwide, no matter in the United States, Europe, Japan, or China. Globally, the incidence of pancreatic cancer is projected to increase to 18.6 per 100000 in 2050, with the average annual growth of 1.1%, meaning that pancreatic cancer will pose a significant public health burden. Due to the special anatomical location of the pancreas, the development of pancreatic cancer is usually diagnosed at a late stage with obvious clinical symptoms. Therefore, a comprehensive understanding of the risk factors for pancreatic cancer is of great clinical significance for effective prevention of pancreatic cancer. In this paper, the epidemiological characteristics, developmental trends, and risk factors of pancreatic cancer are reviewed and analyzed in detail.
Ferroptosis is an iron-dependent, non-apoptotic form of programmed cell death driven by excessive lipid peroxidation (LPO). Mounting evidence suggests that the unique modality of cell death is ...involved in the development and progression of several diseases including cancer, cardiovascular diseases (CVDs), neurodegenerative disorders,
etc.
However, the pathogenesis and signalling pathways of ferroptosis are not fully understood, possibly due to the lack of robust tools for the highly selective and sensitive imaging of ferroptosis analytes in complex living systems. Up to now, various small-molecule fluorescent probes have been applied as promising chemosensors for studying ferroptosis through tracking the biomolecules or microenvironment-related parameters
in vitro
and
in vivo
. In this review, we comprehensively reviewed the recent development of small-molecule fluorescent probes for studying ferroptosis, with a focus on the analytes, design strategies and bioimaging applications. We also provided new insights to overcome the major challenges in this emerging field.
Small-molecule fluorescent probes for studying ferroptosis.
Rechargeable aqueous zinc-ion batteries (RAZIBs) are regarded as competitive alternatives for large-scale energy storage on account of cost-effectiveness and inherent safety. In particular, ...rechargeable Zn-MnO
2
batteries have drawn increasing attention due to high manufacturing readiness level. However, obtaining MnO
2
with high electrochemical activity and high cyclic stability toward Zn
2+
/H
+
storage still remains challenging. Herein, we reveal that incorporating yttrium ions (Y
3+
) into layered MnO
2
can regulate the electronic structure of the MnO
2
cathode by narrowing its band gap (from 3.25 to 2.50 eV), thus boosting the electrochemical performance in RAZIBs. Taking advantage of this feature, the optimized Y-MnO
2
(YMO) sample exhibits greater capacity (212
vs.
152 mA h g
−1
at 0.5 A g
−1
), better rate capability (94
vs.
61 mA h g
−1
at 8 A g
−1
), reduced charge-transfer resistance (79
vs.
148 Ω), and promoted mass transfer kinetics (3.13 × 10
−11
vs.
2.37 × 10
−11
cm
2
s
−1
) in comparison with Y-free MnO
2
(MO). More importantly, compared to MO, YMO-0.1 exhibits enhanced energy storage capability by nearly 40% (309
vs.
222 W h kg
−1
) and stable cycle performance (94
vs.
52 mA h g
−1
after 3000 cycles).
In situ
Raman microscopy further reveals that the presence of Y
3+
endows MnO
2
with remarkable electrochemical reversibility during charge/discharge processes. This work highlights the importance of the Y
3+
preintercalation strategy, which can be further developed to obtain better cathode materials for aqueous batteries.
Preintercalated Y
3+
in layered MnO
2
can elaborately regulate the electronic structure, boost electrochemical activity, and render better electrochemical reversibility of MnO
2
, leading to enhanced energy storage in aqueous Zn-ion batteries.
•The fluorescent probes, chemiluminescent probes and bioluminescent probes for sensing NTRs were reviewed.•The design strategies of those modes were discussed based on different probes.•The ...advantages and drawbacks of those detection modes were discussed.•A prospect for the detection of NTRs activity was proposed.
As one of the most representative hypoxic enzymes, nitroreductases (NTRs) play momentous roles in malignant tumor progression, metastasis, invasion and angiogenesis. They are also a key hallmark of highly aggressive disease in various hypoxic tumor cells. In addition, NTRs participate in essential processes of detoxification, pro-drug activation as well as radiation therapy. Thus, the detection of NTRs has great importance for theranostic and drug development. In this review, we focused on the design principles, sensing mechanisms and biological applications of small-molecule probes for NTRs detection over the past ten years (2010–2020). We also highlighted the challenges and future directions in this rapidly developing field. Significantly, we hope that some insights and inspiration for future research work will be provided to surmount the Achilles’ Heels of the small-molecule probes, such as limited application, for detecting NTRs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•A brief introduction of the categories, advantages, and applications of fluorescent probes.•The advantages of NIR ratiometric small-molecule fluorescent probes.•Details the design principles and ...applications of NIR ratiometric small-molecule fluorescent probes.•The achievements of NIR ratiometric small-molecule fluorescent probes.•The challenges and opportunities that remain in the field of NIR ratiometric small-molecule fluorescent probes.
The burgeoning organic near-infrared (NIR) ratiometric small-molecule fluorescent probes with excellent merits have attracted great attention over the past few years. The traditional intensity-based probes are unable to output reliable and accurate detection signals as well as to realize quantitative determination of analytes due to the lack of an “internal standard method”. The smart dual emission probes with built-in correction ability can overcome the “Achilles' heel” of the single channel fluorescent probes, such as concentration-dependent and microenvironment sensitive, to enable reliable quantitative image analysis. Furthermore, fluorescent chemosensors in the NIR window (650–1700 nm) have great advantages, including high signal-to-noise (S/N) ratio, low tissue damage, and deep tissue penetration. Therefore, the NIR ratiometric fluorescent probes combine the advantage of the ratiometric fluorescent probes and the single-intensity-based NIR probes. Nowadays, these robust multichannel probes have been widely applied for biomedical research and clinical practice. In this review, we systematically summarized the recent advances (2020–2022) in these kinds of probes. The design strategies, sensing mechanisms, and bioapplications of these intelligent fluorescent probes were discussed. Moreover, the challenges and prospects in this promising field were addressed, and we anticipated that our work would inspire the development of organic NIR ratiometric fluorescent probes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Based on OR logic gate, we proposed a smart near-infrared (NIR) fluorescent probe, named VPCPP, 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 VPCPP, 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, VPCPP was utilized for imaging the variations of the two microenvironment parameters and CEs in the inflammation model. Finally, VPCPP 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.
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IJS, KILJ, NUK, PNG, UL, UM
The codling moth, Cydia pomonella (Lepidoptera: Tortricidae) is a major pest of pome fruit and walnuts worldwide. Although environmentally compatible integrated control strategies, such as mating ...disruption, attract-kill strategy, and sterile insect technique have been conducted for management of this notorious pest, effects to control of codling moth have mainly relied on insecticides. In consequence, different levels of insecticide resistance towards organophosphates, neonicotinoids, hydrazines, benzoylureas, pyrethroids, diamides, spinosyns, avermectins, JH mimics, carbamates, oxadiazines and C. pomonella granulovirus (CpGVs) have developed in codling moth in different countries and areas. Both metabolic and target-site mechanisms conferring resistance have been revealed in the codling moth. In this review, we summarize the current global status of insecticide resistance, the biochemical and molecular mechanisms involved, and the implications for resistance management.
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•The coding moth (CM) has developed resistance to almost all classes of insecticides.•Target-site and metabolic mechanisms are involved in insecticide resistance in CM.•Resistance management strategy for preventing resistance development is proposed.•Genomic technologies open an avenue for developing management programs in CM.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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Rechargeable aqueous zinc–ion batteries (RAZIBs) show great potential as a competitive candidate for reliable energy storage by virtue of cost–effectiveness, high safety, and ...environmental friendliness. However, unsatisfactory cycle stability of cathode material impedes the development of high–performance RAZIBs. This study reveals a strategic polyol–mediated process by using glycerol as the solvent for solvothermal reaction. After heat treatment in air, Mn–deficient Mn3O4 spinel (D–Mn3O4) can be obtained with rich Mn valence states (Mn2+/Mn3+/Mn4+), expanded crystal structure, high surface area, and good electrolyte compatability. Compared to well–crystallized Mn3O4, the presence of manganese vacancies in D–Mn3O4 enables lower charge–transfer resistance (86.0 vs 196.5 Ω), reduced activation energy for ion insertion (30.9 vs 50.4 kJ mol−1), and boosted solid–state ion diffusivity (9.45 × 10−12 vs 4.61 × 10−14 cm2 s−1). Therefore, D–Mn3O4 exhibits promising electrochemical performance with high capacity (284 mAh g−1), high specific energy (388.5 Wh kg−1) and stable cycle retention (87% after 200 cyclesat 0.3 A g−1). On the contrary, the well–crystallized Mn3O4 sample suffers from severe capacity fading with only 48% capacity retention. Moreover, the specific energies obtained after 200 cycles are 336.1 and 166.0 Wh kg−1 for D–Mn3O4 and Mn3O4, respectively. The drastic differences between the electrochemical performance of D–Mn3O4 and Mn3O4 manifest that the existing manganese vacancies in Mn3O4 spinel structure enhance energy storage capability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
RNA-binding motif protein 24 (RBM24) acts as a multifunctional determinant of cell fate, proliferation, apoptosis, and differentiation during development by regulating premRNA splicing and mRNA ...stability. It is also implicated in carcinogenesis, but the functions of RBM24 in bladder cancer (BC) remain unclear. In the present study, we revealed that RBM24 was upregulated in BC tissues. Importantly, we found that a higher level of RBM24 was correlated with poor prognosis in BC patients. Overexpression of RBM24 promoted BC cell proliferation, while depletion of RBM24 inhibited BC cell proliferation in vivo and in vitro. Mechanistically, RBM24 positively regulated Runx1t1 expression in BC cells by binding to and enhancing Runx1t1 mRNA stability. Furthermore, Runx1t1 in turn promoted RBM24 expression by interacting with the transcription factor TCF4 and suppressing the transcription of miR-625-5p, which directly targets RBM24 and suppresses RBM24 expression. RBM24-regulated BC cell proliferation was moderated via the Runx1t1/TCF4/miR-625-5p feedback loop. These results indicate that the RBM24/Runx1t1/TCF4/miR-625-5p positive feedback loop participates in BC progression. Disruption of this pathway may be a potential therapeutic strategy for BC treatment.
Objectives
Several population pharmacokinetics (popPK) models for polymyxin B have been constructed to optimize therapeutic regimens. However, their predictive performance remains unclear when ...extrapolated to different clinical centers. Therefore, this study aimed to evaluate the predictive ability of polymyxin B popPK models.
Methods
A literature search was conducted, and the predictive performance was determined for each selected model using an independent dataset of 20 patients (92 concentrations) from the Third Xiangya Hospital. Prediction- and simulation-based diagnostics were used to evaluate model predictability. The influence of prior information was assessed using Bayesian forecasting.
Results
Eight published studies were evaluated. In prediction-based diagnostics, the prediction error within ± 30% was over 50% in two models. In simulation-based diagnostics, the prediction- and variability-corrected visual predictive check (pvcVPC) showed satisfactory predictivity in three models, while the normalized prediction distribution error (NPDE) tests indicated model misspecification in all models. Bayesian forecasting demonstrated a substantially improvement in the model predictability even with one prior observation.
Conclusion
Not all published models were satisfactory in prediction- and simulation-based diagnostics; however, Bayesian forecasting improved the predictability considerably with priors, which can be applied to guide polymyxin B dosing recommendations and adjustments for clinicians.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
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