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Cryptosporidiosis is considered a crucial zoonotic disease caused by widely distributing parasitic protozoa called Cryptosporidium spp. Nitazoxanide is the only FDA-approved drug but is only effective with a good immune response of the host. In addressing this unmet medical need, we previously identified a compound, namely, LN002, as a potent alternative oxidase inhibitor against cryptosporidiosis. To illustrate the pharmacokinetics, absolute bioavailability, and tissue distribution of LN002 in rats, rapid and sensitive high-performance liquid chromatography was developed and validated for the separation and detection of LN002 in plasma, tissue samples, and intestinal contents. In this study, a single dose of oral administration and intravenous injection of LN002 was used to determine the levels of LN002 in plasma, tissue samples, and intestinal contents by UHLC. Results of the study indicated that after intravenous administration of 1 mg/kg LN002, the AUC0–24 h, T1/2,Vd, and Cl were 7024.86 h·ng/mL, 10.91 h, 1.69 L/kg, and 0.11 L/h/kg, respectively. After oral administration of a single dosage of 100, 200, and 400 mg/kg LN002, the Tmax, Cmax, AUC0–24 h, T1/2, F, Vd, and Cl/F in plasma of rats were 1 h, 849.88–4033.21 ng/mL, 2280.41–7498.10 h·ng/mL, 17.96–18.83 h, 0.27%–0.32%, 581.54–869.21 L/kg, and 25.97–39.00 L/h/kg, respectively. After oral administration of 200 mg/kg, LN002 was extensively distributed in the main tissues of rats, and massive amounts of LN002 were distributed in the intestine and intestinal contents, indicating its potential as an effective anti-Cryptosporidium compound. After oral administration of a single dosage of 200 mg/kg, LN002 has a low bioavailability and high levels in the intestine, which is crucial for the safe and effective treatment of cryptosporidiosis. Overall, the results of this study provide valuable data support for the future study of LN002.

Microplastic (MP) pollution has become a global environmental issue, and increasing concern has been raised about its impact on human health. Current studies on the toxic effects and mechanisms of MPs have mostly been conducted in animal models or in vitro cell cultures, which have limitations regarding inter-species differences or stimulation of cellular functions. Organoid technology derived from human pluripotent or adult stem cells has broader prospects for predicting the potential health risks of MPs to humans. Herein, we reviewed the current application advancements and opportunities for different organoids, including brain, retinal, intestinal, liver, and lung organoids, to assess the human health risks of MPs. Organoid techniques accurately simulate the complex processes of MPs and reflect phenotypes related to diseases caused by MPs such as liver fibrosis, neurodegeneration, impaired intestinal barrier and cardiac hypertrophy. Future perspectives were also proposed for technological innovation in human risk assessment of MPs using organoids, including extending the lifespan of organoids to assess the chronic toxicity of MPs, and reconstructing multi-organ interactions to explore their potential in studying the microbiome-gut-brain axis effect of MPs.

Abstract The stress hormone, Abscisic acid (ABA), is crucial for plants to respond to changes in their environment. It triggers changes in cytoplasmic Ca2+ levels, which activate plant responses to external stresses. However, how Ca2+ sensing and signaling feeds back into ABA signaling is not well understood. Here we reveal a calcium sensing module that negatively regulates drought stress via modulating ABA receptor PYLs. Mutants cbl1/9 and cipk1 exhibit hypersensitivity to ABA and drought resilience. Furthermore, CIPK1 is shown to interact with and phosphorylate 7 of 14 ABA receptors at the evolutionarily conserved site corresponding to PYL4 Ser129, thereby suppressing their activities and promoting PP2C activities under normal conditions. Under drought stress, ABA impedes PYLs phosphorylation by CIPK1 to respond to ABA signaling and survive in unfavorable environment. These findings provide insights into a previously unknown negative regulatory mechanism of the ABA signaling pathway, which is mediated by CBL1/9-CIPK1-PYLs, resulting in plants that are more sensitive to drought stress. This discovery expands our knowledge about the interplay between Ca2+ signaling and ABA signaling.

The large-size detector-grade CH3NH3PbI3 single-crystal wafers were fabricated through stress-free gel-confined solution growth process, achieving an energy resolution of 4.9% under 241Am gamma-ray source with ultralow operating bias of 5 V.

Abstract The interactions between hydraulic fracture morphology and fluid transport mechanisms after large-scale fracturing in low-permeability carbonate reservoirs are important factors that could impact post-fracturing productivity. Using an integrated geology-engineering approach that consists of hydraulic fracturing and reservoir simulation, this paper presents the detailed hydraulic fracturing simulation and design of a low-permeability carbonate reservoir in the Middle East based on sweet spot mapping. The fracturing protocol is determined based on productivity charts, which are obtained via sweet spot mapping of the target carbonate reservoir. The daily production of a horizontal well in the reservoir shows an increase from 870 to 2000 bbl/d after the hydraulic fracturing design and implementation, which is the highest among the existing production wells in same oilfield. The results are shown to be consistent with the proposed productivity chart, which suggests that the implemented workflow could be helpful for the large-scale fracturing implementation of similar carbonate reservoirs.

Abstract Lead halide perovskites have received considerable attention from researchers over the past several years due to their superior optical and optoelectronic properties, because of which they can be a versatile platform for fundamental science research and applications. Patterned structures based on lead halide perovskites have much more novel properties compared with their more commonly seen bulk‐, micro‐, and nano‐crystals, such as improvement in antireflection, light‐scattering effects, and light absorption, as a result of their adjustability of spatial distributions. However, there are many challenges yet to be resolved in this field, such as insufficient patterned resolution, imperfect crystal quality, complicated preparation process, and so on. To pave the way to solve these problems, we provide a systematic presentation of current methods for fabricating lead halide perovskite patterned structures, including thermal imprint, use of etching films, two‐step vapor‐phase growth, template‐confined solution growth, and seed‐assisted growth. Furthermore, the advantages and disadvantages of these methods are elaborated in detail. In addition, thanks to the extraordinary properties of lead halide perovskite patterned structures, a variety of potential applications in optics and optoelectronics of these structures are described. Lastly, we put forward existing challenges and prospects in this exciting field.

Abstract Organic–inorganic halide perovskite single crystals (SCs) are promising materials for detecting ionizing radiation owing to their outstanding photoelectric conversion capability and inexpensive solution processability. However, the accuracy and stability of the detectors have been limited due to the charge traps and defects in SCs, especially when operated under high‐precision photon‐counting mode for energy spectrum acquisition. Here, we proposed a trap freezing deactivation route, which obviously suppressed dark current and noise by up to 97% and 92%, respectively. Furthermore, the bulk ion migration effect was essential for the ability to instantly self‐heal defects induced by radiation damage at temperatures down to −30°C. Consequently, the detector exhibits a record high energy resolution of 7.5% at 59.5 keV for 241Am γ‐ray source, which is the best solution‐processed semiconductor radiation detectors at the same energy range. In addition, the detector maintains over 90% of its initial performance after 9 months of storage when tested in the air. Our results will represent a revision of the paradigm that high‐spectral‐resolution and robust radiation detectors can only be realized with high temperature grown inorganic semiconductor single crystals.

Nanomaterials are desirable for sensing applications. Therefore, MnO2 nanosheets and nitrogen-doped carbon dots (NCDs) were used to construct a ratiometric biosensor for quantification of 2,4-dichlorophenoxyacetic acid. The MnO2 nanosheets drove the oxidation of colorless o-phenylenediamine to OPDox, which exhibits fluorescence emission peaks at 556 nm. The fluorescence of OPDox was efficiently quenched and the NCDs were recovered as the ascorbic acid produced by the hydrolyzed alkaline phosphatase (ALP) substrate increased. Owing to the selective inhibition of ALP activity by 2,4-D and the inner filter effect, the fluorescence intensity of the NCDs at 430 nm was suppressed, whereas that at 556 nm was maintained. The fluorescence intensity ratio was used for quantitative detection. The linear equation was F = 0.138 + 3.863·C 2,4-D (correlation coefficient R2 = 0.9904), whereas the limits of detection (LOD) and quantification (LOQ) were 0.013 and 0.040 μg/mL. The method was successfully employed for the determination of 2,4-D in different vegetables with recoveries of 79%~105%. The fluorescent color change in the 2,4-D sensing system can also be captured by a smartphone to achieve colorimetric detection by homemade portable test kit.

Abstract Background Microfluidic chip detection technology is considered a potent tool for many bioanalytic applications. Rapid detection of foodborne pathogens in the early stages is imperative to prevent the outbreak of foodborne diseases, known as a severe threat to human health. Conventional bacterial culture methods for detecting foodborne pathogens are time-consuming, laborious, and lacking in pathogen diagnosis. To overcome this problem, we have created an embedded paper-based microchip based on isothermal loop amplification (LAMP), which can rapidly and sensitively detect foodborne pathogens. Results We embed paper impregnated with LAMP reagent and specific primers in multiple reaction chambers of the microchip. The solution containing the target pathogen was injected into the center chamber and uniformly distributed into the reaction chamber by centrifugal force. The purified DNA of Escherichia coli O157:H7, Salmonella spp., Staphylococcus aureus, and Vibrio parahaemolyticus has been successfully amplified and directly detected on the microchip. The E. coli O157:H7 DNA was identified as low as 0.0134 ng μL− 1. Besides, the potential of this microchip in point-of-care testing was further tested by combining the on-chip sample purification module and using milk spiked with Salmonella spp.. The pyrolyzed milk sample was filtered through a polydopamine-coated paper embedded in the inside of the sample chamber. It was transported to the reaction chamber by centrifugal force for LAMP amplification. Then direct chip detection was performed in the reaction chamber embedded with calcein-soaked paper. The detection limit of Salmonella spp. in the sample measured by the microchip was approximately 12 CFU mL− 1. Conclusion The paper embedded LAMP microchip offers inexpensive, user-friendly, and highly selective pathogen detection capabilities. It is expected to have great potential as a quick, efficient, and cost-effective solution for future foodborne pathogen detection.

The performance of a metal halide perovskite single crystal is governed by the defect density. Here, the authors report a high quality single crystal perovskite grown by a ligand-assisted solution process with DPSI achieving 23-fold smaller trap density than that without DPSI.

The MAPbI3/epoxy composite was prepared by a simple solvothermal method and show high radiation shielding performance.

Grain boundaries are known to be generally detrimental to the operation of metal halide perovskite solar cells. Here Xiao et al. show with scanning photocurrent microscopy that ferroelastic twin boundaries are benign to the electrical properties in crystalline samples, in contrast to grain boundaries.

A novel ratiometric fluorescence probe based on nitrogen-doped blue carbon dots (NCDs) and red gold nanoclusters (Au NCs) for mercuric ion (Hg2+) has been prepared and characterized. A user friendly fluorescent test paper based sensor combined with smartphone was fabricated for rapid visual and quantitative detection. Hg2+ can specifically bind to Au+ on the surface of Au NCs, leading to the quench of red fluorescence while the fluorescence intensity of the NCDs with blue fluorescence remained unchanged as a internal standard signal. The implement of paper-based sensor address some common drawback in analytical process such as the detection time, analysis cost. In a further demonstration, a homemade detection device with smartphone was used to qualify the Hg2+. After adding different concentration of Hg2+, red, purple, and blue colors were obtained on the detection zones of the fluorescent test paper. The Android App Color Grab was used to identify the red, green and blue (RGB) values of fluorescent color. The rapid visual and quantitative detection of Hg2+ was accomplished with the detection limit of 2.7 nM for fluorescence, 25 nM for smartphone and 32 nM for paper strip. The developed multi-mode detection platform was successfully applied to the detection of mercury ions in water samples with acceptable recoveries. The NCDs and Au NCs probe facilitate the one-site environmental monitoring for Hg2+ with “naked-eye” and smartphone.

As the typical aryl-organophosphate flame retardants (OPFRs), triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) were reported to be estrogen disruptors. However, estrogen receptor α (ERα) binding experiments could not explain their biological effects. In this study, their action on ERα, G protein-coupled estrogen receptor (GPER) and the synthesis of 17β-estradiol (E2) were investigated using in vitro assays and molecular docking. The results showed that TPhP acted as an ERα agonist and recruited steroid receptor co-activator 1 (SRC1) and 3 (SRC3), which was found for the first time. Unlike TPhP, TDCIPP acted as an ERα antagonist. However, both TPhP and TDCIPP activated the estrogen pathway by GPER in SKBR3 cells which were lack of ERα. Although molecular docking results revealed that both TPhP and TDCIPP could dock into ERα and GPER, their substituent groups and combination mode might affect the receptor activation. In addition, by using estrogen biosynthesis assay in H295R cells, both of TPhP and TDCIPP were found to promote E2 synthesis and E2/T ratio involving their different alteration on levels of progesterone, testosterone and estrone, and expression of various key genes. Our data proposed estrogen-disrupting mechanism frameworks of TPhP and TDCIPP. Moreover, our results will contribute to future construction of adverse outcome pathway (AOP) framework of endocrine disruptors.

It is well-accepted that the two dimensional layered halide perovskite can improve the device stability of perovskite solar cells but the operation mechanism remains unclear. Here Lin et al. reveal the real morphology of the hot-cast layered perovskite solar cells and understand the working mechanism.

Bisphenol A (BPA) is a typical environmental endocrine disruptor that can migrate into organisms through skin contact, breathing, diet and various other approaches. The reproductive toxicity and neurotoxicity of BPA has been confirmed by several toxicological studies. However, the neurotoxicity of BPA is still controversial. In the present study, we used PC12 cells as a model to investigate the mechanism of BPA-induced neuronal apoptosis. BPA exposure reduced cell viability, altered cell morphology and aggravated intracellular Lactate dehydrogenase (LDH) release, intracellular Ca2+ concentration, Reactive oxygen species (ROS) levels, apoptosis and the reduction in the mitochondrial transmembrane potential (ΔΨm). Moreover, the results of the Western blot (WB) and Real-time quantitative polymerase chain reaction (RT-qPCR) assays indicated that the expression levels of Nur77 in the BPA group were down-regulated and accompanied by the downregulation of the NF-κb/Bcl-2 proteins and the upregulation of cleaved-caspase 3, which is a marker of apoptosis. However, these changes were significantly reversed with the upregulation of the Nur77 protein by introducing plasmids carrying the nur77 gene. These results indicated that BPA-induced apoptosis was closely related to Nur77-mediated inhibition of the NF-κb/Bcl-2 pathway.

Optoelectronic devices based on organic–inorganic halide perovskites show promising performance, but their poor stability impedes the commercialization. Here Lin et al. show that excess free charges are detrimental and efficient charge-carrier extraction is necessary for improved device stability.

The existing hole-transporting materials cause problems in the cost and scalability of the perovskite solar cells. Here Wu et al. fabricate high efficiency cells by molecularly doping the perovskite layer without using hole-transporting layers, thus simplify the device architecture and processing steps.

Thin films of halide perovskites are promising for solar cell technology but they do not perform well at the band edge due to the low optical absorption. Herein, Chen et al. fabricate a high efficiency single crystal perovskite solar cell with thicker single crystals to harvest the below-bandgap photons.

Organic-inorganic halide perovskites (OIHPs) are recognized as the promising next-generation X-ray detection materials. However, the device performance is largely limited by the ion migration issue of OIHPs. Here, we reported a simple atomistic surface passivation strategy with methylammonium iodide (MAI) to remarkably increase the ion migration activation energy of CH3NH3PbI3 single crystals. The amount of MAI deposited on the crystal surface is finely regulated by a self-assemble process to effectively suppress the metallic lead defects, while not introducing extra mobile ions, which results in significantly improved dark current stability of the coplanar-structure devices under a large electric field of 100 V mm-1. The X-ray detectors hence exhibit a record-high sensitivity above 700,000 μC Gyair‐1 cm‐2 under continuum X-ray irradiation with energy up to 50 keV, which enables an ultralow X-ray detection limit down to 1.5 nGyair s-1. Our findings will allow for the dramatically reduced X-ray exposure of human bodies in medical imaging applications.

Fanget al. develop a method to determine the photon recycling efficiency for organic-inorganic hybrid single crystal perovskites by differentiating between emitted and re-absorbed photons based on their polarization difference. For these systems efficiencies of less than 0.5% are reported.

Hydrophobicity is an important parameter to characterize electrical properties of insulated materials. Therefore, it is an urgent task to develop on-line instruments to identify the hydrophobicity of insulated material's surface conveniently, quickly and accurately. For this purpose, a novel evaluation system with image processing and decision tree is proposed which is based on embedded platform. For obtaining satisfactory results, we first propose a mixed image segmentation method to overcome the complex conditions outside, concerning non-controlled illumination, nonstandard surfaces and unfixed shooting angle. Then we adopt four new characteristic parameters to describe the image of each sample. Finally, a classification method based on MultiBoost decision tree is conducted which synthesizes the merits of both AdaBoost and Wagging algorithm. Results indicate the procedures can be applied in the DSP (Digital Signal Processor) platform perfectly and better results can be obtained than those did in our previous study or that of some other research.

A review with 90 references is presented to show the development of acidic chemiluminescence methods for biochemical analysis by use of flow injection technique in the last 10 years. A brief discussion of both the chemiluminescence and flow injection technique is given. The proposed methods for biochemical analysis are described and compared according to the used chemiluminescence system.

A Ru(bpy)3 2+-based electrochemiluminescence (ECL) detection coupled with capillary electrophoresis (CE) was developed for the determination of atropine sulfate on the basis of an Eu-PB modified platinum electrode as the working electrode. The analyte was injected to separation capillary of 50 cm length (25 μm i.d., 360 μm o.d.) by electrokinetic injection for 10 s at 10 kV. Parameters related to the separation and detection were discussed and optimized. It was proved that 10 mM phosphate buffer at pH 8.0 could achieve the most favorable resolution, and the high sensitivity of detection was obtained by using the detection potential at 1.15 V and 5 mM Ru(bpy)3 2+ in 80 mM phosphate buffer at pH 8.0 in the detection reservoir. Under the optimized conditions, the ECL peak area was in proportion to atropine sulfate concentration in the range from 0.08 to 20 μg⋅mL−1 with a detection limit of 50 ng⋅mL−1 (3σ). The relative standard derivations of migration time and peak area were 0.81 and 3.19%, respectively. The developed method was successfully applied to determine the levels of atropine sulfate in urine samples of patients with recoveries between 90.9 and 98.6%.